Early prediction of cytokine release syndrome by measuring phosphate and magnesium levels following chimeric antigen receptor T cell therapy.

Introduction: Cytokine release syndrome (CRS) is a life-threatening side effect of chimeric antigen receptor T (CAR-T) cell therapy. This study investigated whether serum inorganic phosphate (IP) and magnesium (Mg) levels are predictive markers of CRS development. Methods: This single-center retrospective cohort study enrolled 16 consecutive patients with diffuse large B-cell lymphoma who had received CAR-T cell therapy. Logistic regression models with generalized estimating equations were used to evaluate whether changes in IP and Mg levels from their baseline values were associated with the development of CRS within 48 hours. Results: Decreased IP and Mg levels from baseline (per 10% change) were associated with an increased CRS incidence (adjusted odds ratio 2.18 [95% confidence interval (CI), 1.31-3.62], 3.18 [95% CI, 1.57-6.44], respectively). Conclusions: Changes in IP and Mg concentrations within 48 hours may be useful predictive markers of CRS onset.

Prospective multicenter evaluation of moving cell metallic stents in endoscopic multiple stent deployment for hepatic hilar obstruction.

BACKGROUND AND AIM: Bilateral stent deployment for malignant biliary obstruction (MHBO) can be achieved using side-by-side (SBS) or stent-in-stent (SIS) procedures. Compared with SBS techniques, the procedural steps of SIS are technically complex due to the necessity of introducing the delivery system into a contralateral biliary tract through the mesh of the SEMS. To overcome this issue, a novel uncovered SEMS, the HILZO Moving Cell Stent (MCS) has been released. The present study examined the technical feasibility of treating MHBO using bilateral deployment of this novel stent without dilating the mesh of the first stent to achieve insertion of the second stent within a single session, using a prospective, multicenter setting. METHOD: The primary outcome in the present study was the technical success rate. Technical success was defined as deployment of bilateral MCSs into two or more biliary tracts using SIS without a dilation device in a single-session. RESULTS: A total of 27 patients with complications of MHBO were enrolled in this study. Bilateral SIS using two MCS was successfully performed in 23 patients without using dilation devices among 27 patients (initial technical success rate; 85.2%). Median time to recurrent biliary obstruction (TRBO) was 271 days. Stent dysfunction was observed in 12 patients (44.4%), and re-intervention was successfully performed in all patients without one patient who instead received best supportive care. CONCLUSIONS: The SIS technique using MCS without dilation of the mesh may be technically feasible and safe. In addition, this may be useful for re-intervention. Further comparative randomized trials are needed.

Transluminal intrahepatic bile duct stone removal using a novel spiral basket catheter via the endoscopic ultrasound-guided hepaticogastrostomy route (with video).

Recently, endoscopic ultrasound (EUS)-guided biliary drainage has been developed as an alternative biliary drainage technique for failed endoscopic retrograde cholangiopancreatography (ERCP) or inaccessible papilla. Among the various EUS-guided biliary drainage procedures, EUS-guided hepaticogastrostomy (HGS) can be performed in patients with surgically altered anatomy. More recently, various transluminal treatments have been described after EUS-HGS, such as antegrade stone removal. In patients with hepaticojejunostomy strictures, stone extraction into the intestine might be challenging even after performing hepaticojejunostomy stricture dilation using a balloon catheter. In such cases, transluminal stone removal is considered an alternative method. With transluminal stone removal, a small stone that escapes from the conventional basket or from a balloon catheter could migrate into the branch bile ducts. The novel spiral basket catheter available in Japan. The wires form a helix shape, wherein each wire is wound counterclockwise, and the winding pitch becomes gradually tighter from the proximal portion to the tip. As the winding pitch is smaller and the wires are in closer contact with the bile duct wall as compared with conventional basket catheter, small bile duct stones can be easily captured by simply pulling back the catheter while the basket is open. In addition, even during withdrawal inside the bile duct, a high retrieval performance is assured by the special design that maintains the opening width on the top end. Therefore, transluminal stone removal using this novel basket catheter might be clinically useful, although further prospective evaluation of a larger number of cases is needed.

Systemic Lupus Erythematosus from Lupus Enteritis.

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Significance of isolated papillary muscle hypertrophy: A comparison of left ventricular hypertrophy diagnosed using electrocardiography vs echocardiography.

