Table 3.
Frailty Interventions in Patients with Cardiovascular Disease
| Type of Intervention |
Type of Study |
Intervention | Subjects | Frailty Instrument Used |
outcomes |
|---|---|---|---|---|---|
| Physical | RCT | Multicomponent Cardiac Rehabilitation(55) | 136 patients with elective transcatheter aortic valve implantation and subsequent inpatient cardiac rehabilitation | Schoenenberger Frailty Index 6MWD Maximum workload in bicycle ergometry | Improved functional capacity, quality of life, and reduction in frailty |
| RCT | Resistance and Balance Training in Exercise-Based Cardiac Rehabilitation(58) | 252 patients admitted to cardiac rehab early after valve surgery/intervention | 6MWD SPPB 5-minute walk test Strength (one repetition maximum test for leg press) | Improved functional and exercise capacity, physical performance, muscular strength, and reduced physical frailty levels | |
| RCT | Cardiac rehabilitation(68) | 89 cardiovascular disease patients with age ≥65 years old who participated in the outpatient cardiac rehabilitation program for 3 months | Japanese Version of the Cardiovascular Health Study Standard Walking speed Maximal grip strength Lower extremity strength | Reduction in frailty and improved physical function | |
| RCT | Structured physical activity intervention after cardiac rehabilitation(67) | 140 frail elderly patients who completed cardiac rehabilitation after elective cardiac surgery | SPPB | Improved physical function | |
| Observational Study | Cardiac Rehabilitation(56) | 60 patients who underwent TAVI and were thereafter referred to cardiac rehabilitation | 6MWD Cumulative Illness Rating Scale | Improvement in function, autonomy and quality of life | |
| Cross-sectional Study | Exercise-based Cardiac Rehabilitation(102) | 78 patients who underwent TAVI compared to 80 patients who underwent sAVR | 6MWD | Enhanced independence, mobility and functional capacity | |
| Retrospective Observational Study | Cardiac Rehabilitation(103) | 3277 patients hospitalized for acute HF | The CSHA Frailty Index | Improved physical functioning and exercise capacity with favorable long-term outcomes in frail patients with HF | |
| Observational Study | 4-week Inpatient Cardiac Rehabilitation(104) | 160 patients aged 75 years and older referred to an outpatient cardiac rehabilitation unit after an acute coronary event or cardiac surgery | 6MWD Peak torque (strength) using an isokinetic dynamometer | Improvement in all domains of physical performance and particularly in those with poorer baseline performance | |
| Prospective Pilot Study | 8-week Combined Endurance and Resistance Exercise Training(105) | 30 patients who underwent TAVI | Muscular strength 6MWD | Improved exercise capacity, muscular strength, and quality of life | |
| Retrospective Study | 3-week cardiac rehabilitation(62) | 442 patients after TAVI or sAVR who were referred to cardiac rehabilitation | 6MWD Bicycle exercise test | Improved functional status and exercise capacity | |
| Retrospective Cohort Study | Cardiac rehabilitation program enhanced with psychological support(63) | 523 elderly inpatients aged ≥75 years admitted to a cardiac rehabilitation ward due to heart disease | Barthel Index | Improvement in psycho-physical health of elderly subjects and significant delay in re-hospitalization | |
| Observational Study | Home-based preoperative rehabilitation (prehab)(49) | 22 patients planned to undergo CABG or valve surgery | Clinical Frailty Score 6MWD SPPB | Improved clinical frailty score, functional ability, and reduced hospital length of stay | |
| Retrospective Analysis | Cardiac rehabilitation(64) | 243 patients with cardiovascular disease who completed phase II cardiac rehabilitation program | Fried Criteria | Improvement in multiple domains of physical function among frail patients, similar to or greater than those achieved by intermediate-frail and nonfrail patients | |
| Observational Study | Patient-centered cardiac rehabilitation(106) | 160 patients over 70 years old admitted in the cardiac rehabilitation unit soon after cardiac surgery | Not available | Improved objective and subjective functional status | |
