Heart Failure Of Different Etiologies Research Articles

PROGNOSTIC VALUE OF BIOMARKERS IN PATIENTS WITH ISCHEMIC HEART FAILURE

Modern clinical recommendations of medical associations attach great importance to the improvement of methods of early diagnosis, prevention and individualized treatment of heart failure (HF). It is assumed that biological markers that reflect different pathophysiological stages of HF retain their value as a powerful tool for diagnosing acute and chronic HF, stratifying patients into high-risk groups for the occurrence and progression of the specified pathology, and as a probable predictor of treatment effectiveness. Along with this, the levels and prognostic value of serum biomarkers in patients with HF of different etiologies at different stages of treatment remain unclear.The purpose. To study the prognostic value of biomarkers in patients with HF of ischemic origin.Material and methods. 398 were examined with HF aged 45-65 years (54.3±7.2 years. All 398 patients with HF were divided into two groups. The 1st group included 219 (55%) patients who did not have re-hospitalization (RG) due to HF decompensation during the year of observation. The II group consisted of 179 (45%) patients with PG. 226 (56.8%) patients had a permanent form of atrial fibrillation (AF), 102 (25.6%) had type 2 diabetes. Among the examined - 198 (49,7%) women and 200 (50,2%) men. A standardized echocardiographic study was performed to determine the left ventricular ejection fraction (LV EF) and LV dimensions during hospitalization. The levels of thyroid-stimulating hormone, free T3, free T4, blood glucose, glycated hemoglobin, galectin-3, ST-2, BNP, NT-proBNP were determined. The ratios: ST-2 / Galectin-3 (UO), NT-proBNP / BNP (UO), NT-proBNP / ST-2 (UO) and NT-proBNP / Galectin-3 (UO) were calculated. During 1 year, patients were observed, taking into account the presence of repeated hospitalization (RG) due to HF decompensation, mortality. Patients were divided into two groups. The 1st group included 219 (55%) of patients who did not have re-hospitalization (PG) due to HF decompensation. II group - 179 (45%) patients with PG.Results. Compared to patients with a favorable short-term course of the disease, patients with HF of ischemic genesis, who had PG during the year of observation, have HF III and IV PK according to NYHA, diabetes mellitus, and a permanent form of AF more often; higher heart rate, serum levels of galectin-3 (by 11.1%), NT-proBNP (by 31.8%), higher values of NT-proBNP / BNP (by 40.6%) and NT-proBNP / ST- 2 (by 21.1%), but a smaller value of the ST-2 / Galectin-3 ratio (by 9.3%), as well as a higher risk of death during the first year (OR = 3.81). The risk of PG increases when the level of NT-proBNP > 652.6 pg/ml is reached and the ratios: ST-2/Galectin-3 ≤ 17.95 IU, NT-proBNP / BNP > 10.17 IU and NT-proBNP / ST-2 > 13.79 UO. The level of ST-2 > 41.37 ng/ml is prognostically significant for the one-year death of patients within a year.Conclusions. In patients with HF of ischemic genesis, the ratio of NT-proBNP / BNP has a greater prognostic significance regarding the risk of re-hospitalization, compared to NT-proBNP and NT-proBNP / ST-2.

Empagliflozin mitigates ponatinib-induced cardiotoxicity by restoring the connexin 43-autophagy pathway