AIMS: The clinical significance of papillary muscle hypertrophy and its electrocardiography (ECG) findings has not been fully elucidated. This study aimed to investigate the relationship between ECG findings and papillary muscle hypertrophy and to confirm the importance of papillary muscle measurements on transthoracic echocardiography (TTE). METHODS AND RESULTS: Of the 237 consecutive patients who showed left ventricular hypertrophy (LVH) pattern on a 12-lead ECG, TTE data were available for 101 patients. The patients were divided into the two groups according to the presence (ECG-LVH [strain pos] group, n = 60) or absence (ECG-LVH [strain neg] group, n = 41) of LV strain pattern (study 1). The prevalence of papillary muscle hypertrophy using TTE was significantly higher in the ECG-LVH (strain neg) group than in the ECG-LVH (strain pos) group (P = .0002). Of the 42 cases with papillary muscle hypertrophy, 5 cases (12%) showed isolated papillary muscle hypertrophy with normal geometry. ECG data were prospectively analyzed for 36 patients who were diagnosed with papillary muscle hypertrophy by TTE (study 2). The prevalence of LV strain pattern was significantly higher in patients with LV wall hypertrophy than in those without LV wall hypertrophy (P = .04). Of the 25 cases with papillary muscle hypertrophy, 6 cases (24%) showed normal geometry and 4 cases (16%) showed ECG abnormality. CONCLUSIONS: Isolated papillary muscle hypertrophy can cause ECG abnormalities such as LV high voltage and LV strain pattern. Particular attention must be paid to the papillary muscle during echocardiographic examinations.

The analysis of mitral annular disjunction detected by echocardiography and comparison with previously reported pathological data.

BACKGROUND: Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus and is pathologically defined by a separation between the atrial wall-mitral valve junction and the left ventricular attachment. Mitral annular disjunction can cause hypermobility of the mitral valve apparatus and is often associated with mitral valve prolapse (MVP). The aim of this study was to investigate the frequency and characteristics of mitral annular disjunction in the patients referred to an echocardiography laboratory and to compare these with previously reported pathological data. METHODS AND RESULTS: We retrospectively studied 1439 patients (mean age 65 ± 17 years, 58% male) referred to our echocardiography laboratory from 6 January 2014 to 31 March 2014. The echocardiographic parameters were compared between the patients with and without mitral annular disjunction. There were 125 cases (8.7%) with mitral annular disjunction, of which 15 (12%) also had MVP. The number of MVP patients in the group with mitral annular disjunction was significantly larger than in the group without mitral annular disjunction (p < 0.0001). The grade of mitral regurgitation was not significantly different between the two groups. CONCLUSIONS: Mitral annular disjunction was detected not only in patients with a myxomatous mitral valve but also in normal cases. The number of MVPs was significantly larger in patients with mitral annular disjunction than patients without mitral annular disjunction. Further investigation is needed to clarify the clinical significance of the mitral annular disjunction detected by routine echocardiography.

Mitral annular morphology in mitral valve disease with three-dimensional transesophageal echocardiography.

BACKGROUND AND AIM OF THE STUDY: Three-dimensional (3D) transesophageal echocardiography (TEE) is useful for the quantification of mitral valve structures. The study aim was to investigate, in quantitative manner, any differences in mitral valve anatomy among patients with mitral valve prolapse (MVP) or functional mitral regurgitation (FMR), compared to normal control subjects. METHODS: 3D-TEE was performed in 20 MVP patients, 10 FMR patients and in 15 control subjects. Analyses of the full-volume 3D mitral valve data sets were performed offline, using Q-Lab software. RESULTS: Distinctive patterns were identified in annular geometric changes in normal subjects compared to patients with MVP or FMR. Patients with FMR showed significant annular anterior to posterior dilatation (34.6 +/- 8.3 mm versus 28.4 +/- 2.9 mm, p < 0.04: FMR versus control), whereas in patients with MVP dilatation in the anterolateral to posteromedial diameter was more prominent (41.0 +/- 5.9 mm versus 36.6 +/- 2.4 mm, p < 0.03; MVP versus control). CONCLUSION: 3D-TEE represents a useful method for the evaluation of mitral valve geometry.

Left ventricular systolic dyssynchrony index by three-dimensional echocardiography in patients with decreased left ventricular function: comparison with tissue Doppler echocardiography.

