Non-invasive assessment of left ventricular filling pressure in aortic stenosis.

BACKGROUND: The assessment of left ventricular (LV) filling pressure (FP) is important for the management of aortic stenosis (AS) patients. Although, it is often restricted for predict LV FP in AS because of mitral annular calcification and a certain left ventricular hypertrophy. Thus, we tested the predictive ability of the algorithm for elevated LV FP in AS patients and also applied a recently-proposed echocardiographic scoring system of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score. METHODS: We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LV FP. LV diastolic dysfunction (DD) was graded according to the ASE/EACVI guidelines. The VMT score was defined as follows: time sequence of opening of mitral and tricuspid valves was scored to 0-2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava was dilated, one point was added and VMT score was finally calculated as 0-3. RESULTS: Of the 116 patients, 29 patients showed elevated PAWP. Ninety patients (93%) and 67 patients (63%) showed increased values for left atrium volume index (LAVI) and E/e', respectively when the cut-off values recommended by the guidelines were applied and thus the algorism predicted elevated PAWP with a low specificity and positive predictive value (PPV). VMT ≥ 2 predicted elevated PAWP with a sensitivity of 59%, specificity of 90%, PPV of 59%, and negative predictive value of 89%. An alternative algorithm that applied tricuspid regurgitation velocity and VMT scores was tested, and its predictive ability was markedly improved. CONCLUSION: VMT score was applicable for AS patients. Alternative use of VMT score improved diagnostic accuracy of guideline-recommended algorism.

Exercise Capacity and Clinical Outcomes in Chronic Heart Failure Patients with Mild Tricuspid Regurgitation.

AIM: The present study aimed to investigate the impact of mild tricuspid regurgitation (TR) on the exercise capacity or clinical outcomes in patients with chronic heart failure (CHF). METHODS AND RESULTS: The study enrolled 511 patients with CHF who underwent cardiopulmonary exercise testing (CPET) between 2013 and 2018. The primary outcome was a composite of heart failure hospitalization and death. Patients with mild TR (n = 324) or significant TR (moderate or greater; n = 60) displayed worse NHYA class and reduced exercise capacity on CPET than those with non-TR (n = 127), but these were more severely impaired in patients with significant TR. A total of 90 patients experienced events over a median follow-up period of 3.3 (interquartile range 0.8-5.5) years. Patients with significant TR displayed a higher risk of events, while patients with mild TR had a 3.0-fold higher risk of events than patients with non-TR (hazard ratio (HR) 3.01; 95% confidence interval (CI), 1.50-6.07). Multivariate Cox regression analysis showed that, compared with non-TR, mild TR was associated with increased adverse events, even after adjustment for co-variates (HR 2.97; 95% CI, 1.35-6.55). CONCLUSIONS: TR severity was associated with worse symptoms, reduced exercise capacity, and poor clinical outcomes. Even patients with mild TR had worse clinical characteristics than those with non-TR.

Impact of Cardiac Power Output on Exercise Capacity and Clinical Outcome in Patients With Chronic Heart Failure.

Less data are available regarding the impact of cardiac power output on exercise capacity or clinical outcome in patients with chronic heart failure (CHF). The study enrolled 280 consecutive patients with CHF referred for cardiopulmonary exercise testing and right-sided heart catheterization between 2013 and 2018. The primary outcome was composite of heart failure hospitalization or death. Cardiac power output was calculated as (mean arterial pressure × CO) ÷ 451. Patients with low cardiac power output (<0.53 W, n = 99) were older and had a higher brain natriuretic peptide level than patients with high cardiac power output (≥0.53W, n = 181). Cardiac power output was correlated with peak oxygen consumption (peak V̇O2), peak workload achievement, and ventilatory efficiency (V̇E/V̇CO2 slope) in cardiopulmonary exercise testing, whereas each of cardiac output or mean arterial pressure was not. There were 48 patients with events over a median follow-up period of 3.5 (interquartile range 1.0 to 6.0) years. Patients with low cardiac power output had about a 2-fold higher risk of events than those with a high cardiac power output (hazard ratio 1.97, 95% confidence interval 1.12 to 3.48). In the multivariable Cox regression, a 0.1-W decrease in cardiac power output was associated with 19% increased adverse events (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). In conclusion, cardiac power output was associated with reduced exercise capacity and poor clinical outcome, suggesting that cardiac power output is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting cardiac power output to improve the exercise capacity or clinical outcome in patients with CHF.

