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1.
JACC Heart Fail ; 12(8): 1473-1486, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39111953

ABSTRACT

Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF. The study aims to enroll approximately 900 patients with CCC and reduced ejection fraction at around 100 sites in Latin America. The primary outcome is a hierarchical composite of time from randomization to cardiovascular death, first HF hospitalization, or relative change from baseline to week 12 in NT-proBNP levels. PARACHUTE-HF will provide new data on the treatment of this high-risk population. (Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC [PARACHUTE-HF]; NCT04023227).


Subject(s)
Aminobutyrates , Angiotensin Receptor Antagonists , Biphenyl Compounds , Chagas Cardiomyopathy , Drug Combinations , Enalapril , Heart Failure , Tetrazoles , Valsartan , Humans , Biphenyl Compounds/therapeutic use , Aminobutyrates/therapeutic use , Enalapril/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Chagas Cardiomyopathy/drug therapy , Heart Failure/drug therapy , Tetrazoles/therapeutic use , Stroke Volume/physiology , Peptide Fragments/blood , Chronic Disease , Natriuretic Peptide, Brain/blood , Male , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Female , Treatment Outcome
2.
Hipertens Riesgo Vasc ; 41(3): 145-153, 2024.
Article in English | MEDLINE | ID: mdl-38871574

ABSTRACT

BACKGROUND: The COVID-19 pandemic has highlighted the vulnerability of particular patient groups to SARS-CoV-2 infection, including those with cardiovascular diseases, hypertension, and intestinal dysbiosis. COVID-19 affects the gut, suggesting diet and vitamin D3 supplementation may affect disease progression. AIMS: To evaluate levels of Ang II and Ang-(1-7), cytokine profile, and gut microbiota status in patients hospitalized for mild COVID-19 with a history of cardiovascular disease and treated with daily doses of vitamin D3. METHODS: We recruited 50 adult patients. We screened 50 adult patients and accessed pathophysiology study 22, randomized to daily oral doses of 10,000IU vitamin D3 (n=11) or placebo (n=11). Plasma levels of Ang II and Ang-(1-7) were determined by radioimmunoassay, TMA and TMAO were measured by liquid chromatography and interleukins (ILs) 6, 8, 10 and TNF-α by ELISA. RESULTS: The Ang-(1-7)/Ang II ratio, as an indirect measure of ACE2 enzymatic activity, increased in the vitamin D3 group (24±5pg/mL vs. 4.66±2pg/mL, p<0.01). Also, in the vitamin D3-treated, there was a significant decline in inflammatory ILs and an increase in protective markers, such as a substantial reduction in TMAO (5±2µmoles/dL vs. 60±10µmoles/dL, p<0.01). In addition, treated patients experienced less severity of infection, required less intensive care, had fewer days of hospitalization, and a reduced mortality rate. Additionally, improvements in markers of cardiovascular function were seen in the vitamin D3 group, including a tendency for reductions in blood pressure in hypertensive patients. CONCLUSIONS: Vitamin D3 supplementation in patients with COVID-19 and specific conditions is associated with a more favourable prognosis, suggesting therapeutic potential in patients with comorbidities such as cardiovascular disease and gut dysbiosis.


Subject(s)
COVID-19 , Cardiovascular Diseases , Cholecalciferol , Dietary Supplements , Dysbiosis , Gastrointestinal Microbiome , Peptide Fragments , Humans , Cholecalciferol/administration & dosage , Male , Female , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/etiology , Cardiovascular Diseases/epidemiology , Middle Aged , COVID-19/complications , Peptide Fragments/blood , Aged , Angiotensin I/blood , Angiotensin II/blood , COVID-19 Drug Treatment , Vitamins/administration & dosage , Methylamines/blood , Cytokines/blood , Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2 , Double-Blind Method
3.
J Pediatr ; 273: 114116, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38815741

ABSTRACT

OBJECTIVE: To assess the effect of treating pulmonary hypertension (PH) in infants younger than 1 year of age with systemic glucocorticoids while using echocardiographic and diagnostic biomarkers as measures of efficacy. STUDY DESIGN: A retrospective chart review was performed on 17 hospitalized infants younger than 1 year of age at St Louis Children's Hospital who received a 5- to 7-day course of systemic glucocorticoid treatment followed by a 3-week taper with no significant intracardiac shunts from January 1, 2017, to December 31, 2021. Quantitative echocardiographic indices for PH, N-terminal pro b-type natriuretic peptide, and/or b-type natriuretic peptide levels were collected before glucocorticoid treatment, after the glucocorticoid burst, and after the 21-day taper. RESULTS: Mean (±SD) gestational age was 32.1 (±5.8) weeks, 5 infants were (29%) concomitantly treated with sildenafil, and 8 were male. Twelve were classified as World Health Organization group 3 PH (71%) and 5 as World Health Organization group 1 PH. There were significant improvements 30 days after glucocorticoid initiation in b-type natriuretic peptide levels (P = .008), PCO2 (P = .03), eccentricity index (P = .005), right ventricular ejection time (P = .04), pulmonary artery acceleration time (P = .002), and pulmonary artery acceleration time-to-right ventricular ejection time ratio (P = .02). Tricuspid regurgitation velocity was not able to be assessed. There were no mortalities during the study timeline. CONCLUSIONS: In our retrospective study, systemic glucocorticoid therapy was well tolerated and appeared to be associated with significant improvement in cardiopulmonary function in infants with PH. Further prospective study in a larger sample is warranted.


