Dataset Information

Incidental Congestive Heart Failure in Patients With Aldosterone-Producing Adenomas.

ABSTRACT: Background Previous studies show that patients with primary aldosteronism are associated with higher risk of congestive heart failure (CHF). However, the effect of target treatment to the incidental CHF has not been elucidated. We aimed to investigate the risk of new-onset CHF in patients with aldosterone-producing adenomas (APAs) and explore the effect of adrenalectomy on new onset of CHF. Methods and Results From 1997 to 2009, 688 APA were identified and matched with essential hypertension controls. The risks of developing incidental CHF (hazard ratio, 0.49; 95% CI, 0.31-0.75; P=0.001) and mortality (hazard ratio, 0.29; 95% CI, 0.20-0.44; P<0.001) were significantly lower in the APA group after targeted treatment. A total of 605 patients with APAs who underwent adrenalectomy lowered the risks of CHF (subdistribution hazard ratio, 0.55; 95% CI, 0.34-0.90; P=0.017) and mortality (adjusted hazard ratio, 0.27; 95% CI, 0.16-0.44; P<0.001) compared with essential hypertension controls. Conclusions In conclusion, for patients with APAs, adrenalectomy can be associated with lower risk of incidental CHF and all-cause mortality in a long-term follow-up.

SUBMITTER: Huang WC

PROVIDER: S-EPMC6951059 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Incidental Congestive Heart Failure in Patients With Aldosterone-Producing Adenomas.

Huang Wei-Chieh WC Chen Ying-Ying YY Lin Yen-Hung YH Chen Likwang L Lin Po-Chih PC Lin Yu-Feng YF Liu Yu-Chun YC Wu Che-Hsiung CH Chueh Jeff S JS Chu Tzong-Shinn TS Wu Kwan Dun KD Huang Chun-Yao CY Wu Vin-Cent VC

Journal of the American Heart Association 20191205 24

Background Previous studies show that patients with primary aldosteronism are associated with higher risk of congestive heart failure (CHF). However, the effect of target treatment to the incidental CHF has not been elucidated. We aimed to investigate the risk of new-onset CHF in patients with aldosterone-producing adenomas (APAs) and explore the effect of adrenalectomy on new onset of CHF. Methods and Results From 1997 to 2009, 688 APA were identified and matched with essential hypertension con ...[more]

PMID: 31801414

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Project description:ContextThe use of next-generation sequencing has resulted in the identification of recurrent somatic mutations underlying primary aldosteronism (PA). However, significant gaps remain in our understanding of the relationship between tumor aldosterone synthase (CYP11B2) expression and somatic mutation status.ObjectiveThe objective of the study was to investigate tumor CYP11B2 expression and somatic aldosterone-driver gene mutation heterogeneity.MethodsFifty-one adrenals from 51 PA patients were studied. Immunohistochemistry for CYP11B2 was performed. Aldosterone-producing adenomas with intratumor CYP11B2 heterogeneity were analyzed for mutation status using targeted next-generation sequencing. DNA was isolated from CYP11B2-positive, CYP11B2-negative, and adjacent normal areas from formalin-fixed, paraffin-embedded sections.ResultsOf 51 adrenals, seven (14 %) showed distinct heterogeneity in CYP11B2 by immunohistochemistry, including six adenomas with intratumor heterogeneity and one multinodular hyperplastic adrenal with both CYP11B2-positive and -negative nodules. Of the six adrenocortical adenomas with CYP11B2 heterogeneity, three had aldosterone-regulating mutations (CACNA1D p.F747C, KCNJ5 p.L168R, ATP1A1 p.L104R) only in CYP11B2-positive regions, and one had two different mutations localized to two histologically distinct CYP11B2-positive regions (ATP2B3 p.L424_V425del, KCNJ5 p.G151R). Lastly, one adrenal with multiple CYP11B2-expressing nodules showed different mutations in each (CACNA1D p.F747V and ATP1A1 p.L104R), and no mutations were identified in CYP11B2-negative nodule or adjacent normal adrenal.ConclusionsAdrenal tumors in patients with PA can demonstrate clear heterogeneity in CYP11B2 expression and somatic mutations in driver genes for aldosterone production. These findings suggest that aldosterone-producing adenoma tumorigenesis can occur within preexisting nodules through the acquisition of somatic mutations that drive aldosterone production.

Dataset Information

Incidental Congestive Heart Failure in Patients With Aldosterone-Producing Adenomas.

Publications

Incidental Congestive Heart Failure in Patients With Aldosterone-Producing Adenomas.

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