Fabiana G. Marcondes-Braga

Exhaled Acetone as a New Biomarker of Heart Failure Severity

BACKGROUND Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity. METHODS Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded. RESULTS The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 μg/L; interquartile range [IQR], 1.69-10.45 μg/L) than in the control group (median, 0.39 μg/L; IQR, 0.30-0.79 μg/L; P < .001) and higher in the ADHF group (median, 7.8 μg/L; IQR, 3.6-15.2 μg/L) than in the chronic HF group (median, 1.22 μg/L; IQR, 0.68-2.19 μg/L; P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001). CONCLUSIONS EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity.

Mode of Death on Chagas Heart Disease: Comparison with Other Etiologies. A Subanalysis of the REMADHE Prospective Trial

Background Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy. Methods and results We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas) and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1%) died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34–5.69; p = 0.006), LVEDD (left ventricular end diastolic diameter) (HR 1.07; CI 1.04–1.10; p<0.001), creatinine clearance (HR 0.98; CI 0.97–0.99; p = 0.006) and use of amiodarone (HR 3.05; CI 1.47–6.34; p = 0.003) were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01–1.07; p = 0.005) and use of beta-blocker (HR 0.52; CI 0.34–0.94; p = 0.014) were independently associated with sudden death mortality. Conclusions In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death. Trial Registration ClinicalTrails.gov NCT00505050 (REMADHE)

Hypertonic saline solution for prevention of renal dysfunction in patients with decompensated heart failure

BACKGROUND Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure. METHODS In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP2), urea transporter (UT-A1), and sodium/hydrogen exchanger 3 (NHE3). RESULTS Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo. CONCLUSIONS HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis.

Recovery of Renal Function in Heart Transplantation Patients After Conversion From a Calcineurin Inhibitor-Based Therapy to Sirolimus

BACKGROUND Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. METHODS The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance < 50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL, P = .01) and CrCl (24.9 +/- 6.5 to 45.7 +/- 17.2 mL/min, P = .005) at 6 months follow-up. CONCLUSION The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.

Exhaled Breath Analysis in Heart Failure.

Heart failure (HF) is a clinical condition that presents high morbidity and mortality and is one of the main reasons for hospital admissions all over the world. Although biochemical processes that occur in the body during heart failure are known, this syndrome is still associated to poor prognosis. Exhaled breath analysis has emerged as a promising noninvasive tool in different clinical conditions and, recently, it has been also tested in patients with HF. This review presents the main breath HF biomarkers, which reflect metabolic changes that occur in this complex syndrome. It also discusses the diagnostic and prognostic value of exhaled breath compounds for HF and makes a short description of the main technologies involved in this analysis. Some perspectives on the area are presented as well.

Temporal trends in the contribution of Chagas cardiomyopathy to mortality among patients with heart failure

Background Chagas cardiomyopathy (ChC) prevalence is decreasing in Brazil and medical therapies for heart failure (HF) have improved in the last decade. Whether these changes modified the prognosis of ChC relative to non-Chagas cardiomyopathies (NChC) remains unknown. This study evaluated the temporal trends in population attributable risk (PAR) of ChC for 2-year mortality among patients with HF enrolled at years 2002–2004 (era 1) and 2012–2014 (era 2) in a Brazilian university hospital. Methods We prospectively studied 362 (15% with ChC) and 582 (18% with ChC) HF patients with ejection fraction ≤50% in eras 1 and 2, respectively and estimated the PAR of ChC for 2-year mortality. Results There were 145 deaths (29 in ChC) in era 1 and 85 deaths (26 in ChC) in era 2. In multivariable Cox-regression analysis adjusted for age, sex, ejection fraction, heart rate, body mass index, hypertension, diabetes mellitus, systolic blood pressure and ischaemic/valvar aetiology, ChC was associated with higher risk of death in era 1 (HR (95% CI)=1.92 (1.00 to 3.71), p=0.05) and era 2 (HR (95% CI)=3.51 (1.94 to 6.36), p<0.001). In fully adjusted analysis, the PAR of ChC for mortality increased twofold from era 1 (PAR (95% CI)=11.0 (2.8 to 18.5)%) to era 2 (PAR (95% CI)=21.9 (16.5 to 26.9)%; p=0.023 versus era 1). Conclusion Although the absolute death rates decreased over time in the ChC and NChC groups, the PAR of ChC for mortality increased among patients with HF, driven by increases in the HR associated with ChC. Our results highlight the need for additional efforts aiming to prevent and treat ChC.