BACKGROUND: Three-dimensional echocardiography (3DE) can simultaneously assess left ventricular (LV) regional systolic motion and global LV mechanical dyssynchrony. METHODS: We used 3DE to measure systolic dyssynchrony index (SDI) (standard deviation of the time from cardiac cycle onset to minimum systolic volume in 17 LV segments) in 100 patients and analyzed the association of SDI with other parameters for LV systolic function or dyssynchrony. Eighteen patients who underwent cardiac resynchronization therapy (CRT) were also evaluated at 6 months after CRT, and the association of baseline SDI and tissue Doppler imaging (TDI) dyssynchrony index (Ts-SD) with the change of LV end-systolic volume (ESV) analyzed. Ts-SD was calculated using the standard deviation of the time from the QRS complex to peak systolic velocity. RESULTS: There was a significant inverse correlation between LVEF and SDI (r =-0.686, P < 0.0001). QRS duration was also significantly correlated to SDI (r = 0.407, P < 0.0001). There was a significant positive correlation between baseline SDI and the decrease in LVESV after CRT (r = 0.42). Baseline SDI was significantly greater in responders (10 patients) than in nonresponders (16.4 ± 5.1 vs. 7.9 ± 2.4%, P < 0.01), but there was no significant difference in Ts-SD. SDI > 11.9% predicted CRT response with a sensitivity of 90% and a specificity of 75%. CONCLUSIONS: SDI derived from 3DE is a useful parameter to assess global LV systolic dyssynchrony and predict responses to CRT.

Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy.

AIMS: To prospectively evaluate the relationship between left atrial volume (LAV) and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM). METHODS: We enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61±13 years) who met inclusion criteria were followed for 30.8±10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE), a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained. RESULTS: MACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths). Maximum LAV, minimum LAV, and LAV index (LAVI) corrected for body surface area (BSA) were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3±25.0 vs. 51.9±16.0 ml, p=0.005; minimum LAV: 33.9±15.1 vs. 26.2±10.9 ml, p=0.008; LAVI: 40.1±15.4 vs. 31.5±8.7 ml/mm2, p=0.0009), while there were no differences in the other echocardiographic parameters.LAV/BSA of ≥40.4 ml/m2 to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%. CONCLUSION: LAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.

[Left ventricular volume and ejection fraction by the axius auto ejection fraction method: comparison with manual trace method and visual assessment of ejection fraction].

OBJECTIVES: Visual assessment of the ejection fraction (EF) is often used in clinical practice, but is subjective and requires training and experience. The auto EF method has been newly developed for automated detection of the left ventricular (LV) endocardial border throughout the cardiac cycle. The clinical feasibility was assessed of the auto EF method for measuring LV volumes and EF in patients. Manually traced EF measured by the biplane modified Simpson's rule was used as the reference standard. METHODS: The study population consisted of 30 consecutive patients with normal sinus rhythm. All patients underwent two-dimensional echocardiography. The auto EF method incorporated pattern and shape recognition to automatically locate the LV, track the endocardium, and calculate EF from routine digital images. LV end-diastolic and end-systolic volumes and EF measured by the auto EF method were compared those by the manually traced method. LVEF by the Auto EF method was also compared with visual EF determined by nonattending physicians. RESULTS: Auto EF was more reproducible than visual EF by the expert reader. LVEF by the auto EF method had excellent correlation and close limits of agreement with manually traced EF compared with visual EF(4-chamber view: y = 1.10 x - 4.28, r = 0.94, bias = 1.6%, 2-chamber view: y = 0.88 x + 7.25, r = 0.90, bias = 0.4%). LV volumes by the auto EF method underestimated those by manually traced EF (end-diastolic volume by 4-chamber view: y = 0.72 x + 8.92, r = 0.93, bias = - 16.7 ml, end-systolic volume by 4-chamber view: y = 0.82 x - 0.97, r = 0.98, bias = - 8.5 ml, end-diastolic volume by 2-chamber view: y = 0.73 x + 12.4, r = 0.82, bias = - 12.3 ml, end-systolic volume by 2-chamber view: y = 0.65 x + 6.94, r = 0.90, bias = - 6.8 ml). CONCLUSIONS: The auto EF method is a clinically useful tool for the measurement of LV volumes and EF.

Left atrial volume in normal Japanese adults.

