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Journal of Extracellular Biology Oct 2023Pleural effusion occurs in both benign and malignant pleural disease. In malignant pleural effusions, the diagnostic accuracy and sensitivity of pleural fluid cytology...
Pleural effusion occurs in both benign and malignant pleural disease. In malignant pleural effusions, the diagnostic accuracy and sensitivity of pleural fluid cytology is less than perfect, particularly for the diagnosis of malignant pleural mesothelioma, but also in some cases for the diagnosis of metastatic pleural malignancy with primary cancer in the lung, breast or other sites. Extracellular vesicles (EVs) carry an enriched cargo of microRNAs (miRNAs) which are selectively packaged and differentially expressed in pleural disease states. To investigate the diagnostic potential of miRNA cargo in pleural fluid extracellular vesicles (PFEVs), we evaluated methods for isolating the extracellular vesicle (EV) fraction including combinations of ultracentrifugation, size-exclusion chromatography (SEC) and ultrafiltration (10 kDa filter unit). PFEVs were characterized by total and EV-associated protein, nanoparticle tracking analysis and visualisation by transmission electron microscopy. miRNA expression was analyzed by Nanostring nCounter® in separate EV fractions isolated from pleural fluid with or without additional RNA purification by ultrafiltration (3 kDa filter unit). Optimal PFEV yield, purity and miRNA expression were observed when PFEV were isolated from a larger volume of pleural fluid processed through combined ultracentrifugation and SEC techniques. Purification of total RNA by ultrafiltration further enhanced the detectability of PFEV miRNAs. This study demonstrates the feasibility of isolating PFEVs, and the potential to examine PFEV miRNA cargo using Nanostring technology to discover disease biomarkers.
PubMed: 38939736
DOI: 10.1002/jex2.119 -
JACC. Advances Feb 2024Previous studies have linked cardiovascular risk factors during midlife to cognitive function in later life. However, few studies have looked at the association between...
BACKGROUND
Previous studies have linked cardiovascular risk factors during midlife to cognitive function in later life. However, few studies have looked at the association between cardiac function, brain structure, and cognitive function and even less have included diverse middle-aged populations.
OBJECTIVES
The objective of this study was to determine associations between cardiac and brain structure and function in a multiethnic cohort of middle-aged adults.
METHODS
A cross-sectional study was conducted in participants of the Dallas Heart Study phase 2 (N = 1,919; 46% Black participants). Left ventricular (LV) mass, LV ejection fraction, LV concentricity, and peak systolic strain (LV E) were assessed by cardiac magnetic resonance imaging. White matter hyperintensities (WMH) volume was measured by fluid attenuated inversion recovery magnetic resonance imaging. The Montreal Cognitive Assessment was used to measure cognitive functioning. Associations between cardiac and brain measures were determined using multivariable linear regression after adjusting for cardiovascular risk factors, education level, and physical activity.
RESULTS
LV ejection fraction was associated with total Montreal Cognitive Assessment score (β = 0.06 [95% CI: 0.003-0.12], = 0.042) and LV E was associated with WMH volume (β = 0.08 [95% CI: 0.01-0.14], = 0.025) in the overall cohort without significant interaction by race/ethnicity. Higher LV mass and concentricity were associated with larger WMH volume in the overall cohort (β = 0.13 [95% CI: 0.03-0.23], = 0.008 and 0.10 [95% CI: 0.03-0.17], = 0.005). These associations were more predominant in Black than White participants (β = 0.17 [95% CI: 0.04-0.30] vs β = -0.009 [95% CI: -0.16 to 0.14], = 0.036 and β = 0.22 [95% CI: 0.13-0.32] vs β = -0.11 [95% CI: -0.21 to -0.01], < 0.0001, for LV mass and concentricity, respectively).
CONCLUSIONS
Subclinical cardiac dysfunction indicated by LVEF was associated with lower cognitive function. Moreover, LV mass and concentric remodeling were associated with higher WMH burden, particularly among Black individuals.
PubMed: 38939405
DOI: 10.1016/j.jacadv.2023.100777 -
JACC. Advances Jun 2024
PubMed: 38938855
DOI: 10.1016/j.jacadv.2024.101000 -
JACC. Advances Jun 2024Heart failure with reduced ejection fraction (HFrEF) is characterized by ventricular remodeling and impaired myocardial energetics. Left ventricular pressure-volume (PV)...
BACKGROUND
Heart failure with reduced ejection fraction (HFrEF) is characterized by ventricular remodeling and impaired myocardial energetics. Left ventricular pressure-volume (PV) loop analysis can be performed noninvasively using cardiovascular magnetic resonance (CMR) imaging to assess cardiac thermodynamic efficiency.