Subject(s)
Biomarkers , Echocardiography , Glucocorticoids , Hypertension, Pulmonary , Natriuretic Peptide, Brain , Humans , Male , Retrospective Studies , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/diagnostic imaging , Female , Biomarkers/blood , Infant , Infant, Newborn , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Treatment Outcome
4.
Rev Invest Clin ; 76(2): 065-079, 2024 02 15.
Article in English | MEDLINE | ID: mdl-38359843

ABSTRACT

Background: Pan-immuno-inflammation value (PIV) is a new and comprehensive index that reflects both the immune response and systemic inflammation in the body. Objective: The aim of this study was to investigate the prognostic relevance of PIV in predicting in-hospital mortality in acute pulmonary embolism (PE) patients and to compare it with the well-known risk scoring system, PE severity index (PESI), which is commonly used for a short-term mortality prediction in such patients. Methods: In total, 373 acute PE patients diagnosed with contrast-enhanced computed tomography were included in the study. Detailed cardiac evaluation of each patient was performed and PESI and PIV were calculated. Results: In total, 60 patients died during their hospital stay. The multivariable logistic regression analysis revealed that baseline heart rate, N-terminal pro-B-type natriuretic peptide, lactate dehydrogenase, PIV, and PESI were independent risk factors for in-hospital mortality in acute PE patients. When comparing with PESI, PIV was non-inferior in terms of predicting the survival status in patients with acute PE. Conclusion: In our study, we found that the PIV was statistically significant in predicting in-hospital mortality in acute PE patients and was non-inferior to the PESI.


Subject(s)
Hospital Mortality , Inflammation , Pulmonary Embolism , Severity of Illness Index , Humans , Pulmonary Embolism/mortality , Male , Female , Aged , Middle Aged , Acute Disease , Prognosis , Risk Factors , Tomography, X-Ray Computed , Aged, 80 and over , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , L-Lactate Dehydrogenase/blood , Biomarkers , Predictive Value of Tests , Logistic Models
5.
J Pediatr ; 241: 83-89.e2, 2022 02.
Article in English | MEDLINE | ID: mdl-34592260

ABSTRACT

OBJECTIVES: To evaluate the prognostic information derived from the daily measurements of N-terminal pro-B-type natriuretic peptide (proBNP) in neonates with congenital diaphragmatic hernia undergoing extracorporeal life support (ECLS). STUDY DESIGN: Plasma proBNP was prospectively measured daily during the first week of ECLS using an electrochemiluminescence immunoassay. Patients (n = 63) were allocated according to outcome: survivors (group 1, n = 35); nonsurvivors with successful weaning (defined as survival for >12 hours after ECLS discontinuation) (group 2, n = 16); nonsurvivors with unsuccessful weaning (group 3, n = 12). ProBNP kinetics were compared using Kruskal-Wallis testing and correlated with pulmonary hypertension and cardiac dysfunction on echocardiography using the Spearman correlation coefficient. RESULTS: Infants in group 3 presented significantly higher proBNP values from day 3 to day 6 compared with group 1 and 2. Overall mortality among patients with the highest proBNP values on day 1 was 30.6% compared with 63% in those patients with at least 1 higher value on day 2 to day 7. In patients with a late increase (day 4 to day 7) in proBNP the mortality was 70%, compared with 32.6% in those with proBNP below the value on day 1. Weaning failure was 35% in patients with a late increase and 11.6% in those without a late increase. ProBNP correlated significantly with pulmonary hypertension and cardiac dysfunction before and during ECLS. CONCLUSIONS: Absolute proBNP values are associated with weaning failure but not overall mortality in neonates with congenital diaphragmatic hernia undergoing ECLS. Echocardiographic findings correlate well with proBNP values.


Subject(s)
Extracorporeal Membrane Oxygenation , Hernias, Diaphragmatic, Congenital/mortality , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Biomarkers/blood , Echocardiography , Female , Hernias, Diaphragmatic, Congenital/blood , Humans , Infant, Newborn , Male , Prognosis , Prospective Studies
6.
Immunol Invest ; 51(4): 883-898, 2022 May.
Article in English | MEDLINE | ID: mdl-33557640

ABSTRACT

BACKGROUND: Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1ß, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data. METHODS: Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2). RESULTS: Higher IL-10 levels were observed in the case group compared to controls at T1 (p = .006) and T2 (p = .046). The IL-1ß, IL-6 and TNF levels did not change during treatment in each group (p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 (p < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed (p = .048 and p = .004, respectively). CONCLUSION: Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.


