Changes In Ventricular Volume Research Articles

Alzheimer‐like biomarker heterogeneity in a preclinical elderly birth cohort: Insight46

AbstractBackgroundTwo main complexities of Alzheimer’s Disease (AD) arise from pathological changes (such as amyloid accumulation) occurring a decade or more before symptom onset, and AD being a highly heterogeneous disease with various clinical subtypes. Subtype and Stage Inference (SuStaIn), a data‐driven modelling technique, has been previously applied to ADNI to better understand AD. Here we apply SuStaIn to Insight46, a sub‐study of the British 1946 Birth Cohort to detect different trajectories of preclinical neurodegeneration.MethodSuStaIn was applied to cross‐sectional MRI, amyloid PET, plasma biomarkers, and cognition (Preclinical Alzheimer Cognitive Composite [PACC]) from 466 study members (Table 1). 376 Amyloid‐negative individuals (computed as Lane et al. 2019) were designated as controls. SuStaIn subtypes were also estimated in ADNI (N=789; Tables 1 and 2) for comparison. T‐tests and Chi‐squared tests were used to assess subtype differences in baseline APOE, amyloid status, white matter hyperintensity volume (WMHV), and rates of change in whole brain, ventricular and hippocampal volume calculated using the boundary shift integral.ResultFigure 1 shows three subtypes uncovered by SuStaIn: ‘Typical’, ‘Subcortical’ and ‘Cortical’. The ‘Typical’ subtype appears to reflect a typical AD progression pattern, with early involvement of Aβ40/42 ratio and Neurofilament light (NFL), followed by the PACC and finally, plasma tau. MRI volumetric changes appear later. Both ‘Subcortical’ and ‘Cortical’ subtypes are characterised by earlier abnormality in MRI volumes.Figure 2 shows that subjects assigned to the ‘Cortical’ subtype had significantly higher WMHV than the other two subtypes (p‐value < 0.002). No other significant differences in baseline characteristics were found.Figure 3 shows ‘Typical’ subtype has significantly higher rates of ventricular expansion and whole brain atrophy compared with ‘Subcortical’ subtype (p‐values = 0.001).ConclusionThis study reveals three different subtypes (‘Typical’, ‘Subcortical’ and ‘Cortical’) of presumed neurodegeneration in an elderly, preclinical cohort; these are consistent with those found in AD patient cohorts, e.g. ADNI, meaning that these methods may have utility in population based cohorts. These results suggest that SuStaIn may be helpful in determining different subtypes of neurodegeneration at a very early stage with implications for recruitment to, and powering of, clinical trials.

Interpretation of pre-morbid cardiac 3T MRI findings in overweight and hypertensive young adults.

In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different body scales for indexation. We also aimed to explore the presence of myocardial fibrosis, fat and edema, and changes in cellular mass with extracellular volume (ECV), T1 and T2 tissue characteristics. We prospectively recruited 126 asymptomatic subjects (51% male) aged 27-41 years for 3T cardiac magnetic resonance imaging: 40 controls, 40 overweight, 17 hypertensive and 29 hypertensive overweight. Myocyte mass was calculated as (100%-ECV) * height2.7-indexed LVM. Absolute LVM was significantly increased in overweight, hypertensive and hypertensive overweight groups (104 ± 23, 109 ± 27, 112 ± 26 g) versus controls (87 ± 21 g), with similar volumes. Body surface area (BSA) indexation resulted in LVM normalization in overweights (48 ± 8 g/m2) versus controls (47 ± 9 g/m2), but not in hypertensives (55 ± 9 g/m2) and hypertensive overweights (52 ± 9 g/m2). BSA-indexation overly decreased volumes in overweight versus normal-weight (LV end-diastolic volume; 80 ± 14 versus 92 ± 13 ml/m2), where height2.7-indexation did not. All risk groups had lower ECV (23 ± 2%, 23 ± 2%, 23 ± 3%) than controls (25 ± 2%) (P = 0.006, P = 0.113, P = 0.039), indicating increased myocyte mass (16.9 ± 2.7, 16.5 ± 2.3, 18.1 ± 3.5 versus 14.0 ± 2.9 g/m2.7). Native T1 values were similar. Lower T2 values in the hypertensive overweight group related to heart rate. In conclusion, BSA-indexation masks hypertrophy and causes volume overcorrection in overweight subjects compared to controls, height2.7-indexation therefore seems advisable.

