Clinical impact of atrial fibrillation progression in patients with heart failure with preserved ejection fraction: A report from the CHART-2 Study.

AIMS: Atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), and clinical outcomes of patients with AF vary depending on its subtype. While AF progression, characterized by the transition from paroxysmal AF to persistent AF, is sometimes observed, the incidence and clinical impact of AF progression in patients with HFpEF remain to be explored. METHODS AND RESULTS: We enrolled patients with HFpEF and paroxysmal AF from the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study. AF progression was defined as the transition from paroxysmal AF to persistent AF. A total of 718 patients (median age: 72 years, 36% were female) were enrolled. For a median follow-up of 6.0 years (interquartile range: 3.0-10.2 years), AF progression occurred in 105 patients (14.6%), with a cumulative incidence of 16.7% at 10 years. In the multivariable Cox proportional hazards model, previous hospitalization for heart failure (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.16-2.60; P=0.007) and left atrial diameter (per 5-mm increase) (HR 1.37, 95% CI 1.20-1.55; P<0.001) were significantly associated with AF progression. Furthermore, AF progression was significantly linked to worsening heart failure (adjusted HR 1.68, 95% CI 1.18-2.40; P=0.004). Notably, 27 cases (26%) of worsening heart failure occurred within one year following AF progression. CONCLUSION: In patients with HFpEF, AF progression is significantly associated with adverse outcomes, particularly worsening heart failure. An increased risk is observed in the early phases following progression to persistent AF. REGISTRATION: ClinicalTrials.gov Identifier: NCT00418041.

Estimation of inter-individual variability of protein requirement by indicator amino acid oxidation method.

The indicator amino acid oxidation (IAAO) method is a recently developed method to determine the protein requirement and is particularly useful for analyzing human subjects because of its minimal invasiveness. IAAO study is performed using two-phase regression analysis, with the break-point between these phases being the estimated average requirement. However, this method requires that the break-point lie within a certain range in advance, which is in practice difficult. Recently, the change-point regression model (CPRM) has been proposed to be more effective for two-phase regression analysis. There is also a need to re-evaluate the value corresponding to the recommended dietary allowance. Calculation of the recommended dietary allowance requires data on the average requirement and the inter-individual variability of this requirement. However, no inter-individual variability values have been reported in the IAAO method. The aim of this study was thus to estimate the inter-individual variation in protein requirement using CPRM. From seven IAAO studies, the inter-individual variability was estimated as a coefficient of variation of about 20%. The coefficient of variation of the protein requirement determined by IAAO study was wider than the ordinary coefficient of variation obtained from the nitrogen balance test.

Comprehensive Safety Assessment of l-Lysine Supplementation from Clinical Studies: A Systematic Review.

BACKGROUND: Despite the widespread use of l-lysine in dietary supplements, the safety information pertinent to excessive l-lysine ingestion is limited and, to the best of our knowledge, there is no published systematic review of safety. OBJECTIVE: The objective of this study was to assess the clinical safety of l-lysine supplementation of a regular diet. METHODS: We searched PubMed, Cochrane Library, Ichushi Web, and EBSCOhost using the relevant keywords, "l-lysine" and "clinical trial." To investigate all adverse events observed during intervention trials, we included all intervention studies with orally ingested l-lysine without restricting background factors, environment, study designs, and sample sizes. RESULTS: We identified 71 articles, which included 3357 study subjects. The l-lysine doses ranged from 16.8 to 17.5 g/d, and the dosing period ranged from 1 to 1095 d. The observed adverse events were mainly subjective gastrointestinal tract symptoms; however, the risk analysis for incidence of gastrointestinal symptoms was not statistically significant (risk ratio of 1.02). CONCLUSION: The provisional no-observed-adverse-effect level in healthy human subjects was based on gastrointestinal symptoms and identified at 6.0 g/d. The review protocol was registered at umin.ac.jp as UMIN000028914 before the beginning of the study.

Cardiac Resynchronization Therapy for Improving Non-Uniform Thickening of Left Ventricular Wall: Assessment by Quantitative Gated Myocardial Perfusion SPECT.

