Ali A. Weinstein

Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension.

BACKGROUND Pulmonary hypertension (PH) restricts the ability to engage in physical activity and decreases longevity. We examined the impact of aerobic exercise training on function and quality of life in patients with World Health Organization group 1 PH. METHODS Patients were randomized to a 10-week education only (EDU) or education/exercise combined (EXE) group. The exercise program consisted of 24-30 sessions of treadmill walking for 30-45 min per session at 70% to 80% of heart rate reserve. Outcome variables included changes in 6-min walk test (6MWT) distance, time to exercise intolerance, peak work rate (WR) from a cardiopulmonary treadmill test, and quality-of-life measures, including the Short Form Health Survey, version 2 (SF-36v2) and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). RESULTS Data are presented as mean SD. Twenty-three women (age, 54 11 years; BMI, 31 7 kg/m 2 ) were randomized to the EDU (n 5 13) or EXE (n 5 10) groups. Following 10 weeks of intervention, patients in the EXE group demonstrated an improvement in 6MWT distance (56 45 m; P 5 .002), increased time to exercise intolerance (1.9 1.3 min; P 5 .001), and peak WR (26 23 W; P 5 .004). Additionally, the EXE group scored significantly ( P , .050) better on six of the eight scales on SF-36v2, and fi ve of the six scales on CAMPHOR. In contrast, no significant improvement was observed for any of the outcome measures following EDU. No adverse events were noted in either group. CONCLUSION Ten weeks of brisk treadmill walking improved 6MWT distance, cardiorespiratory function, and patient-reported quality of life in female patients with group 1 PH.

Neurohormonal and Inflammatory Hyper-Responsiveness to Acute Mental Stress in Depression

Depression is associated with dysregulated hypothalamic-pituitary-adrenal (HPA) axis function, overactivity of the sympathoadrenal system, and increased levels of inflammation markers. It is not known whether these biological processes are disproportionately elevated in response to acute negative emotional arousal by mental stress (MS). The present study investigates responses of neurohormones and inflammatory markers to MS in 14 clinically depressed (age: 42+/-10 years; 50% female) and 14 non-depressed control (age: 39+/-6 years; 50% female) participants. Heightened acute MS reactivity was documented in depressed participants (adrenocorticotropic hormone, rho=0.001; norepinephrine, rho=0.042; epinephrine, rho=0.039), and a delayed increase in cortisol was observed (rho=0.002). Inflammation markers increased more strongly in depressed versus non-depressed participants (IL-6, rho=0.027; tumor necrosis factor-alpha, rho=0.050; and recovery C-reactive protein, rho=0.003). It is concluded that depressed individuals display hyper-reactivity of neuroimmunological markers in response to acute negative emotions. This hyper-reactivity may serve a pathologic role in the elevated morbidity and mortality risk associated with depression.

Depression in Patients with Nonalcoholic Fatty Liver Disease and Chronic Viral Hepatitis B and C

BACKGROUND Patients with chronic liver disease (CLD) and depression may be at a higher risk for various complications, including impaired quality of life and more advanced liver disease. The purpose of this study was to determine the prevalence of depression in CLD patients (non-alcoholic fatty liver disease (NAFLD), Hepatitis B (HBV), and Hepatitis C (HCV)) and to identify potential clinical and laboratory correlates of depression in these patients. METHODS We used a database of CLD patients that contains extensive clinical (including self-reported depression) and laboratory data for each patient. We compared the prevalence of depression in patients with HBV, HCV, and NAFLD. We also used regression models to find independent predictors of depression in these patients. RESULTS Of 878 CLD patients, 207 (23.6%) had a diagnosis of depression (NAFLD 27.2%, HCV 29.8%, and HBV 3.7%). Examination of predictors of depression differed by the type of chronic liver disease. For NAFLD, independent predictors of depression were the presence of hypertension, smoking, history of lung disease, being female, and non-African-American. For HBV patients, the only independent predictor of depression was excessive alcohol consumption (defined as >10 g/d), while for HCV patients, independent predictors were being female and non-Asian, presence of fatigue, and excessive alcohol intake. CONCLUSIONS This study demonstrates that individuals with NAFLD and HCV have a higher prevalence of depression than HBV patients and the rates of depression reported for the general population. The most consistent correlates of depression status in CLD patients are being female and excessive alcohol consumption.

