A Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension

Background. Pulmonary hypertension Group 2 (PH 2) associated with left-sided heart disease
is relatively common, is associated with a poor prognosis, and unfortunately there are no
proven medical treatments beyond attempts at correcting the left sided heart disease. Many
PH 2 patients have evidence of vasoconstriction and increased sympathetic nervous system
activity. Use of agents or procedures which produce a reversible chemical sympathectomy have
not been systematically tested in PH 2.

Methods. Two groups will be eligible for participation: Group 1 (n=10): Patients with PH 2
previously documented by echocardiography (echo), 6 minute walk test, biomarkers, and right
heart catheterization (RHC) will receive reserpine, 0.05 mg per day for two weeks, then, 0.1
mg per day for an additional two weeks. After one month, patients will be reassessed for New
York Heart Association (NYHA) class and drug side effects, echocardiography, 6 minute walk
assessment, and brain natriuretic peptide (BNP). Group 2 patients (n=10) will have
clinically suspected PH 2 and be scheduled to undergo clinically indicated RHC. If during
RHC PH 2 is confirmed, after assessment of nitric oxide responsiveness, their baseline
hemodynamics will be re-established over 10 minutes, and a left stellate ganglion block with
lidocaine will be performed, and immediate hemodynamic responsiveness assessed. Four hours
post-procedure, a side effect questionnaire will be obtained. Group 2 patients who complete
RHC will then begin reserpine treatment in the same manner as Group I patients.

Hypothesis and Impact. PH 2 is the most common type of pulmonary hypertension. The current
diagnostic and therapeutic strategy aims to treat the left sided heart disease in attempt to
normalize pulmonary artery pressure. The place of selective pulmonary vasodilators is
undefined. The investigator's approach addresses inhibition of adverse pulmonary
vasoconstriction mediated by the sympathetic nervous system in PH 2.

Inclusion criteria:

- Prior right heart catheterization, with mean pulmonary artery pressure > 25 mm Hg,
pulmonary capillary wedge pressure > 15 mm Hg, and diastolic pressure gradient
(pulmonary artery diastolic pressure - mean pulmonary capillary wedge pressure) ≥ 7
mm Hg OR clinically suspected group 2 pulmonary hypertension from non-invasive
testing with planned right heart catheterization (RHC).

- On stable diuretic therapy

- Able to attend end-study visit 4 weeks after study entry

Exclusion criteria:

- Anticipated surgery to correct heart lesion responsible for pulmonary hypertension

- Need for heparinization for right heart catheterization (not standard practice, but
sometimes utilized)

- History of depression, or treatment with tricyclic anti-depressant, serotonin uptake
inhibitor, monamine oxidase inhibitor

- Severe renal or hepatic impairment, creatinine clearance < 30 ml/minute or renal
replacement therapy or post-kidney transplant, abnormal liver function with elevated
enzymes> 1.5 times the upper limit of normal or prior liver transplant.

- Systolic blood pressure <100 mm Hg

- Heart rate < 60 beats per minute

- Inability to independently complete telephone follow-up at two weeks, and clinic
end-study visit at 4 weeks.

- Pulmonary edema

- Infiltrative cardiomyopathy - amyloidosis

- Symptomatic orthostatic hypotension

- Women of childbearing age who have not had surgical sterilization and are not using
oral contraceptives, or who's spouse has not had surgical sterilization will be
excluded due to the length of the trial and the possibility that they could become
pregnant after entry.

- Uncontrolled heartburn

- Prior surgery to the left neck, for example, carotid endarterectomy, or other surgery
which would increase the risk of stellate ganglion block

- Known sensitivity, allergy, or contraindication to lidocaine, any local anesthetic,
or reserpine