Subject(s)
Breast Neoplasms , Cardiotoxicity , Interleukin-10 , Biomarkers , Breast Neoplasms/drug therapy , Cardiotoxicity/etiology , Doxorubicin/adverse effects , Female , Follow-Up Studies , Humans , Interleukin-10/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood
7.
Nutrients ; 13(9)2021 Aug 27.
Article in English | MEDLINE | ID: mdl-34578865

ABSTRACT

The association between bone mineral density (BMD) and hepatic glycogen storage diseases (GSDs) is still unclear. To evaluate the BMD of patients with GSD I, IIIa and IXα, a cross-sectional study was performed, including 23 patients (GSD Ia = 13, Ib = 5, IIIa = 2 and IXα = 3; median age = 11.9 years; IQ = 10.9-20.1) who underwent a dual-energy X-ray absorptiometry (DXA). Osteocalcin (OC, n = 18), procollagen type 1 N-terminal propeptide (P1NP, n = 19), collagen type 1 C-terminal telopeptide (CTX, n = 18) and 25-OH Vitamin D (n = 23) were also measured. The participants completed a 3-day food diary (n = 20). Low BMD was defined as a Z-score ≤ -2.0. All participants were receiving uncooked cornstarch (median dosage = 6.3 g/kg/day) at inclusion, and 11 (47.8%) presented good metabolic control. Three (13%) patients (GSD Ia = 1, with poor metabolic control; IIIa = 2, both with high CPK levels) had a BMD ≤ -2.0. CTX, OC and P1NP correlated negatively with body weight and age. 25-OH Vitamin D concentration was decreased in seven (30.4%) patients. Our data suggest that patients with hepatic GSDs may have low BMD, especially in the presence of muscular involvement and poor metabolic control. Systematic nutritional monitoring of these patients is essential.


Subject(s)
Bone Diseases, Metabolic/epidemiology , Glycogen Storage Disease/epidemiology , Liver Diseases/epidemiology , Absorptiometry, Photon , Adolescent , Adult , Bone Density , Bone Diseases, Metabolic/blood , Brazil/epidemiology , Child , Child, Preschool , Collagen Type I/blood , Comorbidity , Cross-Sectional Studies , Female , Glycogen Storage Disease/blood , Humans , Liver Diseases/blood , Male , Osteocalcin/blood , Peptide Fragments/blood , Procollagen/blood , Vitamin D/blood , Young Adult
8.
Life Sci ; 282: 119792, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34229006

ABSTRACT

AIMS: Exercise training increases circulating and tissue levels of angiotensin-(1-7) [Ang-(1-7)], which was shown to attenuate inflammation and fibrosis in different diseases. Here, we evaluated whether Ang-(1-7)/Mas receptor is involved in the beneficial effects of aerobic training in a chronic model of asthma. MATERIAL AND METHODS: BALB/c mice were subjected to a protocol of asthma induced by ovalbumin sensitization (OVA; 4 i.p. injections) and OVA challenge (3 times/week for 4 weeks). Simultaneously to the challenge period, part of the animals was continuously treated with Mas receptor antagonist (A779, 1 µg/h; for 28 days) and trained in a treadmill (TRE; 60% of the maximal capacity, 1 h/day, 5 days/week during 4 weeks). PGC1-α mRNA expression (qRT-PCR), plasma IgE and lung cytokines (ELISA), inflammatory cells infiltration (enzymatic activity assay) and airway remodeling (by histology) were evaluated. KEY FINDINGS: Blocking the Mas receptor with A779 increased IgE and IL-13 levels and prevented the reduction in extracellular matrix deposition in airways in OVA-TRE mice. Mas receptor blockade prevented the reduction of myeloperoxidase activity, as well as, prevented exercise-induced IL-10 increase. These data show that activation of Ang-(1-7)/Mas receptor pathway is involved in the anti-inflammatory and anti-fibrotic effects of aerobic training in an experimental model of chronic asthma. SIGNIFICANCE: Our results support exercise training as a non-pharmacological tool to defeat lung remodeling induced by chronic pulmonary inflammation. Further, our result also supports development of new therapy based on Ang-(1-7) or Mas agonists as important tool for asthma treatment in those patients that cannot perform aerobic training.


Subject(s)
Angiotensin I/metabolism , Asthma/therapy , Peptide Fragments/metabolism , Pneumonia/therapy , Angiotensin I/blood , Animals , Asthma/blood , Asthma/metabolism , Disease Models, Animal , Exercise Therapy , Male , Mice, Inbred BALB C , Peptide Fragments/blood , Pneumonia/blood , Pneumonia/metabolism
10.
Heart ; 107(18): 1487-1492, 2021 09.
Article in English | MEDLINE | ID: mdl-33361353

ABSTRACT

OBJECTIVE: New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the Rede Brasileira de Estudos em Insuficiência Cardíaca (ReBIC)-1 Trial. METHODS: The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient's self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100). RESULTS: Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14). CONCLUSIONS: Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.


