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1.
Int Heart J ; 61(5): 944-950, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921677

RESUMO

Clinical experience with landiolol use in patients with atrial fibrillation (AF) and a severely depressed left ventricular (LV) function is limited. We compared the efficacy and safety of landiolol with that of digoxin as an intravenous drug in controlling the heart rate (HR) during AF associated with a very low LV ejection fraction (LVEF).We retrospectively analyzed 53 patients treated with landiolol (n = 34) or digoxin (n = 19) for AF tachycardias with an LVEF ≤ 25. The landiolol dose was adjusted between 0.5 and 10 µg/kg/minute according to the patient's condition. The response to treatment was defined as a decrease in the HR of ≤ 110/minute, and that decreased by ≥ 20% from baseline.There were no significant differences between the two groups regarding the clinical characteristics. The responder rate to landiolol at 24 hours was significantly higher than that to digoxin (71.0% versus 41.2%; odds ratio: 4.65, 95% confidence interval: 1.47-31.0, P = 0.048). The percent decrease in the HR from baseline at 1, 2, 12, and 24 hours was greater in the landiolol group than in the digoxin group (P < 0.01, P = 0.071, P = 0.036, and P = 0.016, respectively). The systolic blood pressure (SBP) from baseline within 24 hours after administering landiolol was significantly reduced, whereas digoxin did not decrease the SBP over time. Hypotension (< 80 mmHg) occurred in two patients in the landiolol group and 0 in the digoxin group (P = 0.53).Landiolol could be more effective in controlling the AF HR than digoxin even in patients with severely depressed LV function. However, careful hemodynamic monitoring is necessary when administering landiolol.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Digoxina/uso terapêutico , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Morfolinas/uso terapêutico , Taquicardia/tratamento farmacológico , Ureia/análogos & derivados , Disfunção Ventricular Esquerda/fisiopatologia , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Pressão Sanguínea , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Volume Sistólico , Taquicardia/etiologia , Taquicardia/fisiopatologia , Resultado do Tratamento , Ureia/uso terapêutico , Disfunção Ventricular Esquerda/complicações
2.
Hypertension ; 76(5): 1526-1536, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32981365

RESUMO

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.


Assuntos
Infecções por Coronavirus/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Progressão da Doença , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/fisiopatologia , Peptidil Dipeptidase A/sangue , Pneumonia Viral/epidemiologia , Centros Médicos Acadêmicos , Análise de Variância , Biomarcadores/metabolismo , Estudos de Coortes , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Prognóstico , Modelos de Riscos Proporcionais , Proteômica/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estados Unidos
3.
Lancet ; 396(10254): 819-829, 2020 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-32877652

RESUMO

BACKGROUND: Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials. METHODS: We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model. FINDINGS: Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77-0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76-0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68-0·82; p<0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68-0·84; p<0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43-0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race. INTERPRETATION: The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF. FUNDING: Boehringer Ingelheim.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Índice de Massa Corporal , Estudos de Casos e Controles , Causas de Morte/tendências , Ensaios Clínicos como Assunto , Morte , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/classificação , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/antagonistas & inibidores , Avaliação de Resultados da Assistência ao Paciente , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
4.
Pediatr Clin North Am ; 67(5): 889-901, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32888688

RESUMO

Pediatric heart failure (PHF) affects 0.87 to 7.4 per 100,000 children. It has a 5-year mortality or heart transplant rate of 40%. Diagnosis often is delayed because initial symptoms are similar to common pediatric illnesses. Disease progression is tracked by symptoms, echocardiogram, and biomarkers. Treatment is extrapolated from mostly adult heart failure (HF) literature. Recent studies demonstrate differences between pediatric and adult HF pathophysiology. Increased collaboration among PHF programs is advancing the management of PHF. Unfortunately, there are patients who ultimately require heart transplantation, with increasing numbers supported by a ventricular assist device as a bridge to transplantation.