| Retrospective Study | Geriatric rehabilitation-cardio program(69) | 58 patients hospitalized because of cardiovascular disease | Functional status | Improved functional status and health-related quality of life | |
| Retrospective Study | Comprehensive cardiac rehabilitation, including nutrition, physical exercise and medication(52) | 322 inpatients with cardiovascular disease | Muscle mass (skeletal muscle index) Muscle strength (grip strength) Physical performance (gait speed) | Improved handgrip strength, gait speed, leg weight bearing index, and nutritional intake after exercise training in patients both with and without sarcopenia | |
| RCT | Prehabilitation (PREQUEL Study)(51) | 164 patients who are pre-frail and frail, awaiting CABG with or without valvular repair/replacement | The Clinical Frailty Scale 5m Gait Speed The Essential Frailty Toolset | Unpublished | |
| RCT | Personalized physiotherapy program in-hospital(53) | 224 patients aged 70-87 years who underwent cardiac surgery | Tinetti Performance Oriented Mobility Assessment Get-Up-and-Go Test Mobility Balance Muscle strength | Improved independence and mobility and shorter hospital length of stay | |
| RCT | Pre-operative Rehabilitation (PREHAB Study)(50) | 244 patients age 65 and older who underwent elective cardiac surgery and had a clinical frailty score of 4-7 | Clinical Frailty Score | Unpublished | |
| RCT | Physical activity intervention (HULK Trial)(107) | Elderly (≥70 years) patients with ACS who had an uneventful first month and showed reduced physical performance | SPPB | Unpublished | |
| Retrospective Cohort Study | Early mobilization in the CICU(54) | 264 patients ≥60 years of age admitted to the CICU | Level of Function 1-4 (bedbound to walk >50 ft) Rockwood’s Clinical Frailty Scale | Improvement in functional status in both frail and non-frail older adults | |
| Retrospective Cohort Study | Cardiac rehabilitation(108) | 114 cardiac surgery patients who underwent cardiac rehabilitation | Clinical Frailty Scale Modified Fried Criteria SPPB Functional Frailty Index | No change in frailty scores from baseline to 1-year post-operation, however improvement in cognitive impairment and functional domains of the frailty criteria | |
| Pilot Trial | 6-month cardiac rehabilitation (RECOVER-TAVI Pilot)(57) | 27 patients who underwent TAVI | 6MWD Fried and Edmonton Frailty Scores | Improvement in outcome scores | |
| RCT | Cardiac rehabilitation with resistance training and special balance training(59) | 173 patients aged 75 and older who underwent CABG | 6MWD TUG Test Maximal isometric strength test | Improvements in all measured variables | |
| RCT | 12-week multi-domain physical rehabilitation (REHAB-HF Trial)( 109) | 360 patients age 60 years and older hospitalized with ADHF | SPPB | In process | |
| Pilot Study | 12-week multi-domain physical rehabilitation (REHAB-HF)(60) | 27 patients with ADHF age 60 years and older hospitalized with ADHF | SPPB | Improved SPPB score and reduced all-cause rehospitalization rate | |
| RCT | Acute Phase Intensive Electrical Muscle Stimulation (ACTIVE-EMS Trial)(71) | Frail patients age 75 years and older with AHF | Quadriceps isometric strength Handgrip strength SPPB Gait speed 6MWD Digit Symbol Substitution Test Mini-Cog MOS 36-Item Short-Form Health Survey physical functioning scale Frailty score SARC-F | In process | |
| RCT | Structured physical activity vs health education program (LIFE study)(110) | 1635 sedentary mean and women aged 70-89 years who had physical limitations, defined as a score on SPPB of 9 or below, but able to walk 400 m | Mobility disability defined by loss of ability to walk 400 m | Reduced major mobility disability in the structured, moderate-intensity physical activity program compared with a health education program | |
| Pharmacotherapy | RCT | Rapamycin, an mTOR inhibitor(84) | 13 elderly patients undergoing cardiac rehabilitation | Physical performance Frailty | Some correlation between some senescence markers and physical performance, but no improvement in frailty with rapamycin |
