Abstract Background The safety and efficacy of aerobic exercise in heart failure (HF) patients with atrial fibrillation (AF) has not been well evaluated. Objectives This study examined whether ...outcomes with exercise training in HF vary according to AF status. Methods HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) randomized 2,331 ambulatory HF patients with ejection fraction ≤35% to exercise training or usual care. We examined clinical characteristics and outcomes (mortality/hospitalization) by baseline AF status (past history of AF or AF on baseline electrocardiogram vs. no AF) using adjusted Cox models and explored an interaction with exercise training. We assessed post-randomization AF events diagnosed via hospitalizations for AF and reports of serious arrhythmia caused by AF. Results Of 2,292 patients with baseline rhythm data, 382 (17%) had AF, 1,602 (70%) had sinus rhythm, and 308 (13%) had “other” rhythm. Patients with AF were older and had lower peak V o2 . Over a median follow-up of 2.6 years, AF was associated with a 24% per year higher rate of mortality/hospitalization (hazard ratio HR: 1.53; 95% confidence interval CI: 1.34 to 1.74; p < 0.001) in unadjusted analysis; this did not remain significant after adjustment (HR: 1.15; 95% CI: 0.98 to 1.35; p = 0.09). There was no significant difference in AF event rates by randomized treatment assignment in the overall population or by baseline AF status (all p > 0.10). There was no interaction between AF and exercise training on measures of functional status or clinical outcomes (all p > 0.10). Conclusions AF in patients with chronic HF was associated with older age, reduced exercise capacity at baseline, and a higher overall rate of clinical events, but not a differential response to exercise training for clinical outcomes or changes in exercise capacity. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training HF-ACTION; NCT00047437 )
Abstract Within the last decade, advancements in left ventricular assist device (LVAD) therapy have allowed end-stage heart failure patients to live longer and with better quality of life. Like other ...life-saving interventions, however, there remains the risk of complications including infections, bleeding episodes, and stroke. The candidate for LVAD therapy faces complex challenges going forward, both physical and psychological, many of which may benefit from the application of palliative care principles by trained specialists. Despite these advantages, palliative care remains underused in many advanced heart failure programs. Here, we describe the benefits of palliative care, barriers to use within heart failure, and specific applications to the integrated care of patients on mechanical circulatory support.
In regard to Yamamoto et al Sperduto, Paul W; Sneed, Penny K; Roberge, David ...
International journal of radiation oncology, biology, physics,
11/2012, Volume:
84, Issue:
4
Journal Article
Prior studies suggest similar long-term mortality rates for patients with heart failure (HF) with preserved ejection fraction (HFpEF) vs reduced ejection fraction. However, although coronary heart ...disease (CHD) is associated with worse prognosis in HF, clinical outcomes are less well characterized for HF without CHD. We investigated the characteristics and 5-year mortality outcomes among patients with HF without significant CHD, stratified by EF.
Patients with clinical heart failure who underwent coronary angiography at Duke University Medical Center from 1996 through 2009 and had no significant CHD with EF ≤ 40% were compared with patients without significant CHD with EF > 40%. Survival was examined using Kaplan-Meier methods and multivariable Cox proportional hazards modeling. Analyses were repeated using EF ≥ 50%.
Of 3154 patients with HF without significant CHD, 1530 (48.5%) had HFpEF (EF > 40%). These patients were older and more likely to have a Charlson Index ≥ 2 than patients with reduced EF. Patients with HFpEF had a lower risk of death than those with reduced EF (unadjusted hazard ratio HR 0.85; 95% confidence interval CI 0.74-0.99). From 1996 through 2009, the secular trend of death decreased among patients without CHD and with reduced EF (HR 0.92; 95% CI 0.88-0.97) but not among those with preserved EF (HR 0.99; 95% CI 0.93-1.05; P interaction 0.095). No finding was significant after multivariable risk adjustment. Results were consistent when defining preserved EF as EF ≥ 50%.
Among patients without significant CHD, those with HFpEF had similar risks of 5-year mortality as patients with HF with reduced ejection fraction.
Des études antérieures indiquent des taux de mortalité à long terme similaires entre les patients atteints d’insuffisance cardiaque (IC) avec fraction d’éjection (FE) préservée (ICFEP) vs les patients atteints d’IC avec FE réduite (ICFER). Toutefois, bien que la coronaropathie soit associée à un plus mauvais pronostic de l’IC, les résultats cliniques sont moins bien définis que ceux de l’IC sans coronaropathie. Nous avons examiné les caractéristiques et les résultats des patients atteints d’IC sans coronaropathie importante, stratifiés selon la FE, sur la mortalité dans les cinq ans.
Nous avons comparé les patients montrant des signes cliniques d’IC qui avaient subi une angiographie coronarienne à la Duke University de 1996 à 2009 et n’avait pas de coronaropathie importante avec FE ≤ 40 % aux patients sans coronaropathie importante avec FE > 40 %. Nous avons examiné la survie à l’aide de la méthode de Kaplan-Meier et du modèle multivarié à risques proportionnels de Cox. Nous avons répété les analyses en fonction d’une FE ≥ 50 %.
