Physical activity profile in heart failure patients from a Brazilian tertiary cardiology hospital

Background: Physical activity (PA) has proven benefits in the primary prevention of heart diseases such as heart failure (HF). Although it is well known, HF PA habits and physicians` advice have been poorly described. The aim of this study was to investigate if physicians were advising HF patients to exercise and to quantify patients` exercise profiles in a complex cardiology hospital. Methods: All 131 HF patients (80 male, average age 53 +/- 10 years, NYHA class I-V, left ventricular ejection fraction 35 +/- 11%, 35 ischemic, 35 idiopatic , 32 hypertensive and 29 with Chagas disease) went to the hospital for a HF routine check-up. On this occasion, after seeing the physician, we asked the patients if the physician had advised them about PA. Then, we asked them to fill in the international physical activity questionnaire (IPQA) Short Form to classify their PA level. Results: Our data showed a significant difference between patients who had received any kind of PA advice from physicians (36%) and those who had not (64%, p<0.0001). Using the IPAQ criteria, of the 36% of patients who had received advice, 12.4% were classified as low and 23.6% as moderate. Of the 64% of patients who did not receive advice, 26.8% were classified as lowand 37.2% as moderate. Etiology (except Chagas), functional class, ejection fraction, sex and age did not influence the PA profile. Conclusions: Physicians at a tertiary cardiology hospital were not giving patients satisfactory advice as to PA. Our data supports the need to strengthen exercise encouragement by physicians and for complementary studies on this area. (Cardiol J 2010; 17, 2: 143-148)

The Carvedilol`s Beta-Blockade in Heart Failure and Exercise Training`s Sympathetic Blockade in Healthy Athletes during the Rest and Peak Effort

In recent years, beta-blocker therapy has become a primary pharmacologic intervention in patients with heart failure by blocking the sympathetic activity. To compare the exercise training`s sympathetic blockade in healthy subjects (athletes) and the carvedilol`s sympathetic blockade in sedentary heart failure patients by the evaluation of the heart rate dynamic during an exercise test. A total of 26 optimized and 49 nonoptimized heart failure patients in a stable condition (for, at least, 3 months), 15 healthy athletes and 17 sedentary healthy subjects were recruited to perform a cardiopulmonary exercise test. The heart rate dynamic (rest, reserve, peak and the peak heart rate in relation to the maximum predicted for age) was analyzed and compared between the four groups. The heart rate reserve was the same between optimized (48 +/- 15) and nonoptimized (49 +/- 18) heart failure patients (P < 0.0001). The athletes (188 +/- 9) showed a larger heart rate reserve compared to sedentary healthy subjects (92 +/- 10, P < 0.0001). Athletes and healthy sedentary reached the maximum age-predicted heart ratefor their age, but none of the heart failure patients did. The carvedilol`s sympathetic blockade occurred during the rest and during the peak effort in the same proportion, but the exercise training`s sympathetic blockade in healthy subjects occurred mainly in the rest.

Correlation between CD34(+) and exercise capacity, functional class, quality of life and norepinephrine in heart failure patients

Background: A previous study associated CD34(+) levels with NYHA functional class in heart failure patients. The aim of this study was to correlate CD34(+) levels to exercise capacity, functional class, quality of life and norepinephrine in heart failure patients. Methods: Twenty three sedentary patients (52 +/- 7 years, 78% male) answered the Minnesota Living with Heart Failure Questionnaire and rested for 20 minutes before an investigator collect a blood sample. After this, patients performed a cardiopulmonary exercise test to determine the heart rate at anaerobic and ventilatory threshold and oxygen consumption at peak effort, at anaerobic and ventilatory threshold. One other blood sample was collected during the peak effort to investigate the norepinephrine and CD34(+) levels. Results: Rest percentage of CD34(+) did not show correlation with: left ventricle ejection fraction (r = 0.03, p = 0.888), peakVO(2) (r = 0.32, p = 0.13), VO(2) at anaerobic threshold (VO(2)AT) (r = 0.03, p = 0.86), VO(2) at ventilatory threshold (VO(2)VT) (r = 0.36, p = 0.08), NYHA functional class (r = -0.2, p = 0.35), quality of life (Minnesota) (r = -0.17, p = 0.42). CD34(+) did not show correlation, either, with: peak VO(2) (r = 0.38, p = 0.06), VO(2)AT (r = 0.09, p = 0.65), VO(2)VT (r = 0.43, p = 0.4), NYHA functional class (r = -0.13, p = 0.54), quality of life (r = 0.00, p = 0.99). Conclusions: CD34(+) levels did not correlate with exercise capacity, functional class, quality of life and norepinephrine. Percentage of CD34(+) levels did not increase during the cardiopulmonary exercise test in heart failure patients. (Cardiol J 2009; 16, 5: 426-431)