Paradoxical increase in global longitudinal strain by handgrip exercise despite left ventricular diastolic dysfunction.

BACKGROUND: Although global longitudinal strain (GLS) is recognized as a sensitive marker of intrinsic left ventricular (LV) dysfunction, its afterload dependency has also been pointed. We hypothesized that decrease in GLS during handgrip exercise could be more sensitive marker of intrinsic myocardial dysfunction. METHODS: Handgrip exercise-stress echocardiography was performed in 90 cardiovascular disease patients with preserved LV ejection fraction. LV diastolic function was graded according to the guidelines. Diastolic wall stress (DWS) and ratio of left atrial (LA) volume index to late-diastolic mitral annular velocity (LAVI/a') were measured at rest as LV stiffness. As well, LA strains were measured to assess LA function. GLS was expressed as absolute value and significant changes in GLS by handgrip exercise was defined as changes over prespecified mean absolute test-retest variability (2.65%). RESULTS: While mean value of GLS did not change by the exercise, substantial patients showed significant changes in GLS: decreased (group I, n = 28), unchanged (group II, n = 34), and increased (group III, n = 28). Unexpectedly, patients in group I did not show any clinical and echocardiographic characteristics, while those in group III were characterized by elevated natriuretic peptide levels, blunted heart rate response to handgrip exercise, and advanced LV diastolic dysfunction. Multivariable analyses revealed that DWS, left atrial booster strain, and grade II or more diastolic dysfunction determined the increase in GLS even after adjustment for elevated natriuretic peptides and the changes in heart rate by the exercise. CONCLUSION: In contrast to our hypothesis, paradoxical increase in GLS by handgrip exercise could be associated with advanced LV diastolic dysfunction in cardiovascular patients with preserved LV ejection fraction. Our findings suggest that HG exercise for heart failure patients does not enhance the afterload straightforward, resulting in variable changes of GLS according to the individual conditions.

Multimodal Imaging of Constrictive Pericarditis Induced by Long-term Pergolide Treatment for Parkinson's Disease.

We herein report the first case of constrictive pericarditis (CP) induced by long-term pergolide treatment for Parkinson's disease that was assessed using multimodal imaging in a 72-year-old patient with leg edema and dyspnea. The patient was correctly diagnosed with CP using multimodal imaging and successfully treated with pericardiectomy. The treatment history of Parkinson's disease and pathological findings of the removed pericardium suggested that long-term pergolide was the cause of CP. Properly recognizing pergolide as the cause of CP and accurately diagnosing CP using multimodal imaging may contribute to the early detection and treatment of pergolide-induced CP.

Application of an echocardiographic scoring system of left ventricular filling pressure to diagnose acute heart failure in patients complaining dyspnea.