Assuntos
Insuficiência Cardíaca/diagnóstico , Monitorização Fisiológica/métodos , Volume Sistólico/fisiologia , Criança , Ecocardiografia , Saúde Global , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Morbidade
5.
N Engl J Med ; 383(15): 1413-1424, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-32865377

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODS: In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTS: During a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001). The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28 ml per minute per 1.73 m2 of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes. Uncomplicated genital tract infection was reported more frequently with empagliflozin. CONCLUSIONS: Among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977.).


Assuntos
Compostos Benzidrílicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/efeitos adversos , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico
6.
PLoS One ; 15(9): e0237810, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936824

RESUMO

Cardiovascular diseases are a leading cause of death worldwide. After an ischemic injury, the myocardium undergoes severe necrosis and apoptosis, leading to a dramatic degradation of function. Numerous studies have reported that cardiac fibroblasts (CFs) play a critical role in heart function even after injury. However, CFs present heterogeneous characteristics according to their development stage (i.e., fetal or adult), and the molecular mechanisms by which they maintain heart function are not fully understood. The aim of this study is to explore the hypothesis that a specific population of CFs can repair the injured myocardium in heart failure following ischemic infarction, and lead to a significant recovery of cardiac function. Flow cytometry analysis of CFs defined two subpopulations according to their relative expression of vascular cell adhesion molecule 1 (VCAM1). Whole-transcriptome analysis described distinct profiles for these groups, with a correlation between VCAM1 expression and lymphangiogenesis-related genes up-regulation. Vascular formation assays showed a significant stimulation of lymphatic cells network complexity by VCFs. Injection of human VCAM1-expressing CFs (VCFs) in postinfarct heart failure rat models (ligation of the left anterior descending artery) led to a significant restoration of the left ventricle contraction. Over the course of the experiment, left ventricular ejection fraction and fractional shortening increased by 16.65% ± 5.64% and 10.43% ± 6.02%, respectively, in VCF-treated rats. Histological examinations revealed that VCFs efficiently mobilized the lymphatic endothelial cells into the infarcted area. In conclusion, human CFs present heterogeneous expression of VCAM1 and lymphangiogenesis-promoting factors. VCFs restore the mechanical properties of ventricular walls by mobilizing lymphatic endothelial cells into the infarct when injected into a rat heart failure model. These results suggest a role of this specific population of CFs in the homeostasis of the lymphatic system in cardiac regeneration, providing new information for the study and therapy of cardiac diseases.


Assuntos
Fibroblastos/patologia , Insuficiência Cardíaca/fisiopatologia , Linfangiogênese , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Insuficiência Cardíaca/sangue , Humanos , Vasos Linfáticos/metabolismo , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Neovascularização Fisiológica , Ratos , Molécula 1 de Adesão de Célula Vascular/sangue
7.
Medicine (Baltimore) ; 99(37): e21663, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925713

RESUMO

BACKGROUND: The incidence of heart failure with normal ejection fraction (HFNEF) is increasing yearly, accounting for approximately half of all heart failure cases. Even after standardized treatment, the patient's prognosis is not good. Therefore, it is necessary to explore new treatment methods for HFNEF. Yangyin Shuxin Decoction, a traditional Chinese medicine prescription from our clinical experience in the treatment of HFNEF, has a potential cardioprotective effect. Preliminary clinical trials have shown that this prescription can improve the quality of life of HFNEF. This prompted us to use more objective indicators to further evaluate whether Yangyin Shuxin Decoction can improve the exercise capacity in HENEF patients. METHODS: This is a single-center parallel randomized controlled trial. The 64 patients who met the inclusion criteria were from the Cardiovascular Clinic. They will be randomly assigned to the treatment group (Yangying Shuxin Decoction combined with standard treatment) or the control group (standard treatment) according to the ratio of 1:1. The course of treatment will be 2 weeks. Both groups were interviewed at the following time points: of at enrollment (V1), and week 2 (V2), week 4 (V3), week 8 (V4), and week 12 (V5) after enrollment. The primary indicator is the peak oxygen consumption (Peak VO2) of the cardiopulmonary exercise test (CPET). Secondary indicators include CPET indicators such as anaerobic threshold oxygen consumption, carbon dioxide ventilation equivalent slope, echocardiographic indicators such as the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity(E/e'), left atrial volume index (LAVI), left ventricular mass index (LVMI), the peak velocity of tricuspid regurgitation (TR), B-type natriuretic peptide (BNP), New York Heart Association (NYHA) cardiac function grading, and so on. These indicators will be used to evaluate the effect of Yangyin Shuxin Decoction on exercise capacity in patients with HFNEF. DISCUSSION: At present, it is unclear whether the exercise capacity can be maintained after long-term use of Yangyin Shuxin Decoction. In this study, we will evaluate whether Yangyin Shuxin Decoction can improve the exercise capacity and quality of life of patients with HFNEF. This will provide an objective basis for the therapeutic effect of traditional Chinese medicine on HFNEF. TRIAL REGISTRATION: This study protocol has been listed in the Chinese Clinical Trial Registry (registration number: ChiCTR-IOR-17014206, http://www.chictr.org.cn/showproj.aspx?proj=24304) on December 28, 2017.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico/fisiologia , Adulto , Idoso , Ecocardiografia , Teste de Esforço , Tolerância ao Exercício , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome , Resultado do Tratamento
8.
Int Heart J ; 61(5): 1014-1021, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32879261

