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2.
J Cardiovasc Pharmacol Ther ; 27: 10742484221107799, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35713466

RESUMO

AIM: Changes in QRS duration in patients with heart failure with reduced ejection fraction (HFrEF) after sacubitril/valsartan therapy is not fully understood. This study aimed to assess the association of duration of HFrEF diagnosis with electrocardiographic and echocardiographic outcomes between before and after sacubitril/valsartan. METHODS: We included HFrEF patients who received naïve sacubitril/valsartan therapy for ≥3 months, between January 2016 and March 2018. All patients were divided into 2 groups based on their duration of HFrEF. Generalized linear models were analyzed the cardiac outcomes after sacubitril/valsartan therapy by HFrEF duration. RESULTS: Among these, 42 patients were HFrEF duration of <1 year and 47 patients were ≥1 year. The mean difference of QRS duration was lesser in the <1-year group than in the ≥1-year group (-2.3 msec vs 6.3 msec; P = .029). However, the mean difference of left ventricular ejection fraction (LVEF) was higher in the ≥1-year group (13.8% vs 5.8%; P = .008). After adjusting for patient demographics and clinical characteristics, the ≥1-year group had a significantly prolonged QRS duration (coefficient = 11; 95% confidence interval [CI], 0.3-21.7) and an unfavorable LVEF recovery (coefficient = -10.3; 95% CI -14.5 to -6.1) compared with the <1-year group. CONCLUSION: Prolonged QRS durations and unfavorable LVEF recoveries after sacubitril/valsartan therapy were observed in patients with HFrEF duration of ≥1 year. Earlier diagnosis of HFrEF and appropriate medication treatment may be beneficial in the improvement of QRS duration and LVEF recovery.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Volume Sistólico , Tetrazóis/efeitos adversos , Resultado do Tratamento , Valsartana/uso terapêutico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda
3.
Front Endocrinol (Lausanne) ; 13: 888867, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35733766

RESUMO

Treatment of heart failure with the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan improved glycemic control in individuals with type 2 diabetes. The relative contribution of neprilysin inhibition versus angiotensin II receptor antagonism to this glycemic benefit remains unknown. Thus, we sought to determine the relative effects of the neprilysin inhibitor sacubitril versus the angiotensin II receptor blocker valsartan on beta-cell function and glucose homeostasis in a mouse model of reduced first-phase insulin secretion, and whether any beneficial effects are additive/synergistic when combined in sacubitril/valsartan. High fat-fed C57BL/6J mice treated with low-dose streptozotocin (or vehicle) were followed for eight weeks on high fat diet alone or supplemented with sacubitril, valsartan or sacubitril/valsartan. Body weight and fed glucose levels were assessed weekly. At the end of the treatment period, insulin release in response to intravenous glucose, insulin sensitivity, and beta-cell mass were determined. Sacubitril and valsartan, but not sacubitril/valsartan, lowered fasting and fed glucose levels and increased insulin release in diabetic mice. None of the drugs altered insulin sensitivity or beta-cell mass, but all reduced body weight gain. Effects of the drugs on insulin release were reproduced in angiotensin II-treated islets from lean C57BL/6J mice, suggesting the insulin response to each of the drugs is due to a direct effect on islets and mechanisms therein. In summary, sacubitril and valsartan each exert beneficial insulinotropic, glycemic and weight-reducing effects in obese and/or diabetic mice when administered alone; however, when combined, mechanisms within the islet contribute to their inability to enhance insulin release.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Insulinas , Aminobutiratos/farmacologia , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Angiotensinas , Animais , Compostos de Bifenilo , Peso Corporal , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Camundongos , Camundongos Endogâmicos C57BL , Neprilisina , Receptores de Angiotensina , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Valsartana/farmacologia , Valsartana/uso terapêutico
4.
Medicine (Baltimore) ; 101(23): e29149, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35687770

RESUMO

BACKGROUND: Sacubitril-valsartan has been shown to have superior effects over angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF). However, the effects of sacubitril-valsartan have never been systematically evaluated. Therefore, we performed a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of sacubitril-valsartan in patients with HF. METHODS: We selected 8 databases, including PubMed, the Web of Science, Embase, Cochrane Library, the Chinese National Knowledge Infrastructure, the Chinese Science Journal Database, Wanfang Data, and the Chinese Biomedical Literature Database. The search time was from database establishment to March 2022. Two reviewers will screen the records and include quality studies according to inclusion criteria independently. Two reviewers will assess the risk of bias of the included studies by the "Risk of Bias Assessment Tool" of the Cochrane Handbook for randomized controlled trials. Statistical analysis will be performed with Review Manager software 5.3. RESULTS: A synthesis of current evidence of sacubitril-valsartan for treating HF will be provided in this protocol. CONCLUSION: The results of this study will provide a theoretical basis for the clinical use of sacubitril-valsartan to treat HF.