BACKGROUND: Dyspnea is a common symptom in acute heart failure (AHF) patients. Although an accurate and rapid diagnosis of AHF is essential to improve prognosis, estimation of left ventricular (LV) filling pressure (FP) remains challenging, especially for noncardiologists. We evaluated the usefulness of a recently-proposed parameter of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, to detect AHF in patients complaining of dyspnea. METHODS: Echocardiography and lung ultrasonography (LUS) were performed in 121 consecutive patients (68 ±â€¯14 years old, 75 males) presenting with dyspnea. The VMT score was determined from the atrioventricular valve opening phase (tricuspid valve first: 0, simultaneous: 1, mitral valve first: 2) and inferior vena cava dilatation (absent: 0, present: 1), and VMT ≥2 was judged as positive. LUS was performed with the 8 zones method and judged as positive if 3 or more B-lines were observed in bilateral regions. The AHF diagnosis was performed by certified cardiologists according to recent guidelines. RESULTS: Of the 121 patients, 33 were diagnosed with AHF. The sensitivity and specificity for diagnosing AHF were 64 % and 84 % for LUS and 94 % and 88 % for VMT score. In logistic regression analysis, VMT score showed a significantly higher c-index than LUS (0.91 vs 0.74, p = 0.002). In multivariable analyses, VMT score was associated with AHF independently of clinically relevant covariates and LUS. In addition, serial assessment of VMT score followed by LUS provided a diagnostic flow chart to diagnose AHF (VMT 3: AHF definitive, VMT 2 and LUS positive: AHF highly suspicious; VMT 2 and LUS negative: further investigation is needed; VMT ≤ 1: AHF rejected). CONCLUSIONS: VMT score showed high diagnostic accuracy in diagnosing AHF. Combined assessment of the VMT score and LUS could become a reliable strategy for diagnosis of AHF by non-cardiologists.

Impact of right ventricular stiffness on discordance between hemodynamic parameter and regurgitant volume in patients with pulmonary regurgitation.

BACKGROUND: Accurate detection of significant pulmonary regurgitation (PR) is critical in management of patients after right ventricular (RV) outflow reconstruction in Tetralogy of Fallot (TOF) patients, because of its influence on adverse outcomes. Although pressure half time (PHT) of PR velocity is one of the widely used echocardiographic markers of the severity, shortened PHT is suggested to be seen in conditions with increased RV stiffness with mild PR. However, little has been reported about the exact characteristics of patients showing discrepancy between PHT and PR volume in this population. METHODS: Echocardiography and cardiac magnetic resonance imaging (MRI) were performed in 74 TOF patients after right ventricular outflow tract (RVOT) reconstruction [32 ± 10 years old]. PHT was measured from the continuous Doppler PR flow velocity profile and PHT < 100 ms was used as a sign of significant PR. Presence of end-diastolic RVOT forward flow was defined as RV restrictive physiology. By using phase-contrast MRI, forward and regurgitant volumes through the RVOT were measured and regurgitation fraction was calculated. Significant PR was defined as regurgitant fraction ≥ 25%. RESULTS: Significant PR was observed in 54 of 74 patients. While PHT < 100 ms well predicted significant PR with sensitivity of 96%, specificity of 52%, and c-index of 0.72, 10 patients showed shortened PHT despite regurgitant fraction < 25% (discordant group). Tricuspid annular plane systolic excursion and left ventricular (LV) ejection fraction were comparable between discordant group and patients showing PHT < 100 ms and regurgitant fraction ≥ 25% (concordant group). However, discordant group showed significantly smaller mid RV diameter (30.7 ± 4.5 vs. 39.2 ± 7.3 mm, P < 0.001) and higher prevalence of restrictive physiology (100% vs. 42%, P < 0.01) than concordant group. When mid RV diameter ≥ 32 mm and presence of restrictive physiology were added to PHT, the predictive value was significantly improved (sensitivity: 81%, specificity: 90%, and c-index: 0.89, P < 0.001 vs. PHT alone by multivariable logistic regression model). CONCLUSION: Patients with increased RV stiffness and non-enlarged right ventricle showed short PHT despite mild PR. Although it has been expected, this was the first study to demonstrate the exact characteristics of patients showing discrepancy between PHT and PR volume in TOF patients after RVOT reconstruction.

Non-atrophic gastric mucosa is an independently associated factor for superficial non-ampullary duodenal epithelial tumors: a multicenter, matched, case-control study.

