Characterization of Cardiac Arrhythmias Post Allogeneic Transplant

Cardiac arrhythmias (CA) can be an important complication of cellular therapy. We performed a retrospective, single center, comprehensive analysis to understand the risk factors, outcome and morbidity of cardiac arrhythmias developing in the first 100 days after allogeneic hematopoietic stem cell transplantation in adults. Overall 133 patients received an allogeneic transplant between 01/2008 and 07/2012 and were included in the analysis. Individuals with pre existing arrhythmias were excluded. Patients and transplant characteristics are detailed in table 1.  At least one episode of cardiac arrhythmia developed in 25 individuals (18.8%, 95% C.I. 13.0-26.3%) with 19 individuals developing atrial flutter/fibrillation and 8 individuals developing AV nodal reentrant tachycardia. Median time of onset of the arrhythmia was 27 days (range 1-96) after transplant. Neither underlying disease, conditioning regimen, comorbidities, left ventricular ejection fraction, presence of ventricular diastolic dysfunction, prior use of beta blockers, calcium channel blockers, ACE inhibitors or ARBs were associated with higher risk of developing CA in univariate or multivariate analysis. Patients who developed CA were older (median age 56 years) than patients who did not develop CA (median age 51 years), but this difference was not statistically significant (P=0.08). Of the 25 individuals who developed CA, 13 died prior to day 100 (4 from cardiac causes). Among the remaining 12 patients, 8 had restoration of sinus rhythm by day 100. Median survival was 14+/- 2 weeks for individuals who developed CA vs. 81 +/- 35 weeks   for patients who did not develop CA prior to 100 days (P<0.0001). In multivariate analysis, development of CA prior to 100 days was a strong predictor of mortality (HR=2.87, 95% C.I. 1.67-4.95, P=0.001 ) even when adjusted for age, intensity of the conditioning regimen, comorbidities, chronic medications, left ventricular ejection fraction and presence of ventricular diastolic dysfunction. We concluded that the development of CA after allogeneic transplantation is relatively common, but difficult to predict on the basis of patient and transplant characteristics, representing a strong and independent predictor of post transplant mortality.

 

Demographics	N=133
Median age (range)	54 (18-70)
Male gender	85 (64%)
Race
African American	25 (19%)
Caucasian	107 (80%)
Other	1 (1%)
Diagnosis
Acute Leukemias	75 (56%)
MDS	20 (15%)
Lymphomas	19 (14%)
CML	11 (8%)
CLL/PLL	5 (4%)
MM	2 (2%)
AA	1 (1%)
Graft source
Adult MUD/MMUD	78 (59%)
Sibling	47 (35%)
Haploidentical family	3 (2%)
Cord blood	5 (4%)
Conditioning
Myeloablative	48 (36%)
RIC/NMA	85 (64%)
Comorbidities
Median left ventricle ejection fraction (range)	60% (33-76)
Hypertension	47 (35%)
Diabetes	26 (20%)
Coronary artery disease	5 (4%)
Smoking history	69 (52%)