老年心力衰竭患者多域衰弱的研究进展
2025-02-19沈忆宁滕士超
[摘要]"衰弱好发于老年人群,在老年心力衰竭患者中尤为普遍。除躯体功能下降外,认知障碍、抑郁情绪、社会隔离等多域衰弱问题屡见不鲜。目前认为多域衰弱包含躯体衰弱、认知-心理衰弱和社会衰弱三个维度。在老年人群中,心力衰竭与多域衰弱双向关联,导致不良结局。有必要采取全面的评估方法明确患者的躯体、认知-心理与社会衰弱风险。据此制定的干预策略包括运动、营养、药物管理、认知训练、心理疗法及社会支持等,强调综合性和个体化。本文阐述老年心力衰竭患者多域衰弱的研究进展,旨在探索多域衰弱定义的统一性、评估方法的标准化及干预策略的合理性。
[关键词]"衰弱;心力衰竭;老年人;评估;干预
[中图分类号]"R592""""""[文献标识码]"A""""""[DOI]"10.3969/j.issn.1673-9701.2025.02.031
Fried等[1]于2001年定义衰弱是一种由于多系统累积性衰退而导致患者生理储备、应激能力下降的脆弱状态,患者因此而易受不良后果的影响。该研究团队认为衰弱恶性循环由躯体功能退化主导,据此制定著名的Fried衰弱表型(Fried’s"frailty"phenotype,FFP)诊断标准。FFP仅体现躯体性功能衰退,并非是对衰弱的完美诠释。2010年,Gobbens等[2]基于躯体、精神和社会三领域健全的整体健康理念,强调衰弱与多领域功能受损相关,并编制Tilburg衰弱指数(Tilburg"frailty"indicator,TFI),衰弱的多维性本质可见一斑。衰弱好发于老年人群,基于TFI的社区老年人衰弱患病率为42%[3]。心血管共病患者是并发衰弱的高危群体之一。心力衰竭作为各种心血管疾病的终末阶段,患者多为高龄人群,其共病负担重,再住院率高,躯体退化、认知障碍、抑郁情绪、社会隔离等问题屡见不鲜[4-6]。为此,Gorodeski等[7]提出域管理法,构建包括临床医疗、躯体功能、心理情绪、社会环境四大领域的老年心力衰竭综合管理模型。2019年,心力衰竭协会/欧洲心脏病学会基于该四域模型发布立场文件,强调心力衰竭语境下衰弱概念的多维性与管理的多域化[8]。老年心力衰竭多域衰弱理念呼之欲出。
1""多域衰弱的组成
目前,人们对衰弱多维性的研究多采用躯体、精神(包括认知功能和心理情绪)与社会三维度衰弱模型。尽管心力衰竭的多域衰弱是四域模型,但实际上是在上述三维度衰弱基础增加心力衰竭的临床医疗(如共病、多重用药管理等)。故本文将侧重介绍多域衰弱中的躯体衰弱、认知-心理衰弱和社会衰弱。
躯体衰弱的定义采用经典FFP诊断标准,即瘦(无意的体质量减轻、肌肉减少症)、弱(握力下降)、疲(易觉疲劳、耐力不足)、迟(步速减慢)、惰(活动减少)。值得注意的是,心力衰竭与躯体衰弱均强调运动耐量的下降,但躯体衰弱所关注的运动表现更广泛,包括力量、移动与平衡能力。认知衰弱定义为除痴呆以外的躯体衰弱和轻度认知功能障碍并存[9]。心理衰弱尚无统一定义,目前多认为应包含认知、情绪(尤其是抑郁)、应对能力等障碍,也强调合并躯体衰弱的重要性,故其与认知衰弱有部分重合[10]。社会衰弱方面。Bunt等[11]研究认为社会性健康的核心是基本社会需求的实现。所需资源为一般资源(经济情况、认知功能等)、社会资源(家庭纽带、邻友相伴等)、社交活动(亲密关系、社会参与等)、自主能力(日常生活活动能力、自我决策能力等)。因此社会衰弱定义几近或已丧失上述资源,导致无法满足基本社会需求的持续状态。