Electrocardiogram Belt guidance for left ventricular lead placement and biventricular pacing optimization

Patients with ischemic cardiomyopathy, non-left bundle branch block, or QRS duration <150 ms have a lower response rate to cardiac resynchronization therapy (CRT) than did other indicated patients. The ECG Belt system (EBS) is a novel surface mapping system designed to measure electrical dyssynchrony via the standard deviation of the activation times of the left ventricle. The objectives of this study were to evaluate the efficacy of the EBS in patients less likely to respond to CRT and to determine whether EBS use in lead placement guidance and device programming was superior to standard CRT care. This was a prospective randomized trial of patients with heart failure and EBS-guided CRT implantation and programming vs standard CRT care. The primary end point was relative change in left ventricular end-systolic volume from baseline to 6 months postimplantation. A total of 408 patients from centers in Europe and North America were randomized. Although both patients with EBS and control patients had a mean improvement in left ventricular end-systolic volume, there was no significant difference in relative change from baseline (P = .26). While patients with a higher baseline standard deviation of the activation times derived greater left ventricular reverse remodeling, improvement in electrical dyssynchrony did not correlate with the extent of reverse remodeling. The findings of the present study do not support EBS-guided therapy for CRT management of heart failure with reduced ejection fraction.

Abstract 13633: Differences in Right and Left Ventricular Remodeling After Tetralogy of Fallot Repair in Patients With and Without Pulmonary Valve Replacement

Background: Pulmonary valve replacement (PVR) is required to address residual lesions after tetralogy of Fallot repair (rTOF). We wished to determine the progression of ventricular dilation after rTOF, using cardiac magnetic resonance (CMR) data in children, to determine age related RV and LV volume differences in patients who did or did not require PVR. Methods: Single center, retrospective longitudinal study, including 214 patients with rTOF who had primary repair before 24 months and at least one CMR performed from 2000-2020. During follow-up, 142 patients (66.3%) had PVR at median age 12 years (IQR 9-15.5). Linear mixed effect modeling was used to evaluate time-related changes in ventricular volumes by log-transformed age at CMR adjusted for sex and regurgitant lesion status. Patients were grouped as per need for PVR during follow-up. Results: A total of 323 CMR from 201 patients performed before PVR were analyzed. The median age at first CMR was 9.4 years (IQR 5.9-12.3): 126 (62.7%) patients had one CMR, 34 (16.9%) had 2 and 41 (20.4%) had 3 or more. Prior to PVR there was steeper time-related RV dilation compared to non-PVR requiring patients: RVEDVi = 19.4 (CI 15.1 - 23.7) vs 2.8 (CI -2.5 - 8.2) ml/m 2 /log2year, p&amp;lt0.001; RVESVi = 11.9 (8.9 - 14.8) vs 0.8 (CI -2.9 - 4.4) ml/m 2 /log2year, p&amp;lt0.001. A time-related increase in LV volume also occurred in the PVR group compared to non-PVR: LVEDVi = 7.2 (CI 4.7 - 9.7) vs 1.5 (CI -1.6 - 4.6) ml/m 2 /log2year, p=0.005; LVESVi = 3.2 (CI 1.9 - 4.6) vs -0.4 (CI -2.1 - 1.3) ml/m 2 /log2year, p=0.001) (Figure 1). The factors associated with PVR were presence of regurgitant residual lesion, more prolonged QRS duration and transannular patch as surgical technique for TOF repair. Conclusion: Early and significantly increased progression of RV dilation and LV dilation are identifiable by CMR in patients destined to require PVR following rTOF. Early CMR surveillance may be indicated to permit early identification of progressive remodeling.

SOdium-glucose CO-transporter inhibition in patients with newly detected Glucose Abnormalities and a recent Myocardial Infarction (SOCOGAMI)