Cardiac resynchronization therapy (CRT) improves cardiac dyssynchrony in heart failure patients with a wide QRS electrocardiogram (ECG). Assessment of left ventricular (LV) dyssynchrony using echocardiography or other imaging modalities is important to predict CRT effectiveness. In this study, we retrospectively evaluated cardiac nuclear imaging of ECG-gated myocardial perfusion single-photon emission computed tomography (SPECT) with 99mTc-sestamibi for CRT candidate (n = 120) with severe heart failure and wide QRS (> 120 msec) in ECG. To analyze LV non-uniformity, we used the quantitative gated SPECT (QGS) software to calculate changes in regional LV wall thickness during a cardiac cycle (i.e., wall thickening scores). Cardiac events (heart failure, ventricular arrhythmias and cardiac death) after CRT during 38 ± 22 (SD) months were also evaluated. In 97 of 120 patients who underwent QGS before and 6 months after CRT, CRT homogenized non-uniform wall thickening between septal and lateral of the LV especially in CRT responders. This observation was indicated as increase in the lateral deflection (XWT) of wall thickening scores before CRT and its decrease after CRT. In 120 patients with QGS before CRT, the larger XWT before CRT (≥ 16.5) predicted better prognoses after CRT. This finding was similarly observed even in patients with narrower baseline QRS (≤ 140 msec; n = 41 of 120), who usually have less benefits from CRT. In conclusion, CRT improved non-uniformity of wall thickening between the LV septal and lateral regions evaluated using QGS, which is predictive of better prognosis in the chronic phase after CRT.

Safety assessment of L-lysine oral intake: a systematic review.

Currently, the use of amino acids in supplements and functional foods is increasing globally. However, there are no guidelines for the upper limit of ingestion for the safe use of these amino acids. Safety evaluation of chemical substances is generally performed through non-clinical and clinical studies. However, amino acids that have these safety data are limited. Therefore, we used a systematic review approach for evaluating the safety of amino acids. In the present study, we evaluated the safety of L-lysine added to an ordinary diet in humans. Using PubMed, Cochrane Library, Ichushi Web, and EBSCOhost as search databases, we comprehensively searched human studies on oral ingestion of L-lysine. Ultimately, 71 studies were selected for evaluation. Of these, 12 studies were of relatively high quality with Jadad scores ≥ 3. The dose range of L-lysine in the selected studies was 16.8-17,500 mg/day, and the range of dosing period was 1-1095 days. The observed adverse events were mainly subjective symptoms related to the gastrointestinal tract such as nausea, stomachache, and diarrhea. The provisional no-observed-adverse-effect level obtained based on these gastrointestinal symptoms was 6000 mg/person/day. Integrated analysis of the risk for developing gastrointestinal symptoms revealed that the risk ratio was 1.02 (95% CI, 0.96-1.07; p = 0.49); thus, no significant increase was observed. (UMIN000028914).

Polidocanol injection therapy for small-bowel hemangioma by using double-balloon endoscopy.

BACKGROUND AND AIMS: Small-bowel hemangioma is a rare disease that often causes active bleeding. The standard therapeutic method for small-bowel hemangioma is surgical resection. The aim of this study was to evaluate the usefulness of polidocanol injection (PDI) for small-bowel hemangiomas. METHODS: This study included 12 patients with obscure GI bleeding (6 male; mean age 62 years) with 39 small-bowel hemangiomas; patients were treated with PDI by using double-balloon endoscopy (DBE). EUS with DBE was performed before PDI. The lesions were divided into 2 groups according to tumor size: Group A (size <10 mm; 20 lesions) and group B (size ≥10 mm; 19 lesions). The outcomes of PDI treatment for small-bowel hemangioma were evaluated between the 2 groups. Additionally, in order to standardize the amount of PDI injected, the total amount of polidocanol according to lesion size was calculated. RESULTS: There was no difference in the location of lesions and treatment times between the 2 groups. Group B had a significantly higher injection time per lesion (P < .05) and amount of polidocanol per lesion than group A (P < .01). Rebleeding occurred in only 1 case (8%). There were no adverse events related to PDI. The contribution ratio between the lesion size and amount of polidocanol showed a correlation (r = 0.77). The optimal amount of polidocanol for small-bowel hemangioma was determined to be 0.2 mL/mm. CONCLUSIONS: PDI is an easy, safe, and effective method to treat small-bowel hemangiomas.

Clinical usefulness of transabdominal ultrasonography prior to patency capsule for suspected small-bowel strictures.

