Left ventricular synchrony,torsion, and recoil mechanics in Ebstein’s anomaly: insights from cardiovascular magnetic resonance

Background

Disease progression and heart failure development in Ebstein’s Anomaly (EA) of the tricuspid valve is characterized by both right and left ventricular (LV) deterioration. The mechanisms underlying LV dysfunction and their role in heart failure development are incompletely understood. We hypothesized that LV dyssynchrony and impaired torsion and recoil mechanics induced by paradoxical movement of the basal septum may play a role in heart failure development.

Methods

31 EA patients and 31 matched controls underwent prospective cardiovascular magnetic resonance (CMR). CMR feature tracking (CMR-FT) was performed on apical, midventricular and basal short-axis and 4D–volume analysis was performed using three long-axis views and a short axis cine stack employing dedicated software. Circumferential uniformity ratio estimates (CURE) time-to-peak-based circumferential systolic dyssynchrony index (C-SDI), 4D volume analysis derived SDI (4D–SDI), torsion (Tor) and systolic (sysTR) and diastolic torsion rate (diasTR) were calculated for the LV. QRS duration, brain natriuretic peptide, NYHA and Total R/L-Volume Index (R/L Index) were obtained.

Results

EA patients (31.5 years; controls 31.4 years) had significantly longer QRS duration (123.35 ms?±?26.36 vs. 97.33 ms ±?11.89 p <?0.01) and showed more LV dyssynchrony (4D–SDI 7.60%?±?4.58 vs. 2.54%?±?0.62, p <?0.001; CURE 0.77?±?0.05 vs. 0.86?±?0.03, p?<?0.001; C-SDI 7.70?±?3.38 vs. 3.80?±?0.91, p =?0.001). There were significant associations of LV dyssynchrony with heart failure parameters and QRS duration. Although torsion and recoil mechanics did not differ significantly (p >?0.05) there was an association of torsion and recoil mechanics with dyssynchrony parameters CURE (sysTR r =??0.426; p =?0.017, diasTR r =?0.419; p =?0.019), 4D–SDI (sysTR r =?0.383; p =?0.044) and C-SDI (diasTR r =??0.364; p?=?0.044).

Conclusions

EA is characterized by LV intra-ventricular dyssynchrony, which is associated with heart failure and disease severity parameters. Markers of dyssynchrony can easily be quantified from CMR-FT, and may have a role in the assessment of altered cardiac function, carrying potential management implications for EA patients.

     

Control within a virtual environment is correlated to functional outcomes when using a physical prosthesis

Background

Advances such as targeted muscle reinnervation and pattern recognition control may provide improved control of upper limb myoelectric prostheses, but evaluating user function remains challenging. Virtual environments are cost-effective and immersive tools that are increasingly used to provide practice and evaluate prosthesis control, but the relationship between virtual and physical outcomes—i.e., whether practice in a virtual environment translates to improved physical performance—is not understood.

Methods

Nine people with transhumeral amputations who previously had targeted muscle reinnervation surgery were fitted with a myoelectric prosthesis comprising a commercially available elbow, wrist, terminal device, and pattern recognition control system. Virtual and physical outcome measures were obtained before and after a 6-week home trial of the prosthesis.

Results

After the home trial, subjects showed statistically significant improvements (p <?0.05) in offline classification error, the virtual Target Achievement Control test, and the physical Southampton Hand Assessment Procedure and Box and Blocks Test. A trend toward improvement was also observed in the physical Clothespin Relocation task and Jebsen-Taylor test; however, these changes were not statistically significant. The median completion time in the virtual test correlated strongly and significantly with the Southampton Hand Assessment Procedure (p =?0.05, R =???0.86), Box and Blocks Test (p =?0.007, R =???0.82), Jebsen-Taylor Test (p =?0.003, R =?0.87), and the Assessment of Capacity for Myoelectric Control (p =?0.005,R =???0.85). The classification error performance only had a significant correlation with the Clothespin Relocation Test (p =?0.018, R =?.76).

Conclusions

In-home practice with a pattern recognition-controlled prosthesis improves functional control, as measured by both virtual and physical outcome measures. However, virtual measures need to be validated and standardized to ensure reliability in a clinical or research setting.

Trial registration

This is a registered clinical trial: NCT03097978.

