Cardiopulmonary Performance Among Heart Failure Patients Before and After Left Ventricular Assist Device Implantation.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) have persistent impairments in functional capacity after continuous-flow left ventricular assist device (CF-LVAD) implantation. OBJECTIVES: This study aims to characterize longitudinal changes in exercise hemodynamics and functional capacity among patients with HFrEF before and after CF-LVAD implantation. METHODS: Ten patients underwent 3 invasive cardiopulmonary exercise tests on upright cycle ergometry with pulmonary artery catheterization: 1) Visit 1 before CF-LVAD implantation; 2) Visit 2 after device implantation with CF-LVAD pump speed held constant at baseline speed; and 3) Visit 3 with increases in pump speed during exercise (median: 1,050 rpm [IQR: 750-1,150 rpm] and 220 rpm [IQR: 120-220 rpm] for HeartMate 3 and HeartWare VAD, respectively). Hemodynamics and direct Fick cardiac output were monitored using pulmonary artery catheterization. Gas exchange metrics were determined using indirect calorimetry. RESULTS: Maximal oxygen uptake (Visits 1, 2, and 3: 10.8 ± 2.5 mL/kg/min, 10.7 ± 2.2 mL/kg/min, and 11.5 ± 1.7 mL/kg/min; P = 0.92) did not improve after device implantation. Mean pulmonary arterial and pulmonary capillary wedge pressures increased significantly during submaximal and peak exercise on preimplantation testing (P < 0.01 for rest vs peak exercise) and remained elevated, with minimal change on Visits 2 and 3 regardless of whether pump speed was fixed or increased. CONCLUSIONS: Among patients with HFrEF, cardiovascular hemodynamics and exercise capacity were similar after CF-LVAD implantation, regardless of whether patients exercised at fixed or adjusted pump speeds during exercise. Further research is needed to determine methods by which LVADs may alleviate the HFrEF syndrome after device implantation. (Effect of mechanIcal circulatoRy support ON exercise capacity aMong pAtieNts with heart failure [IRONMAN]; NCT03078972).

Bariatric Surgery Is Associated With Decreased Calcineurin Inhibitor Time in Therapeutic Range After Heart Transplantation.

Bariatric surgery (BSg) is an effective treatment for morbid obesity, but little is known about the outcomes of BSg patients who undergo orthotopic heart transplantation (OHT). The aim of this study was to determine if BSg alters calcineurin inhibitor (CNI) level variability after OHT. Data were collected from 58 consecutive patients who underwent OHT at a single center from 1/2018 to 4/2019: 4 with BSg prior to OHT (BSg + OHT) and 54 without prior BSg (OHT). CNI level, cardiac biopsy, and left ventricular ejection fraction (LVEF) data were collected during the first 6 months post-OHT. Comparisons were made for 3 measures of CNI variability: coefficient of variation, time in therapeutic range (TTR), and TTR by the Rosendaal method. A Pearson's correlation coefficient was calculated to assess the relationship between CNI TTR, episodes of rejection, and LVEF. The results show TTR was lower in BSg + OHT compared to OHT (12.5% vs 31.3%, P < .05). For the entire cohort, greater TTR correlated with fewer episodes of rejection (r = 0.31, P < .05). In conclusion, these findings suggest BSg + OHT patients may warrant closer monitoring of CNI levels post-OHT. Furthermore, episodes of rejection and LVEF were similar for BSg + OHT patients, indicating that BSg should not be a contraindication to transplant.

Coordinated Regulation of Axonal Microtubule Organization and Transport by Drosophila Neurexin and BMP Pathway.

Neurexins are well known trans-synaptic cell adhesion molecules that are required for proper synaptic development and function across species. Beyond synapse organization and function, little is known about other roles Neurexins might have in the nervous system. Here we report novel phenotypic consequences of mutations in Drosophila neurexin (dnrx), which alters axonal microtubule organization and transport. We show that dnrx mutants display phenotypic similarities with the BMP receptor wishful thinking (wit) and one of the downstream effectors, futsch, which is a known regulator of microtubule organization and stability. dnrx has genetic interactions with wit and futsch. Loss of Dnrx also results in reduced levels of other downstream effectors of BMP signaling, phosphorylated-Mad and Trio. Interestingly, postsynaptic overexpression of the BMP ligand, Glass bottom boat, in dnrx mutants partially rescues the axonal transport defects but not the synapse undergrowth at the neuromuscular junctions. These data suggest that Dnrx and BMP signaling are involved in many diverse functions and that regulation of axonal MT organization and transport might be distinct from regulation of synaptic growth in dnrx mutants. Together, our work uncovers a novel function of Drosophila Neurexin and may provide insights into functions of Neurexins in vertebrates.

The impact of carrying supplemental oxygen on exercise capacity and dyspnea in patients with interstitial lung disease.

BACKGROUND: May patients with interstitial lung disease (ILD) require supplementary oxygen (O2) therapy to maintain normoxia. However, ambulatory O2 delivery devices are constraining and cumbersome. The physiologic and symptomatic impact of these devices on ILD patients is unknown. METHODS: We conducted a prospective study of 30 clinically stable ILD patients (with varying disease severity), half of whom used O2 at baseline. Each subject completed two six-minute walk tests (6MWTs); for O2 users, one walk was completed while wearing a backpack (weight 7.2 pounds) containing a tank with compressed O2, and for non-users, one walk was completed with a similarly-weighted backpack. For each subject, during the second walk, no backpack was worn; for the second walk, O2 users received oxygen via a stationary delivery system. For both walks, O2 non-users wore a portable metabolic system, which measured variables related to respiratory physiology and gas exchange. Borg dyspnea and exertion ratings were recorded after each walk. RESULTS: Wearing the O2-containing backpack resulted in decreased distance covered during the 6MWT, and increased dyspnea and perceived exertion among O2 users. While wearing the weighted backpack, O2 non-users had a significantly lower peripheral O2 saturation and distance-saturation product. Compared with carrying O2 in the backpack, receiving O2 via the stationary concentrator resulted in the largest improvement in walk distance for the three subjects with greatest impairment at baseline (6MWT ≤ 300 m). CONCLUSION: Among ILD patients, carrying portable O2 versus receiving O2 via a stationary concentrator results in significantly greater dyspnea and shorter distances covered in timed testing. Patients with the greatest impairment may be affected most. When prescribing O2, practitioners should alert patients to this effect and help patients decide on the best O2 delivery mode to meet their needs.

Genetic aspects of autism spectrum disorders: insights from animal models.

Autism spectrum disorders (ASDs) are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development, and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy, and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute toward the formation, stabilization, and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.