RESUMO
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known. OBJECTIVES: To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i. METHODS: Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane. RESULTS: A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p < 0.001). There was a greater increase in plasma levels of nitrate [5.9 (16.5) vs. 2.6 (11.8); p = 0.001] and nitrite [0.14 (0.72) vs. 0.02 (0.74); p = 0.025] in the EE group than in the E group, respectively. Isoprostane reduction was more pronounced in the EE group when compared to the E group [-1.7 (5.9) vs. -1.1 (5.3); p < 0.001). CONCLUSIONS: In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Anticorpos Monoclonais Humanizados , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Glucosídeos , Humanos , Isoprostanos , Masculino , Pessoa de Meia-Idade , Inibidores de PCSK9 , Pró-Proteína Convertase 9/metabolismo , Resultado do TratamentoRESUMO
Cardiovascular disease resulting from iron accumulation is still a major cause of death in patients with thalassemia major (TM). Voltage-gated calcium-channel blockade prevents iron entry into cardiomyocytes and may provide an adjuvant treatment to chelation, reducing myocardial iron uptake. We evaluated whether addition of amlodipine to chelation strategies would reduce myocardial iron overload in TM patients compared with placebo. In a multicenter, double-blind, randomized, placebo-controlled trial, 62 patients were allocated to receive oral amlodipine 5 mg/day or placebo in addition to their current chelation regimen. The main outcome was change in myocardial iron concentration (MIC) determined by magnetic resonance imaging at 12 months, with patients stratified into reduction or prevention groups according to their initial T2* below or above the normal human threshold of 35 ms (MIC, 0.59 mg/g dry weight). At 12 months, patients in the reduction group receiving amlodipine (n = 15) had a significant decrease in MIC compared with patients receiving placebo (n = 15) with a median of -0.26 mg/g (95% confidence interval, -1.02 to -0.01) vs 0.01 mg/g (95% confidence interval, -0.13 to 0.23), P = .02. No significant changes were observed in the prevention group (treatment-effect interaction with P = .005). The same findings were observed in the subgroup of patients with T2* <20 ms. Amlodipine treatment did not cause any serious adverse events. Thus, in TM patients with cardiac siderosis, amlodipine combined with chelation therapy reduced cardiac iron more effectively than chelation therapy alone. Because this conclusion is based on subgroup analyses, it needs to be confirmed in ad hoc clinical trials. This trial was registered at www.clinicaltrials.gov identifier as #NCT01395199.
Assuntos
Anlodipino/uso terapêutico , Terapia por Quelação , Vasodilatadores/uso terapêutico , Talassemia beta/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Criança , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Prognóstico , Adulto JovemRESUMO
We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats.
Assuntos
Anti-Inflamatórios/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Quimiotaxia de Leucócito/efeitos dos fármacos , Neurônios Colinérgicos/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Macrófagos/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/imunologia , Brometo de Piridostigmina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Neurônios Colinérgicos/metabolismo , Neurônios Colinérgicos/patologia , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Fenótipo , Ratos Endogâmicos WKY , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fatores de Tempo , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
The decrease in insulin sensitivity (IS) during myocardial infarction (MI) is recognized as a possible contributor to poor patient outcomes. Despite its potential relevance, a standardized and convenient IS assessment tool has yet to be established for said clinical scenarios. This study aimed to validate the accuracy of surrogate indexes in determining IS in acute MI patients by comparison with the gold standard reference method for measuring IS, the euglycemic-hyperinsulinemic clamp (EHC). We performed EHCs in 31 consecutive nondiabetic patients who were admitted within the first 24 h of symptoms of ST-segment elevation MI. Patients with prior diagnosis of diabetes, use of hypoglycemic agents, or a glycosylated hemoglobin ≥6.5% were excluded. EHCs were performed at the second day (D2) and sixth day (D6) post-MI. Basal (12-h fasting) blood samples from D2 and D6 were used to evaluate patient blood glucose and insulin levels. We then calculated the following surrogate indexes: homeostatic model