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It remains to be elucidated whether Ca2+ antagonists induce pharmacological preconditioning to protect the heart against ischemia/reperfusion injury. The aim of this study was to determine whether and how pretreatment with a Ca2+ antagonist, azelnidipine, could protect cardiomyocytes against hypoxia/reoxygenation (H/R) injury in vitro. Using HL-1 cardiomyocytes, we studied effects of azelnidipine on NO synthase (NOS) expression, NO production, cell death and apoptosis during H/R. Action potential durations (APDs) were determined by the whole-cell patch-clamp technique. Azelnidipine enhanced endothelial NOS phosphorylation and NO production in HL-1 cells under normoxia, which was abolished by a heat shock protein 90 inhibitor, geldanamycin, and an antioxidant, N-acetylcysteine. Pretreatment with azelnidipine reduced cell death and shortened APDs during H/R. These effects of azelnidipine were diminished by a NOS inhibitor, L-NAME, but were influenced by neither a T-type Ca2+ channel inhibitor, NiCl2, nor a N-type Ca2+ channel inhibitor, ω-conotoxin. The azelnidipine-induced reduction in cell death was not significantly enhanced by either additional azelnidipine treatment during H/R or increasing extracellular Ca2+ concentrations. RNA sequence (RNA-seq) data indicated that azelnidipine-induced attenuation of cell death, which depended on enhanced NO production, did not involve any significant modifications of gene expression responsible for the NO/cGMP/PKG pathway. We conclude that pretreatment with azelnidipine protects HL-1 cardiomyocytes against H/R injury via NO-dependent APD shortening and L-type Ca2+ channel blockade independently of effects on gene expression.
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The increased numbers of older and frail patients with heart failure (HF) means there is an urgent need to establish regional collaborative systems for medical and nursing care. However, expectations related to collaborative HF care among medical and care staff remain unclear. We conducted a questionnaire survey with staff in hospitals, clinics, and nursing care facilities (NCFs) who had experienced collaboration through the common HF collaborative pathway in the western region of Tottori Prefecture, Japan, from July 2019 to July 2020. We received 150 responses from hospitals and 41 responses from clinics and NCFs. Following introduction of the collaborative pathway, 57% of respondents from hospitals, 35% from clinics, and 71% from NCFs rated collaboration as improved. Staff from hospitals and clinics were most satisfied with improved education interventions following implementation of the collaborative pathway, and NCF staff were most satisfied with improved information sharing. Staff from hospitals and NCFs placed the highest importance on improving information sharing through collaboration, and clinic staff placed the highest importance on improving efficiency. The needs for collaborative HF care differ between hospitals, clinics, and NCFs. A collaboration program should be designed to meet the different needs of diverse staff in the community.
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Insuficiência Cardíaca , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hospitais , Humanos , Japão , Inquéritos e QuestionáriosRESUMO
The recommended starting dose of Tolvaptan for heart failure (HF) is 7.5 mg/day in Japan; the recommended dose is 3.75 mg/day for older patients to avoid excessive diuresis and hypernatremia. However, low-dose Tolvaptan may delay the release of congestion in some patients. We aimed to develop a score to predict treatment responders to 3.75 mg tolvaptan.We retrospectively analyzed 106 patients with HF who initially received 3.75 mg/day of Tolvaptan in the derivation cohort (April 2013-December 2017) and 63 patients receiving 3.75 mg/day of Tolvaptan in the validation cohort (January 2018-April 2021). Treatment responders to 3.75 mg tolvaptan did not require dose escalation of Tolvaptan for congestion relief. In multivariate analysis, blood urea nitrogen (BUN) < 39 mg/dL and hematocrit > 35% were selected as variables to predict treatment responders. These were assigned 1 point each, and patients were stratified into groups with 2 points (n = 32), 1 point (n = 39), and 0 points (n = 35). The frequency of treatment responders was 82.9% in the 2-point group, 61.5% in the 1-point group, and 34.4% in the 0-point group (P < 0.05). The predictive ability of the score was acceptable with an area under the receiving operator characteristic curve (AUC) 0.726 (P < 0.05); its performance was maintained in the validation cohort (AUC 0.733, P < 0.05).A simple score using BUN and hematocrit could identify treatment responders to 3.75 mg tolvaptan, which may help determine the appropriate starting dose of Tolvaptan, balancing efficiency with safety for older patients with HF.