OBJECTIVES
The aim of the study was to investigate whether noninvasive PV loop parameters, derived from CMR, could predict major adverse cardiac events (MACE) in HFrEF patients.
METHODS
PV loop parameters (stroke work, ventricular efficiency, external power, contractility, and energy per ejected volume) were computed from CMR cine images and brachial blood pressure. The primary end point was MACE (cardiovascular death, heart failure (HF) hospitalization, myocardial infarction, revascularization, ventricular tachycardia/fibrillation, heart transplantation, or left ventricular assist device implantation within 5 years). Associations between PV loop parameters and MACE were evaluated using multivariable Cox regression.
RESULTS
One hundred and sixty-four HFrEF patients (left ventricular ejection fraction ≤40%, age 63 [IQR: 55-70] years, 79% male) who underwent clinical CMR examination between 2004 and 2014 were included. Eighty-eight patients (54%) experienced at least one MACE after an average of 2.8 years. Unadjusted models demonstrated a significant association between MACE and all PV loop parameters ( < 0.05 for all), HF etiology ( < 0.001), left ventricular ejection fraction ( = 0.003), global longitudinal strain ( < 0.001), and N-terminal prohormone of brain natriuretic peptide level ( = 0.001). In the multivariable Cox regression analysis adjusted for age, sex, hypertension, diabetes, and HF etiology, ventricular efficiency was associated with MACE (HR: 1.04 (95% CI: 1.01-1.08) per-% decrease, = 0.01).
CONCLUSIONS
Ventricular efficiency, derived from noninvasive PV loop analysis from standard CMR scans, is associated with MACE in patients with HFrEF.
PubMed: 38938852
DOI: 10.1016/j.jacadv.2024.100946 -
JACC. Advances Mar 2024Low stroke volume index <35 ml/m despite preserved ejection fraction (paradoxical low flow [PLF]) is associated with adverse outcomes in patients with aortic stenosis...
BACKGROUND
Low stroke volume index <35 ml/m despite preserved ejection fraction (paradoxical low flow [PLF]) is associated with adverse outcomes in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). However, whether the risk associated with PLF is similar in both sexes is unknown.
OBJECTIVES
The purpose of this study was to analyze the risk associated with PLF in severe aortic stenosis for men and women randomized to TAVR or SAVR.
METHODS
Patients with ejection fraction ≥50% from the PARTNER (Placement of Aortic Transcatheter Valves) 2 and 3 trials were stratified by sex and treatment arm. The impact of PLF on the 2-year occurrence of the composite of death or heart failure hospitalization (primary endpoint) and of all-cause mortality alone (secondary endpoint) was analyzed. Analysis of variance was used to assess baseline differences between groups. Multivariate Cox regression analysis was used to identify predictors of the endpoint.
RESULTS
Out of 2,242 patients, PLF was present in 390 men and 239 women (30% vs 26%, = 0.06). PLF was associated with a higher rate of NYHA functional class III to IV dyspnea (60% vs 54%, < 0.001) and a higher prevalence of atrial fibrillation (39% vs 24%, < 0.001). PLF was a significant predictor of the primary endpoint among women undergoing SAVR in multivariate analysis (adjusted HR: 2.25 [95% CI: 1.14-4.43], = 0.02) but was not associated with a worse outcome in any of the other groups (all > 0.05).
CONCLUSIONS
In women with PLF, TAVR may improve outcomes compared to SAVR. PLF appears to have less impact on outcomes in men.
PubMed: 38938841
DOI: 10.1016/j.jacadv.2024.100853 -
JACC. Advances Mar 2024FAV is offered to fetuses with severe aortic valve stenosis and evolving hypoplastic left heart syndrome. An inferential analysis of TS and SAE in a large series has not...
BACKGROUND
FAV is offered to fetuses with severe aortic valve stenosis and evolving hypoplastic left heart syndrome. An inferential analysis of TS and SAE in a large series has not been reported.
OBJECTIVES
The purpose of this study was to determine factors associated with fetal aortic valvuloplasty (FAV) technical success (TS) and serious adverse events (SAEs).
METHODS
Retrospective, single-center, cohort analysis of attempted FAV from March 1, 2000, to December 31, 2020. The primary outcome was the TS of FAV, and the secondary outcome was the presence of an SAE.
