Circulating Aldosterone Levels and Disease Severity in Pulmonary Arterial Hypertension

Safdar, Zeenat; Thakur, Aishwarya; Daniella, Guffey; Minard, Charles G.; Ji, Yingqun

doi:10.1378/chest.2280635

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…Thus, we sought to ascertain the cardioprotective potential of silencing Wipi1 in an in vitro model of HF and its effect on RVF-associated drivers. Specifically, we cultured isolated neonatal rat ventricular myocytes (NRVMs) with aldosterone to mimic the neurohormonal activation predominantly associated with RV dysfunction and failure (23)(24)(25)(26). In control NRVMs transfected with nontargeting siRNA (si-Scramble), neurohormonal stimulation with aldosterone significantly increased the expression of Nppa, Nppb, Acta1, and Myh7, consistent with induction of the fetal gene program in HF (Supplemental Figure 2).…”

Section: Resultsmentioning

confidence: 89%

WIPI1 is a conserved mediator of right ventricular failure

Tzimas¹,

Rau²,

Buergisser³

et al. 2019

JCI Insight

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Section: Resultsmentioning

confidence: 89%

WIPI1 is a conserved mediator of right ventricular failure

Tzimas¹,

Rau²,

Buergisser³

et al. 2019

JCI Insight

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“…We previously investigated the plasma aldosterone levels of 125 PAH patients and determined that although the aldosterone level was not associated with increased mortality in PAH, it was a marker of disease severity. 27 Interestingly, the patients in that study had the contradictory finding that those on spironolactone had a higher RAP than those who were not. This finding may indicate that those receiving spironolactone may have worse disease.…”

Section: Discussionmentioning

confidence: 90%

Effect of spironolactone use in pulmonary arterial hypertension – analysis from pivotal trial databases

Safdar

Cho

2021

Pulm. circ.

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Spironolactone, a common diuretic used in the treatment of pulmonary arterial hypertension (PAH), improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function within pulmonary endothelial cells. Spironolactone has demonstrated vascular remodeling properties and reduced all-cause mortality in patients with severe heart failure. Despite widespread use, however, its effect on morbidity and mortality in PAH have not been fully explored. A large cohort of PAH patients from a harmonized dataset from four pivotal trials were analyzed to characterize the patient population and outcomes associated with spironolactone treatment. Of 1,229 evaluable patients, 74% female, mean age 47Â±15yrs, baseline six-minute walk distance (6MWD) 345Â±74m and 75% World health Organization (WHO) functional class (FC) III/IV. Of the patients receiving spironolactone, 43% were on subcutaneous treprostinil, compared to 29.9% of patients who were not receiving spironolactone. Long-term spironolactone-treated PAH patients were older (P=0.01), had lower baseline 6MWD (P=0.01) and cardiac index (P<0.01), higher baseline Borg dyspnea score (P=0.01), WHO functional class, and right arterial pressure (P<0.01). Spironolactone patients tended to have higher hazard of clinical worsening (P<0.01). However, propensity analysis, when controlled for disease severity, showed that spironolactone treated patients did not demonstrate improved outcomes, in terms of survival and clinical worsening. Across studies, the current analysis has demonstrated that the actions of spironolactone within the context of the PAH disease process may differ from its action in CHF patients. Despite the results reported with spironolactone use in patients with left heart disease, these findings may not translate to right heart failure and pulmonary vascular pathology as similar outcomes have not necessarily been recognized in the PAH patient population. Future studies are needed to explore these findings further.

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“…However, in a larger cohort of PAH patients, aldosterone concentration was not directly associated with cardiac output, 6-minute walking distance (6MWD) or survival [59].…”

Section: Systemic Changes In the Renin-angiotensin-aldosterone Systemmentioning

confidence: 88%

Neurohormonal modulation in pulmonary arterial hypertension

et al. 2021

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Pulmonary hypertension is a fatal condition of elevated pulmonary pressures, complicated by right heart failure. Pulmonary hypertension appears in various forms; one of those is pulmonary arterial hypertension (PAH) and is particularly characterised by progressive remodelling and obstruction of the smaller pulmonary vessels. Neurohormonal imbalance in these patients is associated with worse prognosis and survival. In this back-to-basics review on neurohormonal modulation in PAH, we provide an overview of the pharmacological and non-pharmacological strategies that have been tested preclinically and clinically. The benefit of neurohormonal modulation strategies in PAH patients has been limited by lack of insight in how the neurohormonal system is changed throughout the disease and difficulties in translation from animal models to human trials. We propose that longitudinal and individual assessments of neurohormonal status are required to improve timing and specificity of neurohormonal modulation strategies. Ongoing developments in imaging techniques such as positron emission tomography (PET) may become helpful to determine neurohormonal status in PAH patients in different disease stages and optimise individual treatment responses.

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Circulating Aldosterone Levels and Disease Severity in Pulmonary Arterial Hypertension

Cited by 4 publications

References 24 publications

WIPI1 is a conserved mediator of right ventricular failure

WIPI1 is a conserved mediator of right ventricular failure

Effect of spironolactone use in pulmonary arterial hypertension – analysis from pivotal trial databases

Neurohormonal modulation in pulmonary arterial hypertension

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