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Antagonistas dos Receptores de Hormônios Antidiuréticos , Insuficiência Cardíaca , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Benzazepinas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Estudos Retrospectivos , Tolvaptan/uso terapêuticoRESUMO
This study examined quality indicators (QIs) for heart failure (HF) in patients' referral documents (PRDs).We conducted a nationwide questionnaire survey to identify information that general practitioners (GPs) would like hospital cardiologists (HCs) to include in PRDs and that HCs actually include in PRDs. The percentage of GPs that desired each item included in PRDs was converted into a deviation score, and items with a deviation score of ≥ 50 were defined as QIs. We rated the quality of PRDs provided by HCs based on QI assessment.We received 281 responses from HCs and 145 responses from GPs. The following were identified as QIs: 1) HF cause; 2) B-type natriuretic peptide (BNP) or N-terminal pro-BNP concentration; 3) left ventricular ejection fraction or echocardiography; 4) body weight; 5) education of patients and their families on HF; 6) physical function, and 7) functions of daily living. Based on QI assessment, only 21.7% of HCs included all seven items in their PRDs. HCs specializing in HF and institutions with many full-time HCs were independently associated with including the seven items in PRDs.The quality of PRDs for HF varies among physicians and hospitals, and standardization is needed based on QI assessment.
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Insuficiência Cardíaca , Indicadores de Qualidade em Assistência à Saúde , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Japão , Encaminhamento e Consulta , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: The purpose of this study was to clarify the current status and issues of community collaboration in heart failure (HF) using a nationwide questionnaire survey.MethodsâandâResults:We conducted a survey among hospital cardiologists and general practitioners (GPs) using a web-based questionnaire developed with the Delphi method, to assess the quality of community collaboration in HF. We received responses from 46 of the 47 prefectures in Japan, including from 281 hospital cardiologists and 145 GPs. The survey included the following characteristics and issues regarding community collaboration. (1) Hospital cardiologists prioritized medical intervention for preventing HF hospitalization and death whereas GPs prioritized supporting the daily living of patients and their families. (2) Hospital cardiologists have not provided information that meets the needs of GPs, and few regions have a community-based system that allows for the sharing of information about patients with HF. (3) In the transition to home care, there are few opportunities for direct communication between hospitals and community staff, and consultation systems are not well developed. CONCLUSIONS: The current study clarified the real-world status and issues of community collaboration for HF in Japan, especially the differences in priorities for HF management between hospital cardiologists and GPs. Our data will contribute to the future direction and promotion of community collaboration in HF management.
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Cardiologistas , Clínicos Gerais , Insuficiência Cardíaca , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Japão , Encaminhamento e ConsultaRESUMO
BACKGROUND: Inspiratory muscle weakness is associated with the development of exercise intolerance in patients with heart failure (HF). Ultrasound assessment of the diaphragm is used to evaluate respiratory muscle function, but its application in patients with HF remains undefined. We examined the relationship of diaphragm function as assessed by ultrasonography with inspiratory muscle strength and exercise tolerance in HF. METHODS AND RESULTS: Seventy-seven patients hospitalized with HF were enrolled. Impaired diaphragm muscle function was defined as a diaphragm thickness at end-inspiration of less than the median value of 4.0 mm, which represents diaphragm muscle loss and reduced contraction. Compared with patients with preserved diaphragm muscle function, those with impaired diaphragm muscle function were older; had significantly lower vital capacity, handgrip strength, and inspiratory muscle strength as assessed by the maximum inspiratory pressure; and had a significantly shorter 6-minute walk distance (6MWD; P < .05). Although low handgrip strength was also associated with a short 6MWD, the relationship between impaired diaphragm muscle function and short 6MWD was independent from age, vital capacity, and handgrip strength. CONCLUSION: Diaphragm dysfunction as assessed by ultrasonography represents inspiratory muscle weakness and predicts exercise intolerance independently from comorbid pulmonary dysfunction and dynapenia in patients with HF.