     

Validation of a rapid semi-automated method to assess left atrial longitudinal phasic strains on cine cardiovascular magnetic resonance imaging

Background

Abnormal left atrial (LA) function is a marker of cardiac dysfunction and adverse cardiovascular outcome, but is difficult to assess, and hence not, routinely quantified. We aimed to determine the feasibility and effectiveness of a fast method to measure long-axis LA strain and strain rate (SR) with standard cardiovascular magnetic resonance (CMR) compared to conventional feature tracking (FT) derived longitudinal strain.

Methods

We studied 50 normal controls, 30 patients with hypertrophic cardiomyopathy, and 100 heart failure (HF) patients, including 40 with reduced ejection fraction (HFrEF), 30 mid-range ejection fraction (HFmrEF) and 30 preserved ejection fraction (HFpEF). LA longitudinal strain and SR parameters were derived by tracking the distance between the left atrioventricular junction and a user-defined point at the mid posterior LA wall on standard cine CMR two- and four-chamber views. LA performance was analyzed at three distinct cardiac phases: reservoir function (reservoir strain ε_s and strain rate SR_s), conduit function (conduit strain ε_e and strain rate SR_e) and booster pump function (booster strain ε_a and strain rate SR_a).

Results

There was good agreement between LA longitudinal strain and SR assessed using the fast and conventional FT-CMR approaches (r?=?0.89 to 0.99, p?<?0.001). The fast strain and SRs showed a better intra- and inter-observer reproducibility and a 55% reduction in evaluation time (85?±?10 vs. 190?±?12 s, p?<?0.001) compared to FT-CMR. Fast LA measurements in normal controls were 35.3?±?5.2% for ε_s, 18.1?±?4.3% for ε_e, 17.2?±?3.5% for ε_a, and 1.8?±?0.4, ??2.0?±?0.5, ??2.3?±?0.6 s^??1 for the respective phasic SRs. Significantly reduced LA strains and SRs were observed in all patient groups compared to normal controls. Patients with HFpEF and HFmrEF had significantly smaller ε_s, SR_s, ε_e and SR_e than hypertrophic cardiomyopathy, and HFmrEF had significantly impaired LA reservoir and booster function compared to HFpEF. The fast LA strains and SRs were similar to FT-CMR for discriminating patients from controls (area under the curve (AUC)?=?0.79 to 0.96 vs. 0.76 to 0.93, p?=?NS).

Conclusions

Novel quantitative LA strain and SR derived from conventional cine CMR images are fast assessable parameters for LA phasic function analysis.

     

Effects of Tiotropium Combined with Theophylline on Stable COPD Patients of Group B,D and its Impact on Small Airway Function: A Randomized Controlled Trial

Introduction

Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD). However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD. We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.

Methods

Eligible participants (n?=?170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months. COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.

Results

After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41?±?3.56 and 11.08?±?3.05, p?<?0.0001). The changes of CAT (p?=?0.028) and mMRC scores (p?=?0.049) between the two groups differed after 1 month of treatment. In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF₂₅% pred) was significantly improved after 3 months (4.84?±?8.73%, p?<?0.0001) and 6 months (6.21?±?8.65%, p?<?0.0001). There was a significant difference in small airway function tests (MEF₅₀% pred, MEF₂₅% pred, and MMEF% pred) between the two groups after 6 month of treatment (p?=?0.003, p?<?0.0001, and p?=?0.021, respectively).

Conclusions

Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up. Additionally, this therapy also improved the indicators of small airway function.

Trial Registration

Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).

     

Relevance of transthoracic left atrial appendage wall velocity measurement in addition to left atrial volume for noninvasive and quantitative assessment of left atrial thrombogenesis in patients with atrial fibrillation and normal D-dimer levels

Purpose

This study examined the role of left atrial (LA) appendage wall velocity (LAAWV) measurement in addition to LA size for the noninvasive assessment of thrombogenesis in patients with atrial fibrillation (AF) and normal plasma D-dimer levels.

Methods

In 58 non-valvular AF patients, LAAWV and the LA volume index (LAVI) were determined by transthoracic echocardiography. LA appendage flow velocity and severity of spontaneous echo contrast (SEC) were determined by transesophageal echocardiography.

