Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.398
Filtrar
1.
Am J Chin Med ; 48(6): 1369-1383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32933311

RESUMO

Age-related myocardial dysfunction is a very large healthcare burden. Here, we aimed to investigate whether ginsenoside Rb1 (Rb1) improves age-related myocardial dysfunction and to identify the relevant molecular mechanism. Young mice and aged mice were injected with Rb1 or vehicle for 3 months. Then, their cardiac function was inspected by transthoracic echocardiography. Serum and myocardium tissue were collected from all mice for histological or molecular expression analyses, including aging-related proteins, markers relevant to fibrosis and inflammation, and markers indicating the activation of the nuclear factor-kappa B (NF-[Formula: see text]B) pathway. Compared with the control condition, Rb1 treatment significantly increased the ejection fraction percentage and significantly decreased the internal diameter and volume of the left ventricle at the end-systolic and end-diastolic phases in aged mice. Rb1 treatment reduced collagen deposition and collagen I, collagen III, and transforming growth factor-[Formula: see text]1 protein expression levels in aged hearts. Rb1 also decreased the aging-induced myocardial inflammatory response, as measured by serum or myocardial interleukin-6 and tumor necrosis factor-[Formula: see text] levels. Furthermore, Rb1 treatment in aged mice increased cytoplasmic NF-[Formula: see text]B but decreased nuclear NF-[Formula: see text]B, which indicated the suppression of the NF-[Formula: see text]B signaling pathway by regulating the translocation of NF-[Formula: see text]B. Rb1 could alleviate aging-related myocardial dysfunction by suppressing fibrosis and inflammation, which is potentially associated with regulation of the NF-[Formula: see text]B signaling pathway.


Assuntos
Envelhecimento , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , NF-kappa B/genética , NF-kappa B/metabolismo , Fitoterapia , Animais , Anti-Inflamatórios , Colágeno/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Volume Sistólico/efeitos dos fármacos
2.
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
3.
Cochrane Database Syst Rev ; 8: CD004370, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32835416