Assuntos
Insuficiência Cardíaca , Tetrazóis , Aminobutiratos , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Metanálise como Assunto , Neprilisina , Volume Sistólico , Revisões Sistemáticas como Assunto , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valsartana/uso terapêutico
5.
Kardiologiia ; 62(5): 72-74, 2022 May 31.
Artigo em Russo | MEDLINE | ID: mdl-35692177

RESUMO

Metabolic syndrome is a disease the World Health Organization has called a new pandemic of the 21st century. Arterial hypertension is one of the criteria for this diagnosis and a determinant of damage to major target organs. The present clinical case demonstrates an experience of treatment of arterial hypertension associated with metabolic syndrome with a valsartan/sacubitril molecular complex.


Assuntos
Insuficiência Cardíaca , Hipertensão , Síndrome Metabólica , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Pressão Sanguínea , Método Duplo-Cego , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Volume Sistólico , Tetrazóis/uso terapêutico , Valsartana/uso terapêutico
6.
Ann Palliat Med ; 11(5): 1811-1825, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35672897

RESUMO

BACKGROUND: With the increase of hypertensive patients worldwide, the need for better antihypertensive drugs to achieve blood pressure standards and reduce complications is of great clinical significance. As an angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan has been widely used in the treatment of heart failure, but its efficacy and safety in the treatment of middle-aged and elderly hypertensive patients are still controversial. Therefore, we performed a meta-analysis to compare the efficacy and safety of sacubitril/valsartan and other antihypertensive drugs in the treatment of middle-aged and elderly patients with hypertension. METHODS: The databases of PubMed, Embase, and Web of Science were systematically searched from their establishment to February 2022 to collect the randomized controlled trials (RCTs) of sacubitril/valsartan and other antihypertensive drugs in the treatment of middle-aged and elderly hypertensive patients. The Cochrane Collaboration's tool was used to assess risk of bias for included studies, and the meta-analysis was performed by using RevMan 5.3. RESULTS: In all, 7 studies which met the criteria were included, with a total sample size of 3,323 patients, including 1,899 patients treated with sacubitril/valsartan, and 1,424 patients treated with angiotensin II receptor blockers (ARBs). The meta-analysis showed that compared with other antihypertensive drugs, sacubitril/valsartan can significantly reduce mean reductions in sitting systolic blood pressure [mean difference (MD) =-4.70, 95% confidence interval (CI): -5.79 to -3.61, P<0.001], mean reductions in sitting diastolic blood pressure (MD =-2.29, 95% CI: -2.53 to -2.04, P<0.001), 24-hour mean reductions in ambulatory systolic blood pressure (MD =-3.36, 95% CI: -4.08 to -2.64, P<0.001), and 24-hour mean reductions in ambulatory diastolic blood pressure (MD =-1.49, 95% CI: -1.99 to -0.99, P<0.001), while there was no significant difference in the incidence of adverse events [odds ratio (OR) =1.14, 95% CI: 1.00 to 1.31, P=0.06], serious adverse events (OR =1.06, 95% CI: 0.64 to 1.76, P=0.81), and discontinuations due to adverse events (OR =0.86, 95% CI: 0.51 to 1.46, P=0.58). DISCUSSION: Compared with other antihypertensive drugs, sacubitril/valsartan may be more effective in lowering blood pressure, and its safety may be comparable to that of ARBs. However, these results have to be confirmed by future RCTs with larger sample sizes and higher quality, and the long-term benefits of sacubitril/valsartan require further observation.


Assuntos
Anti-Hipertensivos , Hipertensão , Idoso , Aminobutiratos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo , Humanos , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Tetrazóis/efeitos adversos , Valsartana/uso terapêutico
7.
Adv Pharmacol ; 94: 365-409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35659376