Results

LAAWV was strongly correlated with LA appendage flow velocity (r = 0.82), and LAVI was weakly correlated with LA appendage flow velocity (r = ?0.37). As SEC severity increased, LAAWV decreased (p < 0.001) and LAVI increased (p < 0.001). Among 52 patients with normal D-dimer levels, LAAWV < 10 cm/s had 71 % sensitivity and 94 % specificity for diagnosing severe SEC. Severe SEC was not found in 18/32 large LAVI patients (>34 mL/m²), but 17 of the 18 patients (94 %) had LAAWV < 10 cm/s. Severe SEC was found in 3/20 patients with normal LAVI, but all of them showed LAAWV < 10 cm/s.

Conclusion

The noninvasive measurement of transthoracic LAAWV in addition to LA volume is clinically relevant for quantitatively assessing thrombogenesis in AF patients with normal D-dimer levels.

     

Diagnostic and prognostic significance of cardiovascular magnetic resonance native myocardial T1 mapping in patients with pulmonary hypertension

Background

Native T1 may be a sensitive, contrast-free, non-invasive cardiovascular magnetic resonance (CMR) marker of myocardial tissue changes in patients with pulmonary artery hypertension. However, the diagnostic and prognostic value of native T1 mapping in this patient group has not been fully explored. The aim of this work was to determine whether elevation of native T1 in myocardial tissue in pulmonary hypertension: (a) varies according to pulmonary hypertension subtype; (b) has prognostic value and (c) is associated with ventricular function and interaction.

Methods

Data were retrospectively collected from a total of 490 consecutive patients during their clinical 1.5 T CMR assessment at a pulmonary hypertension referral centre in 2015. Three hundred sixty-nine patients had pulmonary hypertension [58?±?15 years; 66% female], an additional 39 had pulmonary hypertension due to left heart disease [68?±?13 years; 60% female], 82 patients did not have pulmonary hypertension [55?±?18; 68% female]. Twenty five healthy subjects were also recruited [58 ±4 years); 51% female]. T1 mapping was performed with a MOdified Look-Locker Inversion Recovery (MOLLI) sequence. T1 prognostic value in patients with pulmonary arterial hypertension was assessed using multivariate Cox proportional hazards regression analysis.

Results

Patients with pulmonary artery hypertension had elevated T1 in the right ventricular (RV) insertion point (pulmonary hypertension patients: T1?=?1060?±?90 ms; No pulmonary hypertension patients: T1?=?1020?±?80 ms p <?0.001; healthy subjects T1?=?940?±?50 ms p <?0.001) with no significant difference between the major pulmonary hypertension subtypes. The RV insertion point was the most successful T1 region for discriminating patients with pulmonary hypertension from healthy subjects (area under the curve?=?0.863) however it could not accurately discriminate between patients with and without pulmonary hypertension (area under the curve?=?0.654). T1 metrics did not contribute to prediction of overall mortality (septal: p =?0.552; RV insertion point: p =?0.688; left ventricular free wall: p =?0.258). Systolic interventricular septal angle was a significant predictor of T1 in patients with pulmonary hypertension (p <?0.001).

Conclusions

Elevated myocardial native T1 was found to a similar extent in pulmonary hypertension patient subgroups and is independently associated with increased interventricular septal angle. Native T1 mapping may not be of additive value in the diagnostic or prognostic evaluation of patients with pulmonary artery hypertension.

     

Fractal analysis of left ventricular trabeculations is associated with impaired myocardial deformation in healthy Chinese

Background

Left ventricular (LV) non-compaction (LVNC) is defined by extreme LV trabeculation, but is measured variably. Here we examined the relationship between quantitative measurement in LV trabeculation and myocardial deformation in health and disease and determined the clinical utility of semi-automated assessment of LV trabeculations.

Methods

Cardiovascular magnetic resonance (CMR) was performed in 180 healthy Singaporean Chinese (age 20–69 years; males, n?=?91), using balanced steady state free precession cine imaging at 3T. The degree of LV trabeculation was assessed by fractal dimension (FD) as a robust measure of trabeculation complexity using a semi-automated technique. FD measures were determined in healthy men and women to derive normal reference ranges. Myocardial deformation was evaluated using feature tracking. We tested the utility of this algorithm and the normal ranges in 10 individuals with confirmed LVNC (non-compacted/compacted; NC/C ratio?>?2.3 and ≥1 risk factor for LVNC) and 13 individuals with suspected disease (NC/C ratio?>?2.3).