Increased muscle sympathetic nerve activity predicts mortality in heart failure patients

Background: Previous studies have associated neurohumoral excitation, as estimated by plasma norepinephrine levels, with increased mortality in heart failure. However, the prognostic value of neurovascular interplay in heart failure (HF) is unknown. We tested the hypothesis that the muscle sympathetic nerve activity (MSNA) and forearm blood flow would predict mortality in chronic heart failure patients. Methods: One hundred and twenty two heart failure patients, NYHA II-IV, age 50 +/- 1 ys, LVEF 33 +/- 1%, and LVDD 7.1 +/- 0.2 mm, were followed up for one year. MSNA was directly measured from the peroneal nerve by microneurography. Forearm blood flow was obtained by venous occlusion plethysmography. The variables were analyzed by using univariate, stepwise multivariate Cox proportional hazards analysis, and Kaplan-Meier analysis. Results: After one year, 34 pts died from cardiac death. The univariate analysis showed that MSNA, forearm blood flow, LVDD, LVEF, and heart rate were significant predictors of mortality. The multivariate analysis showed that only MSNA (P = 0.001) and forearm blood flow (P = 0.003) were significant independent predictors of mortality. On the basis of median levels of MSNA, survival rate was significantly lower in pts with >49 bursts/min. Similarly, survival rate was significantly lower in pts with forearm blood flow <1.87 ml/min/100 ml (P = 0.002). Conclusion: MSNA and forearm blood flow predict mortality rate in patients with heart failure. It remains unknown whether therapies that specifically target these abnormalities will improve survival in heart failure. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Mucosal leishmaniasis: description of case management approaches and analysis of risk factors for treatment failure in a cohort of 140 patients in Brazil

Background Mucosal leishmaniasis is caused mainly by Leishmania braziliensis and it occurs months or years after cutaneous lesions. This progressive disease destroys cartilages and osseous structures from face, pharynx and larynx. Objective and methods The aim of this study was to analyse the significance of clinical and epidemiological findings, diagnosis and treatment with the outcome and recurrence of mucosal leishmaniasis through binary logistic regression model from 140 patients with mucosal leishmaniasis from a Brazilian centre. Results The median age of patients was 57.5 and systemic arterial hypertension was the most prevalent secondary disease found in patients with mucosal leishmaniasis (43%). Diabetes, chronic nephropathy and viral hepatitis, allergy and coagulopathy were found in less than 10% of patients. Human immunodeficiency virus (HIV) infection was found in 7 of 140 patients (5%). Rhinorrhea (47%) and epistaxis (75%) were the most common symptoms. N-methyl-glucamine showed a cure rate of 91% and recurrence of 22%. Pentamidine showed a similar rate of cure (91%) and recurrence (25%). Fifteen patients received itraconazole with a cure rate of 73% and recurrence of 18%. Amphotericin B was the drug used in 30 patients with 82% of response with a recurrence rate of 7%. The binary logistic regression analysis demonstrated that systemic arterial hypertension and HIV infection were associated with failure of the treatment (P < 0.05). Conclusion The current first-line mucosal leishmaniasis therapy shows an adequate cure but later recurrence. HIV infection and systemic arterial hypertension should be investigated before start the treatment of mucosal leishmaniasis. Conflicts of interest The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g. pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).

The Bone Histology Spectrum in Experimental Renal Failure: Adverse Effects of Phosphate and Parathyroid Hormone Disturbances

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.