躯体活动能力下降在多域衰弱中普遍存在。为满足基本社会需求,正常的活动能力与健全的认知和情绪不可或缺。因此,躯体衰弱是多域衰弱的发生基础,认知-心理衰弱是多域衰弱的重要纽带,社会衰弱是多域衰弱的综合体现。三维度并非孑然独立,而是相互渗透、彼此影响,共同决定多域衰弱患者的脆弱状态。
2""老年心力衰竭与多域衰弱双向关联
心力衰竭的整体性影响与老年患者多系统障碍相关,导致多域衰弱,其主要的生理学基础是慢性炎症与代谢失衡。增龄与机体促炎状态、代谢功能紊乱相关。心力衰竭可诱发心源性炎症,进而促进全身炎症反应,促进胰岛素抵抗与分解代谢,加重代谢失衡[12]。运动系统的衰退是最为明显的,表现为蛋白降解增加、肌肉成分改变和线粒体功能障碍,患者的运动能力下降,甚至出现肌肉减少症[13]。心力衰竭患者的脑灌注不足,致使前额叶皮质、杏仁核等认知和情绪功能脑区发生缺血损伤[14]。炎症反应可破坏血-脑脊液屏障,细胞因子通过激活脑内小胶质细胞介导神经炎症,引发神经元死亡、β-淀粉样蛋白沉积、神经递质功能异常等病理改变,导致患者出现认知与情绪障碍[14-15]。在此基础上,心力衰竭患者的活动困难、饮食缩减、睡眠障碍等症状不仅有损患者的营养水平和躯体功能,还可导致患者出现负面情绪调节、消极价值认同及封闭社会参与[16]。而相应的认知、心理干预与社会支持往往超出心脏专科的日常临床范畴。老年心力衰竭患者在精神与社会层面的病态难有改观,又将进一步限制其躯体活动,陷入多域衰弱的恶性循环。FRAGILE-HF队列研究聚焦老年住院心力衰竭患者的多域衰弱,分别识别出56.1%、37.1%和66.4%的患者存在躯体、认知和社会衰弱,且55.1%的患者至少合并2种衰弱;且增龄将增加多域衰弱风险[17]。
衰弱也是老年人心力衰竭发病的独立危险因素[18]。老年衰弱患者应激能力下降,更易发生心肌缺血、压力和容量超负荷及心律失常,导致心力衰竭。多域衰弱可增加心力衰竭不良预后的风险,躯体衰弱、认知-心理衰弱、社会衰弱均与心力衰竭患者再住院和(或)死亡结局密切相关,且多衰弱合并者风险更高[17,19-21]。老年心力衰竭与多域衰弱双向关联,有必要对老年心力衰竭患者多域衰弱进行综合管理。
3""多域衰弱的评估方法
3.1""躯体衰弱评估
FFP是最经典的躯体衰弱评估方法。老年心力衰竭患者的活动耐量下降,疲劳乏力等症状重叠,体质量减轻又受到容量波动的掣肘,传统FFP可能混淆心力衰竭与衰弱。老年心力衰竭患者多在住院期间活动受限,久卧久坐,完成FFP要求的明尼苏达业余时间活动问卷可行性欠佳。对此,改良版FFP不断涌现。具有代表性的改良版FFP包括欧洲健康、老龄化和退休调查(survey"of"health,"ageing"and"retirement"in"Europe,SHARE)-衰弱工具(frailty"instrument,FI)、圣文森特衰弱工具(St"Vincent’s"frailty"instrument,SVF)[22-23]。二者均采用食欲减退替代体质量减轻,避免容量波动影响,以低-中度体力活动参与频率代替明尼苏达业余时间活动问卷,易于评价操作。步速评估方面,SVF改用5m距离以便于非英制单位的国家和地区操作;而SHARE-FI则替换为2项回顾式提问,更为快捷。研究显示二者在心力衰竭相关认知障碍、抑郁症、生活质量下降等方面的收敛效度及对衰弱分类的区分效度均优于原版FFP[24]。近年来,可穿戴设备等技术的发展有助于测试模式的改进,可结合信息技术与便携终端达到实时监测的目的[25]。
3.2""认知-心理衰弱评估
