Clinical trial NCT03453151
Conditions: Heart Failure
Sponsor: Duke University
Start date: 2018-05-01; Completion date: 2019-12-27
Enrollment: 19 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Patients with chronic heart failure and undergoing right heart catheterization will be enrolled in this study. Subjects will undergo catheterization of the heart to obtain central cardiac pressure and other cardiac hemodynamic parameters. Subsequently, the subject will undergo a regional nerve block of the splanchnic nerves.

This study will be a prospective, uncontrolled clinical trial. The study will not be controlled as invasive monitoring of hemodynamics will be performed, allowing clear demonstration of a cause-effect relationship. The goal of the study is to provide proof of concept.

Patients will undergo detailed physiological testing.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: splanchnic nerve anesthesia with a local anesthetic
Intervention descriptions: intervention 1: regional nerve block with a local anesthetic (Lidocaine/Bupivacaine)

Protocol documents:
Prot_SAP_000.pdf: 
Version 06/02/2020 
1 
 
Cover Page: 
 
Protocol Title: Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic HF II) 
 
NCT number: NCT03453151  
 
Document date: 6/2/2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Version 06/02/2020 
2 
 
1. Protocol Title: 
Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic HF II) 
 
2. Purpose of the Study: 
Splanchnic vasoconstriction may contribute to decompensation of chronic heart failure 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. 
Therefore, we hypothesize that interruption of the efferent/afferent innervation of the 
splanchnic vasculature will decrease cardiac congestion and improve renal function in 
subjects presenting with heart failure. 
 
Objectives: 
1. We will determine if splanchnic nerve blockade decreases cardiac preload as 
measured by invasive hemodynamics. 
2. We will determine if splanchnic nerve blockade will improve invasive 
hemodynamics during exercise. 
3. We will determine if splanchnic nerve blockade improves symptoms of shortness of 
breath. 
 
3. Background & Significance: 
Conventional wisdom dictates that heart failure (HF) exacerbations follow a period of fluid 
accumulation leading to volume overload. However, study of weight in HF shows that 54% 
of subjects have an exacerbation without antecedent weight gain. Invasive monitoring of 
hemodynamics showed that central venous pressure rises in the weeks prior to 
decompensation despite no weight change in both systolic and diastolic heart failure. The 
leading theory for explaining this phenomenon of increased central venous pressure in the 
absence of change in total body water is that subjects with heart failure (HF) have impaired 
ability to store blood in their splanchnic vascular compartment. In a healthy population, the 
splanchnic bed contains about 40% of the total blood volume, 80% of which is stored in 
capacitance veins, and serves as a buffer for the central vascular compartment. Fluid is 
normally mobilized from this compartment via increased sympathetic tone and circulating 
catecholamines in response to a variety of physiologic and pathologic stressors. Given the 
role that the splanchnic circulation plays in hemodynamic regulation, it is hypothesized 
that increased sympathetic tone in the splanchnic vasculature contributes to both acute and 
chronic heart failure decompensation by mobilizing fluid to the central vasculature (Fallick 
C, Circulation Heart Failure 2011). 
 
Animal models provide direct evidence of this pathophysiological effect. In healthy animals, 
splanchnic nerve stimulation shifts blood into the central compartment, increasing preload 
and cardiac output. In dogs with cardiac pacing induced systolic heart failure, splanchnic 
vascular capacitance was decreased (Ogilvie RI, Circulation 1992). In these dogs, surgical 
transection of the splanchnic nerve, 


Version 06/02/2020 
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terminating sympathetic tone, results in decreased preload as measured by systolic and 
diastolic filling pressures and increased compliance of the left ventricle. In humans 
splanchnic nerve blocks are commonly used for pain control in subjects with intractable 
visceral organ cancer pain. The nerve blocks are done temporarily using anesthetic agents 
or more commonly permanently using neurolytic agents. Interestingly, the most common 
“side-effect” of this therapy includes transient orthostatic hypotension due an increase in 
splanchnic vascular storage capacity, which typically is prevented by aggressive pre-
procedural hydration (Eisenberg E, Anesthesia and analgesia 1995). In a pilot study using 
a short acting anesthetic agent (lidocaine) we have applied the splanchnic nerve block to 
acute heart failure subjects and found a reduction in resting cardiac filling pressures and an 
improved cardiac output (Figure 1 for the first 5 analyzed cases of total 10 subjects done 
by today). We found also found that the splanchnic nerve block improved shortness of 
breath and brain natriuretic peptide levels as an indication of cardiac decongestion. 
 