RESUMO

Impaired fatty acid metabolism is associated with heart failure (HF) prognosis. However, specific changes in acylcarnitine profiles and their potential clinical value have not been well explored in patients recovering from acute decompensation.This study recruited 79 HF patients hospitalized because of acute decompensation with a left ventricular ejection fraction (LVEF) of < 40% and 51 normal controls. Patients were dichotomized into two groups, namely, the "improved (IMP) " and the "non-improved (NIMP) " groups, as defined by the changes in LVEF from baseline to 12 months after discharge. Mass spectrometry was used to quantify the acylcarnitine concentrations at baseline and 6 and 12 months after discharge. The IMP and NIMP groups contained 42 and 37 patients, respectively. At baseline, HF patients had higher plasma concentrations of specific long-, medium-, and short-chain acylcarnitines compared to normal controls. From baseline to 12 months post-discharge, the IMP group showed significant decreases in long- and short-chain acylcarnitine concentrations, but significant increases in medium-chain acylcarnitines. In the NIMP group, none of the acylcarnitines significantly decreased, and significant increases were noted in long-, medium-, and short-chain acylcarnitines. Generalized estimating equations demonstrated that nine acylcarnitines could discriminate the IMP group from the NIMP group, including three long-chain (C18:1, C16, and C16:1) and six short-chain acylcarnitines (C5, C5-OH, C4, C4:1-DC, C3, and C2). After adjusting for age, the six short-chain acylcarnitines remained significant. Changes in short-chain acylcarnitine profiles are independently associated with the improvement in cardiac systolic function after acute decompensation.


Assuntos
Carnitina/análogos & derivados , Ácidos Graxos/metabolismo , Insuficiência Cardíaca/metabolismo , Metabolômica , Idoso , Carnitina/metabolismo , Estudos de Casos e Controles , Ésteres/metabolismo , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico , Sístole
9.
Ann Hematol ; 99(10): 2289-2294, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32737633

RESUMO

Iron overload-induced cardiomyopathy is the leading cause of death in patients with transfusion-dependent thalassemia (TDT). The mortality is extremely high in these patients with severe cardiac complications, and how to rescue them remains a challenge. It is reasonable to use combined chelation with deferiprone (L1) and deferoxamine (DFO) because of their shuttle and synergistic effects on iron chelation. Here, seven consecutive patients with TDT who had severe cardiac complications between 2002 and 2019 and received combined chelation therapy with oral high-dose L1 (100 mg/kg/day) and continuous 24-h DFO infusion (50 mg/kg/day) in our hospital were reported. Survival for eight consecutive patients receiving DFO monotherapy for their severe cardiac complications between 1984 and 2001 was compared. We found that combined chelation therapy with high-dose L1 and DFO was efficient to improve survival and cardiac function in patients with TDT presenting severe cardiac complications. Reversal of arrhythmia to sinus rhythm was noted in all patients. Their 1-month follow-up left ventricular ejection fraction increased significantly (P < 0.001). There were no deaths, and all patients were discharged from hospital with good quality of life. In contrast, all the eight patients receiving DFO monotherapy died (P < 0.001). Accordingly, combined chelation therapy with high-dose L1 and DFO should be considered in patients with TDT presenting cardiac complications.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Terapia por Quelação/métodos , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Talassemia/terapia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Transfusão de Sangue , Deferiprona/administração & dosagem , Desferroxamina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/etiologia , Masculino , Qualidade de Vida , Estudos Retrospectivos , Talassemia/complicações , Reação Transfusional , Resultado do Tratamento , Função Ventricular Esquerda
10.
Dtsch Arztebl Int ; 117(21): 376-386, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32843138

