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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.
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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
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 diabetes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. However, the impact on right ventricular (RV) remodeling is unknown. Accordingly, the objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD). METHODS: In EMPA-HEART CardioLink-6, 97 patients with T2DM and CAD were randomly assigned to empagliflozin 10 mg (n = 49) once daily or placebo (n = 48). Cardiac magnetic resonance imaging was performed at baseline and after 6 months. RV mass index (RVMi), RV end-diastolic and end-systolic volume index (RVEDVi, RVESVi) and RV ejection fraction (RVEF) were assessed in blinded fashion. RESULTS: At baseline, mean RVMi (± SD) (11.8 ± 2.4 g/m2), RVEF (53.5 ± 4.8%), RVEDVi (64.3 ± 13.2 mL/m2) and RVESVi (29.9 ± 6.9 mL/m2) were within normal limits and were similar between the empagliflozin and placebo groups. Over 6 months, there were no significant differences in RVMi (- 0.11 g/m2, [95% CI - 0.81 to 0.60], p = 0.76), RVEF (0.54%, [95% CI - 1.4 to 2.4], p = 0.58), RVEDVi (- 1.2 mL/m2, [95% CI - 4.1 to 1.7], p = 0.41) and RVESVi (- 0.81 mL/m2, [95% CI - 2.5 to 0.90], p = 0.35) in the empaglifozin group as compared with the placebo group. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6 months. CONCLUSIONS: In this post-hoc analysis, SGLT2 inhibition with empagliflozin had no impact on RVMi and RV volumes in patients with T2DM and CAD. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ct2/show/NCT02998970?cond=NCT02998970&draw=2&rank=1 . Unique identifier: NCT02998970.
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Compostos Benzidrílicos/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Idoso , Compostos Benzidrílicos/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Método Duplo-Cego , Feminino , Glucosídeos/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ontário , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented. METHODS AND RESULTS: From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE. CONCLUSION: These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.
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Inibidores de Checkpoint Imunológico , Miocardite , Meios de Contraste , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocardite/induzido quimicamente , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND AND AIM: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. METHODS AND RESULTS: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect ß = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. CONCLUSION: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.
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HDL-Colesterol/sangue , Dislipidemias/sangue , Sobrepeso/sangue , Aumento de Peso , Adulto , Idoso , Antioxidantes/análise , Biomarcadores/sangue , Índice de Massa Corporal , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/diagnóstico , Sobrepeso/fisiopatologia , Agregação Plaquetária , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. METHODS: ST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission. RESULTS: The intake of ω-3 below the median (< 1.7 g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24-3.10); p = 0.004], Interleukin-2 [OR:2.46(1.20-5.04); p = 0.014], brain-type natriuretic peptide [OR:2.66(1.30-5.44); p = 0.007], left-ventricle end-diastolic volume [OR:5.12(1.11-23.52)]; p = 0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47-6.88); p = 0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi. CONCLUSION: These findings suggest that a reduced daily intake of ω-3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling. TRIAL REGISTRATION: Clinical Trial Registry number and website: NCT02062554 .
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Ácidos Graxos Ômega-3/farmacologia , Inflamação/sangue , Inflamação/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Remodelação Ventricular/fisiologia , Biomarcadores/sangue , Brasil , Estudos de Coortes , Ecocardiografia Tridimensional/métodos , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy noninvasively are limited. The goal was to validate a cardiac magnetic resonance-based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy. METHODS AND RESULTS: Two murine models of hypertension (n=18, with n=15 controls) induced by l-N(G)-nitroarginine methyl ester (L-NAME) and pressure overload (n=11) from transaortic constriction (TAC) were imaged by cardiac magnetic resonance at baseline and 7 weeks after L-NAME treatment or up to 7 weeks after TAC. T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water (τic), a cell size-dependent parameter, and extracellular volume fraction, a marker of interstitial fibrosis, were determined with a model for transcytolemmal water exchange. Cardiomyocyte diameter and length were measured on FITC-wheat germ agglutinin-stained sections. The τic correlated strongly with histological cardiomyocyte volume-to-surface ratio (r=0.78, P<0.001) and cell volume (r=0.75, P<0.001). Histological cardiomyocyte diameters and cell volumes were higher in mice treated with L-NAME compared with controls (P<0.001). In the TAC model, cardiac magnetic resonance and histology showed cell hypertrophy at 2 weeks after TAC without significant fibrosis at this early time point. Mice exposed to TAC demonstrated a significant, longitudinal, and parallel increase in histological cell volume, volume-to-surface ratio, and τic between 2 and 7 weeks after TAC. CONCLUSION: The τic measured by contrast-enhanced cardiac magnetic resonance provides a noninvasive measure of cardiomyocyte hypertrophy. Extracellular volume fraction and τic can track myocardial tissue remodeling from pressure overload.