 
 
 
Figure 1: 
Panel A: Role of volume redistribution in the congestion of heart failure. 
Panel B: Procedural aspects of the splanchnic nerve block intervention. 
Panel C: Effects of the splanchnic nerve block on intra-cardiac pressures. 
Panel D: Effects on the splanchnic nerve block on symptoms and biomarker. 


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In addition to the strong evidence supporting splanchnic nerve blockade as treatment of 
volume overload, it is possible it will also treat cardiorenal syndrome. The autonomic 
nervous system plays a critical role in the regulation of the kidney. Though this system 
is not fully understood, preclinical and clinical studies indicate the presence of a 
hepatorenal reflex that inhibits the renal function and causes fluid retention. This reflex 
has its origin in the portal vein and is stimulated by portal congestion. The splanchnic 
nerves represent the afferent and partially the efferent arm of the reflex arch. Inhibition 
of this reflex pathway in animals and a small human pilot study was shown to improve 
renal function and urine production. 
 
 
4. Design & Procedures: 
This study will be a prospective, uncontrolled clinical trial. The study will not be controlled 
as invasive monitoring of hemodynamics will be performed, allowing clear demonstration 
of a cause-effect relationship. 
 
This study aims to piggy-back on an elective right heart catheterization (RHC) in subjects 
with chronic heart failure. The right heart catheterization will be part of the subject’s 
standard of clinical care (SOC). Subjects eligible for this study will be referred to the Duke 
cath lab for the evaluation of cardiac filling pressures because it is found to be necessary by 
the outpatient provider. This will occur in the cardiac catheterization lab. Subjects get 
scheduled for RHC days to weeks (2-3) ahead of their procedure. The eligible subject will 
be contacted before the study to be informed about the eligibility for the study and basic 
information about the study will be provided over the phone shortly after they have been 
scheduled. Subject will be consented in person in the morning of the procedure. 
 
 
The subject will undergo pre procedural testing as demonstrated below in the flow chart 
(all part of the clinical study - CS). Besides the RHC (SOC) the subject will undergo an 
invasive cardiopulmonary exercise with the RHC in place. Baseline evaluation is followed 
by a regional nerve block (bilateral splanchnic nerves) while the subject is in the 
catheterization lab. This will be performed by an anesthesiologist experienced in 
splanchnic nerve blocks. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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5 
 
Figure 2: Study flow chart 
 
 
 
 
1.5 h 
1 h 
0.5 h 
1 h 
1.5 h 
Pre 
Baselin
e 
Block 
Post 
Block 
Recover
y 
 
- Exam/orthostatics/ 
bendopnea 
- Labs (BMP, BNP 
) 
- 6 min walk test 
- Pulse wave analysis 
- Heart rate 
variability 
- Lung 
volume 
(impedance) 
- SOB questionnaires 
- Urine output 
1. Baseline 
RHC in supine 
2. Labs 
(Angiotensin II), 
Plasma 
Metanephrines, 
Vasopressin, 
Plasma 
Catecholamines, 
Lactate) 
3. RHC with 
feet up 
4. Echo and 
abdominal 
US 
5. Valsalva 
6. Invasive 
CPX with leg 
raise 
 
- Clear-site 
Splanchni 
c nerve 
block 
1. Baseline 
RHC in supine 
2. RHC with 
feet up 
3. Echo and 
abdominal 
US 
4. Valsalva 
5. Invasive 
CPX with leg 
raise 
6. Labs 
(Angiotensin II), 
Plasma 
Metanephrines, 
Vasopressin, 
Plasma 
Catecholamines, 
Lactate) 
 
