RESUMO
BACKGROUND: Early heart failure prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without heart failure. METHODS: In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100-200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular systolic and diastolic function, indexed left ventricular mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment. RESULTS: Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e') was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e' (0.0, 95%CI [-1.2 to 1.2], P = 0.992) or E/A (-0.1, 95%CI [-0.2 to 0.0], P = 0.191). Mean left ventricular ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks (LVEF: 0.9, 95%CI [-1.1 to 2.8], P = 0.382; GLS: -0.4%, 95%CI [-1.5 to 0.6], P = 0.422), nor in LVMi (-3.8 g/m2 95%CI [-10.2 to 2.7], P = 0.246). CONCLUSION: In the present echo sub-study, no change in left ventricular function was observed following high-dose MRA therapy in patients with type 2 diabetes when evaluated by conventional echocardiography. TRIAL REGISTRATION: Date of registration 25/08/2015 (EudraCT number: 2015-002,519-14).
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Eplerenona/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Função Ventricular Esquerda , Volume Sistólico/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Ecocardiografia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/induzido quimicamenteRESUMO
The lusitropic effect of quercetin was examined on isolated ventricular myocardial tissue preparations from normal and streptozotocin-induced diabetic mice. The time required for 90% relaxation of the myocardium, which was prolonged in the diabetic mice, was shortened by quercetin in both normal and diabetic myocardia. This effect of quercetin was completely inhibited by cyclopiazonic acid but not by SEA0400. These results indicated that quercetin accelerates myocardial relaxation through activation of the sarco-endoplasmic reticulum Ca2+-ATPase.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Ventrículos do Coração/fisiopatologia , Contração Miocárdica/efeitos dos fármacos , Miocárdio , Extratos Vegetais/farmacologia , Quercetina/farmacologia , Disfunção Ventricular Esquerda/etiologia , Adenosina Trifosfatases/metabolismo , Compostos de Anilina/farmacologia , Animais , Cálcio/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Retículo Endoplasmático , Inibidores Enzimáticos , Ventrículos do Coração/metabolismo , Indóis/farmacologia , Masculino , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Éteres Fenílicos/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Comestíveis/química , Quercetina/uso terapêutico , Valores de Referência , Pressão VentricularRESUMO
BACKGROUND: Cardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive. AIMS AND METHODS: We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1ß antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy. RESULTS: Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca2+ transient amplitudes and altered baseline [Ca2+] upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca2+ release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca2+ release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca2+ release or Ca2+ signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity. CONCLUSION: Serum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca2+ signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca2+ imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Arritmias Cardíacas , Tratamento Farmacológico da COVID-19 , COVID-19 , Sinalização do Cálcio/efeitos dos fármacos , Miócitos Cardíacos , SARS-CoV-2/metabolismo , Adulto , Idoso , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , COVID-19/complicações , COVID-19/metabolismo , COVID-19/patologia , Cálcio/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/patologiaRESUMO
This study aimed to evaluate the effect of thiamine supplementation on left ventricular (LV) systolic function in patients of alcoholic cardiomyopathy(ACM) presenting with acute heart failure(HF). 11 newly diagnosed patients were included. They were treated with 3 days of intravenous(IV) therapy with thiamine followed by oral supplementation. LVEF was 30% at baseline which improved by 45% and 53% along with reduction in LV dimensions over 3 and 6 months respectively. The study suggests the benefit of thiamine supplementation on LVEF in ACM patients with HF.
