HFrEF - Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
Baroreflex activation therapy, Exercise hemodynamics, Barostim, Cardiopulmonary exercise testing, Neuromodulation, Functional capacity, Heart failure with reduced ejection fraction
Brief summary
This study evaluates the effects of the implantation and adjustment of the CVRx Barostim device in adult patients with heart failure with reduced ejection fraction who are receiving maximally tolerated doses of guideline directed medical and device therapies. The study aims to assess how therapy using this device affects heart function, symptoms, and exercise capacity, with particular focus on how the device affects blood flow and heart pressures during exercise. Information from this study may help inform patient selection and device management in patients with heart failure.
Detailed description
Heart failure with reduced ejection fraction (HFrEF) remains a major public health concern, associated with high rates of morbidity, hospitalizations, and mortality. Despite advances in medication, as well as device therapies such as implantable devices, a significant proportion of patients continue to experience debilitating symptoms, exercise intolerance, and reduced quality of life. An important feature of HFrEF is autonomic imbalance, which contributes to disease progression and adverse outcomes. While current therapies indirectly try to affect this imbalance, the Barostim™ device (CVRx) is the first to specifically target the autonomic nervous system in this population. This device offers a novel mechanistic approach by directly stimulating the carotid baroreceptors to reduce sympathetic activity and restore autonomic balance. This prospective, multicenter study aims to evaluate the effects of the Barostim device on invasive hemodynamics through right heart catheterization (RHC), exercise capacity, and tolerance to medical therapy in HFrEF patients who remain symptomatic despite maximal guideline-directed medical therapy (GDMT). The study seeks to address key knowledge gaps in the mechanistic and clinical response to baroreflex activation therapy (BAT) and inform future integration of this therapy into standard heart failure care.
Interventions
DEVICEBaroreflex Activation Therapy
Barostim™ device (CVRx Inc.), a commercially available, FDA-approved device for autonomic modulation in HFrEF. The device system includes an implantable pulse generator, carotid sinus lead, and programmer system. No investigational modifications will be made. The device will be implanted per standard labeling and programming guidelines, and therapy titration will follow manufacturer recommendations.
Sponsors
Columbia University
CVRx, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single-group, self-controlled study in which all enrolled participants receive the same intervention. Outcomes are evaluated within participants using pre- and post-implantation assessments following Barostim device implantation and titration.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of heart failure with reduced ejection fraction (defined as ejection fraction ≤ 35% for the purposes of this study) (should be within 12 months of screen) * Symptoms consistent with one of: 1. current New York Heart Association (NYHA) Class III or 2. current NYHA Class II and historical NYHA Class III * Laboratories with last N-terminal pro-B-type natriuretic peptide (NT-proBNP) \< 1600 pg/ml (should be within 3 months of screen) * Management with maximally-tolerated GDMT medications and devices * Age \>= 18 years
Exclusion criteria
* Age \< 18 years * Myocardial infarction (MI), syncope, cerebrovascular accident (CVA), aborted sudden cardiac death (SCD) (and implantable cardioverter defibrillator (ICD) therapy) within 3 months of screening * Bilateral carotid bifurcations located above the level of the mandible * Carotid artery stenosis greater than 50% caused by atherosclerosis * Ulcerative plaques in the carotid artery * Baroreflex failure or autonomic neuropathy * Symptomatic un-controlled bradyarrhythmias * Severe chronic lung disease * Current treatment with inotropes * Pacemaker or ICD within 3 months of screening * Cardiac resynchronization therapy (CRT) devices within 6 months of screening or anticipated to be placed in the next 90 days following screening * Prior surgery, radiation, endovascular stent in the carotid sinus * History or consideration of solid organ transplantation * History or consideration of left ventricular assist device (LVAD) * Life expectancy \<1 year from time of screening * Non-cardiovascular conditions interfering with 6MWT distance assessment * Inability to fulfill protocol requirements * Known allergy to silicone or titanium
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in peak exercise PCWP at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Exercise pulmonary capillary wedge pressure (PCWP) will be measured at peak exercise at approximately six months post-Barostim titration and compared with peak exercise PCWP measured during the pre-implantation phase. Change from baseline will be calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in peak exercise load-adjusted PCWP at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Exercise pulmonary capillary wedge pressure (PCWP) will be measured at peak exercise at approximately six months post-Barostim titration and compared with peak exercise PCWP measured during the pre-implantation phase. PCWP measurements will be normalized to maximal exercise load at each time point. Change from baseline will be calculated. |
| Change in peak exercise output-adjusted PCWP at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Exercise pulmonary capillary wedge pressure (PCWP) will be measured at peak exercise at approximately six months post-Barostim titration and compared with peak exercise PCWP measured during the pre-implantation phase. PCWP measurements will be normalized to cardiac output at each time point. Change from baseline will be calculated. |
| Change in peak exercise cardiac output at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Exercise cardiac output (CO) will be measured at peak exercise at approximately six months post-Barostim titration and compared with peak exercise CO measured during the pre-implantation phase. Change from baseline will be calculated. |
| Proportion of participants with significant reduction in PCWP at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Exercise pulmonary capillary wedge pressure (PCWP) will be measured at peak exercise at approximately six months post-Barostim titration and compared with peak exercise PCWP measured during the pre-implantation phase. Patients will be categorized into "responders" who demonstrate either a 10% reduction in PCWP or a 3 mmHg reduction in PCWP or "non-responders" who do not demonstrate at least this degree of percent or absolute change. The proportion of participants that are considered "responders" by this metric will be collected and assessed. |
| Change in peak exercise mean PA pressures at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Exercise mean pulmonary arterial pressure (PAP) will be measured at peak exercise at approximately six months post-Barostim titration and compared with peak exercise mean PAP measured during the pre-implantation phase. Change from baseline will be calculated. |