A double-blind, placebo-controlled treatment trial of citalopram for major depressive disorder in older patients with heart failure: The relevance of the placebo effect and psychological symptoms

Background: Little is known about the treatment of depression in older patients with heart failure. This Study was developed to investigate the effectiveness of antidepressant treatment for major depressive disorder (MDD) in the elderly with heart failure. Methods: We enrolled 72 older outpatients with ejection fraction < 50 and diagnosed with MDD by the structured clinical interview for DSM-IV. Thirty-seven patients, 19 on citalopram and 18 on placebo, initiated an 8-week double-blind treatment phase. Measurements were performed with the 31-item Hamilton Rating Scale for Depression (Ham-D-31), the Montgomery-Asberg rating scale (MADRS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE). A psychiatrist followed up the patients weekly, performing a consultation for about 20 min to field complaints after the measurements. Results: A trend toward superiority of citalopram over placebo in reducing depression was observed in MADRS scores (15.05 + 9.74 vs 9.44 + 9.25, P = .082) but not on HAM-D scores. The depressive symptomatology significantly decreased in both groups (P < .001). The high rate of placebo response during the double-blind phase (56.3%) led us to conclude the study at the interim analysis with 37 patients. Conclusion: Citalopram treatment of MDD in older patients with heart failure is well-tolerated with low rates of side effects, but was not significantly more effective than placebo in the treatment of depression. Weekly psychiatric follow-up including counseling may contribute to the improvement of depression in this population. Scales weighted on psychological symptoms such as the MADRS are possibly better suited to measure depression severity and improvement in patients with heart failure. (C) 2009 Elsevier Inc. All rights reserved.

Failure of Imiquimod 5% Cream to Prevent Recurrence of Surgically Excised Trunk Keloids

Keloids are characterized by benign proliferation of fibroblasts in the setting of an altered cytokine profile, with a high recurrence rate after surgical treatment. Imiquimod is a topically applied immune-response modifier. Recently, auxiliary therapy using imiquimod 5% cream to prevent keloid recurrence after excisional surgery was reported to have had good results. To evaluate the efficacy of topical imiquimod 5% cream applied after surgical excision and primary closure of trunk keloids in the prevention of recurrence. Nine patients with a keloid lesion on the trunk were treated with surgical excision and primary closure. Daily application of imiquimod 5% cream for 8 weeks was initiated the night of surgery. The patients were evaluated 2, 4, 8, 12, and 20 weeks after. Keloid recurrence occurred in eight patients, seven of them 12 weeks after surgery. We lost track of one patient. The results of this study suggest that imiquimod 5% cream is not effective in preventing recurrence of trunk keloids after surgical excision. Although this is a small case series, results strongly discourage other studies using imiquimod 5% cream in the prevention of surgically excised trunk keloids. The authors have indicated no significant interest with commercial supporters.

Assessment of a New Experimental Model of Isolated Right Ventricular Failure

We assessed a new experimental model of isolated right ventricular (RV) failure, achieved by means of intramyocardial injection of ethanol. RV dysfunction was induced in 13 mongrel dogs via multiple injections of 96% ethanol (total dose 1 mL/kg), all over the inlet and trabecular RV free walls. Hemodynamic and metabolic parameters were evaluated at baseline, after ethanol injection, and on the 14th postoperative day (POD). Echocardiographic parameters were evaluated at baseline, on the sixth POD, and on the 13th POD. The animals were then euthanized for histopathological analysis of the hearts. There was a 15.4% mortality rate. We noticed a decrease in pulmonary blood flow right after RV failure (P = 0.0018), as well as during reoperation on the 14th POD (P = 0.002). The induced RV dysfunction caused an increase in venous lactate levels immediately after ethanol injection and on the 14th POD (P < 0.0003). The echocardiogram revealed a decrease in the RV ejection fraction on the sixth and 13th PODs (P = 0.0001). There was an increased RV end-diastolic volume on the sixth (P = 0.0001) and 13th PODs (P = 0.0084). The right ventricle showed a 74% +/- 0.06% transmural infarction area, with necrotic lesions aged 14 days. Intramyocardial ethanol injection has allowed the creation of a reproducible and inexpensive model of RV failure. The hemodynamic, metabolic, and echocardiographic parameters assessed at different protocol times are compatible with severe RV failure. This model may be useful in understanding the pathophysiology of isolated right-sided heart failure, as well as in the assessment of ventricular assist devices.