蒙特利尔认知评估(Montreal"cognitive"assessment,MoCA)与简易精神状态检查(mini-mental"state"examination,MMSE)量表在认知障碍评估中的应用最为广泛。MoCA的敏感度较高,可识别轻度认知功能障碍,在评估认知衰弱时更受学者青睐[26]。欧洲心脏病学会建议采用贝克抑郁问卷(Beck"depression"inventory,BDI)和心脏抑郁量表(cardiac"depression"scale,CDS)评估心力衰竭患者的抑郁状态,老年抑郁量表(geriatric"depression"scale,GDS)亦可作为备选[27]。第2版BDI依据《精神疾病诊断与统计手册》中的抑郁诊断标准增补相关内容,被认可度高。CDS的优势在于其专为心脏病患者设计,在该群体中有更高的敏感度。GDS则牺牲敏感度,摒弃躯体症状评估,以避免老年慢性病与增龄性不适的干扰。
3.3""社会衰弱评估
基于社会衰弱的定义,实现基本社会需求的必需资源已成为社会衰弱筛查量表的主要内容,核心项目为经济情况、家庭纽带、外出社交与深入交流。Andrew等[28]提出的社会脆弱性指数内容全面,更适合精准评估。社会衰弱筛查量表见表1[29-32]。
3.4""多域衰弱综合评估
Mitnitski等[33]基于累积缺陷模型提出的衰弱指数(frailty"index,FI)包括躯体、认知、心理衰弱及合并症,多域衰弱评估自此初见模型。累积缺陷模型条目繁多,复杂耗时,权重均一必然稀释关键项的评估价值,社会衰弱也因时代局限性并未纳入。当前的多域衰弱评估强调简易、扼要且需囊括社会领域。TFI是标杆性的评估工具。格罗宁根衰弱指标则异曲同工。二者均包括躯体、精神(认知和心理)和社会衰弱的三个维度,共15条目,信效度良好[34]。11条目的埃德蒙顿衰弱量表更为简短,但认知、心理与社会维度均为1条目,全面性有所妥协[35]。近年来,欧洲心力衰竭协会基于四域模型提出心力衰竭协会衰弱评分[8]。除传统三个维度的衰弱外,其考量临床维度的共病负担,有望为心力衰竭患者提供专门的衰弱评估工具。
4""多域衰弱的干预策略
鉴于躯体衰弱在多域衰弱中的重要性,有针对性的运动锻炼和营养指导是干预策略的基础,而药物管理、认知训练、心理疗法与社会支持也不容忽视,应根据患者的综合评估结果制定多维干预方案。
4.1""运动锻炼
运动锻炼是改善躯体衰弱的重要手段。传统心脏康复主要应用提升耐力的有氧运动,但老年心力衰竭患者的躯体衰弱并非耐力下降可一言蔽之。诸如力量、平衡、移动能力的缺陷同样普遍。如未能优先改善上述缺陷,有氧运动不仅使患者耐受不良、收效有限,还增加患者受伤和跌倒的风险[36]。因此,早期增强力量的抗阻运动及改善平衡和移动能力的功能锻炼是改善老年心力衰竭患者躯体衰弱更为安全有效的选择。研究认为阻力训练可提高心力衰竭患者的最大摄氧量与6min步行试验距离,高龄患者也能在安全的低强度训练中获益[37-38]。此外,运动对认知-心理衰弱与社会衰弱的改善值得关注一项。Meta分析结果显示,运动干预可防止心力衰竭伴认知障碍患者的认知功能进一步下降[39]。在改善抑郁方面,抗抑郁药物在心力衰竭患者中铩羽而归,运动疗法则明显优于安慰剂和常规治疗[40]。综合运动干预还可促进老年人群的社交活动,改善社会衰弱[41]。
4.2""营养指导
心力衰竭患者进食减少,营养水平下降,营养治疗自然成为一大干预策略,但其具体获益并不明确。尽管有证据表明补充蛋白质、摄入能量可增加心力衰竭患者的体质量,但部分研究提示体质量标志物三头肌皮褶厚度并未增加[42]。一项Meta分析肯定补充蛋白质和(或)必需氨基酸对提升瘦体质量及运动能力的积极效应,但其对肌肉力量的改善并不明显[43]。综上,营养治疗单行方案作用有限,其联合运动等方式的干预效果仍需探索。