| RCT | Testosterone (intramuscular)(76) | Men 70 years and older, undergoing elective cardiovascular revascularization with extracorporeal circulation | Clinical and functional outcomes | In process | |
| RCT | Vitamin D3(72) | 64 patients with HF | 6MWD TUG test Knee isokinetic muscle strength | No improvement in physical performance for patients with HF despite a robust increase in serum 25OHD | |
| RCT | Vitamin D and Quadriceps Resistance Exercise (FITNESS Trial)(74) | 243 frail older people discharged from the hospital | Physical performance | Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved outcomes in frail older people after hospitalization | |
| RCT | High Omega-3 Fatty Acid Multinutrient Supplement (Efalex Active 50+) for 6 months(77) | 27 non acutely ill postmenopausal women (age 60-84 years) | Mobility (habitual walking speed and fast walking speed) Cognitive performance | Improved cognition and mobility | |
| Cross-sectional Study | Exposure to Metformin(78) | 763 community-dwelling veterans age 65 years and older with type 2 diabetes | Frailty Index | Exposure to metformin was associated with lower risk of frailty | |
| RCT | Metformin(79) | Adults more than 65 years who are prediabetic and not frail at baseline | Fried criteria SPPB | In process | |
| RCT | Antihypertensive medication reduction (OPTIMISE Trial)(85) | 540 adults age 80 years and older with hypertension, prescribed 2 or more antihypertensive treatments | The CSHA Frailty Index Electronic Frailty Index FRAIL Scale | No significant differences in frailty | |
| RCT | Allogeneic human mesenchymal stem cells via intravenous delivery (CRATUS study)(81) | Age 60-95 showing signs of frailty | Activity (CHAMPS questionnaire) Mobility (4-m gait speed test and 6MWD, handgrip strength, SPPB) Exhaustion (multidimensional fatigue inventory questionnaire) | In process | |
| RCT | Testosterone supplementation with and without progressive resistance training(75) | 167 community-dwelling older men with low-normal baseline total testosterone levels | Continuous-scale physical functional performance Bilateral grip strength Leg extensor power Nottingham leg extensor power rig | No effect on functional performance, but improved upper body strength | |
| Meta-analysis | β-Hydroxy-β-Methylbutyrate (HMB) Supplementation(83) | 10 RCTs including 384 participants 50 years or older | Muscle Strength (isokinetic knee flexion, extension, isometric knee extension, handgrip strength, bench press, leg press Physical performance (6MWD, SPPB, gait speed, get-up-and-go) | No or fairly low impact on improving muscle strength or physical performance | |
| Nutrition | RCT | Nutritional Supplement vs Resistance Training(86) | 100 elderly nursing home residents | Muscle strength and size Gait velocity Stair-climbing power | High-intensity resistance exercise training improves muscle strength, however multinutrient supplementation has neither an independent nor an additive effect on these outcomes |
| RCT | Diet, exercise, cognitive training and vascular risk monitoring (FINGER Trial)(96) | 1260 individuals aged 60-77 years with a CAIDE Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age | Change in cognition measured through comprehensive neuropsychological test battery (NTB) Z score | Greater improvement in NTB score in the intervention group | |
| Prospective Cohort Study | Mediterranean-style diet(93) | 690 community-living persons (≥65 years of age) | Frailty defined as at least 2 of the following criteria: poor muscle strength, feeling of exhaustion, low walking speed, and low physical activity | Higher adherence to a Mediterranean-style diet was associated with lower odds of developing frailty compared with those with lower adherence. | |
| Meta-analysis | Mediterranean diet(94) | Analysis of 4 studies including a total 5789 community-dwelling older adults with a mean age of greater than 60 | Frailty | Greater adherence to a Mediterranean diet is associated with significantly lower risk of incident frailty in community-dwelling older people | |
