The Null technique as a novel, potential first-line method of device delivery for complicated lesions during percutaneous coronary intervention.

Aim: During percutaneous coronary intervention (PCI), complicated lesions in the target coronary artery often hinder device delivery. Fluid lubricants have commonly been used to reduce friction between adjacent solid materials in manufacturing, thus achieving smoother action. This ex vivo experimental study examined whether a contrast medium could function as a fluid lubricant during PCI. Methods and results: We used two different coronary artery lesion models with distinct complexities made from silicon. Each model was fit into the ex vivo PCI-simulation system. This ex vivo laboratory equipment consisted of ordinary PCI instruments and an aorta model from the Valsalva sinus to the descending aorta. A Wolverine™ cutting balloon catheter was advanced through each lesion model via a guide catheter set into the system. The maximum force required to push the catheter through the lesion models was measured while the vessel system was filled with either normal saline or contrast medium. The maximum force required was significantly lower with the contrast medium (1.38 ± 0.21 N in the normal-saline condition vs. 0.92 ± 0.05 N in the contrast-medium condition in the lesion model A, p < 0.001; 1.30 ± 0.07 N in the normal-saline condition vs. 1.14 ± 0.04 N in the contrast-medium condition in the lesion model B, p < 0.001). Conclusions: The contrast medium for vessel system filling reduced the force required to push the devices through the lesion models. This contrast medium represents a potential candidate for a liquid lubricant to facilitate device delivery for complicated coronary lesions.

Reduced Plasma NT-proBNP Levels Months after Myocardial Infarction Postconditioned with Lactate-Enriched Blood.

BACKGROUND: We recently reported a new approach, namely postconditioning with lactate-enriched blood (PCLeB), for cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: We examined the effects of PCLeB on plasma NT-proBNP levels months after myocardial infarction (MI). METHODS: The study included consecutive patients (n = 31) undergoing percutaneous coronary intervention (PCI) for anterior STEMI within 12 h of symptom onset in our hospital between March 2014 and August 2018. We retrospectively compared plasma NT-proBNP levels several months after MI in these patients with those in historical control patients (n = 32). The control patients included consecutive patients who underwent successful PCI without PCLeB for anterior STEMI within 12 h of symptom onset in our hospital between March 2009 and February 2014. We compared the highest plasma NT-proBNP values 6-10 months after MI in the postconditioned patients with the lowest plasma NT-proBNP values 6-10 months after MI in the control patients. In the PCLeB protocol, the duration of each brief reperfusion was increased stepwise from 10 to 60 s. Lactated Ringer's solution (30 mL) was injected directly in the culprit coronary artery at the end of each brief reperfusion. Each ischemic episode lasted 60 s. RESULTS: Plasma NT-proBNP levels in the postconditioned patients months after MI (211 ± 207 pg/mL) were significantly lower than those in the control patients (516 ± 598 pg/mL; p < 0.0001). CONCLUSION: PCLeB was associated with reduced plasma NT-proBNP levels months after MI.

Left Ventricular Diastolic Dysfunction Is Associated With the Prevalence of Paroxysmal Atrial Fibrillation Determined on the Latest Echocardiographic Criteria.

Background: The relationship between left ventricular diastolic dysfunction (LVDD) and paroxysmal atrial fibrillation (PAF) remains unclear because of a lack of standard measures to evaluate LVDD. Accordingly, we examined the association between the prevalence of PAF and each LVDD grade determined according to the latest American Society of Echocardiography guidelines. Methods and Results: In all, 2,063 patients without persistent AF who underwent echocardiography at Saitama Municipal Hospital from July 2016 to June 2017 were included in the study. Patients were divided into LVDD 6 categories: No-LVDD (n=1,107), Borderline (n=392), Grade 1 (n=204), Indeterminate (n=62), Grade 2 (n=254), and Grade 3 (n=44). PAF was documented in 111 (10.0%), 81 (20.7%), 28 (13.7%), 6 (9.7%), 52 (20.5%), and 24 (54.5%) patients in the No-LVDD, Borderline, Grade 1, Indeterminate, Grade 2, and Grade 3 categories, respectively. PAF prevalence was higher in patients with Grade 3 LVDD across the whole study population. Subgroup analyses showed that the prevalence of PAF increased with increased LVDD grade in patients with reduced left ventricular ejection fraction. This relationship was significant in multivariate analysis including various patient characteristics. Conclusions: LVDD severity determined on the basis of the latest echocardiographic criteria was associated with the prevalence of PAF. The present findings shed light on the development of new therapeutic markers for PAF.