Assuntos
Cardiomiopatia Alcoólica , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Cardiomiopatia Alcoólica/complicações , Cardiomiopatia Alcoólica/diagnóstico , Cardiomiopatia Alcoólica/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Volume Sistólico , Tiamina , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Função Ventricular EsquerdaRESUMO
Pulmonary regurgitation (PR) after repair of tetralogy of Fallot (rTOF) is associated with progressive right (RV) and left (LV) ventricular dysfunction and fibrosis. However, angiotensin II receptor blockade therapy has shown mixed and often disappointing results. The aim of this study was to serially assess changes in biventricular remodeling, dysfunction, and interactions in a rat model of isolated severe PR and to study the effects of angiotensin II receptor blockade. PR was induced in Sprague-Dawley rats by leaflet laceration. Shams (n = 6) were compared with PR (n = 5) and PR + losartan treatment (n = 6). In the treatment group, oral losartan (50 mg·kg-1·day-1) was started 6 wk after PR induction and continued for 6 wk until the terminal experiment. In all groups, serial echocardiography was performed every 2 wk until the terminal experiment where biventricular myocardium was harvested and analyzed for fibrosis. PR and PR + losartan rats experienced early progressive RV dilatation by 2 wk which then stabilized. RV systolic dysfunction occurred from 4 wk after insult and gradually progressed. In PR rats, RV dilatation caused diastolic LV compression and impaired relaxation. PR rats developed increased RV fibrosis compared with shams. Although losartan decreased RV fibrosis, RV dilatation and dysfunction were not improved. This suggests that RV dilatation is an early consequence of PR and affects LV relaxation. RV dysfunction may progress independent of further remodeling. Reduced RV fibrosis was not associated with improved RV function and may not be a viable therapeutic target in rTOF with predominant RV volume loading.NEW & NOTEWORTHY The time-course of RV dilatation and the mechanisms of biventricular dysfunction caused by PR have not been well characterized and the effect of losartan in volume-overloaded RV remains controversial. Our findings suggest that severe PR induces early onset of RV dilatation and dysfunction with little progression after the first 4 wk. The RV dilatation distorts LV geometry with associated impaired LV relaxation. Losartan reduced RV fibrosis but did not reverse RV dilatation and dysfunction.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Losartan/uso terapêutico , Insuficiência da Valva Pulmonar/complicações , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Direita/tratamento farmacológico , Animais , Modelos Animais de Doenças , Ecocardiografia , Fibrose/tratamento farmacológico , Fibrose/etiologia , Fibrose/fisiopatologia , Insuficiência da Valva Pulmonar/fisiopatologia , Ratos , Ratos Sprague-Dawley , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologiaRESUMO
BACKGROUND: Levosimendan is an effective calcium sensitizer with complementary mechanisms of action: calcium sensitization and opening of adenosine triphosphate-dependent potassium channels, both on the sarcolemma of the smooth muscle cells in the vasculature and on the mitochondria of cardiomyocytes. Levosimendan has a long-acting metabolite with a half-life of approximately 80 h. There have been a few small studies on this drug regarding right ventricular function. In view of this, we investigated the effect of levosimendan on right ventricular function in patients with coronary artery disease. METHODS: This was a prospective, randomized, double-blind study on 50 patients with coronary artery disease and severe left ventricular dysfunction (left ventricular ejection fraction ≤35%) undergoing elective off-pump coronary artery bypass. RESULTS: Levosimendan had an inotropic effect on right ventricular myocardium and a vasodilatory effect on blood vessels. It caused a decline in pulmonary vascular resistance (p < 0.018), right ventricular systolic pressure (p < 0.001), and pulmonary artery systolic pressure (p < 0.001), and improved right ventricular diastolic function as shown by the decrease in right ventricular Tei index (p < 0.001), right ventricular end-diastolic pressure, and the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity (p < 0.006). However, we found no beneficial effects on intensive care unit or hospital stay (p = 0.164, p = 0.349, respectively) nor a mortality benefit. CONCLUSIONS: Levosimendan has salutary effects on right ventricular function in patients with severe left ventricular dysfunction undergoing coronary artery bypass, in terms of improved hemodynamic parameters.