Results

Fractal analysis is a reproducible means of assessing LV trabeculation extent (intra-class correlation coefficient: intra-observer, 0.924, 95% CI [0.761–0.973]; inter-observer, 0.925, 95% CI [0.821–0.970]). The overall extent of LV trabeculation (global FD: 1.205?±?0.031) was independently associated with increased indexed LV end-diastolic volume and mass (sβ =?0.35; p?<?0.001 and sβ =?0.13; p?<?0.01, respectively) after adjusting for age, sex and body mass index. Increased LV trabeculation was independently associated with reduced global circumferential strain (sβ =?0.17, p?=?0.013) and global diastolic circumferential and radial strain rates (sβ =?0.25, p?<?0.001 and sβ =??0.15, p?=?0.049, respectively). Abnormally high FD was observed in all patients with a confirmed diagnosis of LVNC. Five out of 13 individuals with suspected LVNC had normal FD, despite NC/C?>?2.3.

Conclusion

This study defines the normal range of LV trabeculation in healthy Chinese that can be used to make or refute a diagnosis of LVNC using the fractal analysis tool, which we make freely available. We also show that increased myocardial trabeculation is associated with higher LV volumes, mass and reduced myocardial strain.

     

Health-related outcomes of critically ill patients with and without sepsis

Purpose

To determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis.

Methods

We conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years.

Results

We obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p?=?0.86), self-care (24.7% vs. 26.0%, p?=?0.44), usual activities (44.5% vs. 46.8%, p?=?0.28), pain/discomfort (42.4% vs. 41.6%, p?=?0.54) and anxiety/depression (36.9% vs. 37.7%, p?=?0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86–1.18, p?=?0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1?±?11.9 vs. 8.0?±?9.8 days (p?<?0.0001) and 22.8?±?21.2 vs. 19.1?±?19.0 days, (p?=?0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345?±?46,263 (€35,109?±?35,043) versus 34,844?±?38,281 (€28,223?±?31,007), mean difference $8501 (€6885), 95% CI $4342–12,660 (€3517?±?10,254), p?<?0.001 as was the total cost of hospital treatment to 2 years: A$74,120?±?60,750 (€60,037?±?49,207) versus A$65,806?±?59,856 (€53,302?±?48,483), p?=?0.005.

Conclusions

Critically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

     

Comparison of the use of comprehensive point-of-care test panel to conventional laboratory process in emergency department

Background

In this study, we hypothesized that point of care testing (POCT) would reduce length of stay (LOS) in emergency department (ED) when compared to central laboratory testing and be a factor in patient discharge destination.

Methods

A single centre observational study was performed in ED non-ambulatory patients. Blood testing was performed either with POC instruments for blood gases and chemistry panel, full blood count, and CRP, or at central laboratory, or as a combination of both. Blood draw and POCTs were performed by experienced nurses.

Results

During the 4-week study period, 1759 patients underwent sample testing (POCT: n =?160, central lab: n =?951; both n =?648). Median waiting time for blood sampling was 19?min less in POCT than central laboratory (0:52 (95% confidence interval (CI) 0:46–1:02) vs. 1:11 (95% CI 1:05–1:14), p <?0.001). POCT results were available faster in both discharge groups, as expected. When imaging was not required, patients in POCT group were discharged home 55?min faster (4:57 (95% CI 3:59–6:17) vs. 5:52 (95% CI 5:21–6:35), p =?0.012) and 1?h 22?min faster when imaging was performed (5:48 (95% CI 5:26–6:18) vs. 7:10 (95% CI 6:47–8:26), p =?0.010). Similar reduction in sampling time and LOS was not seen among those admitted to hospital.

Conclusions

POCT shortened the laboratory process and made results available faster than the central lab. This allowed patients to be discharged home quicker. Thus, with proper training and education of the ED care team, POCT can be used as an effective tool for improving patient flow.

     

Comparing Entropy and the Bispectral Index with the Ramsay Score in Sedated ICU Patients

Objective

ENTROPY? is a new anesthetic depth monitor based on the analysis of the EEG signal. Our aim has been to evaluate sedation of intubated surgical critically ill patients by means of the Ramsay sedation score, the Bispectral index and ENTROPY?, and to analyse the correlation between these variables.

Methods

Sedation was evaluated every 15 min for a 1 h period in 50 non-paralysed postoperative critically ill, intubated patients, enrolled over a 6 month period. A 5 min steady-state period was allowed before each assessment. Both the Bispectral index and the Entropy parameters Response Entropy (RE) and State Entropy (SE), were collected before assessing the Ramsay scale.

