Heart Failure
Conditions
Keywords
left ventricular assist device, echo-optimization, functional capacity, cardiopulmonary exercise test
Brief summary
After the implantation of a left ventricular assist device (LVAD), many patients continue to experience exercise intolerance. LVAD echo guided optimization (EO) determines a more favorable hemodynamic profile and could provide an improvement on functional capacity (FC). VAFRACT is a prospective randomized trial to evaluate the additional benefit of an EO approach on FC, measured by cardiopulmonary exercise test (CPET), in LVAD optimization free population.
Detailed description
The use of Left Ventricular Assist Devices (LVAD) is a viable therapeutic option to improve survival and quality of life of patients with advanced and refractory heart failure (HF). However, after the implantation of an LVAD, patients' functional capacity (FC) is still reduced with maximum oxygen uptake (VO2 peak) values calculated at the cardiopulmonary exercise test (CPET) ranging from 11 to 20 ml/kg/min. LVAD echo guided optimization (EO) determines a more favorable hemodynamic profile, in particular for the right ventricle, and could provide an improvement on FC. VAFRACT is a prospective randomized trial to evaluate the additional benefit of an EO approach on FC, measured by CPET in LVAD optimization free population. The optimal device speed is defined as the one that allows an intermittent aortic valve opening and a neutral position of the interventricular septum without increasing aortic or tricuspid regurgitation associated or not to a dilatation of the right ventricle (RV). In this condition it is reasonable to expect a more favorable hemodynamic profile for the RV and a better response in terms of functional capacity. Subjects studied are HF patients supported with a continuous-flow LVAD: HeartMate II (Thoratec Inc., Pleasanton, CA) and HeartMate 3 (HM 3, Abbott, North Chicago, IL). Patients are recruited from our Day Hospital of the Cardiac Surgery Department at the University Hospital of Verona.
Interventions
DEVICEecho-optimization
LVAD echo-optimization consists of routine comprehensive transthoracic echocardiography at the baseline speed setting, followed by stepwise incremental adjustments to the LVAD speed (revolutions per minute: rpm), with collection of prespecified echocardiographic parameters at each new speed (eg, left ventricle end-diastolic diameter, interventricular septal position, aortic valve opening frequency/duration, tricuspid and/or mitral regurgitation severity). The optimal velocity is defined as the one that allows an intermittent aortic valve opening and a neutral position of the interventricular septum without increasing aortic or tricuspid regurgitation, associated or not to a dilatation of the right ventricle. The recommended speed range varies according to the indications given in the data sheet for each specific device.
Sponsors
Universita di Verona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* at least 3 months after LVAD implantation; * compliance to the required follow-up schedule; * age 18 or above or of legal age to give informed consent specific to state and national laws.
Exclusion criteria
* distance of less than 150 meters on the six-minute walk test (6MWT) or impossibility to perform CPET * recent finding of any major device-related complication (sepsis, thrombosis …).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| VO2 Peak | three months | peak oxygen uptake measured by cardiopulmonary exercise test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CPET Exercise Time | Three months | Cardiopulmonary exercise time |
| Number of Participants With LVAD-related Hospitalizations | Three months | Rate of hospitalizations for: device thrombosis, hemorrhagic events, infections, right heart failure, arrhythmias. |
| QoL: The EQ-5D Questionnaire | Three months | Changes in quality of life perceived by EuroQoL (quality of life) Scale. It is an instrument which evaluates the quality of life measuring with one question: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers given to these question (1 = no problems; 2 = some problems; 3 = extreme problems) are converted into EQ-5D index, an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status). |
| Nt-proBNP | Three months | Nt-proBNP levels |
| Right Ventricular Function | Three months | Fractional area change of right ventricle assessed by echocardiography |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EO GROUP Patients underwent LVAD echo-optimization; the optimal device speed is confirmed at the end of procedure.