assessment of insulin sensitivity (HOMA2S), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). The IS index measured by EHC (ISiclamp) was correlated to HOMA2S, HOMA-IR, and QUICKI at D2 (r = 0.485, P = 0.009; r = -0.384, P = 0.048; r = 0.479, P = 0.01, respectively) and D6 (r = 0.621, P = 0.002; r = -0.576, P = 0.006; r = 0.626, P = 0.002, respectively). Receiver operator characteristic curves made for discrimination of ISiclamp above the median in D2 and D6 depicted areas under the curve of 0.740, 0.734, and 0.760 for HOMA2S, HOMA-IR, and QUICKI, respectively. Bland-Altman plots displayed no apparent systematic error for indexes, but a propensity for proportional error, particularly with HOMA-IR. Thus, based on EHC, these simple surrogate indexes are feasible for assessing IS during MI.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Resistência à Insulina/fisiologia , Insulina , Infarto do Miocárdio/sangue , Idoso , Diabetes Mellitus Tipo 2/sangue , Jejum/sangue , Feminino , Técnica Clamp de Glucose , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Left ventricular hypertrophy and diastolic dysfunction (LVDD) remain highly frequent markers of cardiac damage and risk of progression to symptomatic heart failure, especially in resistant hypertension (RHTN). We have previously demonstrated that administration of sildenafil in hypertensive rats improves LVDD, restoring phosphodiesterase type 5 (PDE-5) inhibition in cardiac myocytes. METHODS: We hypothesized that the long-acting PDE-5 inhibitor tadalafil may be clinically useful in improving LVDD in RHTN independently of blood pressure (BP) reduction. A single blinded, placebo-controlled, crossover study enrolled 19 patients with both RHTN and LVDD. Firstly, subjects received tadalafil (20 mg) for 14 days and after a 2-week washout period, they received placebo orally for 14 days. Patients were evaluated by office BP and ambulatory BP monitoring (ABPM), endothelial function (FMD), echocardiography, plasma brain natriuretic peptide (BNP-32), cyclic guanosine monophosphate (cGMP) and nitrite levels. RESULTS: No significant differences were detected in BP measurements. Remarkably, at least four echocardiographic parameters related with diastolic function improved accompanied by decrease in BNP-32 in tadalafil use. Although increasing cGMP, tadalafil did not change endothelial function or nitrites. There were no changes in those parameters after placebo. CONCLUSION: The current findings suggest that tadalafil improves LV relaxation through direct effects PDE-5-mediated in the cardiomyocytes with potential benefit as an adjunct to treat symptomatic subjects with LVDD such as RHTN patients.
Assuntos
Carbolinas/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Carbolinas/farmacologia , Estudos Cross-Over , GMP Cíclico/sangue , Diástole/efeitos dos fármacos , Resistência a Medicamentos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Nitritos/sangue , Inibidores da Fosfodiesterase 5/farmacologia , Método Simples-Cego , Tadalafila , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
AIM OF THE STUDY: In contrast to the general population, individuals with primarily persistent elevation of inflammatory activity display a significant association between inflammatory biomarkers and atherosclerotic burden. In older individuals, immunosenescence upregulates the innate response and, by this way, may hypothetically favor the presence of this association. The aim of this study was to evaluate this hypothesis in healthy octogenarians. METHODS: Participants (n = 208) aged 80 years or older, asymptomatic and without medical and laboratory evidence of chronic diseases or use of anti-inflammatory treatments were included in the study. Lipid profile and plasma C-reactive protein (CRP) were measured at baseline and cardiac computed tomography was performed within 1-week interval for measuring coronary calcium score (CCS). RESULTS: The median plasma CRP was 1.9 mg/L (1.03.4) and 33 % of the participants had elevated CRP defined as C3 mg/L. Among those with high CRP, there was an increased frequency of high CCS (C100) as compared with their counterparts (71 vs 50 %, p = 0.001). The association between CRP and CCS persisted even after adjustment for age, sex, cardiovascular risk factors and statin therapy. The area under the receiver-operating curve for CRP was 0.606 using CCS C100 as a binary outcome. The sensitivities for CCS C100 were 40 and 74 % for the cutoff points of CRP C3 or 1 mg/L, respectively. CONCLUSION: The present study was able to confirm that in very elderly individuals, systemic inflammatory activity is independently associated with coronary atherosclerosis burden.