RESUMO

BACKGROUND: This is an update of a previous review. Case reports and case series have described dramatic responses to intravenous immunoglobulin (IVIG) in people with presumed viral myocarditis, and its administration has become commonplace. OBJECTIVES: The primary objective of this review was to compare event-free (death, requirement for a cardiac transplant, or placement of a left ventricular assist device) or overall (death) survival of adults and children with presumed viral myocarditis treated with IVIG versus those who did not receive IVIG. A secondary objective was to determine if a group of patients with presumed viral myocarditis could be identified (on the basis of age, duration of symptoms, acuity of onset of symptoms, cardiac function at presentation, virological results, or the presence or absence of histological evidence of acute myocarditis on cardiac biopsy in patients in whom a biopsy was performed) who would be the most likely to benefit from IVIG. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, DARE, CINAHL, Web of Science Core Collection, and LILACS in July 2019, and two trial registries in November 2019. We contacted authors of trials and checked reference lists of relevant papers. We applied no language restrictions. SELECTION CRITERIA: We included studies if (1) participants had a clinical diagnosis of acute myocarditis with a left ventricular ejection fraction (LVEF) ≤ 0.45, left ventricular end-diastolic diameter (LVEDD) > 2 standard deviations (SDs) above the norm, or a left ventricular shortening fraction (LVSF) > 2 SDs below the mean, with duration of cardiac symptoms < 6 months; (2) participants had no evidence of non-infectious or bacterial cardiac disease; and (3) participants were randomly assigned to receive at least 1 g/kg of IVIG versus no IVIG or placebo. We excluded studies if (1) participants had received immunosuppression before outcome assessment; or (2) onset of myocarditis was reported to have occurred < 6 months postpartum. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and extracted data. We assessed risk of bias with the Cochrane 'Risk of bias' tool. We conducted meta-analysis for two outcomes (overall survival and improvement in LVEF) with two adult trials. Other meta-analyses were not possible because only three relevant trials were included, and researchers analysed markedly different populations and used different outcome measures. MAIN RESULTS: In this update we added two trials to the two previously included trials. A quasi-randomised trial was previously included due to a paucity of evidence from randomised trials; however, with the addition of two new randomised trials, it was removed from this update. For two adult trials, the overall risk of bias was unclear with very low-certainty evidence for all outcomes. The first trial studied 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The effect on event-free survival between groups was uncertain (risk ratio (RR) of any event 1.76, 95% confidence interval (CI) 0.48 to 6.40). The second trial studied 41 adults with acute myocarditis randomised to either high-dose IVIG (1 to 2 g/kg over two days) or no treatment. The IVIG group reported greater survival time after 60 days (no raw data, P < 0.01), but the evidence is uncertain. We pooled the reported number of deaths in both trials, with no evidence of a difference between groups (RR 0.91, 95% CI 0.23 to 3.62, I2 = 31%, very low-certainty evidence). The evidence on the effect of IVIG treatment on LVEF (pooled mean difference (MD) -0.01, 95% CI -0.06 to 0.05) after 12 months and an unknown time frame is uncertain. The results for functional capacity, assessed by peak oxygen consumption at 12 months, were uncertain (MD -0.80, 95% CI -4.57 to 2.97). The results for infusion-related side effects were also uncertain due to a very large CI (RR 20.29, 95% CI 1.25 to 329.93). Lastly, there was uncertain evidence addressing failure to attain complete recovery (RR 0.46, 95% CI 0.19 to 1.14).  Evidence for improvement in LVEDD, left ventricular shortening fraction, and hospitalisation status in adults was not reported.  In the single included paediatric trial, the overall risk of bias was low with very low-certainty evidence for all outcomes. The trial included 86 children in Egypt presenting with acute myocarditis. Children were randomly assigned to 1 g/kg IVIG daily for two consecutive days or placebo followed by echocardiography one and six months post randomisation for recording of LVEDD and LVSF. The evidence for overall survival after six months was uncertain (risk of death RR 0.48, 95% CI 0.20 to 1.15). The evidence was also uncertain for improvement in LVEDD and LVSF after six months (LVEDD MD -4.00, 95% CI -9.52 to 1.52; LVSF no raw data).  Evidence for improvement in LVEF, functional capacity, side effects, complete recovery, and hospitalisation status in children was not reported.  AUTHORS' CONCLUSIONS: Evidence from two trials of very low certainty and with unclear risk of bias provides contradictory evidence on the use of IVIG in the treatment of adults with presumed viral myocarditis. One trial reported that use of IVIG results in longer survival time after 60 days, whilst the other trial found that IVIG does not provide an appreciable benefit. The evidence of a difference in event-free or overall survival, LVEDD, or LVSF is of very low certainty in a single paediatric trial with a low risk of bias. Until higher-quality studies with low risk of bias and larger sample sizes have demonstrated benefit in a particular group of patients, the evidence for treatment with IVIG for presumed viral myocarditis is uncertain. Further studies of the pathophysiology of myocarditis would lead to improved diagnostic criteria, which would facilitate future research.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Miocardite/terapia , Viroses/terapia , Doença Aguda , Adulto , Viés , Criança , Humanos , Miocardite/mortalidade , Miocardite/virologia , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico/efeitos dos fármacos , Viroses/mortalidade
5.
JAMA ; 324(3): 249-258, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32692386

RESUMO

Importance: Thyroid hormones play a key role in modulating myocardial contractility. Subclinical hypothyroidism in patients with acute myocardial infarction is associated with poor prognosis. Objective: To evaluate the effect of levothyroxine treatment on left ventricular function in patients with acute myocardial infarction and subclinical hypothyroidism. Design, Setting, and Participants: A double-blind, randomized clinical trial conducted in 6 hospitals in the United Kingdom. Patients with acute myocardial infarction including ST-segment elevation and non-ST-segment elevation were recruited between February 2015 and December 2016, with the last participant being followed up in December 2017. Interventions: Levothyroxine treatment (n = 46) commencing at 25 µg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L or identical placebo (n = 49), both provided in capsule form, once daily for 52 weeks. Main Outcomes and Measures: The primary outcome measure was left ventricular ejection fraction at 52 weeks, assessed by magnetic resonance imaging, adjusted for age, sex, type of acute myocardial infarction, affected coronary artery territory, and baseline left ventricular ejection fraction. Secondary measures were left ventricular volumes, infarct size (assessed in a subgroup [n = 60]), adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression. Results: Among the 95 participants randomized, the mean (SD) age was 63.5 (9.5) years, 72 (76.6%) were men, and 65 (69.1%) had ST-segment elevation myocardial infarction. The median serum thyrotropin level was 5.7 mU/L (interquartile range, 4.8-7.3 mU/L) and the mean (SD) free thyroxine level was 1.14 (0.16) ng/dL. The primary outcome measurements at 52 weeks were available in 85 patients (89.5%). The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8%, respectively, in the levothyroxine group compared with 54.0% and 56.1%, respectively, in the placebo group (adjusted difference in groups, 0.76% [95% CI, -0.93% to 2.46%]; P = .37). None of the 6 secondary outcomes showed a significant difference between the levothyroxine and placebo treatment groups. There were 15 (33.3%) and 18 (36.7%) cardiovascular adverse events in the levothyroxine and placebo groups, respectively. Conclusions and Relevance: In this preliminary study involving patients with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction. Trial Registration: isrctn.org Identifier: http://www.isrctn.com/ISRCTN52505169.


