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1.
Circulation ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39319469

RESUMO

BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (n=187) or enalapril (n=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.

2.
Circulation ; 150(4): 272-282, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38841854

RESUMO

BACKGROUND: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-ß peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). METHODS: In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSE score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events. RESULTS: Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; P=0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype. CONCLUSIONS: Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.


Assuntos
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Cognição , Combinação de Medicamentos , Insuficiência Cardíaca , Volume Sistólico , Tetrazóis , Valsartana , Humanos , Compostos de Bifenilo/uso terapêutico , Valsartana/uso terapêutico , Valsartana/efeitos adversos , Aminobutiratos/uso terapêutico , Aminobutiratos/efeitos adversos , Masculino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Feminino , Idoso , Cognição/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Pessoa de Meia-Idade , Tetrazóis/uso terapêutico , Tetrazóis/efeitos adversos , Estudos Prospectivos , Neprilisina/antagonistas & inibidores , Resultado do Tratamento , Disfunção Cognitiva/tratamento farmacológico , Idoso de 80 Anos ou mais
3.
Eur Heart J ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39215531

RESUMO

BACKGROUND AND AIMS: The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients. METHODS: This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels. RESULTS: A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident. CONCLUSIONS: In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046).

4.
Biochem Biophys Res Commun ; 690: 149244, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38029488

RESUMO

BACKGROUND: CRC is a common but serious complication or sequela of tumor treatment, and new coping strategies are urgently needed. SV is a classic clinical cardiovascular protective drug, which has been widely used in the treatment of heart failure, hypertension and other diseases. It has good therapeutic effect in other cardiovascular diseases such as diabetes cardiomyopathy, ischemic cardiomyopathy and vascular disease, but it has not been proved by research that SV can prevent and treat CRC. METHOD: In this study, DOX was used to induce a rat CRC model and evaluate the therapeutic effect of SV on it. Subsequently, R software was applied to analyze the control group, SV group, and DOX group in databases GSE207283 and GSE22369, and to screen for common differentially expressed genes. Use the DAVID website for enrichment analysis and visualization. Use STRING website to analyze and visualize protein interaction networks of key genes. Finally, experimental verification was conducted on key genes. RESULT: Our research results show that SV has a protective effect on DOX induced myocardial injury by alleviating Weight loss, increasing Ejection fraction, and reducing the level of biomarkers of myocardial injury. Meanwhile, SV can effectively alleviate the above abnormalities. Bioinformatics and KEGG pathway analysis showed significant enrichment of metabolic and MAPK signaling pathways, suggesting that they may be the main regulatory pathway for SV treatment of CRC. Subsequent studies have also confirmed that SV can inhibit DOX induced myocardial injury through the MAPK signaling pathway, and alleviate DOX induced oxidative stress and inflammatory states. CONCLUSION: Our research indicates that SV is a potential drug for treating CRC and preliminarily elucidates its molecular mechanism of regulating the MAPK pathway to improve oxidative stress and inflammation.


Assuntos
Cardiomiopatias , Traumatismos Cardíacos , Ratos , Animais , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doxorrubicina/farmacologia , Apoptose , Estresse Oxidativo , Transdução de Sinais , Traumatismos Cardíacos/metabolismo , Valsartana/uso terapêutico , Valsartana/metabolismo , Valsartana/farmacologia , Cardiomiopatias/patologia , Inflamação/patologia , Biologia Computacional , Miócitos Cardíacos/metabolismo
5.
J Card Fail ; 30(3): 425-435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37678704