Results

Mean values for SE, RE and BIS were 53 ± 27, 60 ± 30, and 62 ± 24 respectively. The median value for the Ramsay was 6 (range 1–6). Significant correlation was found between the four variables (SE-BIS: r = 0.79, p < 0.001; RE-BIS: r = 0.80, p < 0.001; SE-Ramsay: ρ = ?0.71, p < 0.001, RE-Ramsay: ρ = ?0.72, p < 0.001; BIS-Ramsay: ρ = ?0.78, p < 0.001; RE-SE: r = 0.98, p < 0.001). An overlap of BIS and Entropy values for every Ramsay score value between 4–6 was found.

Conclusions

ENTROPY?, BIS and Ramsay score values correlate significantly in sedated postoperative ICU patients. ENTROPY? does not appear superior to BIS for the assessment of sedation in this context.

     

Effect of steatosis on liver signal and enhancement on multiphasic contrast-enhanced magnetic resonance imaging

Purpose

To investigate the effect of steatosis on liver signal and enhancement in multiphasic contrast-enhanced (MCE) MRI.

Materials and methods

In this IRB-approved, HIPAA-compliant, retrospective, observational study, 1217 MCE abdominal MRIs performed during 2014 at a single institution were reviewed. Of these, 1085 were excluded, due to potential factors other than steatosis that may affect liver signal intensity and/or enhancement. In the remaining 132, liver fat fraction (FF) was calculated from the in- and opposed-phase 2D T1-weighted images. Liver signal intensity, absolute enhancement, and relative enhancement on fat-suppressed (Dixon method) 3D T1-weighted images before and after injection of gadobutrol (arterial, portal venous, and equilibrium phases) were plotted against co-localized FF values and the linear trend was evaluated by Pearson correlation coefficient (r). P values <0.05 were considered statistically significant.

Results

Liver signal intensity negatively correlated with FF for all phases (r = ?0.388 to ?0.544, p < 0.001). Absolute enhancement negatively correlated with FF for the portal venous and equilibrium phases (r = ?0.286 and ?0.289, respectively, p < 0.001), but not for the arterial phase (r = ?0.042, p = 0.632). Relative enhancement did not significantly correlate with FF for any phase (p ≥ 0.125).

Conclusion

Steatosis reduces liver signal intensity in MCE MRI. This effect of steatosis was reduced in calculated absolute enhancement and eliminated in calculated relative enhancement.

     

Impaired aortic distensibility and elevated central blood pressure in Turner Syndrome: a cardiovascular magnetic resonance study

Background

Women with Turner Syndrome have an increased risk for aortic dissection. Arterial stiffening is a risk factor for aortic dilatation and dissection. Here we investigate if arterial stiffening can be observed in Turner Syndrome patients and is an initial step in the development of aortic dilatation and subsequent dissection.

Methods

Fifty-seven women with Turner Syndrome (48 years [29–66]) and thirty-six age- and sex-matched controls (49 years [26–68]) were included. Distensibility, blood pressure, carotid-femoral pulse wave velocity (PWV), the augmentation index (Aix) and central blood pressure were determined using cardiovascular magnetic resonance, a 24-h blood pressure measurement and applanation tonometry. Aortic distensibility was determined at three locations: ascending aorta, transverse aortic arch, and descending aorta.

Results

Mean aortic distensibility in the descending aorta was significantly lower in Turner Syndrome compared to healthy controls (P =?0.02), however, this was due to a much lower distensibility among Turner Syndrome with coarctation, while Turner Syndrome without coarctation had similar distensibility as controls. Both the mean heart rate adjusted Aix (31.4% vs. 24.4%; P?=?0.02) and central diastolic blood pressure (78.8 mmHg vs. 73.7 mmHg; P?=?0.02) were higher in Turner Syndrome compared to controls, and these indices correlated significantly with ambulatory night-time diastolic blood pressure. The presence of aortic coarctation (r = ??0.44, P =?0.005) and a higher central systolic blood pressure (r = ??0.34, P =?0.03), age and presence of diabetes were inversely correlated with aortic distensibility in TS.

Conclusion

Aortic wall function in the descending aorta is impaired in Turner Syndrome with lower distensibility among those with coarctation of the aorta, and among all Turner Syndrome higher Aix, and elevated central diastolic blood pressure when compared to sex- and age-matched controls.