4.3""药物管理
近年来,以血管紧张素受体脑啡肽酶抑制剂(angiotensin"receptor"neprilysin"inhibitor,ARNI)、钠-葡萄糖共转运蛋白2抑制剂(sodium-glucose"cotransporter"2"inhibitor,SGLT2i)为代表的新药已跻身慢性心力衰竭的新四联治疗方案中,其在衰弱领域的应用也得到重视。ARNI的代表性药物是沙库巴曲缬沙坦。给予终末期心力衰竭患者沙库巴曲缬沙坦发现,患者的躯体衰弱显著改善,6min步行试验距离与最大摄氧量均有所增加,抑郁症状也有所缓解[44-45]。武云涛等[46]在老年心力衰竭患者中发现,沙库巴曲缬沙坦干预组患者的心脏功能与衰弱程度均有所改善,且安全性良好。SGLT2i引起的骨骼肌减少效应不免为衰弱老年心力衰竭患者带来用药顾虑。但针对心血管疾病合并2型糖尿病患者的研究支持SGLT2i对患者运动表现的改善作用,患者的力量、步速及6min步行试验距离均有所增加[47]。研究显示与对照组相比,SGLT2i干预组心力衰竭患者的死亡与衰弱相关事件的复合终点发生率更低[48]。综上,SGLT2i有益于改善心力衰竭患者的躯体、认知与心理衰弱,但其在高龄人群中的作用仍需进一步研究证据。
此外,多重用药问题不容忽视。研究显示心力衰竭患者的多重用药发生率为72%~99%[49]。多重用药相关临床不良事件,诸如跌倒、残疾、再住院等在老年衰弱心力衰竭患者中更为常见。有必要多学科联合评估患者的用药方案,舍弃不规范处方,精减低获益药物。
4.4""认知训练与心理疗法
认知训练针对特定认知技能和过程设计标准化任务,通过重复性练习改善认知功能。计算机化认知训练更具可行性与个体化,可改善心力衰竭患者的工作记忆、日常生活活动能力等[50]。认知行为疗法(cognitive"behavioral"therapy,CBT)是一种注重精神症状的心理疗法。除减轻抑郁外,CBT还可提高心力衰竭患者的社会功能与生活质量[51]。相比于单一干预法和常规治疗法,研究发现CBT联合运动疗法的作用全面而持久,患者的抑郁情绪、躯体功能和生活质量等均有显著改善[52]。
4.5""社会支持
帮助社会衰弱患者出院后迅速建立社会联系,需要临床医生、患者自身及社会公益的共同努力。研究表明经过培训的非专业志愿者也能通过定期家访、陪伴外出、交流分享等社会支持措施改善老年患者的营养与衰弱状态[53]。但目前尚缺少体系化的社会衰弱干预措施。
5""小结
由于心力衰竭的多机制发病、多系统影响,加之增龄导致的整体性退化,老年心力衰竭患者往往存在躯体、认知-心理及社会维度的多域衰弱。老年心力衰竭患者的综合管理需要对上述指标进行全面整体的评估及个体化多维度的干预,从而改善该群体的整体预后。目前,相关研究存在衰弱域单一、操作性定义与相应评估模型不尽相同、干预措施循证依据不足等缺陷,且缺少针对老年心力衰竭患者的特化设计。定义的统一性、评估的标准化、干预的合理性仍需进一步探索和优化。
利益冲突:所有作者均声明不存在利益冲突。
[参考文献]
[1] FRIED"L"P,"TANGEN"C"M,"WALSTON"J,"et"al."Frailty"in"older"adults:"Evidence"for"a"phenotype[J]."J"Gerontol"A"Biol"Sci"Med"Sci,"2001,"56(3):"M146–M156.