RESUMO

BACKGROUND: Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging owing to the risk of further deterioration in renal function, especially after acute decompensated HF (ADHF). METHODS AND RESULTS: We assessed the effect of RD (estimated glomerular filtration rate of ≥30 to <60 mL/min/1.73 m2) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized patients with HFrEF admitted for ADHF (RD, n = 476; non-RD, n = 483). At week 10, the target dose of sacubitril/valsartan (97/103 mg twice daily) was achieved by 42% patients in RD subgroup vs 54% in non-RD patients (P < .001). Sacubitril/valsartan was associated with greater estimated glomerular filtration rate improvements in RD subgroup than non-RD (change from baseline least squares mean 4.1 mL/min/1.73 m2, 95% confidence interval 2.2-6.1, P < .001). Cardiac biomarkers improved significantly in both subgroups; however, compared with the RD subgroup, the improvement was greater in those without RD (N-terminal pro-brain natriuretic peptide, -28.6% vs -44.8%, high-sensitivity troponin T -20.3% vs -33.9%) (P < .001). Patients in the RD subgroup compared with those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%, P < .001), investigator-reported cardiac failure (9.7% vs 5.6%, P = .029), and renal impairment (6.4% vs 2.1%, P = .002). CONCLUSIONS: Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated glomerular filtration rate and cardiac biomarkers. CLINICAL TRIAL REGISTRATION: NCT02661217.


Assuntos
Insuficiência Cardíaca , Nefropatias , Disfunção Ventricular Esquerda , Humanos , Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina , Biomarcadores , Compostos de Bifenilo , Combinação de Medicamentos , Volume Sistólico , Tetrazóis/efeitos adversos , Resultado do Tratamento , Valsartana , Disfunção Ventricular Esquerda/tratamento farmacológico
6.
Mol Cell Biochem ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304614

RESUMO

This study aimed to investigate the potential cardioprotective effects of sacubitril/valsartan (Sac/Val) in mice with doxorubicin (DOX)-induced cardiomyopathy, a common manifestation of cancer therapy-related cardiac dysfunction (CTRCD) associated with DOX. A total of thirty-two mice were equally classified into 4 groups: control group, DOX (total 24 mg/kg), Sac/Val (80 mg/kg), and Sac/Val + DOX (Sac/Val was given from seven days before doxorubicin administration). Neonatal rat ventricular myocytes was exposed to 5 µM of DOX for 6 h in vitro to mimic the in vivo conditions. A variety of techniques were used to investigate cardiac inflammation, fibrosis, apoptosis, and autophagy, including western blot, real-time quantitative PCR (RT-qPCR), immunohistochemistry, and fluorescence. Mice with DOX-induced cardiotoxicity displayed impaired systolic and diastolic function, characterized by elevated levels of cardiac inflammation, fibrosis, cardiomyocyte hypertrophy, apoptosis, and autophagy inhibition in the heart. Treatment with Sac/Val partially reversed these effects. In comparison to the control group, the protein expression of NLRP3, caspase-1, collagen I, Bax, cleaved caspase-3, and P62 were significantly increased, while the protein expression of Bcl-2 and LC3-II were significantly decreased in the myocardial tissues of the Dox-induced cardiomyopathy group. The administration of Sac/Val demonstrated the potential to partially reverse alterations in protein expression within the myocardium of mice with DOX-induced cardiotoxicity by modulating the AMPKα-mTORC1 signaling pathway and suppressing oxidative stress. Additionally, Sac/Val treatment may mitigate Dox-induced apoptosis and inhibition of autophagy in primary cardiomyocytes. Sac/Val seems to be cardioprotective against DOX-induced cardiotoxicity in the pre-treatment mice model. These findings could be attributed to the anti-inflammatory, antioxidant, anti-apoptotic, and de-autophagy effects of Sac/Val through regulation of the AMPKα-mTORC1 signaling pathway.

7.
Circ J ; 88(9): 1406-1415, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-38658351

RESUMO

BACKGROUND: Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass. METHODS AND RESULTS: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). CONCLUSIONS: Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.