Assuntos
Hipotireoidismo/complicações , Infarto do Miocárdio sem Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Volume Sistólico/efeitos dos fármacos , Tiroxina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Depressão , Método Duplo-Cego , Feminino , Nível de Saúde , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/patologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Tamanho da Amostra , Tireotropina/sangue , Tiroxina/efeitos adversos , Fatores de Tempo , Reino Unido
6.
Medicine (Baltimore) ; 99(28): e20792, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664071

RESUMO

BACKGROUND: Myocardial ischemia reperfusion injury (MIRI) is 1 of the leading causes of disability and mortality worldwide in the cardiovascular diseases. Acupuncture has been widely applied in the treatment and prevention of cardiovascular diseases in recent years. This systematic review protocol aims to provide the methods for evaluating the efficacy of Neiguan (PC6)-based acupuncture pretreatment in animal models of MIRI. METHODS AND ANALYSIS: The electronic databases of PubMed, Embase, Cochrane Library, as well as the Chinese databases such as China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, China Biology Medicine Database and WanFang Database will be searched from inception to November 2019. The outcome measures were myocardial infarct size, the level of ST-segment elevation, left ventricular ejection fraction, shortening fraction, arrhythmia score, cardiac enzymes, and cardiac troponin. Study inclusion, data extraction and quality assessment will be performed independently by 2 reviewers. RevMan 5.3 software will be used for the data synthesis and the quality of each study will be assessed independently by using the Collaborative Approach To Meta-Analysis And Review Of Animal Data From Experimental Studies checklist with minor modification. RESULTS: This review will provide a high-quality synthesis of Neiguan (PC6)-based acupuncture pretreatment for MIRI in animal models CONCLUSIONS:: This systematic review will provide conclusive evidence for whether Neiguan (PC6)-based acupuncture pretreatment is an effective intervention in animal models of MIRI. TRIAL REGISTRATION NUMBER: PROSPERO CRD42020175144.


Assuntos
Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Terapia por Acupuntura/métodos , Animais , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/terapia , China/epidemiologia , Estudos de Avaliação como Assunto , Modelos Animais , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
7.
Cardiovasc Ther ; 2020: 7262474, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695229

RESUMO

Objectives: Several beneficial effects of resveratrol have already been published. This study evaluated the effect of resveratrol on the hemorheological parameters in patients with heart failure with reduced ejection fraction. Methods: In our double-blind, placebo-controlled human clinical trial, we enrolled 60 outpatients with heart failure. Patients were randomized into two groups: receiving either 100 mg resveratrol capsule daily or placebo for 3 months. Hematocrit was determined by microhematocrit centrifuge. Plasma and whole blood viscosity was evaluated by capillary viscometer. Erythrocyte aggregation was measured by both LORCA and Myrenne aggregometers. LORCA ektacytometer was used for measuring erythrocyte deformability. Exercise capacity was assessed by a 6-minute walk test. Results: Resveratrol treatment did not have any significant effect on hematocrit and viscosity. The erythrocyte deformability also remained unchanged. However, significant improvement of red blood cell aggregation was observed in the resveratrol group compared to baseline after 3 months. Furthermore, positive correlation was found between the exercise capacity and the hemorheological properties (Hct, WBV, and RBC aggregation and deformability) as well. Conclusion: These findings indicate that resveratrol can significantly reduce red blood cell aggregation, which may positively influence microcirculation, which may contribute to the improvement of tissue perfusion and oxygen supply in heart failure.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Agregação Eritrocítica/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Resveratrol/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Fármacos Cardiovasculares/efeitos adversos , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Resveratrol/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
8.
Medicine (Baltimore) ; 99(23): e20402, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501985

