Differences in Fabry cardiomyopathy between female and male patients: consequences for diagnostic assessment.

OBJECTIVES: We hypothesized that Fabry cardiomyopathy in female patients might differ substantially from that in male patients and sought to prove this hypothesis in a large cohort consisting of 104 patients with Fabry disease. BACKGROUND: Fabry cardiomyopathy in male patients is characterized by left ventricular (LV) hypertrophy, impaired myocardial function, and subsequent progressive myocardial fibrosis. In contrast, the occurrence of these 3 cardiomyopathic hallmarks in female patients remains unknown. METHODS: In 104 patients (58 females, age 42 ± 16 years; 46 males, age 42 ± 13 years) with genetically proven Fabry disease, LV hypertrophy, regional myocardial deformation and myocardial fibrosis were assessed by standard echocardiography, strain rate imaging, and cardiac magnetic resonance (CMR) imaging-guided late enhancement (LE). RESULTS: In men, end-diastolic left ventricular wall thickness (LVWT) ranged from 6 to 19.5 mm (LV mass CMR 55 to 200 g/m(2)), and LE was never seen with LVWT <12 mm (LV mass <99 g/m(2)). In contrast in female patients, LVWT ranged from 5 to 15.5 mm, LV mass ranged from 39 to 146 g/m(2), and LE was already detectable with an LVWT of 9 mm (LV mass 56 g/m(2)). When LV mass was examined in CMR, LE was detected in 23% of the female patients without hypertrophy (n=9), whereas LE was never seen in male patients with normal LV mass. LE was always associated with low systolic strain rate, but the severity of impairment was independent of LVWT in female patients (lateral strain rate in patients with LV hypertrophy with LE -0.7 ± 0.2 s(-1); patients without LV hypertrophy with LE -0.8 ± 0.2 s(-1); p=0.45). CONCLUSIONS: In contrast to male patients, the loss of myocardial function and the development of fibrosis do not necessarily require myocardial hypertrophy in female patients with Fabry disease. Thus, in contrast to actual recommendations, initial cardiac staging and monitoring should be based on LV hypertrophy and on replacement fibrosis in female patients with Fabry disease.

Non-invasive functional and biochemical assessment of mitoxantrone cardiotoxicity in patients with multiple sclerosis.

As mitoxantrone is a recently approved immunosuppressant for managing multiple sclerosis, the number of patients treated with this effective but potentially cardiotoxic anthracenedione derivative will increase substantially. To detect subclinical mitoxantrone-induced cardiotoxicity, sensitive non-invasive diagnostic tools are required. Assuming that changes in myocardial high-energy phosphate metabolism and alterations in left ventricular (LV) diastolic performance might be early markers of mitoxantrone-induced cardiotoxicity we examined fifteen MS patients treated with mitoxantrone up to 100 mg/m2 compared with 15 matched control MS patients. 31P-magnetic resonance (MR) spectroscopy was employed to measure myocardial high-energy phosphate metabolism, MR imaging for morphometric evaluation of changes in LV geometry. Indices of diastolic performance were assessed by Doppler echocardiography. In this exploratory study, phosphocreatine/ATP ratios were comparable between mitoxantrone-treated and control patients (1.48 +/- 0.23 and 1.43 +/- 0.41). LV mass, LV end-diastolic and systolic volumes, wall motion score, EF and cardiac output did not differ between both groups. All parameters of diastolic performance (E/A-ratio, isovolumic relaxation time, and E-wave deceleration time) were not different and within normal limits.In conclusion, using advanced diagnostic methodology, including functional, morphometric, and biochemical measurements no cardiotoxic effect of mitoxantrone up to a cumulative dose range of 100 mg/m2 could be detected.