Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure

Background:Testosterone 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.Objective:We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.Methods:Total 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.Results:Length 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).Conclusion:These 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.

Lowering Pulmonary Wedge Pressure after Heart Transplant: Pulmonary Compliance and Resistance Effect

AbstractBackground:Right ventricular (RV) afterload is an important risk factor for post-heart transplantation (HTx) mortality, and it results from the interaction between pulmonary vascular resistance (PVR) and pulmonary compliance (CPA). Their product, the RC time, is believed to be constant. An exception is observed in pulmonary hypertension because of elevated left ventricular (LV) filling pressures.Objective:Using HTx as a model for chronic lowering of LV filling pressures, our aim was to assess the variations in RV afterload components after transplantation.Methods:We retrospectively studied 159 patients with right heart catheterization before and after HTx. The effect of Htx on hemodynamic variables was assessed.Results:Most of the patients were male (76%), and the mean age was 53 ± 12 years. HTx had a significant effect on the hemodynamics, with normalization of the LV and RV filling pressures and a significant increase in cardiac output and heart rate (HR). The PVR decreased by 56% and CPA increased by 86%. The RC time did not change significantly, instead of increasing secondary to pulmonary wedge pressure (PWP) normalization after HTx as expected. The expected increase in RC time with PWP lowering was offset by the increase in HR (because of autonomic denervation of the heart). This effect was independent from the decrease of PWP.Conclusion:The RC time remained unchanged after HTx, notwithstanding the fact that pulmonary capillary wedge pressure significantly decreased. An increased HR may have an important effect on RC time and RV afterload. Studying these interactions may be of value to the assessment of HTx candidates and explaining early RV failure after HTx.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio are Predictors of Heart Failure

Abstract Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory markers used as prognostic factors in various diseases. The aims of this study were to compare the PLR and the NLR of heart failure (HF) patients with those of age-sex matched controls, to evaluate the predictive value of those markers in detecting HF, and to demonstrate the effect of NLR and PLR on mortality in HF patients during follow-up. Methods: This study included 56 HF patients and 40 controls without HF. All subjects underwent transthoracic echocardiography to evaluate cardiac functions. The NLR and the PLR were calculated as the ratio of neutrophil count to lymphocyte count and as the ratio of platelet count to lymphocyte count, respectively. All HF patients were followed after their discharge from the hospital to evaluate mortality, cerebrovascular events, and re-hospitalization. Results: The NLR and the PLR of HF patients were significantly higher compared to those of the controls (p < 0.01). There was an inverse correlation between the NLR and the left ventricular ejection fraction of the study population (r: -0.409, p < 0.001). The best cut-off value of NLR to predict HF was 3.0, with 86.3% sensitivity and 77.5% specificity, and the best cut-off value of PLR to predict HF was 137.3, with 70% sensitivity and 60% specificity. Only NLR was an independent predictor of mortality in HF patients. A cut-off value of 5.1 for NLR can predict death in HF patients with 75% sensitivity and 62% specificity during a 12.8-month follow-up period on average. Conclusion: NLR and PLR were higher in HF patients than in age-sex matched controls. However, NLR and PLR were not sufficient to establish a diagnosis of HF. NLR can be used to predict mortality during the follow-up of HF patients.

Alternatives to Aerobic Exercise Prescription in Patients with Chronic Heart Failure