RESUMO

Tirofiban is widely used in patients with acute ST elevation myocardial infarction (STEMI) underwent percutaneous coronary intervention (PCI). This drug can efficiently improve myocardial perfusion and cardiac function, but its dose still remains controversial. We here investigated the effects of different dose of tirofiban on myocardial reperfusion and heart function in patients with STEMI. A total of 312 STEMI patients who underwent PCI in our hospital from March 2017 to March 2018 were enrolled and randomly divided into control group (75 cases, 0 µg/kg), low-dose group (79 cases, 5 µg/kg), medium-dose group (81 cases, 10 µg/kg) and high-dose group (77 cases, 20 µg/kg). The infarction-targeted artery flow grade evaluated by thrombolysis in myocardial infarction (TIMI), corrected TIMI frame count (CTFC) and sum-ST-segment resolution were recorded. At Day 7 and Day 30 after PCI, the left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter, left ventricular end systolic diameter, major adverse cardiovascular events and the hemorrhage and thrombocytopenia were also evaluated. After PCI, the rate of TIMI grade 3, CTFC and incidence of sum-ST-segment resolution > 50% of high-dose group were significantly higher than those of control group, low-dose group and medium-dose group (P < .05), and the CTFC of medium -dose group were significantly higher than that of control group, low-dose group (P < .05). Moreover, the LVEF, left ventricular end diastolic diameter and left ventricular end systolic diameter of high-dose group were significantly improved than those of other groups, and the LVEF of medium-dose group was significantly superior to that of low-dose group (P < .05). However, the incidence of major adverse cardiac events in high-dose group was significantly decreased, while the hemorrhage and incidence of thrombocytopenia of high-dose group were significantly higher than those of other 3 groups (P < .05). The tirofiban can effectively alleviate the myocardial ischemia-reperfusion injury and promote the recovery of cardiac function in STEMI patients underwent PCI. Although the high-dose can enhance the clinical effects, it also increased the hemorrhagic risk. Therefore, the rational dosage application of tirofiban become much indispensable in view of patient's conditions and hemorrhagic risk, and a medium dose of 10 µg/kg may be appropriate for patients without high hemorrhagic risk.


Assuntos
Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Tirofibana/administração & dosagem , Tirofibana/normas , Idoso , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/normas , Intervenção Coronária Percutânea/estatística & dados numéricos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/normas , Inibidores da Agregação de Plaquetas/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Volume Sistólico/efeitos dos fármacos , Tirofibana/uso terapêutico , Resultado do Tratamento
9.
Zhonghua Nei Ke Za Zhi ; 59(6): 433-438, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32486583

RESUMO

Objective: To investigate the efficacy and safety of different dosage regimens of levosimendan in elderly patients with severe heart failure. Methods: Thirty-two patients 75 years or older were randomly divided into a loading dose group (16 cases) in which levosimendan was maintained at 0.1 µg·kg(-1)·min(-1) for 24 h after loaded with 6 µg/kg, and a maintenance dose group (16 cases) with same schedule without loading dose. The amino-terminal brain natriuretic peptide (NT-proBNP) before and after treatment was detected. Left ventricular ejection fraction (LVEF), stroke volume (SV), stroke volume index (SVI) by echocardiograph were monitored. Adverse events, the length of stay in ICU and 28-day mortality were recorded. Results: The NT-proBNP level in loading group after treatment was 1 950 (922,6 481)ng/L, which was improved than that before treatment [4 018(2 716,9 637)ng/L, P<0.05]. The result was similar in maintenance group [1 390 (599,3 297)ng/L vs. 4 576 (2 681,10 682)ng/L, P<0.05]. LVEF in loading group before and after treatment was (39.4±8.8) % vs. (48.9±9.2) % respectively, while in maintenance group it was (40.4±8.8) % vs. (48.7±12.0) % (both P<0.05). SV were also improved after treatment in both groups compared with baseline levels (P<0.05). NT-proBNP started to decline on day 3 in the loading group, while on day 7 in the maintenance group. SVI recovered on day 14 in the loading group [ (29.4±6.5) ml/m(2) vs. (27.3±6.7) ml/m(2),P<0.05], while it did not change much in the maintenance group. There was no significant differences as to the length of stay in ICU [ (11.1±4.4) d in loading group vs. (9.6±3.5) d in maintenance group] and 28-day mortality rates were comparable (2/16 in loading group vs. 1/16 in maintenance group) . The adverse events were 7 vs. 2 cases in loading group and maintenance group respectively, which were mild and all alleviated. Conclusion: The application of levosimendan only with maintenance dose improves cardiac function in very elderly patients with severe heart failure. Adverse events are mild and manageable.


