Evaluation of the Effectiveness of Hybrid Cardiac Rehabilitation in Peripheral Artery Disease

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and is associated with impaired lower extremity perfusion, intermittent claudication, reduced functional capacity, and diminished quality of life. Supervised exercise therapy (SET) is strongly recommended by international guidelines as a first-line treatment for symptomatic PAD, as it improves pain-free and maximal walking distance and delays the need for invasive interventions. Despite its proven effectiveness, participation in center-based SET programs remains suboptimal due to logistical, socioeconomic, and symptom-related barriers.

Hybrid cardiac rehabilitation (HCR) has emerged as a promising alternative model that integrates center-based supervised exercise with home-based and telerehabilitation-supported interventions. This approach aims to preserve the clinical benefits of supervised exercise while improving accessibility, flexibility, and long-term adherence.

This study is designed as a randomized controlled, single-blind trial to compare the clinical effectiveness of hybrid cardiac rehabilitation with conventional supervised exercise therapy in patients diagnosed with peripheral artery disease. Eligible participants aged 50-70 years with stable intermittent claudication (Fontaine stages I-II or Rutherford categories 1-3) will be randomly allocated to either the hybrid cardiac rehabilitation group or the supervised exercise therapy group.

Both groups will participate in a structured 12-week exercise program conducted three times per week. The supervised exercise therapy group will receive fully center-based, physiotherapist-supervised aerobic and strengthening exercises. The hybrid cardiac rehabilitation group will initially participate in center-based supervised sessions, followed by a home-based telerehabilitation phase supported by real-time or asynchronous remote monitoring. Exercise intensity and progression will be individualized based on perceived exertion, symptom tolerance, and functional assessments. Wearable activity tracking devices will be used to objectively monitor physical activity and adherence.

Outcome assessments will be performed at baseline and after completion of the intervention period. Primary outcome measures will include pain-free walking distance, maximal walking distance, and functional exercise capacity. Secondary outcomes will include exercise adherence, lower extremity muscle strength, walking tolerance, claudication pain severity, daily physical activity levels, and patient-reported outcomes related to quality of life and psychological well-being.

By directly comparing hybrid cardiac rehabilitation with supervised exercise therapy in a randomized controlled design, this study aims to address an important gap in the literature and to determine whether hybrid cardiac rehabilitation represents a feasible and effective alternative treatment strategy for patients with peripheral artery disease.

• Hybrid Cardiac Rehabilitation (Behavioral): The hybrid cardiac rehabilitation intervention consists of a structured exercise program combining center-based supervised treadmill walking sessions with home-based walking and strengthening exercises supported by telerehabilitation. Exercise intensity and progression are individualized based on perceived exertion and symptom tolerance. Participants are remotely monitored using wearable activity tracking devices and regular physiotherapist follow-up.
• Supervised Exercise Therapy (Behavioral): Supervised exercise therapy consists of a center-based exercise program performed under the supervision of a physiotherapist. The program includes treadmill walking and strengthening exercises delivered according to established peripheral artery disease rehabilitation guidelines. Exercise intensity and progression are individualized based on perceived exertion, symptom tolerance, and functional capacity.

Primary outcomes

• Pain-Free Walking Distance [Baseline and Week 12]: Change in Pain-Free Walking Distance during constant-load treadmill test. Distance walked (meters) from the start of treadmill walking (3.2 km/h, 12% incline) until the onset of claudication pain.
• Maximal Walking Distance [Baseline and Week 12]: Total distance walked (meters) from the start of treadmill walking (3.2 km/h, 12% incline) until maximal tolerable claudication pain (Likert scale level 4).
• Functional Capacity [Baseline and Week 12]: Change in functional capacity will be assessed using the 6-Minute Walk Test (6MWT) performed according to the American Thoracic Society (ATS) guidelines (2002). The total distance walked (in meters) during the 6-minute test will be recorded. The test will be conducted in a 30-meter corridor, with standardized instructions and encouragement protocols.

