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Association of Asymmetric Dimethylarginine and Diastolic Dysfunction in Patients with Hypertrophic Cardiomyopathy

Kathrin Cordts1,2, Doreen Seelig3, Natalie Lund3

  • 1Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Biomolecules
|July 25, 2019
PubMed

Insights

Elevated asymmetric dimethylarginine (ADMA) levels are linked to diastolic dysfunction (DD) severity in hypertrophic cardiomyopathy (HCM) patients. Higher ADMA may impair nitric oxide (NO) production, affecting heart muscle relaxation.

Area of Science:

  • Cardiology
  • Biochemistry
  • Molecular Biology

Background:

  • Diastolic dysfunction (DD) is an early and common finding in hypertrophic cardiomyopathy (HCM), despite its genetic heterogeneity.
  • Nitric oxide (NO) plays a crucial role in myocardial relaxation, and its synthesis is regulated by nitric oxide synthases (NOS).
  • Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS, impacting NO bioavailability.

Purpose of the Study:

  • To investigate the association between arginine (Arg) and its derivatives, including l-homoarginine (hArg), ADMA, and symmetric dimethylarginine (SDMA), with diastolic dysfunction (DD) in patients with hypertrophic cardiomyopathy (HCM).

Main Methods:

  • Echocardiographic analysis of transmitral and mitral annulus velocities was performed in 215 HCM patients.
  • Plasma concentrations of Arg derivatives were quantified using liquid chromatography tandem-mass spectrometry.
  • Linear regression analyses were conducted to assess associations, adjusted for clinical covariates.

Main Results:

  • Diastolic dysfunction (DD) was present in 70% of the HCM patients.
  • Asymmetric dimethylarginine (ADMA) demonstrated the strongest association with DD severity (p < 0.01 for trend).
  • Increased ADMA levels were positively correlated with E-wave (p < 0.05) and mean E/E' (p < 0.001), indicating worsening DD.

Conclusions:

  • Elevated ADMA levels are significantly associated with the severity of diastolic dysfunction (DD) in hypertrophic cardiomyopathy (HCM) patients.
  • Higher ADMA may reduce nitric oxide (NO) production, contributing to impaired myocardial relaxation in HCM.
  • These findings highlight ADMA as a potential biomarker for DD in HCM.

Keywords:
arginine derivativesbiomarkerdiastolic dysfunctionhypertrophic cardiomyopathy

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