- Clear-site 
- Exam/orthostatics/ 
bendopnea 
- Labs (BMP, BNP 
) 
- 6 min walk test 
- Pulse wave 
analysis 
- Heart rate variability 
- Lung 
volume 
(impedance) 
- SOB questionnaires 
- Urine output 
Intra-procedure 


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6 
 
Table: Study events 
 
Required 
Assessment 
Pre 
procedure 
(day of) 
Baseline 
(intra- 
procedure) 
Block 
Post Block 
Procedure 
 
Recovery 
24 h after 
procedure 
48 h after 
procedure 
6 Months 
after 
Procedure 
(±14 
days) 
Vitals (BP, 
HR, RR, 
SpO2) 
X 
(SOC) 
X 
(SOC) 
X 
(SOC) 
X 
(SOC) 
X 
(SOC) 
Weight 
X 
(SOC) 
X 
(SOC) 
Orthostatic vitals 
X 
(CS) 
X 
(CS) 
Urine output 
(continuous 
recording) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
Valsalva 
 
X 
(CS) 
 
X 
(CS) 
 
Labs: BMP, pro- 
BNP, urine 
sodium, 
X 
(SOC/CS) 
 
X 
(CS) 
Labs  
(Angiotensin II), 
Plasma 
Metanephrines, 
Vasopressin, 
Plasma 
Catecholamines, 
Lactate 
X 
(CS) 
X 
(CS) 
Dyspnea 
Questionnaire 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
Six minute walk 
test 
X 
(CS) 
X 
(CS) 
Impedance and 
lung fluid content 
measurement 
X 
(CS) 
X 
(CS) 
Heart rate 
variability 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
Echocardiogram 
X 
(CS) 
X 
(CS) 
Invasive CPX 
X 
(SOC/CS) 
X 
(CS) 
Splanchnic nerve 
block 
X 
(CS) 
Phone Call 
X 
(CS) 
X 
(CS) 
X 
(CS) 
 
*Phone call will capture mortality status and number of subject admissions to the hospital since procedure 


Version 06/02/2020 
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Following enrollment into the study the subject will undergo the following tests/measurements. A 
majority of the clinical testing occurs as part of the clinical study (CS) however the main procedure 
of RHC is standard of care (SOC). 
 
Pre-procedure: Following information will be collected from the subject’s charts that will be done 
as standard of care (SOC). Study specific tests/recordings are also listed below: 
- 
If the subject is female and childbearing potential and has not had a pregnancy test 
since the arrival to the hospital, a blood pregnancy test will be done (CS). If 
positive the subject will be excluded from the study. 
- 
Subjects will have strict measurement of urine output (SOC). A urine sample will 
be sent to the laboratory to check for the sodium concentration (CS). Subjects 
requiring a foley catheter will have measurements taken at comparable time 
intervals (SOC). 
- 
Recorded vitals including weight, BP, HR, RR, SPO2 on the day before procedure 
and within 1h before procedure (SOC) and record heart rate variability using a non-
invasive wrist monitor for 5 minutes (CS). 
- 
Orthostatic vitals (5 minutes supine, 1+5 minutes sitting and 1+5 minutes standing) 
on the day before procedure and within 1h before procedure (CS). Also we will 
document whether s has symptoms bending over for 10 seconds (bendopnea). 
- 
Labs: Basic metabolic panel (BMP) (SOC), brain natriuretic peptide (BNP) (CS), 
urine sodium (CS) plasma angiotensin II (CS), plasma arginine vasopressin (CS), 
plasma catecholamines. This will not require an extra lab draw. Total expected 
blood loss is <20ml. 
- 
Dyspnea questionnaire using a 7-point Likert scale and Visual Analog Scale (CS) 
- 
Six minute walk test (CS) 
- 
Echocardiogram at baseline and after the block will be performed while the subject 
is on the cath table (CS). This is considered one continuous echo. This ultrasound 
test will also be used to look at liver blood flow. 
- 
If the subject is on diuretics medications the scheduling of the medication will be 
adjusted to minimize interference with the study intervention. 
- The subject will be asked to hold the morning diuretic medication and 
the morning dose will be given 3 hours after the procedure (CS). This is not 
expected to provide any risk to the stable chronic heart failure subject, 
especially since the diuretic medication will be resumed after completion 
of study that same day. 
 