[2] GOBBENS"R"J,"VAN"ASSEN"M"A,"LUIJKX"K"G,"et"al."The"Tilburg"frailty"indicator:"Psychometric"properties[J]."J"Am"Med"Dir"Assoc,"2010,"11(5):"344–355.
[3] QIU"Y,"LI"G,"WANG"X,"et"al."Prevalence"of"multidimensional"frailty"among"community-dwelling"older"adults:"A"systematic"review"and"Meta-analysis[J]."Int"J"Nurs"Stud,"2024,"154:"104755.
[4] WARRAICH"H"J,"KITZMAN"D"W,"WHELLAN"D"J,"""et"al."Physical"function,"frailty,"cognition,"depression,"and"quality"of"life"in"hospitalized"adults"≥60"years"with"acute"decompensated"heart"failure"with"preserved"versus"reduced"ejection"fraction[J]."Circ"Heart"Fail,"2018,"11(11):"e005254.
[5] YANG"M,"SUN"D,"WANG"Y,"et"al."Cognitive"impairment"in"heart"failure:"Landscape,"challenges,"and"future"directions[J]."Front"Cardiovasc"Med,"2021,"8:"831734.
[6] SAITO"H,"KAGIYAMA"N,"NAGANO"N,"et"al."Social"isolation"is"associated"with"90-day"rehospitalization"due"to"heart"failure[J]."Eur"J"Cardiovasc"Nurs,"2019,"18(1):"16–20.
[7] GORODESKI"E"Z,"GOYAL"P,"HUMMEL"S"L,"et"al."Domain"management"approach"to"heart"failure"in"the"geriatric"patient:"Present"and"future[J]."J"Am"Coll"Cardiol,"2018,"71(17):"1921–1936.
[8] VITALE"C,"JANKOWSKA"E,"HILL"L,"et"al."Heart"Failure"Association/European"Society"of"Cardiology"position"paper"on"frailty"in"patients"with"heart"failure[J]."Eur"J"Heart"Fail,"2019,"21(11):"1299–1305.
[9] KELAIDITI"E,"CESARI"M,"CANEVELLI"M,"et"al."Cognitive"frailty:"Rational"and"definition"from"an"(I.A.N.A./I.A.G.G.)"international"consensus"group[J]."J"Nutr"Health"Aging,"2013,"17(9):"726–734.
[10] ZHAO"J,"LIU"Y"W"J,"TYROVOLAS"S,"et"al."Exploring"the"concept"of"psychological"frailty"in"older"adults:"A"systematic"scoping"review[J]."J"Clin"Epidemiol,"2023,"159:"300–308.
[11] BUNT"S,"STEVERINK"N,"OLTHOF"J,"et"al."Social"frailty"in"older"adults:"A"scoping"review[J]."Eur"J"Ageing,"2017,"14(3):"323–334.
[12] DOEHNER"W,"FRENNEAUX"M,"ANKER"S"D."Metabolic"impairment"in"heart"failure:"The"myocardial"and"systemic"perspective[J]."J"Am"Coll"Cardiol,"2014,"64(13):"1388–1400.
[13] LV"J,"LI"Y,"SHI"S,"et"al."Skeletal"muscle"mitochondrial"remodeling"in"heart"failure:"An"update"on"mechanisms"and"therapeutic"opportunities[J]."Biomed"Pharmacother,"2022,"155:"113833.
[14] WU"Y,"CHEN"L,"ZHONG"F,"et"al."Cognitive"impairment"in"patients"with"heart"failure:"Molecular"mechanism"and"therapy[J]."Heart"Fail"Rev,"2023,"28(4):"807–820.
