PREACTIVE: Preconditioning Exercise Intervention to Improve Symptoms and Quality of Life in Comorbid Atrial Fibrillation and HFpEF

NCT07324772 | Not Yet Recruiting

• 1 other identifier: STU#: 00223545
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are very common conditions that often occur together and result in worsening symptoms and reduced quality of life (QoL). Limitations being able to participate in activities of daily living is a primary complaint for AF-HFpEF patients, yet effective strategies to address this issue remain limited. While exercise interventions targeting aerobic training (AT) are recommended for patients with AF and HFpEF, unique challenges exist in this patient population who tend to be older. Specifically, many older patients with AF and HFpEF have muscle weakness, sarcopenia and frailty, that can make aerobic-focused exercise difficult and less tolerable. This study proposes that starting with progressive resistance training (PRT) before aerobic exercise may overcome these issues by improving muscle strength, making AT more manageable, and leading to better health outcomes. The goal of this study is to assess whether a sequential exercise program, named 'PREACTIVE' improves how people feel, decrease the amount of symptoms, and their ability to participate in exercise and activities. This study will specifically test a sequenced exercise approach of resistance training followed by aerobic exercise to improve symptoms, and quality of life in AF-HFpEF.

Conditions

Atrial Fibrillation (AF); Atrial Fibrillation (Paroxysmal); Persistent Atrial Fibrillation; Heart Failure With Preserved Ejection Fraction (HFPEF)

Keywords

exercise; exercise capacity; symptom severity; quality of life

Outcome Measures

Primary Outcomes (1)

• 6 minute walk test (4 month change)

  Submaximal aerobic capacity by the 6-minute walk test \[6MWT\]

  change from baseline visit to 4 months (post intervention visit)

Secondary Outcomes (5)

• muscle strength

  change from baseline visit to 4 months (post-intervention visit)

• short physical performance battery

  change from baseline to 4 months (post intervention visit)

• Atrial Fibrillation symptom severity by the Atrial Fibrillation Severity Scale (AFSS)

  change from baseline to 4 months (post-intervention visit)

• Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) Questionnaire

  change from baseline to 4 months (post intervention visit)

• Kansas City Cardiomyopathy Questionnaire

  change from baseline to 4 months (post intervention visit)

Study Arms (1)

PREACTIVE

EXPERIMENTAL

During Phase I participants will engage first in progressive resistance training only (3 sessions/week; 24 sessions total) to optimize gains in muscle mass and strength, neuromuscular function, and hemodynamic gains. Phase II includes 8 weeks that focus on aerobic endurance training and also an abbreviated version of PRT (3 sessions/week; 24 sessions total).

Behavioral: progressive resistance training; Behavioral: combined aerobic + resistance training

Interventions

progressive resistance training BEHAVIORAL

2 months of progressive resistance training, performed for 3 sessions/week; 24 sessions total, under supervision with a trainer (1:1 interaction) Sessions include six upper- and lower-extremity exercises performed in alternate pattern as described (e.g., chest press, seated leg press, seated latissimus pull-down, knee/leg extension, shoulder press, leg curls) using pressurized or weighted machines. Participants will start the intensity of 40-50% of their baseline 1 repetition maximum (1-RM), with the goal of progressing to 70-80% of their 1-RM by 8 weeks, if able. Progression in intensity and reps will follow the principles of overload, such that resistance will be incremented only when a subject completes 12 reps for at least 2 of the 3 total sets at a given resistance, complemented by a reduction in the number of reps per set.

PREACTIVE

combined aerobic + resistance training BEHAVIORAL

Phase II comprises of 8 weeks of aerobic training (primary focus) while continuing a shortened PRT protocol comprising of 3-4 exercises targeting upper and lower body. Sessions will be 3 sessions/week; 24 sessions total). Initial training intensity will be 40-50% of the HRR from the 6MWT with the goal of progressing to 60%-70% of HRR and for 20-35min over 8 weeks. Goals will be adjusted to 40%-50% HRR and 15-30min of exercise for those unable to meet targets.

PREACTIVE

Eligibility Criteria

• Age: 60 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants will be age 60 and older, have a primary diagnosis of AF and HFpEF, based on electronic health record review. Patients with persistent AF or Paroxysmal AF are eligible. HFpEF will be defined in accordance to the 2022 AHA/ACC/HFSA Guideline using a clinical composite score, the H2FPEF score, in conjunction with diagnostic criteria below:
• Ejection fraction ≥ 50%
• E/e' ≥15 by Doppler Echocardiography
• High H2FpEF score (≥5)
• Must be in stable medical condition and able to begin an exercise program

You may not qualify if:

• Valvular heart disease as the primary etiology of heart failure (i.e., severe aortic stenosis or mitral regurgitation),
• New York Heart Association Stage IV
• Recent stroke (\<1 year)
• Evidence or History of Cardiac amyloidosis
• Patients with persistent AF and poor rate control (HR \> 110 at rest)
• Significant change in cardiac medication or Heart Failure symptoms \< 2 weeks
• Unstable or severe angina not controlled during daily activity by pharmacological therapy or at \<4 METS activity
• Uncontrolled hypertension (defined as systolic blood pressure \>200 mm Hg and/or diastolic blood pressure\>110 mm Hg) with medications
• Uncontrolled diabetes with recent weight loss, diabetic coma, or frequent insulin reactions
• Hospitalization or urgent care visit \< 4 weeks
• Oxygen dependent Chronic Obstructive Pulmonary Disease (COPD)
• Significant anemia (\<10 g/dL Hgb)
• End stage renal replacement therapy associated with the need for dialysis
• Active treatment for cancer defined as current radiation, chemotherapy, immunotherapy, or cancer recurrence within past 5 years
• Hospice care and indication of life expectancy less than 2 years

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Atrial Fibrillation; Motor Activity

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Deepika Laddu, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mandy Pershing, MS

CONTACT

312-503-3237; mandy.pershing@northwestern.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI, Associate Professor

Model Details: This single arm pilot study will recruit 30 patients aged ≥60 years with persistent AF and HFpEF for a 4-month PREACTIVE intervention. Participants will complete 16 weeks of exercise (3 sessions per week) with a study exercise interventionist (trainer). PREACTIVE comprises of two phases, each lasting 2 months (8 weeks, 3 sessions/week; 24 sessions total). Phase I employs progressive resistance training (PRT)-only to promote gains in muscle mass and strength, and neuromuscular function. Phase II includes 8 weeks (3 sessions/week; 24 sessions total) that will continue with an abbreviated version of PRT while focusing on aerobic endurance training. Aerobic training will gradually progress by workload and the heart rate reserve (HRR) method will be used to guide exercise intensity. The HRR is determined from the 6-minute walk test (6MWT) performed at the baseline visit and rate of perceived exertion (RPE) will be used to guide intensity and progression.

Study Record Dates

• First Submitted: December 24, 2025
• First Posted: January 7, 2026
• Study Start: April 13, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)