- 
Other medications can be continued, unless otherwise specified in the exclusion 
criteria. 
 
Procedure: 
 
1. Subjects will undergo elective right heart catheterization in the Duke catheterization
 
laboratory 
lab 
as 
ordered 
by 
the 
primary 
team. 
A 


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cardiopulmonary exercise test will be added if not already ordered by the primary 
provider. Central hemodynamics will be recorded (baseline, prior to nerve block) 
(SOC). The access site for the right heart catheterization will be radial, brachial or 
cervical (SOC) to allow a prone positioning of the subject for the splanchnic nerve block 
described in the next paragraph. Additional baseline RHC numbers will be recorded 
with legs elevated, which is done to simulate a fluid bolus. 
 
If the subject’s hemodynamics provide any other concern for complications related to the 
splanchnic nerve block (such as underfilling or severe pulmonary hypertension, not related 
to left heart failure) as determined by the study personnel, the splanchnic nerve block and 
associated monitoring will not be performed. The subject will be considered a screen 
failure. Any information and samples collected prior to this will be discarded/destroyed per 
institutional policies. 
 
Before cardiopulmonary exercise begins, the subject will perform the Valsalva maneuver. 
The subject will sit up on the catheterization lab table, after the intravenous lines have been 
placed. The subject will have an empty syringe placed in their mouth.  He/she will blow 
into the syringe for 30 seconds.  This is the standardized method for performing the 
Valsalva maneuver (Saxena, M, Journal of American Heart Association, 2018).  The 
intracardiac pressures will be measured continuously during the 30 seconds.  Following the 
Valsalva maneuver, the subject will be placed supine on the stationary bike for 
cardiopulmonary exercise. Cardiopulmonary exercise testing will include a 20 W initial 
steady phase during which RHC numbers will be recorded and echocardiogram with liver 
blood flow will be obtained. This will take up to 7 minutes followed by quick (every 1 
minute increase in 20W) ramp to peak exercise. At peak exercise repeat hemodynamics 
and echocardiography will be obtained. 
 
Subjects will further be monitored with: 
- 
Telemetry (SOC) 
- 
ClearSite/CheetahMedical/Sphygmocor/ReDS for continuous non-invasive 
hemodynamic/lung fluid content recording (CS) 
- 
Continuous urine output (ml/hour) recording if foley is present (SOC) 
- 
A non-invasive wrist monitor/chest band to monitor the heart rate variability 
 
Baseline hemodynamics and exercise CPX will be performed before and after the nerve 
block detailed below. 
 
2. Unilateral splanchnic nerve block performed by an anesthesiologist (see images below) 
(CS). The anesthesiologist will perform a unilateral block to the splanchnic nerve.  The 
blood pressure will be checked, after 15 minutes, post-block.  If the systolic blood pressure 
is reduced by > 20mmHg, the contralateral splanchnic nerve will not be blocked.  
Following the right heart catheterization procedure the subject will be prone on the 
abdomen. Central venous access remains in place. Needle will be placed under 
fluoroscopic guidance in the posterior chest wall. Anesthetic solution (1.5% lidocaine with 
1:200.000 epinephrine and of 0.5% ropivacaine) will be injected. Lidocaine 1.5% with 
Epinephrine 1:200.000 will be used initially to confirm extravascular administration. The 
subject with will then be placed back on his/her back. The subject will then undergo repeat 
hemodynamic measurement with the RHC catheter that was already in place. Then the 
subject proceeds with invasive cardiopulmonary testing after a 30 minute break. The 
central venous catheter will be removed after the hemodynamic monitoring/testing is 
completed in the catheterization laboratory. 
 
