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Neurohormone in the Pathobiology of PH: Beta-blockers
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Dr. Zeenat Sadfar discusses the role of beta-blockers in pulmonary hypertension. She describes how the targeted blockade of sympathetic nervous system pathways may prove advantageous in the treatment of patients with PAH. Filmed at the 2016 CHEST Annual Meeting.

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Hello. I'm Zeenat Safdar, I'm the Director of Pulmonary Hypertension Care Center in Clinical Research at Houston Methodist Hospital in Houston Texas. Today, we are going to talk about neurohormones in the pathobiology of pulmonary hypertension, specifically relating to the use of beta blockers and the sympathetic nervous system activation in pulmonary hypertension.

As we know, the PAH is associated with high mortality and the resulting in right heart failure and death. Now, there is a compensatory mechanism in the body for no systemic perfusion and the neurohormonal activation specifically of sympathetic nervous system.

Initial activation may be helpful, but in the long run, it would prove to be detrimental for these patients. We are going to see what happens to these patients and what happens if you target these sympathetic pathways.

The list of neurohormones which are activated, this is from a review article, the proposed mechanism of increased neurohormonal access in PAH, as interesting study looked at the patient with RV failure, 21 patients and this show that in patient with pulmonary hypertension as compared to controlled undergoing right heart cath, the peripheral norepinephrine level was elevated and that was associated with worse outcome. Then they divided these patients up into different levels of norepinephrine such that higher-level was associated with worse outcome.

In other study, looking actually at the sympathetic nerve activation in PAH patients, they took, did a neurogram of the peroneal nerve. They put a catheter there, and they saw that there was an increase burst in patient with PAH as compared to control as shown here in the graph. This increase burst was associated with increase in the heart rate, increase in the functional class and worse oxygen saturation. In the same group, when they did the atrial septostomy, there was reduction in this increased sympathetic activity suggesting that sympathetic over activity, it may be a compensatory mechanism that can be targeted in PH patients.

This is a study that is widely quoted from 2006 from French group showing that withdrawal of Propranolol that was given to patients with pulmonary hypertension was associated with improvement in the walk distance and improvement in their cardiac output and that is the reason why beta blockers are taught to be contraindicated in PH based on this one withdrawal study.

A study looking at Carvedilol, a beta blocker in six PH patients shows that there was improvement in the RVEF as shown here in the diagram. There was improvement in the stroke volume in these small amounts of patients suggesting that indeed Carvedilol was safe and maybe there is some efficacy.

A group interestingly did sympathetic nervous system denervation in patients. Actually, this was an animal study in dogs and showed that the increased activation and increased PA pressure was reduced in animals who had the denervation procedure done, again, suggesting that maybe sympathetic over activation can be targeted in these patients.
In conclusion, sympathetic nervous system is activated in PAH and targeting could be helpful, and blocking this would be helpful. There are ongoing clinical trials looking at targeting these pathways and we are waiting those results. 

Thank you.