Background: Exercise is essential for patients with heart failure as it leads to a reduction in morbidity and mortality as well as improved functional capacity and oxygen uptake (v̇O2). However, the need for an experienced physiologist and the cost of the exam may render the cardiopulmonary exercise test (CPET) unfeasible. Thus, the six-minute walk test (6MWT) and step test (ST) may be alternatives for exercise prescription. Objective: The aim was to correlate heart rate (HR) during the 6MWT and ST with HR at the anaerobic threshold (HRAT) and peak HR (HRP) obtained on the CPET. Methods: Eighty-three patients (58 ± 11 years) with heart failure (NYHA class II) were included and all subjects had optimized medication for at least 3 months. Evaluations involved CPET (v̇O2, HRAT, HRP), 6MWT (HR6MWT) and ST (HRST). Results: The participants exhibited severe ventricular dysfunction (ejection fraction: 31 ± 7%) and low peak v̇O2 (15.2 ± 3.1 mL.kg-1.min-1). HRP (113 ± 19 bpm) was higher than HRAT (92 ± 14 bpm; p < 0.05) and HR6MWT (94 ± 13 bpm; p < 0.05). No significant difference was found between HRP and HRST. Moreover, a strong correlation was found between HRAT and HR6MWT (r = 0.81; p < 0.0001), and between HRP and HRST (r = 0.89; p < 0.0001). Conclusion: These findings suggest that, in the absence of CPET, exercise prescription can be performed by use of 6MWT and ST, based on HR6MWT and HRST

Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats

Background: Heart failure prediction after acute myocardial infarction may have important clinical implications. Objective: To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. Methods: The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. Results: Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. Conclusion: In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset.

Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure?

Abstract Background: Heart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression. Objectives: The aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients. Methods: A total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed. Results: Elevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young’s modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions. Conclusions: This study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

Abstract Background: Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. Objective: We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Methods: Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. Results: 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). Conclusions: In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF.

Risk Prediction of Cardiovascular Complications in Pregnant Women With Heart Disease

Abstract Background: Heart disease in pregnancy is the leading cause of non- obstetric maternal death. Few Brazilian studies have assessed the impact of heart disease during pregnancy. Objective: To determine the risk factors associated with cardiovascular and neonatal complications. Methods: We evaluated 132 pregnant women with heart disease at a High-Risk Pregnancy outpatient clinic, from January 2005 to July 2010. Variables that could influence the maternal-fetal outcome were selected: age, parity, smoking, etiology and severity of the disease, previous cardiac complications, cyanosis, New York Heart Association (NYHA) functional class > II, left ventricular dysfunction/obstruction, arrhythmia, drug treatment change, time of prenatal care beginning and number of prenatal visits. The maternal-fetal risk index, Cardiac Disease in Pregnancy (CARPREG), was retrospectively calculated at the beginning of prenatal care, and patients were stratified in its three risk categories. Results: Rheumatic heart disease was the most prevalent (62.12%). The most frequent complications were heart failure (11.36%) and arrhythmias (6.82%). Factors associated with cardiovascular complications on multivariate analysis were: drug treatment change (p = 0.009), previous cardiac complications (p = 0.013) and NYHA class III on the first prenatal visit (p = 0.041). The cardiovascular complication rates were 15.22% in CARPREG 0, 16.42% in CARPREG 1, and 42.11% in CARPREG > 1, differing from those estimated by the original index: 5%, 27% and 75%, respectively. This sample had 26.36% of prematurity. Conclusion: The cardiovascular complication risk factors in this population were drug treatment change, previous cardiac complications and NYHA class III at the beginning of prenatal care. The CARPREG index used in this sample composed mainly of patients with rheumatic heart disease overestimated the number of events in pregnant women classified as CARPREG 1 and > 1, and underestimated it in low-risk patients (CARPREG 0).

The conduction system of the heart in mice chronically infected with Trypanosoma cruzi: histopathological lesions and electrocardiographic correlations

Chronic focal and diffuse myiocarditis with interstitial fibrosis developed in Swiss outbred mice and in the inbred AKR and A/J strains of mice which were chronically infected with several Trypanosoma cruzi strains belonging to three biological types (Type I, II and III). High incidence of electrocardiographic changes with predominance of intraventricular conduction disturbances, 1st. and 2nd. degree AV block, arrhythmias, comparable with those found in human Chagas' disease, were also present. Morphological study of the conduction tissue of the heart revealed inflammatory and fibrotic changes. The presence of inflammation in the inter-atrial septum almost always coincided with the inflammatory involvement of the ventricular conduction system. Focal inflammation was associated with vacuolization and focal necrosis of the specific fibers. Most of the lesions were seen affecting the His bundel (76.3% of the cases), the right bundle branch (73.3%), AV node (43.9%) and left bundle branch (37.5%). Correlation between morphological changes in the conduction tissue and electrocardiographic alteration occured in 53.0 to 62.5% of the cases, according to the experimental groups.