Additional measurements include: 


Version 06/02/2020 
9 
 
- 
Orthostatic vitals (CS). 
- 
Dyspnea questionnaire (CS) 
- 
Echocardiography and liver flow measurements (CS) 
 
 
 
 
Follow up procedures: 
 
Following right heart catheterization and lidocaine splanchnic nerve block the will be 
observed for monitored in the cath lab holding area for 3 hours following nerve block 
(SOC). 
 
- 
Continuous recording of urine output for the procedure day (CS) will be achieved 
by recording urine output at the beginning of pre-testing, just before the cath lab 
procedure, just after the cath lab procedure and before the subject leaves home. 
- 
Basic vitals (SOC) and orthostatic vitals (CS) following the cath lab procedure and 
record heart rate variability using a non-invasive wrist monitor (CS). 
- 
Repeat labs after the procedure before the subject leaves. Pro-BNP, BMP, serum 
sodium (all CS) 
- 
Labs: Angiotensin 2, plasma metanephrines (if on inotropes), plasma 
catecholamines, vasopressin, lactate, and urine sodium will be collected 
immediately before and after the procedure 
- 
Dyspnea questionnaire after nerve block (CS) and again at 48 hours 
- 
Six minute walk test (CS) after the block 
- 
Weight after the procedure. 
 
Phone Call 
Subjects will be contacted by study team 24h, 48h and six months (± 14 days) following their 
nerve block procedure. The purpose of this call will be to obtain shortness of breath status, 
potential long term complications and mortality status and document the number of inpatient 
admissions since the procedure. 
 
Blood samples processing: 
Some blood samples collected before and after the nerve block (plasma metanephrines, 
plasma catecholamines, angiotensin II and arginine vasopressin, lactate) will be processed 
(centrifuged) and stored at -70 degrees Fahrenheit before sent out to an external lab. Storage 


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duration may vary between weeks to months. Samples will be stored in a research freezer 
located on the 7th floor of Duke North (cath lab research freezer). As part of the study, we 
will send blood for study-related laboratory tests to the Mayo clinic and Inter Science 
Institute. These would include laboratory tests such as metanephrines, vasopressin, 
catecholamines, and angiotensin. A data transfer agreement is already in place. 
 
Safety endpoints: 
- 
The duration of the anesthetic block is estimated for 12-24 hours. The subject will be 
monitored for up to 3 hours in the catheterization laboratory/holding area, if there is 
any concern or evidence of procedure related complications the will be kept overnight 
in the cath lab holding area. A potentially observed effect of the block to prevent 
discharge the day of procedure could be orthostatic hypotension. will also be contacted 
at 48 hours post procedure to ascertain any potentially missed complications. Further 
the subject’s medical chart will be observed for 6 months following study enrollment 
to evaluate for admissions for heart failure. 
 
Incidence of major side effects has been reported to be <1:1000 and are expected 
to occur immediately post nerve block. They include: 
- 
Pneumothorax, possibly requiring a chest tube 
- 
Aortic puncture with retroperitoneal bleed or hematothorax 
- 
Spinal cord trauma with possibly paralysis 
 
Incidence of minor side effects like: 
- 
Orthostatic hypotension 
- 
Pain at puncture site and intercostal neuralgia 
- 
Gastrointestinal dysmotility including diarrhea, constipation and 
abdominal cramping 
- 
Bleeding at puncture site 
Efficacy endpoints: 
The following efficacy endpoints will be evaluated: 
 
Primary: 
- Improvement in 20 W and peak exercise PA mean and 
wedge pressure 
- Reduction in central venous pressure and/or pulmonary 
artery pressure (diastolic) and/or pulmonary capillary 
wedge pressure at 30 minutes after nerve block 
 
Secondary: 
 
                 - 
Reduction in central venous pressure and/or pulmonary artery 
 
 pressure (diastolic) and/or pulmonary capillary wedge pressure at 30  
 
minutes after nerve block 
 
- 
Increase 
in 
cardiac 
output 
at 
rest, 
improvement 
in 
echocardiographic parameters like ejection fraction (increase), 
central venous pressure (decrease), pulmonary artery systolic 
pressure (decrease), right ventricular diameter (decrease), left 
ventricular diameter (decrease) 
- 
Reduction in pro brain natriuretic peptide (pro-BNP) 
- 
Increase in UOP (output measured in ml/hour) and renal function 
(BUN and creatinine) in the hours following the procedure. 