BACKGROUND: Two-dimensional (D) echocardiography-derived left atrial (LA) volume has been shown to provide a more accurate assessment of LA size than the M-mode LA dimension. Our objective was to provide reference ranges of LA volume in healthy Japanese adults. METHODS AND RESULTS: The study subjects consisted of 105 Japanese adults, with a mean age of 39+/-13 years (range 20-63 years old). All subjects had normal ejection fraction (>55%), no wall motion abnormalities, normal diastolic function, no valvular disease, and normal sinus rhythm. The maximum LA volume, at left ventricular end-systole just before the opening of the mitral valve, was measured by using the bi-apical (4- and 2-chamber views) Simpson's rule. Both the absolute LA volume and the volume corrected by body surface area (LA volume index) were obtained. The LA volume ranged from 21 to 53 ml (mean 37+/-8 ml) and the LA volume index ranged from 13 to 30 ml/m(2) (mean 22+/-4 ml/m(2)). The mean LA volume index + 2SDs was 30 ml/m(2). CONCLUSIONS: Recognition of the upper limits of LA volume in normal Japanese subjects is of particular clinical relevance because it offers the opportunity of pathological LA remodeling diagnosis.

Left atrial volume and the risk of paroxysmal atrial fibrillation in patients with hypertrophic cardiomyopathy.

Paroxysmal atrial fibrillation (PAF) is a common complication of patients with hypertrophic cardiomyopathy, often leading to acute or progressive heart failure and cerebral infarction. We assessed the echocardiographic data of 141 consecutive patients with hypertrophic cardiomyopathy, with and without PAF. In all, 31 patients (22%) had a history of PAF with spontaneous conversion to in sinus rhythm. Left atrial volume and left atrial volume indexed to body surface area were significantly increased for patients with PAF compared with those without PAF. Maximum left atrial volume was the most sensitive and specific parameter for the occurrence of PAF in patients with hypertrophic cardiomyopathy.

[Validation of a new hand-carried ultrasound device equipped with directional color power Doppler and continuous wave Doppler].

OBJECTIVES: This study evaluated the accuracy of the directional color power Doppler (DCPD) and continuous wave Doppler (CWD) methods incorporated in the new hand-carried SonoSite 180PLUS ultrasound device. METHODS: The hand-held ultrasound system with 2.5 MHz transducer and SONOS 5500 was used as a standard ultrasound system with a 2 to 4 MHz wideband transducer. The experimental study used a Doppler wire phantom to evaluate the influence of target wire speed and angle of transducer on DCPD imaging. The clinical study included 48 consecutive patients. DCPD assessment of valvular regurgitation measured the distances of DCPD signals of mitral, aortic and tricuspid valve regurgitation using the apical four-chamber view for comparison with standard echocardiography. CWD assessment measured the peak velocities of the aortic flow and tricuspid valve regurgitant flow for comparison with standard echocardiography. RESULTS: In the experimental study, DCPD signals were not influenced by target wire speed changes and transducer incident angles. In the clinical study, agreements for mitral, aortic and tricuspid regurgitation between the two methods were 89.6%, 81.8% and 78.7%, respectively. The distances of DCPD valve regurgitant signals by the hand-carried ultrasound device showed good correlation (mitral regurgitation: y = 0.84x + 0.55; r = 0.93, aortic regurgitation: y = 0.95x + 0.27; r = 0.94, tricuspid regurgitation: y = 0.86x + 0.61; r = 0.90) with those by standard echocardiography. Evaluation of CWD velocity measurements showed good agreement for the lower flow velocities (< 2.0 m/sec). However, underestimation occurred for the high flow velocities (> 2.0 m/sec) compared with those by standard echocardiography (aortic flow: y = 0.80x + 0.11; r = 0.95, tricuspid regurgitation: y = 1.00x - 0.23; r = 0.90). CONCLUSIONS: The new hand-carried ultrasound device (SonoSite 180PLUS equipped with DCPD and CWD) is clinically useful for evaluating valvular regurgitations and flow velocities. Further studies are needed to determine the mechanism of the underestimation of high flow velocities by CWD.

Single-beat determination of Doppler-derived aortic flow measurement in patients with atrial fibrillation.