OBJECTIVE: Patency capsule (PC) examination has made it possible to perform capsule endoscopy (CE) in patients with a suspected small-bowel stricture. However, PC has some drawbacks, so we assessed the usefulness of transabdominal ultrasonography (TUS) prior to PC in patients with suspected small-bowel strictures to avoid unnecessary PC examination. PATIENTS AND METHODS: Fifty-two patients who underwent TUS prior to PC were enrolled in this study. TUS findings were classified as follows: intestinal narrowing and distension at the oral side (Type A); extensive bowel wall thickening (Type B); focal bowel wall thickening (Type C) or no abnormality detected (Type D). We evaluated the TUS and PC findings for the detection of small-bowel strictures. RESULTS: Double-balloon endoscopy (DBE) revealed small-bowel strictures in 13 of 50 patients (26%). TUS yielded Type B or C findings in 12 of 13 patients (92%), while PC revealed strictures in all 13 patients. In Crohn's disease (CD) patients with Type B TUS findings, 8 of 9 (89%) had small-bowel strictures on DBE. However, only two of six non-CD patients (33%) with Type B TUS findings had small-bowel strictures. The incidence of Type B strictures was significantly higher in CD patients. CONCLUSIONS: CD patients with Type B TUS findings should not undergo PC or CE because of the high rate of small-bowel strictures. Non-CD patients diagnosed with Type B TUS strictures, as well as patients diagnosed with Type C or D strictures should undergo CE after confirming small-bowel patency using PC.

Effect of Respiratory Therapy on the Prognosis of Chronic Heart Failure Patients Complicated With Sleep-Disordered Breathing　- A Pilot Efficacy Trial.

BACKGROUND: Sleep-disordered breathing (SDB) has been reported to influence mortality and occurrence of ventricular tachyarrhythmia in patients with chronic heart failure (CHF). It remains to be elucidated, however, whether respiratory therapy (RT) can affect the occurrence of fatal ventricular tachyarrhythmia in CHF patients with SDB. METHODS AND RESULTS: We prospectively examined whether the severity of SDB was associated with fatal cardiac events in CHF patients and, if so, whether RT for SDB improved prognosis. We enrolled 95 patients with stable CHF, in whom SDB was examined on overnight polygraphy. The severity of SDB was quantified using the apnea-hypopnea index (AHI). All patients with AHI ≥10 (n=42) at initial evaluation were recommended to have RT, such as home oxygen therapy and continuous positive airway pressure, and 24 agreed to this. During the follow-up period of 29±17 months, 8 ventricular tachyarrhythmias occurred and 14 of the 95 patients died. On multivariate proportional hazard analysis AHI ≥5 was a risk factor for fatal arrhythmic events (P=0.026). Although RT significantly reduced AHI, it did not significantly reduce the event rates, but 4 patients with AHI <5 on RT had no fatal arrhythmic events or death. CONCLUSIONS: SDB is an independent prognostic factor and thus an important therapeutic target in CHF patients.

Overview of the 80(th) Annual Scientific Meeting of the Japanese Circulation Society　- The Past, Present and Future of Cardiovascular Medicine in Japan -　- The 5(th) Anniversary of the Great East Japan Earthquake.

The 80(th)Annual Scientific Meeting of the Japanese Circulation Society was held in Sendai, Japan, on March 18-20, 2016, which coincided with the 5(th)anniversary of the Great East Japan Earthquake that hit the Tohoku area on March 11, 2011. Thus, the main themes for this meeting were "The Past, Present and Future of Cardiovascular Medicine in Japan" and "The 5(th)Anniversary of the Great East Japan Earthquake". Despite the provincial location, approximately 15,000 people attended during the 3-day meeting, and there were in-depth discussions in each of the various sessions on these themes. Especially, to our great pleasure, the Japanese Royals, Emperor Akihito and Empress Michiko, kindly visited the panel exhibition of the Great East Japan Earthquake and spoke words of appreciation to us. The meeting successfully completed and we sincerely appreciate the great cooperation and support from all affiliates. (Circ J 2016; 80: 1689-1694).

Prognostic Significance of Late Potentials in Outpatients with Type 2 Brugada Electrocardiogram.

