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Neurohormonal modulation as therapeutic avenue for right ventricular dysfunction in pulmonary artery hypertension: till the dawn, waiting.

ABSTRACT: Neuro-hormonal activation may lead to or be associated with pulmonary arterial hypertension (PAH) and right ventricular dysfunction. Notwithstanding whether it is the cause or the consequence of PAH-related right ventricle (RV) dysfunction neurohormonal activation contributes to significant morbidity and mortality in patients with PAH and the progression of RV dysfunction. Experimental data regarding the use of beta adrenergic blockade and renin-angiotensin aldosterone system modulation are encouraging. However, clinical studies have largely been negative or neutral; and, neuro-hormonal modulation is discouraged in patients with PAH related RV dysfunction for fear of systemic hypotension. Herein, we summarize the pathophysiological background that supports the potential role of neuro-hormonal modulation in the management of PAH related RV dysfunction; also present current clinical experience; and, discuss the need for controlled studies to move forward. Lastly, we review potential non- pharmacological modalities for neuro-hormonal modulations in PAH patients with RV dysfunction.

SUBMITTER: Emanuel R

PROVIDER: S-EPMC6123204 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Neurohormonal modulation as therapeutic avenue for right ventricular dysfunction in pulmonary artery hypertension: till the dawn, waiting.

Emanuel Roy R Chichra Astha A Patel Nirav N Le Jemtel Thierry H TH Jaiswal Abhishek A

Annals of translational medicine 20180801 15

Neuro-hormonal activation may lead to or be associated with pulmonary arterial hypertension (PAH) and right ventricular dysfunction. Notwithstanding whether it is the cause or the consequence of PAH-related right ventricle (RV) dysfunction neurohormonal activation contributes to significant morbidity and mortality in patients with PAH and the progression of RV dysfunction. Experimental data regarding the use of beta adrenergic blockade and renin-angiotensin aldosterone system modulation are enco ...[more]

PMID: 30211189

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Project description:BackgroundIn pulmonary arterial hypertension (PAH), progressive right ventricular (RV) dysfunction is believed to be largely secondary to RV ischaemia. A recent pilot study has demonstrated the feasibility of Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) to detect in-vivo RV myocardial oxygenation. The aims of the present study therefore, were to assess the prevalence of RV myocardial ischaemia and relationship with RV myocardial interstitial changes in PAH patients with non-obstructive coronaries, and corelate with functional and haemodynamic parameters.MethodsWe prospectively recruited 42 patients with right heart catheter (RHC) proven PAH and 11 healthy age matched controls. The CMR examination involved standard functional imaging, OS-CMR imaging and native T1 mapping. An ΔOS-CMR signal intensity (SI) index (stress/rest signal intensity) was acquired at RV anterior, RV free-wall and RV inferior segments. T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at the inferior RV segment.ResultsThe inferior RV ΔOS-CMR SI index was significantly lower in PAH patients compared with healthy controls (9.5 (- 7.4-42.8) vs 12.5 (9-24.6)%, p = 0.02). The inferior RV ΔOS-CMR SI had a significant correlation to RV inferior wall thickness (r = - 0.7, p < 0.001) and RHC mean pulmonary artery pressure (mPAP) (r = - 0.4, p = 0.02). Compared to healthy controls, patients with PAH had higher native T1 in the inferior RV wall: 1303 (1107-1612) vs 1232 (1159-1288)ms, p = 0.049. In addition, there was a significant difference in the inferior RV T1 values between the idiopathic PAH and systemic sclerosis associated PAH patients: 1242 (1107-1612) vs 1386 (1219-1552)ms, p = 0.007.ConclusionBlunted OS-CMR SI suggests the presence of in-vivo microvascular RV dysfunction in PAH patients. The native T1 in the inferior RV segments is significantly increased in the PAH patients, particularly among the systemic sclerosis associated PAH group.

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Neurohormonal modulation as therapeutic avenue for right ventricular dysfunction in pulmonary artery hypertension: till the dawn, waiting.

Publications

Neurohormonal modulation as therapeutic avenue for right ventricular dysfunction in pulmonary artery hypertension: till the dawn, waiting.

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