Purpose/Objectives:QT interval prolongation is clinically relevant due to increased risk of sudden cardiac death from Torsades de Pointes (TdP), although rates are only 0.0025% - 0.16% for hospitalized patients. Over the past 5 years, there has been increased emphasis on QTc monitoring in patients undergoing hematopoietic stem cell transplantation (HSCT) who now more frequently receive supportive care medications that can increase QTc. As limited data exist on rates of QTc prolongation, cardiac complications, and TdP for patients undergoing HSCT, we compared patients transplanted before these drugs were more consistently monitored at our center to those more recently transplanted.

Materials/Methods:Patients hospitalized at Loyola Medical Center for allogeneic-HSCT between 2005-2015 (Cohort 1) and 2020-2023 (Cohort 2) were retrospectively reviewed and compared. We collected demographic and lab data, transplant hospital course, and cardiac history including pre-admit and post-transplant electrocardiograms (EKGs), and QTc prolonging medications used before and during HSCT. Summary statistics were computed and survival analyses were performed. The two cohorts were compared with respect to demographic and clinical variables, as well as newly categorized variables (normal vs abnormal groups based on QTc on intake EKG and maximum QTc on additional EKGs during transplant). Normal QTc was defined as ≤ 459 msec, while abnormal QTc was defined as ≥ 460 msec.

Results:Consecutive patients, 617 in Cohort 1 and 116 in Cohort 2, were reviewed. Consistent with evolving practice, patients in Cohort 2 were older (55.70 vs 52.97 years, p=0.008), and also had a higher proportion of coronary artery disease (14.66% vs 5.51%, p=0.000), cardiac stenting or bypass (7.76% vs 3.40%, p=0.039), history of myocardial infarction (6.90% vs 1.78%, p=0.005), hypertension (45.69% vs 27.39%, p=0.000), diabetes (21.55% vs 11.18%, p=0.002), hyperlipidemia (22.41% vs 13.45%, p=0.013), and liver disease (6.90% vs 1.94%, p=0.007). While Cohort 2 received more QTc prolonging medications prior to transplant (p=0.001) and during hospitalization (p=0.023), the QTc on intake EKG or changes during HSCT were not statistically significantly different between the cohorts. Cohort 1 patients who had a normal intake QTc (n=512) had a median maximal repeat QTc during hospital stay of 458 (interquartile range: IQR 440-488), while Cohort 1 patients with an abnormal intake QTc (n=105) had a median maximal repeat QTc of 496 (IQR 468-528). Cohort 2 patients with a normal intake QTc (n= 82) had a median repeat QTc during hospital stay of 462 (IQR 443-489), while Cohort 2 patients with an abnormal intake QTc (n= 34) had a median repeat QTc of 493 (IQR 449-514). No cases of TdP were reported in either cohort. There was no association between the number of QTc-prolonging medications received during hospitalization and abnormal QTc on post-treatment EKGs in either cohort (p=0.165 and 0.393 respectively). While 2-year overall survival (OS) for Cohort 2 was 62.96% vs 49.59% for Cohort 1 (p=0.011), 2-year OS was 51.96% for patients with a normal intake QTc and 50.39% for patients with an abnormal intake QTc (p=0.208).

Conclusions:Despite greater age/medical complexity, and emphasis on avoiding QTc prolonging drugs for fear of TdP, we saw the use of QTc prolonging drugs increase in Cohort 2, but this did not significantly prolong QTc during hospitalization or impact clinical outcomes. The improved 2-year OS in Cohort 2 was likely due to better patient selection for transplant and improved GVHD and infection prophylaxis/treatment. In both cohorts, patients with a normal intake QTc had intra-hospital repeat QTc measurements whose IQR did not cross the clinically significant threshold of 500 msec. However, patients in both cohorts with an abnormal intake QTc had repeat QTc whose IQR crossed 500 msec despite similar QTc prolonging drug use. This suggests that patients with a normal intake QTc may not need stringent monitoring of QTc during hospitalization while patients with an abnormal intake QTc should. Although it is often recommended to make medication changes when QTc prolongation is detected, given the rarity of cardiac complications in our patients and no differences in survival at 2 years even for those with a prolonged QTc at entry, the recommendation to withhold potential life-saving medications that could further alter an elevated QTc should be further investigated.

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2025
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