QTc Prolongation in Allogeneic Hematopoietic Stem Cell Transplantation: Assessing Cardiac Complications and Survival...

Increasing numbers of newer effective, yet QTc prolonging medications during hematopoietic stem cell transplantation (HSCT) have led to increased QTc monitoring. When an abnormal QTc is detected, this frequently results in cessation of QTc prolonging medications in order to limit risk of Torsades de Pointes. The clinical impacts of these monitoring changes are unknown. To assess rates and risk factors for QTc prolongation, cardiac complications, and sudden cardiac death in patients undergoing allogeneic HSCT. We then aimed to determine if any differences existed amongst patients treated from earlier time points versus recently when more aggressive practice patterns for QTc monitoring shifted. This single-center, retrospective study compared patients hospitalized for allogeneic HSCT between 2005 to 2015 (Cohort 1) when QTc was infrequently monitored and 2020 to 2023 (Cohort 2) when close QTc monitoring was performed at our center. We collected demographic and lab data, medical history, preadmit and post-transplant EKGs, and QTc-prolonging medication use before and during HSCT. Summary statistics were computed and survival analyses performed. Demographic and clinical variables were compared between Cohorts using chi-square test of association (Fisher's exact test when applicable), Wilcoxon sum-rank test, and Cochran-Mantel-Haenszel test. Normal QTc was defined as ≤459 ms, abnormal ≥460 ms. Overall survival with log-rank test was used to compare survival across various existing subgroups and newly categorized subgroups. A total of 617 and 116 consecutive patients in Cohorts 1 and 2, respectively, were reviewed. Cohort 2 received more QTc prolonging medications prior to (P = .001) and during HSCT (P = .023); however, intake QTc and QTc increases during HSCT were not different between Cohorts. In both Cohorts those with a normal intake QTc (Cohort 1 [n = 512]; Cohort 2 [n = 82]) had median maximal QTc during HSCT of 458 (IQR 440 to 488) and 462 (IQR 443 to 489), ie, less than a maximum 500 ms. However, those with an abnormal intake QTc (Cohort 1 [n = 105]; Cohort 2 [n = 32]) had medians of 496 (IQR 468 to 528) and 493 (IQR 449 to 514) with significant numbers >500 ms. Two-year survival for both normal and abnormal intake QTc patients were 51.96% versus 50.39%, respectively (P = .208). No cardiac complications were seen. Despite greater age, medical complexity, and increased use of QTc-prolonging drugs in Cohort 2, there was no significant increase in QTc prolongation or rate of adverse cardiac events compared to Cohort 1. Patients with a normal intake QTc tended to remain below the clinically significant 500 ms, whereas patients with abnormal intake QTc tended to remain prolonged with some exceeding 500 ms, despite similar QTc-prolonging drug use. This suggests patients with normal intake QTc may not need stringent monitoring of QTc during hospitalization for HSCT, while those with an abnormal intake QTc should continue to be closely monitored. Given the rarity of cardiac complications and no survival difference at 2 years despite prolonged QTc at entry, withholding potential life-saving medications for fear of further prolonging the QTc may not be necessary for those with normal QTc at entry. Prospective data should be obtained for verification.