Assuntos
Piridazinas , Disfunção Ventricular Esquerda , Cardiotônicos/uso terapêutico , Ventrículos do Coração , Humanos , Hidrazonas/uso terapêutico , Estudos Prospectivos , Simendana/farmacologia , Volume Sistólico , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Função Ventricular EsquerdaRESUMO
Cardiac complications are the major cause of mortality in patients with Thalassemia major (TM). Cardiac T2* MRI is currently the gold standard for assessing myocardial iron concentration. The aim of our study was to assess whether any echocardiographic parameter would correlate with these findings in patients well established on chelation therapy. This was a prospective study on patients with TM who are regularly followed in our clinic. Patients had a cardiac MRI and echocardiogram within 2 months of each other. Echo parameters included global longitudinal strain and diastolic function. We also compared these findings with those from a cohort of thalassemia intermedia (TI) and normal controls. A total of 84 patients (mean age 26.3 ± 6.1 years, 42.8% male) with TM were enrolled. All had normal left ventricular ejection fraction and only 8 patients had MRI T2* < 10. As compared to 17 patients with TI and 53 controls, these patients had significantly higher E/E' and lower pulmonary vein s/dd ratio suggesting early diastolic dysfunction. 28 patients fulfilled criteria for diastolic dysfunction even in the presence of normal MRI T2*. Global longitudinal strain (GLS) was significantly lower in the TM group as compared to the TI and controls. We found no correlation between any of the echo findings and the MRI T2*in TM patients. In patients with thalassemia and MRI T2* > 20 ms features of diastolic dysfunction persist even in the presence of normal LV function and normal GLS. This suggests that diastolic function remains abnormal even when myocardial iron concentrations are normal and follow up therefore is essential.
Assuntos
Ecocardiografia Doppler , Quelantes de Ferro/uso terapêutico , Imageamento por Ressonância Magnética , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Talassemia beta/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Estudos Transversais , Diástole , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem , Talassemia beta/complicações , Talassemia beta/diagnósticoRESUMO
Heart failure (HF) represents a major public health burden. Inflammation has been shown to be a critical factor in the progression of HF, regardless of the aetiology. Disappointingly, the majority of clinical trials targeting aspects of inflammation in patients with HF have been largely negative. Many clinical researches demonstrate that danshen has a good efficacy on HF, and however, whether danshen exerts anti-inflammatory effects against HF remains unclear. In our study, the employment of a water extracted and alcohol precipitated of danshen extract attenuated cardiac dysfunction and inflammation response in acute myocardial infarction-induced HF rats. Transcriptome technique and validation results revealed that TLR4 signalling pathway was involved in the anti-inflammation effects of danshen. In vitro, danshen reduced the release of inflammatory mediators in LPS-stimulated RAW264.7 macrophage cells. Besides, the LPS-stimulated macrophage conditioned media was applied to induce cardiac H9C2 cells injury, which could be attenuated by danshen. Furtherly, knock-down and overexpression of TLR4 were utilized to confirm that danshen ameliorated inflammatory injury via MyD88-dependent TLR4-TRAF6-NF-κB signalling pathway in cardiomyocytes. Furthermore, by utilizing co-immunoprecipitation, danshen was proved to suppress MD2/TLR4 complex formation and MyD88 recruitment. In conclusion, our results demonstrated that danshen ameliorates inflammatory injury by controlling MD2/TLR4-MyD88 complex formation and TLR4-TRAF6-NF-κB signalling pathway in acute myocardial infarction-induced HF.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Antígeno 96 de Linfócito/antagonistas & inibidores , Fator 88 de Diferenciação Mieloide/antagonistas & inibidores , Infarto do Miocárdio/complicações , Fitoterapia , Extratos Vegetais/uso terapêutico , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Biomarcadores , Meios de Cultivo Condicionados/farmacologia , Avaliação Pré-Clínica de Medicamentos , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/prevenção & controle , Antígeno 96 de Linfócito/fisiologia , Macrófagos/metabolismo , Camundongos , Complexos Multiproteicos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/fisiologia , Miocardite/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/metabolismo , Transdução de Sinais/genética , Organismos Livres de Patógenos Específicos , Receptor 4 Toll-Like/fisiologia , Transcriptoma/efeitos dos fármacos , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/prevenção & controleRESUMO
Obesity is an independent risk factor to develop cardiac functional and structural impairments. Here, we investigated the effects of supplementation of inositols on the electrical, structural, and functional cardiac alterations in the mouse model of high fat diet (HFD) induced obesity. Three groups of C57BL6 mice (n = 16 each) were studied: j) HFD feeding; jj) HFD feeding + inositols from week 9 to 13; jjj) standard diet feeding. Study observation period was 13 weeks. Inositols were administered as mixture of myo-inositol and d-chiro-inositol in the drinking water. Effects of inositols were evaluated based on electrical, structural, and functional cardiac features, autonomic sympatho-vagal balance and arrhythmogenic susceptibility to adrenergic challenge. Heart samples were collected for histological evaluations and transcriptional analyses of genes involved in defining the shape and propagation of the action potential, fatty acid metabolism and oxidative stress. Inositol supplementation significantly restored control values of heart rate and QTc interval on ECG and of sympatho-vagal balance. Moreover, it blunted the increase in left ventricular mass and cardiomyocyte hypertrophy, reversed diastolic dysfunction, reduced the susceptibility to arrhythmic events and restored the expression level of cardiac genes altered by HFD. The present study shows, for the first time, how a short period of supplementation with inositols is able to ameliorate the HFD-induced electrical, structural and functional heart alterations including ventricular remodeling. Results provide a new insight into the cardioprotective effect of inositols, which could pave the way for a novel therapeutic approach to the treatment of HFD obesity-induced heart dysfunction.