RESUMO

BACKGROUND: Chronic congestive heart failure is a common condition that, if untreated, markedly impairs the quality of life and is associated with a high risk of recurrent hospitalization and death. METHODS: This review is based on articles retrieved by a selective search in PubMed, as well as on relevant guidelines. RESULTS: Evidence-based treatment options are available only for congestive heart failure with a low ejection fraction. Pharma - cotherapy is based on neurohumoral inhibition of the renin-angiotensin-aldosterone system and the adrenergic system. The prognosis of patients with this condition has been further improved recently through the introduction of combined angiotensin receptor antagonists and neprilysin inhibitors. Modern implantable devices are a further component of treatment. Implantable defibrillators and special pacemakers for cardiac resynchronization are well established; the utility of alternative devices (baroreflex modulation or cardiac contractility modulation) needs to be investigated in further studies. It was recently shown that the catheter-based treatment of secondary mitral regurgitation with a MitraClip improves the outcome of selected patients. CONCLUSION: The treatment of chronic systolic heart failure as recommended in the relevant guidelines, with drugs and implanted devices if indicated, can significantly improve the clinical outcome.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Guias de Prática Clínica como Assunto , Volume Sistólico , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(34): e21794, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846812

RESUMO

Patients with cardiovascular diseases frequently experience exertional dyspnea. However, the relationship between respiratory muscle strength including its fatigue and cardiovascular dysfunctions remains to be clarified.The maximal inspiratory pressure/maximal expiratory pressure (MIP/MEP) before and after cardiopulmonary exercise testing (CPX) in 44 patients with heart failure and ischemic heart disease were measured. Respiratory muscle fatigue was evaluated by calculating MIP (MIPpost/MIPpre) and MEP (MEPpost/MEPpre) changes.The mean MIPpre and MEPpre values were 67.5 ±â€Š29.0 and 61.6 ±â€Š23.8 cm H2O, respectively. After CPX, MIP decreased in 25 patients, and MEP decreased in 22 patients. We evaluated the correlation relationship between respiratory muscle function including respiratory muscle fatigue and exercise capacity evaluated by CPX such as peak VO2 and VE/VCO2 slope. Among MIP, MEP, change in MIP, and change in MEP, only the value of change in MIP had an association with the value of VE/VCO2 slope (R = -0.36, P = .017). In addition, multivariate analysis for determining factor of change in MIP revealed that the association between the change in MIP and eGFR was independent from other confounding parameters (beta, 0.40, P = .017). The patients were divided into 2 groups, with (MIP change < 0.9) and without respiratory muscle fatigue (MIP change > 0.9), and a significant difference in peak VO2 (14.2 ±â€Š3.4 [with fatigue] vs 17.4 ±â€Š4.7 [without fatigue] mL/kg/min; P = .020) was observed between the groups.Respiratory muscle fatigue demonstrated by the change of MIP before and after CPX significantly correlated with exercise capacity and renal function in patients with cardiovascular disease.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Fadiga Muscular , Isquemia Miocárdica/fisiopatologia , Músculos Respiratórios/fisiopatologia , Idoso , Exercício Físico/fisiologia , Teste de Esforço , Tolerância ao Exercício , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pressões Respiratórias Máximas , Pessoa de Meia-Idade
12.
PLoS Comput Biol ; 16(8): e1008074, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804929

