Pediatric Cardiology

Outcomes of Dilated Cardiomyopathy in Japanese Children - A Retrospective Cohort Study. Mori H, Yoshikawa T, Kimura H, Ono H, Kato H, Ono Y, Nii M, Shindo T, Inuzuka R, Horigome H, Miura M, Ogawa S, Shiono J, Furutani Y, Ishido M, Nakanishi T. Circ J. 2021 Dec 24;86(1):109-115. doi: 10.1253/circj.CJ-20-1239. Epub 2021 Sep 28. PMID: 34588404    Take Home Points: Pediatric DCM continues to carry significant morbidity and mortality resulting in death or transplantation in about half of patients by 10 years from diagnosis. Of note, LV dysfunction was defined as a FS below 20% per the WHO criteria. Age at diagnosis is not a predictor of outcome in Japanese children, unlike prior reports from the US and Australia. The most significant risk factor for death or transplant is a FS <10% at diagnosis. Family history of DCM was not associated with outcome- that may be related to the specific genetic mutations found in Japan. This study includes patients starting in the early 90s, therefore not all patients were started on ACE inhibitors or beta blockers. The initiation of ACE inhibitors but not beta blockers seemed to be protective in this population Prospective multicenter studies are needed to further delineate the course of pediatric dilated cardiomyopathy in the current era. Commentary from Dr. Anna Tsirka (Connecticut, USA), Section editor of Pediatric & Fetal Cardiology Journal Watch. Introduction Idiopathic dilated cardiomyopathy (DCM) reportedly carries worse prognosis in children than in adults. The outcome may vary by country and health care systems. This represents a retrospective nationwide observational study of children with DCM in Japan between January 2010 and December 2014.   Methods 18 institutions across participated. Children younger than 18 years of age were included. Secondary cardiomyopathies (neuromuscular, metabolic disease or known myocarditis) were excluded. LV dilation was defined as LVIDd z score >2 (adjusted to BSA) by M Mode. Systolic dysfunction was defined as FS by M mode < 20%.   Results: 106 patients were included in the study. 42% were younger than 1 year of age. 9% had a first or second degree relative with DCM. 12% were asymptomatic at the time of presentation while 80% presented with symptoms of CHF, and 4% with arrhythmia or aborted sudden death.   Echocardiographic parameters at diagnosis are presented below:     Median follow up was 3.3 years. At last follow up alive, 98% were receiving medical treatment as shown below:     In patients During the period of the study, 15% of patients underwent heart transplantation and 29% died without transplantation.   Freedom from death or transplantation at 1,3,5,10 and 20 years from diagnosis was 76%, 66%, 61%, 54%, and 43%, respectively. Overall survival rates (with or without transplantation) were 81%, 75%, 72%, and 53%, respectively, as shown below:     On multivariate analysis, the only predictor of death or transplant was a FS at presentation < 10%. Age at diagnosis was not a risk factor. There was no significant difference in freedom from death or transplantation between patients treated with and those without β-blocker treatment as shown below:     

An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia. Peltenburg PJ, Kallas D, Bos JM, Lieve KVV, Franciosi S, Roston TM, Denjoy I, Sorensen KB, Ohno S, Roses-Noguer F, Aiba T, Maltret A, LaPage MJ, Atallah J, Giudicessi JR, Clur SB, Blom NA, Tanck M, Extramiana F, Kato K, Barc J, Borggrefe M, Behr ER, Sarquella-Brugada G, Tfelt-Hansen J, Zorio E, Swan H, Kammeraad JAE, Krahn AD, Davis A, Sacher F, Schwartz PJ, Roberts JD, Skinner JR, van den Berg MP, Kannankeril PJ, Drago F, Robyns T, Haugaa K, Tavacova T, Semsarian C, Till J, Probst V, Brugada R, Shimizu W, Horie M, Leenhardt A, Ackerman MJ, Sanatani S, van der Werf C, Wilde AAM. Circulation. 2022 Feb;145(5):333-344. doi: 10.1161/CIRCULATIONAHA.121.056018. PMID: 34874747   Take Home Points: Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk. β1-selective β-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective β-blockers, specifically nadolol.Nadolol, or propranolol if nadolol is unavailable, should be the preferred β-blocker for treating symptomatic children with CPVT. Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch. These findings are supported by similar studies - JAMA Cardiol. 2022;7(5):504-512; selective β-blockers were associated with a higher risk of “Life threatening arrhythmia event [LTAE]” as compared with nadolol. Independently from treatment, LTAE and syncope before diagnosis and C-terminal domain variants identified patients at higher risk of β-blocker failure, and the ICD was associated with reduced mortality in high-risk patients with CPVT.   HRS PRACTICE GUIDELINES| VOLUME 14, ISSUE 1, E41-E44, JANUARY 01, 2017: There is strong consensus among the authors that nadolol is the preferred antiarrhythmic, antiadrenergic therapy for CPVT patients. Whereas the conventional dosage is that of 1 mg/kg per day, data that support the safety of the highest tolerated dosage indicate the potential to double the standard recommended regimen. Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm Volume 13, Issue 2, February 2016, Pages 433-440   2017 AHA Guidelines     Introduction: CPVT is a rare inherited cardiac arrhythmia syndrome in which bidirectional or polymorphic ventricular arrhythmias (VAs) induced by exercise or emotional stress can trigger syncope, sudden cardiac arrest (SCA), or sudden cardiac death. Results from several small studies have suggested that nadolol, a nonselective β-blocker, may be superior to other types of β-blocker, in particular, β1-selective β-blockers, in the treatment of patients with CPVT.2,7 However, this evidence is limited because of the small size of these cohorts. In addition, nadolol is currently unavailable in many countries. Therefore, there is a compelling need for a large-cohort study comparing the efficacy of the different types of β-blocker in patients with CPVT.1,13 Here, data from 2 large international multicenter CPVT patient registries were used to evaluate the association of nonselective versus β1-selective β-blockers and of specific β-blockers with arrhythmic event rates in a high risk CPVT population of symptomatic children. Results:   A total of 329 symptomatic children with CPVT were included. During a median follow-up duration of 6.7 years (IQR, 2.8–12.5), 99 patients (30.1%) experienced an arrhythmic event and 74 (22.5%) experienced a near-fatal arrhythmic event. Appropriate ICD shock was the most frequent arrhythmic event.     The risk for an arrhythmic event in patients treated with atenolol, bisoprolol, and metoprolol was higher than in patients treated with nadolol (Table 2) after multivariable adjustment.     DISCUSSION β-Blockers vary in elimination half-life, with a half-life of 20 to 24 hours for oral nadolol compared with 3 to 6 hours for propranolol, 9 to 12 hours for bisoprolol, 6 to 7 hours for atenolol, and 3 to 7 hours for metoprolol. Lipophilic β-blockers, such as metoprolol and propranolol, can pass the blood-brain barrier and might therefore be more likely to induce central nervous system–related side effects. This could potentially result in nonadherence and subsequently a higher risk for events. Hydrophilic β-blockers, such as atenolol and nadolol, in general, show a lower pharmacokinetic variability. Food enhances the bioavailability of metoprolol and propranolol, whereas it reduces the bioavailability of atenolol. Nadolol has a low pharmacokinetic variation, which may explain the apparent benefit of nadolol over the other types of β-blocker as is shown in these results. Propranolol affects both the peak and late sodium current, whereas nadolol solely blocks the peak sodium current and metoprolol has no effect on these currents.   Clinical Implications The authors believe that nadolol should be the preferred initial β-blocker for treatment of this population. Even though propranolol did not reach statistical significance over β1-selective β-blockers in terms of a lower risk for arrhythmic events, we would recommend remaining with a nonselective β-blocker, such as propranolol, in situations where nadolol is either unavailable or not tolerated. Furthermore, the rate of nonadherence and suboptimal dosages at the time of an event in this population is high. Clinicians should be aware of this to treat and counsel their patients appropriately.