Subject(s)
Heart Failure/classification , Natriuretic Peptide, Brain/blood , Outpatients , Peptide Fragments/blood , Stroke Volume/physiology , Ventricular Function, Left/physiology , Biomarkers/blood , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Male , Middle Aged , Protein Precursors
11.
Diabetes Care ; 43(9): 2199-2207, 2020 09.
Article in English | MEDLINE | ID: mdl-32616616

ABSTRACT

OBJECTIVE: High-sensitivity cardiac troponin-T (hs-cTnT) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), biomarkers of cardiovascular disease (CVD) and heart failure, respectively, have not been widely studied in type 1 diabetes (T1D). We evaluated whether their assessment in T1D enhances the prediction of CVD and major adverse cardiovascular events (MACE). RESEARCH DESIGN AND METHODS: hs-cTnT and NT-proBNP were analyzed on the Roche Cobas E601 using the first available stored specimen (n = 581; mean age 29 years and diabetes duration 21 years). CVD was defined as CVD death, myocardial infarction, coronary revascularization, angina, ischemia, or stroke, and MACE as CVD death, myocardial infarction, or stroke. RESULTS: Median hs-cTnT (5.0 ng/L; interquartile range <3.0, 10.0) was higher among men (P < 0.0001), whereas median NT-proBNP (22.0 ng/L; 7.0, 61.0) did not differ by sex. In Cox models, log hs-cTnT (hazard ratio [HR] 1.38, P = 0.0006) and log NT-proBNP (HR 1.24, P = 0.0001) independently predicted CVD during 21 years of follow-up. However, their addition to models, singly or together, did not significantly improve CVD prediction. Furthermore, a marginally significant sex interaction was observed (P = 0.06), indicating that the hs-cTnT prediction was limited to men. hs-cTnT and NT-proBNP also predicted MACE, although only NT-proBNP remained significant (HR 1.27, P = 0.0009) when the biomarkers were included in a model simultaneously. Nonetheless, their addition to multivariable models did not enhance MACE prediction. CONCLUSIONS: Sex differences were observed in the concentration and predictive ability of hs-cTnT and NT-proBNP in T1D. Overall, their addition to traditional risk factor models increased the area under the curve for neither CVD nor MACE.


Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetic Angiopathies/diagnosis , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin T/blood , Adult , Biomarkers/analysis , Biomarkers/blood , Cohort Studies , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetic Angiopathies/blood , Female , Heart Failure/blood , Heart Failure/diagnosis , Heart Failure/etiology , Humans , Male , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Myocardial Infarction/etiology , Prognosis , Sex Characteristics , Stroke/blood , Stroke/diagnosis , Stroke/etiology , United States , Young Adult
12.
Sci Rep ; 10(1): 11016, 2020 07 03.
Article in English | MEDLINE | ID: mdl-32620821

ABSTRACT

Carbohydrate antigen 125 (CA125) is a congestion and inflammation biomarker and has been proved to be related to a worse prognosis in heart diseases. However, the precise relationship between elevated CA125 in patients with ST-segment elevation myocardial infarction (STEMI) has not yet been sufficiently studied. We set out to determine the association of CA125 with all-cause mortality at 6 months in STEMI. CA125, N-terminal pro brain natriuretic peptide (NTproBNP) and high sensitive C-reactive protein (hs-CRP) were measured in 245 patients admitted consecutively with STEMI undergoing coronary angioplasty. The mean age in our sample was 63.7 years, 64.9% were males, 28.3% had diabetes and 17.7% presented with acute heart failure (Killip ≥ 2). The median serum level of CA125 was 8.1 U/ml. At 6 months, the rate of all-cause mortality was 18% (44 patients). Receiver operating characteristic curve analysis demonstrated that CA125 presented similar performance to predict mortality as NTproBNP and hs-CRP. Patients with CA125 ≥ 11.48 had a higher rate of mortality (Hazard Ratio = 2.07, 95% confidence interval = 1.13-3.77, p = 0.017) than patients with CA125 < 11.48. This study suggests that elevated CA125 levels might be used to identify patients with STEMI with a higher risk of death at 6 months. CA125 seems to be a similar predictor of mortality compared to NTproBNP and hs-CRP.


Subject(s)
Biomarkers/blood , CA-125 Antigen/blood , ST Elevation Myocardial Infarction/mortality , Up-Regulation , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , Coronary Angiography , Female , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis , Prospective Studies , ROC Curve , ST Elevation Myocardial Infarction/blood , Survival Analysis
13.
Clin Sci (Lond) ; 134(9): 1081-1094, 2020 05 15.
Article in English | MEDLINE | ID: mdl-32352510