Assuntos
Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/metabolismo , Fatores Etários , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/metabolismo , Cálcio/metabolismo , Doença da Artéria Coronariana/sangue , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Inflamação/metabolismo , Lipídeos/sangue , Masculino , Fatores de Risco , Tomografia Computadorizada por Raios X/métodosRESUMO
Risk factors for atherosclerosis may contribute to chronic low-grade inflammation. A highly cytotoxic and inflammatory CD4(+) cell subset (CD4(+)CD28(null) cells) has been associated with inflammatory diseases, including acute coronary syndromes (ACS). The aim of this study was to quantify and characterize CD4(+)CD28(null) cells in individuals with risk factors for atherosclerosis and patients with coronary artery disease (CAD). In order to achieve this goal, peripheral blood mononuclear cells (PBMCs) from individuals with risk factors for atherosclerosis and patients with CAD were analyzed using flow cytometry to detect cytotoxic molecules and evaluate the expression of homing receptors and inflammatory cytokines in CD4(+) cell subsets. The cells were evaluated ex vivo and after stimulation in culture. We found no differences in the proportions of CD4(+)CD28(null) cells among the groups. Compared with the CD4(+)CD28(+) population, the ex vivo CD4(+)CD28(null) subset from all groups expressed higher levels of granzymes A and B, perforin, granulysin and interferon-γ (IFN-γ). Individuals with risk factors and patients with ACS showed the highest levels of cytotoxic molecules. After stimulation, tumor necrosis factor-α (TNF-α) expression in the CD4(+)CD28(null) subset from these groups increased more than in the other groups. Stimulation with LPS decreased the expression of cytotoxic molecules by CD4(+)CD28(null) cells in all groups. In conclusion, our results show that risk factors for atherosclerosis may alter the CD4(+)CD28(null) cells phenotype, increasing their cytotoxic potential. Our findings also suggest that CD4(+)CD28(null) cells may participate in the early phases of atherosclerosis.
Assuntos
Aterosclerose/imunologia , Antígenos CD28/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Doença da Artéria Coronariana/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Diferenciação de Linfócitos T/biossíntese , Linfócitos T CD4-Positivos/imunologia , Feminino , Granzimas/biossíntese , Humanos , Interferon gama/biossíntese , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Perforina/biossíntese , Receptores CCR7/metabolismo , Receptores CXCR3/metabolismo , Fatores de Risco , Subpopulações de Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Introduction: Data on patients hospitalized with acute heart failure in Brazil scarce. Methods: We performed a cross-sectional, retrospective, records-based study using data retrieved from a large public database of heart failure admissions to any hospital from the Brazilian National Public Health System (SUS) (SUS Hospital Information System [SIHSUS] registry) to determine the in-hospital all-cause mortality rate, in-hospital renal replacement therapy rate and its association with outcome. Results: In total, 910,128 hospitalizations due to heart failure were identified in the SIHSUS registry between April 2017 and August 2021, of which 106,383 (11.7%) resulted in in-hospital death. Renal replacement therapy (required by 8,179 non-survivors [7.7%] and 11,496 survivors [1.4%, p < 0.001]) was associated with a 56% increase in the risk of death in the univariate regression model (HR 1.56, 95% CI 1.52 -1.59), a more than threefold increase of the duration of hospitalization, and a 45% or greater increase of cost per day. All forms of renal replacement therapy remained independently associated with in-hospital mortality in multivariable analysis (intermittent hemodialysis: HR 1.64, 95% CI 1.60 -1.69; continuous hemodialysis: HR 1.52, 95% CI 1.42 -1.63; peritoneal dialysis: HR 1.47, 95% CI 1.20 -1.88). Discussion: The in-hospital mortality rate of 11.7% observed among patients with acute heart failure admitted to Brazilian public hospitals was alarmingly high, exceeding that of patients admitted to North American and European institutions. This is the first report to quantify the rate of renal replacement therapy in patients hospitalized with acute heart failure in Brazil.
