Abstract
Background
High dose melphalan and autologous stem cell transplantation (HDM/SCT) can induce hematologic responses and prolong survival in selected patients with AL amyloidosis. However, cardiac toxicity associated with HDM/SCT remains an ongoing concern in patients with AL amyloidosis. Atrial fibrillation (AF) may complicate SCT 4-10% of the time (Olivieri et al. 1998, Hidalgo et al. 2004). The development of AF in the SCT period can be challenging to manage. Studies identifying risk factors for the development of AF in amyloidosis are limited (Abhishek et al. 2013).
Objective
We sought to determine the incidence of atrial fibrillation in patients with AL amyloidosis undergoing SCT.
Patients and methods
We retrospectively analyzed charts of 91 consecutive patients undergoing HDM/SCT for AL amyloidosis between January 2011 and May 2015. The peri-transplant period was defined from the first day of stem cell mobilization until the time to engraftment. For all patients, medical records were reviewed for age, gender, prior history of AF, baseline troponin I, brain natriuretic peptide (BNP), baseline echocardiography, dose of Melphalan, ventricular rate at the time of AF event, hemodynamic stability (based on blood pressure), AF management and the return to normal sinus rhythm (NSR).
Results
Ninety-one patients with AL Amyloidosis underwent HDM/SCT from January 2011 to May 2015. Overall, twelve patients (13.1%) developed AF during SCT period, at a median of D+9 (range, D-10 to D+21). Baseline characteristics of these patients are listed in Table 1. Patient characteristics and AF management are listed in Table 2.
Of note, there were three patients who had a history of PAF who did not develop AF during the peri-transplant period.
Conclusion
AF occurred in 13.1% of patients with AL amyloidosis undergoing HDM/SCT in the peri-transplant period, a rate higher than previously reported in other patient populations. Four of seven patients with a history of supraventricular tachyarrhythmia (SVT) developed AF during the peri-transplant period, making prior SVT a potential risk factor. The presence of cardiac amyloidosis, even in early stages, in combination with high dose Melphalan, may also predispose this group of patients to supraventricular arrhythmias. The identification of risk factors for developing AF in patients with AL amyloidosis may enable the use of preventative action in the future.
Patient Characteristics at Baseline
| . | N = 12 (%) . |
|---|---|
| Median Age, years (range) | 59.5 (40-68) |
| Gender Male Female | 6 (50) 6 (50) |
| Organ Involvement Cardiac only Renal only Pulmonary only Cardiac and renal | 3 (25.0) 4 (33.3) 1 (8.3) 4 (33.3) |
| History of Afib Prior anticoagulation Prior rate control | 4 (33.3) 2/4 (50.0) 4/4 (100.0) |
| Median BNP, pg/mL (range) | 59.5 (17-558) |
| Median Troponin, ng/mL (range) | 0.0385 (0.006 - 0.446) |
| Median TSH*, IU/mL (range) | 1.56 ( 0.24-5.39) |
| Cardiac Echo IVSD**, mm (range) Presence of diastolic dysfunction Diastolic Dysfunction, grade (range) LVEF***, % (range) Left atrial size****, mm (range) | 11.5 ( 8.0-17.0) 8 (66.6) 1.0 ( 0.0-3.0) 61.6 ( 44-71) 36.5 ( 23-43) |
| Median PR interval on EKG in ms, (range) | 183 (132-230) |
| Dose of Melphalan 140mg/m2 200mg/m2 | 4(33.3) 8(66.6) |
| . | N = 12 (%) . |
|---|---|
| Median Age, years (range) | 59.5 (40-68) |
| Gender Male Female | 6 (50) 6 (50) |
| Organ Involvement Cardiac only Renal only Pulmonary only Cardiac and renal | 3 (25.0) 4 (33.3) 1 (8.3) 4 (33.3) |
| History of Afib Prior anticoagulation Prior rate control | 4 (33.3) 2/4 (50.0) 4/4 (100.0) |
| Median BNP, pg/mL (range) | 59.5 (17-558) |
| Median Troponin, ng/mL (range) | 0.0385 (0.006 - 0.446) |
| Median TSH*, IU/mL (range) | 1.56 ( 0.24-5.39) |
| Cardiac Echo IVSD**, mm (range) Presence of diastolic dysfunction Diastolic Dysfunction, grade (range) LVEF***, % (range) Left atrial size****, mm (range) | 11.5 ( 8.0-17.0) 8 (66.6) 1.0 ( 0.0-3.0) 61.6 ( 44-71) 36.5 ( 23-43) |
| Median PR interval on EKG in ms, (range) | 183 (132-230) |
| Dose of Melphalan 140mg/m2 200mg/m2 | 4(33.3) 8(66.6) |
*TSH: Thyroid stimulating hormone
**IVSD: Interventricular septal diastolic thickness (normal < 10mm for women and < 11mm for men)
***LVEF: Left ventricular ejection fraction
**** Left atrial size in parasternal long axis view (normal < 40mm)
Patient Characteristics at Time of AF Event
| . | N = 12 (%) . |
|---|---|
| Median Day to event as it relates to stem cell infusion, (range) | D+9 (D-10 to D+21) |
| Median Ventricular Rate, beats per minute (range) | 130 (83-159) |
| Hemodynamic Stability Stable Unstable | 5(41.6) 7(58.3) |
| Treatment of rate/rhythm Beta blocker alone Calcium channel blocker Amiodarone and beta blocker No specific intervention | 5(41.7) 0 (0.0) 3(33.3) 4(33.3) |
| Anticoagulation Yes No | 3(33.3) 9(75.0) |
| . | N = 12 (%) . |
|---|---|
| Median Day to event as it relates to stem cell infusion, (range) | D+9 (D-10 to D+21) |
| Median Ventricular Rate, beats per minute (range) | 130 (83-159) |
| Hemodynamic Stability Stable Unstable | 5(41.6) 7(58.3) |
| Treatment of rate/rhythm Beta blocker alone Calcium channel blocker Amiodarone and beta blocker No specific intervention | 5(41.7) 0 (0.0) 3(33.3) 4(33.3) |
| Anticoagulation Yes No | 3(33.3) 9(75.0) |
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
