Assessment of Heart Rate Variability in Children with Cancer after Elevated Cumulative Anthracycline Dose: A Prospective Study

Abstract

Objective: Anthracyclines which are the main drug of chemotherapy protocols had cardiotoxicity as the most frequent and well-known side effect. We aimed to evaluate prospectively the heart rate variability with 24-hour Holter electrocardiography (ECG) in children with cancer who treated with anthracycline drugs.

Material and Methods: The 24-hour Holter ECG monitoring was performed at the baseline, at time of 120 mg/m² and ≥240 mg/m² of cumulative anthracycline dose in patients with cancer who treated with anthracycline. The time-domain and frequency-domain measurements of heart rate variability (HRV) were obtained. The patients were classified into three groups as Group1:at baseline (n=54), Group 2:≥120mg/m² (n=54), Group 3:≥240mg/m² (n=54).

Results: The median age was 48 months (range 9-192 months). All types of cancer were 38 patients (70.4%) of acute leukemia, two patients (3.8%) of T lymphoblastic lymphoma, and 14patients (25.8%) of other childhood cancer who treated with anthracycline. However, all heart rate variability parameters were decreased after each increased cumulative anthracycline dose, especially time-domain parameters such as nSDNN index, rMSSD, pNN50, frequency parameters such as LF, HF, and Total power were significantly altered among Group1 and Group 3. LF/HF ratio was also statistically significantly increased in Group 3. According the heart rate parameters, the mean average heart rate, mean minimum heart rate and mean RR were statistically significantly prolonged from Group1 to Group 3.

Conclusion: Heart rate variability parameters are a noninvasive technique to demonstrate cardiac autonomic neural dysfunction and early myocardial injury. The 24-hour Holter ECG may be used for detecting early cardiac dysautonomia effect during anthracycline treatment with each elevated 120mg/m² anthracycline of cumulative dose.

Keywords

• Cumulative anthracycline
• heart rate variability
• cardiotoxicity

Kanserli Çocuklarda Artan Kümülatif Antrasiklin Dozunda Kalp Hızı Değişkenliğinin Değerlendirilmesi: Prospektif Bir Çalışma

Abstract

Amaç: Kemoterapi protokollerinin temel ilacı olan antrasiklinler en sık kardiyotoksisite yan etkisine sahiptir. Antrasiklin ile tedavi edilen kanserli çocuklarda kalp hızı değişkenliğini 24 saatlik Holter elektrokardiyografi (EKG) ile prospektif olarak değerlendirmeyi amaçladık.

Gereç ve Yöntemler: Antrasiklin ile tedavi edilen kanserli hastalarda hiç tedavi almadan, 120mg/m2 ve ≥240 mg/m² kümülatif antrasiklin dozunda 24 saatlik Holter EKG monitörizasyonu yapıldı. Kalp atış hızı değişkenliğinin (HRV) zaman alanı ve frekans alanı ölçümleri elde edildi. Hastalar üç gruba ayrıldı: hiç tedavi almadan Grup 1 (n = 54), Grup 2 :≥120 mg/m² (n = 54), Grup 3: ≥240 mg/m² (n = 54) seklinde ayrıldı.

Bulgular: Ortanca yaş 48 aydı (aralık 9-192 ay). 38 (% 70.4) hasta akut lösemi, iki hasta T lenfoblastik lenfoma (% 3.8) ve 14 hasta (% 25.8) diğer çocukluk çağı kanserleridir. Bununla birlikte, tüm kalp hızı değişkenleri, nSDNN indeksi, rMSSD, pNN50 gibi zaman parametreleri ve LF, HF ve Toplam güç gibi frekans parametreleri gibi her artan kümülatif antrasiklin dozu ile azalma görüldüğü belirlendi. LF/HF oranı da Grup 3’te istatistiksel olarak anlamlı şekilde artış gösterdiği saptandı. Kalp hızı parametrelerine göre, ortalama kalp hızı, ortalama minimum kalp hızı ve ortalama RR, kümülatif doz artıkça istatistiksel olarak anlamlı şekilde uzadığı belirlendi.

Sonuç: Kalp hızı değişkenleri, kardiyak otonomik nöral disfonksiyonu ve erken miyokardiyal hasarın gösterilmesi için invazif olmayan bir tekniktir. 24 saatlik Holter EKG’si, her artan 120 mg/m2 antrasiklin kümilatif dozu ile antrasiklin tedavisi sırasında erken kardiyak dysautonomia etkisini saptamak için kullanılabilir.

Keywords

• kardiyotoksisite
• Kümülatif antrasiklin
• kalp hızı değişkenliği

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