RESULTS
A total of 165 FAVs were attempted in 163 patients with a median gestational age of 24.6 weeks (IQR: 22.9-27.1 weeks). FAV TS was 85% (141/165) and was higher in the 2010 to 2020 era (94% [85/90] vs 75% [56/75]; < 0.001). Pre-FAV echocardiographic left ventricle (LV) long axis dimension z-score >-0.10 ( < 0.001) and higher LV ejection fraction ( = 0.037) were independently associated with a higher odds of TS. There were 117 SAEs in 67 attempted FAVs (41%), 13 of which were fetal deaths (7.9%). By classification and regression tree analysis, gestational age <21 weeks or in older fetuses, a procedure time of ≥39.6 minutes was associated with higher SAE rate. In the multivariable logistic regression model correcting for gestational age, fetuses with an LV end-diastolic volume <4.09 mL had an age-adjusted OR of 4.71 (95% CI: 1.67-13.29; = 0.004) for experiencing an SAE.
CONCLUSIONS
TS of FAV has improved over time, and failure is associated with smaller fetal left heart sizes. SAEs are common and are associated with smaller left hearts and longer procedure times.
PubMed: 38938833
DOI: 10.1016/j.jacadv.2024.100835 -
JACS Au Jun 2024Reductive catalytic fractionation (RCF) is a promising method to extract and depolymerize lignin from biomass, and bench-scale studies have enabled considerable progress...
Reductive catalytic fractionation (RCF) is a promising method to extract and depolymerize lignin from biomass, and bench-scale studies have enabled considerable progress in the past decade. RCF experiments are typically conducted in pressurized batch reactors with volumes ranging between 50 and 1000 mL, limiting the throughput of these experiments to one to six reactions per day for an individual researcher. Here, we report a high-throughput RCF (HTP-RCF) method in which batch RCF reactions are conducted in 1 mL wells machined directly into Hastelloy reactor plates. The plate reactors can seal high pressures produced by organic solvents by vertically stacking multiple reactor plates, leading to a compact and modular system capable of performing 240 reactions per experiment. Using this setup, we screened solvent mixtures and catalyst loadings for hydrogen-free RCF using 50 mg poplar and 0.5 mL reaction solvent. The system of 1:1 isopropanol/methanol showed optimal monomer yields and selectivity to 4-propyl substituted monomers, and validation reactions using 75 mL batch reactors produced identical monomer yields. To accommodate the low material loadings, we then developed a workup procedure for parallel filtration, washing, and drying of samples and a H nuclear magnetic resonance spectroscopy method to measure the RCF oil yield without performing liquid-liquid extraction. As a demonstration of this experimental pipeline, 50 unique switchgrass samples were screened in RCF reactions in the HTP-RCF system, revealing a wide range of monomer yields (21-36%), S/G ratios (0.41-0.93), and oil yields (40-75%). These results were successfully validated by repeating RCF reactions in 75 mL batch reactors for a subset of samples. We anticipate that this approach can be used to rapidly screen substrates, catalysts, and reaction conditions in high-pressure batch reactions with higher throughput than standard batch reactors.
PubMed: 38938803
DOI: 10.1021/jacsau.4c00126 -
JACC. Advances Dec 2023Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the...
BACKGROUND
Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the pathogenic pathways underlying this relationship are unclear. Subclinical myocardial fibrosis has been found to be a common pathway in a large proportion of patients with heart failure with preserved ejection fraction.
OBJECTIVES
This study examined the relationship between vital reproductive factors (parity, pregnancy, age at menopause, and use of hormone replacement therapy [HRT]) with interstitial myocardial fibrosis (IMF) and myocardial scar measured by cardiac magnetic resonance imaging (CMR) T1 mapping and late gadolinium enhancement, respectively.
METHODS
There were 596 female participants (mean age 67 ± 8 years) enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) who had complete parity data and underwent CMR. Parity was categorized as 0 live births, 1 to 2, 3 to 4, and ≥5 live births. Multivariable regression models were constructed to assess the associations of parity status, history of null gravidity, age at menopause and HRT with CMR obtained measures of IMF (extracellular volume [ECV], native-T1 time) and myocardial scar.
RESULTS
Women with a history of nulliparity had greater ECV% (β = 0.95 ± 0.28, = 0.001) and native-T1 ms (β = 10.6 ± 4.9, = 0.03) than those who had 1 to 2 live births. These associations were independent of age, traditional cardiovascular risk factors, and interim cardiovascular events. Similar associations were found for women with a history of null gravidity compared to those with a history of pregnancy (ECV% [β = 0.7 ± 0.3, = 0.02] and native-T1 ms [β = 10.6 ± 5.2, = 0.04]). There was no association between age at menopause and HRT with markers of IMF. There were no associations between parity status, null gravidity, and age of menopause with the presence of myocardial scar; however, those who used HRT were independently associated with a lesser risk of myocardial scar (OR: 0.20; 95% CI: 0.05-0.82).