The clinical assessment of left ventricular systolic function in patients with atrial fibrillation is unreliable and difficult because of beat-to-beat variation. We initially evaluated an index that is on the basis of the ratio of preceding R-R (RR1) to pre-preceding R-R (RR2) intervals (RR1/RR2) for the measurement of Doppler aortic flow (peak flow velocity [Vp] and time-velocity integral [TVI] proportional to stroke volume) in 20 patients (aged 65 +/- 9.6 years) with atrial fibrillation. We obtained each parameter for >13 cardiac cycles, and the relationship between each parameter at a given cardiac beat and the RR1/RR2 ratio were evaluated by linear regression analysis. The value of each parameter at RR1/RR2 = 1 was calculated from the equation of linear regression line and compared with measured average value over all cardiac cycles. Both parameters showed a significant positive correlation with the RR1/RR2 ratio (Vp, r = 0.98, y = 1.01x + 0.61; TVI, r = 0.99, y = 1.01x + 0.26). The calculated value of each parameter at RR1/RR2 = 1 was quite similar to the average value (Vp, 97.4 +/- 30.8 vs 95.7 +/- 29.8 cm/s; TVI, 17.7 +/- 6.8 vs 17.3 +/- 6.7 cm, respectively). In the additional 20 patients (aged 77.4 +/- 15.2 years), Doppler aortic flow parameters of a single beat with identical RR1 and RR2 intervals were compared with measured average value over all cardiac cycles and showed similar results (Vp, r = 0.99, y = 0.99x + 3.4, P <.0001, bias -0.5 cm/s; TVI, r = 0.99, y = 0.92x + 1.5, P <.0001, bias 0.1 cm). In conclusion, the Doppler aortic flow at RR1/RR2 = 1 allows the left ventricular systolic parameters to be accurately evaluated during atrial fibrillation and obviates the less reliable process of averaging multiple irregular beats.

[Assessment of the clinical feasibility of OptiGo for hand-held echocardiography].

OBJECTIVES: Hand-held ultrasound devices are becoming available for clinical examination, but the accuracy and precision of such devices are unclear. This study compared the accuracy of a hand-held echo device to a standard echo system. METHODS: Twenty-two patients were examined with the OptiGo (Phillips Medial Systems) hand-held ultrasound system with a 2.5 MHz transducer and SONOS 5500 (Phillips Medial Systems) standard ultrasound system with a 2 to 4 MHz wideband transducer. Patients with cardiac arrhythmia and tachycardia were excluded. Image quality, chamber size (left ventricle, left atrium), global and regional left ventricular function, valve morphology and severity of valve regurgitation were assessed. RESULTS: There was good agreement between the two imaging devices for image quality (77.3%), left ventricular ejection fraction (90.5%), regional wall motion score (> 90%), valve morphology (> 90%), severity of valve regurgitation (> 81.0%) and there was good correlation and agreement for left ventricular and left atrial size. CONCLUSIONS: Although the OptiGo has limitations, the hand-held examination appropriately estimates global and regional left ventricular function, valve morphology, valve regurgitation and chamber size.

Rapid freehand scanning three-dimensional echocardiography: accurate measurement of left ventricular volumes and ejection fraction compared with quantitative gated scintigraphy.

This study was performed to assess clinical feasibility of rapid freehand scanning 3-dimensional echocardiography (3DE) for measuring left ventricular (LV) end-diastolic and -systolic volumes and ejection fraction using quantitative gated myocardial perfusion single photon emission computed tomography as the reference standard. We performed transthoracic 2-dimensional echocardiography and magnetic freehand 3DE using a harmonic imaging system in 15 patients. Data sets (3DE) were collected by slowly tilting the probe (fan-like scanning) in the apical position. The 3DE data were recorded in 10 to 20 seconds, and the analysis was performed within 2 minutes after transferring the raw digital ultrasound data from the scanner. For LV end-diastolic and -systolic volume measurements, there was a high correlation and good agreement (LV end-diastolic volume, r = 0.94, P <.0001, standard error of the estimates = 21.6 mL, bias = 6.7 mL; LV end-systolic volume, r = 0.96, P <.0001, standard error of the estimates = 14.8 mL, bias = 3.9 mL) between gated single photon emission computed tomography and 3DE. There was an overall underestimation of volumes with greater limits of agreement by 2-dimensional echocardiography. For LV ejection fraction, regression and agreement analysis also demonstrated high precision and accuracy (y = 0.82x + 5.1, r = 0.93, P <.001, standard error of the estimates = 7.6%, bias = 4.0%) by 3DE compared with 2-dimensional echocardiography. Rapid 3DE using a magnetic-field system provides precise and accurate measurements of LV volumes and ejection fraction in human beings

Pulsed Doppler echocardiographic detection of the origin of musical murmurs in a case of pacemaker implantation.

We report a case of systolic and diastolic musical murmurs that developed 4 years after DDD pacemaker implantation. Echocardiographic examination disclosed no evidence of serious pacemaker-related complications. Pulsed Doppler examination with a sample volume at the right ventricular portion of a pacemaker lead showed prominent harmonic signals. The timing of the signals was consistent with that of musical murmurs. We considered vibration of the pacemaker lead as a possible origin of the musical murmurs. Systolic and diastolic musical murmurs can develop without serious cause in a patient with a transvenous pacemaker. Pulsed Doppler examination was useful in detecting the origin of musical murmurs.