echo-optimization: LVAD echo-optimization consists of routine comprehensive transthoracic echocardiography at the baseline speed setting, followed by stepwise incremental adjustments to the LVAD speed (revolutions per minute: rpm), with collection of prespecified echocardiographic parameters at each new speed (eg, left ventricle end-diastolic diameter, interventricular septal position, aortic valve opening frequency/duration, tricuspid and/or mitral regurgitation severity). The optimal velocity is defined as the one that allows an intermittent aortic valve opening and a neutral position of the interventricular septum without increasing aortic or tricuspid regurgitation, associated or not to a dilatation of the right ventricle. The recommended speed range varies according to the indications given in the data sheet for each specific device. | 13 |
| CONTROL GROUP Patients underwent LVAD echo-optimization, but the optimal device speed is not confirmed at the end of procedure. | 14 |
| Total | 27 |
Baseline characteristics
| Characteristic | EO GROUP | CONTROL GROUP | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Continuous | 60.3 years STANDARD_DEVIATION 10 | 63 years STANDARD_DEVIATION 6.4 | 61.7 years STANDARD_DEVIATION 8.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 00 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 14 Participants | 27 Participants |
| Region of Enrollment Italy | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
| VO2 peak | 13.2 mL/kg/min STANDARD_DEVIATION 2.5 | 13.8 mL/kg/min STANDARD_DEVIATION 2.4 | 13.5 mL/kg/min STANDARD_DEVIATION 2.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 0 / 13 | 0 / 14 |
| serious Total, serious adverse events | 0 / 13 | 0 / 14 |
Outcome results
Primary
VO2 Peak
peak oxygen uptake measured by cardiopulmonary exercise test
Time frame: three months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EO GROUP | VO2 Peak | BASELINE | 13.2 mL/Kg/min | Standard Deviation 2.5 |
| EO GROUP | VO2 Peak | 3 MONTHS-FOLLOW UP | 14.2 mL/Kg/min | Standard Deviation 2.5 |
| CONTROL GROUP | VO2 Peak | BASELINE | 13.8 mL/Kg/min | Standard Deviation 2.4 |
| CONTROL GROUP | VO2 Peak | 3 MONTHS-FOLLOW UP | 13.2 mL/Kg/min | Standard Deviation 2.6 |
Secondary
CPET Exercise Time
Cardiopulmonary exercise time
Time frame: Three months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EO GROUP | CPET Exercise Time | BASELINE | 490 seconds | Standard Deviation 98 |
| EO GROUP | CPET Exercise Time | 3 MONTHS-FOLLOW UP | 526 seconds | Standard Deviation 116 |
| CONTROL GROUP | CPET Exercise Time | 3 MONTHS-FOLLOW UP | 499 seconds | Standard Deviation 107 |
| CONTROL GROUP | CPET Exercise Time | BASELINE | 504 seconds | Standard Deviation 103 |
Secondary
Nt-proBNP
Nt-proBNP levels
Time frame: Three months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EO GROUP | Nt-proBNP | BASELINE | 1743 ng/L | Standard Deviation 1453 |
| EO GROUP | Nt-proBNP | 3 MONTHS-FOLLOW UP | 1484 ng/L | Standard Deviation 1251 |
| CONTROL GROUP | Nt-proBNP | BASELINE | 1759 ng/L | Standard Deviation 1154 |
| CONTROL GROUP | Nt-proBNP | 3 MONTHS-FOLLOW UP | 1538 ng/L | Standard Deviation 1020 |
Secondary
Number of Participants With LVAD-related Hospitalizations
Rate of hospitalizations for: device thrombosis, hemorrhagic events, infections, right heart failure, arrhythmias.
Time frame: Three months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EO GROUP | Number of Participants With LVAD-related Hospitalizations | 0 Participants |
| CONTROL GROUP | Number of Participants With LVAD-related Hospitalizations | 0 Participants |
Secondary
QoL: The EQ-5D Questionnaire
Changes in quality of life perceived by EuroQoL (quality of life) Scale. It is an instrument which evaluates the quality of life measuring with one question: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers given to these question (1 = no problems; 2 = some problems; 3 = extreme problems) are converted into EQ-5D index, an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).
Time frame: Three months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EO GROUP | QoL: The EQ-5D Questionnaire | BASELINE | 0.796 score on a scale | Standard Deviation 0.1 |
| EO GROUP | QoL: The EQ-5D Questionnaire | 3 MONTHS-FOLLOW UP | 0.85 score on a scale | Standard Deviation 0.08 |
| CONTROL GROUP | QoL: The EQ-5D Questionnaire | BASELINE | 0.804 score on a scale | Standard Deviation 0.09 |
| CONTROL GROUP | QoL: The EQ-5D Questionnaire | 3 MONTHS-FOLLOW UP | 0.8 score on a scale | Standard Deviation 0.08 |
Secondary
Right Ventricular Function
Fractional area change of right ventricle assessed by echocardiography
Time frame: Three months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EO GROUP | Right Ventricular Function | BASELINE | 36.5 percentage of fractional area change | Standard Deviation 3.8 |
| EO GROUP | Right Ventricular Function | 3 MONTHS-FOLLOW UP | 36.8 percentage of fractional area change | Standard Deviation 3.2 |
| CONTROL GROUP | Right Ventricular Function | BASELINE | 35.8 percentage of fractional area change | Standard Deviation 4.1 |
| CONTROL GROUP | Right Ventricular Function | 3 MONTHS-FOLLOW UP | 35.7 percentage of fractional area change | Standard Deviation 4.2 |