Chronic Heart Failure
Conditions
Keywords
heart failure, exercise, splanchnic nerve block
Brief summary
Splanchnic vasoconstriction may contribute to decompensation of chronic heart failure (HF) via volume redistribution from the splanchnic vascular bed to the central compartment. This is a sympathetically mediated reflex and can be interrupted through a splanchnic nerve block (SNB). We hypothesize that interruption of the efferent/afferent innervation of the splanchnic vasculature will decrease cardiac congestion in patients presenting with HF. Based on preliminary safety and efficacy data in acute and chronic heart failure patients with temporary (\<24 h) SNB. Now we will apply a prolonged SNB in chronic heart failure patients using a long acting agent. We will test the effects of SNB on long term exercise capacitance.
Detailed description
Activation of splanchnic nerves results in vasoconstriction and reduces splanchnic capacitance, therefore recruiting blood volume into the central circulation. In heart failure, a reduced splanchnic vascular capacitance could be the mechanism underlying symptoms of exercise intolerance and could predispose to rapid decompensation with external fluid intake or retention. A compromised vascular reservoir is likely unable to buffer shifts of fluid and actively contributes to the acute or chronic expulsion of fluid from the splanchnic vascular compartment to the central thoracic compartment. The redistribution of blood volume into the central circulation may lead to a sudden rise in pulmonary and left-sided cardiac pressures in HF. This makes the splanchnic vascular compartment an attractive target in heart failure. Our preliminary proof-of-concept work in patients with acute decompensated and chronic heart failure showed promise for the concept of splanchnic nerve modulation in heart failure. In a series of two small first-in-human studies for acute decompensated heart failure (N=13) (NCT02669407) and chronic heart failure (N=17) (NCT03453151), we found that a splanchnic nerve block (SNB) with lidocaine (90 min duration of action) and ropivacaine (24 hours duration of action) acutely reduced resting and exercise-induced intra-cardiac filling pressures, associated with improved patient symptoms and functional capacity. The present study will be a prospective open-label pilot study to help establish feasibility, safety and enable dose finding for botulinumtoxin. Following a baseline invasive (right heart catheterization) cardiopulmonary exercise testing (CPX) patients will undergo unilateral celiac plexus block, followed by repeat hemodynamic testing. Functional testing at baseline and follow up will be supplemented by measures of blood volume and autonomic tone.
Interventions
Percutaneous splanchnic nerve block
Sponsors
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Followed at DUMC for known or suspected diagnosis of HF (NYHA stage 2-4, Class C-D), including patients on inotropic medication * Systolic blood pressure (SBP) \> 100 mmHg * History of HF hospitalization or ER visit or iv diuretic use in last 12 months. * Patients will be included regardless of left ventricular ejection fraction.
Exclusion criteria
* Anticoagulation at the time the procedure or in case of recent warfarin use an INR \>1.4. Anticoagulation includes: warfarin, or novel oral anticoagulants like dabigatran, rivaroxaban, apixaban, endoxaban or full dose intravenous heparin products or bivalirudin and fondaparinux). Antiplatelet agents besides aspirin such as ticagrelor, prasugrel, Plavix are also considered to be a contraindication if used at time point of procedure. * Immunosuppressive medications for solid organ transplant * Acute MI (STEMI or Type I NSTEMI) within 7 days? * Evidence of progressive cardiogenic shock within 48 hours * Restrictive cardiomyopathy * Constrictive pericarditis * Pericardial effusion with evidence of tamponade * Severe valvular stenosis requiring intervention * Known history of an increased bleeding risk * Thrombocytopenia (\< 50,000) * End-stage renal disease CKD stage 5 due to primary renal pathology