Postconditioning with Lactate-enriched Blood for Cardioprotection in ST-segment Elevation Myocardial Infarction.

The beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) is attenuated by reperfusion injury. No approach has been proven successful in preventing this injury in the clinical setting to date. Meanwhile, a novel approach for cardioprotection in patients with STEMI, i.e., postconditioning with lactate-enriched blood (PCLeB), has recently been reported. PCLeB is a modification of the original protocol of postconditioning, aimed at increasing the delay in the recovery from tissue acidosis produced during ischemia. This was sought to achieve controlled reperfusion with tissue oxygenation and minimal lactate washout. In this modified postconditioning protocol, the duration of each brief reperfusion is gradually increased in a stepwise manner from 10 to 60 s. Each brief ischemic period lasts for 60 s. At the end of each brief reperfusion, injection of lactated Ringer's solution (20-30 mL) is performed directly into the culprit coronary artery immediately before the balloon inflation and the balloon is quickly inflated at the lesion site, so that the lactate is trapped inside the ischemic myocardium during each brief repetitive ischemic period. After seven cycles of balloon inflation and deflation, full reperfusion is performed. Stenting is performed thereafter, and the percutaneous coronary intervention is completed. Excellent in-hospital and 6 month outcomes in a limited number of patients with STEMI treated using PCLeB have already been reported. This method article provides a detailed description of each step of the PCLeB procedures.

Muscle squeezing immediately after coronary reperfusion therapy using postconditioning with lactate-enriched blood.

BACKGROUND: We recently reported a new approach for cardioprotection, postconditioning with lactate-enriched blood (PCLeB), and a patient with ST-segment elevation myocardial infarction (STEMI), in whom muscle squeezing of the culprit coronary artery was observed immediately after reperfusion with PCLeB. In this study, we examined the prevalence of muscle squeezing immediately after reperfusion in patients with anterior STEMI treated using PCLeB. METHODS AND RESULTS: PCLeB is a modified postconditioning protocol that comprises intermittent reperfusion and timely coronary injections of lactated Ringer's solution. We treated 30 consecutive patients with anterior STEMI using PCLeB. Among the 30 patients, 4 patients exhibited muscle squeezing of the left anterior descending artery (LAD) immediately after reperfusion. We performed follow-up coronary angiography in 23 patients and found another patient who exhibited muscle squeezing of the LAD. Thus, of 30 patients, 5 were confirmed to have myocardial bridging and 4 exhibited muscle squeezing immediately after reperfusion with PCLeB. No patient died or experienced re-hospitalization for heart failure or recurrent ischemic events at 6 months except for one patient with malignancy. CONCLUSION: Muscle squeezing immediately after reperfusion therapy is not a rare phenomenon in patients with anterior STEMI treated using PCLeB.

Impact of postconditioning with lactate-enriched blood on in-hospital outcomes of patients with ST-segment elevation myocardial infarction.

BACKGROUND: Reperfusion injury offsets the beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI). In our previous reports, postconditioning with lactate-enriched blood (PCLeB) induced excellent microcirculation recovery and less inflammation in STEMI patients. This study aimed to determine the in-hospital outcomes of STEMI patients treated using PCLeB. METHODS: Fifty-five consecutive STEMI patients were treated using PCLeB (Age 66.6±13.8years, 76.4% men) within 12h of symptom onset. In our modified postconditioning protocol, the duration of each brief reperfusion was prolonged from 10s to 60s in a stepwise manner. Lactated Ringer's solution (20-30mL) was injected directly into the culprit coronary artery at the end of each brief reperfusion and the balloon was quickly inflated at the lesion site, whereby lactate could be trapped inside the ischemic myocardium. Each brief ischemic period lasted 60s. After 7cycles of balloon inflation and deflation, full reperfusion was performed. Thereafter, stenting was performed and percutaneous coronary intervention (PCI) was completed. RESULTS: The mean corrected thrombolysis in myocardial infarction frame count was 20.1±10.1 after PCI completion. The mean peak serum creatine kinase and creatine kinase-MB levels were 2751±2227IU/L and 276±181IU/L respectively. None of the study patients died during their hospital stay or required continuation of oral diuretic or inotropic therapy for heart failure on discharge. CONCLUSIONS: PCLeB led to zero in-hospital mortality and no overt heart failure on discharge in 55 consecutive STEMI patients undergoing reperfusion therapy.