BACKGROUND/AIMS: The etiology of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. Recent studies have reported conflicting associations between duodenal tumor development and Helicobacter pylori infection or endoscopic gastric mucosal atrophy. As such, the present study aimed to clarify the relationship between SNADETs and H. pylori infection and/or endoscopic gastric mucosal atrophy. METHODS: This retrospective case-control study reviewed data from 177 consecutive patients with SNADETs who underwent endoscopic or surgical resection at seven institutions in Japan over a three-year period. The prevalence of endoscopic gastric mucosal atrophy and the status of H. pylori infection were compared in 531 sex- and age-matched controls selected from screening endoscopies at two of the seven participating institutions. RESULTS: For H. pylori infection, 85 of 177 (48.0%) patients exhibited SNADETs and 112 of 531 (21.1%) control patients were non-infected (p<0.001). Non-atrophic mucosa (C0 to C1) was observed in 96 of 177 (54.2%) patients with SNADETs and 112 of 531 (21.1%) control patients (p<0.001). Conditional logistic regression analysis revealed that non-atrophic gastric mucosa was an independent risk factor for SNADETs (odds ratio, 5.10; 95% confidence interval, 2.44-8.40; p<0.001). CONCLUSION: Non-atrophic gastric mucosa, regardless of H. pylori infection status, was a factor independently associated with SNADETs.

Usefulness of the pulmonary venous flow waveform for assessing left atrial stiffness.

PURPOSE: This study investigated the novel non-invasive left atrial (LA) stiffness parameter using pulmonary venous (PV) flow measurements and the clinical usefulness of the novel LA stiffness parameter. METHODS: We retrospectively analyzed 237 patients who underwent right heart catheterization and echocardiography less than one week apart. From the pulmonary artery wedge pressure waveform, the difference between x-descent and v-wave (ΔP) was measured. Using the echocardiographic biplane method of disks, the difference between LA maximum volume and that just before atrial contraction (ΔVMOD) was calculated, and the ΔP/ΔVMOD was calculated as a standard LA stiffness index. From the PV flow waveform, the peak systolic velocity (S), peak diastolic velocity (D), and minimum velocity between them (R) were measured, and S/D, S/R, and D/R were calculated. From the speckle tracking echocardiography-derived time-LA volume curve, the difference between LA maximum volume and that just before atrial contraction (ΔVSTE) was measured. Each patient's prognosis was investigated until three years after echocardiography. RESULTS: Among the PV flow parameters, D/R was significantly correlated with ΔP (r = 0.62), and the correlation coefficient exceeded that between S/D and ΔP (r = - 0.39) or S/R and ΔP (r = 0.14). The [D/R]/ΔVSTE was significantly correlated with ΔP/ΔVMOD (r = 0.61). During the follow-up, 37 (17%) composite endpoints occurred. Kaplan-Meier analysis showed that patients with [D/R]/ΔVSTE greater than 0.13 /mL were at higher risk of cardiac events. CONCLUSION: The [D/R]/ΔVSTE was useful for assessing LA stiffness non-invasively and might be valuable in the prognostic evaluation of patients with cardiac diseases.

Associations of right ventricular pulsatile load and cardiac power output to clinical outcomes in heart failure: Difference from systemic circulation.