BackgroundEmpagliflozin (EMPA), a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been shown to reduce major adverse cardiovascular events in patients with heart failure of different etiologies, although the underlying mechanism still remains unclear. Ponatinib (PON) is a multi-tyrosine kinase inhibitor successfully used against myeloid leukemia and other human malignancies, but its cardiotoxicity remains worrisome. Cardiac connexins (Cxs) are both substrates and regulators of autophagy and responsible for proper heart function. Alteration in connexin expression and localization have been described in patients with heart failure. AimsTo assess whether EMPA can mitigate PON-induced cardiac dysfunction by restoring the connexin 43-autophagy pathway. Methods and ResultsMale C57BL/6 mice, randomized into four treatment groups (CNTRL, PON, EMPA, PON+EMPA) for 28 days, showed increased autophagy, decreased Cx43 expression as well as Cx43 lateralization, and attenuated systo-diastolic cardiac dysfunction after treatment with EMPA and PON compared with PON alone. Compared with CNTRL (DMSO), cardiomyocyte-differentiated H9c2 (dH9c2) cells treated with PON showed significantly reduced cell viability to approximately 20 %, decreased autophagy, increased cell senescence and reduced DNA binding activity of serum response factor (SRF) to serum response elements (SRE), which were paralleled by reduction in cardiac actin expression. Moreover, PON induced a significant increase of Cx43 protein and its S368-phosphorylated form (pS368-Cx43), as well as their displacement from the plasma membrane to the perinuclear and nuclear cellular region. All these effects were reverted by EMPA. ConclusionEMPA attenuates PON-induced cardiotoxicity by reducing senescence, enhancing the SRE-SRF binding and restoring the connexin 43-autophagy pathway. This effect may pave the way to use of SGLT2 inhibitors in attenuating tyrosine-kinase inhibitor cardiotoxicity.

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

Metabolic markers of myocardium insulin resistance in dogs with heart failure.

Background:Heart failure syndrome is an aspect of primary or secondary heart disease and is associated with decompensation, formation, and activation of pathological interactions between regulation systems. This results in myocardial energy metabolism alteration. This study was carried out to defy some metabolic aspects of myocardial tissue insulin resistance (IRM) development in canine heart failure.Aim:To investigate the myocardial tissue concentration of adenosine triphosphate (ATP), glucose transporters 1 and 4, pyruvate dehydrogenase (PDH), hexokinase 2, insulin receptor (InsR), and adropin (ADR) protein and to screen metabolic changes and IRM in canine myocardium with heart failure.Methods:We studied 28 dogs of different sexes, ages, and breeds. Groups were formed according to primary pathology: apparently healthy dogs (HD, n = 6); dogs with CDVD (CDVDD, n = 8); dogs with DCM (DCMD, n = 6); and dogs with doxorubicin chemotherapy and doxorubicin-induced cardiomyopathy (DoxCMD, n = 8). Animals in the study were diagnosed for primary disease by standard methods and algorithms. Animals were euthanized due to incurable neurological disease, refractory heart failure, or by owners will. The material was obtained immediately after death, fixed in liquid nitrogen, and stored in −80°C refrigerator. Studied proteins concentrations were analyzed in a specialized research laboratory, using ELISA kits, provided by Cloud-Clone Corp.Results:ATP, GLUT1, and GLUT4 concentrations in myocardial tissue from the valvular disease group did not differ from the HD group. In CDVD, we found depression of PDH, hexokinase II (HX2), and ADR concentrations in comparison to HD. InsR was significantly lower in the CDVD and DoxCMD groups in comparison to the HD group, but in the DCM group, it was twofold higher than in the HD group. In the DCMD and DoxCMD groups, all parameters were lower than in the HD group. ATP, HX2, ADR, GLUT1, and GLUT4 were higher in the CDVD group, than in the DCM and DoxCM groups. PDH in the CDVD and DoxCM groups did not differ. PDH was depleted in the DCM to CDVD and DoxCM groups. InsR did not differ between the CDVD and DoxCM groups, but was upregulated in the DCM to CDVD and DoxCM groups.Conclusion:Development of myocardial tissue IRM is a part of the structural, functional and metabolic remodeling in dogs with heart failure of different etiology. At the late stages, we found significant changes in energy supply availability and production in the myocardium.

Electrophysiological remodeling of the right ventricle in experimental heart failure of different etiologies