RESUMO

Cancer patients are at an increased risk of cardiovascular events. Both old-generation cytostatics/cytotoxics and new-generation "targeted" drugs can in fact damage cardiomyocytes, endothelial cells of veins and arteries, specialized cells of the conduction system, pericardium, and valves. A new discipline, cardio-oncology, has therefore developed with the aim of protecting cancer patients from cardiovascular events, while also providing them with the best possible oncologic treatment. Anthracyclines have long been known to elicit cardiotoxicity that, depending on treatment- or patient-related factors, may progress with a variable velocity toward cardiomyopathy and systolic heart failure. However, early compromise of diastolic function may precede systolic dysfunction, and a progression of early diastolic dysfunction to diastolic rather than systolic heart failure has been documented in long-term cancer survivors. This chapter first describes general notions about hypertension in the cancer patient and then moves on reviewing the pathophysiology and clinical trajectories of diastolic dysfunction, and the molecular mechanisms of anthracycline-induced diastolic dysfunction. Diastolic dysfunction can in fact be caused and/or aggravated by hypertension. Pharmacologic foundations and therapeutic opportunities to prevent or treat diastolic dysfunction before it progresses toward heart failure are also reviewed, with a special emphasis on the mechanisms of action of drugs that raised hopes to treat diastolic dysfunction in the general population (sacubitril/valsartan, guanylyl cyclase activators, phosphodiesterase inhibitors, ranolazine, inhibitors of type-2 sodium-glucose-inked transporter). Cardio-oncologists will be confronted with the risk:benefit ratio of using these drugs in the cancer patient.


Assuntos
Antineoplásicos , Cardiomiopatias , Insuficiência Cardíaca Sistólica , Hipertensão , Neoplasias , Aminobutiratos , Antraciclinas/efeitos adversos , Antineoplásicos/farmacologia , Compostos de Bifenilo , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/tratamento farmacológico , Células Endoteliais , Insuficiência Cardíaca Sistólica/induzido quimicamente , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Neoplasias/tratamento farmacológico
8.
PLoS One ; 17(6): e0267960, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35679273

RESUMO

Tobacco black shank is a kind of soil-borne disease caused by the Oomycete Phytophthora parasitica. This disease is one of the most destructive diseases to tobacco (Nicotiana tabacum L.) growth worldwide. At present, various measures have been taken to control this disease, but they still have different challenges and limitations. Studies have shown that ß-aminobutyric acid (BABA), a nonprotein amino acid, can enhance disease resistance in plants against different varieties of pathogens. However, it is unclear whether BABA can induce plants to resist Phytophthora parasitica infection. Therefore, this study aims to explore the effect and related mechanism of BABA against tobacco black shank. Our results showed that 5 mmol.L-1 BABA had an obvious anti-inducing effect on the pathogenic fungus and could effectively inhibit the formation of dark spots in the stems. The results also showed that a large amount of callose deposition was observed in BABA-treated tobacco. Furthermore, the application of BABA induced the accumulation of H2O2 in tobacco and effectively regulated the homeostasis of reactive oxygen in tobacco plants, reducing the toxicity of H2O2 to plants while activating the defense system. In addition, BABA spray treatment could induce an increase in the concentrations of salicylic acid (SA) and jasmonic acid-isoleucine (JA-Ile) in tobacco, and the gene expression results confirmed that BABA upregulated the expression of SA-related genes (PR1, PR2 and PR5), JA-related genes (PDF1.2) and ET-related genes (EFE26 and ACC oxidase) in tobacco plants. Taken together, BABA could activate tobacco resistance to black shank disease by increasing H2O2 accumulation, callose deposition, plant hormone (SA and JA-Ile) production, and SA-, JA-, and ET- signaling pathways.


Assuntos
Arabidopsis , Tabaco , Aminobutiratos , Arabidopsis/genética , Ciclopentanos/metabolismo , Ciclopentanos/farmacologia , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Oxilipinas/metabolismo , Doenças das Plantas/microbiologia , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia , Tabaco/genética
9.
Cardiovasc Diabetol ; 21(1): 110, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717169

RESUMO

BACKGROUND: Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes. METHODS: We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF. RESULTS: Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: - 0.24%, 95% CI - 0.33 to - 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62-1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05-2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (Pinteraction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63-0.89, P = 0.001), compared with enalapril or valsartan. CONCLUSIONS: Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711.


Assuntos
Diabetes Mellitus , Insuficiência Cardíaca , Hipoglicemia , Insulinas , Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Glicemia , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Enalapril/efeitos adversos , Hemoglobina A Glicada , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipoglicemia/induzido quimicamente , Insulinas/farmacologia , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos , Função Ventricular Esquerda
10.
JACC Heart Fail ; 10(6): 380-392, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35654522