BACKGROUND: Although left ventricular (LV) cardiac power output (CPO) is a powerful prognostic indicator in heart failure (HF), the significance of right ventricular (RV) CPO is unknown. In contrast, RV pulsatile load is a key prognostic marker in HF. We investigated the impact of RV-CPO and pulsatile load on cardiac outcome and the prognostic performance of the combined systemic and pulmonary circulation parameters in HF. METHODS: Right heart catheterization and echocardiography were performed in 231 HF patients (62 ±â€¯16 years, LV ejection fraction 42 ±â€¯18 %). Invasive and noninvasive CPOs were calculated from mean systemic or pulmonary arterial pressure and cardiac output. LV-CPO was then normalized to LV mass (LV-P/M). Pulmonary arterial capacitance and the ratio of acceleration time to ejection time (AcT/ET) of RV outflow were used as parameters of RV pulsatile load. The primary endpoints, defined as a composite of cardiac death, HF hospitalization, ventricular arrythmia, and LVAD implantation after the examination, were recorded. RESULTS: Noninvasive CPOs were moderately correlated with invasive ones (LV: ρ = 0.787, RV: ρ = 0.568, and p < 0.001 for both). During a median follow-up period of 441 days, 57 cardiovascular events occurred. Lower LV-P/M and higher RV pulsatile load were associated with cardiovascular events; however, RV-CPO was not associated with the outcome. Echocardiographic LV-P/M and AcT/ET showed significant incremental prognostic value over the clinical parameters. CONCLUSIONS: RV pulsatile load assessed by AcT/ET may be a predictor of clinical events in HF patients. The combination of echocardiographic LV-P/M and AcT/ET could be a novel noninvasive prognostic indicator in HF patients.

Applicability of new proposed criteria for iron deficiency in Japanese patients with heart failure.

AIMS: Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). A recent study showed that ID defined by the current guideline criteria was not associated with worse clinical outcomes, and new ID criteria was proposed in patients with HF. However, the external applicability of the new proposed criteria is unclear. We sought to investigate the applicability of the proposed ID criteria in Japanese patients with HF. METHODS AND RESULTS: We prospectively examined 763 patients with chronic HF from a Japanese multicentre registry. The proposed ID criteria were transferrin saturation (TSAT) < 20% and serum iron ≤13 mmol/L and the guideline ID criteria were serum ferritin <100 ng/mL or, when ferritin was 100-299 ng/mL, TSAT <20%. Among all patients (456 male, mean age 71 ± 13 years), 213 (28%) and 444 (58%) met the proposed and guideline ID criteria, respectively. During a median follow-up period of 436 days (interquartile range 297-565), the primary outcome of all-cause mortality occurred in 56 (7%) patients. There was no significant difference in the primary outcome between the patients with and without guideline ID criteria (P = 0.32), whereas patients with serum iron ≤10 µmol/L showed higher mortality (P = 0.002). In multivariable Cox regressions, the proposed ID criteria, but not guideline ID criteria, were independently associated with the risk of all-cause mortality (HR 2.01, 95% CI 1.16-3.51 and HR 1.32, 95% CI 0.76-2.28, respectively), even after adjustment for covariates. CONCLUSIONS: When defined by the proposed criteria and not the guideline criteria, ID was associated with higher mortality in patients with chronic HF, suggesting that the proposed ID criteria is applicable to the Japanese population.

Determinants of exercise capacity in patients with heart failure without left ventricular hypertrophy.

BACKGROUND: Determinants of exercise intolerance in a phenotype of heart failure with preserved ejection fraction (HFpEF) with normal left ventricular (LV) structure have not been fully elucidated. METHODS: Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 44 HFpEF patients without LV hypertrophy. Exercise capacity was determined by peak oxygen consumption (peak VO2). Doppler-derived cardiac output (CO), transmitral E velocity, systolic (LV-s') and early diastolic mitral annular velocities (e'), systolic pulmonary artery (PA) pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and peak systolic right ventricular (RV) free wall velocity (RV-s') were measured at rest and exercise. E/e' and TAPSE/SPAP were used as an LV filling pressure parameter and RV-PA coupling, respectively. RESULTS: During exercise, CO, LV-s', RV-s', e', and SPAP were significantly increased (p < 0.05 for all), whereas E/e' remained unchanged and TAPSE/SPAP was significantly reduced (p < 0.001). SPAP was higher and TAPSE/SPAP was lower at peak exercise in patients showing lower-half peak VO2. In univariable analyses, LV-s' (R = 0.35, p = 0.022), SPAP (R = -0.40, p = 0.008), RV-s' (R = 0.47, p = 0.002), and TAPSE/SPAP (R = 0.42, p = 0.005) were significantly correlated with peak VO2. In multivariable analyses, not only SPAP, but also TAPSE/SPAP independently determined peak VO2 even after the adjustment for clinically relevant parameters. CONCLUSIONS: In HFpEF patients without LV hypertrophy, altered RV-PA coupling by exercise could be associated with exercise intolerance, which might not be caused by elevated LV filling pressure.

Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers.

We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan-Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38-90 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8-82.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient's condition. The median follow-up of surviving patients was 63 months (range, 1-126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events ≥ grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications.

Usefulness of the clip-and-snare method using the pre-looping technique for endoscopic submucosal dissection of gastric neoplasia: a randomized controlled trial.

BACKGROUND: The clip-and-snare method using the pre-looping technique (CSM-PLT) was developed as a traction method for endoscopic submucosal dissection (ESD) of gastric neoplasia. However, its usefulness has not been clearly established; thus, we aimed to assess the efficacy of CSM-PLT in gastric ESD. METHODS: In this multicenter, randomized controlled trial, patients with gastric adenoma or carcinoma with absolute or expanded indications for ESD were randomized into conventional ESD and CSM-PLT groups, using the minimization method based on operator experience, tumor location, tumor size, and excision device. The primary endpoint was ESD procedure time. Secondary endpoints were en bloc and R0 resection rates, and complications. RESULTS: We enrolled 402 patients between July 2017 and February 2020. After excluding patients with deviations from the protocol, we finally analyzed the data of 192 and 186 patients in the conventional and CSM-PLT groups, respectively. The procedure time was significantly shorter in the CSM-PLT group than in the conventional group (58.0 vs. 69.7 min; P=0.009). All lesions were resected en bloc. The R0 resection rate tended to be higher in the CSM-PLT group (P=0.09). No significant differences in complications were observed between the 2 groups. CONCLUSIONS: CSM-PLT is beneficial for gastric ESD when compared with the conventional technique. CSM-PLT significantly reduced procedure times and improved R0 resection rates.

Determinants of altered left ventricular suction in pre-capillary pulmonary hypertension.

AIMS: Although the left ventricular (LV) dysfunction in pre-capillary pulmonary hypertension (PH) has been recently recognized, the mechanism of LV dysfunction in this entity is not completely understood. We thus aimed to elucidate the determinants of intraventricular pressure difference (IVPD), a measure of LV suction, in pre-capillary PH. METHODS AND RESULTS: Right heart catheterization and echocardiography were performed in 86 consecutive patients with pre-capillary PH (57 ± 18 years, 85% female). IVPD was determined using colour M-mode Doppler to integrate the Euler equation. In overall, IVPD was reduced compared to previously reported value in normal subjects. In univariable analyses, QRS duration (P = 0.028), LV ejection fraction (P = 0.006), right ventricular (RV) end-diastolic area (P < 0.001), tricuspid annular plane systolic excursion (P = 0.004), and LV early-diastolic eccentricity index (P = 0.009) were associated with IVPD. In the multivariable analyses, RV end-diastolic area and LV eccentricity index independently determined the IVPD. CONCLUSION: Aberrant ventricular interdependence caused by RV enlargement could impair the LV suction. This study first applied echocardiographic IVPD, a reliable marker of LV diastolic suction, to investigate the mechanism of LV diastolic dysfunction in pre-capillary PH.

Difference in left atrial myocardial dynamics during reservoir phase between hypertrophic cardiomyopathy and hypertensive heart determined using three-dimensional speckle tracking echocardiography.