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Imageamento por Ressonância Magnética/métodos , Miócitos Cardíacos/patologia , Remodelação Ventricular/fisiologia , Algoritmos , Animais , Estenose da Valva Aórtica/complicações , Biomarcadores , Água Corporal/metabolismo , Cardiomiopatia Hipertrófica/etiologia , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Tamanho Celular , Meios de Contraste , Gadolínio DTPA , Hipertensão/induzido quimicamente , Hipertensão/etiologia , Hipertensão/patologia , Hipertrofia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos , NG-Nitroarginina Metil Éster/toxicidade , Fenótipo , Distribuição AleatóriaRESUMO
BACKGROUND: 123Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. METHODS AND RESULTS: Prospectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from 123iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) 123iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P<0.001), and correlated negatively with diffuse fibrosis assessed by ECV (R=-0.34, P<0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, P<0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); (R=-0.41, P<0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels. CONCLUSIONS: Abnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.
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Biomarcadores , Insuficiência Cardíaca , Volume Sistólico , Sistema Nervoso Simpático , Remodelação Ventricular , Humanos , Masculino , Feminino , Insuficiência Cardíaca/fisiopatologia , Pessoa de Meia-Idade , Remodelação Ventricular/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Idoso , Biomarcadores/sangue , Volume Sistólico/fisiologia , Estudos Prospectivos , Função Ventricular Esquerda/fisiologia , Fragmentos de Peptídeos/sangue , Peptídeo Natriurético Encefálico/sangue , Tolerância ao Exercício/fisiologia , Fibrose , 3-Iodobenzilguanidina , Teste de Esforço , Miocárdio/patologia , Miocárdio/metabolismo , Coração/inervação , Coração/fisiopatologia , Ecocardiografia , Compostos Radiofarmacêuticos , CintilografiaRESUMO
Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling. Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system). Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = -0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = - 0.29, p = 0.04) and intracellular water lifetime (τic) (r = -0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = -0.63, p < 0.01). Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.
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AIMS: Patients with aortic dissection have a high prevalence of left ventricular structural alterations, including left ventricular hypertrophy (LVH), but little is known about the impact of sex on this regard. This study compared clinical, cardiac, and prognostic characteristics between men and women with aortic dissection. METHODS: We retrospectively assessed clinical and echocardiographic characteristics, and 1-year mortality in 367 aortic dissection patients (30% women; 66% with Stanford-A) who underwent echocardiography 60âdays before or after the diagnosis of aortic dissection from three Brazilian centers. RESULTS: Men and women had similar clinical characteristics, except for higher age (59.4â±â13.4 vs. 55.9â±â11.6âyears; P â=â0.013) and use of antihypertensive classes (1.4â±â1.3 vs. 1.1â±â1.2; P â=â0.024) and diuretics (32 vs. 19%; P â=â0.004) in women compared with men. Women had a higher prevalence of LVH (78 vs. 65%; P â=â0.010) and lower prevalence of normal left ventricular geometry (20 vs. 10%; P â=â0.015) than men. Logistic regression analysis adjusted for confounding factors showed that women were less likely to have normal left ventricular geometry (odds ratio, 95% confidence intervalâ=â0.42, 0.20-0.87; P â=â0.019) and were more likely to have LVH (odds ratio, 95% confidence intervalâ=â1.91, 1.11-3.27; P â=â0.019). Conversely, multivariable Cox-regression analysis showed that women had a similar risk of death compared to men 1 year after aortic dissection diagnosis (hazard ratio, 95% confidence intervalâ=â1.16, 0.77-1.75; P â=â0.49). CONCLUSION: In aortic dissection patients, women were typically older, had higher use of antihypertensive medications, and exhibited a greater prevalence of LVH compared with men. However, 1-year mortality after aortic dissection diagnosis did not differ between men and women.