Assuntos
Arritmias Cardíacas/prevenção & controle , Suplementos Nutricionais , Sistema de Condução Cardíaco/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/prevenção & controle , Inositol/administração & dosagem , Miócitos Cardíacos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Disfunção Ventricular Esquerda/prevenção & controle , Potenciais de Ação/efeitos dos fármacos , Administração Oral , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Obesidade/complicações , Fatores de Tempo , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
8-oxoguanine (8-oxoG) is one of the most prevalent genotoxic lesions, and it is generated in DNA attacked by reactive oxygen species (ROS). Adenine misincorporated opposite to 8-oxoG during replication is excised by MutY homolog (MUTYH), an important protein of the base excision repair (BER) system. Mutyh plays an important role in the maintenance of genomic integrity, but the functional consequences of Mutyh deficiency are not fully understood. In the current study, we investigated the histological and functional changes of five tissues (hippocampus, heart, liver, kidney and lung) and their molecular basis in Mutyh-/- and wild-type mice exposed to D-galactose (D-gal). Our data indicated that Mutyh deficiency hindered the weight gain of experimental mice and induced substantial alterations of 8-oxoG content and superoxide dismutase (SOD) activity, but no significant histological and functional impairment appeared in the investigated tissues of Mutyh- deficient mice without D-gal exposure. Under low-dose D-gal exposure, Mutyh deficiency altered expression of genes involved in mitochondrial unfolded protein response (UPRmt) in the heart, liver and lung, and caused an enhanced expression of mitochondrial dynamics proteins (MDPs) in hippocampus and liver. The stress responses could maintain mitochondrial proteostasis and function. However, such responses were not noted when experiencing excessive damage burden induced by high-dose D-gal exposure, in which Mutyh deficiency increased accumulation of 8-oxoG and aggravated mitonuclear protein imbalance, as well as histological lesions in heart, liver and kidney. A higher sensitivity to ROS-induced cardiotoxicity with high-dose D-gal exposure was noticed in Mutyh-/- mice. However, no differences in learning and memory impairments were observed between Mutyh-/- and wild-type mice with high-dose D-gal exposure. In conclusion, our data demonstrated that Mutyh deficiency has different impacts on various tissues based on the degree of oxidative stress.