Brain natriuretic peptide and left ventricular dysfunction in chagasic cardiomyopathy

Global left ventricular (LV) systolic dysfunction is the strongest predictor of morbidity and mortality in Chagas disease. Echocardiography is considered the gold standard for the detection of LV dysfunction, but not always available in endemic areas where chagasic cardiomyopathy is most common. Brain natriuretic peptide (BNP) is a neurohormone that has been recently described as a simple and inexpensive diagnostic and prognostic marker for patients with congestive heart failure. Chagasic patients (n = 63) and non-infected healthy individuals (n = 18) were recruited prospectively and underwent complete clinical examination, echocardiography and 24-h Holter monitoring. BNP was measured from thawed plasma samples using the Triage BNP test. We observed high levels of BNP in association with depression of LV ejection fraction, with increase of LV end-diastolic diameter and with LV premature complexes. An elevated concentration of BNP, defined as a concentration of 60 pg/ml or more, had a sensitivity of 91.7%, specificity of 82.8%, positive predictive value of 52.4%, and negative predictive value of 98% for detecting LV dysfunction (LV ejection fraction < 40%).BNP measurement using a simple, relatively inexpensive and rapid test has a promising role in identifying LV dysfunction associated with chagasic cardiomyopathy. Equally important, patients with Trypanosoma cruzi infection who have low levels of BNP level in plasma have a very low likelihood of severe cardiac involvement, and echocardiography is probably not necessary.

Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification

Chagas heart disease (CHD) results from infection with the protozoan parasite Trypanosoma cruzi and is the leading cause of infectious myocarditis worldwide. It poses a substantial public health burden due to high morbidity and mortality. CHD is also the most serious and frequent manifestation of chronic Chagas disease and appears in 20-40% of infected individuals between 10-30 years after the original acute infection. In recent decades, numerous clinical and experimental investigations have shown that a low-grade but incessant parasitism, along with an accompanying immunological response [either parasite-driven (most likely) or autoimmune-mediated], plays an important role in producing myocardial damage in CHD. At the same time, primary neuronal damage and microvascular dysfunction have been described as ancillary pathogenic mechanisms. Conduction system disturbances, atrial and ventricular arrhythmias, congestive heart failure, systemic and pulmonary thromboembolism and sudden cardiac death are the most common clinical manifestations of chronic Chagas cardiomyopathy. Management of CHD aims to relieve symptoms, identify markers of unfavourable prognosis and treat those individuals at increased risk of disease progression or death. This article reviews the pathophysiology of myocardial damage, discusses the value of current risk stratification models and proposes an algorithm to guide mortality risk assessment and therapeutic decision-making in patients with CHD.

Morbidity of Chagas heart disease in the microregion of Rio Negro, Amazonian Brazil: a case-control study

A case-control study on the morbidity of Chagas heart disease was carried out in the municipality of Barcelos in the microregion of the Rio Negro, state of Amazonas. One hundred and six individuals, who were serologically positive for Trypanosoma cruzi infection, as confirmed by at least two techniques with different principles, were matched according to age and sex with an equal number of seronegative individuals. The cases and controls were evaluated using an epidemiological questionnaire and clinical, electrocardiograph and echocardiograph examinations. In the seroepidemiological evaluation, 62% of the interviewees recognised triatomines and most of them confirmed that they had seen these insects in the piassava plantations of the riverside communities of the Negro River tributaries. Of the seropositive patients, 25.8% affirmed that they had been stung by the triatomines and 11.7% denied having been stung. The principal clinical manifestations of the seropositive individuals were palpitations, chest pain and dyspnoea upon effort. Cardiac auscultation revealed extrasystoles, bradycardia and systolic murmurs. The electrocardiographic alterations were ventricular extrasystoles, left and right bundle branch block, atrioventricular block and primary T wave alterations. The echocardiogram was altered in 22.6% of the seropositive individuals and in 8.5% of the seronegative individuals.