Myocardial tissue alterations in patients with alkaptonuria
J Groeschel, A Ziagaki, E Daud, R F Trauzeddel, J Hella, S Hadzibegovic, M Anker, J Schulz-Menger, K MaiAbstract
Background/Introduction
Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder with a prevalence of 1-9/1,000,000 caused by mutations in the homogentisate 1,2-dioxygenase gene, leading to the accumulation of homogentisic acid (1). This results in ochronosis, a dark brown to black pigmentation of connective tissues affecting multiple organ systems, with progressive course over time. Although cardiovascular involvement in AKU, particularly valvular calcification, is well established, myocardial tissue characterization using cardiovascular magnetic resonance (CMR) has not previously been reported, and the presence and mechanistic basis of myocardial remodeling remain undefined (2).
Purpose
To assess the relationship between AKU and myocardial tissue alterations.
Methods
We conducted a prospective single-center study comparing cardiovascular clinical, laboratory, and imaging parameters in genetically confirmed AKU patients and a control group with similar age, sex, and comorbidities. All participants underwent standardized 3T CMR (Siemens Healthineers) assessing ventricular volumes, function, mass, atrial volumes, and aortic valve opening. Native T1 and T2 mapping were performed, followed by adenosine stress perfusion (AKU only) and late gadolinium enhancement imaging to detect focal fibrosis.
Results
We could include 14 patients with AKU (median age 54.5 years (IQR 46-57.0), 50% female). Age, sex distribution, BMI and cardiovascular comorbidities were similar compared to the CG (Table 1). Median global T1 values were significantly elevated in the AKU group compared to controls (median: 1229 ms (IQR 1198-1244) vs. 1197 ms (1161-1215; p = 0.009)). Segmental evaluation confirmed increased native T1 values across all slices (table 1). Increased myocardial T1 level were not related to patients’ age, disease duration, Alkaptonuria Severity Score Index (AKUSSI), cardiac biomarkers (CK-MB, NT-proBNP), or lipid profile parameters (p >0.05). Neither global nor segmental myocardial T2 differed between the groups. Three patients in the AKU group had focal fibrosis, two in a non-ischemic and one in an ischemic location. The CG had no LGE findings. In the AKU cohort one patient had a severe aortic stenosis (aortic valve opening 0,7 cm2). No patient had inducible ischemia on adenosine stress imaging. All available cardiac functional and volumetric parameters were similar between the groups (Table 1).
Conclusion
In this prospective CMR study, AKU patients showed increased diffuse and focal myocardial fibrosis despite normal ventricular volumes and systolic function, consistent with subclinical remodeling. The lack of T2 abnormalities suggests chronic interstitial expansion rather than active inflammation or edema. Elevated T1 values were independent of conventional disease severity markers and cardiac biomarkers, highlighting the added value of multiparametric CMR for early myocardial tissue characterization in AKU.Table 1Figure 1