| RCT | Protein-energy supplementation for 12 weeks(90) | 87 frail older adults | Change of physical functioning SPPB Gait speed TUG test Hand grip strength One-legged stance | Physical functioning increased and SPPB remained stable with the intervention although it decreased in the control group. | |
| RCT | Co-supplementation with creatine and protein supplementation combined with resistance training (from the Pro-Elderly study) (87) | 18 subjects | Handgrip strength TUG test Timed-stands test | Whey protein plus creatine and whey protein alone were similarly effective in improving muscle function | |
| RCT | Whey protein supplementation(88) | 47 frail, hospitalized elderly | Grip strength Knee extensor force | Improvements in grip strength and knee extensor force | |
| RCT | Vitamin D and leucine-enriched whey protein nutritional supplement for 13 weeks (PROVIDE study)(89) | 380 sarcopenic primarily independent-living older adults with SPPB scores between 4 and 9 and a low skeletal muscle mass index | Handgrip strength SPPB score Chair-stand test Gait speed Balance score Appendicular muscle mass | Improvement in muscle mass and lower-extremity function | |
| Prospective Cohort Study | ‘Prudent’ dietary pattern characterized by high intake of olive oil and vegetables compared to a ‘Westernized’ pattern with high intake of refined bread, whole dairy products, and red and processed meat(111) | 1872 non-institutionalized individuals aged ≥60 | Fried Criteria | A prudent dietary pattern showed an inverse dose-response relationship with the risk of frailty while a Westernized pattern had a direct relationship with slow walking speed and weight loss. | |
| Meta-analysis | Alcohol consumption(112) | 4 studies on 44,051 subjects age 55 and older | Frailty | Heavier alcohol consumption is associated with lower incident frailty compared with no alcohol consumption among community-dwelling middle-aged and older people | |
| Prospective Cohort Study | Dairy products(95) | 1871 community-dwelling aduls age 60 years and older | Modified version of the Fried criteria | Increased use of low-fat milk or yogurt was associated with a lower risk of frailty, however consumption of whole-milk dairy or cheese did not affect frailty status. | |
| Cognitive | |||||
| RCT | Cognitive stimulation and physical exercise (MIND&GAIT Project)(99) | Older adults age 65 years or more who are supported by the consortium end-user organizations who are frail or at risk of developing frailty | Barthel Index | In process | |
| RCT | Nutritional supplementation vs cognitive training vs physical training vs combination treatment(97) | 246 community-dwelling prefrail and frail old adults with a mean age of 70 years | Fried Criteria | Combination training resulted in the greatest frailty reduction, followed by physical, and then cognitive and nutritional interventions | |
| RCT | Multi-component physical exercise, cognitive training, dietary counseling, and promotion of psychosocial support (WE-RISE trial)(98) | Community-dwelling older adults aged 60 years and above with cognitive frailty | Cognitive frailty status as proposed by I.A.N.A./I.A.G.G. | In process | |
| Social | RCT | Physical training and nutritional intervention program vs social support intervention that included cognitive training(100) | 80 community-dwelling pre-frail and frail adults age 65 years or older | Frailty Status (SHARE-FI) | Decreased frailty with both interventions. Social support alone also resulted in improvement in frailty. |
Abbreviations: 6MWD= 6-Minute Walk Distance; CABG= Coronary Artery Bypass Graft; CHS= Cardiovascular Health Study; HF= Heart Failure; MMSE= Mini-Mental State Exam; RCT= Randomized Control Trial; SPPB= Short Physical Performance Battery; SARC-F= strength, assistance walking, rise from a chair, climb stairs, and falls; SAVR= Surgical Aortic Valve Repair; TAVI= Transcatheter Aortic Valve Intervention; TUG= Timed-up-and-go