RESUMO
Thalassemia major (TM) patients have altered ventricular volumes and ejection fraction compared to normals, although evidence for these findings stem from restricted patient groups and has never been reproduced. We sought to evaluate cardiac parameters by cardiovascular magnetic resonance (CMR) in a group of young TM patients not covered by previous studies that are more representative of the TM population in many countries. Seventy patients including 40 TM with normal myocardial iron concentrations, and 30 age- and gender-matched normal (NL) volunteers underwent a CMR study for assessment of left and right ventricle volumes and function using a 1.5-T scanner. Left and right ventricle ejection fraction, indexed systolic and diastolic volumes, and indexed mass were compared between the two groups. Mean age of TM patients was 18.2 ± 7.1 versus 17.5 ± 8.5 years in NL with no significant differences (P = 0.73). There was no difference in left ventricular (LV) ejection fraction between the groups (TM 64.9 ± 5.7 %, NL 64.9 ± 5.2 %; P = 0.97). LV normalized end-diastolic and end-systolic volumes were significantly higher in patients with TM compared to NL volunteers (76.8 ± 19.4 versus 66.6 ± 11.7 mL/m², P = 0.008, and 27.0 ± 8.8 versus 23.6 ± 5.0 mL/m², P = 0.045). LV indexed mass was also higher in TM patients compared to NL (51.2 ± 11.9 versus 42.0 ± 8.5 g/m², P < 0.001). No significant differences were observed in right ventricular parameters. In conclusion, younger patients with TM do not present different left or right ventricular function values compared to normal controls despite having increased left ventricular volumes and mass.
Assuntos
Ventrículos do Coração/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Talassemia beta/fisiopatologia , Adolescente , Adulto , Brasil , Volume Cardíaco , Criança , Estudos de Coortes , Diagnóstico Precoce , Feminino , Ventrículos do Coração/química , Ventrículos do Coração/patologia , Humanos , Ferro/análise , Imageamento por Ressonância Magnética , Masculino , Miocárdio/química , Miocárdio/patologia , Índice de Gravidade de Doença , Caracteres Sexuais , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/patologia , Adulto JovemRESUMO
OBJECTIVE: Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. METHODS AND RESULTS: ST-elevation MI patients (n=125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0±4.1 mg/L) and patients treated with 20 (8.5±4.0 mg/L), 40 (3.8±2.5 mg/L), and 80 mg/day (1.4±1.5 mg/L), and the daily differences remained significant until the seventh day (P<0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-α, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P<0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-α, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P<0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P=0.001). CONCLUSIONS: This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00906451.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Mediadores da Inflamação/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Sinvastatina/administração & dosagem , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Brasil , Relação Dose-Resposta a Droga , Esquema de Medicação , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/imunologia , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Vasodilatação/efeitos dos fármacosRESUMO
OBJECTIVES: To assess the level of agreement and interchangeability among different software programs for calculation of T2 values for iron overload. METHODS: T2 images were analysed in 60 patients with thalassaemia major using the truncation method in three software programs. Levels of agreement were assessed using Pearson correlation and Bland-Altman plots. Categorical classification for levels of iron concentration by each software program was also compared. RESULTS: For the heart, all correlation coefficients were significant among the software programs (P < 0.001 for all coefficients). The mean differences and 95% limits of agreement were 0.2 (-4.73 to 5.0); 0.1 (-4.0 to 3.9); and -0.1 (-4.3 to 4.8). For the liver all correlations were also significant with P < 0.001. Bland-Altman plots showed differences of -0.02 (-0.7 to 0.6); 0.01 (-0.4 to 0.4); and -0.02 (-0.6 to 0.6). There were no significant differences in clinical classification among the software programs. CONCLUSIONS: All tools used in this study provided very good agreement among heart and liver T2 values. The results indicate that interpretation of T2 data is interchangeable with any of the software programs tested. KEY POINTS: Magnetic resonance imaging in iron overload assessment has become an essential tool. Post processing options to establish T2 values have not been compared. No differences were found on T2 of the liver or heart using 3 different techniques. Availability of these methods should allow more widespread interpretation of iron overload by MRI.
