Citations

Introduction: Papillary fibroelastomas (PFEs) are the 3rd most common primary cardiac tumors with a prevalence of around 0.01% in patients with echocardiograms. The pathogenesis is controversial but endocardial trauma has been implicated. We hypothesized that increased turbulence in hypertrophic cardiomyopathy (HCM) would be a risk factor for PFE development and characterized PFEs in HCM. Around 5% of HCM patients had neurologic events. We postulated that patients with both PFE and HCM had a higher risk of neurologic events. Methods: We reviewed pathology records from 1990 –2006 and identified 129 subjects with PFEs and 2479 patients with HCM. We then identified the subjects who had both HCM and PFE (n = 19). All subjects signed release for use of their medical records for research. Results: 19 subjects (68.4% female) had both HCM and PFE. Mean age at diagnosis of HCM was 49 (range 21– 81) years. All had outflow tract obstruction with resting gradient >/=30 mm Hg except 2 who had resting gradients <30 mm Hg but elevated gradients on provocation. PFE diagnosis was after a mean of 9.7 years (SD 8.3) following HCM diagnosis. 5 subjects were diagnosed pre-operatively by transthoracic echocardiography, 2 subjects by transesophageal echocardiography and 12 subjects at surgery only. Most subjects had only 1 PFE (57.9%) but 1 subject had as many as 40 tumors. Most PFEs were on the aortic valve (47.4%) and the left ventricular side of the septum and left ventricular outflow tract (42.1%). Only 2 patients had right heart lesions that were presumably unrelated to HCM. 3 patients had previous septal myectomies and all 3 had PFEs near the previous resection. 5 of 19 subjects (26.3%) with PFE and HCM had neurologic events (either strokes or transient ischemic attacks) compared to 199 of 2261 subjects (8.8%) with HCM alone (OR = 4.1; 95% CI 1.4 –11.4, p < 0.05). Conclusion: Nearly 90% of PFEs in HCM are located in the septum, left ventricular outflow tract and aortic valve. This may be supportive of endocardial trauma as a risk factor for PFE development in HCM. About a quarter of patients with PFEs and HCM had neurologic events. This may indicate that these lesions are not innocuous and should perhaps be actively searched for in patients with HCM and unexplained neurologic events.

Introduction: Individuals born premature have smaller ventricular chambers volumes and a reduced cardiac reserve during exercise. Epidemiologic studies demonstrate increased risk of developing heart failure by young adulthood, though whether this is due primarily to systolic or diastolic dysfunction remains unresolved. Hypothesis: We hypothesize that either systolic or diastolic function, quantified as intraventricular kinetic energy (KE) during systolic and diastolic phases, respectively, will be altered in both ventricles of young adults born premature. Methods: A total of 56 young adults participated in this observational cardiac MRI study: 35 subjects born moderately to extremely premature (birth weight <1500 g or gestational age ≤32 weeks), and 21 age-matched term-born subjects. Each subject underwent cardiac MRI, including cine cardiac structure/function assessment and four-dimensional flow-encoded MRI (4D flow MRI). Five 4D flow parameters, normalized by end diastolic volume (EDV) to control for heart size, were extracted from each ventricle’s KE-time curve: average KE/EDV, peak systolic KE/EDV, early diastolic (E-wave) KE/EDV, late diastolic (A-wave) KE/EDV, and the ratio of E-wave KE to A-wave KE. Results: Average KE/EDV and peak systolic KE/EDV were similar between term and preterm subjects. Preterm-born subjects had increased A-wave KE/EDV in the RV and decreased E/A KE ratio in both ventricles (Table 1), indicating subtle diastolic dysfunction. The E/A KE ratio was moderately correlated with stroke volume index in both ventricles (LV: R=0.37, P=0.005; RV: R=0.32, P=0.02). Conclusions: Our results suggest that diastolic dysfunction, along with reduced chamber size, contributes to the reduced stroke volume seen in individuals born premature. In addition, diastolic dysfunction may further limit cardiac functional reserve and increase early heart failure risk in this population.

HIV is an independent risk factor for lung disease, including chronic obstructive pulmonary disease (COPD) and emphysema. Angiotensin receptor blockers may be beneficial in COPD and emphysema through pathways that have been implicated in HIV-related lung disease. We performed a randomized comparison of the effects of losartan versus placebo on the plasma concentrations of the pneumoproteins, surfactant protein D (SPD) and club cell secretory protein (CCSP), in people living with HIV (PLWH). A total of 108 PLWH were included (52 assigned to losartan and 56 assigned to placebo). We found no difference in the change from baseline in log 2 concentrations of CCSP or SPD over 1 year of follow-up. For SPD, we found a strong interaction by CD4+ counts, where those with CD4+ counts >350 cells/mm 3 treated with losartan had more reduction (improvement) in SPD concentration than those treated with placebo ( p value for interaction <.001). In conclusion, we did not find a beneficial effect of losartan on pneumoprotein concentrations in PLWH, but PLWH with higher CD4+ counts may have improvement in SPD when treated with losartan.

Abstract Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.

Abstract BACKGROUND Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial. OBJECTIVE To compare the outcomes of observation versus intervention for low-grade dAVFs. METHODS We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up. RESULTS The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort ( P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively. CONCLUSION Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs.

ObjectivesTo quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms.MethodsTwo elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz.ResultsThe SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a − 0.27 ± 0.027‐m/s (−12.2% ± 1.2%) bias when using the clinically implemented 60‐Hz vibration source.ConclusionsShear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140‐Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

Abstract Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q &lt; 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.