RESUMO

BACKGROUND: Hypertension is common in patients with heart failure (HF), but less is known about resistant hypertension. OBJECTIVES: This study sought to investigate apparent treatment-resistant hypertension (aTRH) in patients with HF in the SwedeHF (Swedish Heart Failure Registry), across the spectrum of HF phenotypes (heart failure with reduced ejection fraction [HFrEF], heart failure with mildly reduced ejection fraction [HFmrEF], and heart failure with preserved ejection fraction [HFpEF]). METHODS: aTRH was defined as systolic blood pressure ≥140 mm Hg (≥135 mm Hg in diabetes) despite treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or sacubitril-valsartan, as well as a calcium-channel blocker and a diuretic; non-treatment-resistant hypertension (TRH) was defined as systolic blood pressure above these thresholds but not on the 3-drug combination; and normal blood pressure was defined as under these thresholds. In each left ventricular ejection fraction (LVEF) category, patient factors associated with aTRH and non-TRH and outcomes (HF hospitalization and cardiovascular death composite, its components, and all-cause death) according to hypertension category were examined. RESULTS: Among 46,597 patients, aTRH was present in 2,693 (10%), 1,514 (14%), and 1,450 (17%) patients with HFrEF, HFmrEF, and HFpEF, respectively. Older age, obesity, diabetes, and kidney disease were associated with a greater likelihood of aTRH and non-TRH (vs normal blood pressure). Associations were generally similar irrespective of LVEF category. Compared with normal blood pressure, aTRH was associated with a lower adjusted risk of the composite outcome in HFrEF and HFmrEF (HR: 0.79 [95% CI: 0.74-0.85] and HR: 0.86 [95% CI: 0.77-0.96]) but not in HFpEF (HR: 0.93 [95% CI: 0.84-1.04]). CONCLUSIONS: aTRH was most common in HFpEF and least common in HFrEF. Associated patient characteristics were similar irrespective of LVEF category. aTRH (vs normal blood pressure) was associated with a lower risk of first HF hospitalization or cardiovascular death in HFrEF and HFmrEF but not in HFpEF.


Assuntos
Insuficiência Cardíaca , Hipertensão , Aminobutiratos , Compostos de Bifenilo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Fenótipo , Prognóstico , Sistema de Registros , Volume Sistólico/fisiologia , Suécia , Função Ventricular Esquerda
11.
JACC Heart Fail ; 10(6): 415-427, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35654526

RESUMO

BACKGROUND: Up to 20% of patients in heart failure with reduced ejection fraction (HFrEF) trials are not taking diuretic agents at baseline, but little is known about them. OBJECTIVES: The aim of this study was to examine outcomes in patients with HFrEF not taking diuretic medications and after diuretic medications are started. METHODS: Patient characteristics and outcomes were compared between patients taking or not taking diuretic drugs at baseline in the ATMOSPHERE (Aliskiren Trial of Minimizing Outcomes for Patients With Heart Failure) and PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) trials combined. Patients starting diuretic medications were also compared with those remaining off diuretic drugs during follow-up. Symptoms (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ-CSS]), hospitalization for worsening heart failure (HF), mortality, and kidney function (estimated glomerular filtration rate slope) were examined. RESULTS: At baseline, the 3,079 of 15,415 patients (20%) not taking diuretic medications had a less severe HF profile, less neurohumoral activation, and better kidney function. They were less likely to experience the primary outcome (hospitalization for HF or cardiovascular death) than patients taking diuretic agents (adjusted HR: 0.77; 95% CI: 0.74-0.80; P < 0.001) and death of any cause. Commencement of a diuretic drug was associated with higher subsequent risk for death (adjusted HR: 2.05; 95% CI: 1.99-2.11; P < 0.001) and greater decreases in KCCQ-CSS and estimated glomerular filtration rate. The 5 strongest predictors of initiation of diuretic medications were higher N-terminal pro-B-type natriuretic peptide, higher body mass index, older age, history of diabetes, and worse KCCQ-CSS. In PARADIGM-HF, fewer patients who were treated with sacubitril/valsartan commenced diuretic agents (OR: 0.72; 95% CI: 0.58-0.88; P = 0.002). CONCLUSIONS: Patients with HFrEF not taking diuretic medications and those who remained off them had better outcomes than patients treated with diuretic agents or who commenced them.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Estudos Prospectivos , Volume Sistólico/fisiologia , Tetrazóis/uso terapêutico
12.
Medicine (Baltimore) ; 101(21): e29427, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35623077