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Diafragma/fisiopatologia , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/complicações , Debilidade Muscular/etiologia , Idoso , Diafragma/diagnóstico por imagem , Teste de Esforço , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Debilidade Muscular/diagnóstico , Debilidade Muscular/fisiopatologia , Curva ROC , Músculos Respiratórios/fisiopatologia , Estudos Retrospectivos , UltrassonografiaRESUMO
Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.
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Gerenciamento Clínico , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/fisiologia , Serviços de Assistência Domiciliar , Monitorização Fisiológica/métodos , Telemedicina/métodos , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Morbidade/tendências , Estudos ProspectivosRESUMO
BACKGROUND: The relationship between inspiratory muscle weakness (IMW) and exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains unestablished. METHODS AND RESULTS: The present study enrolled 40 patients with HFpEF (EF ≥45%). IMW was defined as maximum inspiratory pressure <70% normal predicted values. The function of the diaphragm was assessed by means of ultrasound measurement of muscle thickening of the diaphragm. IMW was prevalent in 27.5% of patients. Patients with IMW had significantly lower vital capacity relative to normal predicted values (%VC), lower knee extensor muscle strength in relation to body weight (%KEMS), poorer nutritional status as assessed by means of the Geriatric Nutritional Risk Index, and shorter 6-minute walk distance (6MWD) compared with patients without IMW (all P < .05). Impaired diaphragm muscle thickening at end-inspiration (median value < 3.9 mm) was significantly associated with a high prevalence of IMW and reduced 6MWD (all P < .05). Subgroup analysis showed that IMW was accompanied by a further decrease in 6MWD in patients with restrictive pulmonary dysfunction (%VC <80%) or lower-limb muscle weakness (median %KEMS <30%; all P < .05). CONCLUSIONS: IMW is associated with exercise intolerance in patients with HFpEF.
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Diafragma/fisiopatologia , Tolerância ao Exercício , Insuficiência Cardíaca/fisiopatologia , Debilidade Muscular/fisiopatologia , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Diafragma/diagnóstico por imagem , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Debilidade Muscular/etiologia , Estado Nutricional , Testes de Função Respiratória , UltrassonografiaRESUMO
BACKGROUND: Several reports have evaluated the association between seasonal variation and acute heart failure (AHF) onset. Cold weather may induce AHF, but the clinical characteristics of patients susceptible to AHF during winter have not been established. Clinical Scenario (CS) is used in the early clinical management of AHF, so we investigated the relationship between CS classification and winter onset of AHF in Japan. METHODS AND RESULTS: We enrolled 582 patients hospitalized for AHF and compared the frequency of AHF among the 4 seasons in each CS group to clarify the clinical characteristics of the winter onset group. Significant increase of AHF during winter was seen in CS1 (systolic blood pressure [SBP] (>140 mmHg) (P=0.01) but not in CS2 (SBP ≥ 100 and ≤ 140 mmHg) or CS3 (SBP <100 mmHg). CS1 patients were divided into winter and other season admission groups. In multivariate analysis, only lack of loop diuretic use was associated with winter admission of CS1 patients (odds ratio 0.562, 95% confidence interval: 0.256-0.798, P=0.006). CONCLUSIONS: Winter predominance of AHF was seen only in CS1, and lack of loop diuretic use was a risk factor for winter onset. Future studies are necessary to confirm whether loop diuretics are useful in preventing AHF with CS1 in winter.