Aims/hypothesisEstablished dysglycaemia (impaired glucose tolerance [IGT] or type 2 diabetes [T2DM]) is a risk factor for further cardiovascular events in patients with coronary artery disease. Sodium-glucose cotransporter 2 inhibitors reduce this risk. The aim of the present investigation was to test the hypothesis that empagliflozin exerts beneficial effects on myocardial function in patients with a recent acute coronary syndrome and newly detected dysglycaemia. MethodsForty-two patients (mean age 67.5 years, 81 % male) with recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected IGT (n = 27) or T2DM (n = 15) were randomised to 25 mg of empagliflozin daily (n = 20) or placebo (n = 22) on top of ongoing therapy. They were investigated with oral glucose tolerance tests, stress-perfusion cardiac magnetic resonance imaging (CMR) and echocardiography at three occasions: before randomisation, after seven months on study drug and three months following cessation of such drug. Primary outcome was a change in left ventricular (LV) end-diastolic volume (LVEDV) and secondary outcomes were a change in a) systolic and diastolic LV function; b) coronary flow reserve; c) myocardial extracellular volume (ECV) in non-infarcted myocardium; d) aortic pulse wave velocity. ResultsEmpagliflozin induced a significant decrease in fasting and post load glucose (p < 0.05) and body weight (p < 0.01). Empagliflozin did not influence LVEDV, LV systolic or mass indexes, coronary flow reserve, ECV or aortic pulse wave velocity. Echocardiographic indices of LV diastolic function (E/e’ and mitral E/A ratio) were not influenced. No safety concerns were identified. Conclusions/interpretationEmpagliflozin had predicted effects on the dysglycaemia but did not influence variables expressing LV function, coronary flow reserve and ECV. An explanation may be that the LV function of the patients was within the normal range.

Differences in patterns of progression of secondary mitral regurgitation.

Little data exist about the natural history and disease progression of secondary mitral regurgitation (SMR). We sought to study the temporal progression of left-sided volumes and functions in patients who progress to develop severe SMR. We screened patients with chronic severe SMR who had at least one previous transthoracic echocardiography showing non-severe MR. Unsupervised phenotypic clustering based on baseline and rate of change in left ventricular (LV) and left atrial (LA) volumes, ejection fraction (EF), and MR severity progression identified two different phenotypes. We then compared them in terms of clinical characteristics, mechanistic and anatomical features, management, and outcomes. A total of 257 patients were included. Cluster 1 started with lower EF and LA strain and higher LV and LA volumes compared with Cluster 2, with a slower progression into severe SMR. At the onset of severe MR, Cluster 2 still had higher EF, lower LV volumes, but similar LA volumes and strain, and less proportionate SMR, compared with Cluster 1. They also had higher tenting height and more compensatory leaflet growth. On follow-up, Cluster 1 had more ventricular-directed therapies, whereas Cluster 2 received more mitral valve interventions. While the heart failure burden was higher in Cluster 1, there was no difference in mortality rates. Based on disease progression, two distinct progression patterns of SMR exist, having different anatomical and mechanistic features with variation in management and outcomes.

IRX2 activated by jumonji domain-containing protein 2A is crucial for cardiac hypertrophy and dysfunction in response to the hypertrophic stimuli

BackgroundIroquois homeobox 2 (IRX2) is a member of the Iroquois family whose upregulation has been potentially correlated to cardiac hypertrophy. This work studied the function of IRX2 and its related molecules in hypertrophic cardiomyopathy (HCM). MethodsA GEO dataset GSE32453 was analyzed to identify aberrantly expressed genes in HCM. Altered expression of IRX2 was induced in mice by lentivirus injection, followed by angiotensin II (Ang II) treatment to induce HCM. The function of IRX2 knockdown in ventricular dysfunction, heart volume and pathological changes in mice, and in surface area, oxidative stress and apoptosis of isolated cardiomyocytes were examined. Binding relationship between jumonji domain-containing protein 2A (JMJD2A) and IRX2 was predicted by online tools and validated. The interaction between JMJD2A and IRX2 in HCM development was examined by joint interventions. ResultsIRX2 was highly expressed in heart tissues with HCM. IRX2 knockdown prevented mice from Ang II-induced ventricular dysfunction, cardiac hypertrophy, inflammation and fibrosis in mouse heart, and it decreased the levels of cardiac hypertrophy-related markers, oxidative stress response, and apoptosis of Ang II-treated cardiomyocytes. JMJD2A catalyzed demethylation of H3K9me3 near the IRX2 promoter to activate its transcription. JMJD2A knockdown similarly exerted protective functions against cardiac hypertrophy in vivo and in vitro, but the protection was blocked upon further IRX2 upregulation. IRX2 was found to increase the Wnt/β-catenin signaling activation. ConclusionThis work reports that JMJD2A activates IRX2 transcription and the Wnt/β-catenin signaling to induce cardiac hypertrophy and dysfunction in HCM.

Brain Atrophy Is Substantially Accelerated in Neurological Wilson's Disease: A Longitudinal Study.