Assuntos
Comportamento Animal/efeitos dos fármacos , Dano ao DNA , DNA Glicosilases/fisiologia , Mitocôndrias/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Disfunção Ventricular Esquerda/etiologia , Animais , Galactose/farmacologia , Guanina/análogos & derivados , Guanina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Superóxido Dismutase/metabolismo , Disfunção Ventricular Esquerda/patologiaRESUMO
OBJECTIVES: This study sought to determine the long-term right atrial (RA) electrical and structural changes in a subgroup from the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-Magnetic Resonance Imaging) study. BACKGROUND: Catheter ablation (CA) is successful in restoring ventricular function in patients with atrial fibrillation (AF) and otherwise unexplained cardiomyopathy, as demonstrated in the randomized study of CA versus rate control (CAMERA-MRI). It is unknown if this is associated with atrial remodeling. METHODS: Detailed electroanatomical (EA) mapping of the RA using CARTO3 and a force sensing catheter was performed at initial CA and electively at least 12 months after CA in patients with >90% reduction in AF burden following ablation. Bipolar voltage, fractionation, and conduction velocity were collected in 4 segments together with echo and cardiac magnetic resonance imaging. RESULTS: Fifteen patients (mean age 59.1 ± 6.8 years) underwent repeat RA EA mapping. At a mean follow-up of 23.4 ± 11.9 months, left ventricular (LV) ejection fraction improved from 33.6 ± 3.2% to 54.1 ± 3.2% (p = 0.001), RA area decreased from 28.4 ± 2.0 cm2 to 20.8 ± 1.2 cm2 (p < 0.001), and left atrial area decreased from 32.9 ± 2.3 cm2 to 26.8 ± 1.4 cm2 (p = 0.007). On EA mapping, RA bipolar voltage increased from 1.6 ± 0.1 mV to 1.9 ± 0.1 mV (p = 0.04). Tissue voltage increased across all regions, which achieved statistical significance at the posterior (p = 0.002) and septal (p = 0.01) segments. There was a significant decrease in complex fractionated electrograms from 21.7 ± 3.5% to 8.3 ± 1.8% (p = 0.002); however, no significant change occurred in global or regional conduction velocities (p = 0.5). CONCLUSIONS: Recovery of atrial electrical and structural changes was observed following restoration of sinus rhythm and recovery of LV function in patients who underwent CA for persistent AF and LV systolic dysfunction. The randomized CAMERA MRI study demonstrated significant improvement in LV systolic function with AF ablation compared with rate control. The present study demonstrated reverse electrical and structural atrial recovery in concert with recovery of LV systolic function at 2 years post-AF ablation. This may partially explain the long-term success of CA in patients with AF and otherwise unexplained cardiomyopathy.
Assuntos
Fibrilação Atrial/cirurgia , Remodelamento Atrial , Cardiomiopatias/fisiopatologia , Ablação por Cateter , Átrios do Coração/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Idoso , Fibrilação Atrial/complicações , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/etiologia , Ecocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
The chymase inhibitor fulacimstat is developed as a first-in-class treatment option for the inhibition of adverse cardiac remodeling in patients with left ventricular dysfunction (LVD) after acute myocardial infarction (MI). The aim of the study was to examine the safety and tolerability of fulacimstat in patients with LVD after remote MI. A multicenter, multinational randomized, placebo-controlled study was performed in clinically stable patients (40-79 years of age, left ventricular ejection fraction ≤ 45% because of MI in medical history) who were on stable evidence-based standard-of-care therapies for LVD post-MI including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker at doses of at least half the recommended target dose. Patients were treated for 2 weeks with either placebo (n = 12) or 4 different doses of fulacimstat (5 mg twice daily, n = 9; 10 mg twice daily, n = 9; 25 mg twice daily, n = 10; 50 mg once daily, n = 9). Fulacimstat was safe and well tolerated at all examined doses. There were no clinically relevant effects on vital signs or potassium levels compared with placebo treatment. Mean plasma concentrations of fulacimstat increased with the administered dose and reached exposures predicted to be therapeutically active. The safety profile and the absence of effects on blood pressure or heart rate in a chronic patient population having similar comorbidities and receiving similar comedication as patients after acute MI support future clinical trials with fulacimstat in patients after acute MI.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Ácidos Carboxílicos/administração & dosagem , Insuficiência Cardíaca/prevenção & controle , Indenos/administração & dosagem , Infarto do Miocárdio/complicações , Pirimidinas/administração & dosagem , Disfunção Ventricular Esquerda/tratamento farmacológico , Adulto , Idoso , Ácidos Carboxílicos/efeitos adversos , Ácidos Carboxílicos/farmacocinética , Quimases/antagonistas & inibidores , Esquema de Medicação , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Indenos/efeitos adversos , Indenos/farmacocinética , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologiaAssuntos
Intoxicação por Monóxido de Carbono/complicações , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Direita/etiologia , Intoxicação por Monóxido de Carbono/terapia , Cardiotônicos/uso terapêutico , Ecocardiografia , Humanos , Oxigenoterapia Hiperbárica/métodos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/terapia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/terapiaAssuntos
