Key result
Elevated asymmetric dimethylarginine was significantly associated with diastolic dysfunction severity in hypertrophic cardiomyopathy (beta coefficient for mean E/E' 1.76; 95% CI 0.73-2.79; p<0.001).
Why the study?
Diastolic dysfunction is common in HCM and nitric oxide may contribute to myocardial relaxation, but the association of Arg and its derivatives with diastolic dysfunction in HCM patients was unknown.
Is elevated asymmetric dimethylarginine (ADMA) associated with diastolic dysfunction in patients with hypertrophic cardiomyopathy?
Observational (n=215)
Is elevated asymmetric dimethylarginine (ADMA) associated with diastolic dysfunction in patients with hypertrophic cardiomyopathy?
Effect estimate: beta 1.76 (95% CI 0.73-2.79)
p-value: p=<0.001
Elevated ADMA levels are associated with the severity of diastolic dysfunction in patients with hypertrophic cardiomyopathy, suggesting a role for impaired nitric oxide production in myocardial relaxation.
May inform NO pathway research in HCM diastolic dysfunction; hypothesis-generating and should not change practice.
Despite genetic heterogeneity, early manifestation of diastolic dysfunction (DD) is common in hypertrophic cardiomyopathy (HCM). Nitric oxide (NO) may contribute to myocardial relaxation. NO synthases (NOS) use l-arginine (Arg) as a substrate, as asymmetric dimethylarginine (ADMA) is a direct endogenous inhibitor of NOS. This study aimed to analyze the association of Arg and its derivates, i.e., l-homoarginine (hArg), ADMA and symmetric dimethylarginine (SDMA), with DD in HCM patients. In 215 HCM patients (mean age 54 ± 15 years, 58% male) transmitral and mitral annulus velocities were echocardiographically analyzed. Plasma concentrations of Arg derivatives were measured by liquid chromatography tandem-mass spectrometry. In 143 (70%) patients suffering from DD, ADMA showed the strongest association with DD (0.66 ± 0.16, 0.72 ± 0.24, and 0.76 ± 0.26 µmol/L, p < 0.01 for trend). In linear regression analyses, positive association per standard deviation increase of ADMA was found with E-wave (beta coefficient (95% confidence interval): 4.72 (0.43–9.01); p < 0.05) and mean E/E’ (1.76 (0.73–2.79) p < 0.001). Associations were adjusted for age, sex, body mass index (BMI), diabetes mellitus, coronary artery disease, and arterial hypertension. Elevated ADMA is associated with the severity of DD in HCM. Higher ADMA level might lead to decreased NO production and thus an impaired myocardial relaxation pattern.
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Cordts et al. (2019) conducted an observational in Hypertrophic cardiomyopathy (n=215). Asymmetric dimethylarginine (ADMA) was evaluated on Diastolic dysfunction severity (mean E/E') (beta 1.76, 95% CI 0.73-2.79, p=<0.001). Elevated asymmetric dimethylarginine was significantly associated with diastolic dysfunction severity in hypertrophic cardiomyopathy (beta coefficient for mean E/E' 1.76; 95% CI 0.73-2.79; p<0.001).
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