We aimed to investigate left atrial (LA) myocardial dynamics during reservoir phase using three-dimensional speckle-tracking echocardiography (3DSTE) focusing on its longitudinal-circumferential relationship in patients with left ventricular (LV) hypertrophy and clarifying the difference in LA myocardial reservoir dynamics between hypertrophic cardiomyopathy (HCM) and hypertension with LV hypertrophy (HT-LVH). We studied 4 age-matched groups consisting of 27 patients with HCM, 16 with HT-LVH, 22 hypertensive patients without LV hypertrophy (HT), and 18 normal controls. Using 3DSTE, we measured LA global longitudinal strain (LA-LSR), global circumferential strain (LA-CSR), and global area strain (LA-ASR) during the reservoir phase, as well as LV global longitudinal strain (LV-LS), global circumferential strain (LV-CS), and global area strain (LV-AS). LA-LSR was significantly lower in the HCM and HT-LVH groups than in the controls, but there was no significant difference between the HCM and HT-LVH groups. LA-CSR and LA-ASR were significantly lower in the HCM group than in the other three groups, among which no significant difference was detected. In all subjects, LA-LSR was significantly correlated with LV-LS but not with LV-CS. LA-CSR was correlated with neither LV-LS nor LV-CS. In conclusion, both longitudinal and circumferential LA myocardial expansion during reservoir phase were reduced in HCM, while only the longitudinal one was reduced in HT-LVH. Reduction of LA circumferential expansion may reflect a more serious and intrinsic impairment of LA myocardial distensibility in HCM. Measuring LA-CSR and LA-ASR using 3DSTE would contribute to a more accurate understanding of LA reservoir function abnormality in HCM.

Efficacy of polyglycolic acid sheeting with fibrin glue for perforations related to gastrointestinal endoscopic procedures: a multicenter retrospective cohort study.

OBJECTIVES: Gastrointestinal (GI) perforations are one of the major adverse events of endoscopic procedures. Polyglycolic acid (PGA) sheets with fibrin glue have been reported to close GI perforations. However, its clinical outcome has not yet been fully investigated; thus, we conducted a multicenter retrospective observational study to assess the efficacy of PGA sheeting for GI perforation. METHODS: The medical records of patients who underwent PGA sheeting for endoscopic GI perforations between April 2013 and March 2018 in 18 Japanese institutions were retrospectively analyzed. PGA sheeting was applied when the clip closure was challenging or failed to use. Perforations were filled with one or several pieces of PGA sheets followed by fibrin glue application through an endoscopic catheter. Nasal or percutaneous drainage and endoscopic clipping were applied as appropriate. Clinical outcomes after PGA sheeting for intraoperative or delayed perforations were separately evaluated. RESULTS: There were 66 intraoperative and 24 delayed perforation cases. In intraoperative cases, successful closure was attained in 60 cases (91%). The median period from the first sheeting to diet resumption was 6 days (interquartile range [IQR], 4-8.8 days). Large perforation size (≥ 10 mm) and duodenal location showed marginal significant relationship to higher closure failure of intraoperative perforations. In delayed perforation cases, all cases had successful closure. The median period from the first sheeting to diet resumption was 10 days (IQR, 6-37.8 days). No adverse events related to PGA sheeting occurred. CONCLUSION: Endoscopic PGA sheeting could be a therapeutic option for GI perforations related to GI endoscopic procedures.

Visual echocardiographic scoring system of the left ventricular filling pressure and outcomes of heart failure with preserved ejection fraction.