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- 
Symptomatic improvement like a decrease in dyspnea (dyspnea 
questionnaire) and 6-minute walk test 
Exploratory aims: 
- 
Change in cardiac and autonomic markers after nerve block (i.e. 
angiotensin and catecholamines) 
 
7. Selection of Subjects: 
 
Subjects will be recruited from Duke University Medical Center outpatient environment. 
All potential study subjects will be scheduled electively by the cardiologist for a RHC +/- 
an invasive cardiopulmonary exercise. Subjects will be identified via a routine screen of 
the outpatient cath schedule weeks ahead of time. 
 
The study will enroll subjects who meet the criteria as detailed below. Potentially eligible 
subjects will be contacted and informed about the possibility of the study. The actual 
consent process will occur on the morning of the procedure. The primary enrollment target 
is up to 30 subjects (15 HF with preserved ejection fraction and 15 HF with reduced 
ejection fraction). 
 
Inclusion criteria: 
- 
Age 18-90 
- 
Followed at DUMC for known or suspected diagnosis of HF (NYHA stage 1-3, Class C-
D), including subjects on inotropic medication 
- 
Systolic blood pressure (SBP) > 100 mmHg 
- 
Planned for elective diagnostic right heart catheterization 
 
Exclusion criteria: 
Contraindicated medications: 
- 
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 
HF medication regimen: 
- 
Initiation of HF medications (in the 48 hours preceding the study) such as beta blockers, ACEI, 
ARB, aldosterone receptor blockers, calcium channel blockers of any type, central 
sympatholytics like clonidine, moxonidine, 
- 
Recent acute MI or hemodynamic instability: 
- 
Acute MI (STEMI or Type I NSTEMI) within 7 days? 
- 
Evidence of progressive cardiogenic shock within 48 hours 
- 
Repeat systolic blood pressure <90mmHg or >180mmHg 
Certain forms of HF: 
- 
Restrictive cardiomyopathy 
- 
Constrictive pericarditis 
- 
Pericardial effusion with evidence of tamponade 
- 
Severe valvular stenosis 
Severe bleeding risk: 
- 
Known history of an increased bleeding risk 
- 
Thrombocytopenia (<50,000) 
Significant comorbidities: 


Version 06/02/2020 
12 
 
- 
NYHA class symptoms 
- 
End-stage renal disease CKD stage 5 due to primary renal pathology 
- 
Any form of preceding acute or chronic use of ultrafiltration or hemodialysis 
- 
History of thoracic spine surgery 
- 
Severe scoliosis of the thoracic spine 
- 
History of lung surgery or history of pneumothorax or chest tube placement during the 
current admission 
- 
History of lung disease other than asthma and COPD (like interstitial fibrosis, cystic 
fibrosis, pneumonitis, lung cancer etc.) 
- 
Respiratory instability (dependent on >4 L nasal cannula for a saturation >90% SpO2) 
- 
Exclude severe pulmonary hypertension 
- 
History of organ transplant (heart, lung, liver, pancreases, small bowel, kidney). 
Pregnancy 
Procedure 
- 
Unable to tolerate procedure as determined by subject or investigator 
- 
will be excluded if invasive hemodynamics on study date determine that the subject does not 
have elevated filling pressures at rest or stress. Following pressures/situations will exclude the 
subject: wedge pressure <15mmHg (<12mmHg on inotrope) at rest and <25mmHg with peak 
stress (<22 with inotropes) and greater than the central venous pressure or determined by study 
personnel to be at risk for nerve block related complications. 
 
8. Subject Recruitment & Compensation: 
Potential subjects will be identified via two potential pathways. Research team will screen 
the outpatient scheduled RHC cases and send a recruitment letter to the subject once their 
primary care provider has agreed to this. The subject will be contacted over the phone if 
the subject has not replied to the letter in at least 10 days per policy. The subject will be 
provided with any additional information he/she wants. In a second scenario the primary 
provider approaches the study team with a potential cases. In both cases the subject will be 
given a heads up about being 
approached on the day of the study about a second approach in person by a health care 
provider known to the patient for potential consent. 
 