RESUMO

Congestive heart failure is characterized by suppressed cardiac output and arterial filling pressure, leading to renal retention of salt and water, contributing to further volume overload. Mathematical modeling provides a means to investigate the integrated function and dysfunction of heart and kidney in heart failure. This study updates our previously reported integrated model of cardiac and renal functions to account for the fluid exchange between the blood and interstitium across the capillary membrane, allowing the simulation of edema. A state of heart failure with reduced ejection fraction (HF-rEF) was then produced by altering cardiac parameters reflecting cardiac injury and cardiovascular disease, including heart contractility, myocyte hypertrophy, arterial stiffness, and systemic resistance. After matching baseline characteristics of the SOLVD clinical study, parameters governing rates of cardiac remodeling were calibrated to describe the progression of cardiac hemodynamic variables observed over one year in the placebo arm of the SOLVD clinical study. The model was then validated by reproducing improvements in cardiac function in the enalapril arm of SOLVD. The model was then applied to prospectively predict the response to the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin, which has been shown to reduce heart failure events in HF-rEF patients in the recent DAPAHF clinical trial by incompletely understood mechanisms. The simulations predict that dapagliflozin slows cardiac remodeling by reducing preload on the heart, and relieves congestion by clearing interstitial fluid without excessively reducing blood volume. This provides a quantitative mechanistic explanation for the observed benefits of SGLT2i in HF-rEF. The model also provides a tool for further investigation of heart failure drug therapies.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Rim/fisiopatologia , Modelos Cardiovasculares , Volume Sistólico/fisiologia , Compostos Benzidrílicos/uso terapêutico , Cardiomegalia/fisiopatologia , Líquido Extracelular/fisiologia , Glucosídeos/uso terapêutico , Coração/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/fisiologia , Humanos , Miócitos Cardíacos/fisiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
13.
Ann Afr Med ; 19(3): 188-190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32820731

RESUMO

Introduction: Proportional Pulse Pressure (PPP) is a significant risk indicator in heart failure. PPP is a simple, inexpensive and easily measurable clinical index. This non-invasive test provides useful prognostic information for patients with heart failure with reduced ejection fraction (EF) particularly in those with an EF < 30% where lower proportional pulse pressure independently predicts mortality. Methods: A prospective observational study involving 150 patients with reduced ejection fraction was done. Detailed history, clinical examination and parameters like pulse pressure, proportional pulse pressure were evaluated and correlated with ejection fraction. Results: The mean age of the patients was 58.99 ± 11.03 years and the majority of the study participants (57.33 %) were between 45 and 65 years of age. The most common etiology of heart failure (HF) was coronary heart disease in this study (76%). Proportional Pulse pressure showed significant association with ejection fraction. The specificity for detecting heart failure was more for proportional pulse pressure and systolic blood pressure (95 % each). Conclusion: Proportional Pulse Pressure may help to identify HF patients who present with low cardiac output, low ejection fraction, and worse prognosis. Our current observations reinforce the importance of clinically based skills that must not be forgotten when managing HF.


Assuntos
Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença
14.
High Blood Press Cardiovasc Prev ; 27(5): 399-408, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32770527

RESUMO

INTRODUCTION: The association of patients with heart failure (HF) and preserved ejection fraction (HFpEF) and with type 2 diabetes mellitus (T2DM) is strong and related additionally to blood pressure (BP). AIMS: To analyze distinctive clinical profiles among patients with HFpEF both with and without T2DM. METHODS: The study was based on a Spanish National Registry (multicenter and prospective) of patients with HF (DICUMAP), that enrolled outpatients with HF who underwent an ambulatory BP monitoring (ABPM) and then were followed-up for 1 year. We categorized patients according to the presence/absence of T2DM then building different clusters based on K-medoids algorithm. RESULTS: 103 patients were included. T2DM was present in 44.7%. The patients with T2DM were grouped into two clusters and those without T2DM into three. All patients with T2DM had kidney disease and anemia. Among them, cluster 2 had higher systolic blood pressure and pulse pressure (PP) with a bad outcome (p = 0.03) regarding HF mortality and readmissions, influenced by eGFR (HR 0.93, 95% CI 0.97-0.87, p = 0.04), and hemoglobin (HR 0.65, 95% CI 0.71-0.63, p = 0.03). Among those without T2DM, cluster 3 had a pathological ABPM pattern with the highest PP, cluster 4 was slightly similar to cluster 2, and cluster 5 expressed a more benign pattern without differences on both, HF mortality and readmissions. CONCLUSIONS: Patients with HFpEF and T2DM expressed two different profiles depending on neurohormonal activation and arterial stiffness with prognostic implications. Patients without T2DM showed three profiles depending on ABPM pattern, kidney disease and PP without prognostic repercussion.