Feixe Acessório Atrioventricular , Cardiomiopatia Dilatada/etiologia , Disfunção Ventricular Esquerda/etiologia , Síndrome de Wolff-Parkinson-White/complicações , Potenciais de Ação , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Ablação por Cateter , Ecocardiografia , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca , Humanos , Masculino , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/fisiopatologia , Síndrome de Wolff-Parkinson-White/cirurgia , Adulto JovemRESUMO
BACKGROUND: Postresuscitation myocardial dysfunction (PRMD) can develop after successful resuscitation from cardiac arrest. However, echocardiographic patterns of PRMD remain unknown. This study aimed to investigate PRMD manifestations with serial echocardiography during the post-cardiac arrest period. METHODS: We enrolled non-traumatic out-of-hospital cardiac arrest patients older than 19 years who underwent successful cardiopulmonary resuscitation (CPR). We excluded patients with myocardial infarction or pre-existing cardiac disease, including heart failure or myocardial disease. Transthoracic echocardiography (TTE) was performed within 24â¯h, between 24 and 48â¯h, and between 72 and 96â¯h after restoration of spontaneous circulation (ROSC). RESULTS: Of 280 patients, 138 (93 men) were analysed. PRMD was observed in 45 patients (33%), including global dysfunction in 28 patients (20%), regional wall motion abnormalities (RWMA) in 10 (7%), and Takotsubo pattern in 7 (5%). There were no differences in clinical characteristics, laboratory findings, or hospital mortality according to PRMD pattern. Global left ventricular (LV) systolic function gradually improved with time and had recovered to normal by Day 3 in all patients except one with the Takotsubo pattern, which remained on follow-up echocardiography two weeks after ROSC. CONCLUSIONS: PRMD occurs in about one-third of patients resuscitated from cardiac arrest. Echocardiographic patterns of post-cardiac arrest LV dysfunction include global hypokinesia, regional wall motion abnormalities, and Takotsubo pattern.
Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/terapia , Disfunção Ventricular Esquerda/etiologia , Idoso , Ecocardiografia , Cardioversão Elétrica/estatística & dados numéricos , Feminino , Humanos , Hipertermia Induzida/métodos , Hipertermia Induzida/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Estudos ProspectivosAssuntos
Inibidores do Fator Xa/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Rivaroxabana/uso terapêutico , Trombose/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Adulto , Cardiomiopatia Dilatada/complicações , Ecocardiografia , Ectromelia/complicações , Feminino , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Coeficiente Internacional Normatizado , Trombose/diagnóstico , Trombose/etiologia , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Varfarina/efeitos adversosRESUMO
RATIONALE: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disorder related to thrombosis. Anticoagulant therapy is suggested for the treatment of this disease. The success of the novel oral anticoagulant rivaroxaban as a treatment option for this disorder is unclear. PATIENT CONCERNS: A 43-year-old man who felt dizzy at rest was found to have an intraventricular thrombus. DIAGNOSES: The thrombus was confirmed by echocardiography. And LVNC was diagnosed by cardiac magnetic resonance (CMR) and echocardiography. INTERVENTIONS: He was prescribed a low dose (10âmg daily) of rivaroxaban as treatment. OUTCOMES: After 3 months, the thrombus diminished, and the manifestation disappeared. LESSONS: Low dose of rivaroxaban may serve as a viable option for anticoagulation therapy in LVNC patients, with large clinical trials needed to determine the best course of treatment.
Assuntos
Inibidores do Fator Xa/administração & dosagem , Miocárdio Ventricular não Compactado Isolado/complicações , Rivaroxabana/administração & dosagem , Trombose/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Adulto , Humanos , Masculino , Trombose/etiologia , Disfunção Ventricular Esquerda/etiologiaRESUMO
Aims: The relationship between ventricular pre-excitation and left ventricular dysfunction has been described in the absence of sustained supraventricular tachycardia in a series of case reports. There have been no systematic studies about the effect of ventricular pre-excitation with different accessory pathway locations on ventricular wall motion and left ventricular (LV) systolic function. Methods and results: Thirty patients were selected for each of 4 groups, including those with right septal pathways (Group 1), right free-wall pathways (Group 2), left free-wall pathways (Group 3), and non-pre-excited patients undergoing electrophysiological evaluation for supraventricular tachycardia. We analysed the influence of the location of the accessory pathway on ventricular wall motion, systolic function, ventricular synchronism, and LV size. Right-sided accessory pathways were associated with abnormal motion of the interventricular septum, LV dyssynchrony, decreased LV systolic function, and increased LV diameter. Eighteen of 60 cases (30.0%) with right-sided accessory pathways had LV dyssynchrony, and these patients had lower LV ejection fraction and higher LV end-diastolic diameter. Conclusion: Right-sided accessory pathways may impair ventricular wall motion and LV systolic function, resulting in decreased LV ejection fraction and increased LV end-diastolic diameter. These effects occurred in patients with LV dyssynchrony. These effects, including LV dyssynchrony, resolved after radiofrequency ablation. A right-sided free-wall accessory pathway may have more detrimental effects than a septal accessory pathway. Left ventricular dyssynchrony and abnormal interventricular septal motion appeared to be responsible for the pathogenesis of LV dysfunction and remodelling.