Although brain atrophy is common in neurological Wilson's disease, longitudinal studies are lacking. The objective of this study was to measure longitudinal brain atrophy rate and to relate it to the change in neurological impairment in Wilson's disease. We included patients with brain imaging done at diagnosis and at least 12months later. The atrophy rate was measured as percentage change in ventricular volume, whereas the change in neurological impairment was scored on the Unified Wilson's Disease Rating Scale. Of 57 patients, 36 had neurological presentation, 17 had hepatic presentation, and 4 were presymptomatic. The annualized atrophy rate was significantly greater in patients with the neurological presentation than in other patients (P=0.001). In the neurological presentation, the atrophy rate correlated with the change in impairment (rho=0.39, P=0.018) and was significantly greater in those with worsening after diagnosis than in those without worsening (P < 0.001). Brain atrophy rate appears as a promising marker of neurodegeneration in Wilson's disease. © 2022 International Parkinson and Movement Disorder Society.

Neurofilament-light and contactin-1 association with long-term brain atrophy in natalizumab-treated relapsing-remitting multiple sclerosis

Background: Despite highly effective treatment strategies for patients with relapsing-remitting multiple sclerosis (RRMS), long-term neurodegeneration and disease progression are often considerable. Accurate blood-based biomarkers that predict long-term neurodegeneration are lacking. Objective: To assess the predictive value of serum neurofilament-light (sNfL) and serum contactin-1 (sCNTN1) for long-term magnetic resonance imaging (MRI)–derived neurodegeneration in natalizumab-treated patients with RRMS. Methods: sNfL and sCNTN1 were measured in an observational cohort of natalizumab-treated patients with RRMS at baseline (first dose) and at 3 months, Year 1, Year 2, and last follow-up (median = 5.2 years) of treatment. Disability progression was quantified using “EDSS-plus” criteria. Neurodegeneration was measured by calculating annualized percentage brain, ventricular, and thalamic volume change (PBVC, VVC, and TVC, respectively). Linear regression analysis was performed to identify longitudinal predictors of neurodegeneration. Results: In total, 88 patients (age = 37 ± 9 years, 75% female) were included, of whom 48% progressed. Year 1 sNfL level (not baseline or 3 months) was associated with PBVC (standardized (std.) β = −0.26, p = 0.013), VVC (standardized β = 0.36, p < 0.001), and TVC (standardized β = −0.24, p = 0.02). For sCNTN1, only 3-month level was associated with VVC (standardized β = −0.31, p = 0.002). Conclusion: Year 1 (but not baseline) sNfL level was predictive for long-term brain atrophy in patients treated with natalizumab. sCNTN1 level did not show a clear predictive value.

Evaluation of the Physical Parameters on Ischemic Heart Disease Patients Using Echocardiography

Background: Left ventricular function and volumes have major diagnostic and prognostic importance in patients with various cardiac diseases, such as ischemic heart disease which is a life-threatening heart disease condition characterized by systolic dysfunction and a decrease in cardiac output. According to left ventricular ejection fraction, the degree of ischemic heart disease was classified as mild, moderate, and severe. To determine cardiac function and hemodynamics, the echocardiography technique is used, which is a noninvasive diagnostic method. Patients and Methods: The study included 216 patients between 25 and 75 years old; 121 males and 95 females; 265 normal individuals (age range: 25 to 75 years old); 84 males and 181 females. Doppler echocardiography was used to assess left ventricular function. The measurements included left ventricular end-diastole diameter (LVIDd), left ventricular end-systole diameter (LVIDs), and left ventricular ejection fraction (LVEF%). Results show a significant correlation in the values of EDV, ESV and LVEF (all: p &lt; 0.05). The change difference in left ventricular ejection fraction (LVEF) was (61.88%), (47.57%), and (36.76%), respectively, for all degrees of ischemia. While the change difference in left ventricular end diastolic volume (LVEDV)between patients and control groups was (173.38%), (248.83%), and (289.82%), respectively. On the other hand, the change in left ventricular end systolic volume (LVESV) was (258.73%), (495.13%), and (569.72%), respectively, for all degree of ischemia. Conclusion: The findings suggest that diastolic dysfunction is more common in patients than in healthy people. This could be due to the adverse effects of ischemic heart disease on the cardiac muscle. These changes in left ventricular structure may include left ventricular hypertrophy, increase in stiffness, and reduction in compliance.

Assessment of left ventricular function by spatio-temporal image correlation in fetuses with fetal growth restriction.