Brugada syndrome is characterized by distinguishing electrocardiogram (ECG) patterns (coved and saddle-back types with day-to-day variation) and occurrence of lethal tachy-arrhythmias. The appearance of coved type ECG (type 1) is required for the diagnosis of Brugada syndrome, whereas the significance of saddle-back type ECG (type 2), which is inadequate for the diagnosis, has not been fully established. We enrolled 34 consecutive patients with type 2 ECG on outpatient-clinic. Among them, 7 patients were ventricular fibrillation (VF) survivors who were diagnosed as Brugada syndrome with transient appearance of type 1 ECG, and showed type 2 ECG on their first outpatient-clinic visit after the VF event (VF group). The remaining 27 were asymptomatic and never showed type 1 ECG on repeated ECG examinations (control group). The VF group showed significantly longer RJ intervals in leads V1 and V2 and QTc intervals in lead V2 compared with the control group (P < 0.030, P < 0.017, and P < 0.030, respectively). Late potentials, detected on the signal-averaged ECG (SA-ECG), reflect conduction abnormalities and are known as one of the risk markers of arrhythmic events. Among the 34 patients, late potentials were negative in 12 patients belonging to the control group. In conclusion, the SA-ECG could be helpful to identify high-risk patients for its high negative predictive value as the first step, and ECG parameters, including RJ intervals in leads V1 and V2 and QTc interval in lead V2, could be useful for further risk stratification in patients with type 2 Brugada ECG.

Major predictors and management of small-bowel angioectasia.

BACKGROUND: Small-bowel angioectasias are frequently diagnosed with capsule endoscopy (CE) or balloon endoscopy however, major predictors have not been defined and the indications for endoscopic treatment have not been standardized. The aim of this study was to evaluate the predictors and management of small-bowel angioectasia. METHODS: Among patients with obscure gastrointestinal bleeding (OGIB) who underwent both CE and double-balloon endoscopy at our institution, we enrolled 64 patients with small-bowel angioectasia (angioectasia group) and 97 patients without small-bowel angioectasia (non-angioectasia group). The angioectasia group was subdivided into patients with type 1a angioectasia (35 cases) and type 1b angioectasia (29 cases) according to the Yano-Yamamoto classification. Patient characteristics, treatment, and outcomes were evaluated. RESULTS: Age (P = 0.001), cardiovascular disease (P = 0.002), and liver cirrhosis (P = 0.003) were identified as significant predictors of small-bowel angioectasia. Multivariate logistic regression analysis identified cardiovascular disease (odds ratio 2.86; 95% confidence interval, 1.35-6.18) and liver cirrhosis (odds ratio 4.81; 95% confidence interval, 1.79-14.5) as independent predictors of small-bowel angioectasia. Eleven type 1a cases without oozing were treated conservatively, and 24 type 1a cases with oozing were treated with polidocanol injection (PDI). Re-bleeding occurred in two type 1a cases (6%). Seventeen type 1b cases were treated with PDI and 12 type 1b cases were treated with PDI combined with argon plasma coagulation (APC) or clipping. Re-bleeding occurred in five type 1b cases (17%) that resolved after additional endoscopic hemostasis in all cases. There was one adverse event from endoscopic treatment (1.6%). CONCLUSIONS: Cardiovascular disease and liver cirrhosis were significant independent major predictors of small-bowel angioectasia. Type 1a angioectasias with oozing are indicated for PDI and type 1b angioectasias are indicated for PDI with APC or clipping.

Current status of primary prevention of sudden cardiac death with implantable cardioverter defibrillator in patients with chronic heart failure--a report from the CHART-2 Study.

BACKGROUND: The current status of primary prevention of sudden cardiac death (SCD) with implantable cardioverter defibrillator (ICD) in patients with heart failure with reduced ejection fraction remains to be fully elucidated in Japan. METHODS AND RESULTS: In the chronic heart failure (CHF) cohort study, the CHART-2 Study, we enrolled 2,778 consecutive patients with NYHA class II-III. According to the Japanese Circulation Society guideline of prophylactic ICD, we divided them into 3 groups: group A, class I indication; B, class IIa; and C, no indication. During the (median) 3.2-year follow-up, 79 fatal arrhythmic events (FAE), defined as composite of sudden cardiac/arrhythmic death, ventricular tachycardia/fibrillation and appropriate ICD therapy, occurred. In the groups A, B and C, the prevalence of FAE was 16.1%, 8.9% and 1.9%, respectively; the use of prophylactic ICD among those with FAE, however, was only 44%, 9% and 6%, respectively. In the groups A and B combined, chronic atrial fibrillation (cAF) and left ventricular end-diastolic dimension (LVDd) ≥ 65 mm were independent predictors of FAE, and, when combined, their prognostic impact was highly significant (hazard ratio, 7.01; P<0.001). CONCLUSIONS: Primary prevention of SCD with ICD in CHF patients is validated but is still underused in Japan, and the combination of cAF and LVDd ≥ 65 mm may be a useful indication of prophylactic ICD implantation.