Association between Symptoms of Depression and Anxiety with Heart Rate Variability in Patients with Implantable Cardioverter Defibrillators

Objective: This study investigated whether depression and anxiety symptoms are associated with measures of autonomic nervous system dysfunction in patients with implantable cardioverter defibrillators who are at high risk of cardiac rhythm disturbances. Depression and anxiety are associated with autonomic nervous system dysfunction, which may promote the risk of malignant cardiac arrhythmias. Methods: Patients with an implantable cardioverter defibrillator (ICD) underwent ambulatory electrocardiographic (ECG) monitoring (n = 44, mean age = 62.1 ± 9.3 years). Depression was assessed using the Beck Depression Inventory and anxiety was evaluated using the Taylor Manifest Anxiety Scale. Heart rate variability was assessed using time (RMSSD, pNN50, and SDNN) and frequency domain measures derived from 24-hour R-R intervals. Multivariate models were adjusted for age, sex, hypertension, diabetes, and smoking status. Results: Defibrillator patients with elevated depression symptoms (n = 12) had significantly lower RMSSD (15.25 ± 1.66 ms versus 24.97 ± 2.44 ms, p = .002) and pNN50 (1.83 ± 0.77 versus 5.61 ± 1.04, p = .006) than defibrillator patients with low depression symptoms (n = 32). These associations remained significant after multivariate adjustment for covariates. ICD patients with high anxiety levels (n = 10) displayed lower RMSSD (p = .013), which became marginally significant when adjusting for covariates (p = .069). Conclusions: Depression and anxiety in defibrillator patients are associated with autonomic nervous system dysfunction indices of reduced parasympathetic control. Autonomic nervous system dysfunction may partially explain the association between depression and anxiety with life-threatening cardiac outcomes in vulnerable patients. ICD = implantable cardioverter defibrillators; HRV = heart rate variability; BDI = Beck Depression Inventory; BMI = body mass index.

Effects of Viral Eradication With Ledipasvir and Sofosbuvir, With or Without Ribavirin, on Measures of Fatigue in Patients With Chronic Hepatitis C Virus Infection.

BACKGROUND & AIMS Fatigue is a disturbing symptom of chronic hepatitis C virus (HCV) infection. We assessed the effects of sustained virologic response 12 weeks after the end of therapy (SVR12) on fatigue. METHODS We performed a retrospective analysis of 100 patients with chronic HCV infection who achieved an SVR12 after treatment with ledipasvir and sofosbuvir, with or without ribavirin. Data were collected on fatigue-related patient-reported outcomes (PROs) and assessed by using the Functional Assessment of Cancer Therapy-Fatigue scoring system and the Vitality subscale of Short Form 36. We measured levels of cytokines and growth factors in frozen serum samples collected at baseline, week 12 of treatment, and 4 weeks after treatment. Central fatigue and peripheral or muscle fatigue (PF) were determined by using items from PROs. Serum levels of cytokines, growth factors, serotonin, alanine aminotransferase, and aspartate aminotransferase were measured by using the Bio-Plex, enzyme-linked immunosorbent, and enzymatic assays. RESULTS Compared with baseline, 4 weeks after the end of treatment, all fatigue-associated PROs improved significantly. Baseline PROs correlated inversely with serum level of interferon-γ; level of platelet-derived growth factor correlated with PF, central fatigue, and total fatigue score. Only PF correlated with serum level of serotonin. At baseline, high PF scores correlated with high serum levels of serotonin and low levels of interleukin-10 and tumor necrosis factor-α. In multivariate analysis, serum level of interleukin-8 was associated with greater fatigue (P < .02). Reductions in levels of chemokine (C-C motif) ligand 2 (also called monocyte chemotactic protein 1) were associated with fatigue after treatment (P = .0165). CONCLUSIONS In an analysis of data from patients with chronic HCV infection participating in a clinical trial of ledipasvir and sofosbuvir, SVR12 was associated with reduced fatigue, compared with baseline. High baseline serum levels of interferon-γ were associated with fatigue. Reductions in levels of chemokine (C-C motif) ligand 2 were associated with persistent fatigue after SVR12. Central and peripheral fatigue each associated with different biomarkers, suggesting different pathogenic pathways.