To compare the evaluation of left ventricular function by spatio-temporal image correlation (STIC) between fetal growth restriction (FGR) fetuses and normal fetuses. Forty-two FGR fetuses and 50 normal fetuses with gestational age ranging from 28 to 35weeks, were chosen for the study group and control group, respectively. The fetal heart was acquired using the STIC modality, beginning with a four-chamber view. A 7.5-12.5 s acquisition time and 20-35°angle of the acquisition were used for the acquisition. The resulting STIC dataset was saved for offline analysis. Ventricular volumes were measured using the Virtual Organ Computer-aided Analysis (VOCAL) mode, where the observer defines the contours of the ventricle and traces the endocardia. Stroke volume (SV)=end diastolic volume (EDV)-end systolic volume (ESV) and ejection fraction (EF)=SV/EDV × 100%. The data of the two groups were analyzed. (1) SV increased with fetal growth in both groups and was positively correlated with gestational age (p <.01), whereas EF remained constant throughout gestation and had no correlation with gestational age (p >.05). (2) There was no difference found in EF between the two groups, (p >.05), SV was significantly lower in FGR group than those in the normal group (p <.01). The STIC is a precise method for calculating fetal ventricular volume changes and functions. Reduced SV occurred at the initial stage of fetal deterioration before the discovery of abnormal EF in FGR fetuses, indicating cardiac dysfunction. SV could be a sensitive indicator of cardiac dysfunction. The use of EF to assess fetal cardiac function is not perfect.

Left ventricular volume change and long-term outcomes in ischaemic cardiomyopathy with or without surgical revascularisation: A post-hoc analysis of a randomised controlled trial.

SummaryBackgroundWhether the association between post-therapeutic left ventricular volume change and long-term outcomes in ischaemic cardiomyopathy is influenced by the performance of coronary artery bypass grafting (CABG) remains unclear. We sought to perform a post-hoc analysis of the Surgical Treatment of Ischaemic Heart Failure (STICH) trial to investigate this association in patients treated with medical therapy (MED) with or without CABG.MethodsFrom July 24, 2002, to May 5, 2007, 1212 patients with ischaemic cardiomyopathy were enrolled in the STICH trial (NCT00023595) from 99 sites in 22 countries, and were randomly assigned to undergo CABG plus MED or MED alone. We completed a post-hoc analysis of this trial. Patients with paired left ventricular end-systolic volume index (ESVI) measured at baseline and 4-months were included in our analysis. The association between change in ESVI from baseline to 4-months and cardiovascular mortality or all-cause mortality was assessed in MED arm and CABG plus MED arm.Findings523 patients were included, with 291 (55.6%) assigned to MED arm and 232 (44.4%) to CABG plus MED arm. At a 4-month follow-up, ESVI reduction was more likely to occur among patients undergoing CABG plus MED. After a median follow-up of 10.3 years, for each 26% (1- standard deviation) decrement in ESVI, it was associated with a 22% lower risk of cardiovascular mortality (HR 0.78; 95% CI, 0.65-0.94) and 19% lower risk of all-cause mortality (HR 0.81; 95% CI, 0.69-0.95) in MED arm, whereas this association was not shown in CABG plus MED arm (cardiovascular mortality: HR 0.90; 95%CI, 0.74-1.10; all-cause mortality: HR 0.93; 95%CI, 0.79-1.09). A 16% reduction in ESVI was determined to be the most appropriate threshold of change in ESVI in the MED arm.InterpretationIn patients with ischaemic cardiomyopathy, left ventricular volume change was associated with long-term prognosis after medical therapy alone, whereas was likely not an optimal benchmark for evaluating the survival benefits associated with CABG. A more than 16% reduction in ESVI might assist in therapeutic efficacy assessment and prognostic evaluation in medically treated patients.FundingNational Natural Science Foundation of China; Natural Science Funds of Guangdong Province.

Myocardial Injury After COVID-19 Vaccine-Associated Myocarditis: Natural History

Background : An uncommon side effect of the mRNA-based COVID-19 vaccine is acute myocarditis. The natural history of this problem is poorly understood. Methods : In 20 consecutive patients meeting the criteria, baseline and convalescent cardiac magnetic resonance (CMR) imaging evaluations were carried out. current Lake Louise mRNA-based vaccination criteria within 10 days of acute myocarditis. Between baseline and convalescence, CMR-based changes in left ventricular volumes, mass, ejection fraction (LVEF), tissue inflammation markers (native T1 and T2 mapping), and fibrosis markers (late gadolinium enhancement [LGE] and extracellular volume [ECV]) were evaluated. Clinical results and cardiac symptoms were recorded. Conclusions : Beyond three months of recovery in this young patient group, COVID-19 mRNA vaccineeassociated myocarditis demonstrated rapid improvements in CMRbased indices of edoema, contractile function, and overall LGE burden. However, regional fibrosis after edoema resolution was frequently seen, which supported the need for continuous observation.