[15] FELGER"J"C,"LOTRICH"F"E."Inflammatory"cytokines"in"depression:"Neurobiological"mechanisms"and"therapeutic"implications[J]."Neuroscience,"2013,"246:"199–229.
[16] RASHID"S,"QURESHI"A"G,"NOOR"T"A,"et"al."Anxiety"and"depression"in"heart"failure:"An"updated"review[J]."Curr"Probl"Cardiol,"2023,"48(11):"101987.
[17] MATSUE"Y,"KAMIYA"K,"SAITO"H,"et"al."Prevalence"and"prognostic"impact"of"the"coexistence"of"multiple"frailty"domains"in"elderly"patients"with"heart"failure:"The"FRAGILE-HF"cohort"study[J]."Eur"J"Heart"Fail,"2020,"22(11):"2112–2119.
[18] KHAN"H,"KALOGEROPOULOS"A"P,"GEORGIOPOULOU"V"V,"et"al."Frailty"and"risk"for"heart"failure"in"older"adults:"The"health,"aging,"and"body"composition"study[J]."Am"Heart"J,"2013,"166(5):"887–894.
[19] HEIDARI"GORJI"M"A,"FATAHIAN"A,"FARSAVIAN"A."The"impact"of"perceived"and"objective"social"isolation"on"hospital"readmission"in"patients"with"heart"failure:"A"systematic"review"and"Meta-analysis"of"observational"studies[J]."Gen"Hosp"Psychiatry,"2019,"60:"27–36.
[20] YAMADA"S,"ADACHI"T,"IZAWA"H,"et"al."Prognostic"score"based"on"physical"frailty"in"patients"with"heart"failure:"A"multicenter"prospective"cohort"study"(FLAGSHIP)[J]."J"Cachexia"Sarcopenia"Muscle,"2021,"12(6):"1995–2006.
[21] MURAD"K,"GOFF"D"C,"MORGAN"T"M,"et"al."Burden"of"comorbidities"and"functional"and"cognitive"impairments"in"elderly"patients"at"the"initial"diagnosis"of"heart"failure"and"their"impact"on"total"mortality:"The"cardiovascular"health"study[J]."JACC"Heart"Fail,"2015,"3(7):"542–550.
[22] ROMERO-ORTUNO"R,"WALSH"C"D,"LAWLOR"B"A,"et"al."A"frailty"instrument"for"primary"care:"Findings"from"the"survey"of"health,"ageing"and"retirement"in"Europe"(SHARE)[J]."BMC"Geriatr,"2010,"10:"57.
[23] JHA"S"R,"HANNU"M"K,"CHANG"S,"et"al."The"prevalence"and"prognostic"significance"of"frailty"in"patients"with"advanced"heart"failure"referred"for"heart"transplantation[J]."Transplantation,"2016,"100(2):"429–436.
[24] MCDONAGH"J,"SALAMONSON"Y,"FERGUSON"C,"""et"al."Evaluating"the"convergent"and"discriminant"validity"of"three"versions"of"the"frailty"phenotype"in"heart"failure:"Results"from"the"FRAME-HF"study[J]."Eur"J"Cardiovasc"Nurs,"2020,"19(1):"55–63.
[25] ANABITARTE-GARCÍA"F,"REYES-GONZÁLEZ"L,"RODRÍGUEZ-COBO"L,"et"al."Early"diagnosis"of"frailty:"Technological"and"non-intrusive"devices"for"clinical"detection[J]."Ageing"Res"Rev,"2021,"70:"101399.
[26] ALAGIAKRISHNAN"K,"MAH"D,"DYCK"J"R,"et"al."Comparison"of"two"commonly"used"clinical"cognitive"screening"tests"to"diagnose"mild"cognitive"impairment"in"heart"failure"with"the"golden"standard"European"Consortium"criteria[J]."Int"J"Cardiol,"2017,"228:"558–562.