Trial registration

The study was registered at ClinicalTrials.gov (#NCT01678274) on September 3, 2012.

     

The Impact of Adding a Training Device to Familiar Counselling on Inhalation Technique and Pulmonary Function of Asthmatics

Introduction

We have investigated the effect of adding a pressurized metered dose inhaler (pMDI) training device to verbal counselling on pulmonary function and inhalation technique.

Methods

A total of 304 adult asthmatic subjects (>?18 years old) were enrolled in a 3-month study of assessment and education. They were divided into an investigation group (Trainhaler plus Flo-Tone and verbal counselling, n?=?261, mean age 49.2 years) and a control group (verbal counselling only, n?=?43, mean age 48.7 years). Pulmonary function and inhalation technique were evaluated, mistakes noted, and the correct technique advised at three consecutive monthly visits. Visits also included verbal pMDI counselling (both groups) and training device coaching (investigation group).

Results

By visit 2, the mean number of technique errors decreased significantly (p?<?0.05) in both groups (investigation group p?<?0.001). The investigation group demonstrated a marked decrease in the frequency of the critical error of maintaining a slow inhalation rate until the lungs are full—a technique difficult to learn via verbal counselling alone. The improvement in pulmonary function was significant from the second clinic visit in the investigation group (p?<?0.05) and from the third visit in both groups (p?<?0.001).

Conclusions

Use of a training device combined with verbal counselling improved inhalation technique. An earlier, significant improvement was also noted in pulmonary function.

     

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice

Introduction

Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients’ satisfaction and adherence.

Methods

ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting.

Results

A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p?<?0.001) decrease in angina attack frequency (from 4.7?±?3.5 to 0.9?±?1.3/week) and SAN use (from 4.5?±?3.9 to 0.7?±?1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p?<?0.0001) and non-adherence by 3% (vs. 36% at baseline, p?<?0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p?<?0.01), slight limitation (46% vs. 5% at baseline, p?<?0.001) or moderate limitation (30% vs. 23%, p?<?0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p?<?0.001) or very marked reduction (1% vs. 19% at baseline, p?<?0.01) at month 3.

Conclusion

In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients.

Trial Registration

ISRCTN registry Identifier, ISRCTN97780949.

Funding

Servier.

Plain Language Summary

Plain language summary available for this article.

     

Comparison of quality of chest compressions during training of laypersons using Push Heart and Little Anne manikins using blinded CPRcards

Background

Mass Cardio-Pulmonary Resuscitation (CPR) training using less expensive and easily portable manikins is one way to increase the number of trained laypeople in a short time. The easy-to-carry, low-cost CPR training model called Push Heart (PH) is widely used in Japan. The aim of this study was to examine if PH can achieve chest compression quality that is similar to that using more conventional Little Anne (LA) manikins for training laypersons.

Methods

This prospective randomized crossover study was done during routine community CPR training of laypersons in Singapore. The participants were randomly allocated into two groups, using the PH and LA models respectively. They crossed over during the training so that both groups had measurements using both models. Chest compression data were collected using blinded CPRcards, which are credit card-sized devices with accelerometers and data capture. Participants did not receive any CPR feedback during measurement.

Results

Forty-two people had data captured for the study with 15 males. The median compression depth was 41.5 mm on LA and 38.0 mm on PH (p?=?0.0664), and median compression rate was 105 cpm on LA and 103 cpm on PH (p?=?0.2429). Overall, only 1.5% of compressions performed on the PH achieved adequate depth of between 50–70 mm compared to 5.5% achieved on LA (p?=?0.049). In contrast, 84% of all compressions performed on the PH were within the adequate rate of 100–120 cpm compared to 79.5% on LA (p?=?0.457). Only the under 20-year-old group was able to achieve adequate median compression depth (50.5 mm) on LA, while the older age groups did not (p?=?0.0024). The other age groups performed similar quality of chest compression regardless of the model used. 73.8% of participants preferred the LA for training. After the training, participants felt similarly well-prepared with either model with a median score of 8/10 on LA compared to 7/10 on PH (p?=?0.0011).

Conclusions

The PH can be an alternative mass CPR training model. Both models achieved satisfactory chest compression rates, but the majority of participants, especially the elderly, had difficulty achieving adequate depth.