The aim of the study was to evaluate electrophysiological remodeling of the right ventricle in rats in experimental heart failure of different etiologies. Materials and methods. Isadrin-, doxorubicin- and monocrotaline-induced heart failure models were developed. Unipolar epicardial electrograms of the ventricles (256 recording sites) were recorded using a 144-channel system. The cardiac output and pressure in both ventricles of the heart were measured. Activation-recovery intervals were used as an index of duration of local repolarization, and the general and local dispersions of activation-recovery intervals were used as an index of heterogeneity of ventricular repolarization. Results. In all models of heart failure, the following were identified: 1) non-uniform prolongation of repolarization with the greatest elongation at the apex of the right ventricle; 2) an increase in apicobasal differences of repolarization with the greatest change in the right ventricle; 3) an increase in the heterogeneity of the repolarization of the epicardial layer of the ventricles with heterogeneous changes in the local heterogeneity of repolarization and a decrease in the interregional differences in the heterogeneity of the electrophysiological properties of the myocardium; 4) more pronounced changes in the repolarization of the right ventricle than in the repolarization of the left ventricle. Conclusion. Thus, irrespective of the cause of the heart failure, the following changes occur: 1) prolongation of the right ventricular repolarization occurs non-uniformly (mostly due to the apical area), which results in an increase in the right ventricular repolarization heterogeneity; 2) an increase in the heterogeneity of right ventricular repolarization is observed, which causes an increase in the overall heterogeneity of the ventricular epicardial surface.

P5666Long-term survival analysis of patients with heart failure of different etiologies in a Brazilian cohort of outpatients - a bayesian approach

P5666Long-term survival analysis of patients with heart failure of different etiologies in a Brazilian cohort of outpatients - a bayesian approach

Pathogenetic and prognostic significance of molecular markers of myocardial remodeling in patients suffering from chronic heart failure

It is known that there are features of myocardial remodeling in various heart diseases. However, the influence of signaling regulatory factors in its development and their significance in predicting a course of chronic heart failure remains unclear. The importance of key markers of apoptosis, extracellular matrix, p-38α in myocardium of patients with chronic heart failure of different etiology in the development of cardiovascular complications after cardiac surgery is considered. It has been established that the combination of heart failure with coronary heart disease, heart failure with valvular defects are specific phenotypes with a special reorganization of myocardium. With the combination of heart failure with coronary heart disease without cardiovascular complications in the myocardium, higher activity of caspase-9 and TIMP-1 was noted, and differences in morphometric data were revealed in comparison with the group of heart failure with valvular defects. In groups with an unfavorable outcome of cardiosurgical operations of different etiology of chronic heart failure, there were no differences in the morphological indices and activity of molecular markers of the myocardium. This fact allows one to consider the activation of caspase-9, MMP-9, p38α in the myocardium as prognostic markers of the unfavorable outcome of cardiac surgery in patients suffering from heart failure regardless of etiology. A higher percentage of cardiovascular complications in the combination of chronic heart failure with coronary heart disease is probably associated with a less favorable myocardial phenotype and requires a specific pharmacological correction before cardiac surgery.

Cytokines and the Role of Immunomodulation in Heart Failure of Different Etiologies

Cytokines and the Role of Immunomodulation in Heart Failure of Different Etiologies

PROADRENOMEDULIN AS A PREDICTOR OF MORTALITY IN MAJOR NON-CARDIAC SURGERY

Anesthesiologists are in daily contact with patients who are preparing for noncardiosurgical interventions, and who have an increased risk of developing cardiovascular complications in the perioperative period. Less than 1% of patients develop perioperative IM, however the mortality rate for this complication ranges from 30% to 50%. The first step is the identification of patients in whom the cardiovascular system is a potential source of complications during and after surgery. The risk of perioperative complications depends on the condition of the patient prior to the intervention, prevalence of comorbidities and the extent, urgency and duration of the operation. The modern concept of preoperative preparation of patients for major non-cardiac surgery is now based on the measurement and interpretation of various biomarkers as prognosticators of perioperative cardiovascular complications and fatal outcomes. For these purposes, high-performance natriuretic peptides and cardiac troponins are used. There is evidence that the levels of cardiac-specific troponins, and especially highsensitivity troponin T(hs-TnT), have been elevated in patients with various cardiovascular diseases such as: cardiac insufficiency and coronary disease, reflecting in this way a lower degree of damage that can be of significant benefit in the preoperative assessment of cardiovascular morbidity and mortality in elective, major non-cardiac surgery. Although various natriuretic peptides have been in the greatest focus of interest as prognostic biomarkers over the past decade, the interest in other circulating biomarkers, such as midregional proadrenomedulin (MR-pro ADM), has been growing in recent years. This new biomarker represents a stable circulating peptide, and is the prohormone of adrenomedulin, a hormone responsible for regulating the volume of circulating fluid and electrolyte homeostasis. Elevated levels of this biomarker are seen in heart failure of different etiologies and can therefore serve as a useful prognostic marker of the development of perioperative cardiovascular complications in patients with different cardiovascular comorbid conditions.

Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy

Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. Invitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. Invivo blockade of Gal-3 with N-acetyl-d-lactosamine in T. cruzi-infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy.

Myocardial fibrosis: Current aspects of the problem

Fibrosis is one of the main components in the progression of most cardiovascular diseases, including coronary heart disease, by causing structural changes in the myocardium and vascular wall. The quantitative and qualitative characteristics of fibrosis of the myocardium are responsible for decreasing its elastic properties, developing diastolic dysfunction, impairing myocardial contractility, developing systolic dysfunction and cardiac arrhythmias, and worsening coronary blood flow in patients with heart failure of different etiologies. The important aspect of studying fibrosis is not only its interpretation as a model of the typical pathological process, but also its consideration as a systemic lesion of various organs and tissues. At the same time, the identification of myocardial fibrosis biomarkers that are available for their determination in circulating blood is of particular interest. Since there was evidence for the role of fibrosis in developing dysfunction of various organs and ensuring the systematicity of most diseases, especially at their development stages, the process of fibrosis came to be regarded as a promising therapeutic target. It is relevant to further investigate myocardial fibrosis, which is aimed at increasing the efficiency of its diagnosis and predicting its course and pathogenetically sound therapy.

Automatic multi-vessel volume flow calculation with 4D flow CMR

Volume flow analysis is essential in the assessment of many cardiovascular diseases such as valvular regurgitation, intra-cardiac shunt, and complex congenital heart diseases. Clinically, CMR-based volume flow analysis is performed using 2D flow CMR. This requires user-dependent and time-consuming positioning of 2D planes in each vessel while the patient is still in the scanner. Previous studies have demonstrated that 4D flow CMR permits accurate volume flow assessment. However, retrospective plane-positioning and region-of-interest delineation requires time-consuming user interaction. The aim of this study was to develop an automatic method for volume flow analysis in the great thoracic vessels using 4D flow CMR. Methods The automatic multi-vessel volume flow calculation method is illustrated in Figure 1. An atlas (reference vessel segmentation) was created by manual segmentation of the great thoracic vessels in one healthy volunteer. The segmentation was done on a 3D PC-MRA which was derived from the 4D flow CMR data. Analysis planes for volume flow determination were positioned in the proximal ascending aorta and pulmonary trunk. For each subject, the atlas’ PC-MRA was registered to the subject’s PC-MRA. In this way, the atlas’ vessels and analysis planes were transformed into the subject’s vessels. The transformed atlas was transferred to all timeframes using the 4D flow CMR magnitude image, resulting in a time-resolved segmentation that follows the motion of the vessels over the cardiac cycle. Finally, the volume flow was automatically calculated for each plane using the time-resolved atlas as a mask to account for vessel location, shape and movement. The method was evaluated in a group of subjects composed of 10 healthy volunteers and 11 patients with heart failure of different etiologies. Results in the proximal ascending aorta were compared against volume flow values obtained by manual segmentation. Additionally, the pulmonary-to-aortic flow ratio (Qp/Qs) was assessed. Results

GW25-e4609 Effects of left ventricular lead position on cardiac resynchronization therapy in heart failure of different etiologies

GW25-e4609 Effects of left ventricular lead position on cardiac resynchronization therapy in heart failure of different etiologies

How can we cure a heart “in flame”? A translational view on inflammation in heart failure

The prevalence of chronic heart failure is still increasing making it a major health issue in the 21st century. Tremendous evidence has emerged over the past decades that heart failure is associated with a wide array of mechanisms subsumed under the term “inflammation”. Based on the great success of immuno-suppressive treatments in auto-immunity and transplantation, clinical trials were launched targeting inflammatory mediators in patients with chronic heart failure. However, they widely lacked positive outcomes. The failure of the initial study program directed against tumor necrosis factor-α led to the search for alternative therapeutic targets involving a broader spectrum of mechanisms besides cytokines. We here provide an overview of the current knowledge on immune activation in chronic heart failure of different etiologies, summarize clinical studies in the field, address unresolved key questions, and highlight some promising novel therapeutic targets for clinical trials from a translational basic science and clinical perspective.

