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

Emanuel, Roy; Chichra, Astha; Patel, Nirav; Jemtel, Thierry H. Le; Jaiswal, Abhishek

doi:10.21037/atm.2018.06.04

Cited by 8 publications

(5 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The focus of this review is on the molecular mechanisms that may contribute to maladaptive remodeling in the RV. Although many pathways are currently under study in the pathogenesis of RV failure (13)(14)(15), this review will specifically focus on select molecular events and pathways that are supported by strong pre-clinical and human (clinical) data that have resulted in, or will lead to, clinical trials in PAH patients.…”

Section: Review Article On Right Ventricular Dysfunctionmentioning

confidence: 99%

Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism

Agrawal¹,

Lahm²,

Hansmann³

et al. 2020

Cardiovasc Diagn Ther

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is a rare, life-threatening condition characterized by dysregulated metabolism, pulmonary vascular remodeling, and loss of pulmonary vascular cross-sectional area due to a variety of etiologies. Right ventricular (RV) dysfunction in PAH is a critical mediator of both long-term morbidity and mortality. While combinatory oral pharmacotherapy and/or intravenous prostacyclin aimed at decreasing pulmonary vascular resistance (PVR) have improved clinical outcomes, there are currently no treatments that directly address RV failure in PAH. This is, in part, due to the incomplete understanding of the pathogenesis of RV dysfunction in PAH. The purpose of this review is to discuss the current understanding of key molecular mechanisms that cause, contribute and/or sustain RV dysfunction, with a special focus on pathways that either have led to or have the potential to lead to clinical therapeutic intervention. Specifically, this review discusses the mechanisms by which vessel loss and dysfunctional angiogenesis, sex hormones, and metabolic derangements in PAH directly contribute to RV dysfunction. Finally, this review discusses limitations and future areas of investigation that may lead to novel understanding and therapeutic interventions for RV dysfunction in PAH.

show abstract

Section: Review Article On Right Ventricular Dysfunctionmentioning

confidence: 99%

Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism

Agrawal¹,

Lahm²,

Hansmann³

et al. 2020

Cardiovasc Diagn Ther

View full text Add to dashboard Cite

show abstract

“…Finally, considering the aforementioned upregulation of the neurohormonal axis in PAH and its deleterious properties on worsening right heart failure in the long-run, a direct favorable implication of NEUi on right ventricular function and pulmonary circulation in this study population may be also taken into account[ 2 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease

Scagliola¹,

Brunelli²,

Balbi³

2022

WJCCM

View full text Add to dashboard Cite

BACKGROUND Despite major advances in pharmacologic treatment, patients with pulmonary arterial hypertension (PAH) still have a considerably reduced life expectancy. In this context, chronic hyperactivity of the neurohormonal axis has been shown to be detrimental in PAH, thus providing novel insights on the role of neurohormonal blockade as a potential therapeutic target. AIM To evaluate the application and prognostic effect of neurohormonal inhibitors (NEUi) in a single-center sample of patients with idiopathic PAH and risk factors for left heart disease. METHODS We analyzed data retrospectively collected from our register of right heart catheterizations performed consecutively from January 1, 2005 to October 31, 2018. Patients on beta-blocker, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker or mineralocorticoid receptor antagonist at the time of right heart catheterization were classified as NEUi users and compared to NEUi non-recipients. RESULTS Complete data were available for 57 PAH subjects: 27 of those (47.4%) were taking at least one NEUi at the time of right heart catheterization and were compared with the remaining 36 NEUi non-recipients. NEUi users were older and had a higher cardiovascular risk profile compared to non-recipients. Additionally, NEUi non-users had a higher probability of dying during the course of follow-up than NEUi recipients (56.7% vs 25.9%, log-rank P = 0.020). CONCLUSION The above data highlighted a subgroup of patients with PAH and comorbidities for left heart disease in which NEUi use has shown to be associated with improved survival. Future prospective studies are needed to identify the most appropriate therapeutic strategies in this subset population.

show abstract

“…Although IPAH can be managed with targeted drugs (such as endothelin receptor antagonists and prostacyclin inhibitors) which have increased the survival rate of patients with IPAH and improved their outcome, the long-term prognosis of IPAH remains poor (13). Traditionally, IPAH has been considered a disease predominantly affecting women (14,15).…”

Section: Discussionmentioning

confidence: 99%

Acute vasoreactivity testing predicts outcome of idiopathic pulmonary arterial hypertension patients with a negative acute response

Sun¹,

Li²,

Meng³

et al. 2020

Ann Transl Med

View full text Add to dashboard Cite

Background: Acute vasoreactivity testing (AVT) during right heart catheterization (RHC) is performed in certain subsets of patients with pulmonary arterial hypertension (PAH) in order to identify those who benefit from calcium channel blockers. The present study aimed to investigate the prognostic value of pre-AVT, post-AVT, and changes in AVT (ΔAVT) parameters for idiopathic PAH (IPAH) patients with a negative acute response, and to identify sex differences that could be of prognostic value.Methods: A total of 487 incident IPAH patients (171 males and 316 females) with a negative acute response to AVT were recruited from Shanghai Pulmonary Hospital between 2009 and 2018. Outcomes were predicted using the Kaplan-Meier curve and univariate/multivariate Cox regression analyses. All patients were followed up till January 2020, with outcome specified as all-cause mortality.Results: Inhalation of iloprost aerosol improved the hemodynamic parameters for all patients. Post-PVR was decreased, and post-cardiac output (post-CO) and post-cardiac index (post-CI) were increased compared with pre-AVT parameters among males. Increased post-artery oxygen saturation (post-SaO 2 ) and decreased post-mean right atrium pressure (post-mRAP) were also observed in females. For all patients, pre-CO ≥3.25 L/min, post-mPAP <53 mmHg, and post-mixed venous oxygen saturation (post-SvO 2 ) ≤63% were parameters suggesting better prognosis. For males, patients with pre-PVR <12.47 Wood units, pre-SvO 2 ≥64%, and post-mean pulmonary artery pressure (post-mPAP) <51 mmHg had a better prognosis. For females, patients with ΔmPAP ≥−4 mmHg and ΔPVR ≥−0.25 Wood units had better outcomes.Conclusions: AVT parameters, including pre-AVT, post-AVT and ΔAVT, have a more important prognostic value than currently used for identify a small subgroup of patients with PAH who are suitable for high-dose calcium channel blockers. Sex differences in AVT parameters suggest that sex should be taken into account in estimating prognosis.

show abstract

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

Cited by 8 publications

References 53 publications

Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism

Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease

Acute vasoreactivity testing predicts outcome of idiopathic pulmonary arterial hypertension patients with a negative acute response

Contact Info

Product

Resources

About