RESUMO

RATIONALE: Fabry disease (FD) is a rare, X-linked lysosomal deposition disease characterized by multi-system symptoms. The accumulation of globotriaosylceramide in various organs, such as the kidneys and heart, as well as the nervous system, has been speculated to be the mechanism involved in tissue damage, including vascular impairment with thrombotic events. PATIENT CONCERNS: Here, we describe a 72-year-old male patient diagnosed with FD, who first presented with acute myocardial infarction, left ventricular thrombosis, and pericardial effusion, accompanied by cardiac hypertrophy. DIAGNOSES: A physical examination showed that he was hemodynamically stable and an electrocardiogram showed ventricular tachycardia (Fig. 1A). The single obvious abnormality was an ST segment depression with a preterminal negative T wave in leads I and aVL (Fig. 1B). Coronary angiography revealed regular findings (Fig. 2). Echocardiogram conducted at our hospital revealed hypertrophy, ejection fraction 40%, pericardial effusion (Fig. 3). Speckle tracking two-dimensional echocardiography strain analysis technology confirmed left ventricular thrombosis, and also revealed decreased movement of the inferior and posterior walls, the basal segment of the posterior wall was locally fibrotic (Fig. 4A and B). Further, myocardial contrast echocardiography confirmed left ventricular thrombosis (Fig. 4C). Cardiovascular magnetic resonance imaging indicated biventricular uneven hypertrophy, which was considered metabolic cardiomyopathy, with diffuse fibrosis of biventricular walls, apical thrombosis, and ischemic cardiomyopathy in the basal segment of the left ventricular lateral wall and left ventricular anterior wall (Fig. 5). Serum alpha-galactosidase concentration was 0.7 nmol/h/mgPr (normal range, 29.0-64.4 nmol/h/mgPr). Subsequent genetic testing revealed that he was hemizygous for a previously reported missense mutation (c.902G>A) inexon 6 of the GLA gene,[1] which induce p.R301Q (p.Arg301Gln), confirming a diagnosis of FD (Fig. 6). INTERVENTIONS: Orally administered drugs included rivaroxaban, sacubitril valsartan, beta blockers, dapagliflozin, and mineralocorticoid receptor antagonist. Cardiac resynchronization therapy with an implanted defibrillator was implemented to prevent sudden death. OUTCOMES: At present, he is still in follow-up and there have been no adverse events. CONCLUSION: Our case suggests that clinicians should consider the possibility of FD in patients with acute myocardial infarction and cardiomyopathy. A detailed analysis of subtle historical clues would help promote earlier diagnosis of FD.


Assuntos
Doença de Fabry , Infarto do Miocárdio , Derrame Pericárdico , Trombose , Idoso , Aminobutiratos , Arritmias Cardíacas/complicações , Compostos de Bifenilo , Cardiomegalia/complicações , Doença de Fabry/complicações , Doença de Fabry/diagnóstico , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/etiologia , Trombose/complicações
13.
Am Heart J ; 250: 23-28, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35525261

RESUMO

BACKGROUND: In clinical trials, sacubitril/valsartan has demonstrated significant survival benefits compared to angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Whether older patients with heart failure with reduced ejection fraction (HFrEF) benefit as much, due to higher rates of comorbidities, frailty and drug discontinuation, is unknown. METHODS AND RESULTS: Using a cohort of Medicare beneficiaries hospitalized with HFrEF between 2016 and 2018, we determined all-cause mortality and HF-readmission rates among patients not given ACEi/ARB or sacubitril/valsartan at hospital discharge, by age. We then used risk reductions from the SOLVD, PARADIGM-HF and PIONEER-HF trials to estimate the benefits of ACEi/ARB and sacubitril/valsartan. We then incorporated age-specific estimates of drug discontinuation from Medicare. A Markov decision process model was used to simulate 5-year survival and estimate number needed to treat, comparing discharge on ACEi/ARB vs sacubitril/valsartan by age. After accounting for drug discontinuation rates, which were surprisingly slightly higher among those discharged on ACEi/ARB (2.3%/month vs 1.9%/month), there was a small but significant survival advantage to discharge on sacubitril/valsartan over 5 years (+0.81 months [95% CI 0.80, 0.81]). The benefit of sacubitril/valsartan over ACEi/ARB did not decrease with increasing age - the number needed to treat among 66 to 74-year-old patients was 84 and among 85+ year-old patients was 67. CONCLUSIONS: Even after accounting for "real world" rates of drug discontinuation, discharge on sacubitril/valsartan after conferred a small, but significant, survival advantage which does not appear to wane with increasing age.


Assuntos
Insuficiência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Técnicas de Apoio para a Decisão , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Medicare , Alta do Paciente , Volume Sistólico/fisiologia , Análise de Sobrevida , Estados Unidos/epidemiologia , Valsartana/uso terapêutico
14.
Clin Drug Investig ; 42(6): 533-540, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35635714

