MRI assessment of excess cardiac iron in thalassemia major: When to initiate?

BACKGROUND: To determine optimal initial age of cardiac iron screening with magnetic resonance imaging (MRI) T2* in patients with thalassemia major (TM). METHODS: We retrospectively reviewed black blood cardiac T2* assessments from 102 TM patients from the ages of 3 to 32 years. Cases of patients under and above 7 years old with detectable cardiac iron overload were analyzed separately. Associations between cardiac T2* and various factors, such as serum ferritin (SF), patient age and hepatic T2*, were assessed using either scatterplots or regression. Images were evaluated by two independent radiologists. RESULTS: With a T2* cut-off value of 20 ms, no patient under 5 years old showed cardiac iron overload. Three of 19 (15.8%) patients under 7 years of age had a cardiac T2* ≤ 20 ms (5.5 to 7 years) but none had ≤10 ms, while 35 of 83 (42.2%) patients above 7 years old had a cardiac T2* ≤ 20 ms (8 to 32 years) and 18 of them ≤10 ms. Cardiac T2* correlated weakly with serum ferritin and liver T2* (r = -0.39 and 0.41, respectively, both P < 0.001), but not with patient age (P > 0.05). CONCLUSION: Cardiac iron overload can occur in young TM patients, even as young as 5.5 years old. Assessment of cardiac iron with T2* might need to begin as early as 5 years old if suboptimal chelation therapy is administered.

Berberine attenuates spontaneous action potentials in sinoatrial node cells and the currents of human HCN4 channels expressed in Xenopus laevis oocytes.

The present study investigated the electropharmacological effects of a traditional Chinese herbal drug, berberine, on the spontaneous activity of sinoatrial nodes (SANs) of the rabbit heart and on human hyperpolarization-activated cyclic nucleotide-gated 4 (hHCN4) channels, which are heterologously expressed in xenopus oocytes, and which contribute to pacemaker currents (Ifs). A standard microelectrode technique and standard two­electrode voltage­clamp recordings were employed to examine the properties of transmembrane potentials and cloned hHCN4 subunit currents, respectively, under control conditions and berberine administration. Berberine decreased the rate of pacemaker firing and the rate of diastolic depolarization, and modified the action potential parameters. In addition, berberine suppressed the hHCN4 channel currents in a concentration­ (1­300 µM) and use­dependent manner, and simultaneously decreased the activation and deactivation kinetics of the hHCN4 channels. The ability of berberine to modulate the If of cardiac pacemaker cells may contribute to its antiarrhythmic action.