Assuntos
Sobrecarga de Ferro/diagnóstico , Fígado/patologia , Imageamento por Ressonância Magnética , Miocárdio/patologia , Software , Talassemia beta/diagnóstico , Adulto , Estudos Transversais , Feminino , Humanos , Ferro/metabolismo , Sobrecarga de Ferro/patologia , Fígado/metabolismo , Masculino , Miocárdio/metabolismo , Talassemia beta/patologiaRESUMO
BACKGROUND: Manganese based agents are intracellular and accumulate inside myocytes allowing for different imaging strategies compared to gadolinium contrasts. While previous agents release manganese very slowly in the circulation, MnCl2 allows for rapid Mn2+ uptake in myocytes, creating a memory effect that can be potentially explored. Data on animal models are very encouraging but the safety and efficacy of this approach in humans has not yet been investigated. Therefore, our objectives were to study the safety and efficacy of a rapid infusion of manganese chloride (MnCl2) for cardiovascular magnetic resonance (CMR) in humans. METHODS: Fifteen healthy volunteers underwent a CMR scan on a 1.5 T scanner. Before the infusion, cardiac function was calculated and images of a short axis mid-ventricular slice were obtained using a 2D and 3D gradient-echo inversion recovery (GRE-IR) sequence, a phase-sensitive IR sequence and a single breath-hold segmented IR prepared steady-state precession acquisition for T1 calculations. MnCl2 was infused over three minutes at a total dose of 5 µMol/kg. Immediately after the infusion, and at 15 and 30 minutes later, new images were obtained and cardiac function re-evaluated. RESULTS: There was a significant decrease in T1 values compared to baseline, sustained up to 30 minutes after the MnCl2 infusion (pre,839 ± 281 ms; 0 min, 684 ± 99; 15 min, 714 ± 168; 30 min, 706 ± 172, P = 0.003). The 2D and 3D GRE-IR sequence showed the greatest increase in signal-to-noise ratio compared to the other sequences (baseline 6.6 ± 4.2 and 9.7 ± 5.3; 0 min, 11.3 ± 4.1 and 15.0 ± 8.7; 15 min, 10.8 ± 4.0 and 16.9 ± 10.2; 30 min, 10.6 ± 5.2 and 16.5 ± 8.3, P < 0.001 for both). There was a slight increase in systolic pressure and heart rate after three and four minutes of the infusion with normalization of these parameters thereafter. Patients showed good tolerance to MnCl2 with no major adverse events, despite all reporting transient facial flush. CONCLUSIONS: In the short term, MnCl2 appears safe for human use. It effectively decreases myocardium T1, maintaining this effect for a relatively long period of time and allowing for the development of new imaging strategies in CMR, especially in ischemia research.
Assuntos
Cloretos , Meios de Contraste , Coração/fisiologia , Imagem Cinética por Ressonância Magnética/métodos , Compostos de Manganês , Adulto , Pressão Sanguínea , Brasil , Cloretos/administração & dosagem , Cloretos/efeitos adversos , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Feminino , Coração/anatomia & histologia , Frequência Cardíaca , Humanos , Interpretação de Imagem Assistida por Computador , Infusões Intravenosas , Imagem Cinética por Ressonância Magnética/efeitos adversos , Masculino , Compostos de Manganês/administração & dosagem , Compostos de Manganês/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Volume Sistólico , Fatores de Tempo , Função Ventricular EsquerdaRESUMO
BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2is) prevent hospitalization resulting from heart failure (HHF). However, patients with type 2 diabetes mellitus use multiple antihyperglycemic drugs to achieve glycosylated hemoglobin (HbA1c) targets. In these drug combinations, the risk of HHF is unpredictable and so is the parallel effect of glucose-lowering. PURPOSE: To examine the impact of antihyperglycemic drugs and their association on HHF. DATA SOURCES: Forty randomized controlled trials (RCTs) reporting HHF. STUDY SELECTION: Published RCTs were the data source. DATA EXTRACTION: Incidence rates of HHF. DATA SYNTHESIS: Random additive-effects network meta-analysis showed that metformin (Pâ =â 0.55), sulfonylureas (Pâ =â 0.51), glucagon-like peptide-1 receptor-agonist (Pâ =â 0.16), and dipeptidyl peptidase 4 inhibitors (DPP4is; Pâ =â 0.54) were neutral on the risk of HHF. SGLT2is and SGLT2isâ +â DPP4is reduced the risk of HHF with a hazard ratio (HR) of 0.68 (95% CI, 0.60-0.76; Pâ <â 0.0001) and 0.70 (95% CI, 0.60-0.81; Pâ <â 0.0001), respectively. Increased risk of HHF was associated with thiazolidinediones (TZDs) as monotherapy or in combination with DPP4is (HR: 1.45; 95% CI, 1.18-1.78; Pâ =â 0.0004) and 1.49 (95% CI, 1.18-1.88; Pâ =â 0.0008), respectively. Regardless of the therapy, a 1% reduction in HbA1c reduced the risk of HHF by 31.3% (95% CI, 9-48; Pâ =â 0.009). LIMITATIONS: There are no data to verify drug combinations available for clinical use and to discriminate the effect of drugs within each of the therapeutic classes. CONCLUSIONS: The risk of HHF is reduced by SGLT2is as monotherapy or in combination with DPP4is and increased by TZDs as monotherapy or in combination. Glucose-lowering provides an additive effect of reducing HHF.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/epidemiologia , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Hipoglicemiantes/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Tiazolidinedionas/administração & dosagem , Resultado do TratamentoRESUMO
RATIONALE, AIMS AND OBJECTIVES: Emergency short-stay unit (SSU) alleviates emergency department (ED) overcrowding, but may affect in-hospital indicators. Cardiology patients comprise a substantial part of patients admitted at SSU. This study evaluated whether SSU opening differentially modified in-hospital indicators at a whole general hospital and at its cardiology division (CARD). METHODS: We retrospectively analysed indicators based on 859 686 ED visits, and 171 547 hospital admissions, including 12 110 CARD admissions, from 2007 to 2018 at a general tertiary hospital, and compared global ED indicators and in-hospital indicators at the hospital and CARD before (2007-2011) and after (2011-2018) SSU opening. RESULTS: After SSU opening, monthly ED bed occupancy rate decreased (mean ± SD 200 ± 18% vs 187 ± 22%; P < .001) and in-hospital admissions from ED increased at the hospital (median [interquartile range] 460 [81] vs 524 [41], P < .001) and CARD (50 [12] vs 54 [12], P = .004). In parallel, monthly in-hospital elective admissions decreased at CARD (34 [18] vs 28 [17], P = .019), but not at the hospital (712 [73] vs 700 [104], P = .54). Average length of stay (LOS) increased at both hospital (8.5 ± 0.3 vs 8.7 ± 0.4 days, P < .001) and CARD (9.2 ± 1.5 vs 10.3 ± 2.3 days, P = .002) after SSU opening, but percent admissions at SSU showed a direct relationship with LOS solely at CARD. Furthermore, cardiology patients admitted at SSU had greater LOS, prevalence of coronary heart disease and age than those admitted at the conventional cardiology ward. CONCLUSIONS: SSU opening improved ED crowding, but was associated with changes in in-hospital indicators, particularly at CARD, and in the characteristics of hospitalized cardiology patients. These findings suggest that in-hospital cardiology services may need re-evaluation following SSU opening at a general hospital.
Assuntos
Cardiologia , Serviço Hospitalar de Emergência , Humanos , Tempo de Internação , Admissão do Paciente , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.