ABSTRACT

The relationship between disturbances in glucose homeostasis and heart failure (HF) progression is bidirectional. However, the mechanisms by which HF intrinsically impairs glucose homeostasis remain unknown. The present study tested the hypothesis that the bioavailability of intact glucagon-like peptide-1 (GLP-1) is affected in HF, possibly contributing to disturbed glucose homeostasis. Serum concentrations of total and intact GLP-1 and insulin were measured after an overnight fast and 15 min after the ingestion of a mixed breakfast meal in 49 non-diabetic patients with severe HF and 40 healthy control subjects. Similarly, fasting and postprandial serum concentrations of these hormones were determined in sham-operated rats, and rats with HF treated with an inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP4), vildagliptin, or vehicle for 4 weeks. We found that HF patients displayed a much lower increase in postprandial intact and total GLP-1 levels than controls. The increase in postprandial intact GLP-1 in HF patients correlated negatively with serum brain natriuretic peptide levels and DPP4 activity and positively with the glomerular filtration rate. Likewise, the postprandial increases in both intact and total GLP-1 were blunted in HF rats and were restored by DPP4 inhibition. Additionally, vehicle-treated HF rats displayed glucose intolerance and hyperinsulinemia, whereas normal glucose homeostasis was observed in vildagliptin-treated HF rats. We conclude that the postprandial increase in GLP-1 is blunted in non-diabetic HF. Impaired GLP-1 bioavailability after meal intake correlates with poor prognostic factors and may contribute to the establishment of a vicious cycle between glucose disturbance and HF development and progression.


Subject(s)
Blood Glucose/metabolism , Glucagon-Like Peptide 1/metabolism , Heart Failure/etiology , Postprandial Period/physiology , Aged , Animals , C-Peptide/blood , Female , Glucose Intolerance/physiopathology , Heart Failure/physiopathology , Humans , Insulin/blood , Male , Middle Aged , Obesity/metabolism , Obesity/physiopathology , Peptide Fragments/blood , Rats, Wistar
14.
J Pediatr ; 220: 139-145, 2020 05.
Article in English | MEDLINE | ID: mdl-32113658

ABSTRACT

OBJECTIVE: To assess the association between serially measured N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum levels and disease severity in children with pulmonary arterial hypertension (PAH), and to assess its predictive value for death or (heart-)lung transplantation. STUDY DESIGN: This was a longitudinal cohort study of the Dutch National Network for Pediatric Pulmonary Hypertension conducted between 2003 and 2017. Data on NT-proBNP and disease severity markers (World Health Organization Functional Class [WHO-FC], 6-minute walking distance [6MWD], and tricuspid annular plane systolic excursion [TAPSE]) were collected every 3 to 6 months from 82 children with PAH. The outcome measure was death or (heart-)lung transplantation. Also, NT-proBNP levels over time were compared between survivors and nonsurvivors. RESULTS: The median patient age was 8.8 years (IQR, 4.6-13.5 years), and 61% were female. The median duration of follow-up was 4.8 years (IQR, 1.9-10.0 years). At all times during the course of disease, higher NT-proBNP levels were associated with higher WHO-FC (ß = 0.526; 95% CI, 0.451-0.600), lower 6MWD z-score (ß = -0.587; 95% CI, -0.828 to -0.346), lower TAPSE z-score (ß = -0.783; 95% CI, -1.016 to -0.549), and elevated risk of death or (heart-)lung transplantation (hazard ratio 16.61; 95% CI, 7.81-35.33). Compared with survivors, nonsurvivors had NT-proBNP levels that were higher at first measurement and increased exponentially over time (P = .005). Changes in NT-proBNP serum level over time were predictive of outcome. CONCLUSIONS: Throughout the disease course of pediatric PAH, serial measurements of NT-proBNP are associated with disease severity and transplant-free survival. Monitoring NT-proBNP levels over time provides important prognostic information that can support clinical decision making in combination with other established prognostic markers.


Subject(s)
Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Pulmonary Arterial Hypertension/blood , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Hematologic Tests/methods , Humans , Longitudinal Studies , Male , Monitoring, Physiologic , Predictive Value of Tests , Severity of Illness Index
15.
J Am Heart Assoc ; 9(6): e014176, 2020 03 17.
Article in English | MEDLINE | ID: mdl-32157953

ABSTRACT

Background Risk stratification of Chagas disease patients in the limited-resource setting would be helpful in crafting management strategies. We developed a score to predict 2-year mortality in patients with Chagas cardiomyopathy from remote endemic areas. Methods and Results This study enrolled 1551 patients with Chagas cardiomyopathy from Minas Gerais State, Brazil, from the SaMi-Trop cohort (The São Paulo-Minas Gerais Tropical Medicine Research Center). Clinical evaluation, ECG, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were performed. A Cox proportional hazards model was used to develop a prediction model based on the key predictors. The end point was all-cause mortality. The patients were classified into 3 risk categories at baseline (low, <2%; intermediate, ≥2% to 10%; high, ≥10%). External validation was performed by applying the score to an independent population with Chagas disease. After 2 years of follow-up, 110 patients died, with an overall mortality rate of 3.505 deaths per 100 person-years. Based on the nomogram, the independent predictors of mortality were assigned points: age (10 points per decade), New York Heart Association functional class higher than I (15 points), heart rate ≥80 beats/min (20 points), QRS duration ≥150 ms (15 points), and abnormal NT-proBNP adjusted by age (55 points). The observed mortality rates in the low-, intermediate-, and high-risk groups were 0%, 3.6%, and 32.7%, respectively, in the derivation cohort and 3.2%, 8.7%, and 19.1%, respectively, in the validation cohort. The discrimination of the score was good in the development cohort (C statistic: 0.82), and validation cohort (C statistic: 0.71). Conclusions In a large population of patients with Chagas cardiomyopathy, a combination of risk factors accurately predicted early mortality. This helpful simple score could be used in remote areas with limited technological resources.