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Temperatura Baixa/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Hipertensão/epidemiologia , Estações do Ano , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/uso terapêutico , Comorbidade , Gerenciamento Clínico , Suscetibilidade a Doenças , Uso de Medicamentos , Feminino , Insuficiência Cardíaca/classificação , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/tratamento farmacológico , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Sistema Nervoso Simpático/fisiopatologia , Sístole , VasoconstriçãoAssuntos
Cardiologia/normas , Insuficiência Cardíaca/terapia , Desnutrição/terapia , Avaliação Nutricional , Estado Nutricional , Apoio Nutricional/normas , Consenso , Medicina Baseada em Evidências/normas , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/fisiopatologia , Valor Preditivo dos Testes , PrognósticoAssuntos
Terapia de Ressincronização Cardíaca/normas , Procedimentos Cirúrgicos Cardíacos/normas , Cardiologia/normas , Fármacos Cardiovasculares/uso terapêutico , Cardioversão Elétrica/normas , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Serviços Preventivos de Saúde/normas , Doença Aguda , Terapia de Ressincronização Cardíaca/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fármacos Cardiovasculares/efeitos adversos , Doença Crônica , Consenso , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/instrumentação , Insuficiência Cardíaca/fisiopatologia , Humanos , Cuidados Paliativos/normas , Valor Preditivo dos Testes , Fatores de Risco , Comportamento de Redução do Risco , Resultado do TratamentoRESUMO
BACKGROUND: Heart failure (HF) patients living in rural areas have a lack of HF knowledge and poor self-care because of limited medical care access. Multidisciplinary education to improve self-care behavior is indispensable for such patients. The present study evaluated whether intensive inpatient education improved outcomes of hospitalized HF patients in a Japanese rural setting. METHODS: An inpatient HF management program based on multidisciplinary team intervention was applied to hospitalized HF patients in a Japanese rural area. We defined patients treated within the program from May 2009 to April 2011 as the intervention group (n = 144), and those treated with the usual care from May 2006 to April 2009 as the usual care group (n = 133). The composite endpoints of HF hospitalization and all-cause mortality were compared between the two groups. RESULTS: Compared with patients in the usual care group, those in the intervention group more often received the optimal interventions such as discharge use of ß-blockers, cardiac rehabilitation, pre-discharge diagnostic tests, and multidisciplinary intensive education including nurse-led patient education, pharmacist's medication teaching, and dietitian's nutritional guidance (all P < 0.05). The incidence of the composite endpoints significantly decreased after introducing the program (P < 0.001). Among a number of interventions, multidisciplinary intensive education was the most effective intervention to improve the primary outcome (P < 0.001). CONCLUSIONS: Multidisciplinary intensive education is a key strategy for helping improve the outcome for Japanese HF patients in a rural setting. Our data may give a positive impact on the improvement of healthcare system in Japan.
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Insuficiência Cardíaca/reabilitação , Hospitalização , Educação de Pacientes como Assunto , Serviços de Saúde Rural , Autocuidado , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Feminino , Humanos , Japão , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
AIMS: A high extracellular water (ECW) to intracellular water (ICW) ratio of skeletal muscle as assessed by bioelectrical impedance analysis is reportedly associated with loss of muscle strength. However, the validity of this index for heart failure (HF), which is likely associated with changes in the water distribution, is unclear. METHODS AND RESULTS: This study involved 190 patients with HF. The total ECW and ICW of both upper and lower extremities were measured, and a high ECW/ICW ratio was defined as an ECW/ICW ratio higher than the median (≥0.636 for men, ≥0.652 for women). Low muscle strength was defined as reduced handgrip strength according to the criteria established by the Asian Working Group for Sarcopenia. Patients with a high ECW/ICW ratio had a lower handgrip strength (21.1 ± 8.1 kg vs. 27.6 ± 9.3 kg, P ≤ 0.05) and 6 min walk distance (329 ± 116 m vs. 440 ± 114 m) than those with a low ECW/ICW ratio. An increasing ECW and/or decreasing ICW was associated with a higher ECW/ICW ratio and a lower handgrip strength (P < 0.05). In the multivariate logistic regression analysis, a high ECW/ICW ratio and low skeletal muscle mass were independently associated with low muscle strength (P < 0.05). CONCLUSIONS: A high ECW/ICW ratio in limb muscles, that is, the water imbalance of increasing ECW and/or decreasing ICW, is useful in assessing muscle quality in patients with HF.