Assuntos
Feixe Acessório Atrioventricular/fisiopatologia , Taquicardia Supraventricular/complicações , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Síndrome de Wolff-Parkinson-White/complicações , Feixe Acessório Atrioventricular/cirurgia , Potenciais de Ação , Criança , Pré-Escolar , Ecocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Frequência Cardíaca , Humanos , Masculino , Ablação por Radiofrequência , Recuperação de Função Fisiológica , Volume Sistólico , Sístole , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/cirurgia , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Remodelação Ventricular , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/fisiopatologia , Síndrome de Wolff-Parkinson-White/cirurgiaRESUMO
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with end-stage renal disease. Chronic kidney disease (CKD)-associated cardiovascular mortality is more prevalent in those with diastolic heart failure and is an early predictor, while increased left ventricular mass (LVM) is a strong independent risk factor. Hypovitaminosis D is extensively being studied as a nontraditional risk factor for CVD. The aim of the present study is to look at the association of Vitamin D and other parameters of mineral bone disorder (MBD) with diastolic dysfunction and LVM in nondiabetic young adult patients with CKD. This was a hospital-based, cross-sectional observational study. Groups I and II comprised nondiabetic predialysis CKD patients (stage 4 and 5) and healthy controls, respectively. Groups IA and IB comprised cases with and without diastolic dysfunction, respectively. Vitamin D level was measured by enhanced chemiluminescence method and intact parathyroid hormone (iPTH) by electrochemiluminescence method. Parameters for diastolic function and LVM were assessed by Doppler echocardiography, tissue Doppler imaging, and M-mode echocardiography. Vitamin D level was significantly lower in Group I as compared to Group II. Diastolic dysfunction was present in 48.8% of the cases and was significantly associated with serum phosphorus and calcium-phosphorous product, but not with Vitamin D level. A statistically significant positive correlation between LVM and iPTH was found in our study. Hyperphosphatemia and high calcium-phosphorous product can be a better early predictor of diastolic dysfunction than Vitamin D while secondary hyperpara-thyroidism with increased LVM may be a bad prognostic marker.
Assuntos
Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Hipertrofia Ventricular Esquerda/etiologia , Insuficiência Renal Crônica/complicações , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Remodelação Ventricular , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Adulto , Biomarcadores/sangue , Cálcio/sangue , Estudos de Casos e Controles , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Estudos Transversais , Diástole , Ecocardiografia Doppler , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Hormônio Paratireóideo/sangue , Fósforo/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/fisiopatologiaRESUMO
A case of a 32-year-old nulliparous white woman referred for a 5-year history of severe hypertension, hypokalemia, and resultant systolic dysfunction is presented. She additionally had a left ventricular ejection fraction of 30% including left ventricular dilation and normal left ventricular mass index, as measured by cardiac magnetic resonance imaging when she initially presented to us. Her history revealed that her severe hypertension episodes were monthly and would occur around the catamenial (menses-associated) time. Two weeks following her menses, blood pressure decreased significantly but remained elevated above 140/90 mm Hg. This cycle repeated monthly and required multiple hospitalizations for hypertensive emergency in the form of acute decompensated heart failure and severe headaches. She required potassium supplementation. This prompted a complete evaluation for secondary causes of hypertension, which was negative. Female and male sex hormone levels, including testosterone, were also within normal limits. She received an injection of leuprolide acetate depot (11.25 mg every 3 months), a gonadotropin-releasing hormone agonist. This significantly reduced the magnitude of these episodes.