Natural History of Myocardial Injury After COVID-19 Vaccine-Associated Myocarditis.

BackgroundAcute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. Little is known about the natural history of this complication.MethodsBaseline and convalescent (≥ 90 days) cardiac magnetic resonance (CMR) imaging assessments were performed in 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination. CMR-based changes in left ventricular volumes, mass, ejection fraction (LVEF), markers of tissue inflammation (native T1 and T2 mapping), and fibrosis (late gadolinium enhancement [LGE] and extracellular volume [ECV]) were assessed between baseline and convalescence. Cardiac symptoms and clinical outcomes were captured.ResultsMedian age was 23.1 years (range 18-39 years), and 17 (85%) were male. Convalescent evaluations were performed at a median (IQR) 3.7 (3.3-6.2) months. The LVEF showed a mean 3% absolute improvement, accompanied by a 7% reduction in LV end-diastolic volume and 5% reduction in LV mass (all P < 0.015). Global LGE burden wa reduced by 66% (P < 0.001). Absolute reductions in global T2, native T1, and ECV of 2.1 ms, 58 ms, and 2.9%, repectively, were documented (all P ≤ 0.001). Of 5 patients demonstrating LVEF ≤ 50% at baseline, all recovered to above this threshold in convalescence. A total of 18 (90%) patients showed persistence of abnormal LGE although mean fibrosis burden was < 5% of LV mass in 85% of cases. No patient experienced major clinical outcomes.ConclusionsCOVID-19 mRNA vaccine–associated myocarditis showed rapid improvements in CMR-based markers of edema, contractile function, and global LGE burden beyond 3 months of recovery in this young patient cohort. However, regional fibrosis following edema resolution was commonly observed, justifying need for ongoing surveillance.

Mechanisms of central brain atrophy in multiple sclerosis

Background: Change in ventricular volume has been suggested as surrogate measure of central brain atrophy (CBA) applicable to the everyday management of multiple sclerosis (MS) patients. Objectives: We investigated the contribution of inflammatory activity (including the severity of lesional tissue damage) to CBA. Methods: Fifty patients with relapsing–remitting multiple sclerosis (RRMS) were enrolled. Lesional activity during 4 years of follow-up was analysed using custom-build software, which segmented expanding part of the chronic lesions, new confluent lesions and new free-standing lesions. The degree of lesional tissue damage was assessed by change in mean diffusivity (MD). Volumetric change of lateral ventricles was used to measure CBA. Results: During follow-up, ventricles expanded on average by 12.6% ± 13.7% (mean ± SD). There was a significant increase of total lesion volume, 69.3% of which was due to expansion of chronic lesions. Correlation between volume of combined lesional activity and CBA (r2 = 0.67) increased when lesion volume was adjusted by the degree of tissue damage severity (r2 = 0.81). Regression analysis explained 90% of CBA variability, revealing that chronic lesion expansion was by far the largest contributor to ventricular enlargement. Discussion: CBA is almost entirely explained by the combination of the volume and severity of lesional activity. The expansion of chronic lesions plays a central role in this process.

Clinically important changes in right ventricular volume and function in pulmonary arterial hypertension assessed with cardiac magnetic resonance imaging.

Right ventricular (RV) dilatation predicts clinical worsening in pulmonary arterial hypertension (PAH) and RV volumes can be measured with high precision using cardiovascular magnetic resonance imaging. In regular follow‐up of patients and in studies of improvement in RV function, knowledge of clinically significant changes of RV volumes and function are of relevance. Patients with PAH were followed with cardiovascular magnetic resonance imaging and clinical assessment at 6‐month intervals. Changes in RV volumes associated with changes in clinical status were assessed. Twenty‐five patients with PAH (Group 1) were included and examined every 6 months for 2.5 years, with a total of 107 MRI scans. For a step change in WHO functional class, the associated change in RV volume was 11% (confidence interval 7%−14%, p < 0.0001) and in stroke volume 9% (confidence interval 3%−15%, p = 0.003). This study found an 11% change in RV volume to be clinically significant. The combination of clinically significant changes and the known precision in the measurements enables individualized follow‐up of RV‐function in PAH. To our knowledge, this study is the first to use repeated assessments to suggest clinically significant changes of RV volume based on changes in clinical presentation.

