Trial Outcomes & Findings for Exercise Training Following Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure (NCT NCT02413151)

NCT ID: NCT02413151

Last Updated: 2019-05-14

Results Overview

The New York Heart Association (NYHA) Functional Classification provides a simple way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina. I - Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. no shortness of breath when walking, climbing stairs etc. II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest. IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 62 participants
• Primary outcome timeframe: 6 months after CRT implantation
• Results posted on: 2019-05-14

Participant Flow

Participant milestones

Measure	Exercise Training Program The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of HRpeak.	Control Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Overall Study STARTED	32	30
Overall Study COMPLETED	22	28
Overall Study NOT COMPLETED	10	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Exercise Training Following Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

Baseline characteristics by cohort

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of HRpeak.	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.	Total n=50 Participants Total of all reporting groups
Age, Continuous	67.5 years STANDARD_DEVIATION 9.8 • n=5 Participants	66.7 years STANDARD_DEVIATION 10.8 • n=7 Participants	67.1 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	21 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months after CRT implantation

The New York Heart Association (NYHA) Functional Classification provides a simple way of classifying the extent of heart failure. It places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina.

I - Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. no shortness of breath when walking, climbing stairs etc.

II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.

III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).

Comfortable only at rest. IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in a Composite Measure of Clinical Status - New York Heart Association Functional Class	-1.52 scores on a scale Interval -1.82 to -1.23	-1.0 scores on a scale Interval -1.34 to -0.65

PRIMARY outcome

Timeframe: 6 months after CRT implantation

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in Cardiac Function - Left Ventricular Ejection Fraction	11.86 percentage of blood eject Interval 6.66 to 17.06	10.41 percentage of blood eject Interval 4.69 to 16.12

PRIMARY outcome

Timeframe: 6 months after CRT implantation

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in Exercise Testing Variables - Maximum Rate of Oxygen Consumption (VO2peak)	2.18 ml/kg/min Interval -0.53 to 4.8	0.25 ml/kg/min Interval -2.59 to 3.09

SECONDARY outcome

Timeframe: 6 months after CRT implantation

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in Exercise Testing Variables - Heart Rate Recovery at 1st Minute (HRR1)	-2.19 bpm Interval -12.73 to 8.35	-15.46 bpm Interval -29.35 to -1.58

SECONDARY outcome

Timeframe: 6 months after CRT implantation

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in Inflammatory Markers - Plasmatic Tumor Necrotic Factor Alpha (TNF-alpha)	-1.08 µg/ml Interval -1.84 to -0.32	0.12 µg/ml Interval -0.19 to 0.43

SECONDARY outcome

Timeframe: 6 months after CRT implantation

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in Inflammatory Markers - Plasmatic Brain Natriuretic Peptide (BNP)	-67.81 pg/mL Interval -151.67 to 16.05	-116.29 pg/mL Interval -227.54 to -5.05

SECONDARY outcome

Timeframe: 6 months after CRT implantation

HeartQoL scale response of 0-3 (poor-better), higher scores indicate better quality of life. Maximum score: 42 (better prognosis); Minimum score:0 (poor prognosis)

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in a Composite Measure of Quality of Life - HeartQoL T Score	1.26 t scores Interval 0.84 to 1.68	0.94 t scores Interval 0.5 to 1.38

SECONDARY outcome

Timeframe: 6 months after CRT implantation

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in Exercise Testing Variables - Duration of Cardiopulmonary Testing (CPETduration)	235.13 seconds Interval 83.07 to 387.18	24.00 seconds Interval -50.42 to 98.42

SECONDARY outcome

Timeframe: 6 months after CRT implantation

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in 123I-MIBG Cardiac Scintigraphy - Heart-to-mediastinum Ratio (HMR) Early	-0.012 mGy/MBq Interval -0.14 to 0.1	-0.04 mGy/MBq Interval -0.42 to 0.21

SECONDARY outcome

Timeframe: 6 months after CRT implantation

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in 123I-MIBG Cardiac Scintigraphy - Heart-to-mediastinum Ratio (HMR) Late	-0.07 mGy/MBq Interval -0.19 to 0.05	-0.02 mGy/MBq Interval -0.3 to 0.23

SECONDARY outcome

Timeframe: 6 months after CRT implantation

washout provides information on the sympathetic drive. The in-vivo visualization of cardiac innervation is evaluated on planar anterior images, which are acquired early and 3 to 5 hours after tracer injection.

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in 123I-MIBG Cardiac Scintigraphy - Wash Out (WO)	3.56 percent change Interval -2.46 to 9.59	-3.34 percent change Interval -48.13 to 34.16

SECONDARY outcome

Timeframe: 6 months after CRT implantation

Reactive hyperaemia index (RHI) is a functional marker of endothelial dysfunction. The RHI was measured using an EndoPAT recorder.

Outcome measures

Measure	Exercise Training Program n=22 Participants The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 Participants Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Changes in Peripheral Artery Tonometry - Reactive Hyperemia (RHI)	1.1 ratio of the post-to pre occlusion Interval -1.22 to 3.34	0.20 ratio of the post-to pre occlusion Interval -0.17 to 0.57

Adverse Events

Exercise Training Program

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Control

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Exercise Training Program n=22 participants at risk The exercise sessions will be hospital-based, 3times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. Exercise training program: The exercise sessions will be hospital-based, 3 times a week for 60 minutes each, on non-consecutive days for 6 months. Selected the aerobic interval training (AIT) method for the development of cardiopulmonary system and the inclusion of resistance and sensorimotores exercises. The AIT comprises 4 interval training periods (high intensity) and 3 active pauses (moderate intensity) between interval training periods. The patient will warmup for 10 minutes at 50% to 60% of HRpeak from CPET, before walking to four 4 minutes intervals at 90 to 95% of	Control n=28 participants at risk Regular lifestyle Cardiac resynchronization therapy (CRT): Implantation will be performed according to standard techniques of biventricular pacing. The CRT includes a generator and three leads, used to correct ventricular dyssynchrony.
Cardiac disorders Ventricular Tachycardia	9.1% 2/22	7.1% 2/28
Cardiac disorders Hospital Admission	4.5% 1/22	10.7% 3/28

Other adverse events

Adverse event data not reported

Additional Information

Maria Helena Santa-Clara Pombo Rodrigues

University of Lisbon

Phone: 00351917377277

Email: santaclara@fmh.ulisboa.pt

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place