Assuntos
Pressão Sanguínea , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Anemia/mortalidade , Anemia/fisiopatologia , Monitorização Ambulatorial da Pressão Arterial , Análise por Conglomerados , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/terapia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Masculino , Readmissão do Paciente , Prognóstico , Sistema de Registros , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo
16.
Am Heart J ; 228: 47-56, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32798787

RESUMO

AIMS: To investigate the effect of the sodium-glucose co-transporter-2 inhibitor empagliflozin on N-terminal pro-b-type natriuretic peptide (NT-proBNP) in patients with heart failure (HF) and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Empire HF was an investigator-initiated, multi-center, double-blinded, placebo-controlled, randomized trial. Patients with mildly symptomatic HFrEF, mean (standard deviation (SD)) age 64 (11) years, 85% male, and mean left ventricular ejection fraction 29% (8), on recommended HF therapy were assigned to receive either empagliflozin 10 mg once daily or placebo for 12 weeks. The primary endpoint was the between-group difference in the change of NT-proBNP from baseline to 12 weeks. In total, 95 patients were assigned to empagliflozin and 95 to placebo. No significant difference in the change of NT-proBNP with empagliflozin versus placebo was observed [Empagliflozin: baseline, median (interquartile range (IQR)) 582 (304-1020) pg/mL, 12 weeks, 478 (281-961) pg/mL; Placebo: baseline, 605 (322-1070) pg/mL, 12 weeks, 520 (267-1075) pg/mL, adjusted ratio of change empagliflozin/placebo 0.98; 95% confidence interval (CI) 0.82-1.11, P = 0.7]. Further, no significant difference was observed in accelerometer-measured daily activity level [adjusted mean difference of change, empagliflozin versus placebo, -26.0 accelerometer counts; 95% CI -88.0 to 36.0, P = 0.4] or Kansas City Cardiomyopathy Questionnaire Overall Summary Score [adjusted mean difference of change, empagliflozin versus placebo 0.8; 95% CI -2.3 to 3.9, P = 0.6]. CONCLUSION: In low-risk patients with HFrEF with mild symptoms and on recommended HF therapy, empagliflozin did not change NT-proBNP after 12 weeks. Further, no change in daily activity level or health status was observed.


Assuntos
Acelerometria/métodos , Atividades Cotidianas , Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Disfunção Ventricular Esquerda/diagnóstico , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Método Duplo-Cego , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Volume Sistólico
17.
PLoS One ; 15(8): e0231234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804947

RESUMO

Cardiometabolic syndrome has become a global health issue. Heart failure is a common comorbidity of cardiometabolic syndrome. Successful drug development to prevent cardiometabolic syndrome and associated comorbidities requires preclinical models predictive of human conditions. To characterize the heart failure component of cardiometabolic syndrome, cardiometabolic, metabolic, and renal biomarkers were evaluated in lean and obese ZSF1 19- to 32-week-old male rats. Histopathological assessment of kidneys and hearts was performed. Cardiac function, exercise capacity, and left ventricular gene expression were also analyzed. Obese ZSF1 rats exhibited multiple features of human cardiometabolic syndrome by pathological changes in systemic renal, metabolic, and cardiovascular disease circulating biomarkers. Hemodynamic assessment, echocardiography, and decreased exercise capacity confirmed heart failure with preserved ejection fraction. RNA-seq results demonstrated changes in left ventricular gene expression associated with fatty acid and branched chain amino acid metabolism, cardiomyopathy, cardiac hypertrophy, and heart failure. Twelve weeks of growth differentiation factor 15 (GDF15) treatment significantly decreased body weight, food intake, blood glucose, and triglycerides and improved exercise capacity in obese ZSF1 males. Systemic cardiovascular injury markers were significantly lower in GDF15-treated obese ZSF1 rats. Obese ZSF1 male rats represent a preclinical model for human cardiometabolic syndrome with established heart failure with preserved ejection fraction. GDF15 treatment mediated dietary response and demonstrated a cardioprotective effect in obese ZSF1 rats.