Non-invasive quantification of pressure–volume loops in patients with Fontan circulation

BackgroundPressure–volume (PV) loops provide comprehensive information of cardiac function, but commonly implies an invasive procedure under general anesthesia. A novel technique has made it possible to non-invasively estimate PV loops with cardiac magnetic resonance (CMR) and brachial pressure which would enable good volume estimation of often anatomically complex ventricles without the need of anesthesia in most cases. In this study we aimed to compare how hemodynamic parameters derived from PV loops in patients with Fontan circulation differ to controls.MethodsPatients with Fontan circulation (n = 17, median age 12 years, IQR 6–15) and healthy controls (n = 17, 14 years, IQR 13–22) were examined with CMR. Short axis balanced steady-state free-precession cine images covering the entire heart were acquired. PV loops were derived from left ventricular volumes in all timeframes and brachial blood pressure from cuff sphygmomanometry.ResultsFontan patients had lower stroke work, ventricular mechanical efficiency and external power compared to controls. Fontan patients with dominant right ventricle had higher potential energy indexed to body surface area but lower contractility (Ees) compared to controls. Fontan patients had higher arterial elastance (Ea) and Ea/Ees ratio than controls. Contractility showed no correlation with ejection fraction (EF) in Fontan patients irrespective of ventricular morphology. No difference was seen in energy per ejected volume between Fontan patients and controls.ConclusionsThis non-invasive PV-loop method could be used in future studies to show the potential prognostic value of these measures and if changes in ventricular function over time can be detected earlier by this method compared to changes in ventricular volumes and EF. In contrast to patients with acquired heart failure, Fontan patients had similar energy per ejected volume as controls which suggests similar ventricular oxygen consumption to deliver the same volume in Fontan patients as in controls.

A controlled comparison of cerebral volume loss after brain irradiation with proton versus photon radiotherapy.

2017 Background: Previous work has demonstrated cerebral volume loss after glioma treatment with concurrent photon radiotherapy (PHT) and chemotherapy. Proton radiotherapy (PRT) minimizes exposure of normal brain tissue compared with PHT. The objective of this study was to compare neurotoxic effects of PRT vs PHT in a retrospective case-matched control series of WHO grade 2 and 3 gliomas. Methods: PRT subjects were selected from ongoing longitudinal single-arm outcome studies being conducted at our institution (NCT01358058, NCT03286335). PHT subjects were identified via medical record search and were individually matched to PRT subjects using an eleven-tiered criterion (i.e., age, sex, tumor type, tumor location, laterality, IDH mutation status, 1p19q deletion status, concurrent chemotherapy, adjuvant chemotherapy, total Gy dose, and number of fractions). When individual matching was not possible on all 11 variables, efforts were made to identify the closest possible match. Only those subjects with at least two years of progression free survival and available T1 and T2/FLAIR MRI at baseline, one year, and two years following RT were included. The resulting sample included 17 PRT and 17 PHT patients with grade 2 and 3 gliomas (19 male; mean age = 40.10y; SD = 11.27). Non-parametric analyses were used to compare groups on demographic and tumor/treatment-related variables. Diffuse cerebral volume loss was estimated by manually measuring lateral ventricular volume in the tumor-free hemisphere. Results: Mann-Whitney tests of independence showed no significant differences between groups on any of the demographic variables or clinical characteristics. One-way ANOVA demonstrated that ventricular volume increase after two years was significantly greater in patients treated with PHT than with PRT, (F(1, 32.00) = 5.90, p &lt;.021, η2 =.156). Change in ventricular volume in the PHT group was 24.85% (SD = 14.45%) and in the PRT group was 12.03% (SD = 16.3%). Conclusions: The findings of this study suggest that 2 years post treatment for glioma, PRT is associated with less brain volume loss and ventricular expansion than PHT. The findings support the hypothesis that PRT can reduce neurotoxicity within the tumor-free hemisphere. This study is limited by the retrospective design and lack of randomization to treatment arms, though cohorts were well-matched following a rigorous set of criteria. The effects of PRT beyond 2 years after treatment remain unknown. Preservation of brain structure may be critically important for maintenance of brain function in this population of patients who have prolonged survival. Longitudinal cognitive assessment in brain tumor patients undergoing PHT vs PRT is needed and is currently being collected in NRG BN-005 (NCT03180502), which may provide important data regarding functional impact of the brain changes we have demonstrated.

