Ischemic etiology of heart failure identifies patients with more severely impaired exercise capacity

BACKGROUND: Peak oxygen uptake (peak VO2) and the regression slope of ventilation against CO2 production during exercise (VE/VCO2 slope) are powerful prognostic indicators in patients with chronic heart failure (CHF). Our purpose was to evaluate the influence of CHF etiology on peak VO2 and VE/VCO2 slope, independently of demographic, clinical, Doppler-echocardiographic and neurohormonal factors. METHODS: Data were collected from 239 CHF patients referred for a cardiopulmonary exercise test as part of their clinical evaluation. Patients were stratified according to their CHF etiology (ischemic versus non-ischemic). RESULTS: The etiology of heart failure was ischemic in 143 patients (60%) and non-ischemic in 96 (40%). Patients with ischemic etiology, compared with those with non-ischemic etiology, showed a lower peak VO2 (15.4+/-4.2 versus 17.8+/-4.8 ml/kg/min, p<0.0001) and a steeper VE/VCO2 slope (38.1+/-6.8 versus 34+/-5.3, p<0.0001). In the univariate model, age (r=-0.36, p<0.0001), female sex (r=-0.21, p=0.001), ischemic CHF etiology (r=-0.26, p<0.0001) and NYHA class (r=-0.52, p<0.0001) correlated with peak VO2. At multivariate analysis, ischemic CHF etiology (beta=-0.23, p=0.001) was a predictor of peak VO2 (R(2)=0.49) independently of age (beta=-0.23, p=0.001), female sex (beta=-0.25, p=0.0006) and NYHA class (beta=-0.31, p<0.0001). Similarly, ischemic etiology (beta=0.29, p=0.001) predicted the VE/VCO2 slope (R(2)=0.38) independently of E/A ratio (beta=0.27, p=0.01) and resting heart rate (beta=0.22, p=0.01). CONCLUSIONS: Etiology of heart failure may influence the functional capacity and the ventilatory response to exercise.     

Correlates of HIV-1 shedding in cervicovaginal secretions and effects of antiretroviral therapies

OBJECTIVES: To evaluate the determinants of HIV-1 RNA shedding in cervicovaginal secretions and the effects of antiretroviral therapy in a group of infected women. METHODS: A total of 122 women from whom paired peripheral blood and cervicovaginal lavage samples were available were enrolled in the study. HIV-1 RNA was quantified in the plasma and cell-free fraction of cervicovaginal lavages by the nucleic acid sequence-based amplification assay (lower limit of detection 80 copies/ml). RESULTS: Seventy-one per cent of the women had detectable viral load in the cervicovaginal lavage and this appeared to be correlated to plasma viral load and to the degree of immunodeficiency as expressed by the absolute number of CD4 cells. Antiretroviral-treated patients had a lower risk of shedding the virus in the genital tract, but this association was limited to patients treated with highly active antiretroviral therapy (HAART). However, in 25% of women with undetectable plasma viral load, a genital shedding of the virus was demonstrated. CONCLUSION: Plasma viral load may fail as a marker of infectivity of genital secretions. HAART treatment seems to be more efficacious in suppressing viral shedding at the genital level. The female genital tract represents a distinct compartment for HIV-1 replication/evolution.     

Role of iron deficiency and anemia in cardio-renal syndromes

Chronic heart failure is a common disorder associated with unacceptably high mortality rates. Chronic renal disease and anemia are two important comorbidities that significantly influence morbidity and mortality in patients with chronic heart failure (CHF). Progress in CHF again may cause worsening of kidney function and anemia. To describe this vicious cycle, the term cardio-renal anemia syndrome has been suggested. Iron deficiency is part of the pathophysiology of anemia in both CHF and chronic kidney disease, which makes it an interesting target for treatment of anemia in cardio-renal anemia syndrome. Recently, studies have highlighted the potential clinical benefits of treating iron deficiency in patients with CHF, even if these patients are nonanemic. This article summarizes studies investigating the influence of iron deficiency with or without anemia in chronic kidney disease and CHF and gives an overview of preparations of intravenous iron currently available.     