     

Histogram Analysis of T1-Weighted,T2-Weighted,and Postcontrast T1-Weighted Images in Primary CNS Lymphoma: Correlations with Histopathological Findings—a Preliminary Study

Purpose

Previously, some reports mentioned that magnetic resonance imaging (MRI) can predict histopathological features in primary CNS lymphoma (PCNSL). The reported data analyzed diffusion-weighted imaging findings. The aim of this study was to investigate possible associations between histopathological findings, such as tumor cellularity, nucleic areas and proliferation index Ki-67, and signal intensity on T1-weighted and T2-weighted images in PCNSL.

Procedures

For this study, 18 patients with PCNSL were retrospectively investigated by histogram analysis on precontrast and postcontrast T1-weighted and fluid-attenuated inversion recovery (FLAIR) images. For every patient, histopathology parameters, nucleic count, total nucleic area, and average nucleic area, as well as Ki-67 index, were estimated.

Results

Correlation analysis identified several statistically significant associations. Skewness derived from precontrast T1-weighted images correlated with Ki-67 index (p = ? 0.55, P = 0.028). Furthermore, entropy derived from precontrast T1-weighted images correlated with average nucleic area (p = 0.53, P = 0.04). Several parameters from postcontrast T1-weighted images correlated with nucleic count: maximum signal intensity (p = 0.59, P = 0.017), P75 (p = 0.56, P = 0.02), and P90 (p = 0.52, P = 0.04) as well as SD (p = 0.58, P = 0.02). Maximum signal intensity derived from FLAIR sequence correlated with nucleic count (p = 0.50, P = 0.03).

Conclusion

Histogram-derived parameters of conventional MRI sequences can reflect different histopathological features in PSNCL.

     

A retrospective comparison of helicopter transport versus ground transport in patients with severe sepsis and septic shock

Background

Helicopter emergency medical services (HEMS) extend the reach of a tertiary care center significantly. However, its role in septic patients is unclear. Our study was performed to clarify the role of HEMS in severe sepsis and septic shock.

Methods

This is a single-center retrospective cohort study. This study was performed at Mayo Clinic, Rochester, MN, in years 2007–2009. This study included a total of 181 consecutive adult patients admitted to the medical intensive care unit meeting criteria for severe sepsis or septic shock within 24 h of admission and transported from an acute care facility by a helicopter or ground ambulance. The primary predictive variable was the mode of transport. Multiple demographic, clinical, and treatment variables were collected and analyzed with univariate analysis followed by multivariate analysis.

Results

The patients transported by HEMS had a significantly faster median transport time (1.3 versus 1.7 h, p?<?0.01), faster time to meeting criteria for severe sepsis or septic shock (1.2 versus 2.9 h, p?<?0.01), a higher SOFA score (9 versus 7, p?<?0.01), higher incidence of acute respiratory distress syndrome (38 versus 18 %, p?=?0.013), higher need for invasive mechanical ventilation (60 versus 41 % p?=?0.014), higher ICU mortality (13.3 versus 4.1 %, p?=?0.024), and an increased hospital mortality (17 versus 30 %, p?=?0.04) when compared to those transported by ground. Distance traveled was not an independent predictor of hospital mortality on multivariate analysis.

Conclusions

HEMS transport is associated with faster transport time, carries sicker patients, and is associated with higher hospital mortality compared with ground ambulance services for patients with severe sepsis or septic shock.

     

Comparison of tumor vascularity and hemodynamics in three rat hepatoma models

Purpose

To compare tumor vascularity and hemodynamics in three rat hepatoma models: N1-S1 cells in Sprague–Dawley rats, McA-RH7777 cells in Sprague–Dawley rats, and 13762 MAT B III cells in F344 rats.

Methods

The three rat hepatoma models were induced in five rats per group. After confirming that the tumors grew up to 10 mm on magnetic resonance imaging, the rats underwent dynamic contrast-enhanced ultrasonography (DCE-US). Afterward, the rats were euthanized for histologic analyses. The Kruskal–Wallis test was used to compare the rat hepatoma models. Correlation coefficients were calculated between the microvessel density (MVD) and DCE-US parameters.

Results

On DCE-US imaging, arterial enhancement and washout were demonstrated in all N1-S1 tumors, while persistent peripheral enhancement on arterial to portal phases was shown in all 13762 MAT B III tumors. The McA-RH7777 tumors presented diverse enhancement patterns on arterial and portal phases. There were no significant differences in DCE-US parameters among the three hepatoma groups, while MVD was correlated with peak intensity (r = 0.565, p = 0.044), mean transit time (r = ?0.559, p = 0.047), and time to peak (r = ? 0.617, p = 0.025) of individual rats. The necrosis ratio was significantly different between the models (p = 0.031); 13762 MAT B III showed a significantly higher necrosis ratio than N1-S1 (p < 0.050 by post hoc test).