Assuntos
Fator 15 de Diferenciação de Crescimento/metabolismo , Fator 15 de Diferenciação de Crescimento/farmacologia , Síndrome Metabólica/metabolismo , Animais , Biomarcadores/metabolismo , Coração/fisiologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Rim/metabolismo , Masculino , Síndrome Metabólica/complicações , Miocárdio/metabolismo , Obesidade/complicações , Ratos , Ratos Endogâmicos , Ratos Zucker , Volume Sistólico/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia
18.
Int Heart J ; 61(4): 848-850, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32728003

RESUMO

Right ventricular (RV) dysfunction may occur after cardiac surgery and it is not rare after corrective repair of tetralogy of Fallot (TOF). If traditional treatments with volume management, infusion of inotropic agents, and use of pulmonary vasodilators cannot stabilize the patient, extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD) will be considered as the last resort. Here, we report a young infant patient with RV failure after corrective repair of TOF and without closure of an atrial septal defect (ASD), who was rescued by veno-venous (VV) -ECMO.


Assuntos
Septo Interatrial/cirurgia , Oxigenação por Membrana Extracorpórea/métodos , Tetralogia de Fallot/cirurgia , Disfunção Ventricular Direita/terapia , Assistência ao Convalescente , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ecocardiografia/métodos , Insuficiência Cardíaca/fisiopatologia , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/fisiopatologia , Comunicação Interatrial/cirurgia , Coração Auxiliar , Humanos , Lactente , Masculino , Dispositivo para Oclusão Septal/normas , Tetralogia de Fallot/diagnóstico por imagem , Resultado do Tratamento
19.
Cardiol Young ; 30(9): 1346-1349, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32600496

RESUMO

We present our recent experience with a 6-month-old infant with a personal history of short bowel syndrome that presented with fever, cyanosis, and cardiogenic shock secondary to severe pulmonary hypertension and right ventricular failure without pulmonary thromboembolism. He did not present signs of toxin-mediated disease or Kawasaki disease. He was finally diagnosed with SARS-CoV-2 infection. If this presentation is confirmed in future research, the severe cardiovascular impairment in children with COVID-19 could be also attributable to the primary pulmonary infection, not only to a multisystem inflammatory syndrome but also in children without heart disease.


Assuntos
Angiografia por Tomografia Computadorizada , Infecções por Coronavirus , Insuficiência Cardíaca , Hipertensão Pulmonar , Pandemias , Pneumonia Viral , Choque Cardiogênico , Síndrome de Resposta Inflamatória Sistêmica , Betacoronavirus/isolamento & purificação , Angiografia por Tomografia Computadorizada/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Ecocardiografia/métodos , Eletrocardiografia/métodos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Lactente , Masculino , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Radiografia Torácica , Respiração Artificial/métodos , Índice de Gravidade de Doença , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Resultado do Tratamento
20.
JACC Heart Fail ; 8(10): 789-799, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32641226

RESUMO

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients ≥18 years of age with advanced HF, defined as an EF ≤35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/ml), and ≥1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736).


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Tetrazóis/uso terapêutico , Betacoronavirus , Cardiotônicos/uso terapêutico , Infecções por Coronavirus , Relação Dose-Resposta a Droga , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Coração Auxiliar , Hospitalização/estatística & dados numéricos , Humanos , Hipotensão/induzido quimicamente , Peptídeo Natriurético Encefálico/metabolismo , Pandemias , Fragmentos de Peptídeos/metabolismo , Pneumonia Viral , Volume Sistólico
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