NT-proANP and NT-proBNP as prognostic markers in patients with acute decompensated heart failure of different etiologies

Background and purposePeak NT-proANP and NT-proBNP plasma levels after hospital admission may be of additional prognostic value in patients with acute decompensation of heart failure. The time-course of natriuretic plasma levels after hospital admission, and a possible influence of the underlying etiology on the time-course have not been sufficiently investigated. Methods and resultsNatriuretic peptide plasma levels of 85 patients with decompensated heart failure from ischemic and non-ischemic origins were measured at baseline and at 12h after hospital admission. NT-proBNP plasma levels on admission were lower compared to 12-hour-plasma levels, whereas NT-proANP plasma levels on admission were higher compared to 12-hour-plasma levels. Twenty-six patients (31%) died within the first 30days. In patients who died within the first 30days after admission NT-proANP and NT-proBNP plasma levels on admission and 12h later were significantly higher compared to survivors. Irrespective of different etiologies NT-proANP on admission and NT-proBNP 12h after admission were highest and demonstrated superior impact with respect to the prediction of 30-day-mortality. ConclusionsNT-proANP and NT-proBNP are powerful markers of 30-day-mortality in patients with acute heart failure of ischemic and non-ischemic origins. With respect to the prediction of 30-day-mortality, NT-proBNP plasma levels at 12h after admission are comparable with NT-proANP plasma levels on admission. These data underline the fact that with regard to etiology-dependent hemodynamic changes and plasma half-time, the determination of peak plasma levels is of highest importance for the estimation of the impact of natriuretic peptides on the prognosis of patients with decompensated heart failure.

Peak oxygen uptake in relation to total heart volume discriminates heart failure patients from healthy volunteers and athletes.

BackgroundAn early sign of heart failure (HF) is a decreased cardiac reserve or inability to adequately increase cardiac output during exercise. Under normal circumstances maximal cardiac output is closely related to peak oxygen uptake (VO2peak) which has previously been shown to be closely related to total heart volume (THV). Thus, the aim of this study was to derive a VO2peak/THV ratio and to test the hypothesis that this ratio can be used to distinguish patients with HF from healthy volunteers and endurance athletes. Thirty-one patients with HF of different etiologies were retrospectively included and 131 control subjects (60 healthy volunteers and 71 athletes) were prospectively enrolled. Peak oxygen uptake was determined by maximal exercise test and THV was determined by cardiovascular magnetic resonance. The VO2peak/THV ratio was then derived and tested.ResultsPeak oxygen uptake was strongly correlated to THV (r2 = 0.74, p < 0.001) in the control subjects, but not for the patients (r2 = 0.0002, p = 0.95). The VO2peak/THV ratio differed significantly between control subjects and patients, even in patients with normal ejection fraction and after normalizing for hemoglobin levels (p < 0.001). In a multivariate analysis the VO2peak/THV ratio was the only independent predictor of presence of HF (p < 0.001).ConclusionsThe VO2peak/THV ratio can be used to distinguish patients with clinically diagnosed HF from healthy volunteers and athletes, even in patients with preserved systolic left ventricular function and after normalizing for hemoglobin levels.

Avaliação do metabolismo dos fosfatos de alta energia em pacientes com doença de Chagas

