Clinical trial NCT01914315: Rehabilitation Program in Heart Failure With Preserved Ejection Fraction
Official title: Multi-Disciplinary Rehabilitation Program in Recently Hospitalized Patients With Preserved Ejection Fraction Heart Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heart Failure
Keywords: Rehabilitation
Heart failure
HFPEF
Exercise training
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: The Gertner Institute
First posted: 2013-08-02
Enrollment: 1100
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this prospective study is to determine whether comprehensive cardiac rehabilitation is superior to usual disease management in the treatment of patients with heart failure with preserved systolic function (HFpEF) recently discharged after an acute heart failure event.

The investigators hypothesize that the addition of bi-weekly structured exercise training and interaction with medical personnel will lead to a greater reduction in all cause hospitalization and mortality while providing additional functional and clinical benefits such as exercise capacity, quality of life and well-being.

Furthermore the investigators seek to establish clinical, laboratory and echocardiographic predictors of hospital readmissions and cardiovascular events in the predefined HFpEF population.

Detailed description: Our primary objective is to test the hypothesis that comprehensive multi-disciplinary cardiac rehabilitation program is superior to usual care in the treatment of patients with HFpEF discharged after an acute heart failure event, and will result in a 25% reduction in the composite outcome of all cause hospitalizations and all-cause mortality after 1-year of follow-up. This objective represents both safety and efficacy end-point in a patient population with a high rate of co-morbidities, which may be affected as well. Previous observation has shown that these patients have a high rate of non-cardiac death in comparison with HFrEF, thus enhancing the importance of all-cause hospitalization and mortality as a primary end-point.

Secondary end-points that will be recorded include separate components of the primary end-point, time to first hospitalization, functional capacity measured by NYHA class, 6-minute walk test (6MWT), blood pressure during rest and exercise, fasting glucose and Hb A1C levels, BNP values and quality of life EQ5-D questionnaire.

Eligibility criteria: Inclusion Criteria:

* Patients \>=21 years of age willing and able to sign consent forms
* Hospitalization for acute heart failure (AHF) in one of the internal medicine departments participating in the study
* AHF as the primary diagnosis as defined by:

  * (I) The presence of pulmonary congestion or edema on chest radiography OR
  * (II) Evidence of fluid retention (pedal edema, pleural effusion, ascites) not otherwise explained by other conditions (i.e. malignancy, nephrotic syndrome, liver cirrhosis, severe hypo-albuminemia, etc) AND
  * (III) Echocardiography demonstrating the presence of preserved systolic function

    * In cases where diagnosis is unclear BNP testing (with a cutoff value of \>300 ng/dl) will be used.
    * If there is clinical suspicion of pulmonary disease investigators are encouraged to perform pulmonary function tests after the patient condition is stabilized.
* Preserved systolic function as determined by in-hospital or recent (within 3 months) echocardiographic examination according to ESC guidelines and in the absence of hemodynamic significant valvular disease.
* Stable clinical condition prior to discharge permitting the initiation of an exercise training program

Exclusion Criteria:

* Hemodynamically significant valvular disease (severity \> mild other than TR)
* Acute coronary syndrome as the primary diagnosis
* End stage heart failure - NYHA IV
* Severe renal dysfunction - eGFR\<30 ml/min/1.73m2 or renal replacement therapy
* Inability to participate in an exercise program and comply with study protocol
* Severe chronic obstructive pulmonary disease (COPD) (FEV1\<50%) or asthma defined as severe
* First episode of a hypertensive crisis event (without history of chronic heart failure)
* Cognitive decline or major psychiatric pathology
* Non ambulatory condition
* Life expectancy \< 12 months
* Substance dependency
* Inability to participate due to technical barriers such as a significant distance from a cardiac rehabilitation center

Primary outcomes:
measure: Combined primary endpoint
timeFrame: 12 months following randomization
Secondary outcomes:
measure: Secondary endpoint - change in functional capacity and clinical status
timeFrame: 3 and 6 month follow-up after randomization
measure: All cause mortality end-point
timeFrame: 12 months after randomization
measure: Heart failure hospitalizations
timeFrame: 12 months after randomization
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba medical Center
city: Tel Hashomer , Ramat Gan
country: Israel
facility: Sheba Medical Center, Cardiac Rehabilitation Institute
Study officials:
References:
citation: Stankovic I, Neskovic AN, Putnikovic B, Apostolovic S, Lainscak M, Edelmann F, Doehner W, Gelbrich G, Inkrot S, Rau T, Herrmann-Lingen C, Anker SD, Dungen HD. Sinus rhythm versus atrial fibrillation in elderly patients with chronic heart failure--insight from the Cardiac Insufficiency Bisoprolol Study in Elderly. Int J Cardiol. 2012 Nov 29;161(3):160-5. doi: 10.1016/j.ijcard.2012.06.004. Epub 2012 Jun 21.
citation: Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon CP, Hernandez AF, Fonarow GC; Get With the Guidelines Scientific Advisory Committee and Investigators. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012 Jul 3;126(1):65-75. doi: 10.1161/CIRCULATIONAHA.111.080770. Epub 2012 May 21.
citation: Lewis BS, Shotan A, Gottlieb S, Behar S, Halon DA, Boyko V, Leor J, Grossman E, Zimlichman R, Porath A, Mittelman M, Caspi A, Garty M; HFSIS Investigators. Late mortality and determinants in patients with heart failure and preserved systolic left ventricular function: the Israel Nationwide Heart Failure Survey. Isr Med Assoc J. 2007 Apr;9(4):234-8.