Assuntos
Antraciclinas/toxicidade , Antineoplásicos/toxicidade , Ventrículos do Coração/diagnóstico por imagem , Disfunção Ventricular/etiologia , Remodelação Ventricular , Idoso , Cardiotoxicidade , Feminino , Ventrículos do Coração/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular/diagnóstico por imagemRESUMO
This study was designed to evaluate the changes in arterial blood pressure (BP) and heart rate (HR) in moderate smokers during smoking abstinence after 7 days of treatment with bupropion alone, transdermal nicotine or bupropion combined with transdermal nicotine. Twenty-four healthy moderate smokers (12 female/12 male; 40+/-7 years) were evaluated randomly on five occasions and their systolic, diastolic, mean arterial blood pressure (MAP) and HR were measured by a Finapres device for 10 h, immediately after smoking interruption. All of the 24 smokers participated on five protocols during 7 days: control group (C) - no drugs; placebo group (PL); bupropion group (BUP) 150-300 mg; transdermal nicotine group (TN) - 21 mg; and BUP+TN-nicotine patch. Concomitantly, the subjects were evaluated by ABPM (ambulatory BP monitoring). All of BP parameters monitored shown significant statistical differences in the BUP, TN and BUP+TN groups compared with the controls (p<0.05), when measured by Finapres. The HR remained unaltered in all of the groups. No significant differences were seen in the BP or HR during the 24-h ABPM. These findings indicate that in moderate smokers, bupropion, transdermal nicotine or bupropion associated with transdermal nicotine caused an elevation in the BP after acute smoking interruption.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Bupropiona/administração & dosagem , Nicotina/administração & dosagem , Abandono do Hábito de Fumar/métodos , Fumar/fisiopatologia , Adulto , Bupropiona/efeitos adversos , Estudos Cross-Over , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/efeitos adversos , Método Simples-Cego , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: In ST-elevation myocardial infarction, 7-15% of patients admitted as Killip I will develop symptomatic heart failure or decreased ejection fraction. However, available clinical scores do not predict the risk of severe outcomes well, such as heart failure, recurrent myocardial infarction, and sudden death in these Killip I individuals. Therefore, we evaluated whether one vs two measurements of BNP would improve prediction of adverse outcomes in addition to the GRACE score in ST-elevation myocardial infarction/Killip I individuals. METHODS: Consecutive patients with ST-elevation myocardial infarction/Killip I (n=167) were admitted and followed for 12 months. The GRACE score was calculated and plasma BNP levels were obtained in the first 12 h after symptom onset (D1) and at the fifth day (D5). RESULTS: Fifteen percent of patients admitted as Killip I developed symptomatic heart failure and/or decreased ejection fraction in 12 months. The risk of developing symptomatic heart failure or ejection fraction <40% at 30 days was increased by 8.7-fold (95% confidence interval: 1.10-662, p=0.046) per each 100 pg/dl increase in BNP-change. Both in unadjusted and adjusted Cox-regressions, BNP-change as a continuous variable was associated with incident sudden death/myocardial infarction at 30 days (odds ratio 1.032 per each increase of 10 pg/dl, 95% confidence interval: 1.013-1.052, p<0.001), but BNP-D1 was not. The GRACE score alone showed a moderate C-statistic=0.709 (p=0.029), but adding BNP-change improved risk discrimination (C-statistic=0.831, p=0.001). Net reclassification confirmed a significant improvement in individual risk prediction by 33.4% (95% confidence interval: 8-61%, p=0.034). However, GRACE +BNP-D1 did not improve risk reclassification at 30 days compared to GRACE (p=0.8). At 12 months, BNP-change was strongly associated with incident sudden death/myocardial infarction, but not BNP-D1. CONCLUSIONS: Only BNP-change following myocardial infarction was associated with poorer short- and long-term outcomes. BNP-change also improves risk reclassification in addition to the GRACE score.
Assuntos
Eletrocardiografia , Insuficiência Cardíaca/epidemiologia , Peptídeo Natriurético Encefálico/sangue , Alta do Paciente/tendências , Medição de Risco/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Volume Sistólico/fisiologia , Biomarcadores/sangue , Brasil/epidemiologia , Seguimentos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Prognóstico , Estudos Prospectivos , Recidiva , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
INTRODUCTION: In acute myocardial infarction (AMI), each 18 mg/dl (1 mmol/L) increment is associated with a 3% increase in mortality rates. All strategies applied for reducing blood glucose to this date, however, have not presented encouraging results. METHODOLOGY: We searched the Medline (PubMed) and Cochrane Library databases for randomized clinical trials (RCTs) from 1995 to 2017 that used the intensive strategy or GIK therapy for blood glucose control during the acute stage of the AMI. We included eight studies. In order to identify the effects of GIK or insulin therapy, we calculated a overall risk ratio (RR) with meta-analysis of fixed and random effects models. A two-tail p-value of < 0.05 was considered statistically significant. RESULTS: A total of 28,151 patients were included: 1,379 intensively treated with insulin, 13,031 in GIK group, and 13,741 in the control group. The total mortality was 10.5% (n=2,961) and the RR of 1.03 [95%CI 0.96-1.10]; I2 = 31%; p = 0.41 for the combined intensive insulin plus GIK groups in comparison with the control group. In meta-regression analyses, intense reductions in blood glucose (> 36 mg/dL) in relation to the estimated average blood glucose (estimated by HbA1c) were associated with higher mortality, whereas lower reductions in blood glucose (< 36 mg/dL) were not associated with mortality. The lowering of blood glucose in the acute phase of MI compared with the average blood glucose was more effective around 18 mg/dL. CONCLUSION: This meta-analysis suggests that there may be a tenuous line between the effectiveness and safety of reducing blood glucose in the acute phase of MI. The targets must not exceed a reduction greater than 36 mg/dL in relation to estimated average blood glucose.
Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina/administração & dosagem , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: Diabetes is one of the leading causes of cardiovascular mortality. Over the last years, mortality has decreased significantly, more in individuals with diabetes than in healthy ones. That is mostly due to the control of other cardiovascular risk factors. The objective of our study was to analyze the dyslipidemia control in two diabetes cohorts. METHODS: Patients from two distinct cohorts were studied, 173 patients from the BHS (Brasília Heart Study) and 222 patients from the BDS (Brazilian Diabetes Study). The data on dyslipidemia control were studied in both different populations. All patients had diabetes. RESULTS: There are significant differences concerning comorbidities between the LDL-C and BDS groups. The average glycated hemoglobin is of 8.2 in the LDL-C > 100 group in comparison with 7.7 and 7.5 in the 70-100 and < 70 groups, respectively (p = 0.024). There is a higher percentage of hypertensive patients with LDL between 70-100 (63.9%), when comparing the < 70 and > 100 groups (54.3% and 54.9%, respectively; p = 0.005). Diastolic pressure is higher in the group with LDL > 100, with an average of 87 mmHg, in comparison with 82.6 mmHg and 81.9 mmHg in the 70-100 and < 70 groups, respectively (p = 0.019). The group with LDL > 100 has the greatest percentage of smokers (8.7%) in comparison with the groups with LDL between 70-100 and < 70 (5.6% and 4.3%, respectively; p = 0.015). There is also a difference in the previous incidence of coronaropathy. In the group with LDL < 70, 28.3% of patients had already experienced a previous infarction, compared with 11.1% and 10.6% in the 70-100 and > 100 groups, respectively (p < 0.001). CONCLUSIONS: The data in our study have shown that the dyslipidemia control in diabetic patients is inadequate and there is a tendency of direct association between lack of blood glucose control and lack of dyslipidemia control, in addition to the association with other cardiovascular risk factors, such as diastolic hypertension and smoking. This worsened control might be related to the plateau in the descending curve of mortality, and investments in this regard can improve the cardiovascular health in diabetic patients.
Assuntos
Anticolesterolemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Dislipidemias/complicações , Sinvastatina/uso terapêutico , Pressão Sanguínea , Brasil/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Comorbidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Dislipidemias/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Triglicerídeos/sangueRESUMO
Atherosclerosis of peripheral arteries typically affects vessels of the lower limbs, suggesting that local hemodynamic stimuli play a role in this process. Our study evaluated the effects of body postural changes on carotid and popliteal blood pressure, circumferential wall tension (CWT) and arterial strain, and investigated the relationship between such hemodynamic parameters and intima-media thickness (IMT) of these arteries. One hundred seventeen nondiabetic, nonhypertensive, nonsmoker subjects (48 men and 69 women) were enrolled and had their blood pressure measured in the arm and calf in supine and orthostatic positions. Echo-doppler analysis evaluated the common carotid and popliteal arteries after blood pressure measurements, while CWT was calculated according to Laplace's law. The results showed that changing from supine to orthostatic posture increased blood pressure and CWT in popliteal but not in carotid arteries. Partial correlation analysis adjusted for age and body mass index revealed no major relationship between IMT of the studied vessels and local blood pressure or arterial strain. Conversely, supine and orthostatic CWT exhibited comparable correlation coefficients with carotid IMT, while orthostatic CWT displayed a stronger relationship with popliteal IMT than with supine CWT. These results were confirmed by multiple linear regression analysis that included age, sex, body mass index, lipid fractions and glucose as independent variables. Overall, our results indicate that orthostatic CWT is a stronger hemodynamic predictor of popliteal IMT than supine CWT, suggesting that erectile posture may be a potential risk factor for popliteal atherosclerosis because it increases the local hemodynamic burden. (Hypertens Res 2008; 31: 2059-2064).