[27] MCDONAGH"T"A,"METRA"M,"ADAMO"M,"et"al."2021"ESC"guidelines"for"the"diagnosis"and"treatment"of"acute"and"chronic"heart"failure[J]."Eur"Heart"J,"2021,"42(36):"3599–3726.
[28] ANDREW"M"K,"MITNITSKI"A"B,"ROCKWOOD"K."Social"vulnerability,"frailty"and"mortality"in"elderly"people[J]."PloS"One,"2008,"3(5):"e2232.
[29] MA"L,"SUN"F,"TANG"Z."Social"frailty"is"associated"with"physical"functioning,"cognition,"and"depression,"and"predicts"mortality[J]."J"Nutr"Health"Aging,"2018,"22(8):"989–995.
[30] CHEN"Z,"JIANG"X,"SHI"G,"et"al."Social"frailty"and"longitudinal"risk"of"depressive"symptoms"in"a"Chinese"population:"The"Rugao"longevity"and"aging"study[J]."Psychogeriatrics,"2021,"21(4):"483–490.
[31] YAMADA"M,"ARAI"H."Social"frailty"predicts"incident"disability"and"mortality"among"community-dwelling"Japanese"older"adults[J]."J"Am"Med"Dir"Assoc,"2018,"19(12):"1099–1103.
[32] PEK"K,"CHEW"J,"LIM"J"P,"et"al."Social"frailty"is"independently"associated"with"mood,"nutrition,"physical"performance,"and"physical"activity:"Insights"from"a"theory-guided"approach[J]."Int"J"Environ"Res"Public"Health,"2020,"17(12):"4239.
[33] MITNITSKI"A"B,"MOGILNER"A"J,"ROCKWOOD"K."Accumulation"of"deficits"as"a"proxy"measure"of"aging[J]."SciWorld"J,"2001,"1:"323–336.
[34] PETERS"L"L,"BOTER"H,"BUSKENS"E,"et"al."Measurement"properties"of"the"Groningen"frailty"indicator"in"home-dwelling"and"institutionalized"elderly"people[J]."J"Am"Med"Dir"Assoc,"2012,"13(6):"546–551.
[35] ROLFSON"D"B,"MAJUMDAR"S"R,"TSUYUKI"R"T,"""et"al."Validity"and"reliability"of"the"Edmonton"frail"scale[J]."Age"Ageing,"2006,"35(5):"526–529.
[36] KITZMAN"D"W,"WHELLAN"D"J,"DUNCAN"P,"et"al."Physical"rehabilitation"for"older"patients"hospitalized"for"heart"failure[J]."N"Engl"J"Med,"2021,"385(3):"203–216.
[37] FISHER"S,"SMART"N"A,"PEARSON"M"J."Resistance"training"in"heart"failure"patients:"A"systematic"review"and"Meta-analysis[J]."Heart"Fail"Rev,"2022,"27(5):"1665–1682.
[38] GRGIC"J,"GAROFOLINI"A,"ORAZEM"J,"et"al."Effects"of"resistance"training"on"muscle"size"and"strength"in"very"elderly"adults:"A"systematic"review"and"Meta-analysis"of"randomized"controlled"trials[J]."Sports"Med,"2020,"50(11):"1983–1999.
[39] PENG"J"Y,"CHEN"Y"H,"YEN"J"H,"et"al."Effects"of"exercise"training"on"cognitive"function"in"individuals"with"heart"failure:"A"Meta-analysis[J]."Phys"Ther,"2023,"103(6):"pzad027.
[40] DAS"A,"ROY"B,"SCHWARZER"G,"et"al."Comparison"of"treatment"options"for"depression"in"heart"failure:"A"network"Meta-analysis[J]."J"Psychiatr"Res,"2019,"108:"7–23.