Assuntos
Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Simendana/uso terapêutico , Vasodilatadores/uso terapêutico , Idoso , Ecocardiografia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Função Ventricular Esquerda
11.
Cardiovasc Drugs Ther ; 34(3): 419-436, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32350793

RESUMO

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new drug class designed to treat patients with type 2 diabetes (T2D). However, cardiovascular outcome trials showed that SGLT2i also offer protection against heart failure (HF)-related events and cardiovascular mortality. These benefits appear to be independent of glycaemic control and have recently been demonstrated in the HF population with reduced ejection fraction (HFrEF), with or without T2D. This comprehensive, evidence-based review focuses on the published studies concerning HF outcomes with SGLT2i, discussing issues that may underlie the different results, along with the impact of these new drugs in clinical practice. The potential translational mechanisms behind SGLT2i cardio-renal benefits and the information that ongoing studies may add to the already existing body of evidence are also reviewed. Finally, we focus on practical management issues regarding SGLT2i use in association with other T2D and HFrEF common pharmacological therapies. Safety considerations are also highlighted. Considering the paradigm shift in T2D management, from a focus on glycaemic control to a broader approach on cardiovascular protection and event reduction, including the potential for wide SGLT2i implementation in HF patients, with or without T2D, we are facing a promising time for major changes in the global management of cardiovascular disease.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Animais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
12.
Lancet ; 396(10244): 121-128, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-32446323

RESUMO

BACKGROUND: Three drug classes (mineralocorticoid receptor antagonists [MRAs], angiotensin receptor-neprilysin inhibitors [ARNIs], and sodium/glucose cotransporter 2 [SGLT2] inhibitors) reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF) beyond conventional therapy consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and ß blockers. Each class was previously studied with different background therapies and the expected treatment benefits with their combined use are not known. Here, we used data from three previously reported randomised controlled trials to estimate lifetime gains in event-free survival and overall survival with comprehensive therapy versus conventional therapy in patients with chronic HFrEF. METHODS: In this cross-trial analysis, we estimated treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, ß blocker, MRA, and SGLT2 inhibitor) versus conventional therapy (ACE inhibitor or ARB and ß blocker) in patients with chronic HFrEF by making indirect comparisons of three pivotal trials, EMPHASIS-HF (n=2737), PARADIGM-HF (n=8399), and DAPA-HF (n=4744). Our primary endpoint was a composite of cardiovascular death or first hospital admission for heart failure; we also assessed these endpoints individually and assessed all-cause mortality. Assuming these relative treatment effects are consistent over time, we then projected incremental long-term gains in event-free survival and overall survival with comprehensive disease-modifying therapy in the control group of the EMPHASIS-HF trial (ACE inhibitor or ARB and ß blocker). FINDINGS: The hazard ratio (HR) for the imputed aggregate treatment effects of comprehensive disease-modifying therapy versus conventional therapy on the primary endpoint of cardiovascular death or hospital admission for heart failure was 0·38 (95% CI 0·30-0·47). HRs were also favourable for cardiovascular death alone (HR 0·50 [95% CI 0·37-0·67]), hospital admission for heart failure alone (0·32 [0·24-0·43]), and all-cause mortality (0·53 [0·40-0·70]). Treatment with comprehensive disease-modifying pharmacological therapy was estimated to afford 2·7 additional years (for an 80-year-old) to 8·3 additional years (for a 55-year-old) free from cardiovascular death or first hospital admission for heart failure and 1·4 additional years (for an 80-year-old) to 6·3 additional years (for a 55-year-old) of survival compared with conventional therapy. INTERPRETATION: Among patients with HFrEF, the anticipated aggregate treatment effects of early comprehensive disease-modifying pharmacological therapy are substantial and support the combination use of an ARNI, ß blocker, MRA, and SGLT2 inhibitor as a new therapeutic standard. FUNDING: None.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Volume Sistólico/efeitos dos fármacos , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Morte , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Intervalo Livre de Progressão , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/fisiologia , Resultado do Tratamento
13.
J Cardiothorac Surg ; 15(1): 108, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448319