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Dissecção Aórtica , Hipertrofia Ventricular Esquerda , Remodelação Ventricular , Humanos , Masculino , Feminino , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/fisiopatologia , Dissecção Aórtica/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Idoso , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Brasil/epidemiologia , Prevalência , Adulto , Fatores de Risco , Ecocardiografia , Aneurisma Aórtico/epidemiologia , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/fisiopatologia , Prognóstico , Fatores de TempoRESUMO
BACKGROUND: Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy and a proposed substrate for arrhythmias and heart failure. In animal models, profibrotic genetic pathways are activated early, before hypertrophic remodeling. Data showing early profibrotic responses to sarcomere-gene mutations in patients with hypertrophic cardiomyopathy are lacking. METHODS: We used echocardiography, cardiac magnetic resonance imaging (MRI), and serum biomarkers of collagen metabolism, hemodynamic stress, and myocardial injury to evaluate subjects with hypertrophic cardiomyopathy and a confirmed genotype. RESULTS: The study involved 38 subjects with pathogenic sarcomere mutations and overt hypertrophic cardiomyopathy, 39 subjects with mutations but no left ventricular hypertrophy, and 30 controls who did not have mutations. Levels of serum C-terminal propeptide of type I procollagen (PICP) were significantly higher in mutation carriers without left ventricular hypertrophy and in subjects with overt hypertrophic cardiomyopathy than in controls (31% and 69% higher, respectively; P<0.001). The ratio of PICP to C-terminal telopeptide of type I collagen was increased only in subjects with overt hypertrophic cardiomyopathy, suggesting that collagen synthesis exceeds degradation. Cardiac MRI studies showed late gadolinium enhancement, indicating myocardial fibrosis, in 71% of subjects with overt hypertrophic cardiomyopathy but in none of the mutation carriers without left ventricular hypertrophy. CONCLUSIONS: Elevated levels of serum PICP indicated increased myocardial collagen synthesis in sarcomere-mutation carriers without overt disease. This profibrotic state preceded the development of left ventricular hypertrophy or fibrosis visible on MRI. (Funded by the National Institutes of Health and others.)
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Cardiomiopatia Hipertrófica/complicações , Miocárdio/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adolescente , Adulto , Biomarcadores/sangue , Miosinas Cardíacas , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/genética , Proteínas de Transporte/genética , Criança , Pré-Escolar , Colágeno/biossíntese , Colágeno Tipo I , Ecocardiografia , Feminino , Fibrose/diagnóstico , Fibrose/etiologia , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Miocárdio/metabolismo , Cadeias Pesadas de Miosina/genética , Peptídeos , Adulto JovemRESUMO
Contrast material-enhanced myocardial perfusion imaging by using cardiac magnetic resonance (MR) imaging has, during the past decade, evolved into an accurate technique for diagnosing coronary artery disease, with excellent prognostic value. Advantages such as high spatial resolution; absence of ionizing radiation; and the ease of routine integration with an assessment of viability, wall motion, and cardiac anatomy are readily recognized. The need for training and technical expertise and the regulatory hurdles, which might prevent vendors from marketing cardiac MR perfusion imaging, may have hampered its progress. The current review considers both the technical developments and the clinical experience with cardiac MR perfusion imaging, which hopefully demonstrates that it has long passed the stage of a research technique. In fact, cardiac MR perfusion imaging is moving beyond traditional indications such as diagnosis of coronary disease to novel applications such as in congenital heart disease, where the imperatives of avoidance of ionizing radiation and achievement of high spatial resolution are of high priority. More wide use of cardiac MR perfusion imaging, and novel applications thereof, are aided by the progress in parallel imaging, high-field-strength cardiac MR imaging, and other technical advances discussed in this review.