A second-look endoscopy may not reduce the bleeding after endoscopic submucosal dissection for gastric epithelial neoplasm.

BACKGROUND: Gastric endoscopic submucosal dissection (ESD) has gradually come to be recommended as the optimal treatment for early gastric cancer; however, one of the primary issues is postoperative bleeding. Although second-look endoscopy is conventionally performed to reduce the risk of postoperative bleeding, its benefit has not yet been clearly elucidated. The objective of this study was to elucidate the benefit of second-look endoscopy. METHODS: A total of 459 lesions in patients were underwent gastric ESD from May 2004 to April 2013 at our hospital were included in the analysis. The patients were divided into those who had bleeding within 24 hours after ESD (immediate bleeding) and those in whom bleeding occurred 24 hours or more after the procedure (delayed bleeding); the underlying disease, age, lesion site, diameter of the resected specimen, and lesion diameter were analyzed to identify the risk factors for postoperative bleeding after ESD. RESULTS: Post-ESD immediate or delayed bleeding occurred in 23 of the 459 cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%) excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases (53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the 210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant difference between the two groups. Overall, the following factors were identified as the risk factors for postoperative bleeding: young age (P = 0.005), lesions in the L segment (P = 0.042), and large size of the resected specimen (P = 0.005). The risk factors identified in the immediate bleeding group were lesions in the L segment (P = 0.032), large size of the resected specimen (P < 0.001), and large tumor size (P = 0.011), and those in the delayed bleeding group were young age (P = 0.013) and concomitant renal disease (P = 0.011). CONCLUSIONS: The results of this study suggest that second-look endoscopy after gastric ESD may not be useful for preventing postoperative bleeding.

Acute aortic regurgitation due to aortic dissection confined to the sinus of Valsalva.

A 34-year-old man with severe heart failure was diagnosed with acute aortic regurgitation (AR) by transthoracic echocardiography (TTE). However, this differential diagnosis was incomplete. Only transesophageal echocardiography (TEE) revealed an intimal flap, leading to a diagnosis of Stanford type A aortic dissection. No abnormal findings were observed in the ascending aorta by contrast-enhanced computed tomography (CT). Aortic dissection confined to the sinus of Valsalva has rarely been reported; however, TEE should still be considered for the differential diagnosis of acute AR, even if there is no evidence of dissection by TTE or contrast-enhanced CT.

The usefulness of measuring liver stiffness by transient elastography for assessing hepatic fibrosis in patients with various chronic liver diseases.

BACKGROUND/AIMS: The degree of hepatic fibrosis is an important factor for prognosis and management of patients with chronic liver disease; however, liver biopsy is an invasive method of measuring fibrosis. Here, we investigated the diagnostic utility of liver stiffness, as measured by transient elastography in assessing hepatic fibrosis of viral chronic liver disease and nonalcoholic fatty liver disease (NAFLD). METHODOLOGY: Four hundred and nine eligible patients underwent transient elastography to measure liver stiffness. Liver biopsy for histopathological assessment of fibrosis (F0-F4) was performed in 71 of these patients. Serum levels of hyaluronic acid were determined in 110 patients. We assessed liver stiffness in several chronic liver diseases and compared correlations among liver stiffness, hepatic fibrosis stage and serum hyaluronic acid levels. RESULTS: A steady stepwise increase in liver stiffness was observed with progressing severity of hepatic fibrosis (p<0.0001) in 71 patients who underwent liver biopsy. In 32 chronic viral hepatitis patients, measuring liver stiffness was useful for differentiating between F1, or F2, or F3 and F4, while in 32 NAFLD liver stiffness can differentiate between F0 and F1, F2, or F3, F1 and F3 or F4 and F2 and F4. There was no significant correlation between liver fibrotic stages and serum hyaluronic levels. CONCLUSIONS: The present data advocates measuring liver stiffness for assessing hepatic fibrosis is more sensitive in NAFLD than viral chronic diseases, and liver stiffness is useful compared to serum hyaluronic acid level in estimating hepatic fibrosis.

Longitudinal heterogeneity of coronary artery distensibility in plaques related to acute coronary syndrome.