RESUMO

BACKGROUND AND OBJECTIVE: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has been shown to significantly reduce cardiovascular mortality, heart failure hospitalizations, and all-cause mortality in patients with heart failure with reduced ejection fraction. This study aims to investigate the long-term impact of the sacubitril/valsartan combination on lipid parameters in patients with heart failure with reduced ejection fraction. METHODS: For this single-center retrospective cross-sectional study, data of patients using sacubitril/valsartan because of heart failure with reduced ejection fraction were collected. In addition to routine controls, the patients' lipid levels were measured at 3-month intervals. The parameters that were obtained over 3 years included total cholesterol, high-density lipoprotein cholesterol, triglyceride, and N-terminal pro-B-type natriuretic peptide levels. RESULTS: A total of 192 patients with a functional capacity New York Heart Association II-V, and who were using sacubitril/valsartan because of heart failure with reduced ejection fraction, were included in this study. Independent of statin use, there was a decrease in total cholesterol levels (196.1 ± 44.8 mg/dL vs 161.5 ± 41.7 mg/dL, p < 0.001) and triglyceride levels (159.1 ± 10.4 mg/dL vs 121.4 ± 6.9 mg/dL, p < 0.001), and there was an improvement in high-density lipoprotein cholesterol levels (44.9 ± 1.9 mg/dL vs 48.2 ± 2.4 mg/dL, p < 0.001) when comparing baseline levels with third-year levels. CONCLUSIONS: Sacubitril/valsartan in patients with heart failure with reduced ejection fraction, independent of statin use, may cause a decrease in total cholesterol and triglyceride levels and an improvement in high-density lipoprotein cholesterol levels.


Assuntos
Insuficiência Cardíaca , Inibidores de Hidroximetilglutaril-CoA Redutases , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/farmacologia , Colesterol , Estudos Transversais , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Lipídeos , Lipoproteínas HDL/farmacologia , Estudos Retrospectivos , Volume Sistólico , Tetrazóis/uso terapêutico , Resultado do Tratamento , Triglicerídeos , Valsartana/farmacologia
15.
Hypertens Res ; 45(7): 1097-1110, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35501475

RESUMO

Angiotensin receptor-neprilysin inhibitors have multiple beneficial effects on the cardiovascular system. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to effectively reduce ambulatory 24-h blood pressure in patients with hypertension, and improvements in many aspects of hemodynamic function have also been reported. Overall hemodynamic effects on arterial stiffness and nocturnal blood pressure play an important role in the pathogenesis of hypertensive heart disease. Therefore, these could represent mechanistic targets underlying the effects of angiotensin receptor-neprilysin inhibitors on the continuum of cardiovascular disease from hypertension to heart failure. Other potential mechanisms include reductions in circulating volume and sympathetic activity, both of which contribute to the protection against target organ damage and positive changes in cardiac biomarkers seen during angiotensin receptor-neprilysin inhibitor therapy. The mechanisms of action and beneficial effects of angiotensin receptor-neprilysin inhibitors are complementary to those of a number of other treatment options for hypertension, suggesting the possibility of additive or even synergistic benefits. Based on available data, there are a number of patient groups who will benefit from antihypertensive treatment with an angiotensin receptor-neprilysin inhibitor, including those with salt-sensitive hypertension, structural hypertension, resistant hypertension, and hypertension in the presence of heart failure. Overall, angiotensin receptor-neprilysin inhibitors regulate blood pressure and pulse pressure via multiple mechanisms and provide cardiovascular protection. This provides an option for effective intervention early in the vicious cycle of elevated blood pressure and central pressures with progression toward heart failure that should help to address the growing worldwide heart failure epidemic.


Assuntos
Insuficiência Cardíaca , Hipertensão , Aminobutiratos/farmacologia , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica , Humanos , Hipertensão/tratamento farmacológico , Neprilisina , Receptores de Angiotensina , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Valsartana/uso terapêutico
16.
Sci Rep ; 12(1): 8186, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35581275

RESUMO

Angiotensin inhibition remains a cornerstone for pharmacologic management of heart failure (HF), despite being associated with decreased hemoglobin (Hb) levels. To investigate the effect of anemia and its treatment on patients with HF treated with sacubitril-valsartan (S/V), we conducted a retrospective study involving patients with recorded left ventricular ejection fractions (LVEFs) of < 40% between January 2017 and December 2019. We identified 677 patients, 37.7% of whom received S/V. The median follow-up period was 868 days. Anemia was associated with significantly decreased survival, increased mortality rates, and higher all-cause hospitalizations in S/V-using patients. We further analyzed 236 patients with HF who had recorded renal function, LVEF, and Hb at the initiation of S/V therapy to identify Hb patterns after S/V therapy. Of these patients, 35.6% exhibited decreasing Hb 12 months after S/V initiation, which was associated with a lower survival rate. Among the patients who were not prescribed anemia medications, Hb of ≥ 12 (vs. < 12 g/dL) was associated with a higher survival rate; this association was absent among the patients undergoing anemia treatment. These results emphasize that consistent screening and treatment for anemia should be implemented to reduce the morbidity and mortality of patients with HF receiving S/V.


