Clinical trial NCT02638961: Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of HFpEF
Official title: Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure With Normal Ejection Fraction
Keywords: heart failure with preserved ejection fraction
physical therapy
exercise capacity
quality of life
Lead sponsor: Universitat Jaume I
Sponsor class: OTHER
Collaborators: name: INCLIVA
name: Hospital Clínico Universitario de Valencia
First posted: 2015-12-23
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Heart failure (HF) with preserved ejection fraction (HFpEF) has become the most prevalent form of HF in developed countries. Despite its increasing in prevalence, there is no evidence-based effective therapy for HFpEF The purpose of this study was to evaluate whether inspiratory muscle training (IMT), functional electrical stimulation (FES), or combination of both improve exercise capacity as well as left ventricular diastolic function, biomarkers' profile, quality of life (QoL) and prognosis in patients with HFpEF.

Detailed description: This study was designed as a prospective, controlled, randomized, four-armed, efficacy trial of patients with the diagnosis of HFpEF and New York Heart Association functional class II-III/IV, diagnosed according to criteria of the European Society of Cardiology. A computer-generated randomization scheme was used to allocate participants (in a 1:1:1:1 ratio) to receive: 1) a home-based 12-week program of inspiratory muscle training (IMT) or; 2) a 12-week program of functional electrical stimulation (FES) of lower limb muscles or; 3) standard treatment (ST) alone or; 4) combination of IMT and FES. The study is being conducted in a single center in Spain. Independently of staggered entry, the minimum duration of a patient's participation is 6 months (from first to last visit). All patients will provide signed informed consent and the protocol has been approved by the research ethics committee of our center in accordance with the principles of the Declaration of Helsinki and national regulations.

Study population Candidate patients are selected from the outpatient's clinics of HF of the Hospital Clínico Universitario of Valencia.

Study objectives The primary endpoint of the study is a clinical endpoint of three and six months change in peak oxygen uptake (peak VO2).

Secondary endpoints are three and six month changes in echocardiogram parameters, QoL and prognostic biomarkers. The investigators also will specifically focus on number of episodes of worsening HF at 6 months:

1. Change in E/e' after three and six months.
2. Change in left atrial volume index after three and six months.
3. Change in health-related QoL measured by the Minnesota Living With Heart Failure Questionnaire (MLHF) after three and six months.
4. Change in natriuretic peptide (NT-proBNP) after three and six months.
5. Change in minute ventilation/carbon dioxide production (VE/VCO2) slope after three and six months.
6. Number of episodes of acute HF hospitalizations and number of episodes of worsening HF not requiring hospitalization at 6 months.

Intervention

Eligibility assessment and screening visit After reviewing the inclusion/exclusion criteria and signing the informed consent form, a comprehensive medical history, physical examination, anthropometry and examination tests will be performed. The examination tests include: electrocardiogram (ECG) echocardiography, cardiopulmonary exercise testing (CPET), 6-minute walk test (6-MWT), inspiratory muscle function test, QoL assessment by the Minnesota Living With Heart Failure Questionnaire (MLHF) and blood samples for a panel of baseline biomarkers.

Finally, patients are randomized (1:1:1:1) to four groups: 1) ST alone or; 2) a home-based 12-week program of IMT or; 3) a 12-week program of FES or; 4) combination of IMT and FES (IMT+FES) during 12 weeks.

12-week and six months visits All patients will be evaluated after 12-week supervised training, and six months after randomization. Evaluation will include medical history, physical examination, anthropometry and functional and QoL assessment tests (ECG, CPET, 6-MWT, inspiratory muscle function test, MLHF and blood tests).

Eligibility criteria: Inclusion Criteria:

* Previous history of symptomatic heart failure NYHA (New York Heart Association )functional class ≥II with Normal left ventricular ejection fraction:

  * ejection fraction \>0.50 by Simpson method
  * end-diastolic diameter \<60 mm
* Structural heart disease:

  * left ventricle hypertrophy/left atrial enlargement and/or
  * diastolic dysfunction estimated by 2D echocardiography
* Previous admission for acute heart failure
* Clinical stability, without hospital admissions in the past 3 month

Exclusion Criteria:

* Perform a valid baseline exercise test
* Significant primary moderate to severe valvular disease
* Acute coronary syndrome or cardiac surgery within the previous three months
* Signs of ischemia during cardiopulmonary exercise testing
* Significant primary pulmonary disease; including pulmonary arterial hypertension, chronic thromboembolic pulmonary disease or chronic obstructive pulmonary disease
* Any other comorbidity with an expectancy of life less than one year

Primary outcomes:
measure: Functional capacity measured as peak oxygen uptake (peak VO2) in ml/min/kg .
timeFrame: changes at 12 weeks and 6 months
Secondary outcomes:
measure: Functional capacity measured as distance walked in 6 minutes
timeFrame: changes at 12 weeks and 6 months
measure: Change in echocardiographic parameter of diastolic disfunction: e' septal (cm/s)
timeFrame: changes in rest at 12 weeks and 6 months
measure: Change in echocardiographic parameter of diastolic disfunction: left atrial volume index (mm/m2)
timeFrame: changes in rest at 12 weeks and 6 months
measure: Change in echocardiographic parameter of diastolic disfunction: E/e' ratio
timeFrame: changes in rest at 12 weeks and 6 months
measure: Change in health-related QoL
timeFrame: changes at 12 weeks and 6 months
measure: Number of rehospitalizations or worsening HF at 6 months
timeFrame: changes at 6 months
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital clínico universitario de Valencia
Study officials:
affiliation: Universitat Jaume I
name: Patricia Palau, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitat Jaume I
name: Eloy Domínguez, M.D
role: STUDY_DIRECTOR
affiliation: Universitat de Valencia
name: Julio Núñez, M.D., PhD
role: STUDY_CHAIR
References:
citation: Palau P, Dominguez E, Nunez E, Schmid JP, Vergara P, Ramon JM, Mascarell B, Sanchis J, Chorro FJ, Nunez J. Effects of inspiratory muscle training in patients with heart failure with preserved ejection fraction. Eur J Prev Cardiol. 2014 Dec;21(12):1465-73. doi: 10.1177/2047487313498832. Epub 2013 Jul 17.
citation: Palau P, Nunez E, Dominguez E, Sanchis J, Nunez J. Physical therapy in heart failure with preserved ejection fraction: A systematic review. Eur J Prev Cardiol. 2016 Jan;23(1):4-13. doi: 10.1177/2047487314562740. Epub 2014 Dec 8.
citation: Palau P, Dominguez E, Lopez L, Ramon JM, Heredia R, Gonzalez J, Santas E, Bodi V, Minana G, Valero E, Mollar A, Bertomeu Gonzalez V, Chorro FJ, Sanchis J, Lupon J, Bayes-Genis A, Nunez J. Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction: The TRAINING-HF Trial. Rev Esp Cardiol (Engl Ed). 2019 Apr;72(4):288-297. doi: 10.1016/j.rec.2018.01.010. Epub 2018 Mar 16. English, Spanish.