Breast cancer: achievements in adjuvant systemic therapies in the pre-genomic era

In recent decades, the use of adjuvant systemic therapies for early breast cancer has increased extensively and has most likely contributed to the decline in breast cancer mortality observed in the U.S. and in some European countries. The last few years have witnessed accelerated progress in the treatment of early breast cancer, with the introduction of taxanes and aromatase inhibitors and, most impressively, trastuzumab to the adjuvant portfolio. When compared with anthracycline-based regimens, the addition of taxanes to treatments for patients with node-positive breast cancer has shown benefits in disease-free survival and, in some trials, in overall survival; however, these drugs are not yet universally accepted as standard treatment. Significant improvements in endocrine therapy in both pre- and postmenopausal patients with endocrine-responsive disease have been made. In the postmenopausal setting, aromatase inhibitors have shown superiority over tamoxifen in a direct comparison upfront or when given in sequence after 2-5 years of tamoxifen, but the optimal modality of administration remains unclear. For premenopausal women, ovarian function suppression with luteinizing hormone-releasing hormone analogues combined with tamoxifen has generated similar results to cyclophosphamide, methotrexate, 5-fluorouracil (CMF)-based regimens. Recently, trastuzumab has had a dramatic impact on the evolution of human epidermal growth factor receptor 2 (HER-2)-positive early breast cancer treated with standard adjuvant modalities; specifically, relapses, including distant relapses, have been halved. In this review, we summarize these main achievements, discuss the currently available adjuvant treatment options for breast cancer patients, and emphasize the need for more efficient translational research to improve individual treatment tailoring.     

Oxidative stress and hyperuricaemia: pathophysiology,clinical relevance,and therapeutic implications in chronic heart failure

Heart failure (HF) is a state of chronic deterioration of oxidative mechanisms due to enhanced oxidative stress and consequent subcellular alterations. In this condition, oxidant‐producing enzymes, in particular xanthine oxidase (XO), the major cardiovascular source of reactive oxygen species (ROS), are up‐regulated. Growing evidence shows that this impaired oxidative metabolism due to enhanced ROS release is implicated in the development of cardiac hypertrophy, myocardial fibrosis, left ventricular remodelling, and contractility impairment responsible for worsening of cardiac function in CHF. Uric acid (UA) has long been linked with cardiovascular diseases, and hyperuricaemia is a common finding in patients with CHF. Hyperuricaemia is associated with impairment of peripheral blood flow and reduced vasodilator capacity, which relate closely to clinical status and reduced exercise capacity. Recent studies also suggest an association between UA levels and parameters of diastolic function; more importantly, UA has emerged as a strong independent prognostic factor in patients with CHF. In this review, we describe the up‐to‐date experimental and clinical studies that have begun to test whether the inhibition of XO translates into meaningful beneficial pathophysiological changes. This treatment gives evidence that myocardial energy, endothelial dysfunction, and vasodilator reactivity to exercise are improved by reducing markers of oxidative stress responsible for vascular dysfunction, so it represents an interesting therapeutic alternative for better outcome in CHF patients.     

Chronic heart failure with preserved left ventricular ejection fraction: diagnostic and prognostic value of left atrial size

BACKGROUND: Almost 40% of patients with heart failure (HF) have preserved left ventricular (LV) ejection fraction (EF) and prognosis similar to those with reduced EF. Data on prognostic markers in such patients are limited. We analyzed the prevalence and prognostic value of left atrial (LA) size in this condition. METHODS: 89 normal subjects (Group I), 38 asymptomatic hypertensive patients (Group II) and 183 HF patients with preserved EF (EF >45%) (Group III) were studied. LA diameter (LAD), LV diastolic (LVD) and systolic (LVS) dimensions and mass (LVmass) and EF were measured. E and A wave velocities and E/A were measured. The primary end point was all cause mortality in group III patients. RESULTS: Groups did not differ in age, gender or EF. Group III patients had larger LAD (4.6+-1.0 cm) compared with both Group I (3.7+/-0.6) and Group II (3.7+/-0.5 cm) (p<0.0001). A markedly enlarged (arbitrarily defined as LAD higher or equal 5 cm) had an odds ratio of 34 (95% CI 8-144) in distinguishing HF patients from normals. After a mean follow-up period of 29+/-27 months, 40 patients (21.9%) died. In Cox univariate analysis, NYHA class (HR 2.8 95% C.I. 1.8-4.3; p<0.0001), diastolic blood pressure (DBP) (HR 0.92 95% C.I. 0.88-0.96; p<0.0001), age (HR 1.059 95% C.I. 1.01-1.11; p=0.02) and LAD (HR 1.72 95% C.I. 1.27-2.3; p=0.0005) were predictors of mortality. LAD predicted survival independently of other variables. CONCLUSION: The left atrium is frequently dilated in HF patients compared with controls despite similar EF. LAD showed powerful prognostic value independent of clinical variables.