Assuntos
Anemia , Insuficiência Cardíaca , Aminobutiratos/farmacologia , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/farmacologia , Compostos de Bifenilo/farmacologia , Combinação de Medicamentos , Humanos , Estudos Retrospectivos , Volume Sistólico/fisiologia , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valsartana/farmacologia , Valsartana/uso terapêutico
17.
Comput Math Methods Med ; 2022: 9765884, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35637842

RESUMO

Objective: To investigate the effects of metoprolol succinate combined with Entresto (Sacubitril Valsartan Sodium Tablets) on cardiac function and coagulation function in patients with congestive heart failure (CHF). Methods: About 120 patients with CHF treated from April 2018 to April 2021 were enrolled in our hospital. The patients were arbitrarily assigned into control group and study group. The control group was cured with metoprolol succinate sustained-release tablets, and the study group was cured with metoprolol succinate sustained-release tablets combined with Entresto. The curative effect, cardiac function, vascular endothelial function, oxidative stress, and coagulation function were compared. Results: First of all, we compared the general data, and there exhibited no difference in age, sex, course of disease, hypertension, coronary heart disease, diabetes, atrial fibrillation, and other general data (P > 0.05). Second, we compared the clinical efficacy. The effective rate of the study group (98.33%) was higher (90.00%) (P < 0.05). There exhibited no significant difference in cardiac function indexes before treatment, but after treatment, LVEF increased, LVESD and LVEDD decreased, LVESD and LVEDD in the study group were lower, and LVEF in the study group was higher (P < 0.05). Before treatment, there exhibited no significant difference in vascular endothelial function. However, the levels of CGRP and ET increased and the level of NO decreased, and the level of NO in the study group was lower, while the levels of CGRP and ET in the study group were higher after treatment (P < 0.05). There exhibited no significant difference in oxidative stress indexes before treatment, however, the levels of GSH-Px and SOD increased and the levels of MDA decreased after treatment, while the level of MDA in the study group was lower, while the levels of GSH-Px and SOD in the study group were higher (P < 0.05). Finally, we compared the indexes of blood coagulation function. There exhibited no significant difference before treatment, but after treatment, the levels of APTT, PT, and FIB decreased, and the levels of APTT, PT, and FIB in the study group were lower (P < 0.05). Conclusion: Clinical practice demonstrated that LVESD and LVEDD decreased and LVEF increased after treatment with Entresto combined with metoprolol in CHF patients, which can effectively facilitate cardiac function and vascular endothelial function, reduce oxidative stress reaction, and improve blood coagulation indexes, suggesting that Entresto combined with metoprolol can improve ventricular remodeling with good safety.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Coagulação Sanguínea , Insuficiência Cardíaca , Metoprolol , Valsartana , Aminobutiratos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/sangue , Preparações de Ação Retardada , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Metoprolol/uso terapêutico , Superóxido Dismutase , Valsartana/uso terapêutico
18.
Artigo em Inglês | MEDLINE | ID: mdl-35564359

RESUMO

The extensive use of herbicides, such as glyphosate and glufosinate, in crop production during recent decades has raised concerns about human exposure. Nevertheless, analysis of trace levels of these herbicides in human biospecimens has been challenging. Here, we describe a method for the determination of urinary glyphosate, its degradation product aminomethylphosphonic acid (AMPA), and glufosinate using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was optimized using isotopically labelled internal standards (13C2, 15N-glyphosate, 13C, 15N, D2-AMPA, and D3-glufosinate) and solid-phase extraction (SPE) with cation-exchange and anion-exchange cartridges. The method provides excellent chromatographic retention, resolution and peak shape of target analytes without the need for strong acidic mobile phases and derivatization steps. The instrument linearity was in the range of 0.1-100 ng/mL, with R > 0.99 in the matrix for all analytes. The method detection limits (MDLs) and the method quantification limits (MQLs) were in the ranges of 0.12 (AMPA and glufosinate)-0.14 (glyphosate) ng/mL and 0.40 (AMPA)-0.48 (glyphosate) ng/mL, respectively. The recoveries of analytes spiked into urine matrix ranged from 79.1% to 119%, with coefficients of variation (CVs) of 4-10%. Repeated analysis of samples for over 2 weeks showed intra-day and inter-day analytical variations of 3.13-10.8% and 5.93-12.9%, respectively. The matrix effects for glyphosate, AMPA, and glufosinate spiked into urine matrix averaged -14.4%, 13.2%, and 22.2%, respectively. The method was further validated through the analysis of external quality assurance proficiency test (PT) urine samples. The method offers optimal sensitivity, accuracy, and precision for the urine-based assessment of human exposure to glyphosate, AMPA, and glufosinate.