AIMS: Elevated left ventricular filling pressure (LVFP) is a powerful indicator of worsening clinical outcomes in heart failure with preserved ejection fraction (HFpEF); however, detection of elevated LVFP is often challenging. This study aimed to determine the association between the newly proposed echocardiographic LVFP parameter, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, and clinical outcomes of HFpEF. METHODS AND RESULTS: We retrospectively investigated 310 well-differentiated HFpEF patients in stable conditions. VMT was scored from 0 to 3 using two-dimensional echocardiographic images, and VMT ≥2 was regarded as a sign of elevated LVFP. The primary endpoint was a composite of cardiac death or heart failure hospitalization during the 2 years after the echocardiographic examination. In all patients, Kaplan-Meier curves showed that VMT ≥2 (n = 54) was associated with worse outcomes than the VMT ≤1 group (n = 256) (P < 0.001). Furthermore, VMT ≥2 was associated with worse outcomes when tested in 100 HFpEF patients with atrial fibrillation (AF) (P = 0.026). In the adjusted model, VMT ≥2 was independently associated with the primary outcome (hazard ratio 2.60, 95% confidence interval 1.46-4.61; P = 0.001). Additionally, VMT scoring provided an incremental prognostic value over clinically relevant variables and diastolic function grading (χ2 10.8-16.3, P = 0.035). CONCLUSIONS: In patients with HFpEF, the VMT score was independently and incrementally associated with adverse clinical outcomes. Moreover, it could also predict clinical outcomes in HFpEF patients with AF.

Lenvatinib-induced tumor lysis syndrome in a patient with advanced hepatocellular carcinoma: a case report.

Tumor lysis syndrome (TLS) is an oncologic emergency caused by release of intracellular tumor components due to massive tumor lysis and is rare in patients with hepatocellular carcinoma (HCC). We describe a case of TLS with rupture of HCC induced by lenvatinib in a patient with advanced HCC. A 72-year-old man who presented with right upper abdominal pain was diagnosed as having advanced HCC with a high tumor burden by contrast-enhanced computed tomography and percutaneous hepatic tumor biopsy. He was started on lenvatinib 12 mg once daily when his tumor progressed despite one-shot hepatic arterial infusion chemotherapy. On day 2 of treatment with lenvatinib, he developed severe upper abdominal pain and was diagnosed as having TLS with HCC rupture by laboratory tests and contrast-enhanced computed tomography. Urgent treatment with transarterial embolization, hemodialysis, and blood transfusion therapy was successful. The patient was then restarted on oral lenvatinib at a reduced dose without recurrence of TLS. TLS is a rare potential complication of lenvatinib in patients with advanced HCC and a high tumor burden.

Efficacy of Endoscopic Evaluation of Acute Radiation Esophagitis during Chemoradiotherapy with Proton Beam Therapy Boost for Esophageal Cancer.

BACKGROUND/AIM: To evaluate the utility of endoscopy for assessing radiation esophagitis during chemoradiotherapy (CRT) with proton beam therapy (PBT) boost for esophageal cancer. METHODS: Between December 2012 and December 2016, 38 patients with esophageal cancer were treated with CRT with PBT boost. To evaluate radiation esophagitis, endoscopy was performed after administration of CRT with standard PBT boost (total dose 50-60 Gy relative biological effectiveness [RBE]). Radiation esophagitis was evaluated and classified into 5 newly developed endoscopic grades (Fukui Acute Radiation Esophagitis [FARE] grade). The additional PBT boost was then adjusted and delivered (2-20 Gy [RBE]) to a maximum total dose of 74.4 Gy (RBE) based on the degree of radiation esophagitis, probability of residual tumor, and patient's general condition. To evaluate the utility of endoscopic examination, the incidences of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) were determined at the time of endoscopic examination after CRT with standard PBT boost (50-60 Gy [RBE]) and at the completion of treatment (60-74.4 Gy [RBE]), as well as during the 90 days from the beginning of treatment. RESULTS: There was a significant correlation between FARE grade and CTCAE esophagitis grade (ρ = 0.48; p = 0.03). Moreover, endoscopy detected severe esophagitis in an asymptomatic patient. Radiation dose escalation was achieved without severe acute adverse events. There was no significant difference between the incidence of acute toxicity at the time of the CRT with standard PBT boost (50-60 Gy [RBE]) and the higher dose at the completion of treatment (60-74.4 Gy [RBE]), which suggests this dose escalation strategy is safe. CONCLUSION: Endoscopic evaluation of radiation esophagitis using FARE grades was safely performed and useful for adjusting added radiation to ensure the safety of escalations in CRT with PBT boost for esophageal cancer.