9. Consent Process 
 
Candidate subjects will be informed of the risks and benefits of participation in the study. 
They will be informed of the study process and demands. They will be given a copy of the 
informed consent document to review and afforded adequate time to do so. 
 
Informed consent will be obtained prior to the right heart catheterization. Consent will be 
obtained by Study PI, Duke Heart Center study coordinators who are trained on the study 
and who have been trained on Informed Consent Process and other key personnel as 
designated by the PI. Consent will be obtained in the catheterization laboratory holding 
area. A subject is considered enrolled in this clinical study at the time at which the subject 
and investigator or authorized designee have personally signed and dated the Informed 
Consent Form. 
 
10. Subject’s Capacity to Give Legally Effective Consent: 
 
Subject has to be able to understand the English language and understand the study process 
including all potential risk and benefits to the subject. Any subject where the study 
personnel or treatment team has cause for concern regarding the subject’s ability to 
understand the study process or follow the consent process capacity, will be excluded from 


Version 06/02/2020 
13 
 
the study. 
 
11. Study Interventions: 
 
- 
Regional nerve block under fluoroscopic guidance 
- 
Cardiopulmonary exercise 
- 
Lab draws 
- 
Vital signs 
- 
Orthostatic vital signs 
- 
6-minute walk test 
- 
Non-invasive imaging with ultrasound 
- 
Non-invasive 
hemodynamic 
monitoring 
(heart 
rate 
variability, 
sphygmocor, ReDS, Cheetah Medical) 
- 
Optional: Foley placement 
 
12. Risk/Benefit Assessment: 


Version 06/02/2020 
14 
 
Procedural risks of splanchnic nerve blocks have been extensively studied. Risks 
associated with this anesthetic nerve block are uncommon. Patients undergoing this 
procedure have a small risk (<1%) risk of developing local anesthetic systemic toxicity as 
a complication of regional anesthesia. Symptoms include non-specific central nervous 
system effects (altered mental status, agitation, seizures) and cardiac arrest. We have now 
completed 10 cases in the first pilot trial using lidocaine and found no acute or chronic 
complications. 
 
Mild complications like local pain at injection site, orthostatic hypotension and 
gastrointestinal dysmotility are time limited and improve with resolution of the anesthetic 
block. Severe complications like pneumothorax possibly requiring a chest tube, aortic 
vessel puncture with retroperitoneal bleed or hematothorax and spinal cord injury with 
possible paralysis. These are very rare since placement of the needle occurs under 
fluoroscopic guidance. 
 
Other minor risks can include (in order of report in literature and experience at Duke): 
- 
Pain at puncture site and intercostal neuralgia 
- 
Gastrointestinal dysmotility including diarrhea, constipation and 
abdominal cramping as well as nausea 
- 
Bleeding at puncture site 
 
We will perform the splanchnic block for chronic heart failure, which is a new indication. 
The splanchnic nerve block has now been studied by us for acute heart failure but not been 
studied in the setting of chronic disease. We do not expect unexpected side effects other 
than stated above but unexpected side effects cannot be excluded. For safety purposes 
subjects enrolled in this study will remain monitored for several hours after the SNB and 
re-contacted at 48h. 
 
Anticipated benefits to the subject include improvement in central vascular congestion with 
a reduction in cardiac preload and pulmonary arterial pressures as well as left sided filling 
pressures. A reduction in cardiac pressures is also likely to improve symptoms of 
congestion, including shortness of breath. 
 
Further it is expected that a decongestion of the central veins and interruption of the 
cardiorenal reflex loop will result in an improvement in renal function as measured by urine 
output. This will further contribute to the decongestion of the subject’s vasculature. 
 