Major predictors of portal hypertensive enteropathy in patients with liver cirrhosis.

BACKGROUND AND AIM: Portal hypertensive enteropathy (PHE) is acknowledged as a source of bleeding, and predicting its presence has become more important. We assessed PHE using capsule endoscopy (CE) and investigated factors that may predict its presence, including portosystemic shunts (PSs). METHODS: We analyzed data from 134 consecutive patients with liver cirrhosis, from February 2009 to September 2013. All patients had undergone dynamic computed tomography and esophagogastroduodenoscopy before CE examination. The frequencies and types of PHE lesions, and the relationships between the presence of PHE and patients' clinical characteristics were evaluated. The distribution of the lesions was also determined. RESULTS: PHE was found in 91 (68%), erythema in 70 (52%), erosions in 25 (19%), angioectasia in 24 (18%), villous edema in 18 (13%), and varices in 10 (7%) patients. Most lesions were located in the jejunum. The clinical characteristics associated with the presence of PHE were a Child-Pugh grade of B or C (P = 0.0058), and the presence of PSs (P < 0.0001), ascites (P = 0.0017), portal thrombosis (P = 0.016), esophageal varices (P = 0.0017), and portal hypertensive gastropathy (P = 0.0029). The presence of PSs was an independent predictor of PHE (odds ratio [OR]: 3.15; 95% confidence interval [CI]: 1.27-7.95). Among the shunt types, left gastric vein (OR: 5.31; 95% CI: 1.97-17.0) and splenorenal shunts (OR: 4.26; 95% CI: 1.29-19.4) were independent predictors of PHE. CONCLUSION: PSs, especially left gastric vein and splenorenal shunts, appear to reliably predict the presence of PHE.

Is small-bowel capsule endoscopy effective for diagnosis of esophagogastric lesions related to portal hypertension?

BACKGROUND AND AIM: Effectiveness of capsule endoscopy (CE) for screening the small bowel in patients with portal hypertension (PHT) has been reported. However, few reports discuss CE detection of specific esophagogastric lesions related to PHT. Thus, we assessed whether CE is useful for detecting such lesions. METHODS: One hundred nineteen consecutive patients with PHT comprised the study group. All had undergone esophagogastroduodenoscopy (EGD) prior to CE. The diagnostic yield of CE for esophageal varices (EVs), gastric varices (GVs), and portal hypertensive gastropathy (PHG) was evaluated. In addition, diagnostic yield in relation to form, location of the varices, grade, and extent of PHG was evaluated. RESULTS: EVs were found by EGD in 71 patients. The overall diagnostic yield of CE for EVs was 72% (51/71). The diagnostic yield was significantly greater for F2/F3 EVs than for F1 EVs (87% vs 61%, P = 0.03). The diagnostic yield was significantly greater for Lm/Ls EVs than for Li EVs (85% vs 55%, P = 0.01). The diagnostic yield was significantly greater for locus superior/locus medialis EVs than for locus inferior EVs (85% vs 55%, P = 0.01). GVs were found by EGD in 29 patients. Only one case was detected by CE. PHG was found by EGD in 35 patients. The diagnostic yield of CE for PHG was 69% (24/35). There was no difference in diagnostic yield between cases of severe and mild PHG (82% vs 63%, P = 0.44). Diagnostic yield of CE for PHG in the gastric body was significantly greater than that in the fundus (100% vs 48%, P = 0.0009). CONCLUSION: CE is reliable for diagnosis of F2/F3 and/or Lm/Ls EVs and of PHG in the gastric body.