Assuntos
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Ponte Cardiopulmonar , Combinação de Medicamentos , Neprilisina , Sistema Renina-Angiotensina , Valsartana , Humanos , Idoso , Masculino , Feminino , Neprilisina/antagonistas & inibidores , Neprilisina/sangue , Ponte Cardiopulmonar/efeitos adversos , Sistema Renina-Angiotensina/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Fator Natriurético Atrial/sangue , Renina/sangue , Tetrazóis/uso terapêutico , Tetrazóis/farmacologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos
8.
Ann Pharmacother ; : 10600280241277354, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39229914

RESUMO

BACKGROUND: Sacubitril/valsartan (SV) is recommended for patients with heart failure (HF). In addition, a combination of 4 HF medications, including SV, is recommended in patients with HF with reduced ejection fraction (HFrEF). However, evidence on the characteristics of patients who could continue SV and its initiation methods is limited. OBJECTIVE: To investigate the factors associated with SV continuation and methods of combining HF medications. METHODS: This retrospective cohort study included HF patients who initiated with SV at our institution. The endpoint was SV continuation for 6 months after its initiation. Multivariate analysis was used to extract factors associated with SV continuation. The relationship between the methods of combining HF medications (renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, or sodium-glucose cotransporter 2 inhibitors), including the number of HF medications, their combination patterns, and the timing of their initiation, and SV continuation was examined in patients with HFrEF. RESULTS: Of 186 eligible patients, 68.8% had HFrEF, and 79.0% continued SV for 6 months. Significant factors associated with SV continuation were albumin ≥ 3.5 g/dL (odds ratio, 4.81; 95% confidence interval, 2.19-10.59), body mass index (BMI) ≥ 18.5 kg/m2 (4.17; 1.10-15.85), and systolic blood pressure (SBP) ≥ 110 mmHg (2.66; 1.12-6.28). In patients with HFrEF, the proportion of HF medications not initiated simultaneously with SV was significantly higher in the continuation group than in the discontinuation group (67.3% vs 33.3%, P = 0.002). The number of HF medications and their combination patterns were not significantly associated with SV continuation. CONCLUSION AND RELEVANCE: Albumin, BMI, and SBP are useful indicators for selecting patients who are likely to continue SV. In addition, initiating only SV without simultaneously initiating other HF medications in patients with HFrEF may lead to SV continuation.

9.
Eur J Clin Pharmacol ; 80(8): 1113-1120, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38597935

RESUMO

PURPOSE: The objective of this meta-analysis is to determine how sacubitril/valsartan (SV) compares to equivalent and sub-equivalent angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: The databases of PubMed and EMBASE were used to identify those randomized controlled trials which compared SV to ARB/ACEI in patients with HFrEF. Only those trials that reported outcomes regarding total mortality, cardiovascular mortality, and worsening heart failure were considered. Meta-analysis was performed separately in those patients receiving equivalent doses of ARB/ACEI and those receiving sub-equivalent doses. Equivalent doses were SV 97/103 = valsartan 160 mg twice daily = enalapril 20 mg twice daily = ramipril 5 mg twice daily. Meta-analyses were performed using Review Manager 5.4. RESULTS: Twelve randomized trials were identified involving 17,484 patients: 11,291 in the sub-equivalent group (8 trials) and 6193 in the equivalent group (4 trials). Meta-analyses showed there were no statistical differences regarding the outcomes of total mortality, cardiovascular mortality, and worsening heart failure in the equivalent dosing group. However, SV reduced total mortality (risk ratio (RR) = 0.85, 95% confidence interval (CI) = 0.78-0.93, p < 0.001), cardiovascular mortality (RR = 0.81, 95% CI = 0.73-0.90, p ≤ 0.001) and worsening heart failure (RR = 0.77, 95% CI = 0.64-0.92, p = 0.005) in the sub-equivalent group. CONCLUSION: When compared to equivalent doses of ARB/ACEI, SV is not superior in reducing mortality and worsening heart failure. SV is superior when compared to sub-equivalent doses of ACEI.


Assuntos
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Compostos de Bifenilo , Insuficiência Cardíaca , Tetrazóis , Valsartana , Humanos , Aminobutiratos/administração & dosagem , Aminobutiratos/uso terapêutico , Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico/efeitos dos fármacos , Tetrazóis/administração & dosagem , Tetrazóis/uso terapêutico , Valsartana/administração & dosagem
10.
BMC Cardiovasc Disord ; 24(1): 106, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355423

RESUMO

AIMS: To explore the role and mechanism of Notch signaling and ERK1/2 pathway in the inhibitory effect of sacubitril/valsartan on the proliferation of vascular smooth muscle cells (VSMCs). MAIN METHODS: Human aortic vascular smooth muscle cells (HA-VSMCs) were cultured in vitro. The proliferating VSMCs were divided into three groups as control group, Ang II group and Ang II + sacubitril/valsartan group. Cell proliferation and migration were detected by CCK8 and scratch test respectively. The mRNA and protein expression of PCNA, MMP-9, Notch1 and Jagged-1 were detected by qRT-PCR and Western blot respectively. The p-ERK1/2 expression was detected by Western blot. KEY FINDINGS: Compared with the control group, proliferation and migration of VSMCs and the expression of PCNA, MMP-9, Notch1, Jagged-1 and p-ERK1/2 was increased in Ang II group. Sacubitril/valsartan significantly reduced the proliferation and migration. Additionally, pretreatment with sacubitril/valsartan reduced the PCNA, MMP-9, Notch1, Jagged-1 and p-ERK1/2 expression.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Sistema de Sinalização das MAP Quinases , Metaloproteinase 9 da Matriz , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Músculo Liso Vascular/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Antígeno Nuclear de Célula em Proliferação/farmacologia , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Proteína Jagged-1/farmacologia , Células Cultivadas , Valsartana/farmacologia , Proliferação de Células , Miócitos de Músculo Liso/metabolismo , Angiotensina II/metabolismo , Movimento Celular
11.
BMC Cardiovasc Disord ; 24(1): 79, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291395

RESUMO

BACKGROUND: This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF). METHODS: This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day. RESULTS: Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e') improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P < 0.001). Age, diabetes mellitus, and pulmonary arterial pressure were independent risk factors for HF hospitalization and cardiovascular mortality in patients with HFpEF. CONCLUSIONS: SV improved LV hypertrophy, diastolic function, and the ADQI class for HF; however, it failed to reduce the composite endpoints of HF hospitalization and cardiovascular disease-related mortality over 12 months of follow-up in patients on maintenance hemodialysis with EF of > 40%.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Doenças Cardiovasculares , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Estudos Prospectivos , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Diálise Renal/efeitos adversos , Função Ventricular Esquerda
12.
Pharmacoepidemiol Drug Saf ; 33(9): e5849, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39289955

RESUMO

BACKGROUND: Following the mass recall of valsartan products with nitrosamine impurities in July 2018, the number of patients exposed to these products, the duration of exposure, and the potential for cancer remains unknown. Therefore, we assessed the extent and duration of use of valsartan products with a nitrosamine impurity in the United States, Canada, and Denmark. METHODS: We conducted a retrospective cohort study using administrative healthcare data from the US FDA Sentinel System, four Canadian provinces that contribute to the Canadian Network for Observational Drug Effect Studies (CNODES), and the Danish National Prescription Registry. Patients, 18 years and older between May 2012 and December 2020 with a valsartan dispensing were identified in each database. Patients were followed from the date of valsartan dispensing until discontinuation. We defined four valsartan exposure categories based on nitrosamine impurity status; recalled generic products with confirmed NDMA/NDEA levels (recalled-tested); recalled generic products that were not tested (recalled); non-recalled generic and non-recalled branded products. In Denmark, the recalled-tested category was not included due to absence of testing data. The proportion and duration of use of valsartan episodes stratified by nitrosamine-impurity status was calculated. RESULTS: We identified 3.3 and 2.8 million (United States) and 51.3 and 229 thousand (Canada) recalled-tested and recalled valsartan exposures. In Denmark, where valsartan exposure was generally low, there were 10 747 recalled exposures. Immediately after the recall notices were issued, there was increased rates of switching to a non-valsartan ARB. The mean duration of use of the recalled-tested products was 167 (±223.1) and 146 (±255.8) days in the United States and Canada respectively. For the recalled products, mean cumulative duration of use was 178 (±249.6), 269 (±397.3) and 166 (±251.0) days in the United States, Canada, and Denmark, respectively. CONCLUSION: In this cohort study, despite widespread use of recalled generic valsartan between 2012 and 2018, the duration of use was relatively short and probably did not pose an elevated risk of nitrosamine-induced cancer. However, since products with nitrosamine impurity could have been on the market over a 6-year period, patients exposed to these products for longer durations could have a potentially different risk of cancer.


Assuntos
Contaminação de Medicamentos , Nitrosaminas , Valsartana , Valsartana/química , Valsartana/análise , Humanos , Dinamarca , Estados Unidos , Canadá , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Nitrosaminas/análise , Idoso , Recall de Medicamento , Adulto , Bases de Dados Factuais , Estudos de Coortes , Idoso de 80 Anos ou mais
13.
Pharmacoepidemiol Drug Saf ; 33(4): e5777, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38511239

RESUMO

BACKGROUND: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives. METHODS: We conducted a cohort study of Optum's de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups. RESULTS: Of the 87 130 adherent patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95% CI 0.96-1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95% CI 0.97-1.12). CONCLUSIONS: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Insuficiência Cardíaca , Humanos , Idoso , Estados Unidos , Valsartana/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Estudos de Coortes , Medicare , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/induzido quimicamente , Tetrazóis/efeitos adversos
14.
Biol Pharm Bull ; 47(7): 1360-1367, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39085075

RESUMO

The current study aimed to investigate the anti-atrial fibrillatory (AF) effects of a combination of valsartan and a calcium channel blocker (cilnidipine or amlodipine) in Dahl salt-sensitive (Dahl S) rats. Seven-week-old male Dahl S rats were fed an 8% salt diet. Six weeks later, valsartan (60 mg/kg, Val group), cilnidipine + valsartan (10 + 60 mg/kg, CV group), amlodipine + valsartan (3 + 60 mg/kg, AV group), or vehicle was orally administered daily for 5 weeks. Echocardiography and atrial electrophysiological evaluations were performed on the last day of treatment. Blood pressure in each drug treatment group was lower than in the Vehicle group. The duration of AF induced by atrial burst stimulation was shorter in the Val group (3.2 ± 1.6 s) than in the Vehicle group (11.2 ± 6.0 s), which was further shortened in the CV and AV groups (1.1 ± 0.3 and 1.3 ± 0.3 s, respectively). Left ventricular ejection fraction and left ventricular fractional shortening were greater in the CV and AV groups than those in the Vehicle group. Urinary albumin excretion in the CV group was the lowest among the drug-treated groups. The results collectively suggest that the combination of a calcium channel blocker with valsartan could be useful in terms of its anti-AF action as well as for improving cardiac and renal functions.


Assuntos
Pressão Sanguínea , Bloqueadores dos Canais de Cálcio , Di-Hidropiridinas , Ratos Endogâmicos Dahl , Valsartana , Animais , Valsartana/farmacologia , Di-Hidropiridinas/farmacologia , Masculino , Bloqueadores dos Canais de Cálcio/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Fibrilação Atrial/tratamento farmacológico , Quimioterapia Combinada , Rim/efeitos dos fármacos , Ratos , Anlodipino/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Átrios do Coração/efeitos dos fármacos
15.
Heart Vessels ; 39(2): 95-104, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37733071

RESUMO

Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. However, the impact of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for such patients with low blood pressure, remains uncertain. We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group (≤ 100 mmHg in systole) than for the non-low blood pressure group (> 100 mmHg in systole) (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P < 0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P < 0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups. In conclusion, significant LV reverse remodeling occurred after initiation of sacubitril/valsartan, even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Insuficiência Cardíaca , Hipotensão , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico/fisiologia , Estudos Retrospectivos , Tetrazóis/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Resultado do Tratamento , Valsartana/uso terapêutico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Função Ventricular Esquerda/fisiologia , Combinação de Medicamentos , Remodelação Ventricular
16.
Heart Vessels ; 39(8): 673-686, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38635062

RESUMO

Effects of angiotensin receptor/neprilysin inhibitors (ARNI) on ventricular remodeling in patients with heart failure, especially heart failure with reduced ejection fraction (HFrEF), are better than those of angiotensin-converting enzyme inhibitors (ACEI). Acute myocardial infarction (AMI) complicated by mitral regurgitation exacerbates ventricular remodeling and increases the risk of heart failure. There is limited evidence on the effects of early administration of ARNI in patients with AMI complicated by mitral regurgitation. The aim of this trial was to examine the effectiveness and the safety of early administration of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation. This was a randomized, single-blind, parallel-group, controlled trial. From June 2021 to June 2022, we enrolled 142 consecutive patients with AMI complicated by moderate-to-severe mitral regurgitation and followed them for 12 months. The patients received standard treatment for AMI and were randomly assigned to receive ARNI or benazepril. The primary efficacy end points were the differences in mitral regurgitant jet area (MRJA), mitral regurgitant volume (MRV), concentration of n-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume and end-systolic volume (LVEDV and LVESV) between groups and within groups at baseline, 1, 3, 6, and 12 months. Secondary end points included the rates of heart failure hospitalization, all-cause mortality, refractory angina, malignant arrhythmias, recurrent myocardial infarction, and stroke. Safety end points included the rates of hyperkalemia, renal dysfunction, hypotension, angioedema, and cough. The ARNI group had significantly lower NT-proBNP levels than the benazepril group at 1 month and later (P < 0.001). MRJA and MRV significantly improved in the ARNI group compared with the benazepril group at 12 months (MRJA: - 3.21 ± 2.18 cm2 vs. - 1.83 ± 2.81 cm2, P < 0.05; MRV: - 27.22 ± 15.22 mL vs. - 13.67 ± 21.02 mL, P < 0.001). The ARNI group also showed significant reductions in LVEDV and LVESV (P < 0.05) and improvement in LVEF (P < 0.05). Secondary end point analysis showed a significantly higher rate of heart failure hospitalization in the benazepril group compared with the ARNI group (HR = 2.03, 95% CI 1.12-3.68, P = 0.021). Safety end point analysis showed a higher rate of hypotension in the ARNI group (P < 0.05). Early use of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation can significantly reduce mitral regurgitation, improve ventricular remodeling, and decrease heart failure hospitalization. Nevertheless, caution is needed to avoid hypotension. Chinese Clinical Trial Registry (ChiCTR2100054255) registered on December 11, 2021.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência da Valva Mitral , Infarto do Miocárdio , Intervenção Coronária Percutânea , Valsartana , Humanos , Valsartana/administração & dosagem , Valsartana/efeitos adversos , Masculino , Feminino , Aminobutiratos/administração & dosagem , Aminobutiratos/efeitos adversos , Aminobutiratos/uso terapêutico , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Pessoa de Meia-Idade , Resultado do Tratamento , Infarto do Miocárdio/complicações , Método Simples-Cego , Idoso , Intervenção Coronária Percutânea/métodos , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/uso terapêutico , Volume Sistólico/fisiologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia , Função Ventricular Esquerda/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Índice de Gravidade de Doença , Fatores de Tempo
17.
Lipids Health Dis ; 23(1): 63, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419057

RESUMO

BACKGROUND AND OBJECTIVE: Dyslipidemia is significantly more common in those with concurrent chronic kidney disease (CKD) and chronic heart failure (CHF). Sacubitril/valsartan has showcased its influence on both cardiac and renal functions, extending its influence to the modulation of lipid metabolism pathways. This study aimed to examine how sacubitril/valsartan affects lipid metabolism within the context of CKD and CHF. METHODS: This study adopted a retrospective design, focusing on a single center and involving participants who were subjected to treatment with sacubitril/valsartan and valsartan. The investigation assessed the treatment duration, with a particular emphasis on recording blood lipid indicators, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB). Furthermore, cardiac and renal functions, blood pressure, potassium levels, and other factors influencing the blood lipids were analyzed in both groups at identical time points. RESULTS: After 16 weeks of observation, the sacubitril/valsartan group exhibited lower TG levels compared to the valsartan group. Noteworthy was the fact that individuals undergoing sacubitril/valsartan treatment experienced an average reduction of 0.84 mmol/L in TG levels, in stark contrast to the valsartan group, which registered a decline of 0.27 mmol/L (P < 0.001). The sacubitril/valsartan group exhibited elevated levels of HDL-C and ApoA in comparison to the valsartan group (PHDL-C = 0.023, PApoA = 0.030). While TC, LDL-C, and ApoB decreased compared to baseline, the differences between groups were not statistical significance. Regarding cardiac indicators, there was an observed enhancement in the left ventricular ejection fraction (LVEF) within the sacubitril/valsartan group when compared to the baseline, and it was noticeably higher than that of the valsartan group. Spearman correlation analysis and multiple linear regression analysis revealed that medication, body mass index(BMI), and hemoglobin A1c (HbA1c) had a direct influencing effect on TG levels. CONCLUSION: Sacubitril/valsartan demonstrated improvements in lipid metabolism and cardiac indicators in patients with CKD and CHF. Specifically, it presented promising benefits in reducing TG levels. In addition, both BMI and HbA1c emerged as influential factors contributing to alterations in TG levels, independent of the administration of sacubitril/valsartan.


Assuntos
Aminobutiratos , Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Estudos Retrospectivos , Volume Sistólico/fisiologia , LDL-Colesterol , Hemoglobinas Glicadas , Metabolismo dos Lipídeos , Tetrazóis/uso terapêutico , Tetrazóis/farmacologia , Função Ventricular Esquerda/fisiologia , Valsartana/uso terapêutico , Valsartana/farmacologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Compostos de Bifenilo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Combinação de Medicamentos , Apolipoproteínas A/farmacologia , Apolipoproteínas B , Apolipoproteínas
18.
Blood Purif ; 53(8): 657-664, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38824921

RESUMO

INTRODUCTION: The aim of this study was to investigate the role of sacubitril/valsartan in managing hypertension and cardiac remodeling in patients undergoing hemodialysis. METHODS: Hemodialysis patients with stable blood pressure control were enrolled in the study. Sacubitril/valsartan was prescribed to replace previously used angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or other antihypertensive drugs. During a 6-month follow-up period, pre-dialysis blood pressure, routine biochemical markers, and N-terminal pro-brain natriuretic peptide levels were measured. Volume status was assessed using bioelectrical impedance analysis. Endothelial damage was evaluated by measuring asymmetric dimethylarginine expression, while echocardiography and life quality assessed by Short Form-12 Health Survey were conducted at baseline and after treatment. RESULTS: The median daily dose of sacubitril/valsartan in 32 participants was 200 mg, and no obvious adverse reactions were reported. The defined daily dose of other antihypertensive drugs (baseline 2.00 ± 1.18, end point 1.46 ± 1.30, t = 3.216, p = 0.003) reduced significantly. After treatment with sacubitril/valsartan, left ventricular ejection fraction significantly increased from 64.81 ± 8.16% to 67.55 ± 5.85% (t = -4.022, p ≤ 0.001) and the thickness of posterior wall of the left ventricle reduced from 1.05 ± 0.14 cm to 1.00 ± 0.11 cm (t = 2.063, p = 0.048). The interventricular septal thickness (baseline 1.08 ± 0.16 cm, endpoint 1.02 ± 0.12 cm, t = 2.260, p = 0.031) remarkably reduced by the end of follow-up. The tricuspid regurgitation pressure gradient decreased from 28.47 ± 8.26 mm Hg at baseline to 23.79 ± 6.61 mm Hg (t = 2.531, p = 0.020) after treatment. CONCLUSION: Sacubitril/valsartan effectively manages hypertension in hemodialysis patients and may also independently improve left ventricular hypertrophy and systolic function, regardless of changes in the blood pressure or the volume load.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Hipertensão , Hipertrofia Ventricular Esquerda , Diálise Renal , Tetrazóis , Valsartana , Humanos , Compostos de Bifenilo/uso terapêutico , Valsartana/uso terapêutico , Aminobutiratos/uso terapêutico , Masculino , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Pessoa de Meia-Idade , Feminino , Idoso , Tetrazóis/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico
19.
Herz ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313691

