Risk related to pre–diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial

Background—The prevalence of pre–diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results—We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: <6.0% [<42 mmol/mol], 6.0%–6.4% [42–47 mmol/mol; pre–diabetes mellitus], and ≥6.5% [≥48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52;P<0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre–diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, >6.5%) and known diabetes mellitus compared with those with HbA1c<6.0% was 1.39 (1.17–1.64); P<0.001 and 1.64 (1.43–1.87); P<0.001, respectively. Patients with pre–diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10–1.47];P<0.001) compared with those with HbA1c<6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions—In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre–diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c <6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status

Respiratory muscle training with normocapnic hyperpnea improves ventilatory pattern and thoracoabdominal coordination, and reduces oxygen desaturation during endurance exercise testing in COPD patients

Background: Few data are available about the effects of respiratory muscle training with normocapnic hyperpnea (NH) in COPD. The aim is to evaluate the effects of 4 weeks of NH (Spirotiger®) on ventilatory pattern, exercise capacity, and quality of life (QoL) in COPD patients. Methods: Twenty-six COPD patients (three females), ages 49-82 years, were included in this study. Spirometry and maximal inspiratory pressure, St George Respiratory Questionnaire, 6-minute walk test, and symptom-limited endurance exercise test (endurance test to the limit of tolerance [tLim]) at 75%-80% of peak work rate up to a Borg Score of 8-9/10 were performed before and after NH. Patients were equipped with ambulatory inductive plethysmography (LifeShirt®) to evaluate ventilatory pattern and thoracoabdominal coordination (phase angle [PhA]) during tLim. After four supervised sessions, subjects trained at home for 4 weeks 10 minutes twice a day at 50% of maximal voluntary ventilation. The workload was adjusted during the training period to maintain a Borg Score of 5-6/10. Results: Twenty subjects completed the study. After NH, maximal inspiratory pressure significantly increased (81.5±31.6 vs 91.8±30.6 cmH2O, P<0.01); exercise endurance time (+150 seconds, P=0.04), 6-minute walk test (+30 meters, P=0.03), and QoL (-8, P<0.01) all increased. During tLim, the ventilatory pattern changed significantly (lower ventilation, lower respiratory rate, higher tidal volume); oxygen desaturation, PhA, and dyspnea Borg Score were lower for the same work intensity (P<0.01, P=0.02, and P<0.01, respectively; one-way ANOVA). The improvement in tidal volume and oxygen saturation after NH were significantly related (R2=0.65, P<0.01). Conclusion: As expected, NH improves inspiratory muscle performance, exercise capacity, and QoL. New results are significant change in ventilatory pattern, which improves oxygen saturation, and an improvement in thoracoabdominal coordination (lower PhA). These two facts could explain the reduced dyspnea during the endurance test. All these results together may play a role in improving exercise capacity after NH training

Aerospace medicine and biology: A continuing bibliography with indexes

This bibliography lists 180 reports, articles and other documents introduced into the NASA scientific and technical information system in February 1985

Testosterone deficiency increases hospital readmission and mortality rates in male patients with heart failure.

BackgroundTestosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.ObjectiveWe investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.MethodsTotal testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.ResultsLength of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58-4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67-8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23-8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001).ConclusionThese results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Many conditions culminate in heart failure (HF), a multi-organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence-base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite

Psychological Factors and Treatment Adherence Behavior in Patients With Chronic Heart Failure

Background: Chronic heart failure adversely affects 300,000 Australians. Symptom stabilization and prognosis are partially determined by patients following medical and lifestyle recommendations. Methods: To test the hypothesis that depression, anxiety, and self-efficacy are independent predictors of such adherence, 115 predominately male (70.6%) volunteers with a mean age of 63 years were recruited from a major teaching hospital in Australia. Results: Depression (Beck Depression Inventory score >10, 33.3%) failed to predict adherence. Trait anxiety (State-Trait Anxiety Inventory score >40, 31%) explained minimal variability regarding smoking and alcohol adherence. Self-efficacy strongly predicted adherence behavior. Conclusions: Findings will assist cardiac nurses to prepare strategies to optimize adherence and quality of life while minimizing public health costs

Development of an international standard set of outcome measures for patients with atrial fibrillation: a report of the International Consortium for Health Outcomes Measurement (ICHOM) atrial fibrillation working group.

AIMS: As health systems around the world increasingly look to measure and improve the value of care that they provide to patients, being able to measure the outcomes that matter most to patients is vital. To support the shift towards value-based health care in atrial fibrillation (AF), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international Working Group (WG) of 30 volunteers, including health professionals and patient representatives to develop a standardized minimum set of outcomes for benchmarking care delivery in clinical settings. METHODS AND RESULTS: Using an online-modified Delphi process, outcomes important to patients and health professionals were selected and categorized into (i) long-term consequences of disease outcomes, (ii) complications of treatment outcomes, and (iii) patient-reported outcomes. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, comorbidities, cognitive function, date of diagnosis, disease duration, medications prescribed and AF procedures, as well as smoking, body mass index (BMI), alcohol intake, and physical activity. Where appropriate, and for ease of implementation, standardization of outcomes and case-mix variables was achieved using ICD codes. The standard set underwent an open review process in which over 80% of patients surveyed agreed with the outcomes captured by the standard set. CONCLUSION: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of chronic AF care. Their consistent definition and collection, using ICD codes where applicable, could also broaden the implementation of more patient-centric clinical outcomes research in AF

Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations

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Quality of life assessment in heart failure interventions: a 10-year (1996-2005) review.

The increasing prevalence and poor prognosis associated with heart failure have prompted research to focus on improving quality of life (QoL) for heart failure patients. Research from 1996-2005 was systematically reviewed to identify randomized controlled trials that assessed QoL in heart failure. In 120 studies, 44 were medication trials; 19 surgical/procedural interventions; and 57 patient care/service delivery interventions. Studies were summarized in terms of aim, population, QoL measures used and QoL findings. Studies used 47 different measures of QoL-generic, health-related, condition-specific, domain-specific and utility measures. Most used a single QoL measure. In 87%, a condition specific QoL measure was used, with the Minnesota Living with Heart Failure Questionnaire being the favoured assessment tool. The range of QoL measures in use poses challenges for development of cumulative knowledge. Although comparability across studies is important, this must be informed by the responsiveness of the instrument selected. As carried out in other cardiac groups, comparative evaluations of instrument responsiveness are needed in heart failure