Comparison of small-bowel mucosal injury between low-dose aspirin and non-aspirin non-steroidal anti-inflammatory drugs: a capsule endoscopy study.

BACKGROUND/AIMS: The differences in the severity of small-bowel toxicity induced by aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) remain unclear. This study aimed at clarifying these differences in small-bowel mucosal injury by using capsule endoscopy (CE). METHODS: We retrospectively compared the records of 78 and 40 obscure gastrointestinal bleeding patients receiving low-dose aspirin (LDA) and non-aspirin NSAIDs, respectively. All patients were found to have small-bowel mucosal injuries on CE. The two groups were compared for the number of small-bowel mucosal injuries and CE scores on the basis of the findings of CE. RESULTS: The mean numbers of reddened lesions in the LDA group and non-aspirin NSAID group were 2.49 ± 3.15 and 1.65 ± 3.04; the mean numbers of erosions/ulcers 1.56 ± 3.75 and 6.08 ± 10.4, and the mean CE scores 154 ± 294 and 520 ± 758, respectively. The mean number of reddened lesions was significantly higher and the mean number of erosions/ulcers and CE scores significantly lower in the LDA group than in the other non-aspirin NSAID group. CONCLUSION: Small-bowel mucosal injuries were significantly milder in the LDA group than in the non-aspirin NSAID group, though reddened lesions were more frequent in the LDA group.

Clinical experience of J-VAC drain for skin closure in the laparotomy of obstetrics and gynecology.

AIM: The frequency of wound dehiscence after abdominal surgery has been reported to be approximately 4-29%, and that of surgical site infections is said to be of about 20%. We examined the effectiveness of the subcutaneous J-VAC drain (JVD) in the drainage of bleeding and exudates from surgical wounds. MATERIAL AND METHODS: The study was conducted on 192 patients who underwent abdominal surgery from October 2009 to February 2011, and in whom indwelling JVD were placed. During the study period, JVD (10-Fr) were placed subcutaneously on the anterior surface of the fascia in all patients. We examined the frequency of surgical wound complications. RESULTS: A longitudinal incision was used in 101 patients, and a transverse abdominal incision was used in 91 patients. Subjects with a subcutaneous fat thickness of 2 cm or thicker accounted for 115 patients. Subcutaneous hematoma was present in three patients, but only two patients (1%) showed dehiscence that required treatment. CONCLUSIONS: This study revealed that subcutaneous JVD is useful for the closure of surgical incisions in gynecology and obstetrics, and that there are no limitations to their applicability.

Sturge-Weber syndrome with cemento-ossifying fibroma in the maxilla and giant odontoma in the mandible: A case report.

Sturge-Weber syndrome (SWS) is a neurocutaneous syndrome with vascular lesions of the cerebral meninges, port wine spots on the face, and glaucoma of the eyes; it is a congenital, non-genetic disease whose etiology and mechanisms are unknown. In this report, we describe a rare case of SWS with unilateral large odontogenic tumors in the maxilla and mandible. The histopathological diagnosis of the maxillary bone lesion on biopsy was juvenile psammomatoid ossifying fibroma, which is considered a type of ossifying fibroma of craniofacial bone origin. However, the final pathological diagnosis of the excision was cemento-ossifying fibroma derived from periodontal ligament cells, and we discuss the histopathology in detail. In addition, the mandibular lesion was one of the largest odontomas reported to date. Furthermore, in this case, we suggest the possibility that the maxillary and mandibular bone lesions are not separate lesions, but a series of lesions related to SWS.