RESUMO

BACKGROUND: Patients with moderate-severe systolic dysfunction undergoing coronary artery bypass graft have a higher incidence of postoperative low cardiac output. Preconditioning with levosimendan may be a useful strategy to prevent this complication. In this context, design cost-effective strategies like preconditioning with levosimendan may become necessary. METHODS: In a sequential assignment of patients with Left Ventricle Ejection Fraction less than 40%, two strategies were compared in terms of cost-effectiveness: standard care (n = 41) versus preconditioning with Levosimendan (n = 13). The adverse effects studied included: postoperative new-onset atrial fibrillation, low cardiac output, renal failure and prolonged mechanical ventilation. The costs were evaluated using deterministic and probabilistic sensitivity analysis, and Monte Carlo simulations were performed. RESULTS: Preconditioning with levosimendan in moderate to severe systolic dysfunction (Left Ventricle Ejection Fraction < 40%), was associated with a lower incidence of postoperative low cardiac output in elective coronary artery bypass graft surgery 2(15.4%) vs 25(61%) (P < 0.01) and lesser intensive care unit length of stay 2(1-4) vs 4(3-6) days (P = 0.03). Average cost on levosimendan group was 14,792€ while the average cost per patient without levosimendan was 17,007€. Patients with no complications represented 53.8% of the total in the levosimendan arm, as compared to 31.7% in the non-levosimendan arm. In all Montecarlo simulations for sensitivity analysis, use of levosimendan was less expensive and more effective. CONCLUSIONS: Preconditioning with levosimendan, is a cost-effective strategy preventing postoperative low cardiac output in patients with moderate-severe left ventricular systolic dysfunction undergoing elective coronary artery bypass graft surgery.


Assuntos
Baixo Débito Cardíaco/prevenção & controle , Ponte de Artéria Coronária/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Simendana/farmacologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Baixo Débito Cardíaco/epidemiologia , Baixo Débito Cardíaco/etiologia , Cardiotônicos/farmacologia , Ponte de Artéria Coronária/economia , Doença da Artéria Coronariana/cirurgia , Análise Custo-Benefício , Feminino , Humanos , Incidência , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Espanha/epidemiologia , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
14.
Adv Exp Med Biol ; 1177: 269-295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32246448

RESUMO

Heart failure (HF) is defined as a clinical syndrome resulting from structural or functional impairment of ventricular fillings or ejections of blood. Currently, HF is divided into three groups which include HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF) and HF with midrange EF (HFmrEF). Even though major advances have been made in treating HFrEF during the past decades, heart failure is a fatal disease. In this review, we briefly summarize the current advances in pharmaceutical managements for heart failure, which includes drugs used in acute heart failure as well as those that prevent heart failure progression, in each category major clinical trials are also described. In addition, information about some of potential new drugs are also mentioned. Traditional Chinese medicine also shows its potential in treating HF, and we are still lack of medicine to treat HFpEF.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Progressão da Doença , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologia
15.
Medicine (Baltimore) ; 99(14): e19526, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243368

RESUMO

BACKGROUND: Danhong injection (DHI) has been widely in the treatment of chronic heart failure (CHF) in China; however, there is not enough clinical evidence DHI for treating CHF. METHODS: Two researchers will search literatures of DHI for CHF in databases. Extracted data are analyzed with Review Manager 5.3 software. The selected studies should be conducted quality evaluation, forest plots and funnel plots will be run by RevMan5.3. RESULTS: This systematic review validates the clinical efficacy and safety of DHI in the treatment of CHF through the analysis of New York Heart Association functional classification, left ventricular ejection fraction, left ventricular end-diastolic dimension, cardiac output, brain natriuretic peptide, adverse events. CONCLUSIONS: This systematic review will be provided a rational clinical evidence to evaluate the effectiveness and safety of DHI for the treatment of CHF. REGISTRATION NUMBER: PROSPERO CRD42019144686.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Doença Crônica , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
16.
Circ Heart Fail ; 13(4): e006645, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32248695