Subject(s)
Chagas Cardiomyopathy/mortality , Decision Support Techniques , Endemic Diseases , Health Status Indicators , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , Brazil/epidemiology , Chagas Cardiomyopathy/diagnosis , Chagas Cardiomyopathy/therapy , Clinical Decision-Making , Electrocardiography , Female , Health Status , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Predictive Value of Tests , Prognosis , Prospective Studies , Reproducibility of Results , Risk Assessment , Risk Factors , Young Adult
16.
BMC Pulm Med ; 19(1): 258, 2019 Dec 21.
Article in English | MEDLINE | ID: mdl-31864342

ABSTRACT

BACKGROUND: There is little information about vitamin D (Vit D) deficiency in patients with pulmonary hypertension (PH). The objective of this study was: 1) compare Vit D levels between patients with PH, left ventricular failure (LVF) and healthy subjects (HS); 2) correlate, in patients with PH, Vit D levels with prognosis-related variables, such as the 6-min walk test (6MWT). METHODS: Vitamin D levels were measured in a cross-sectional study in 126 patients from one of three groups: patients with PH (n = 53), patients with LVF (n = 42) and healthy subjects (n = 31). In all groups, 8-h fasting blood samples were obtained in the morning. In the PH and the LVF group, functional class (WHO criteria), metres covered in the 6MWT and echocardiographic parameters were analysed. In the PH group, plasma N terminal pro B type natriuretic peptide (NT-proBNP) level was analysed and a complete haemodynamic evaluation by right heart catheterisation was made. RESULTS: Mean Vit D levels were lower in PH than in both other groups (ng/ml, mean ± SD): PH 19.25 ± 10, LVF 25.68 ± 12, HS 28.8 ± 12 (PH vs LVF p = 0.017, PH vs HS p = 0.001 and HS vs LVF p = 0.46). Vit D deficiency prevalence was higher in PH as compared to the other groups (PH 53.8%, LVF 45.2%, HS 25%, p = 0.01). Patients with PH in functional class (FC; WHO criteria) III-IV had higher Vit D deficiency prevalence than those in FC I-II (86.7% vs 40.5%, p = 0.003). There was a significant linear correlation between the 6MWT and Vit D levels in PH (p < 0.01), but not in LVF (p = 0.69). CONCLUSIONS: Vit D levels were lower in patients with PH as compared to patients with LVF and HS and correlated directly with 6-min walk distance.


Subject(s)
Hypertension, Pulmonary/epidemiology , Vitamin D Deficiency/epidemiology , Adult , Aged , Case-Control Studies , Cross-Sectional Studies , Echocardiography , Female , Heart Failure/epidemiology , Humans , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prevalence , Prognosis , Ventricular Dysfunction, Left/epidemiology , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Walk Test , Young Adult
17.
Arch Cardiol Mex ; 89(4): 376-381, 2019.
Article in English | MEDLINE | ID: mdl-31834316

ABSTRACT

Introduction: The clinical utility of brain natriuretic peptide (NT-proBNP) as a prognostic marker in pediatric patients with heart failure is controversial. The maximum vasoactive inotropic score at 24 h after cardiac surgery in pediatric patients is an important predictor of morbidity and postoperative mortality. Objective: To determine if there is a correlation between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours after cardiac surgery in pediatric patients seen in the Intensive Care Unit. Material and methods: An analytical cross-sectional study. A Spearman correlation analysis (rs) was performed between the serum level of NT-proBNP and the maximum inotropic score both taken at 24 hours postoperatively. A value of p < 0.05 was considered statistically significant. Results: 40 patients were included, 52.5% to the male sex, 72.5% were older than 1 year of age at the time of surgery. A low correlation (rs = 0.26) was found between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours, this correlation was not statistically significant (p = 0.09). Conclusions: To our understanding, the present study is the first to investigate whether there is a correlation between these markers, so our results could set an important precedent that marks the beginning of multiple investigations in our critically ill patients in order to establish new diagnostic, prognostic and therapeutic approaches.