While both of those effects are only temporary (12-24h), the benefit provided by the brief 
episode of decongestion can provide lasting symptomatic improvement. Our intervention 
serves an additional diagnostic purpose by confirming an increased sympathetic tone in the 
abdominal innervation and could prompt the treatment team to adjust medical therapy to 
address the increased sympathetic tone and possible benefit on increased splanchnic 
capacitance. 


Version 06/02/2020 
15 
 
13. Costs to the Subject: 
 
The study will be at no additional cost to the subject on top of his regular hospitalization 
for heart failure and elective catheterization. 
 
14. Data Analysis & Statistical Considerations: 
 
Descriptive statistics of continuous outcomes will include sample size, mean, median, 
standard deviation, minimum and maximum. For categorical outcomes, the number and 
percentage of subjects in each category will be presented. Statistical comparisons will be 
made using t-tests for continuous outcomes and chi square or Fisher’s exact test (depending 
on overall event rates) for categorical outcomes. Paired t-tests will be used to compare 
changes from baseline to post-intervention. All statistical analyses will be performed using 
SAS for Windows (version 8.2 or higher) or other widely accepted statistical or graphical 
software. Subject data listings and tabular and graphical presentations of results will be 
provided. Unless otherwise specified, a two-sided 0.05 level of significance will be used 
to declare change in pre- and post-procedure variables different. 
 
For power analysis, our primary endpoint is decreased in central venous pressure following 
nerve blockade. Based on preliminary animal experiments, we anticipate a reduction of 
CVP of 25%. For a sample size of 16, If the true difference in the experimental and control 
means is 25%, we will be able to reject the null hypothesis that the population means of the 
experimental and control groups are equal with probability (power) .90. The Type I error 
probability associated with this test of this null hypothesis is 0.05. 
 
There is no direct measure of technical success following attempted block of the splanchnic 
nerves. The location of the splanchnic nerves is estimated biased on human anatomy 
dissections and established nerve block protocols used by the anesthesiology department. 
Procedural success to block the splanchnic nerves will be assumed in 70% of the cases 
based on the experience in splanchnic nerve blocks in subjects with intractable cancer. 
 
15. Data & Safety Monitoring: 
 
Due to the experimental nature of this intervention, data will be recorded after each subject 
completes the intervention for signs of unintended negative effects. These include 
hypotension, worsening renal function, or clinical deterioration. Additionally, subject’s 
electronic medical data will be screened for any traumatic complications from the nerve 
block at 48 hours post-procedure. 
 
Unanticipated adverse events, which are severe (listed above), will be reported to the IRB 
within 24 hours. Any other adverse event will be reported to IRB within 10 working days 
or per IRB policy. The Principal Investigator will also provide an annual report of any side 
effects or problems to the IRB during the study renewal process. 


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16 
 
Following discharge, the subject’s medical record will be monitored for readmission to the 
Duke hospital for heart failure for 6 months. 
 
No PHI is sent outside of Duke. 
 
16. Privacy, Data Storage & Confidentiality – see Section 12 of the e-IRB submission form 
and complete the questions in that section. 
 
1. Data will be obtained by approved study personnel. An enrollment log will also be 
maintained in Excel Spreadsheet on the Heart Center’s S:drive. The subject ID will also be 
stored on the folder to track subject enrollment and collection of data. Data will be recorded 
in Excel. Only deidentified data will be available for statistical analysis. All subject 
identifiers will be removed for database storage, statistical analysis and data reporting. This 
data will be stored on a study specific folder on the Duke server behind the Duke firewall. 
The subject ID code will be destroyed after data analysis is completed. Protected health 
information will not be used for any other purposes than those described in this protocol 
without obtaining further IRB approval. This information will be used for research 
purposes only and subjects will never be contacted regarding information obtained through 
chart review. A designated statistician from the DCRI will provide support with statistical 
analysis. 
 
The adequacy of the Research Data Security Plan (RDSP) will be evaluated and approved 
by the Cardiology CRU prior to study conduct. 
 
Any publications or presentations that result from this research will not identify any 
subjects individually, and will present data in aggregate form only. 
 
 
     Gathered data will be stored for at least 6 years.