RESUMO

BACKGROUND: In PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-pro BNP in Patients Stabilized From an Acute Heart Failure Episode), the in-hospital initiation of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure (ADHF) was well-tolerated and led to improved outcomes. We aim to determine the representativeness of the PIONEER-HF trial among patients hospitalized for ADHF using real-world data. METHODS: The study population was derived from all patients discharged alive for ADHF in the Get With The Guidelines-HF registry from 2006 to 2018 with HF with reduced ejection fraction (HFrEF; all HFrEF with ADHF). We then determined the proportion of patients meeting PIONEER-HF eligibility criteria (PIONEER-HF eligible) and those meeting a set of limited eligibility criteria (actionable cohort). Rates of HF readmissions and all-cause mortality were then compared between the all HFrEF with ADHF, PIONEER-HF eligible, and actionable cohorts using linked Medicare claims data. RESULTS: A total of 99 767 patients with HFrEF in Get With The Guidelines-HF were hospitalized for ADHF. PIONEER-HF inclusion criteria were met by 71 633 (71.8%) patients, and both inclusion and exclusion criteria were met by 20 704 (20.8%) patients. Further, 68 739 (68.9%) patients met the criteria for the actionable cohort. Among the Centers for Medicare and Medicaid-linked patients, the HF rehospitalization rate at 1 year was 35.1% (95% CI, 34.5-35.8) for all HFrEF with ADHF patients, 32.6% (95% CI, 31.3-33.9) for the PIONEER-HF eligible cohort, and 33.1% (95% CI, 32.3-33.9) for the actionable cohort. The 1-year all-cause mortality was 36.7% (95% CI, 36.1-7.4) for all HFrEF with ADHF patients, 31.6% (95% CI, 30.3-32.9) for the PIONEER-HF eligible cohort, and 32.2% (95% CI, 31.4-33.0) for the actionable cohort. CONCLUSIONS: Patient characteristics and clinical outcomes for patients eligible for PIONEER-HF only modestly differ when compared with those encountered in routine practice, suggesting that the in-hospital initiation of sacubitril/valsartan should be routinely considered for patients with HFrEF hospitalized for ADHF.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Admissão do Paciente , Inibidores de Proteases/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Tetrazóis/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Biomarcadores/sangue , Tomada de Decisão Clínica , Definição da Elegibilidade , Medicina Baseada em Evidências , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Neprilisina/antagonistas & inibidores , Seleção de Pacientes , Fragmentos de Peptídeos/sangue , Inibidores de Proteases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Sistema de Registros , Fatores de Risco , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
17.
Am J Cardiol ; 125(12): 1906-1912, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32331711

RESUMO

To determine the impact of radiation therapy (XRT) in addition to trastuzumab (TZB) adjuvant chemotherapy for HER2+ breast cancer on left ventricular systolic function, we assessed demographics, oncologic treatment history including XRT exposure, and serial measurements of left ventricular ejection fraction (LVEF) in 135 consecutively identified women receiving TZB for treatment of adjuvant breast cancer. Longitudinal mixed effects models were fit to identify baseline to treatment changes in LVEF among those receiving TZB with or without concomitant anthracycline or XRT. Women averaged 53 ± 3 years in age, 77% were white, 62% patients had 1 or more cardiovascular risk factors at baseline, and mean duration of TZB was 11 ± 5 months. Seventy-seven women were treated with XRT and received between 4000 and 5500 cGy of radiation. The LVEF declined by an average of 3.4% after 1 year for those in the study. Relative to baseline upon completion of adjuvant TZB, LVEF remained reduced for those receiving anthracycline with or without XRT (p=0.002 for both), or XRT alone (p=0.002), but not in those without these therapies. Amongst patients treated only with XRT and TZB, LVEF declined 3.1% on average in those with left-sided disease and 6.9% on average in those with right-sided disease (p= 0.06, p= 0.008 respectively). Among women receiving TZB for adjuvant treatment of HER-2 positive breast cancer, the administration of XRT, anthracycline, or the combination of the 2 is associated with a persistent post-treatment as opposed to a temporary treatment related decline in LVEF.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Doenças Cardiovasculares/etiologia , Volume Sistólico , Trastuzumab/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2 , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/efeitos da radiação
18.
Am J Clin Oncol ; 43(7): 510-516, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32304433