Abnormalities in myocardial metabolism have been observed in patients with heart failure of different etiologies. Magnetic resonance spectroscopy (MRS) with phosphorus-31 is a noninvasive technique that allows detection of myocardial metabolic changes. To determine the resting metabolism of high-energy phosphates in patients with Chagas' disease (CD) by MRS with phosphorus-31. We studied 39 patients with CD, 23 with preserved ventricular function (PF Group) and 16 with ventricular dysfunction (VD Group), assessed by Doppler echocardiography. MRS of the anterosseptal region was performed in 39 patients and 8 normal subjects (C Group) through a Phillips 1.5 Tesla device, obtaining the phosphocreatine/beta-adenosine triphosphate myocardial ratio (PCr/β-ATP). The levels of cardiac PCr/β-ATP were reduced in VD Group in relation to PF Group, and the latter presented reduced levels compared to C Group (VD Group: 0.89 ± 0.31 vs PF Group: 1.47 ± 0.34 vs C Group: 1.88 ± 0.08, p < 0.001). A correlation was found between left ventricular ejection fraction and PCr/β-ATP in 39 patients (r = 0.64, p < 0.001). Patients under functional class I (n = 22) presented PCr/β-ATP of 1.45 ± 0.35, and those in functional classes II and III (n = 17), PCr/β-ATP of 0.94 ± 0.36 (p < 0.001). The 31-phosphorus MRS was able to detect non-invasively changes in the rest energy metabolism of patients with Chagas' disease, with and without systolic dysfunction. These changes were related to the severity of heart impairment.

Mortality and Cause of Death in Patients With Heart Failure: Findings at a Specialist Multidisciplinary Heart Failure Unit

Heart failure mortality is similar to or even higher than that due to various cancers. It is usually associated with disease progression, though sudden death has also been reported as a frequent cause of mortality. The objectives of this study were to investigate mortality and its causes in outpatients with heart failure of different etiologies who were treated in a specialist multidisciplinary unit, and to identify associated factors. The follow-up cohort study (median duration 36 months) involved 960 patients (70.9% male; median age 69 years; ejection fraction 31%; and the majority had an ischemic etiology and were in functional class II or III). Overall, 351 deaths (36.5%) occurred: 230 due to cardiovascular causes (65.5%), mainly heart failure (33.2%) and sudden death (16%); 94 due to non-cardiovascular causes (26.8%), mainly malignancies (10.5%) and septic processes (6.8%); and 27 (7.7%) due to unknown causes. Mortality was independently associated with age, sex, functional class, ejection fraction, time since symptom onset, ischemic etiology, diabetes, creatinine clearance rate, peripheral vascular disease, fragility, and the absence of treatment with an angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker, beta-blockers, statins or antiplatelet agents. The principal factor associated with cardiovascular death was an ischemic etiology. No factor studied clearly predicted sudden death. Even though mortality in patients treated at a specialist heart failure unit was not low, a quarter died from non-cardiovascular causes. The principal factor associated with cardiovascular death was an ischemic etiology. Only 5.8% of the study population experienced sudden death.

Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure

Background -Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies.Methods -We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism.Results -During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (χ2 = 9.797;p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals.Conclusion -In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.

Efeito do bisoprolol sobre a função cardíaca e o exercício em pacientes com insuficiência cardíaca

To assess the effects of bisoprolol on exercise capacity and ventricular function in patients with heart failure. Clinical and hemodynamic variables, ventricular function and remodeling, and ergospirometry of patients with heart failure of different etiologies were evaluated before and after the administration of bisoprolol. Twenty-two patients were analyzed; one patient did not tolerate medication and 14 patients reached the study goal. The group consisted of 9 men and 5 women, the mean age was 52 (36-64) years, and patients were followed during 551 days (238-1109). We observed an improvement in NYHA functional class, reduction in resting heart rate (78.8+/-8.7 vs 63+/-6.4 bpm, p <0.001), increase in left ventricular ejection fraction (31.3+/-8.5% vs 39+/-14.7%. p=0.043), and a tendency towards improved quality of life scores (31+/-20.6 vs 17.8+/-14.8. p=0.058). The maximum heart rate dropped during exercise (138.1+/-20.2 vs 116.7+/-27.1. p=0.01), as did peak oxygen consumption (20.9+/-6.8 vs 15.1+/-3.5. p<0.001); no change was observed on the EV/VCO2 slope. The effects were observed for all etiologies, including Chagas disease. Bisoprolol was safe and well tolerated in patients with heart failure. Bisoprolol therapy improved the symptoms, hemodynamic variables, as well as the cardiac function for all etiologies; however, it did not result in improved exercise capacity.