Heart failure disease management program experience in 4,545 heart failure admissions to a community hospital

Background Disease management programs (DMPs) are developed to address the high morbi-mortality and costs of congestive heart failure (CHF). Most studies have focused on intensive programs in academic centers. Washington County Hospital (WCH) in Hagerstown, MD, the primary reference to a semirural county, established a CHF DMP in 2001 with standardized documentation of screening and participation. Linkage to electronic records and state vital statistics enabled examination of the CHF population including individuals participating and those ineligible for the program. Methods All WCH inpatients with CHF International Classification of Diseases, Ninth Revision code in any position of the hospital list discharged alive. Results Of 4,545 consecutive CHF admissions, only 10% enrolled and of those only 52.2% made a call. Enrollment in the program was related to: age (OR 0.64 per decade older, 95% CI 0.58-0.70), CHF as the main reason for admission (OR 3.58, 95% CI 2.4-4.8), previous admission for CHF (OR 1.14, 95% CI 1.09-1.2), and shorter hospital stay (OR 0.94 per day longer, 95% CI 0.87-0.99). Among DMP participants mortality rates were lowest in the first month (80/1000 person-years) and increased subsequently. The opposite mortality trend occurred in nonenrolled groups with mortality in the first month of 814 per 1000 person-years in refusers and even higher in ineligible (1569/1000 person-years). This difference remained significant after adjustment. Re-admission rates were lower among participants who called consistently (adjusted incidence rate ratio 0.62, 95% CI 0.52-0.77). Conclusion Only a small and highly select group participated in a low-intensity DMP for CHF in a community-based hospital. Design of DMPs should incorporate these strong selective factors to maximize program impact. (Am Heart J 2009; 15 8:459-66.)

Influence of Glomerular Filtration Rate on the Pharmacokinetics of Cyclophosphamide Enantiomers in Patients With Lupus Nephritis

The pharmacokinetics of cyclophosphamide (CYC) enantiomers were evaluated in patients with lupus nephritis distributed in 2 groups according to creatinine clearance: group 1 (90.6-144.6 mL/min/1.73 m(2)) and group 2 (42.8-76.4 mL/min/ 1.73 m(2)). All patients were treated with 0.75 to 1.3 g of racemic CYC as a 2-hour infusion and with 1 mg intravenous midazolam as a drug-metabolizing marker. CYC enantiomers and midazolam concentrations in plasma were measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The following differences (Wilcoxon test, P <= .05) were observed between the (S)-(-) and (R)-(+) enantiomers: AUC(0-infinity) 152.41 vs 129.25 mu g.h/mL, CL 3.28 vs 3.89 L/h, Vd 31.38 vs 29.74 L, and t(1/2) 6.79 vs 5.56 h for group 1 and AUC(0-infinity) 167.20 vs 139.08 mu g.h/mL, CL 2.99 vs 3.59 L/h, and t(1/2) 6.15 vs 4.99 h for group 2. No differences (Mann test, P <= .05) were observed between groups 1 and 2 in the pharmacokinetic parameters of both enantiomers. No significant relationship was observed between midazolam clearance (2.92-16.40 mL/min.kg) and clearance of each CYC enantiomer. In conclusion, CYC kinetic disposition is enantioselective, resulting in higher exposures of the (S)-(-) enantiomer in lupus nephritis patients, and the pharmacokinetic parameters of both enantiomers are not altered by the worsening of renal condition.

HbA(1c) as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study

Heart failure (HF) incidence in diabetes in both the presence and absence of CHD is rising. Prospective population-based studies can help describe the relationship between HbA(1c), a measure of glycaemia control, and HF risk. We studied the incidence of HF hospitalisation or death among 1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes and no evidence of HF at baseline. Cox proportional hazard models included age, sex, race, education, health insurance status, alcohol consumption, BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL-cholesterol levels, and smoking). In this population of persons with diabetes, crude HF incidence rates per 1,000 person-years were lower in the absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive, p < 0.001). The adjusted HR of HF for each 1% higher HbA(1c) was 1.17 (95% CI 1.11-1.25) for the non-CHD group and 1.20 (95% CI 1.04-1.40) for the CHD group. When the analysis was limited to HF cases which occurred in the absence of prevalent or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11-1.29). These data suggest HbA(1c) is an independent risk factor for incident HF in persons with diabetes with and without CHD. Long-term clinical trials of tight glycaemic control should quantify the impact of different treatment regimens on HF risk reduction.