RESUMO

BACKGROUND: Trastuzumab improves therapeutic outcomes among patients with human epidermal growth factor receptor 2-positive breast cancer (BC). However, it is associated with a risk of treatment-induced cardiotoxicity. The aims of this study were to determine the frequency of trastuzumab-induced cardiotoxicity (TIC) in Tunisian patients, to study the effects of trastuzumab on cardiac biomarkers and echocardiographic parameters using the speckle tracking technique and to identify risk factors of occurrence of TIC. PATIENTS AND METHODS: Fifty women with newly diagnosed human epidermal growth factor receptor 2-positive BC treated with or without anthracycline followed by taxane and trastuzumab were enrolled, from November 2016 to December 2018, to be evaluated every 3 months during trastuzumab treatment (total of 15 mo) using echocardiograms and blood samples. Left ventricular ejection fraction (LVEF) and peak systolic left ventricular longitudinal myocardial strain were calculated. Ultrasensitive troponin I (TNI) and N-terminal pro-B-type natriuretic peptide (NT pro-BNP) were also measured. RESULTS: LVEF decreased from 62±3.12% to 59±3.3% (P=0.005) over 15 months. Seven patients (14%) developed cardiotoxicity, as defined by the European Society of Cardiology; of these patients, 2 (4%) had symptoms of heart failure. Hypertension, left ventricular longitudinal myocardial strain, Log TNI, and NT pro-BNP measured at the completion of anthracyclines were significantly correlated to TIC occurrence. At multivariate analysis, the degree of LVEF decline was the only independent factor correlated to TIC (hazard ratio=2.4; 95% confidence interval=1.2-6.03; P=0.049). This TIC was reversible in 86% of cases. CONCLUSION: In patients with BC treated with trastuzumab, in addition to the evaluation of the LVEF, systolic longitudinal strain, TNI, and NT pro-BNP measured at the completion of anthracyclines are useful in the prediction of subsequent TIC.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade , Trastuzumab/efeitos adversos , Adulto , Idoso , Neoplasias da Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Receptor ErbB-2/genética , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Tunísia , Disfunção Ventricular Esquerda/induzido quimicamente , Função Ventricular Esquerda/efeitos dos fármacos
19.
Infection ; 48(5): 773-777, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32277408

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.


Assuntos
Infecções por Bacteroides/complicações , Betacoronavirus/patogenicidade , Candidíase/complicações , Infecções por Coronavirus/complicações , Miocardite/complicações , Pneumonia Viral/complicações , Doença Aguda , Antivirais/uso terapêutico , Infecções por Bacteroides/diagnóstico por imagem , Infecções por Bacteroides/tratamento farmacológico , Infecções por Bacteroides/virologia , Betacoronavirus/efeitos dos fármacos , Biomarcadores/sangue , Candidíase/diagnóstico por imagem , Candidíase/tratamento farmacológico , Candidíase/virologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Combinação de Medicamentos , Ecocardiografia , Evolução Fatal , Humanos , Interleucina-6/sangue , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico por imagem , Miocardite/tratamento farmacológico , Miocardite/virologia , Pandemias , Combinação Piperacilina e Tazobactam/uso terapêutico , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Ritonavir/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Tomografia Computadorizada por Raios X , Troponina I/sangue
20.
Circ Heart Fail ; 13(3): e006331, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32164435

RESUMO

BACKGROUND: Chronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is associated with impaired aerobic capacity. We investigated the integrity of cardiac ß-receptor responsiveness, an important mechanism involved in exertional increases in HR, in HFpEF and control subjects. METHODS: Thirteen carefully screened patients with HFpEF and 13 senior controls underwent exercise testing and graded isoproterenol infusion to quantify cardiac ß-receptor-mediated HR responses. To limit autonomic neural influences on heart rate (HR) during isoproterenol, dexmedetomidine and glycopyrrolate were given. Isoproterenol doses were increased incrementally until HR increased by 30 beats per minute. Plasma levels of isoproterenol at each increment were measured by liquid chromatography with electrochemical detection and plotted against HR. RESULTS: Peak VO2 and HR (117±15 versus 156±15 beats per minute; P<0.001) were lower in HFpEF than senior controls. Cardiac ß-receptor sensitivity was lower in HFpEF compared to controls (0.156±0.133 versus 0.254±0.166 beats per minute/[isoproterenol ng/mL]; P<0.001). Seven of 13 HFpEF subjects had ß-receptor sensitivity similar to senior controls but still had lower peak HRs (122±14 versus 156±15 beats per minute; P<0.001). CONCLUSIONS: Contrary to our hypothesis, patients with HFpEF displayed impaired cardiac ß-receptor sensitivity compared with senior controls. In the 7 out of 13 patients with HFpEF with age-appropriate ß-receptor sensitivity, peak HR remained low, suggesting impaired sinus node ß-receptor function may not fully account for low exercise HR response. Rather in some patients with HFpEF, chronotropic incompetence might reflect premature cessation of exercise before maximal sinus node activation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02524145.


Assuntos
Tolerância ao Exercício , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Receptores Adrenérgicos beta/metabolismo , Nó Sinoatrial/fisiopatologia , Volume Sistólico , Função Ventricular Esquerda , Adaptação Fisiológica , Agonistas Adrenérgicos beta/administração & dosagem , Idoso , Estudos de Casos e Controles , Teste de Esforço , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Humanos , Isoproterenol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Receptores Adrenérgicos beta/efeitos dos fármacos , Nó Sinoatrial/efeitos dos fármacos , Nó Sinoatrial/metabolismo , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA