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Rehman MU, Zuo Y, Tu N, Guo J, Liu Z, Cao S, Long S. Diverse pharmacological activities of β-carbolines: Substitution patterns, SARs and mechanisms of action. Eur J Med Chem 2025; 287:117350. [PMID: 39933403 DOI: 10.1016/j.ejmech.2025.117350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 01/26/2025] [Accepted: 01/30/2025] [Indexed: 02/13/2025]
Abstract
β-Carbolines, a class of indole-containing heterocyclic alkaloids, are widely distributed in nature and possess diverse bioactivities, making them promising drug candidates against a wide range of diseases. The remarkable medicinal potential of β-carbolines has spurred the pharmaceutical research community to study their derivatives extensively. This review updates the development of β-carboline derivatives in recent years (2015-2024), particularly with a focus on their anticancer, antiparasitic, antimicrobial, antiviral, and neuroprotective properties, based on the modification approaches such as substitution on indole N (ring B), pyridine or its reduced forms (ring C), and dimerization of β-carbolines. Moreover, the mechanisms of action and structure-activity relationships of these β-carboline derivatives are highlighted to offer valuable insights on the design and development of new β-carbolines with better pharmacological activities.
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Affiliation(s)
- Muneeb Ur Rehman
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 1st Rd Optics Valley, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Yujie Zuo
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 1st Rd Optics Valley, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Ni Tu
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 1st Rd Optics Valley, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Ju Guo
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 1st Rd Optics Valley, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Ziwei Liu
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 1st Rd Optics Valley, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Shuang Cao
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 1st Rd Optics Valley, East Lake New Technology Development District, Wuhan, Hubei, 430205, China.
| | - Sihui Long
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 1st Rd Optics Valley, East Lake New Technology Development District, Wuhan, Hubei, 430205, China.
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Pagel PS, Hang D, Freed JK, Crystal GJ. Advances in Cardiovascular Pharmacotherapy. II. Ivabradine, an Inhibitor of the Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel. J Cardiothorac Vasc Anesth 2025:S1053-0770(25)00247-2. [PMID: 40199701 DOI: 10.1053/j.jvca.2025.03.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 03/15/2025] [Accepted: 03/17/2025] [Indexed: 04/10/2025]
Abstract
Ivabradine selectively reduces heart rate by inhibiting the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel in the sinoatrial node. Unlike other medications that produce negative chronotropic effects [beta-blockers, calcium channel blockers], ivabradine does not affect systemic, pulmonary, and coronary hemodynamics. Despite several proof-of-concept clinical studies suggesting that ivabradine may exert anti-ischemic effects, two large randomized trials did not support its use in patients with chronic stable angina. Preliminary data also did not support the use of ivabradine in patients with acute ST-segment elevation myocardial infarction or acutely decompensated heart failure. However, ivabradine improved outcome in patients with heart failure with reduced ejection fraction (HFrEF), leading to its approval by the Food and Drug Administration, but the drug failed to do so in those with heart failure with preserved ejection fraction (HFpEF). Ivabradine may also be useful in cardiac electrophysiology disorders characterized by tachycardia (e.g., inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome), but it has not yet gained wide acceptance for these indications. In this article, the authors briefly review the structure and function of the cardiac HCN channel; discuss the development and actions of drugs, including ivabradine, that modulate the channel's activity; describe in detail the potential clinical applications of ivabradine in patients with coronary artery disease, HFrEF and HFpEF, and cardiac electrophysiology; comment on the adverse effects of ivabradine therapy; and finally, consider the potential anesthetic implications of ivabradine in patients undergoing noncardiac and cardiac surgery.
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Affiliation(s)
- Paul S Pagel
- Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI.
| | - Dustin Hang
- Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI
| | - Julie K Freed
- Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI
| | - George J Crystal
- Department of Anesthesiology, University of Illinois College of Medicine, Chicago, IL
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Gómez-Ochoa SA, Serrano-García AY, Hurtado-Ortiz A, Aceros A, Rojas LZ, Echeverría LE. A systematic review and meta-analysis of mortality in chronic Chagas cardiomyopathy versus other cardiomyopathies: higher risk or fiction? REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2024; 77:843-850. [PMID: 38485084 DOI: 10.1016/j.rec.2024.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 02/28/2024] [Indexed: 04/05/2024]
Abstract
INTRODUCTION AND OBJECTIVES Although multiple studies suggest that chronic Chagas cardiomyopathy (CCC) has higher mortality than other cardiomyopathies, the absence of meta-analyses supporting this perspective limits the possibility of generating robust conclusions. The aim of this study was to systematically evaluate the current evidence on mortality risk in CCC compared with that of other cardiomyopathies. METHODS PubMed/Medline and EMBASE were searched for studies comparing mortality risk between patients with CCC and those with other cardiomyopathies, including in the latter nonischemic cardiomyopathy (NICM), ischemic cardiomyopathy, and non-Chagas cardiomyopathy (nonCC). A random-effects meta-analysis was performed to combine the effects of the evaluated studies. RESULTS A total of 37 studies evaluating 17 949 patients were included. Patients with CCC had a significantly higher mortality risk compared with patients with NICM (HR, 2.04; 95%CI, 1.60-2.60; I2, 47%; 8 studies) and non-CC (HR, 2.26; 95%CI, 1.65-3.10; I2, 71%; 11 studies), while no significant association was observed compared with patients with ischemic cardiomyopathy (HR, 1.72; 95%CI, 0.80-3.66; I2, 69%; 4 studies) in the adjusted-measures meta-analysis. CONCLUSIONS Patients with CCC have an almost 2-fold increased mortality risk compared with individuals with heart failure secondary to other etiologies. This finding highlights the need for effective public policies and targeted research initiatives to optimally address the challenges of CCC.
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Affiliation(s)
- Sergio A Gómez-Ochoa
- Clínica de Falla Cardiaca y Trasplante Cardiaco, Fundación Cardiovascular de Colombia, Floridablanca, Colombia; Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany.
| | | | | | - Andrea Aceros
- Departamento de Administración en Salud, Fundación Cardiovascular de Colombia, Floridablanca, Colombia
| | - Lyda Z Rojas
- Grupo de Investigación y Desarrollo de Conocimiento en Enfermería (GIDCEN-FCV), Research Center, Fundación Cardiovascular de Colombia, Floridablanca, Colombia
| | - Luis E Echeverría
- Clínica de Falla Cardiaca y Trasplante Cardiaco, Fundación Cardiovascular de Colombia, Floridablanca, Colombia
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Bocchi EA, Echeverria LE, Demacq C, de Barros E Silva PGM, Mazza Barbosa L, Chiang LM, Damiani L, Morillo CA, Kevorkian R, Ramires F, Bahit MC, Ferrari A, Chavez-Mendoza A, Magaña-Serrano JA, McMurray JJV, Gimpelewicz C, Lopes RD. Sacubitril/Valsartan Versus Enalapril in Chronic Chagas Cardiomyopathy: Rationale and Design of the PARACHUTE-HF Trial. JACC. HEART FAILURE 2024; 12:1473-1486. [PMID: 39111953 DOI: 10.1016/j.jchf.2024.05.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 05/03/2024] [Accepted: 05/28/2024] [Indexed: 11/08/2024]
Abstract
Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF. The study aims to enroll approximately 900 patients with CCC and reduced ejection fraction at around 100 sites in Latin America. The primary outcome is a hierarchical composite of time from randomization to cardiovascular death, first HF hospitalization, or relative change from baseline to week 12 in NT-proBNP levels. PARACHUTE-HF will provide new data on the treatment of this high-risk population. (Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC [PARACHUTE-HF]; NCT04023227).
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Affiliation(s)
- Edimar Alcides Bocchi
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Luis E Echeverria
- Division of Cardiology, Fundación Cardiovascular de Colombia, Floridablanca, Colombia
| | | | | | | | | | - Lucas Damiani
- Brazilian Clinical Research Institute (BCRI), São Paulo, Brazil
| | - Carlos A Morillo
- Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada
| | - Ruben Kevorkian
- Division of Cardiology Hospital D.F. Santojanni, Buenos Aires University, Buenos Aires, Argentina
| | - Felix Ramires
- Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | | | | | - Adolfo Chavez-Mendoza
- Division of Heart Failure and Cardiac Transplantation, Hospital de Cardiologia, Centro Medico Nacional Siglo XXI, Instituto Mexicano Del Seguro Social, Mexico City, Mexico
| | - Jose Antonio Magaña-Serrano
- Division of Heart Failure and Cardiac Transplantation, Hospital de Cardiologia, Centro Medico Nacional Siglo XXI, Instituto Mexicano Del Seguro Social, Mexico City, Mexico
| | - John J V McMurray
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom
| | | | - Renato D Lopes
- Brazilian Clinical Research Institute (BCRI), São Paulo, Brazil; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
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Khan ZM, Briere JB, Olewinska E, Khrouf F, Nikodem M. Ivabradine in patients with heart failure: a systematic literature review. JOURNAL OF MARKET ACCESS & HEALTH POLICY 2023; 11:2262073. [PMID: 37808119 PMCID: PMC10552613 DOI: 10.1080/20016689.2023.2262073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 09/15/2023] [Indexed: 10/10/2023]
Abstract
Background: Heart failure is a chronic disease linked with significant morbidity and mortality, and uncontrolled resting heart rate is a risk factor for adverse outcomes. This systematic literature review aimed to assess the efficacy, safety, and patient-reported outcomes (PROs) of ivabradine in patients with heart failure (HF) with reduced ejection fraction (HFrEF) in randomized controlled trials (RCTs) and observational studies. Methods: We searched electronic databases from their inception to July 2021 to include studies that reported on efficacy, safety, or PROs of ivabradine in patients with HFrEF. Results: Of 1947 records screened, 51 RCTs and 6 observational studies were identified. Ivabradine on top of background therapy demonstrated a significant reduction in composite outcomes including hospitalization for HF or cardiovascular death. In addition, observational studies suggested that ivabradine was associated with a significant reduction in mortality. Across all studies, ivabradine use on top of background therapy was associated with greater reductions in heart rate, improved EF, and improved health-related quality of life (QoL) and comparable risk of total adverse events compared to those treated with background therapy alone. Conclusions: Ivabradine on top of background therapy is beneficial for heart rate, hospitalization risk for HF, mortality, EF, and patients' QoL. Moreover, these benefits were achieved with no significant increase in the overall risk of total adverse events.
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Affiliation(s)
| | | | | | - Fatma Khrouf
- Health Economics and Outcome Research, Putnam PHMR, Tunis, Tunisia
| | - Mateusz Nikodem
- Health Economics and Outcome Research, Putnam PHMR, Cracow, Poland
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Marin-Neto JA, Rassi A, Oliveira GMM, Correia LCL, Ramos Júnior AN, Luquetti AO, Hasslocher-Moreno AM, Sousa ASD, Paola AAVD, Sousa ACS, Ribeiro ALP, Correia Filho D, Souza DDSMD, Cunha-Neto E, Ramires FJA, Bacal F, Nunes MDCP, Martinelli Filho M, Scanavacca MI, Saraiva RM, Oliveira Júnior WAD, Lorga-Filho AM, Guimarães ADJBDA, Braga ALL, Oliveira ASD, Sarabanda AVL, Pinto AYDN, Carmo AALD, Schmidt A, Costa ARD, Ianni BM, Markman Filho B, Rochitte CE, Macêdo CT, Mady C, Chevillard C, Virgens CMBD, Castro CND, Britto CFDPDC, Pisani C, Rassi DDC, Sobral Filho DC, Almeida DRD, Bocchi EA, Mesquita ET, Mendes FDSNS, Gondim FTP, Silva GMSD, Peixoto GDL, Lima GGD, Veloso HH, Moreira HT, Lopes HB, Pinto IMF, Ferreira JMBB, Nunes JPS, Barreto-Filho JAS, Saraiva JFK, Lannes-Vieira J, Oliveira JLM, Armaganijan LV, Martins LC, Sangenis LHC, Barbosa MPT, Almeida-Santos MA, Simões MV, Yasuda MAS, Moreira MDCV, Higuchi MDL, Monteiro MRDCC, Mediano MFF, Lima MM, Oliveira MTD, Romano MMD, Araujo NNSLD, Medeiros PDTJ, Alves RV, Teixeira RA, Pedrosa RC, Aras Junior R, Torres RM, Povoa RMDS, Rassi SG, Alves SMM, Tavares SBDN, Palmeira SL, Silva Júnior TLD, Rodrigues TDR, Madrini Junior V, Brant VMDC, Dutra WO, Dias JCP. SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease - 2023. Arq Bras Cardiol 2023; 120:e20230269. [PMID: 37377258 PMCID: PMC10344417 DOI: 10.36660/abc.20230269] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2023] Open
Affiliation(s)
- José Antonio Marin-Neto
- Universidade de São Paulo , Faculdade de Medicina de Ribeirão Preto , Ribeirão Preto , SP - Brasil
| | - Anis Rassi
- Hospital do Coração Anis Rassi , Goiânia , GO - Brasil
| | | | | | | | - Alejandro Ostermayer Luquetti
- Centro de Estudos da Doença de Chagas , Hospital das Clínicas da Universidade Federal de Goiás , Goiânia , GO - Brasil
| | | | - Andréa Silvestre de Sousa
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz , Rio de Janeiro , RJ - Brasil
| | | | - Antônio Carlos Sobral Sousa
- Universidade Federal de Sergipe , São Cristóvão , SE - Brasil
- Hospital São Lucas , Rede D`Or São Luiz , Aracaju , SE - Brasil
| | | | | | | | - Edecio Cunha-Neto
- Universidade de São Paulo , Faculdade de Medicina da Universidade, São Paulo , SP - Brasil
| | - Felix Jose Alvarez Ramires
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | - Fernando Bacal
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | | | - Martino Martinelli Filho
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | - Maurício Ibrahim Scanavacca
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | - Roberto Magalhães Saraiva
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz , Rio de Janeiro , RJ - Brasil
| | | | - Adalberto Menezes Lorga-Filho
- Instituto de Moléstias Cardiovasculares , São José do Rio Preto , SP - Brasil
- Hospital de Base de Rio Preto , São José do Rio Preto , SP - Brasil
| | | | | | - Adriana Sarmento de Oliveira
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | | | - Ana Yecê das Neves Pinto
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz , Rio de Janeiro , RJ - Brasil
| | | | - Andre Schmidt
- Universidade de São Paulo , Faculdade de Medicina de Ribeirão Preto , Ribeirão Preto , SP - Brasil
| | - Andréa Rodrigues da Costa
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz , Rio de Janeiro , RJ - Brasil
| | - Barbara Maria Ianni
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | | | - Carlos Eduardo Rochitte
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
- Hcor , Associação Beneficente Síria , São Paulo , SP - Brasil
| | | | - Charles Mady
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | - Christophe Chevillard
- Institut National de la Santé Et de la Recherche Médicale (INSERM), Marselha - França
| | | | | | | | - Cristiano Pisani
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | | | | | | | - Edimar Alcides Bocchi
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | - Evandro Tinoco Mesquita
- Hospital Universitário Antônio Pedro da Faculdade Federal Fluminense , Niterói , RJ - Brasil
| | | | | | | | | | | | - Henrique Horta Veloso
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz , Rio de Janeiro , RJ - Brasil
| | - Henrique Turin Moreira
- Hospital das Clínicas , Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , SP - Brasil
| | | | | | | | - João Paulo Silva Nunes
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
- Fundação Zerbini, Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | | | | | | | | | | | - Luiz Cláudio Martins
- Universidade Estadual de Campinas , Faculdade de Ciências Médicas , Campinas , SP - Brasil
| | | | | | | | - Marcos Vinicius Simões
- Universidade de São Paulo , Faculdade de Medicina de Ribeirão Preto , Ribeirão Preto , SP - Brasil
| | | | | | - Maria de Lourdes Higuchi
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | | | - Mauro Felippe Felix Mediano
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz , Rio de Janeiro , RJ - Brasil
- Instituto Nacional de Cardiologia (INC), Rio de Janeiro, RJ - Brasil
| | - Mayara Maia Lima
- Secretaria de Vigilância em Saúde , Ministério da Saúde , Brasília , DF - Brasil
| | | | | | | | | | - Renato Vieira Alves
- Instituto René Rachou , Fundação Oswaldo Cruz , Belo Horizonte , MG - Brasil
| | - Ricardo Alkmim Teixeira
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | - Roberto Coury Pedrosa
- Hospital Universitário Clementino Fraga Filho , Instituto do Coração Edson Saad - Universidade Federal do Rio de Janeiro , RJ - Brasil
| | | | | | | | | | - Silvia Marinho Martins Alves
- Ambulatório de Doença de Chagas e Insuficiência Cardíaca do Pronto Socorro Cardiológico Universitário da Universidade de Pernambuco (PROCAPE/UPE), Recife , PE - Brasil
| | | | - Swamy Lima Palmeira
- Secretaria de Vigilância em Saúde , Ministério da Saúde , Brasília , DF - Brasil
| | | | | | - Vagner Madrini Junior
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo , São Paulo , SP - Brasil
| | | | | | - João Carlos Pinto Dias
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz , Rio de Janeiro , RJ - Brasil
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Bazoukis G, Hill B, Tse G, Naka KK. Ivabradine: pre-clinical and clinical evidence in the setting of ventricular arrhythmias. Hippokratia 2022; 26:49-54. [PMID: 37188047 PMCID: PMC10177854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
BACKGROUND Ivabradine, an agent lowering the heart rate, acting as a funny current (If) specific inhibitor, is responsible for the sinoatrial node's spontaneous depolarization. According to current guidelines, it is indicated in specific heart failure populations and as a second-line treatment option to improve angina in chronic coronary syndromes. REVIEW OF LITERATURE The role of ivabradine in the setting of ventricular arrhythmias has been studied in both experimental and clinical studies. Specifically, experimental studies have examined the role of ivabradine in acute myocardial ischemia, reperfusion, digitalis-induced ventricular arrhythmias, and catecholaminergic polymorphic ventricular tachycardia showing promising results. In addition, clinical studies have shown a beneficial role of ivabradine in reducing ventricular arrhythmias. Ivabradine reduced premature ventricular contractions in combination with beta-blockers in dilated cardiomyopathy patients. Similarly, in catecholaminergic polymorphic ventricular tachycardia, ivabradine reduced dobutamine-induced premature ventricular complexes and improved ventricular arrhythmias burden. On the other hand, current data show no beneficial role of ivabradine in reducing ventricular arrhythmias in myocardial ischemia. CONCLUSIONS Randomized clinical trials are needed to elucidate the role of ivabradine in reducing the burden of ventricular arrhythmias in various clinical settings. HIPPOKRATIA 2022, 26 (2):49-54.
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Affiliation(s)
- G Bazoukis
- Department of Cardiology, Larnaca General Hospital, Larnaca, Cyprus
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus
| | - B Hill
- Department of Medicine, Queen's University, Kingston, Ontario, Canada
| | - G Tse
- Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China
- Kent and Medway Medical School, Canterbury, Kent, United Kingdom
| | - K K Naka
- Second Department of Cardiology and Michaelidion Cardiac Center, Medical School University of Ioannina, Ioannina, Greece
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Ivabradine and Atrial Fibrillation: A Meta-analysis of Randomized Controlled Trials. J Cardiovasc Pharmacol 2021; 79:549-557. [PMID: 34983905 DOI: 10.1097/fjc.0000000000001209] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 11/20/2021] [Indexed: 11/26/2022]
Abstract
ABSTRACT This was a meta-analysis of randomized control trials (RCTs) to evaluate the effect of ivabradine on the risk of atrial fibrillation (AF) as well as its effect on the ventricular rate in patients with AF. The PubMed, EMBASE, Cochrane Controlled Trials Register, and other databases were searched for RCTs of ivabradine. Thirteen trials with 37,533 patients met the inclusion criteria. The incidence of AF was significantly higher in the ivabradine treatment group than in the control group (odds ratio (OR), 1.23; 95% confidence interval (CI), 1.08-1.41), although it was reduced after cardiac surgery (OR, 0.70; 95% CI, 0.23-2.12). Regarding left ventricular ejection fraction (LVEF), ivabradine increased the risk of AF in both LVEF >40% (OR, 1.42; 95% CI, 1.24 to 1.63) and LVEF ≤40% subgroups (OR, 1.16; 95% CI, 0.98-1.37). The risk of AF was increased by both small and large cumulative doses of ivabradine (small cumulative dose: OR, 3.00; 95% CI, 0.48 to 18.93; large cumulative dose: OR, 1.05; 95% CI, 0.83-1.34). Furthermore, ivabradine may reduce the ventricular rate in patients with AF. In conclusion, we found that both large and small cumulative doses of ivabradine were associated with an increased incidence of AF, and the effect was more marked in the LVEF >40% subgroup. Nevertheless, ivabradine therapy is beneficial for the prevention of post-operative AF. Furthermore, ivabradine may be effective in controlling the ventricular rate in patients with AF, although more RCTs are needed to support this conclusion.
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Saraiva RM, Mediano MFF, Mendes FSNS, Sperandio da Silva GM, Veloso HH, Sangenis LHC, Silva PSD, Mazzoli-Rocha F, Sousa AS, Holanda MT, Hasslocher-Moreno AM. Chagas heart disease: An overview of diagnosis, manifestations, treatment, and care. World J Cardiol 2021; 13:654-675. [PMID: 35070110 PMCID: PMC8716970 DOI: 10.4330/wjc.v13.i12.654] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/11/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
Chagas heart disease (CHD) affects approximately 30% of patients chronically infected with the protozoa Trypanosoma cruzi. CHD is classified into four stages of increasing severity according to electrocardiographic, echocardiographic, and clinical criteria. CHD presents with a myriad of clinical manifestations, but its main complications are sudden cardiac death, heart failure, and stroke. Importantly, CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies, and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies. Among patients with CHD, approximately 90% of deaths can be attributed to complications of Chagas disease. Sudden cardiac death is the most common cause of death (55%–60%), followed by heart failure (25%–30%) and stroke (10%–15%). The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with. Therefore, the management of CHD is challenging, and in this review, we present the most updated available data to help clinicians and cardiologists in the care of these patients. We describe the clinical manifestations, diagnosis and classification criteria, risk stratification, and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.
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Affiliation(s)
- Roberto M Saraiva
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Mauro Felippe F Mediano
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Fernanda SNS Mendes
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | | | - Henrique H Veloso
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Luiz Henrique C Sangenis
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Paula Simplício da Silva
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Flavia Mazzoli-Rocha
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Andréa S Sousa
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Marcelo T Holanda
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Alejandro M Hasslocher-Moreno
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
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10
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Chadalawada S, Rassi A, Samara O, Monzon A, Gudapati D, Vargas Barahona L, Hyson P, Sillau S, Mestroni L, Taylor M, da Consolação Vieira Moreira M, DeSanto K, Agudelo Higuita NI, Franco-Paredes C, Henao-Martínez AF. Mortality risk in chronic Chagas cardiomyopathy: a systematic review and meta-analysis. ESC Heart Fail 2021; 8:5466-5481. [PMID: 34716744 PMCID: PMC8712892 DOI: 10.1002/ehf2.13648] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 09/13/2021] [Accepted: 09/23/2021] [Indexed: 11/09/2022] Open
Abstract
Aims This study aimed to estimate the annual mortality risk and its determinants in chronic Chagas cardiomyopathy. Methods and results We conducted a systematic search in MEDLINE, Web of Science Core Collection, Embase, Cochrane Library, and LILACS. Longitudinal studies published between 1 January 1946 and 24 October 2018 were included. A random‐effects meta‐analysis using the death rate over the mean follow‐up period in years was used to obtain pooled estimated annual mortality rates. Main outcomes were defined as all‐cause mortality, including cardiovascular, non‐cardiovascular, heart failure, stroke, and sudden cardiac deaths. A total of 5005 studies were screened for eligibility. A total of 52 longitudinal studies for chronic Chagas cardiomyopathy including 9569 patients and 2250 deaths were selected. The meta‐analysis revealed an annual all‐cause mortality rate of 7.9% [95% confidence interval (CI): 6.3–10.1; I2 = 97.74%; T2 = 0.70] among patients with chronic Chagas cardiomyopathy. The pooled estimated annual cardiovascular death rate was 6.3% (95% CI: 4.9–8.0; I2 = 96.32%; T2 = 0.52). The annual mortality rates for heart failure, sudden death, and stroke were 3.5%, 2.6%, and 0.4%, respectively. Meta‐regression showed that low left ventricular ejection fraction (coefficient = −0.04; 95% CI: −0.07, −0.02; P = 0.001) was associated with an increased mortality risk. Subgroup analysis based on American Heart Association (AHA) classification revealed pooled estimate rates of 4.8%, 8.7%, 13.9%, and 22.4% (P < 0.001) for B1/B2, B2/C, C, and C/D stages of cardiomyopathy, respectively. Conclusions The annual mortality risk in chronic Chagas cardiomyopathy is substantial and primarily attributable to cardiovascular causes. This risk significantly increases in patients with low left ventricular ejection fraction and those classified as AHA stages C and C/D.
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Affiliation(s)
- Sindhu Chadalawada
- Department of Medicine, Alameda Health System-Highland Hospital, Oakland, CA, USA
| | - Anis Rassi
- Division of Cardiology, Anis Rassi Hospital, Goiânia, GO, Brazil
| | - Omar Samara
- School of Medicine, University of Colorado Denver, Aurora, CO, USA
| | - Anthony Monzon
- School of Medicine, University of Colorado Denver, Aurora, CO, USA
| | | | | | - Peter Hyson
- Hospital Infantil de México, Federico Gómez, México City, Mexico
| | - Stefan Sillau
- Department of Neurology, University of Colorado Denver School of Medicine, Aurora, CO, USA
| | - Luisa Mestroni
- Adult Medical Genetics Program, Cardiovascular Institute, University of Colorado Denver School of Medicine, Aurora, CO, USA
| | - Matthew Taylor
- Adult Medical Genetics Program, Cardiovascular Institute, University of Colorado Denver School of Medicine, Aurora, CO, USA
| | - Maria da Consolação Vieira Moreira
- Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.,Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Kristen DeSanto
- Health Sciences Library, University of Colorado Denver, Aurora, CO, USA
| | | | - Carlos Franco-Paredes
- Hospital Infantil de México, Federico Gómez, México City, Mexico.,Department of Medicine, Division of Infectious Diseases, University of Colorado Denver School of Medicine, 12700 E. 19th Avenue, Mail Stop B168, Aurora, CO, 80045, USA
| | - Andrés F Henao-Martínez
- Department of Medicine, Division of Infectious Diseases, University of Colorado Denver School of Medicine, 12700 E. 19th Avenue, Mail Stop B168, Aurora, CO, 80045, USA
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11
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Romero J, Velasco A, Pisani CF, Alviz I, Briceno D, Díaz JC, Della Rocca DG, Natale A, de Lourdes Higuchi M, Scanavacca M, Di Biase L. Advanced Therapies for Ventricular Arrhythmias in Patients With Chagasic Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol 2021; 77:1225-1242. [PMID: 33663741 DOI: 10.1016/j.jacc.2020.12.056] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 11/30/2020] [Accepted: 12/07/2020] [Indexed: 11/24/2022]
Abstract
Chagas disease is caused by infection from the protozoan parasite Trypanosoma cruzi. Although it is endemic to Latin America, global migration has led to an increased incidence of Chagas in Europe, Asia, Australia, and North America. Following acute infection, up to 30% of patients will develop chronic Chagas disease, with most patients developing Chagasic cardiomyopathy. Chronic Chagas cardiomyopathy is highly arrhythmogenic, with estimated annual rates of appropriate implantable cardioverter-defibrillator therapies and electrical storm of 25% and 9.1%, respectively. Managing arrhythmias in patients with Chagasic cardiomyopathy is a major challenge for the clinical electrophysiologist, requiring intimate knowledge of cardiac anatomy, advanced training, and expertise. Endocardial-epicardial mapping and ablation strategy is needed to treat arrhythmias in this patient population, owing to the suboptimal long-term success rate of endocardial mapping and ablation alone. We also describe innovative approaches to improve acute and long-term clinical outcomes in patients with refractory ventricular arrhythmias following catheter ablation, such as bilateral cervicothoracic sympathectomy and bilateral renal denervation, among others.
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Affiliation(s)
- Jorge Romero
- Cardiac Arrhythmia Center, Montefiore-Einstein Center for Heart and Vascular Care, Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA
| | - Alejandro Velasco
- Cardiac Arrhythmia Center, Montefiore-Einstein Center for Heart and Vascular Care, Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA
| | - Cristiano F Pisani
- Arrhythmia Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | - Isabella Alviz
- Cardiac Arrhythmia Center, Montefiore-Einstein Center for Heart and Vascular Care, Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA
| | - David Briceno
- Cardiac Arrhythmia Center, Montefiore-Einstein Center for Heart and Vascular Care, Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA
| | - Juan Carlos Díaz
- Cardiac Arrhythmia Center, Montefiore-Einstein Center for Heart and Vascular Care, Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA
| | | | - Andrea Natale
- Cardiac Arrhythmia Center, Montefiore-Einstein Center for Heart and Vascular Care, Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA; Texas Cardiac Arrhythmia Institute at St David's Medical Center, Austin, Texas, USA
| | - Maria de Lourdes Higuchi
- Arrhythmia Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | - Mauricio Scanavacca
- Arrhythmia Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
| | - Luigi Di Biase
- Cardiac Arrhythmia Center, Montefiore-Einstein Center for Heart and Vascular Care, Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA; Texas Cardiac Arrhythmia Institute at St David's Medical Center, Austin, Texas, USA.
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12
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Tomasoni D, Adamo M, Anker MS, von Haehling S, Coats AJS, Metra M. Heart failure in the last year: progress and perspective. ESC Heart Fail 2020; 7:3505-3530. [PMID: 33277825 PMCID: PMC7754751 DOI: 10.1002/ehf2.13124] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 11/11/2020] [Indexed: 12/11/2022] Open
Abstract
Research about heart failure (HF) has made major progress in the last years. We give here an update on the most recent findings. Landmark trials have established new treatments for HF with reduced ejection fraction. Sacubitril/valsartan was superior to enalapril in PARADIGM-HF trial, and its initiation during hospitalization for acute HF or early after discharge can now be considered. More recently, new therapeutic pathways have been developed. In the DAPA-HF and EMPEROR-Reduced trials, dapagliflozin and empagliflozin reduced the risk of the primary composite endpoint, compared with placebo [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.65-0.85; P < 0.001 and HR 0.75; 95% CI 0.65-0.86; P < 0.001, respectively]. Second, vericiguat, an oral soluble guanylate cyclase stimulator, reduced the composite endpoint of cardiovascular death or HF hospitalization vs. placebo (HR 0.90; 95% CI 0.82-0.98; P = 0.02). On the other hand, both the diagnosis and treatment of HF with preserved ejection fraction, as well as management of advanced HF and acute HF, remain challenging. A better phenotyping of patients with HF would be helpful for prognostic stratification and treatment selection. Further aspects, such as the use of devices, treatment of arrhythmias, and percutaneous treatment of valvular heart disease in patients with HF, are also discussed and reviewed in this article.
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Affiliation(s)
- Daniela Tomasoni
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public HealthUniversity of BresciaBresciaItaly
- Cardiology and Cardiac Catheterization Laboratory, Cardio‐thoracic DepartmentCivil HospitalsBresciaItaly
| | - Marianna Adamo
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public HealthUniversity of BresciaBresciaItaly
- Cardiology and Cardiac Catheterization Laboratory, Cardio‐thoracic DepartmentCivil HospitalsBresciaItaly
| | - Markus S. Anker
- Division of Cardiology and Metabolism, Department of Cardiology (CVK)Charité–University Medicine BerlinBerlinGermany
- Berlin Institute of Health Center for Regenerative Therapies (BCRT)BerlinGermany
- German Centre for Cardiovascular Research (DZHK), partner site BerlinBerlinGermany
- Department of Cardiology (CBF)Charité–University Medicine BerlinBerlinGermany
| | - Stephan von Haehling
- Department of Cardiology and PneumologyUniversity of Göttingen Medical CenterGöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Andrew J. S. Coats
- Centre for Clinical and Basic Research, Department of Medical SciencesIRCCS San Raffaele PisanaRomeItaly
| | - Marco Metra
- Department of Medical and Surgical Specialties, Radiological Sciences, and Public HealthUniversity of BresciaBresciaItaly
- Cardiology and Cardiac Catheterization Laboratory, Cardio‐thoracic DepartmentCivil HospitalsBresciaItaly
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13
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Benstoem C, Kalvelage C, Breuer T, Heussen N, Marx G, Stoppe C, Brandenburg V. Ivabradine as adjuvant treatment for chronic heart failure. Cochrane Database Syst Rev 2020; 11:CD013004. [PMID: 33147368 PMCID: PMC8094176 DOI: 10.1002/14651858.cd013004.pub2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Chronic heart failure is one of the most common medical conditions, affecting more than 23 million people worldwide. Despite established guideline-based, multidrug pharmacotherapy, chronic heart failure is still the cause of frequent hospitalisation, and about 50% die within five years of diagnosis. OBJECTIVES To assess the effectiveness and safety of ivabradine in individuals with chronic heart failure. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, and CPCI-S Web of Science in March 2020. We also searched ClinicalTrials.gov and the WHO ICTRP. We checked reference lists of included studies. We did not apply any time or language restrictions. SELECTION CRITERIA We included randomised controlled trials in which adult participants diagnosed with chronic heart failure were randomly assigned to receive either ivabradine or placebo/usual care/no treatment. We distinguished between type of heart failure (heart failure with a reduced ejection fraction or heart failure with a preserved ejection fraction) as well as between duration of ivabradine treatment (short term (< 6 months) or long term (≥ 6 months)). DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion, extracted data, and checked data for accuracy. We calculated risk ratios (RR) using a random-effects model. We completed a comprehensive 'Risk of bias' assessment for all studies. We contacted authors for missing data. Our primary endpoints were: mortality from cardiovascular causes; quality of life; time to first hospitalisation for heart failure during follow-up; and number of days spent in hospital due to heart failure during follow-up. Our secondary endpoints were: rate of serious adverse events; exercise capacity; and economic costs (narrative report). We assessed the certainty of the evidence applying the GRADE methodology. MAIN RESULTS We included 19 studies (76 reports) involving a total of 19,628 participants (mean age 60.76 years, 69% male). However, few studies contributed data to meta-analyses due to inconsistency in trial design (type of heart failure) and outcome reporting and measurement. In general, risk of bias varied from low to high across the included studies, with insufficient detail provided to inform judgement in several cases. We were able to perform two meta-analyses focusing on participants with heart failure with a reduced ejection fraction (HFrEF) and long-term ivabradine treatment. There was evidence of no difference between ivabradine and placebo/usual care/no treatment for mortality from cardiovascular causes (RR 0.99, 95% confidence interval (CI) 0.88 to 1.11; 3 studies; 17,676 participants; I2 = 33%; moderate-certainty evidence). Furthermore, we found evidence of no difference in rate of serious adverse events amongst HFrEF participants randomised to receive long-term ivabradine compared with those randomised to placebo, usual care, or no treatment (RR 0.96, 95% CI 0.92 to 1.00; 2 studies; 17,399 participants; I2 = 12%; moderate-certainty evidence). We were not able to perform meta-analysis for all other outcomes, and have low confidence in the findings based on the individual studies. AUTHORS' CONCLUSIONS We found evidence of no difference in cardiovascular mortality and serious adverse events between long-term treatment with ivabradine and placebo/usual care/no treatment in participants with heart failure with HFrEF. Nevertheless, due to indirectness (male predominance), the certainty of the available evidence is rated as moderate.
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Affiliation(s)
- Carina Benstoem
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Christina Kalvelage
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Thomas Breuer
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Nicole Heussen
- Department of Medical Statistics, Medical Faculty RWTH Aachen University, Aachen, Germany
- Center of Biostatistic and Epidemiology, Medical School, Sigmund Freud Private University, Vienna, Austria
| | - Gernot Marx
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Christian Stoppe
- Department of Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Vincent Brandenburg
- Department of Cardiology, Medical Faculty, University Hospital RWTH Aachen, Aachen, Germany
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14
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Anker MS, von Haehling S, Papp Z, Anker SD. ESC Heart Failure receives its first impact factor. Eur J Heart Fail 2019; 21:1490-e8. [PMID: 31883221 DOI: 10.1002/ejhf.1665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Markus S Anker
- Division of Cardiology and Metabolism, Department of Cardiology, Charité and Berlin Institute of Health Center for Regenerative Therapies (BCRT) and DZHK (German Centre for Cardiovascular Research), partner site Berlin and Department of Cardiology, Charité Campus Benjamin Franklin, Berlin, Germany
| | - Stephan von Haehling
- Department of Cardiology and Pneumology, Heart Center Göttingen, University of Göttingen Medical Center, George August University, Göttingen, Germany and German Center for Cardiovascular Medicine (DZHK), partner site Göttingen, Göttingen, Germany
| | - Zoltán Papp
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Stefan D Anker
- Division of Cardiology and Metabolism, Department of Cardiology, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany, DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany
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15
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Martinez F, Perna E, Perrone SV, Liprandi AS. Chagas Disease and Heart Failure: An Expanding Issue Worldwide. Eur Cardiol 2019; 14:82-88. [PMID: 31360228 PMCID: PMC6659042 DOI: 10.15420/ecr.2018.30.2] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 04/01/2019] [Indexed: 01/28/2023] Open
Abstract
Chagas disease, originally a South American endemic health problem, is expanding worldwide because of people migration. Its main impact is on the cardiovascular system, producing myocardial damage that frequently results in heart failure. Pathogenic pathways are mainly related to inmunoinflamatory reactions in the myocardium and, less frequently, in the gastrointestinal tract. The heart usually shows fibrosis, producing dilatation and damage of the electrogenic cardiac system. These changes result in cardiomyopathy with heart failure and frequent cardiac arrhythmias and heart blocks. Diagnosis of the disease must include a lab test to detect the parasite or its immune reactions and the usual techniques to evaluate cardiac function. Therapeutic management of Chagas heart failure does not differ significantly from the most common treatment for dilated cardiomyopathy, with special focus on arrhythmias and several degrees of heart block. Heart transplantation is reserved for end-stage cases. Major international scientific organisations are delivering recommendations for prevention and early diagnosis. This article provides an analysis of epidemiology, prevention, treatment and the relationship between Chagas disease and heart failure.
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Affiliation(s)
- Felipe Martinez
- Cordoba National University, Instituto DAMIC Córdoba, Argentina.,Docencia, Asistencia Médica e Investigación Clínica (DAMIC) Medical Institute, Rusculleda Foundation for Research Córdoba Argentina
| | - Eduardo Perna
- Coronary Care Unit and Heart Failure Division, Juana Cabral Cardiovascular Institute Corrientes, Argentina
| | - Sergio V Perrone
- El Cruce Hospital Buenos Aires, Argentina.,Argentine Catholic University Buenos Aires, Argentina
| | - Alvaro Sosa Liprandi
- Cardiovascular Division, Sanatorio Güemes Hospital Buenos Aires, Argentina.,Postgraduate Medical School in Cardiology Universidad de Buenos Aires, Argentina
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16
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Affiliation(s)
- Edimar Alcides Bocchi
- Heart Failure Team, Heart Institute (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Vera Maria Cury Salemi
- Heart Failure Team, Heart Institute (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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17
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Xue EZ, Zhang MH, Liu CL. Efficacy of ivabradine for heart failure: A protocol for a systematic review of randomized controlled trial. Medicine (Baltimore) 2019; 98:e15075. [PMID: 30946357 PMCID: PMC6455899 DOI: 10.1097/md.0000000000015075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Previous clinical trials have reported that ivabradine can effectively treat heart failure (HF). However, no systematic review has explored its efficacy and safety for HF. This systematic review will aim to evaluate the efficacy and safety of ivabradine for the treatment of patients with HF. METHODS We will search the literature from the following electronic databases from inception to the January 31, 2019: Cochrane Central Register of Controlled Trials, EMBASE, MEDILINE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. All randomized controlled trials (RCTs) of ivabradine for HF will be fully considered for inclusion without any restrictions. Additionally, grey literature including clinical trial registries, dissertations, and reference lists of included studies, conference abstracts will also be searched. Two researchers will review these literatures, extract data, and assess risk of bias of included RCTs separately. Data will be pooled by either fixed-effects model or random-effects model, and meta-analysis will be conducted if it is appropriate. RESULTS The primary outcome is all-cause mortality. The secondary outcomes comprise of change in body weight, urine output, change in serum sodium, and all adverse events. CONCLUSIONS The results of this study will summary provide up-to-dated evidence for assessing the efficacy and safety of ivabradine for HF. ETHICS AND DISSEMINATION It is not necessary to acquire ethical approval for this systematic review, because no individual patient data will be used in this study. The results of this systematic review will be published through peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019120814.
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Affiliation(s)
| | - Ming-hui Zhang
- Department of Endocrinology, The People's Hospital of Yan’an, Yan’an, China
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18
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Bocchi EA, Rassi S, Veiga Guimarães G. Reply: Sacubitril/valsartan for Chagas' heart disease heart failure? ESC Heart Fail 2018; 5:1072-1073. [PMID: 30298997 PMCID: PMC6300805 DOI: 10.1002/ehf2.12344] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 06/22/2018] [Indexed: 01/04/2023] Open
Affiliation(s)
| | - Salvador Rassi
- Medical School, Federal University of Goias, Goiania, Brazil
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19
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Ramires FJA, Martinez F, Gómez EA, Demacq C, Gimpelewicz CR, Rouleau JL, Solomon SD, Swedberg K, Zile MR, Packer M, McMurray JJV. Post hoc analyses of SHIFT and PARADIGM-HF highlight the importance of chronic Chagas' cardiomyopathy Comment on: "Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial" by Bocchi et al. ESC Heart Fail 2018; 5:1069-1071. [PMID: 30298996 PMCID: PMC6300803 DOI: 10.1002/ehf2.12355] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 07/20/2018] [Accepted: 08/30/2018] [Indexed: 12/11/2022] Open
Affiliation(s)
- Felix J A Ramires
- Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Felipe Martinez
- Cordoba National University, Instituto DAMIC/Fundación Rusculleda, Córdoba, Argentina
| | | | | | | | - Jean L Rouleau
- Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Canada
| | - Scott D Solomon
- Department of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Karl Swedberg
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.,National Heart and Lung Institute, Imperial College London, London, UK
| | - Michael R Zile
- Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA
| | - Milton Packer
- Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA
| | - John J V McMurray
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK
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20
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Chagas Cardiomyopathy: Evidence in Medical and Nutritional Management. CURRENT TROPICAL MEDICINE REPORTS 2018. [DOI: 10.1007/s40475-018-0155-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Bocchi EA, Rassi S, Guimarães GV. Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial. ESC Heart Fail 2018; 5:249-256. [PMID: 29266804 PMCID: PMC5933959 DOI: 10.1002/ehf2.12240] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Revised: 09/12/2017] [Accepted: 11/14/2017] [Indexed: 12/11/2022] Open
Abstract
AIMS The SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients. METHODS AND RESULTS SHIFT was a randomized, double-blind, placebo-controlled trial in symptomatic systolic stable HF, HR ≥ 70 b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta-blocker. ChD HF presented a poor prognosis (all-cause mortality at 2 years was ~60%). The mean twice-daily dose of ivabradine was 6.26 ± 1.15 mg and placebo 6.43 ± 1.55 mg. Ivabradine reduced HR from 77.9 ± 3.8 to 62.3 ± 10.1 b.p.m. (P = 0.005) and improved functional class (P = 0.02). A trend towards reduction in all-cause death was observed in ivabradine arm vs. placebo (P = 0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope. CONCLUSIONS ChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit-risk profile in ChD HF patients.
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Affiliation(s)
- Edimar Alcides Bocchi
- Heart Institute (InCor)São Paulo University Medical School (HC‐FUMSP)Rua Dr Melo Alves 690, 4o andar, Bairro Cerqueira CesarSão PauloSão PauloCEP 014170‐010Brazil
| | - Salvador Rassi
- Medical SchoolFederal University of GoiásGoiâniaGoiásBrazil
| | - Guilherme Veiga Guimarães
- Heart Institute (InCor)São Paulo University Medical School (HC‐FUMSP)Rua Dr Melo Alves 690, 4o andar, Bairro Cerqueira CesarSão PauloSão PauloCEP 014170‐010Brazil
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