Assuntos
Herbicidas , Espectrometria de Massas em Tandem , Aminobutiratos , Cromatografia Líquida/métodos , Glicina/análogos & derivados , Herbicidas/análise , Humanos , Organofosfonatos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico
19.
BMC Cardiovasc Disord ; 22(1): 217, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562650

RESUMO

AIMS: To evaluate the circulating levels of remodeling biomarkers procollagen type 1 C-terminal propeptide (PICP), human cartilage glycoprotein-39 (YKL-40), plasma renin activity (PRA), aldosterone (Aldo) as well as clinical and echocardiographic parameters in patients with heart failure with reduced ejection fraction (HFrEF), before and after treatment with Sacubitril/Valsartan (S/V). METHODS AND RESULTS: A total of 26 consecutive patients with HFrEF on stable clinical conditions were studied. Clinical, echocardiographic parameters and circulating biomarkers were measured at baseline, after 30 and 60 days of S/V treatment. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased, from 126 ± 15 to 113 ± 4 mmHg (p < 0.001) and from 77 ± 11 to 72 ± 9 mmHg (p = 0.005), respectively, at the end of study. Concomitantly, left ventricular ejection fraction (LVEF) increased by 22.8% from 29.5 ± 5% to 36.2 ± 5%, (p < 0.001) and indexed left ventricular end-systolic volume (LVESVi) decreased by 12% from 38.6 ± 8.7 ml/m2 to 34.0 ± 10.0 ml/m2. (p = 0.007). Circulating levels of PICP, YKL-40, PRA and Aldo decreased by - 42.2%, - 46.8%, - 79.1% and - 76.7%, respectively (p < 0.001 for all), the decrements being already maximal within 30 days of S/V treatment. No significant changes of plasma electrolytes and creatinine were observed during the study (all p > 0.05). CONCLUSIONS: A decrease of circulating markers of inflammation and fibrosis during chronic treatment with S/V is associated with an improvement of hemodynamic and echographic parameters in patients with HRrEF. These data are compatible with an anti-fibrotic and anti-inflammatory effect of S/V, that may contribute to the beneficial outcomes of the drug in this clinical setting.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Biomarcadores , Compostos de Bifenilo/uso terapêutico , Proteína 1 Semelhante à Quitinase-3 , Fibrose , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Inflamação/complicações , Volume Sistólico , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Valsartana/uso terapêutico , Disfunção Ventricular Esquerda/complicações , Função Ventricular Esquerda
20.
Circ Res ; 130(11): e44-e57, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35485239

RESUMO

BACKGROUND: Sacubitril/valsartan (S/V) treatment is beneficial in patients with heart failure with reduced ejection fraction (HFrEF), but its mode of action remains elusive, although it involves the increase in ANP (atrial natriuretic peptide). METHODS: Combining mass spectrometry and enzymatic assay in the plasma of 73 HFrEF patients treated with S/V and controls, we deciphered proANP processing that converts proANP into 4 vasoactive peptides. RESULTS: We found that proANP processing is sequential and involved meprin B, ECE (endothelin-converting enzyme) 1, and ANPEP (aminopeptidase N). This processing is limited in HFrEF patients via the downregulation of proANP production, corin, and meprin B activities by miR-425 and miR1-3p. S/V restored or compensated proANP processing by downregulating miR-425 and miR1-3p, hence increasing levels of proANP-derived bioactive peptides. In contrast, S/V directly and indirectly partially inhibited ECE1 and ANPEP. ECE1 partial inhibition resulted in a lower-than-expected increase in ET1 (endothelin 1), tilting the vasoactive balance toward vasodilation, and possibly hypotension. Furthermore, proANP glycosylation interferes with the midregional proANP assay -a clinical surrogate for proANP production, preventing any pathophysiological interpretation of the results. The analysis of S/V dose escalation with respect to baseline treatments suggests S/V-specific effects. CONCLUSIONS: These findings offer mechanistic evidence to the natriuretic peptide -defective state in HFrEF, which is improved by S/V. These data also strongly suggests that S/V increases plasma ANP by multiple mechanisms that involve 2 microRNAs, besides its protection from NEP (neprilysin) cleavage. Altogether, these data provide new insights on HFrEF pathophysiology and the mode of action of S/V.


Assuntos
Insuficiência Cardíaca , Hipotensão , MicroRNAs , Aminobutiratos , Fator Natriurético Atrial/metabolismo , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Neprilisina , Volume Sistólico , Valsartana/uso terapêutico
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