Faculty Bibliography

With advances in clinical oncology, the burden of morbidity and mortality for cancer survivors due to the cardiac side effects of the chemotherapy is steadily increasing. Treatment-related cardiac damage is progressive and often irreversible. Primary prevention of cardiotoxicity during treatment is possible with strategies like limiting the cumulative anthracycline dose, the use of anthracycline structural analogs, and especially cardioprotective agents. Areas covered: This review covers the various cardiotoxic chemotherapeutic agents, the pathophysiology of cardiotoxicity due to anthracyclines, and the clinical and subclinical presentations and progression of childhood anthracycline cardiotoxicity. We also discuss preventive measures and strategies, especially the cardioprotectant agent dexrazoxane where there is strong evidence-based support for its use with anthracycline chemotherapy. However, there is a paucity of evidence-based recommendations for diagnosing and treating cancer therapy-induced cardiovascular complications. Finally, we discuss the potential of cardio-oncology. Expert opinion: There is no 'safe' anthracycline dose if the goal is normal long-term cardiovascular status but higher lifetime cumulative doses of anthracyclines, higher dose rates, female sex, longer follow-up, younger age at anthracycline treatment, pre-existing cardiovascular disease, and cardiac irradiation are associated with more severe cardiotoxicity. With deeper understanding of the mechanisms of the adverse cardiac effects and identification of driver mutations causing these effects, personalized cancer therapy to limit cardiotoxic effects can be achieved, such as with the cardioprotectant dexrazoxane.

BACKGROUND:Patients with congenital heart defects (CHD) often present more challenges to pacing therapy due to anatomy than those without CHD. The lumenless, 4.1Fr diameter M3830 pacing lead (Medtronic, Inc., Minneapolis, MN, USA), approved for use in 2005, has, to date, reported to have excellent short-term (<6 years) lead performance. Unfortunately, very long-term performance is unknown, especially among CHD patients and with implants at alternate pacing (AP) sites. This study reports a 10-year clinical experience with the M3830 lead. METHODS:Records of patients who received the M3830 lead were reviewed: patient demographics, implant techniques and locations, sensing and pacing characteristics, impedances (Imp), and any complications at implant and follow-up. RESULTS:From 2005 to 2015, 141 patients (ages 2-50, mean 20.1 years, 57% males) received 212 leads: atrial 115; ventricle 97. CHD was present in 62% of patients. Leads were inserted at AP sites in 96% of patients. Postimplant follow-up was from 3 months to 10 years (mean 56.3 months). Comparative implant versus follow-up values (mean ± standard deviation) were available on 196 leads (92.5%), showing persistently low (<1 v @ 0.4-0.5 ms) pacing thresholds (P = 0.57). Sensing was also comparable (atrial leads, P = 0.41; ventricular leads, P = 0.9). Impedances differed (P < 0.05) but remained within the normal range. Two A leads became dislodged and one was repositioned while two other leads (1 A, 1 V) were extracted. There are no differences observed in the pacing characteristics between the CHD and non-CHD groups on follow-up. CONCLUSIONS:The 4.1Fr lumenless pacing lead shows ease of implant regardless of CHD or AP site, excellent very long-term (10 years) stability, and performance indices with a very low rate of complications.

Accelerated junctional rhythm has been reported in children in the setting of acute rheumatic fever; however, we describe a hitherto unreported case of isolated junctional tachycardia in a child with streptococcal pharyngitis, not meeting revised Jones criteria for rheumatic fever. A previously healthy, 9-year-old girl presented to the emergency department with complaints of sore throat, low-grade fever, and intermittent chest pain. She was found to have a positive rapid streptococcal antigen test. The initial electrocardiogram showed junctional tachycardia with atrioventricular dissociation in addition to prolonged and aberrant atrioventricular conduction. An echocardiogram revealed normal cardiac anatomy with normal biventricular function. The patient responded to treatment with amoxicillin for streptococcal pharyngitis. The junctional tachycardia and other electrocardiogram abnormalities resolved during follow-up.

Cardiomyopathy is a rare disorder of the heart muscle, affecting 1.13 cases per 100,000 children, from birth to 18 years of age. Cardiomyopathy is the leading cause of heart transplantation in children over the age of 1. The Pediatric Cardiomyopathy Registry funded in 1994 by the National Heart, Lung, and Blood Institute was established to examine the epidemiology of the disease in children below 18 years of age. More than 3500 children across the United States and Canada have been enrolled in the Pediatric Cardiomyopathy Registry, which has followed-up these patients until death, heart transplantation, or loss to follow-up. The Pediatric Cardiomyopathy Registry has provided the most in-depth illustration of this disease regarding its aetiology, clinical course, associated risk factors, and patient outcomes. Data from the registry have helped in guiding the clinical management of cardiomyopathy in children under 18 years of age; however, questions still remain regarding the most clinically effective diagnostic and treatment approaches for these patients. Future directions of the registry include the use of next-generation whole-exome sequencing and cardiac biomarkers to identify aetiology-specific treatments and improve diagnostic strategies. This article provides a brief synopsis of the work carried out by the Pediatric Cardiomyopathy Registry since its inception, including the current knowledge on the aetiologies, outcomes, and treatments of cardiomyopathy in children.

Drug-resistant tuberculosis (DR-TB) has been reported in India, but has been rarely documented in children. HIV co-infection has led to resurgence of tuberculosis (TB), making treatment even more difficult due to complex drug interactions. Poly-resistant TB is rare in children, especially in HIV-infected children. We report an HIV-infected child who developed poly-resistant TB (resistance to Streptomycin and Isoniazid) after 3 years of completion of anti-tuberculosis treatment (ATT). His mother had also received ATT 3 years back. We conclude that DR-TB in HIV-infected children should be considered if the child had been treated with ATT in the past or there is contact with adults on second-line ATT therapy.