Impact of Exhaled Breath Acetone in the Prognosis of Patients with Heart Failure with Reduced Ejection Fraction (HFrEF). One Year of Clinical Follow-up.

Background The identification of new biomarkers of heart failure (HF) could help in its treatment. Previously, our group studied 89 patients with HF and showed that exhaled breath acetone (EBA) is a new noninvasive biomarker of HF diagnosis. However, there is no data about the relevance of EBA as a biomarker of prognosis. Objectives To evaluate whether EBA could give prognostic information in patients with heart failure with reduced ejection fraction (HFrEF). Methods After breath collection and analysis by gas chromatography-mass spectrometry and by spectrophotometry, the 89 patients referred before were followed by one year. Study physicians, blind to the results of cardiac biomarker testing, ascertained vital status of each study participant at 12 months. Results The composite endpoint death and heart transplantation (HT) were observed in 35 patients (39.3%): 29 patients (32.6%) died and 6 (6.7%) were submitted to HT within 12 months after study enrollment. High levels of EBA (≥3.7μg/L, 50th percentile) were associated with a progressively worse prognosis in 12-month follow-up (log-rank = 11.06, p = 0.001). Concentrations of EBA above 3.7μg/L increased the risk of death or HT in 3.26 times (HR = 3.26, 95%CI = 1.56–6.80, p = 0.002) within 12 months. In a multivariable cox regression model, the independent predictors of all-cause mortality were systolic blood pressure, respiratory rate and EBA levels. Conclusions High EBA levels could be associated to poor prognosis in HFrEF patients.

How to treat acute decompensated heart failure in the ‘beta-blocker era’?

at that time) as support of the beneficial survival result in beta-blocked levosimendan patients in the SURVIVE study. Actually, Mebazaa et al. referred (correctly) only to the haemodynamic results—not to survival. Omerovic et al. state that the full results of the REVIVE II study have not yet been published. Although this was correct when their editorial was written, a very recent pharmacoeconomic analysis of REVIVE II includes the primary results of the study, including mortality data. Therefore, we believe that in centres where there is a frequent use of inotropes, levosimendan may be a valuable addition to amines and pure vasodilators in many of such patients.

Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda

Parte 1: Diretriz Brasileira de Insuficiencia Cardiaca Cronica […] Diretriz Brasileira de Insuficiencia Cardiaca Cronica e Aguda

Genomic ancestry as a predictor of haemodynamic profile in heart failure

Objective The aim of this study is to assess the association between genetic ancestry, self-declared race and haemodynamic parameters in patients with chronic heart failure (HF). Methods Observational, cross-sectional study. Eligible participants were aged between 18 and 80 years; ejection fraction was ≤50%. Patients underwent genetic analysis of ancestry informative markers, echocardiography and impedance cardiography (ICG). Race was determined by self-classification into two groups: white and non-white. Genomic ancestry was estimated using a panel of 101 348 polymorphic markers and three continental reference populations (European, African and Native American). Results Our study included 362 patients with HF between August 2012 and August 2014. 123 patients with HF declared themselves as white and 234 patients declared themselves as non-white. No statistically significant differences were found regarding the ICG parameters according to self-declared race. The Amerindian ancestry was positively correlated with systolic time ratio (r=0.109, p<0.05). The thoracic fluid content index (r=0.124. p<0.05), E wave peak (r=0.127. p<0.05) and E/e′ ratio (r=0.197. p<0.01) were correlated positively with African ancestry. In multiple linear regression, African ancestry remained associated with the E/e′ ratio, even after adjustment to risk factors. Conclusions The African genetic ancestry was associated with worse parameters of diastolic function; the Amerindian ancestry correlated with a worse pattern of ventricular contractility, while self-declared colour was not helpful to infer haemodynamic profiles in HF. Trials registration number NTC02043431.