Controlled study of myocardial recovery after interval training in heart failure: SMARTEX-HF - rationale and design

Background: The large randomized controlled multicentre clinical trial, HF-ACTION, recently demonstrated that a programme of recommendation of regular exercise training at moderate intensity is safe, improves quality of life, and reduces the combined endpoint of all-cause death and hospitalization in patients with chronic heart failure. However, the size of beneficial effects was modest compared to results published in smaller single studies and meta-analyses. Objective: Based on results of a pilot study, the objective of the present investigation is to test the hypothesis that a programme comprising interval training at high relative intensity would yield significantly larger effects in terms of left ventricular remodelling compared to moderate continuous exercise training. Study design: In a three-armed randomized multicentre study of stable heart failure patients with left ventricular ejection fraction <= 35%, the effects of a 12-week programme of high-intensity interval training (HIT; 85-90% of peak oxygen uptake, VO2peak) will be compared to actual practice in Europe, represented by either an isocaloric programme of moderate continuous training (MCT; 50-60% of VO2peak) and a recommendation of regular exercise (RE) of the individual patients' own preference based on clinical practice at the local centre. The primary endpoint is reverse remodelling, defined as change in left ventricular end-diastolic diameter assessed by echocardiography. Secondary endpoints include peak oxygen uptake (VO2peak), biomarkers, quality of life, and level of physical activity assessed by questionnaires. In addition, long-term maintenance of effects after the supervised training period will be determined. Assessments will be made at baseline, after the 12-week intervention programme, and at 1-year follow up. A total number of 200 patients on treatment per protocol, randomized to the three groups in a 1 : 1 : 1 manner, is estimated to detect clinically relevant differences in effect with HIT vs. MCT and RE (p < 0.05; statistical power 0.90) for the primary endpoint. Inclusion of patients started May 2009 and will run until total number has been reached.