BACKGROUND: How coronary distensibility contributes to stable or unstable clinical manifestations remains obscure. We postulated that the heterogeneous plaque distensibility is associated with unstable clinical presentations in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: Seventeen and 19 ACS-related and -unrelated lesions, respectively, were visualized using intravascular ultrasound imaging with simultaneous intracoronary pressure recording. Systolic and diastolic lumen cross-sectional areas were measured at the lesion site and at five evenly spaced sites between the proximal and distal reference sites. The coronary distensibility index and stiffness index ß were calculated for each site and averaged for each coronary segment. Maximal distensibility index, standard deviation and the difference between maximal and minimal distensibility indices within each segment were significantly higher in the ACS-related than -unrelated plaques (5.6 ± 2.3 vs. 3.7 ± 1.8, p < 0.001, 2.1 ± 0.9 vs. 1.1 ± 0.6, p < 0.001 and 5.3 ± 2.3 vs. 2.8 ± 1.5, p < 0.001, respectively). Moreover, the difference in the distensibility index between the lesion site of ACS-related plaques and the immediate proximal site was significantly larger (2.88 ± 2.35 vs. 1.17 ± 1.44, p = 0.022) than that in ACS-unrelated plaques. CONCLUSIONS: Coronary artery distensibility is longitudinally more heterogeneous in ACS-related than-unrelated plaques, especially between the lesion and the immediate proximal site.

Liver stiffness measured by transient elastography is a predictor of hepatocellular carcinoma development in viral hepatitis.

AIM: To investigate the value of liver stiffness in diagnosing hepatocellular carcinoma (HCC) among patients with viral hepatitis, and to prospectively investigate relationships between liver stiffness and HCC development. METHODS: Liver stiffness was measured by transient elastography for 157 patients with viral hepatitis, along with various other parameters potentially associated with HCC. HCC was initially present in 41 patients and absent in 116 patients, of whom 106 patients were followed prospectively for HCC development. Diagnostic performances of liver stiffness and other clinical parameters in predicting presence of HCC were evaluated using receiver operating characteristic (ROC) curves and area under the ROC curve (AUROC). RESULTS: Liver stiffness was significantly higher in patients with HCC (24.9 ± 19.5 kPa) than in patients without HCC (10.9 ± 8.4 kPa; P < 0.0001). Age (P < 0.0001), platelet cell count (P = 0.0001), prothrombin activity (P = 0.0009), alpha fetoprotein (P = 0.0091), and des-gamma-carboxy prothrombin (DCP) (P = 0.0099) also differed significantly between patients with and without HCC. The largest AUROC was for liver stiffness. Differences between liver stiffness and age, platelet cell count, prothrombin activity, and DCP were not significant, but the AUROC of liver stiffness was superior to that of alpha fetoprotein (P = 0.03850). Using a cut-off liver stiffness of 12.5 kPa, development of HCC was identified in 10 of the 106 patients followed. Multivariate analysis identified liver stiffness ≥12.5 kPa, age ≥60 years, and serum total bilirubin ≥1.0 mg/dL as significantly correlated with development of HCC. CONCLUSIONS: Liver stiffness as measured by transient elastography is a predictor of HCC development in viral hepatitis.

[Prophylaxis and treatment of NSAID-related peptic ulceration: present status and prospects].

Non-steroidal anti-inflammatory drugs (NSAIDs) including low dose aspirin have been widely prescribed to elderly patients for treatment of OA and RA as well as for primary and secondary prevention of atherosclerotic thrombotic events. Nonetheless, NSAIDs' effectiveness in the treatment and prophylaxis of such diseases may be limited by the risk of upper gastrointestinal (GI) complications such as ulceration, hemorrhage and perforation. NSAID administration is associated with several-fold increase in the upper GI bleeding in the Japanese general population. Such GI risk is known to increase in patients with a prior history of peptic ulcer disease, advanced age, and concomitant use of corticosteroids, clopidogrel, or anticoagulants with NSAIDs or aspirin. Mechanisms of NSAID-induced GI injury are believed to be through local effects within the GI mucosa that cause topical injury and through systemic inhibition of cyclo-oxygenase (CO) resulting in depletion of mucosal protective prostaglandins. Herein, we focus on the strategy to manage NSAID- or aspirin-induced peptic ulcerations and their complications, based on the scientific evidence.

Surgical treatment of HCC in a patient with lamivudine-resistant hepatitis B cirrhosis with adefovir dipivoxil.

We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine. She was started on adefovir (10 mg daily) while still continuing lamivudine therapy. Four mo later her liver function improved and serum Hepatitis B virus (HBV)-DNA level became undetectable. Three years after the start of additional adefovir treatment, hepatocellular carcinoma (HCC) was detected and the patient underwent a successful hepatectomy. Our findings suggest that the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis, but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis, allowing HCC surgery.