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Meios de Contraste , Doença da Artéria Coronariana/diagnóstico , Angiografia por Ressonância Magnética/tendências , Imagem de Perfusão do Miocárdio/tendências , HumanosRESUMO
Background Meta-analysis can identify biological factors that moderate cardiac magnetic resonance myocardial tissue markers such as native T1 (longitudinal magnetization relaxation time constant) and T2 (transverse magnetization relaxation time constant) in cohorts recovering from COVID-19 infection. Methods and Results Cardiac magnetic resonance studies of patients with COVID-19 using myocardial T1, T2 mapping, extracellular volume, and late gadolinium enhancement were identified by database searches. Pooled effect sizes and interstudy heterogeneity (I2) were estimated with random effects models. Moderators of interstudy heterogeneity were analyzed by meta-regression of the percent difference of native T1 and T2 between COVID-19 and control groups (%ΔT1 [percent difference of the study-level means of myocardial T1 in patients with COVID-19 and controls] and %ΔT2 [percent difference of the study-level means of myocardial T2 in patients with COVID-19 and controls]), extracellular volume, and the proportion of late gadolinium enhancement. Interstudy heterogeneities of %ΔT1 (I2=76%) and %ΔT2 (I2=88%) were significantly lower than for native T1 and T2, respectively, independent of field strength, with pooled effect sizes of %ΔT1=1.24% (95% CI, 0.54%-1.9%) and %ΔT2=3.77% (95% CI, 1.79%-5.79%). %ΔT1 was lower for studies in children (median age: 12.7 years) and athletes (median age: 21 years), compared with older adults (median age: 48 years). Duration of recovery from COVID-19, cardiac troponins, C-reactive protein, and age were significant moderators for %ΔT1 and/or %ΔT2. Extracellular volume, adjusted by age, was moderated by recovery duration. Age, diabetes, and hypertension were significant moderators of the proportion of late gadolinium enhancement in adults. Conclusions T1 and T2 are dynamic markers of cardiac involvement in COVID-19 that reflect the regression of cardiomyocyte injury and myocardial inflammation during recovery. Late gadolinium enhancement and to a lesser extent extracellular volume, are more static biomarkers moderated by preexisting risk factors linked to adverse myocardial tissue remodeling.
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COVID-19 , Meios de Contraste , Criança , Humanos , Idoso , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Gadolínio , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Valor Preditivo dos TestesRESUMO
Ischemic heart disease continues to be the leading cause of death and disability worldwide. For the diagnosis of ischemic heart disease, some form of cardiac stress test involving exercise or pharmacological stimulation continues to play an important role, despite advances within modalities like computer tomography for the noninvasive detection and characterization of epicardial coronary lesions. Among noninvasive stress imaging tests, cardiac magnetic resonance (CMR) combines several capabilities that are highly relevant for the diagnosis of ischemic heart disease: assessment of wall motion abnormalities, myocardial perfusion imaging, and depiction of replacement and interstitial fibrosis markers by late gadolinium enhancement techniques and T1 mapping. On top of these qualities, CMR is also well tolerated and safe in most clinical scenarios, including in the presence of cardiovascular implantable devices, while in the presence of renal disease, gadolinium-based contrast should only be used according to guidelines. CMR also offers outstanding viability assessment and prognostication of cardiovascular events. The last 2019 European Society of Cardiology guidelines for chronic coronary syndromes has positioned stress CMR as a class I noninvasive imaging technique for the diagnosis of coronary artery disease in symptomatic patients. In the present review, we present the current state-of-the-art assessment of myocardial ischemia by stress perfusion CMR, highlighting its advantages and current shortcomings. We discuss the safety, clinical, and cost-effectiveness aspects of gadolinium-based CMR-perfusion imaging for ischemic heart disease assessment.