Inflammatory markers and negative mood symptoms following exercise withdrawal

OBJECTIVE Physical inactivity is associated with elevated inflammatory markers, but little is known about the time trajectories of reduced physical activity and inflammatory markers. Changes in inflammatory markers in response to withholding regular aerobic exercise were prospectively examined and correlated with increased negative mood symptoms and fatigue that accompany exercise withdrawal. METHODS Participants with regular exercise habits (N=40, mean age of 31.3+/-7.5 years, 55% women) were randomized to aerobic exercise withdrawal or to continue regular exercise for 2 weeks. Protocol adherence was documented using ambulatory actigraphy. Inflammatory markers (interleukin-6, C-reactive protein, fibrinogen and soluble intercellular adhesion molecule-1) were assessed at weekly intervals. Negative mood was measured with the Profile of Mood States (POMS) and the Beck Depression Inventory (BDI), and fatigue with the Multidimensional Fatigue Inventory (MFI). Autonomic nervous system activity was examined using heart rate variability-based indices. RESULTS Changes in inflammatory markers did not differ between exercise withdrawal and control groups (multivariate p interaction=0.25). Exercise withdrawal resulted in increased negative mood symptoms and fatigue from baseline to day 14 compared to controls (p DeltaPOMS=0.008, p DeltaBDI=0.002; p DeltaMFI=0.003), but these responses were not associated with changes in inflammatory markers (p-values >0.10). Inflammatory markers were also not correlated with autonomic nervous system dysregulation (p-values >0.10). CONCLUSION Inflammatory markers were not increased following 2 weeks of exercise withdrawal. Negative mood symptoms and fatigue were not accounted for by changes in inflammatory markers. Compensatory feedback mechanisms may operate among healthy individuals to promote resilience from the effects of reduced exercise.

Expert consensus guidelines: Examining surgical ablation for atrial fibrillation

From the Department of Cardiovascular and Thoracic Surgery, and WVU Heart and Vascular Institute, West Virginia University Morgantown, WVa; Washington Adventist Hospital, Adventist HealthCare, Takoma Park, Md; Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St Louis, Mo; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md; Department of Cardiothoracic Surgery, Academic Hospital Maastricht, Maastricht, The Netherlands; Department of Cardiovascular Surgery, Nippon Medical School, Tokyo, Japan; Sana Cardiac Surgery Stuttgart GmbH, Stuttgart, Germany; Center for the Study of Chronic Illness and Disability, George Mason University, Fairfax, Va; and Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic, Cleveland, Ohio. Received for publication Dec 21, 2016; revisions received Jan 27, 2017; accepted for publication Feb 1, 2017; available ahead of print April 5, 2017. Address for reprints: Niv Ad, MD, Department of Cardiovascular and Thoracic Surgery, West Virginia University School of Medicine, 1 Medical Center Drive, Morgantown, WV 26506 (E-mail: nivadmd14@gmail.com). J Thorac Cardiovasc Surg 2017;153:1330-54 0022-5223/

Association of work productivity with clinical and patient-reported factors in patients infected with hepatitis C virus.

36.00 Copyright 2017 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2017.02.027 Forest plot: Improved perioperative survival (<30 days) with concomitant surgical ablation.

Exploratory Analysis of the Relationships between Aerobic Capacity and Self-Reported Fatigue in Patients with Rheumatoid Arthritis, Polymyositis, and Chronic Fatigue Syndrome

Patients with HCV infection have reduced work productivity (WP), in terms of both presenteeism (impairment in work productivity while working) and absenteeism (productivity loss due to absence from work). The aim of this study was to identify clinical and patient‐reported factors that are predictive of WP in HCV‐infected patients. HCV‐infected patients enrolled in clinical trials completed 3 PRO questionnaires (CLDQ‐HCV, SF‐36 and FACIT‐F) and one work productivity (WPAI:SHP) questionnaire. In employed subjects, work productivity and its absenteeism and presenteeism components were calculated using WPAI:SHP instrument. Of 4121 HCV‐infected patients with work productivity data, 2480 (60.2%) reported to be employed, and of those, 2190 had completed all PRO questionnaires before treatment initiation. Of the study cohort, 519/2190 (23.7%) had severe work impairment. In multiple linear regression analysis, work productivity was predicted by lower scores in activity/energy domain of CLDQ‐HCV, physical well‐being domain of FACIT‐F, worry domain of CLDQ‐HCV and role physical domain of SF‐36 (all P < 0.0005). Furthermore, presenteeism was independently predicted by the activity/energy of CLDQ‐HCV, physical well‐being of FACIT‐F, worry domain of CLDQ‐HCV, role physical scale of SF‐36 and fatigue scale of FACIT‐F (P < 0.002). Finally, absenteeism was independently predicted by physical well‐being scale of FACIT‐F and role physical scale of SF‐36 (all P < 0.002). Clinically, work productivity impairment was predicted by the presence of cirrhosis, anxiety, depression and clinically overt fatigue (P < 0.01). Thus, the most important drivers of WP in HCV are impairment of physical aspects of PROs and clinical history of depression, anxiety, fatigue and cirrhosis.

Multiple factors predict physical performance in people with chronic liver disease.

To determine if self‐reported levels of physical activity and fatigue are related to peak oxygen uptake (VO2peak) and whether these relationships differ among the patient groups (rheumatoid arthritis [RA], polymyositis [PM], and chronic fatigue syndrome [CFS]).