RESUMO

BACKGROUND: Patients who have undergone catheter ablation for atrial fibrillation (AF) may experience recurrence of this condition. The efficacy of sacubitril-valsartan (S/V) in preventing AF recurrence compared with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is not established. This meta-analysis aimed to establish the best therapeutic choice for preventing AF recurrence after catheter ablation. METHOD: A systematic search of the PubMed, Embase, and Cochrane databases was conducted for randomized controlled trials (RCTs) and observational studies comparing the use of S/V with ACEI/ARB in patients who underwent catheter ablation. Results are presented as mean difference (MD) with 95% confidence interval (CI). Heterogeneity was assessed with the I2 statistic, and outcomes are expressed as relative risk (RR). R software version 4.2.3 was used for the analysis. RESULTS: Three RCTs and one cohort study, comprising 642 patients with 319 patients in the S/V group and 323 in the control group, were included. Follow-up ranged from 6 to 36 months, with mean ages ranging from 58.9 to 65.8 years. A significant reduction in persistent AF occurrence was demonstrated favoring the S/V group (RR: 0.54; 95% CI: [0.41, 0.70]; p = 0.000004; I2: 80%) over the ACEI/ARB group. There was no significant difference in left ventricular ejection fraction with S/V use (MD: 1.23; 95% CI: [-0.12, 2.60]; p = 0.076; I2: 0%) compared with ACEI/ARB. The analysis also showed a significant reduction in left atrial volume index (MD: -5.33; 95% CI: [-8.76, -1.90]; p = 0.002; I2: 57%) in the S/V group compared with the ACEI/ARB group. CONCLUSION: This meta-analysis demonstrated the efficacy of S/V in reducing the incidence of AF in patients undergoing catheter ablation compared with the use of ACEI/ARB. However, more RCTs are needed for a comprehensive evaluation of its efficacy in reducing AF recurrence after catheter ablation in clinical practice.

20.
J Electrocardiol ; 84: 104-108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38615617

RESUMO

BACKGROUND: Sacubitril/valsartan (SV) is currently recommended as a first-line therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to its significant clinical and prognostic benefit; however, not all patients respond to therapy and predictors of clinical response to SV remain under-studied. AIMS: To identify electrocardiographic (ECG) predictors of response to SV therapy in HFrEF patients. METHODS: A retrospective analysis of a hospital heart failure registry was undertaken. Consecutive HFrEF patients (New York Heart Association class II-III) on maximal-dose SV were studied. Response to SV was defined as ≥10% relative improvement in left ventricular ejection fraction (LVEF) at 3-months post-maximal-dose therapy. Pre-therapy ECGs were retrospectively analyzed for axes and standard wave and interval durations. Logistic regression was used to estimate odds ratios and 95% confidence intervals for associations between predictors and therapeutic response. Backward stepwise regression was employed to develop a parsimonious model. RESULTS: P-wave duration (PWD) 100-120 ms, PWD >120 ms, and QTc >460 ms were associated with response to SV on univariate analysis: OR 18.00 (4.45-122.90), 5.00 (1.47-20.42), and 3.10 (1.18-9.22), respectively. The preferred model that included the former two predictors in combination with pre-therapy creatinine, mineralocorticoid receptor antagonist use, and LVEF was highly selective (area under the ROC curve = 0.868). CONCLUSIONS: Prolongation of both PWD and QTc interval on baseline ECG in HFrEF patients is predictive of therapeutic response to maximal-dose SV therapy and may indicate early cardiac remodeling that is highly amenable to reversal.


Assuntos
Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Eletrocardiografia , Insuficiência Cardíaca , Volume Sistólico , Valsartana , Humanos , Valsartana/uso terapêutico , Aminobutiratos/uso terapêutico , Masculino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Antagonistas de Receptores de Angiotensina/uso terapêutico , Resultado do Tratamento , Tetrazóis/uso terapêutico , Sistema de Registros , Valor Preditivo dos Testes
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