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AIMS: Higher left ventricular (LV) ejection fraction (EF) is related to unfavourable prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The cause of this finding needs to be haemodynamically explained. Thus, we investigated this crucial issue from the perspective of LV-arterial (A) and right ventricular (RV)-pulmonary arterial (PA) coupling. METHODS AND RESULTS: Study patients were derived from our prospective cohort study of patients hospitalized due to acute decompensated HF and LVEF > 40%. We divided the 255 patients into three groups: HF with mildly reduced EF (HFmrEF), HFpEF with 50% ≤ LVEF < 60%, and HFpEF with LVEF ≥ 60%. We compared LV end-systolic elastance (Ees), effective arterial elastance (Ea), and Ees/Ea as a representative of LV-A coupling among groups and compared the ratio of tricuspid annular plane excursion to peak pulmonary arterial systolic pressure (TAPSE/PASP) as a representative of RV-PA coupling. All-cause death and readmission due to HF-free survival was worse in the group with a higher LVEF range. Ees/Ea was greater in HFpEF patients with LVEF ≥ 60% (2.12 ± 0.57) than in those with 50% ≤ LVEF < 60% (1.20 ± 0.14) and those with HFmrEF (0.82 ± 0.09) (P < 0.001). PASP was increased in the groups with higher LVEF; however, TAPSE/PASP did not differ among groups (n = 168, P = 0.17). In a multivariate Cox proportional hazard model, TAPSE/PASP but not PASP was significantly related to event-free survival independent of LVEF. CONCLUSION: HFpEF patients with higher LVEF have unfavourable prognosis and distinctive LV-A coupling: Ees/Ea is elevated up to 2.0 or more. Impaired RV-PA coupling also worsens prognosis in such patients. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000017725.
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Insuficiência Cardíaca , Artéria Pulmonar , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico por imagem , Masculino , Feminino , Volume Sistólico/fisiologia , Idoso , Estudos Prospectivos , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/diagnóstico por imagem , Prognóstico , Estudos de Coortes , Pessoa de Meia-Idade , Medição de Risco , EcocardiografiaRESUMO
Background: With the aging of heart failure (HF) patients, collaboration between medical and nursing care facilities is essential for HF care. The aims of this study were: (1) to identify the factors that affect willingness of nursing care staffs to cooperate with HF care; (2) to test whether the internet video education is useful in improving their willingness to collaborate. Methods: A web-based questionnaire was e-mailed to 417 registered medical corporations that operated nursing care facilities in the prefecture where the authors work. Medical and care staff working at each facility were asked their willingness to cooperate with HF care and their problems about collaboration. Machine learning analysis was used to assess the factors associated with unwillingness to cooperate. After watching a 6-min YouTube video explaining HF and community collaboration, we reaffirmed their willingness to cooperate. Results: We received responses from 76 medical and care staff members. Before watching the video, 32.9% of participants stated that they were unwilling to cooperate with HF care. Machine learning analysis showed that job types, perceived problems of collaboration, and low opportunities to learn about HF were associated with unwillingness to cooperation. After watching the video, we observed an increase from 67.1% to 80.3% (p < 0.05) of participants willing to cooperate with HF care. Conclusions: Job types, perceived problems of collaboration, and low opportunities to learn about HF are associated with unwillingness of nursing care staff for HF care. Internet videos are potential learning tool that can easily promote community collaboration for HF.