Left ventricular dysfunction in ADPKD and effects of octreotide-LAR: A cross-sectional and longitudinal substudy of the ALADIN trial.

Abstract

BACKGROUND AND AIM:

In autosomal dominant polycystic kidney disease (ADPKD) cardiac abnormalities have been observed before the onset of hypertension or renal dysfunction. We sought to characterize, in ADPKD patients, left ventricular (LV) function and its changes after somatostatin-analogue octreotide-LAR treatment.

METHODS:

In a 1:1:1 cross-sectional study, we evaluated LV function by speckle-tracking echocardiography in 34 ADPKD patients from one ALADIN-trial center and in 34 age- and gender-matched healthy controls and 34 equally-matched renal controls with non-cystic chronic kidney disease. Changes in LV function were compared in the 16 and 18 ADPKD patients originally randomized to 3 year-treatment with octreotide-LAR or placebo, respectively.

RESULTS:

LV twist and untwisting rates were lower in ADPKD patients that in healthy or renal controls (6.1 ± 2.6° vs. 11.1 ± 2.1° and 10.2 ± 3.7°; -49.5 ± 18.1°/s vs. -79.8 ± 12.2°/s and -84.3 ± 25.9°/s, respectively, all p < 0.001). The correlation between LV mass or diastolic BP and untwisting rate was positive in ADPKD patients (r = 0.38, p = 0.025 and r = 0.44, p = 0.011, respectively), not significant in healthy controls and negative in renal controls (r = -0.38; p = 0.023 and r = -0.40, p = 0.012, respectively. LV untwisting rate improved from -49.9 ± 18.6°/s to -70.3 ± 27.5°/s with octreotide-LAR, but did not change with placebo (p = 0.027 for treatment effect). At adjusted linear regression analysis, octreotide-LAR therapy emerged as the only independent predictor of untwisting rate improvement at final visit [beta coefficient -0.504 (95% CI -46.905--6.367), p = 0.014].

CONCLUSIONS:

In ADPKD patients LV function is early impaired. Somatostatin-analogue therapy might help in preventing or ameliorating LV dysfunction in this population. Clinical Trial Registration http://www.clinicaltrials.gov, NCT0030928.

• Authors: Letizia Spinelli, Antonio Pisani, Giuseppe Giugliano, Bruno Trimarco, Eleonora Riccio, Bianca Visciano, Giuseppe Remuzzi, Piero Ruggenenti, ALADIN-Cardiovascular Study Group
• Journal: International journal of cardiology (Int J Cardiol) Vol. 275 Pg. 145-151 (Jan 15 2019) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 30509370 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Hormonal
• Octreotide

Topics

• Administration, Oral
• Adult
• Antineoplastic Agents, Hormonal (administration & dosage)
• Cross-Sectional Studies
• Dose-Response Relationship, Drug
• Echocardiography, Doppler
• Female
• Follow-Up Studies
• Glomerular Filtration Rate
• Heart Ventricles (diagnostic imaging, drug effects, physiopathology)
• Humans
• Male
• Middle Aged
• Octreotide (administration & dosage)
• Polycystic Kidney, Autosomal Dominant (complications, drug therapy, physiopathology)
• Prospective Studies
• Stroke Volume (drug effects, physiology)
• Time Factors
• Treatment Outcome
• Ventricular Dysfunction, Left (diagnosis, etiology, prevention & control)
• Ventricular Function, Left (drug effects)