Introducción: La utilidad clínica del péptido natriurético cerebral (NT-proBNP) como marcador pronóstico en pacientes pediátricos con falla cardíaca es controversial. El puntaje inotrópico vasoactivo 24 horas después de la operación cardíaca en pacientes pediátricos es un importante predictor de morbilidad y mortalidad posoperatoria. Objetivo: Determinar si existe correlación entre los valores séricos de NT-proBNP y el puntaje inotrópico vasoactivo a las 24 horas posteriores a la intervención cardíaca en pacientes pediátricos atendidos en una unidad de terapia intensiva. Material y métodos: Estudio transversal analítico. Se realizó un análisis de correlación de Spearman (rs) entre la cifra sérica de NT-proBNP y el puntaje inotrópico máximo tomados ambos a las 24 horas del postoperatorio. Se consideró estadísticamente significativo un valor de p < 0.05. Resultados: Se incluyó a 40 pacientes, 52.5% del sexo masculino, 72.5% era mayor de un año de edad al momento de la operación. Se encontró una baja correlación (rs = 0.26) entre las concentraciones séricos de NT-proBNP y el puntaje inotrópico vasoactivo máximo a las 24 horas; dicha correlación no fue estadísticamente significativa (p = 0.09). Conclusiones: Este estudio es el primero en investigar la correlación entre estos marcadores y los resultados podrían sentar un antecedente que marque el inicio de múltiples investigaciones, con la finalidad de establecer nuevas herramientas diagnósticas, pronósticas y terapéuticas.


Subject(s)
Cardiac Surgical Procedures/methods , Heart Failure/surgery , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Adolescent , Biomarkers/blood , Child , Child, Preschool , Critical Illness , Cross-Sectional Studies , Female , Humans , Infant , Male , Postoperative Period , Prognosis , Retrospective Studies
18.
Arch. cardiol. Méx ; Arch. cardiol. Méx;89(4): 376-381, Oct.-Dec. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1149096

ABSTRACT

Resumen Introducción: La utilidad clínica del péptido natriurético cerebral (NT-proBNP) como marcador pronóstico en pacientes pediátricos con falla cardíaca es controversial. El puntaje inotrópico vasoactivo 24 horas después de la operación cardíaca en pacientes pediátricos es un importante predictor de morbilidad y mortalidad posoperatoria. Objetivo: Determinar si existe correlación entre los valores séricos de NT-proBNP y el puntaje inotrópico vasoactivo a las 24 horas posteriores a la intervención cardíaca en pacientes pediátricos atendidos en una unidad de terapia intensiva. Material y métodos: Estudio transversal analítico. Se realizó un análisis de correlación de Spearman (rs) entre la cifra sérica de NT-proBNP y el puntaje inotrópico máximo tomados ambos a las 24 horas del postoperatorio. Se consideró estadísticamente significativo un valor de p menor que 0.05. Resultados: Se incluyó a 40 pacientes, 52.5% del sexo masculino, 72.5% era mayor de un año de edad al momento de la operación. Se encontró una baja correlación (rs = 0.26) entre las concentraciones séricos de NT-proBNP y el puntaje inotrópico vasoactivo máximo a las 24 horas; dicha correlación no fue estadísticamente significativa (p = 0.09). Conclusiones: Este estudio es el primero en investigar la correlación entre estos marcadores y los resultados podrían sentar un antecedente que marque el inicio de múltiples investigaciones, con la finalidad de establecer nuevas herramientas diagnósticas, pronósticas y terapéuticas.


Abstract Introduction: The clinical utility of brain natriuretic peptide (NT-proBNP) as a prognostic marker in pediatric patients with heart failure is controversial. The maximum vasoactive inotropic score at 24 h after cardiac surgery in pediatric patients is an important predictor of morbidity and postoperative mortality. Objective: To determine if there is a correlation between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours after cardiac surgery in pediatric patients seen in the Intensive Care Unit. Material and methods: An analytical cross-sectional study. A Spearman correlation analysis (rs) was performed between the serum level of NT-proBNP and the maximum inotropic score both taken at 24 hours postoperatively. A value of p less 0.05 was considered statistically significant. Results: 40 patients were included, 52.5% to the male sex, 72.5% were older than 1 year of age at the time of surgery. A low correlation (rs = 0.26) was found between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours, this correlation was not statistically significant (p = 0.09). Conclusions: To our understanding, the present study is the first to investigate whether there is a correlation between these markers, so our results could set an important precedent that marks the beginning of multiple investigations in our critically ill patients in order to establish new diagnostic, prognostic and therapeutic approaches.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Peptide Fragments/blood , Natriuretic Peptide, Brain/blood , Heart Failure/surgery , Cardiac Surgical Procedures/methods , Postoperative Period , Prognosis , Biomarkers/blood , Cross-Sectional Studies , Retrospective Studies , Critical Illness
19.
Arq. bras. cardiol ; Arq. bras. cardiol;113(6): 1129-1137, Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055060