Secondary outcomes

• Muscle Strength [Baseline and Week 12]: Lower extremity muscle strength, balance, and functional mobility assessed using the Short Physical Performance Battery (SPPB), which includes a 4-meter gait speed test, chair stand test, and standing balance test. Each component is scored from 0 to 4, with a total score ranging from 0 to 12. Higher scores indicate better lower extremity physical performance.
• Walking Tolerance [Baseline and Week 12]: Walking tolerance will be assess with Walking Impairment Questionnaire (WIQ) total score. Self-reported walking limitation assessed using WIQ (score 0-100). The higher scores indicating better walking ability.
• Claudication Pain Severity [Baseline and Week 12]: Severity of claudication pain will be assessed using a 5-point Likert-type pain scale developed specifically for intermittent claudication, rated by the patient. The scale ranges from 0 (no pain) to 4 (maximum pain - unable to continue walking). Patients will be instructed to rate their worst pain during walking on this scale. Higher scores indicate worse pain severity.
• LDL Cholesterol (mg/dL) [Baseline and Week 12]: Serum LDL cholesterol concentration will be measured in mg/dL at baseline and week 12 using standard enzymatic colorimetric methods performed at the hospital's central biochemistry laboratory. Fasting blood samples (≥8 hours) will be used.
• HDL Cholesterol (mg/dL) [Baseline and Week 12]: Serum HDL cholesterol level will be measured using direct enzymatic colorimetric assay in mg/dL. Fasting samples collected by venipuncture.
• Total Cholesterol (mg/dL) [Baseline and Week 12]: Total serum cholesterol will be assessed by enzymatic methods using a spectrophotometric autoanalyzer, reported in mg/dL.
• Triglycerides (mg/dL) [Baseline and Week 12]: Triglyceride levels in fasting serum samples will be measured in mg/dL using standard enzymatic assays (GPO-PAP method).
• Fasting Plasma Glucose (mg/dL) [Baseline and Week 12]: Fasting blood glucose levels (mg/dL) will be measured with hexokinase-based enzymatic methods at the hospital's laboratory.
• HbA1c (%) [Baseline and Week 12]: Glycated hemoglobin (HbA1c) will be measured using high-performance liquid chromatography (HPLC) and expressed as a percentage (%).
• Daily Physical Activity Level [Throughout the 12-week intervention period]: Daily physical activity level assessed using wearable activity monitoring devices. Steps per day measured using wearable activity monitor.

Sex: All, ages: 50 Years to 70 Years

Inclusion Criteria:

* Diagnosis of peripheral artery disease with stable intermittent claudication.
* Fontaine stage I-II or Rutherford category 1-3.
* Age between 50 and 70 years.
* Ability to walk independently without assistive devices.
* Medically stable and eligible for exercise-based rehabilitation.
* Willingness to participate in the study and to comply with the exercise program.
* Provision of written informed consent prior to participation.

Exclusion Criteria:

* Critical limb ischemia or rest pain.
* Recent lower extremity revascularization or major surgery within the past 6 months.
* Unstable cardiovascular conditions (e.g., unstable angina, uncontrolled arrhythmias).
* Severe pulmonary, neurological, or musculoskeletal disorders limiting exercise participation.
* Severe cognitive impairment or psychiatric conditions affecting compliance.
* Participation in another structured exercise or rehabilitation program within the past 3 months.
* Any medical condition deemed by the investigator to interfere with safe participation in the study.

• Scherrenberg M, Falter M, Abreu A, Aktaa S, Busnatu S, Casado-Arroyo R, Dendale P, Dilaveris P, Locati ET, Marques-Sule E, Neunhaeuserer D, Pedretti R, Perone F, Salzwedel A, Wilhelm M, Back M. Standards for cardiac telerehabilitation. Eur Heart J. 2025 Oct 7;46(38):3714-3737. doi: 10.1093/eurheartj/ehaf408. PMID 40742158
• Gornik HL, Aronow HD, Goodney PP, Arya S, Brewster LP, Byrd L, Chandra V, Drachman DE, Eaves JM, Ehrman JK, Evans JN, Getchius TSD, Gutierrez JA, Hawkins BM, Hess CN, Ho KJ, Jones WS, Kim ESH, Kinlay S, Kirksey L, Kohlman-Trigoboff D, Long CA, Pollak AW, Sabri SS, Sadwin LB, Secemsky EA, Serhal M, Shishehbor MH, Treat-Jacobson D, Wilkins LR; Peer Review Committee Members. 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024 Jun 11;149(24):e1313-e1410. doi: 10.1161/CIR.0000000000001251. Epub 2024 May 14. PMID 38743805
• Mazzolai L, Teixido-Tura G, Lanzi S, Boc V, Bossone E, Brodmann M, Bura-Riviere A, De Backer J, Deglise S, Della Corte A, Heiss C, Kaluzna-Oleksy M, Kurpas D, McEniery CM, Mirault T, Pasquet AA, Pitcher A, Schaubroeck HAI, Schlager O, Sirnes PA, Sprynger MG, Stabile E, Steinbach F, Thielmann M, van Kimmenade RRJ, Venermo M, Rodriguez-Palomares JF; ESC Scientific Document Group. 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases. Eur Heart J. 2024 Sep 29;45(36):3538-3700. doi: 10.1093/eurheartj/ehae179. No abstract available. PMID 39210722