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Doença da Artéria Coronariana , Isquemia Miocárdica , Imagem de Perfusão do Miocárdio , Humanos , Meios de Contraste , Gadolínio , Isquemia Miocárdica/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem de Perfusão do Miocárdio/métodos , Espectroscopia de Ressonância Magnética , Imagem Cinética por Ressonância Magnética/métodos , Valor Preditivo dos TestesRESUMO
BACKGROUND: In-hospital delays in permanent cardiac pacemaker (PPM) implantation are common and may result in in-hospital infection among patients waiting for PPM implantation (pre-PPM-HI). This study investigated the predictors and prognostic impact of these events. METHODS: We retrospectively evaluated 905 consecutive patients (68.2 ± 16.0 years; 54% males) who underwent PPM implantation. Clinical characteristics, pre-PPM-HI and 30-day mortality were recorded and a risk score for pre-PPM-HI was generated using multivariable logistic regression coefficients. RESULTS: Eigthy-nine patients (10% of the sample) developed pre-PPM-HI. Multivariable logistic regression analysis identified urinary catheter use, complete atrioventricular block, implantation of temporary pacemaker and diabetes mellitus as independent predictors of pre-PPM-HI. The generated score (range 0-10.1) played a better role in predicting pre-PPM-HI than individual factors, yielding an area under the curve [95%CI] of 0.754 [0.705-0.803]. Patients with score ≥ 7.5 had 18-fold greater risk of developing pre-PPM-HI than those with score < 2.5. Furthermore, multivariable Cox-regression analysis showed that patients who developed pre-PPM-HI had greater 30-day mortality after PPM implantation (hazard ratio [95%CI] = 2.90 [1.18-7.16], p = 0.021) compared with their counterparts. CONCLUSIONS: This study reveals that pre-PPM-HI is an independent predictor of early mortality after PPM implantation. In addition, a clinical score developed from simple clinical variables accurately identified patients at high risk of pre-PPM-HI. In scenarios where delays in PPM implantation are unavoidable, such as reference hospitals with high demand, the use of this tool can potentially help in the hierarchy of patients and in the reduction of this adverse event.
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Estenose da Valva Aórtica , Infecção Hospitalar , Próteses Valvulares Cardíacas , Marca-Passo Artificial , Substituição da Valva Aórtica Transcateter , Masculino , Humanos , Feminino , Estenose da Valva Aórtica/cirurgia , Estimulação Cardíaca Artificial/efeitos adversos , Estudos Retrospectivos , Prognóstico , Razão de Chances , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
Stricter control of risk factors has been pursued as a compelling strategy to mitigate cardiovascular events (CVE) in type 2 diabetes (T2D) individuals. However, the achievement rate of the recommended goals has remained low in clinical practice. This study investigated the 2019 ESC guideline recommendation attainment among T2D individuals enrolled in a national cohort held in Brazil. Data from 1030 individuals (mean age: 58 years old; 54% male; mean T2D duration: 9.7 years) were analyzed. The control rates were 30.6% for SBP, 18.8% for LDL-C, and 41% for A1c, and only 3.2% of the study participants met all three targets. Statins and high-intensity lipid-lowering therapy prescription rates were 45% and 8.2%, respectively. Longer T2D duration and those at higher CV risk were less likely to be controlled. Longer diabetes duration and higher CV risk were inversely related to the chance of achieving the recommended targets. Treatment escalation using conventional therapies would be sufficient to gain optimal control in most of the study sample. In conclusion, a minimal proportion of T2D individuals comply with guidelines-oriented CV prevention targets. Given the significant burden of the disease, and the substantial effect size predicted for these therapies, bridging this gap between guidelines and clinical practice should be considered an urgent call to public health managers.
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Objective: Left ventricular hypertrophy (LVH) is a common complication of hypertension and microRNAs (miRNAs) are considered to play an important role in cardiac hypertrophy development. This study evaluated the relationship between circulating miRNAs and LVH in hypertensive patients. Methods: Two cohorts [exploratory (n = 42) and validation (n = 297)] of hypertensive patients were evaluated by clinical, laboratory and echocardiography analysis. The serum expression of 754 miRNAs in the exploratory cohort and 6 miRNAs in the validation cohort was evaluated by the TaqMan OpenArray® system and quantitative polymerase chain reaction, respectively. Results: Among the 754 analyzed miRNAs, ten miRNAs (miR-30a-5p, miR-let7c, miR-92a, miR-451, miR-145-5p, miR-185, miR-338, miR-296, miR-375, and miR-10) had differential expression between individuals with and without LVH in the exploratory cohort. Results of multivariable regression analysis adjusted for confounding variables showed that three miRNAs (miR-145-5p, miR-451, and miR-let7c) were independently associated with LVH and left ventricular mass index in the validation cohort. Functional enrichment analysis demonstrated that these three miRNAs can regulate various genes and pathways related to cardiac remodeling. Furthermore, in vitro experiments using cardiac myocytes demonstrated that miR-145-5p mimic transfection up-regulated the expression of brain and atrial natriuretic peptide genes, which are markers of cardiac hypertrophy, while anti-miR-145-5p transfection abrogated the expression of these genes in response to norepinephrine stimulus. Conclusions: Our data demonstrated that circulating levels of several miRNAs, in particular miR-145-5p, miR-451, and let7c, were associated with LVH in hypertensive patients, indicating that these miRNAS may be potential circulating biomarkers or involved in hypertension-induced LV remodeling.