Longitudinal MRI-visible perivascular space (PVS) changes with long-duration spaceflight.

Humans are exposed to extreme environmental stressors during spaceflight and return with alterations in brain structure and shifts in intracranial fluids. To date, no studies have evaluated the effects of spaceflight on perivascular spaces (PVSs) within the brain, which are believed to facilitate fluid drainage and brain homeostasis. Here, we examined how the number and morphology of magnetic resonance imaging (MRI)-visible PVSs are affected by spaceflight, including prior spaceflight experience. Fifteen astronauts underwent six T1-weighted 3 T MRI scans, twice prior to launch and four times following their return to Earth after ~ 6-month missions to the International Space Station. White matter MRI-visible PVS number and morphology were calculated using an established, automated segmentation algorithm. We validated our automated segmentation algorithm by comparing algorithm PVS counts with those identified by two trained raters in 50 randomly selected slices from this cohort; the automated algorithm performed similarly to visual ratings (r(48) = 0.77, p < 0.001). In addition, we found high reliability for four of five PVS metrics across the two pre-flight time points and across the four control time points (ICC(3,k) > 0.50). Among the astronaut cohort, we found that novice astronauts showed an increase in total PVS volume from pre- to post-flight, whereas experienced crewmembers did not (p = 0.020), suggesting that experienced astronauts may exhibit holdover effects from prior spaceflight(s). Greater pre-flight PVS load was associated with more prior flight experience (r = 0.60–0.71), though these relationships did not reach statistical significance (p > 0.05). Pre- to post-flight changes in ventricular volume were not significantly associated with changes in PVS characteristics, and the presence of spaceflight associated neuro-ocular syndrome (SANS) was not associated with PVS number or morphology. Together, these findings demonstrate that PVSs can be consistently identified on T1-weighted MRI scans, and that spaceflight is associated with PVS changes. Specifically, prior spaceflight experience may be an important factor in determining PVS characteristics.

Regulation of Ncbe in the Choroid Plexus of Mice after Hemorrhage‐Induced Hydrocephalus

The choroid plexus (CP) is a small tissue located inside brain ventricles. It is responsible for the production of most of the cerebrospinal fluid (CSF); approximately 500 mL of CSF per day in the adult human [1, 2]. CSF production occurs as a net result of transcellular movement of salt and water, carried out by various cellular transporters.Ncbe is a sodium‐coupled bicarbonate transporter located in the basolateral membrane of the choroid plexus epithelial (CPE) cells. It transports Na+ and HCO3‐ into the cell in exchange for Cl‐. Ncbe is the main sodium loader of the cell and CSF production is probably dependent on this transporter [3].Posthemorrhagic hydrocephalus (PHH) is a pathological state, caused by an accumulation of CSF in the ventricular system following intraventricular hemorrhage. CSF buildup is caused by a disproportion in CSF production and reabsorption. This leads to an expansion of the brain ventricles. Intraventricular hemorrhage (IVH) is known to cause inflammation in the CP, which is coupled to an over‐production of CSF [4‐6].Initially we hypothesized that IVH would stimulate Ncbe in the CPE through increased protein abundance as well as transporter activity. This would lead to increased CSF formation, similar to the response found after treatment with e.g. the cyclic‐AMP agonist forskolin [7]. Our preliminary data, however, suggest that Ncbe abundance is reduced by 24% (n=4, p=0.0329) in mice in the initial stages of PHH and then normalizes.The aim of this study is to investigate which role Ncbe plays in PHH and how Ncbe knock down affects CSF production in both healthy mice and a disease model.An adeno‐associated virus (AAV) shRNA knockdown vector system has been developed to knock down Ncbe gene expression by intracerebroventricular injections. Our preliminary data shows that the CPE cells incorporate the vector when tagged with GFP.We have established an IVH model and recording of CSF secretion rates in mice. Increased CSF formation rate was validated with ventriculo‐cisternal perfusion (data shown in figure). The resulting changes in ventricular volume will be investigated using magnetic resonance imaging (MRI).We propose that Ncbe knock down inhibits CSF production and could potentially target inflammation‐dependent hypersecretion by reducing the availability of the sodium supplying the apical transporters in the CP.