Parmi les 3 154 patients atteints d’IC sans coronaropathie importante, 1 530 (48,5 %) avaient une ICFEP (FE > 40 %). Ces patients étaient plus âgés et plus susceptibles d’avoir un indice de Charlson ≥ 2 que les patients atteints d’ICFER. Les patients atteints d’ICFEP avaient un risque plus faible de mortalité que ceux atteints d’une ICFER (rapport de risque RR non ajusté 0,85; intervalle de confiance IC à 95 % 0,74-0,99). De 1996 à 2009, la tendance séculaire de la mortalité avait diminué chez les patients sans coronaropathie et qui avaient une FE réduite (RR 0,92; IC à 95 % 0,88-0,97), mais non chez ceux qui avaient une FE préservée (RR 0,99; IC à 95 % 0,93-1,05; valeur P de l’interaction 0,095). Aucun résultat n’était significatif après l’ajustement multivarié en fonction du risque. Les résultats étaient cohérents lorsque la FE préservée était définie par une FE ≥ 50 %.
Chez les patients sans coronaropathie importante, ceux atteints d’une ICFEP avaient des risques similaires de mortalité dans les cinq ans aux patients atteints d’ICFER.
ABSTRACT BACKGROUND Infant mortality is higher in Indigenous than non-Indigenous populations, but comparable data on infant morbidity are lacking in Canada. We evaluated disparities in infant ...morbidities experienced by Indigenous populations in Canada. METHODS We used linked population-based birth and health administrative data from Quebec, Canada, to compare hospitalization rates, an indicator of severe morbidity, in First Nations, Inuit and non-Indigenous singleton infants (< 1 year) born between 1996 and 2010. RESULTS Our cohort included 19 770 First Nations, 3930 Inuit and 225 380 non-Indigenous infants. Compared with non-Indigenous infants, all-cause hospitalization rates were higher in First Nations infants (unadjusted risk ratio RR 2.05, 95% confidence interval CI 1.99–2.11; fully adjusted RR 1.43, 95% CI 1.37–1.50) and in Inuit infants (unadjusted RR 1.96, 95% CI 1.87–2.05; fully adjusted RR 1.37, 95% CI 1.24–1.52). Higher risks of hospitalization (accounting for multiple comparisons) were observed for First Nations infants in 12 of 16 disease categories and for Inuit infants in 7 of 16 disease categories. Maternal characteristics (age, education, marital status, parity, rural residence and Northern residence) partly explained the risk elevations, but maternal chronic illnesses and gestational complications had negligible influence overall. Acute bronchiolitis (risk difference v. non-Indigenous infants, First Nations 37.0 per 1000, Inuit 39.6 per 1000) and pneumonia (risk difference v. non-Indigenous infants, First Nations 41.2 per 1000, Inuit 61.3 per 1000) were the 2 leading causes of excess hospitalizations in Indigenous infants. INTERPRETATION First Nations and Inuit infants had substantially elevated burdens of hospitalizations as a result of diseases of multiple systems. The findings identify substantial unmet needs in disease prevention and medical care for Indigenous infants.
The respective life histories of human subjects and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the ...underpinnings of biochemical, cellular, and physiologic pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils, their effector functions, or both. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide experimental details comparing and contrasting eosinophils and eosinophil effector functions in human subjects versus mice. In particular, our review will provide a summation and an easy-to-use reference guide to important studies demonstrating that although differences exist, more often than not, their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function but instead species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients.
Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor ...voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.
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Background Contact toxicant reactions are accompanied by localized skin inflammation and concomitant increases in site-specific itch responses. The role(s) of eosinophils in these reactions is poorly ...understood. However, previous studies have suggested that localized eosinophil-nerve interactions at sites of inflammation significantly alter tissue innervation. Objective To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching. Methods BALB/cJ mice were exposed to different contact toxicants, identifying trimellitic anhydride (TMA) for further study on the basis of inducing a robust eosinophilia accompanied by degranulation. Subsequent studies using TMA were performed with wild type versus eosinophil-deficient PHIL mice, assessing edematous responses and remodeling events such as sensory nerve innervation of the skin and induced pathophysiological responses (ie, itching). Results Exposure to TMA, but not dinitrofluorobenzene, resulted in a robust eosinophil skin infiltrate accompanied by significant levels of degranulation. Follow-up studies using TMA with wild type versus eosinophil-deficient PHIL mice showed that the induced edematous responses and histopathology were, in part, causatively linked with the presence of eosinophils. Significantly, these data also demonstrated that eosinophil-mediated events correlated with a significant increase in substance P content of the cutaneous nerves and an accompanying increase in itching, both of which were abolished in the absence of eosinophils. Conclusions Eosinophil-mediated events following TMA contact toxicant reactions increase skin sensory nerve substance P and, in turn, increase itching responses. Thus, eosinophil-nerve interactions provide a potential mechanistic link between eosinophil-mediated events and neurosensory responses following exposure to some contact toxicants.
Results EPX knockout mice displayed decreases the skin inflammation (i.e., decreases in eosinophil accumulation, mast cell activation, and skin thickness) that were similar to the reduced ...inflammatory events (relative to wild type controls) occurring in eosinophil deficient PHIL mice.
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