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Carotid intima-media thickness (cIMT) is considered a marker of subclinical atherosclerosis and is related to target-organ damage in hypertensive patients. However, increased cIMT may be due to increases in the thickness of intima (cIT) and media (cMT) layers. This study evaluated whether cIMT layers (cIT and cMT) had a greater association with carotid atherosclerotic plaques and left ventricular hypertrophy (LVH) than cIMT in hypertensive subjects. We cross-sectionally evaluated clinical, carotid, and echocardiography characteristics of 186 hypertensive patients followed at an outpatient clinic. High-resolution images of common carotid arteries were obtained by ultrasonography equipped with 10-MHz transducers, and cIT, cMT, and cIMT were manually measured using an image-processing software. Among all participants (n = 186; age = 60.8 ± 10.9 years, 43% males), there were 58% with carotid plaques and 58% with LVH. Mean cIT, cMT, and cIMT values were 0.267 ± 0.060, 0.475 ± 0.107, and 0.742 ± 0.142 mm, respectively. In logistic regression analysis adjusted for relevant covariates, carotid plaques showed stronger association with cIT than with cMT and cIMT. Furthermore, cIT showed greater area under the ROC curve (0.92; 95% CI 0.87-0.96) than cIMT (0.79; 95% CI 0.72-0.85) and cMT (0.64; 95% CI 0.56-0.72) to identify plaques. Conversely, cIT, cMT, and cIMT had modest association and accuracy to identify LVH (area under the ROC curve = 0.61, 0.57, and 0.60, respectively). In conclusion, cIT is a more accurate marker of atherosclerosis than cMT or cIMT, while cIT and cMT provide no incremental value in identifying LVH when compared with cIMT among hypertensive subjects.
Assuntos
Aterosclerose , Hipertensão , Placa Aterosclerótica , Idoso , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Fatores de RiscoRESUMO
Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, responsible for an atypical pneumonia that can progress to acute lung injury. MicroRNAs are small non-coding RNAs that control specific genes and pathways. This study evaluated the association between circulating miRNAs and lung injury associated with COVID-19. Methods: We evaluated lung injury by computed tomography at hospital admission and discharge and the serum expression of 754 miRNAs using the TaqMan OpenArray after hospital discharge in 27 patients with COVID-19. In addition, miR-150-3p was validated by qRT-PCR on serum samples collected at admission and after hospital discharge. Results: OpenArray analysis revealed that seven miRNAs were differentially expressed between groups of patients without radiological lung improvement compared to those with lung improvement at hospital discharge, with three miRNAs being upregulated (miR-548c-3p, miR-212-3p, and miR-548a-3p) and four downregulated (miR-191-5p, miR-151a-3p, miR-92a-3p, and miR-150-3p). Bioinformatics analysis revealed that five of these miRNAs had binding sites in the SARS-CoV-2 genome. Validation of miR-150-3p by qRT-PCR confirmed the OpenArray results. Conclusions: The present study shows the potential association between the serum expression of seven miRNAs and lung injury in patients with COVID-19. Furthermore, increased expression of miR-150 was associated with pulmonary improvement at hospital discharge.
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COVID-19 , Lesão Pulmonar , MicroRNAs , COVID-19/genética , Biologia Computacional/métodos , Humanos , MicroRNAs/metabolismo , SARS-CoV-2RESUMO
Background: Chronic Chagas cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR). Methods: We performed a prospective observational cohort of patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τic, a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τic with CV death. Results: A total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = -0.51; P = 0.0015). τic decreased linearly with NYHA class (P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (r = 0.47; P = 0.004). Over a median follow-up of 734 days (range: 6-2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (heart rate [HR] = 1.3; 95% CI = [1.0, 1.8]; P = 0.028) and ECV (HR = 3.4 for 0.1 change, 95% CI = [1.1, 11.0], P = 0.039) were simultaneously associated with CV death. Conclusion: In patients with intermediate-to-high-risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events.