CONCLUSIONS
In a multiethnic cohort, women with a history of nulliparity or null gravidity had greater IMF defined by CMR, while those who used HRT were less likely to have myocardial scar.
PubMed: 38938498
DOI: 10.1016/j.jacadv.2023.100703 -
JACC. Advances Dec 2023Clinical significance of an integrated evaluation of epicardial adipose tissue (EAT) and the right ventricle (RV) in heart failure with preserved ejection fraction...
BACKGROUND
Clinical significance of an integrated evaluation of epicardial adipose tissue (EAT) and the right ventricle (RV) in heart failure with preserved ejection fraction (HFpEF) is unknown.
OBJECTIVES
The authors investigated the potential of EAT and RV quantification for obesity-related pathophysiology and risk stratification in obese HFpEF patients using cardiovascular magnetic resonance (CMR).
METHODS
A total of 150 patients (obese, body mass index ≥30 kg/m; n = 73, nonobese, body mass index <30 kg/m; n = 77) with a clinical diagnosis of HFpEF undergoing CMR were retrospectively identified. EAT volume surrounding both ventricles were quantified with manual delineation on cine images. Total RV volume (TRVV) was calculated as the sum of RV cavity and mass at end-diastole. The endpoint was the composite of all-cause mortality and first HF hospitalization.
RESULTS
During a median follow-up of 46 months, 39 nonobese patients (51%) and 32 obese patients (44%) experienced the endpoint. EAT was a prognostic biomarker regardless of obesity and was independently correlated with TRVV. In obese HFpEF, EAT correlated with RV longitudinal strain (r = 0.32, = 0.006), and increased amount of EAT and TRVV was associated with greater left ventricular end-diastolic eccentric index (r = 0.36, = 0.002). The integration of RV quantification into EAT provided improved risk stratification with a C-statistic increase from 0.70 to 0.79 in obese HFpEF. Obese patients with EAT<130 ml and TRVV<180 ml had low risk (annual event rate 3.2%), while those with increased EAT ≥130 ml and TRVV ≥180 ml had significantly higher risk (annual event rate 11.8%; < 0.001).
CONCLUSIONS
CMR quantification of EAT and RV structure provides additive risk stratification for adverse outcomes in obese HFpEF.
PubMed: 38938495
DOI: 10.1016/j.jacadv.2023.100730 -
JACC. Advances Dec 2023Studies comparing COVID-19 vaccine-associated and classical myocarditis (CM) are lacking.
BACKGROUND
Studies comparing COVID-19 vaccine-associated and classical myocarditis (CM) are lacking.
OBJECTIVES
The purpose of this study was to compare cardiac magnetic resonance (CMR) imaging findings and short-term clinical outcomes in patients with messenger RNA COVID-19 postvaccination myocarditis (PVM) and CM.
METHODS
This was a retrospective study of patients with myocarditis: 31 with PVM and 46 with CM. Patients underwent a CMR protocol scan including T1 and T2 sequences. Late gadolinium enhancement (LGE) was expressed as percentage of left ventricular myocardial mass and the extracellular volume was calculated based on precontrast and postcontrast T1 images. Clinical outcomes included heart failure hospitalizations and mortality.
RESULTS
Study patients were predominantly male (81% in PVM vs 89% in CM, = 0.330). Patients with PVM had lower T1 values compared with CM (1,064.2 ± 67.0 ms vs 1,081.6 ± 41.9 ms, = 0.032), although T2 and extracellular volume values were similar in both groups. Left ventricular ejection fraction and LGE were similar in both groups. The most frequent location of LGE was the basal inferolateral wall. PVM more commonly demonstrated a mid-wall LGE pattern while CM demonstrated a subepicardial LGE pattern. Compared with CM, patients with PVM were more likely to have a pericardial effusion (42% vs 17%, = 0.018) and pericardial LGE (38% vs 13%, = 0.009). During short-term follow-up (median 300 days for PVM, 319 days for CM), there were no deaths or heart failure hospitalizations in either group.
CONCLUSIONS
Our study shows similar CMR imaging findings and short-term outcomes in PVM and CM, although PVM was associated with milder myocardial abnormalities and more frequent pericardial involvement.
PubMed: 38938491
DOI: 10.1016/j.jacadv.2023.100726