A retrospective study shows that early propranolol-induced heart rate reductions fail to predict clinical response of infantile hemangiomas.
It has been suggested that heart rate (HR) reductions of more than 20% versus baseline may predict clinical response to propranolol, the first-line medical agent for complicated infantile angioma (IH).
To test this assertion, investigators led by Jin Ho Chong, M.B.B.S., of KK Women's & Children's Hospital in Singapore, reviewed charts of all patients with IH treated with propranolol at the Children's Hospital of Bordeaux, France, from January 2010 through December 2015. Researchers examined HR data at baseline and 1-4 hours post-propranolol administration, including absolute and percentage HR reduction and patients with any reduction greater than 20% below baseline. To help compare data of poor and moderate responders versus that of good responders, 2 blinded investigators individually compared baseline IH photos with those taken after 6 months' treatment and assigned global scores for erythema, size, telangectasias, soft tissue swelling and anatomical distortion.
Among 101 patients, the number of patients classified as poor, moderate and good responders were 3, 39 and 59, respectively. Median initiating dose was 2/mg/kg/day. Altogether, 40 patients (39.6%) had at least one HR reading greater than 20% below baseline. But researchers found no significant relationship between these figures and clinical responses (p=0.437). Nor were clinical responses at 6 months significantly related to absolute reductions, percentage reductions or average HRs over the first 4 hours post-propranolol. Mean absolute HR reductions for the poor, moderate and good responders were 12 beats per minutes (BPM, or 7.9%), 14.5 BPM (9%) and 14.1 BPM (9%), respectively.
"Propranolol causes statistically but usually not clinically significant beta-1 receptor-mediated reduction in HR,3" investigators wrote. Nevertheless, they said it remains prudent to practice in-office HR and clinical monitoring, as patients in this age group cannot verbalize bradycardia symptoms (defined as HR of less than 90 BPM for patients less than 3 months old, and less than 80 BPM for patients 3-12 months old).
HR reductions peaked at 3 hours post-propranolol administration. Average HRs at this point for poor responders, partial responders and good responders were 117 ± 15.4, 124.2 ± 14.8 and 122.8 ± 13.3, respectively (total: 123.1 ± 13.8). Because these figures remained within the normal range, however, the observation failed to reach statistical significance. The observation might stem from the variability of HR values in the infantile population both at baseline and during treatment, authors surmised. The largest average HR reduction at any point, 18.3 BPM, occurred at 3 hours in the poor responders group, although this group's small size limits such comparisons.
"Our study did not demonstrate a relationship between the extent of HR decline after propranolol administration and clinical response 6 months after propranolol therapy." Clinical and biological markers of favorable responses to treatment will be useful for prognostication and counseling purposes, the authors said. Identifying such predictors will require further study.
Co-author Christine Léauté-Labrèze, M.D., is a consultant for Pierre Fabre Dermatologie.
1. Sondhi V, Patnaik SK. Propranolol for infantile hemangioma (PINCH): an open-label trial to assess the efficacy of propranolol for treating infantile hemangiomas and for determining the decline in heart rate to predict response to propranolol. J Pediatr Hematol Oncol. 2013; 35(7):493-9.
2. Chong JH, Prey S, Mya HT, Delarue A, Labrèze C. Can the extent of heart rate reduction predict the clinical response of infantile hemangiomas to propranolol? Br J Dermatol. 2017 Sep 8. doi: 10.1111/bjd.15966. [Epub ahead of print]
3. Salice P, Giovanni Bianchetti M, Giavarini A, et al. Cardiovascular profile of propranolol after multiple dosing in infantile angioma. Pharmacology. 2016;99:75-78.