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Most patients with acute myeloid leukaemia (AML) are older, with many unsuitable for conventional chemotherapy. Low-dose Ara-C (LDAC) is superior to best supportive care but is still inadequate. The combination of arsenic trioxide (ATO) and LDAC showed promise in an unrandomised study. We report a randomised trial of LDAC versus LDAC+ATO. Patients with AML according to WHO criteria or myelodysplastic syndrome with >10% blasts, considered as unfit for conventional chemotherapy, were randomised between subcutaneous Ara-C (20 mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25 mg/kg) on days 1–5, 9 and 11, for at least four courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC, as the projected benefit was not observed. Overall 14% of patients achieved complete remission (CR) and 7% CRi. Median survival was 5.5 months and 19 months for responders (CR: not reached; CRi: 14 months; non-responders: 4 months). There were no differences in response or survival between the arms. Grade 3/4 cardiac and liver toxicity, and supportive care requirements were greater in the ATO arm. This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML.

To determine the impact of cardiorespiratory fitness (FIT) on survival in relation to the obesity paradox in patients with systolic heart failure (HF). We studied 2066 patients with systolic HF (body mass index [BMI] ≥18.5 kg/m2) between April 1, 1993 and May 11, 2011 (with 1784 [86%] tested after January 31, 2000) from a multicenter cardiopulmonary exercise testing database who were followed for up to 5 years (mean ± SD, 25.0±17.5 months) to determine the impact of FIT (peak oxygen consumption <14 vs ≥14 mL O2 ∙ kg−1 ∙ min−1) on the obesity paradox. There were 212 deaths during follow-up (annual mortality, 4.5%). In patients with low FIT, annual mortality was 8.2% compared with 2.8% in those with high FIT (P<.001). After adjusting for age and sex, BMI was a significant predictor of survival in the low FIT subgroup when expressed as a continuous (P=.03) and dichotomous (<25.0 vs ≥25.0 kg/m2) (P=.01) variable. Continuous and dichotomous BMI expressions were not significant predictors of survival in the overall and high FIT groups after adjusting for age and sex. In patients with low FIT, progressively worse survival was noted with BMI of 30.0 or greater, 25.0 to 29.9, and 18.5 to 24.9 (log-rank, 11.7; P=.003), whereas there was no obesity paradox noted in those with high FIT (log-rank, 1.72; P=.42). These results indicate that FIT modifies the relationship between BMI and survival. Thus, assessing the obesity paradox in systolic HF may be misleading unless FIT is considered.

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO 2 ), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO 2 ) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO 2 (7,319), VE/VCO 2 slope (5,044), EOV (1,617), and OUES (584). Peak VO 2 , the VE/VCO 2 slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies ( n  = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO 2 and the VE/VCO 2 slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.

Practitioners need access to and the ability to openly discuss advances in practice and concepts as they apply to the practice of cardiovascular and pulmonary physical therapy. Lack of accessibility of research, limited clinical and personal time, or insufficient knowledge of article synopses can hinder this process. This article provides an overview of cardiovascular and pulmonary research published in 2014 that the authors believe most important and relevant to the practice of cardiovascular and pulmonary physical therapy. Several key sections are used to describe selected articles and are followed by a brief overview of clinical relevance as indicated by the authors and input provided during the oral presentation of this material at the 2015 Combined Sections Meeting.

The projected increase in persons with advanced heart failure and associated costs warrant the examination of exercise in patients receiving inotropic therapy. Literature supports the use of exercise and inotropic therapy in the treatment of patients with advanced heart failure. The purposes of this paper are to illustrate the use of exercise prescription and outcomes assessment with a 6-minute walk test in a patient with acute decompensated heart failure receiving tailored therapy with dobutamine and to discuss potential relationships resulting in observed improvements. A 67-year old man was admitted to an acute care hospital with acute decompensated heart failure for tailored medical therapy including dobutamine. The patient received 14 days of tailored medical therapy, of which 12 days included exercise training by a physical therapist. Functional outcomes showed a clinically significant improvement in distance walked and improvement in the cardiorespiratory response. The improvement in estimated peak oxygen consumption was 7% greater than that predicted to be from tailored medical therapy. Exercise was safely provided to a patient hospitalized with advanced heart failure on continuous inotropic therapy. The 6-minute walk test was effectively used to prescribe exercise and examine patient outcomes.

Resistance training (RT) has been proposed as a potential management technique for persons with congestive heart failure (CHF) with the possibility of improving the vicious CHF cycle of pump failure, neuroendocrine abnormalities, skeletal muscle myopathies, dyspnea, fatigue, increased ventilation, and increased sympathetic nervous system activity (the Muscle Hypothesis of CHF). However, very little research has examined the effects of RT in persons with CHF or the effects of RT on the Muscle Hypothesis. The purposes of this paper are to describe the long-term effects of RT in persons with CHF and attempt to describe how these effects will impact the Muscle Hypothesis of CHF. A Medline search of English articles on RT in CHF was performed with the following keywords: resistance training, strength training, weight training, resistance exercise, heart failure, and muscle hypothesis. The references of published articles were further reviewed for additional articles pertaining to RT in CHF and the potential effects on the Muscle Hypothesis. Inclusion criteria for this review were studies of RT alone or RT with aerobic exercise (AE) in persons with CHF. Three review articles and 24 studies of RT were found of which 6 studies examined RT alone, 7 studies examined RT with short bouts of AE (≤ 5 minutes of continuous AE), and 11 studies examined the effects of RT combined with long bouts of AE. The results of these studies revealed significant improvements in muscle strength and endurance, peak oxygen consumption, forearm blood flow, left ventricular function, and quality of life with very few complications from RT. Differences in the methods of RT were found which likely affected the observed results. Chronic RT alone or with AE appears to favorably influence many aspects of the muscle hypothesis of chronic CHF. The improvements in skeletal muscle strength and endurance, peak oxygen consumption, forearm blood flow, left ventricular function, and quality of life in persons with CHF suggest that RT prescribed alone or with AE can be done safely and has favorable effects on the CHF Muscle Hypothesis. Further examination of isolated RT and RT with short versus long bouts of AE is needed. [PUBLICATION ABSTRACT]