Clinical trial NCT03184311: High-intensity Interval Training in Heart Failure Patients With Preserved Ejection Fraction
Official title: High-intensity Interval Training as Treatment Strategy for Heart Failure Patients With Preserved Ejection Fraction: A Prospective, Single-blind, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heart Failure With Normal Ejection Fraction
Keywords: Therapy response prediction
Exercise tolerance
High-intensity interval training
Lead sponsor: University of Basel
Sponsor class: OTHER
Collaborators: name: Clinical Trial Unit, University Hospital Basel, Switzerland
First posted: 2017-06-12
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * Intervention group: 12-week high-intensity interval training on a bicycle ergometer.
* Control group: 12-week moderate-intensity continuous training on a bicycle ergometer.
Primary purpose: TREATMENT

Brief summary: This study investigates the effects of a 12-week high-intensity interval training (HIT) on exercise tolerance, functional status and quality of life in patients with chronic heart failure with preserved ejection fraction (HFpEF), in comparison to a control group undergoing a 12-week moderate-intensity continuous training.

Detailed description: Heart failure (HF) with preserved ejection fraction (HFpEF) occurs in about 50% of all HF patients. Remodeling and fibrosis stimulated by inflammation appear to be main factors for the progression of HFpEF. The lack of prognostic treatment options in HFpEF urgently calls for new therapeutic approaches. While beneficial effects of exercise training have been demonstrated in HF with reduced ejection fraction, they have not yet been evaluated in HFpEF. Therefore, the aim of this study is to investigate the effects of high-intensity interval training (HIT) in HFpEF patients.

The proposed study will be a prospective, single-blind, randomized controlled trial in a primary care setting including 86 patients with stable HFpEF. Patients will undergo 3 study visits (a screening visit, a baseline visit and a post-intervention visit) including measurements of disease-specific biomarkers (using blood samples), cardiac and arterial vessel structure and function (using electrocardiogram, echocardiography, pulse wave velocity, flow-mediated dilation, retinal vessel analysis, cold pressure test), exercise tolerance (using spiroergometry), muscle function (using near-infrared spectroscopy, muscle strength tests), habitual physical activity (using accelerometry) and QoL. After the baseline visit, patients will be randomized to either the intervention or control group. The intervention group (n=43) will attend a supervised 12-week HIT on a bicycle ergometer, while the control group (n=43) will attend a supervised 12-week moderate-intensity continuous training (MCT). After 12 weeks, the study measurements will be repeated in all patients (intervention and control group) in order to monitor the effects of the intervention (post-intervention visit). At 6 months, 1, 2 and 3 years after the last study visit, telephone interviews will be performed to assess medical outcomes and QoL.

Outlook: This study is expected to add important knowledge about the potential utility of a novel treatment strategy in HFpEF patients, which may help to improve both, QoL and functional status. Moreover, the analysed biomarkers might be able to provide further insight into prognosis and pathogenesis of HFpEF.

Eligibility criteria: Inclusion Criteria:

* Informed consent as documented by the patient's signature
* NYHA functional classes II-III
* Signs and symptoms of chronic HF:

  * Dyspnea, paroxysmal nocturnal dyspnea
  * Reduced exercise capacity, extended recovery after exercising
  * Fatigue
  * Peripheral edema (lower leg, ankle)
* EF (Ejection fraction) \>50%
* Structural or functional changes in echocardiography:

  * LAVI (left atrial volume index) \>34 ml/m2 OR
  * LVMI (left ventricular mass index) \>115 g/m2 (men), \>95 g/m2 (women) OR
  * E/E' (ratio between mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E')) \>13 AND mean E' septal and lateral wall \<9 cm/s
* NT-proBNP \>125 pg/ml
* At least 4 weeks on stable medical treatment or without signs and symptoms of cardiac decompensation
* Trainable: Ventilatory threshold \>40% of predicted VO2max AND VO2peak \>10 ml/kg/min at the screening visit

Exclusion Criteria:

* Planned cardiac interventions in the following 6 months
* Unstable angina pectoris
* Paroxysmal atrial fibrillation
* Severe uncorrected valvular heart disease
* Uncontrolled brady- or tachyarrhythmia and hypertonic blood pressure
* Clinically significant concomitant disease states (e.g. advanced renal failure, hepatic dysfunction, insulin-dependent diabetes, COPD (chronic obstructive pulmonary disease) in grades III-IV, on-going cancer treatment)
* Significant musculoskeletal disease limiting exercise tolerance
* Active infection
* Immunosuppressive medical therapy
* Earlier hypersensitivity to parenteral iron preparation
* Anemia and iron deficiency due to active and/or chronic bleeding
* Blood transfusion within the previous 30 days
* Vulnerable persons (age \<18 years, pregnant and breastfeeding women)
* Known or suspected non-compliance, drug or alcohol abuse
* Inability to follow the study procedures due to insufficient language skills, psychological disorders, dementia, etc.
* Participation in another intervention study
* Life-expectancy \<6 months

Primary outcomes:
measure: Change in peak oxygen uptake (VO2peak) due to training
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in disease-specific biomarkers
timeFrame: Baseline and 12 weeks
measure: Change in echocardiographic parameters of the left ventricular systolic and diastolic function
timeFrame: Baseline and 12 weeks
measure: Change in arteriovenous oxygen difference (Da-vO2)
timeFrame: Baseline and 12 weeks
measure: Change in pulse wave velocity (PWV)
timeFrame: Baseline and 12 weeks
measure: Change in daily physical activity
timeFrame: Baseline and 12 weeks
measure: Change in NYHA functional class
timeFrame: Baseline and 12 weeks
measure: Change in quality of life (QoL): The 36-Item Short Form Health Survey (SF-36)
timeFrame: Baseline and 12 weeks
measure: Change QoL: The Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Baseline and 12 weeks
measure: Change in QoL: The Minnesota Living With Heart Failure Questionnaire (MLWHFQ)
timeFrame: Baseline and 12 weeks
measure: Change in body composition: Body Mass Index (BMI)
timeFrame: Baseline and 12 weeks
measure: Change in body composition: Waist-to-Hip-Ratio (WHR)
timeFrame: Baseline and 12 weeks
measure: Change in macrovascular function: flow-mediated dilation (FMD)
timeFrame: Baseline and 12 weeks
measure: Change in microvascular function: retinal vessel analysis
timeFrame: Baseline and 12 weeks
measure: Change in macrovascular function: carotid artery reactivity
timeFrame: Baseline and 12 weeks
measure: Change in cardiovascular function: cardiac output
timeFrame: Baseline and 12 weeks
measure: Change in muscular function: muscle oxygen saturation
timeFrame: Baseline and 12 weeks
measure: Change in muscular function: muscle strength
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Department for Sport, Exercise and Health, Section Sports and Exercise Medicine, University of Basel
Study officials:
affiliation: University of Basel
name: Arno Schmidt-Trucksäss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Basel
name: Thomas Dieterle, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gasser BA, Boesing M, Schoch R, Brighenti-Zogg S, Kropfl JM, Thesenvitz E, Hanssen H, Leuppi JD, Schmidt-Trucksass A, Dieterle T. High-Intensity Interval Training for Heart Failure Patients With Preserved Ejection Fraction (HIT-HF)-Rational and Design of a Prospective, Randomized, Controlled Trial. Front Physiol. 2021 Sep 24;12:734111. doi: 10.3389/fphys.2021.734111. eCollection 2021.