| Change in peak VO2 at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Exercise peak VO2 will be measured via cardiopulmonary exercise testing (CPET) at approximately six months post-Barostim titration and compared with peak VO2 measured via CPET during the pre-implantation phase. Change from baseline will be calculated. |
| Change in average daily step count | Pre-implantation phase (baseline, 0-2 months) and post-implantation phase monthly (approximately 0-9 months post-implantation). | Average daily step counts will be measured via study-provided Fitbit Inspire 3 fitness trackers. Absolute change and trends will be assessed from baseline to monthly time points in the post-implantation phase. |
| Change in average daily step count at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | The most recent 30-day period of daily step counts will be measured via study-provided Fitbit Inspire 3 fitness trackers and evaluated for the average daily step count. This will be assessed at approximately six months post-Barostim titration and compared with the average of the last 30-day period of daily step counts prior to the end of the pre-implantation phase. Change from baseline will be calculated. |
| Change in highest daily step count at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | The most recent 30-day period of daily step counts will be measured via study-provided Fitbit Inspire 3 fitness trackers and evaluated for the maximum daily step count. This will be assessed at approximately six months post-Barostim titration and compared with the maximum of the last 30-day period of daily step counts prior to the end of the pre-implantation phase. Change from baseline will be calculated. |
| Change in estimated peak VO2 at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | The most recent Fitbit cardio fitness score (estimated peak VO2) will be measured via study-provided Fitbit Inspire 3 fitness trackers. This will be assessed at approximately six months post-Barostim titration and compared with the most recent Fitbit cardio fitness score prior to the end of the pre-implantation phase. Change from baseline will be calculated. |
| Change in heart rate variability at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | The most recent 30-day average of heart rate variability will be measured via study-provided Fitbit Inspire 3 fitness trackers. This will be assessed at approximately six months post-Barostim titration and compared with the average of the last 30-day period prior to the end of the pre-implantation phase. Change from baseline will be calculated. |
| Change in proportion of exercise days per month at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | The most recent 30-day proportion of exercise days will be measured via study-provided Fitbit Inspire 3 fitness trackers. This will be assessed at approximately six months post-Barostim titration and compared with the proportion of exercise days of the last 30-day period prior to the end of the pre-implantation phase. Change from baseline will be calculated. |
| Change in six-minute walk test at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | A six-minute walk test (6MWT) will be performed, and distances will be measured. This will be assessed at approximately six months post-Barostim titration and compared with the 6MWT performed during the pre-implantation phase. Change from baseline will be calculated. |
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | The KCCQ in its 12-question version will be performed to assess quality of life, and each question has 5-7 Likert-style response options. Responses are grouped according to domain for domain-specific scores. Overall and domain-specific scores are transformed and standardized and final scores are reported from 0-100, where higher scores reflect less functional limitation and better quality of life (better outcome). This will be assessed at approximately six months post-Barostim titration and compared with the KCCQ scores obtained during the pre-implantation phase. Change from baseline will be calculated. |
| Change in heart failure medication score at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | A heart failure medication score (0-9 points) will be calculated based upon participants' current heart failure medications, with 9 indicating a better outcome. Scored are allocated in the following manner: 2 points for being on a mineralocorticoid receptor antagonist or a sodium-glucose cotransporter 2 inhibitor; 2 points for being on a heart failure-specific beta blocker (carvedilol, metoprolol succinate, or bisoprolol; 2 points for \>= 50% max guideline-directed dose, 1 point for \<50% dose, 0 points if not); and 3 points for being on a renin-angiotensin-aldosterone system inhibitor (3 points for an angiotensin receptor-neprilysin inhibitor, or 1-2 points for either an angiotensin-converting-enzyme inhibitor or an angiotensin receptor blocker at \<50% or \>=50% max guideline-directed dose). This will be assessed at approximately six months post-Barostim titration and compared with the medication scores obtained during the pre-implantation phase. Change from baseline will be calculated. |
| Change in N-terminal prohormone of brain natriuretic peptide at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Participants' levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) will be obtained via blood draw. This will be assessed at approximately six months post-Barostim titration and compared with the NT-proBNP levels obtained during the pre-implantation phase. Change from baseline will be calculated. |
| Change in sleep score at 6 months post-titration | Pre-implantation phase (baseline, 0-2 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | The most recent 30-day average of sleep scores will be measured via study-provided Fitbit Inspire 3 fitness trackers. This sleep score is calculated by Fitbit as a proprietary algorithm to assess sleep quality based upon time asleep, time in sleep stages, movement during sleep, and sleeping heart rate, derived from measurements obtained by the fitness tracker. It is a score graded from 0-100, with 100 being the best score. This will be assessed at approximately six months post-Barostim titration and compared with the proportion of exercise days of the last 30-day period prior to the end of the pre-implantation phase. Change from baseline will be calculated. |
| Change in heart failure admissions at 6 months post-titration | Pre-implantation phase (baseline, approximately 0 months) and post-titration phase (approximately 6 months after completion of device titration, i.e. approx. 7-9 months post-implantation). | Participants' heart failure-related hospital admission counts will be obtained for the preceding six months at each time point. This will be calculated at approximately six months post-Barostim titration and compared with the same calculation of admissions at the time of study intake. Change from baseline will be calculated. |
Countries
United States
Contacts
CONTACTMorgan Smith, MD
PRINCIPAL_INVESTIGATORNir Uriel, MD
Columbia University
Outcome results
None listed