[41] TARAZONA-SANTABALBINA"F"J,"GÓMEZ-CABRERA"M"C,"PÉREZ-ROS"P,"et"al."A"multicomponent"exercise"intervention"that"reverses"frailty"and"improves"cognition,"emotion,"and"social"networking"in"the"community-"dwelling"frail"elderly:"A"randomized"clinical"trial[J]."J"Am"Med"Dir"Assoc,"2016,"17(5):"426–433.
[42] HABAYBEH"D,"DE"MORAES"M"B,"SLEE"A,"et"al."Nutritional"interventions"for"heart"failure"patients"who"are"malnourished"or"at"risk"of"malnutrition"or"cachexia:"A"systematic"review"and"Meta-analysis[J]."Heart"Fail"Rev,"2021,"26(5):"1103–1118.
[43] NICHOLS"S,"MCGREGOR"G,"AL-MOHAMMAD"A,"""et"al."The"effect"of"protein"and"essential"amino"acid"supplementation"on"muscle"strength"and"performance"in"patients"with"chronic"heart"failure:"A"systematic"review[J]."Eur"J"Nutr,"2020,"59(5):"1785–1801.
[44] CACCIATORE"F,"AMARELLI"C,"MAIELLO"C,"et"al."Sacubitril/valsartan"in"patients"listed"for"heart"transplantation:"Effect"on"physical"frailty[J]."ESC"Heart"Fail,"2020,"7(2):"757–762.
[45] CACCIATORE"F,"AMARELLI"C,"MAIELLO"C,"et"al."Effect"of"sacubitril-valsartan"in"reducing"depression"in"patients"with"advanced"heart"failure[J]."J"Affect"Disord,"2020,"272:"132–137.
[46] 武云涛,"姚璐,"陈艳梅,"等."ARNI对90岁以上老年慢性心力衰竭患者心功能及衰弱的影响[J]."中国循证心血管医学杂志,"2023,"15(4):"432–435.
[47] KASHIMA"A,"KAMIYA"K,"HAMAZAKI"N,"et"al."Association"between"SGLT2"inhibitors"and"cardiac"rehabilitation"outcomes"in"patients"with"cardiovascular"disease"and"type"2"diabetes"mellitus[J]."J"Clin"Med,"2022,"11(19):"5956.
[48] HORIUCHI"Y,"ASAMI"M,"YAHAGI"K,"et"al."Sodium-"glucose"cotransporter-2"inhibitors"in"heart"failure"with"malnutrition,"frailty,"sarcopenia,"or"cachexia[J]."J"Clin"Med,"2024,"13(6):"1670.
[49] BEEZER"J,"AL"HATRUSHI"M,"HUSBAND"A,"et"al."Polypharmacy"definition"and"prevalence"in"heart"failure:"A"systematic"review[J]."Heart"Fail"Rev,"2022,"27(2):"465–492.
[50] KUA"Z"J,"VALENZUELA"M,"DONG"Y."Can"computerized"cognitive"training"improve"cognition"in"patients"with"heart"failure?:"A"review[J]."J"Cardiovasc"Nurs,"2019,"34(2):"E19–E27.
[51] MHANNA"M,"SAUER"M"C,"AL-ABDOUH"A,"et"al."Cognitive"behavioral"therapy"for"depression"in"patients"with"heart"failure:"A"systematic"review"and"Metanalysis"of"randomized"control"trials[J]."Heart"Fail"Rev,"2023,"28(5):"1091–1100.
[52] GARY"R"A,"DUNBAR"S"B,"HIGGINS"M"K,"et"al."Combined"exercise"and"cognitive"behavioral"therapy"improves"outcomes"in"patients"with"heart"failure[J]."""""J"Psychosom"Res,"2010,"69(2):"119–131.
[53] LUGER"E,"DORNER"T"E,"HAIDER"S,"et"al."Effects"of"a"home-based"and"volunteer-administered"physical"training,"nutritional,"and"social"support"program"on"malnutrition"and"frailty"in"older"persons:"A"randomized"controlled"trial[J]."J"Am"Med"Dir"Assoc,"2016,"17(7):"671.
(收稿日期:2024–09–21)
(修回日期:2024–11–20)