ABSTRACT

Abstract Background: Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. In this study, we investigated the role of N- Terminal pro B type natriuretic peptide level to predict the LVA development after acute ST-segment elevation myocardial infarction (STEMI). Methods: We prospectively enrolled 1519 consecutive patients with STEMI. Patients were divided into two groups according to LVA development within the six months after index myocardial infarction. Patients with or without LVAs were examined to determine if a significant relationship existed between the baseline N- Terminal pro B type natriuretic peptide values and clinical characteristics. A p-value < 0.05 was considered statistically significant. Results: LVA was detected in 157 patients (10.3%). The baseline N- Terminal pro- B type natriuretic peptide level was significantly higher in patients who developed LVA after acute MI (523.5 ± 231.1 pg/mL vs. 192.3 ± 176.6 pg/mL, respectively, p < 0.001). Independent predictors of LVA formation after acute myocardial infarction was age > 65 y, smoking, Killip class > 2, previous coronary artery bypass graft, post-myocardial infarction heart failure, left ventricular ejection fraction < 50%, failure of reperfusion, no-reflow phenomenon, peak troponin I and CK-MB and NT-pro BNP > 400 pg/mL at admission. Conclusions: Our findings indicate that plasma N- Terminal pro B type natriuretic peptide level at admission among other variables provides valuable predictive information regarding the development of LVA after acute STEMI.


Resumo Fundamento: O aneurisma do ventrículo esquerdo (AVE) é uma importante complicação do infarto agudo do miocárdio (IAM). Objetivo: Investigar o papel da porção N-terminal do pró-hormônio do peptídeo natriurético do tipo B (NT-proBNP) para predizer o desenvolvimento de AVE após infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCST). Métodos: Incluímos prospectivamente 1519 pacientes consecutivos com IAMCST. Os pacientes foram divididos em dois grupos de acordo com o desenvolvimento de AVE nos seis meses após o infarto do miocárdio. Os pacientes com ou sem AVE foram examinados para determinar se existia uma relação significativa entre os valores basais do NT-proBNP e as características clínicas. Um valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: O AVE foi detectado em 157 pacientes (10,3%). O nível basal do NT-proBNP foi significativamente maior em pacientes que desenvolveram AVE após IAM (523,5 ± 231,1 pg/mL vs. 192,3 ± 176,6 pg/mL, respectivamente, p < 0,001). Os preditores independentes da formação de AVE após IAM foram idade > 65 anos, tabagismo, classe Killip > 2, cirurgia de revascularização miocárdica anterior, insuficiência cardíaca pós-infarto do miocárdio, fração de ejeção do ventrículo esquerdo < 50%, falha de reperfusão, fenômeno de no-reflow, pico de troponina I e CK-MB e NT-proBNP > 400 pg/mL na internação. Conclusões: Nossos achados indicam que o nível plasmático do fragmento N-terminal do peptídeo natriurético tipo B na admissão, entre outras variáveis, fornece informações preditivas valiosas sobre o desenvolvimento de AVE após o IAMCST agudo.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Peptide Fragments/blood , Ventricular Dysfunction, Left/diagnosis , Natriuretic Peptide, Brain/blood , ST Elevation Myocardial Infarction/complications , Heart Aneurysm/diagnosis , Severity of Illness Index , Biomarkers/blood , Prospective Studies , ROC Curve , Sensitivity and Specificity , Coronary Angiography , Ventricular Dysfunction, Left/etiology , Heart Aneurysm/etiology
20.
Arq Bras Cardiol ; 113(6): 1129-1137, 2019 12.
Article in English, Portuguese | MEDLINE | ID: mdl-31664316

ABSTRACT

BACKGROUND: Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. In this study, we investigated the role of N- Terminal pro B type natriuretic peptide level to predict the LVA development after acute ST-segment elevation myocardial infarction (STEMI). METHODS: We prospectively enrolled 1519 consecutive patients with STEMI. Patients were divided into two groups according to LVA development within the six months after index myocardial infarction. Patients with or without LVAs were examined to determine if a significant relationship existed between the baseline N- Terminal pro B type natriuretic peptide values and clinical characteristics. A p-value < 0.05 was considered statistically significant. RESULTS: LVA was detected in 157 patients (10.3%). The baseline N- Terminal pro- B type natriuretic peptide level was significantly higher in patients who developed LVA after acute MI (523.5 ± 231.1 pg/mL vs. 192.3 ± 176.6 pg/mL, respectively, p < 0.001). Independent predictors of LVA formation after acute myocardial infarction was age > 65 y, smoking, Killip class > 2, previous coronary artery bypass graft, post-myocardial infarction heart failure, left ventricular ejection fraction < 50%, failure of reperfusion, no-reflow phenomenon, peak troponin I and CK-MB and NT-pro BNP > 400 pg/mL at admission. CONCLUSIONS: Our findings indicate that plasma N- Terminal pro B type natriuretic peptide level at admission among other variables provides valuable predictive information regarding the development of LVA after acute STEMI.


Subject(s)
Heart Aneurysm/diagnosis , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , ST Elevation Myocardial Infarction/complications , Ventricular Dysfunction, Left/diagnosis , Adult , Aged , Biomarkers/blood , Coronary Angiography , Female , Heart Aneurysm/etiology , Humans , Male , Middle Aged , Prospective Studies , ROC Curve , Sensitivity and Specificity , Severity of Illness Index , Ventricular Dysfunction, Left/etiology , Young Adult
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