The Association of Hemoglobin A1c With Incident Heart Failure Among People Without Diabetes: The Atherosclerosis Risk in Communities Study

OBJECTIVE-This study sought to investigate an association of HbA1c (A1C) with incident heart failure among individuals without diabetes and compare it to fasting glucose. RESEARCH DESIGN AND METHODS-We studied 11,057 participants of the Atherosclerosis Risk in Communities (ARIC) Study without heart failure or diabetes at baseline and estimated hazard ratios of incident heart failure by categories of A1C (<5.0, 5.0-5.4 [reference], 5 5-59, and 6.0-6.4%) and fasting glucose (<90, 90-99 [reference], 100-109, and 110-125 mg/dl) using Cox proportional hazards models. RESULTS-A total of 841 cases of incident heart failure hospitalization or deaths (International Classification of Disease, 9th/10th Revision, 428/150) occurred during a median follow-up of 14.1 years (incidence rate 5.7 per 1,000 person-years). After the adjustment for covariates including fasting glucose, the hazard ratio of incident heart failure was higher in individuals with A1C 6.0-6.4% (1.40 [95% CI, 1 09-1.79]) and 5.5-6.0% (1.16 [0.98-1 37]) as compared with the reference group. Similar results were observed when adjusting for insulin level or limiting to heart failure cases without preceding coronary events or developed diabetes during follow-up. In contrast, elevated fasting glucose was not associated with heart failure after adjustment for covariates and A1C. Similar findings were observed when the top quartile (A1C, 5.7-6.4%, and fasting glucose, 108-125 mg/dl) was compared with the lowest quartile (<5 2% and <95 mg/dl, respectively). CONCLUSIONS-Elevated A1C (>= 5.5-6 0%) was associated with incident heart failure in a middle-aged population without diabetes, suggesting that chronic hyperglycemia prior to the development of diabetes contributes to development of heart failure. Diabetes 59:2020-2026, 2010

Day-night pattern of autonomic nervous system modulation in patients with heart failure with and without sleep apnea

Introduction: Among patients with congestive heart failure (CHF) both obstructive and central sleep apnea (SA) are associated with increased sympathetic activity. However, the day-night pattern of cardiac autonomic nervous system modulation in CHF patients with and without sleep apnea is unknown. Material and methods: Twenty-five CHF patients underwent polysomnography with simultaneous beat-to-beat blood pressure (Portapres), respiration and electrocardiogram monitoring. Patients were divided according to the presence (SA, n=17) and absence of SA (NoSA, n=8). Power spectral analyses of heart rate variability (HRV) and spontaneous baroreflex sensitivity (BRS) were determined in periods with stable breathing while awake at 6 AM, 10 AM, 10 PM, as well as during stage 2 sleep. In addition, muscle sympathetic nerve activity (MSNA) was evaluated at 10 AM. Results: RR variance, low-frequency (LF), high-frequency (HF) powers of HRV, and BRS were significantly lower in patients with SA compared with NoSA in all periods. HF power, a marker of vagal activity, increased during sleep in patients with NoSA but in contrast did not change across the 24-hour period in patients with SA. MSNA was significantly higher in patients with SA compared with NoSA. RR variance, LF and HF powers correlated inversely with simultaneous MSNA (r=-0.64, -0.61, and -0.61 respectively; P < 0.01). Conclusions: Patients with CHF and SA present a reduced and blunted cardiac autonomic modulation across the 24-hour period. These findings may help to explain the increased cardiovascular risk in patients with CHF and SA. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

A general hazard model for lifetime data in the presence of cure rate

Historically, the cure rate model has been used for modeling time-to-event data within which a significant proportion of patients are assumed to be cured of illnesses, including breast cancer, non-Hodgkin lymphoma, leukemia, prostate cancer, melanoma, and head and neck cancer. Perhaps the most popular type of cure rate model is the mixture model introduced by Berkson and Gage [1]. In this model, it is assumed that a certain proportion of the patients are cured, in the sense that they do not present the event of interest during a long period of time and can found to be immune to the cause of failure under study. In this paper, we propose a general hazard model which accommodates comprehensive families of cure rate models as particular cases, including the model proposed by Berkson and Gage. The maximum-likelihood-estimation procedure is discussed. A simulation study analyzes the coverage probabilities of the asymptotic confidence intervals for the parameters. A real data set on children exposed to HIV by vertical transmission illustrates the methodology.