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Exercise Wedge Pressure | 4 weeks | Measured with cardiopulmonary exercise testing |
| Peak Pulmonary Arterial Pressure | 4 weeks | Measured on exercise cardiopulmonary stress test |
| Absence of Nerve Block Related Complications | 8 weeks | Assessment of orthostasis, gastrointestinal symptoms were observed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting Pulmonary Arterial Pressure | 4 weeks | Assessed on right heart catheterization |
| Peak Oxygen Uptake | 4 weeks | — |
| Dyspnea - Visual Analog Scale (VAS) | 4 weeks | The VAS for dyspnea has a range of 0 to 100, where 0 corresponds to the patient's subjective feeling of I Can Breathe Normally and a score of 100 corresponds to I Can't Breathe At All. |
| Resting Wedge Pressure | 4 weeks | Assessed with right heart cath |
| Resting Central Venous Pressure | 4 weeks | Assessed with right heart cath |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Splanchnic Nerve Block Splanchnic nerve block: Percutaneous splanchnic nerve block | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Splanchnic Nerve Block |
|---|---|
| Age, Continuous | 73 years STANDARD_DEVIATION 6 |
| Left ventricular ejection fraction >55% | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Absence of Nerve Block Related Complications
Assessment of orthostasis, gastrointestinal symptoms were observed
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Splanchnic Nerve Block | Absence of Nerve Block Related Complications | 0 Participants |
Primary
Peak Exercise Wedge Pressure
Measured with cardiopulmonary exercise testing
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Splanchnic Nerve Block | Peak Exercise Wedge Pressure | Pre nerve block | 44 Mmhg | Standard Deviation 6.2 |
| Splanchnic Nerve Block | Peak Exercise Wedge Pressure | Post nerve block | 34 Mmhg | Standard Deviation 8.2 |
Primary
Peak Pulmonary Arterial Pressure
Measured on exercise cardiopulmonary stress test
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Splanchnic Nerve Block | Peak Pulmonary Arterial Pressure | Baseline | 56 Mmhg | Standard Deviation 9.2 |
| Splanchnic Nerve Block | Peak Pulmonary Arterial Pressure | Post nerve block | 47 Mmhg | Standard Deviation 10.6 |
Secondary
Dyspnea - Visual Analog Scale (VAS)
The VAS for dyspnea has a range of 0 to 100, where 0 corresponds to the patient's subjective feeling of I Can Breathe Normally and a score of 100 corresponds to I Can't Breathe At All.
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Splanchnic Nerve Block | Dyspnea - Visual Analog Scale (VAS) | After nerve block | 81 units on a scale | Standard Deviation 21 |
| Splanchnic Nerve Block | Dyspnea - Visual Analog Scale (VAS) | Baseline | 76 units on a scale | Standard Deviation 11 |
Secondary
Peak Oxygen Uptake
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Splanchnic Nerve Block | Peak Oxygen Uptake | Baseline | 10.5 mL/min/m2 | Standard Deviation 2 |
| Splanchnic Nerve Block | Peak Oxygen Uptake | Post nerve block | 9.1 mL/min/m2 | Standard Deviation 3 |
Secondary
Resting Central Venous Pressure
Assessed with right heart cath
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Splanchnic Nerve Block | Resting Central Venous Pressure | Baseline | 9.3 mmHg | Standard Deviation 4.9 |
| Splanchnic Nerve Block | Resting Central Venous Pressure | Post nerve block | 5.8 mmHg | Standard Deviation 2.4 |
Secondary
Resting Pulmonary Arterial Pressure
Assessed on right heart catheterization
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Splanchnic Nerve Block | Resting Pulmonary Arterial Pressure | Baseline | 24 mmHg | Standard Deviation 9 |
| Splanchnic Nerve Block | Resting Pulmonary Arterial Pressure | Post nerve block | 20 mmHg | Standard Deviation 4 |
Secondary
Resting Wedge Pressure
Assessed with right heart cath
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Splanchnic Nerve Block | Resting Wedge Pressure | Baseline | 17.5 mmHg | Standard Deviation 9.5 |
| Splanchnic Nerve Block | Resting Wedge Pressure | Post nerve block | 14 mmHg | Standard Deviation 1.6 |