Hypocalcemia-Induced QT Interval Prolongation

An 87-year-old man with a history of transcatheter aortic valve replacement, pulmonary hypertension, diastolic dysfunction with preserved systolic function, and myelofibrosis had a 12-lead ECG showed a prolonged QT interval of 508 ms with heart-rate correction placing it in the 99th percentile of the population. Reduction in the dose of furosemide and calcium supplementation increased serum calcium and shortened the QT interval. This case provides an opportunity to examine newer concepts for the understanding of the mechanisms by which hypocalcemia might induce QT prolongation. Hypocalcemia likely produces corrected QT interval prolongation primarily through a calcium-dependent inactivation (CDI) mechanism on the L-type calcium channel (LTCC). Lower extracellular calcium leads to a decreased ICaL, subsequently causing intracellular calcium to take longer to reach the critical threshold to induce CDI of the LTCC. The resulting prolonged repolarization of the ventricular myocyte can lead to early after-depolarizations and ensuing life-threatening ventricular arrhythmias. Genetic polymorphisms in Ca2+-binding protein calmodulin which can prolong QT, underscore the role for disturbances of intracellular myocardial calcium handling in arrhythmogenesis. Hypocalcemia is an under-recognized cause of QT prolongation and should be taken into careful consideration in patients presenting with incidental findings of a prolonged QT interval.