Conclusion

The N1-S1 tumor may be suitable as a model to investigate hypervascular hepatic tumors of the liver in DCE-US such as hepatocellular carcinoma among the three tumors.

     

Multidimensional fetal flow imaging with cardiovascular magnetic resonance: a feasibility study

Purpose

To image multidimensional flow in fetuses using golden-angle radial phase contrast cardiovascular magnetic resonance (PC-CMR) with motion correction and retrospective gating.

Methods

A novel PC-CMR method was developed using an ungated golden-angle radial acquisition with continuously incremented velocity encoding. Healthy subjects (n?=?5, 27?±?3 years, males) and pregnant females (n?=?5, 34?±?2 weeks gestation) were imaged at 3 T using the proposed sequence. Real-time reconstructions were first performed for retrospective motion correction and cardiac gating (using metric optimized gating, MOG). CINE reconstructions of multidimensional flow were then performed using the corrected and gated data.

Results

In adults, flows obtained using the proposed method agreed strongly with those obtained using a conventionally gated Cartesian acquisition. Across the five adults, bias and limits of agreement were ??1.0 cm/s and [??5.1, 3.2] cm/s for mean velocities and???1.1 cm/s and [??6.5, 4.3] cm/s for peak velocities. Temporal correlation between corresponding waveforms was also high (R~?0.98). Calculated timing errors between MOG and pulse-gating RR intervals were low (~?20 ms). First insights into multidimensional fetal blood flows were achieved. Inter-subject consistency in fetal descending aortic flows (n =?3) was strong with an average velocity of 27.1?±?0.4 cm/s, peak systolic velocity of 70.0?±?1.8 cm/s and an intra-class correlation coefficient of 0.95 between the velocity waveforms. In one fetal case, high flow waveform reproducibility was demonstrated in the ascending aorta (R =?0.97) and main pulmonary artery (R =?0.99).

Conclusion

Multidimensional PC-CMR of fetal flow was developed and validated, incorporating retrospective motion compensation and cardiac gating. Using this method, the first quantification and visualization of multidimensional fetal blood flow was achieved using CMR.

     

Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized,sham-controlled,double-blind PRESTO trial

Background

Non-invasive vagus nerve stimulation (nVNS) has been shown to be practical, safe, and well tolerated for treating primary headache disorders. The recent multicenter, randomized, double-blind, sham-controlled PRESTO trial provided Class I evidence that for patients with episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. We report additional pre-defined secondary and other end points from PRESTO that demonstrate the consistency and durability of nVNS efficacy across a broad range of outcomes.

Methods

After a 4-week observation period, 248 patients with episodic migraine with/without aura were randomly assigned to acute treatment of migraine attacks with nVNS (n =?122) or a sham device (n =?126) during a double-blind period lasting 4 weeks (or until the patient had treated 5 attacks). All patients received nVNS therapy during the subsequent 4-week/5-attack open-label period.

Results

The intent-to-treat population consisted of 243 patients. The nVNS group (n =?120) had a significantly greater percentage of attacks treated during the double-blind period that were pain-free at 60 (P =?0.005) and 120 min (P =?0.026) than the sham group (n =?123) did. Similar results were seen for attacks with pain relief at 60 (P =?0.025) and 120 min (P =?0.018). For the first attack and all attacks, the nVNS group had significantly greater decreases (vs sham) in pain score from baseline to 60 min (P?= 0.029); the decrease was also significantly greater for nVNS at 120 min for the first attack (P =?0.011). Results during the open-label period were consistent with those of the nVNS group during the double-blind period. The incidence of adverse events (AEs) and adverse device effects was low across all study periods, and no serious AEs occurred.

Conclusions

These results further demonstrate that nVNS is an effective and reliable acute treatment for multiple migraine attacks, which can be used safely while preserving the patient’s option to use traditional acute medications as rescue therapy, possibly decreasing the risk of medication overuse. Together with its practicality and optimal tolerability profile, these findings suggest nVNS has value as a front-line option for acute treatment of migraine.

Trial registration

ClinicalTrials.gov identifier: NCT02686034.