Clinical utility of QRS duration normalized to left ventricular volume for predicting cardiac resynchronization therapy efficacy in patients with "mid-range" QRS duration.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective for patients with heart failure with QRS duration (QRSd) ≥150 ms. However, its beneficial effect seems to be limited for those with "mid-range" QRSd (120-149 ms). Recent studies have demonstrated that modifying QRSd to left ventricular end-diastolic volume (LVEDV)-modified QRSd-improves the prediction of clinical outcomes of CRT. OBJECTIVE: The purpose of this study was to investigate the clinical impact of the modified QRSd on the efficacy of CRT in patients with "mid-range" QRSd. METHODS: We conducted a retrospective, multicenter, observational study, with heart failure hospitalization (HFH) after CRT as the primary endpoint. Modified QRSd is defined as QRSd divided by LVEDV, determined through the Teichholtz method of echocardiography. RESULTS: Among the 506 consecutive patients considered, 119 (mean age 61 ± 15 years; 80% male, QRSd 135 ± 9 ms) with a "mid-range" QRSd who underwent de novo CRT device implantation were included for analysis. During median follow-up of 878 days [interquartile range 381-1663 days], HFH occurred in 45 patients (37%). Fine-Gray analysis revealed modified QRSd was an independent predictor of HFH (hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.96-0.99; P <.01). Receiver operating characteristic curve analysis revealed a cutoff value of 0.65 ms/mL for the modified QRSd in predicting HFH. Patients above the threshold exhibited a significantly lower incidence of HFH than patients below the threshold (HR 0.46; 95% CI 0.25-0.86; P = .01). CONCLUSION: Modified QRSd can effectively predict the efficacy of CRT in patients with a "mid-range" QRSd.

Clinical usefulness of classification by transabdominal ultrasonography for detection of small-bowel stricture.

OBJECTIVE: To assess the clinical usefulness of transabdominal ultrasonography (TUS) for detection of small-bowel stricture. PATIENTS AND METHODS: Subjects were 796 patients undergoing double-balloon endoscopy (DBE), December 2003-October 2011. All underwent TUS prior to DBE. The TUS findings were classified by type as intestinal narrowing and distension at the oral side (Type A); extensive bowel wall thickening (Type B); focal bowel wall thickening (Type C) or no abnormality detected (Type D). We compared TUS findings against DBE findings with respect to small-bowel stricture, defined as failure of the enteroscope to pass through the small bowel. RESULTS: Small-bowel stricture was detected by DBE in 11.3% (90/796) of patients. Strictures resulted from Crohn's disease (n = 36), intestinal tuberculosis (n = 24), malignant lymphoma (n = 9), ischemic enteritis (n = 6), NSAID ulcer (n = 5), radiation enteritis (n = 2), surgical anastomosis (n = 2) and other abnormalities (n = 6). Stricture was detected by TUS in 93.3% (84/90) of patients, and each such stricture fell into one of the three types of TUS abnormality. The remaining 6 strictures were detected only by DBE. DBE-identified strictures corresponded to TUS findings as follows: 100% (43/43) to Type A, 59.1% (29/49) to Type B, 14.8% (12/81) to Type C and 1% (6/623) to Type D. Correspondence between stricture and the Type A classification (vs. Types B, C and D) was significantly high, as was correspondence between stricture and Type B (vs. Types C and D). CONCLUSIONS: TUS was shown to be useful for detecting small-bowel stricture. We recommend performing TUS first when a small-bowel stricture is suspected.

Rho-kinase activation in patients with heart failure.

BACKGROUND: Heart failure (HF) is a complex clinical syndrome, resulting from structural and/or functional cardiac disease. The aim of this study was to determine whether the activity of Rho-kinase, which has been identified as an important therapeutic target of cardiovascular disease, is enhanced in HF patients. METHODS AND RESULTS: Total and phosphorylated forms of myosin binding subunit (t-MBS and p-MBS), a substrate of Rho-kinase, were measured on western blotting in circulating leukocytes, and the p-MBS/t-MBS ratio was defined as an index of systemic Rho-kinase activity. First, during the time-course of acute HF (n=12), Rho-kinase activity was significantly elevated in the acute phase compared to the chronic phase (1.19 ± 0.06 vs. 0.97 ± 0.04, P<0.05). Next, Rho-kinase activity was examined in 30 controls and 130 chronic HF patients (cardiomyopathy, n=57; valvular heart disease, n=35; ischemic heart disease [IHD], n=33; and others, n=5). As compared with the controls, Rho-kinase activity was significantly elevated in the total HF group (1.14 ± 0.02 vs. 0.77 ± 0.05, P<0.0001) and in each underlying heart disease (P<0.05 each). Importantly, in the high-risk non-IHD group, Rho-kinase activity was significantly associated with plasma brain nutriuretic peptide level. Finally, p-MBS was expressed in myocardial biopsy samples (immunohistochemistry) in chronic HF patients (n=36), independent of Rho-kinase activity in leukocytes. CONCLUSIONS: Rho-kinase is activated in HF patients, suggesting that it could be a new therapeutic target of the disorder.