Mortality rates in patients with Ebstein anomaly (EA) have improved significantly in the past 2 decades; however, mortality remains higher compared with the general population and is dependent on the severity of EA, according to new registry data. The study, published online Monday and in the June 27 issue of the Journal of the American College of Cardiology, noted that EA is among the rarest congenital cardiac malformations, with a prevalence of 4.4 per 100,000 live births – and is characterized by varying degrees of apical displacement of the functional tricuspid valve through incomplete delamination of its posterior and septal leaflets, resulting in an incompetent tricuspid valve and a dysfunctional right ventricle. Led by Filip Eckerström, MD, PhD, from Rigshospitalet, Copenhagen, and Copenhagen University, the authors said that a low birth prevalence and referral bias have constituted significant obstacles to clarifying the natural history of EA – adding that reports on long-term survival are almost exclusively limited to single-center series of patients who have undergone surgical correction with a resultant risk of referral bias. “Only 1 study to date has described long-term survival beyond adolescence and included a large proportion of patients with non-operated EA,” they noted. “We merged nationwide registry data of patients from Denmark and Sweden who were diagnosed with EA and born from 1970 to 2017.” Study setup Eckerström and colleagues analyzed the contemporary and historical mortality of patients with EA and investigated the influence of early vs. late diagnosis, surgery, and presence or absence of concomitant congenital cardiac malformations on mortality. The study identified 530 patients born between 1970 and 2017 and diagnosed with EA within the Danish and Swedish nationwide medical registries. Each patient was matched by birth year and sex with 10 control subjects from the general population, meaning the analysis also included 5,300 matched control subjects with a median follow-up of 11 years. The average age at end of follow-up for the survivors was 20.9 years (interquartile range [IQR]: 9.0-31.5 years). Cumulative mortality and hazard ratios (HR) of mortality were computed using Kaplan-Meier failure function and Cox proportional regression model, said the team. Key findings Within the EA cohort, 43% (228) underwent cardiac surgery, reported Eckerström and colleagues, adding that at the end of follow-up, 15% (80) of the total EA patient cohort had died. The 20- year cumulative mortality in the total EA cohort was 16% (95% confidence interval [CI]: 13% to 20%), and 40-year cumulative mortality was 20% (95% CI: 15% to 25%), they added, noting that cumulative mortality was lower for patients diagnosed in the modern era (2000 and later) than for those diagnosed in the prior era (P < 0.001). Furthermore, patients with isolated lesions displayed lower cumulative mortality than patients with complex lesions did (P < 0.001), said the team – noting that patients with a presumed mild EA anatomy displayed a 35-year cumulative mortality of 11% (vs 4% for the matched control subjects; P < 0.001), yielding an HR for mortality of 6.0 (95% CI: 2.7-13.6), whereas patients with presumed severe EA demonstrated an HR of 36.2 (95% CI: 15.5-84.4) compared with control subjects and a cumulative mortality of 18% at 35 years following diagnosis. “EA is associated with an unpredictable course and often with high mortality, independent of time of diagnosis and concomitant congenital cardiac abnormalities,” said the researchers, adding that further research is needed to evaluate specific interventions to improve long-term outcomes in patients with EA. “Decisions regarding whether, how, and when to intervene surgically in patients with EA remain among the most challenging of all congenital heart diseases because of the low prevalence of the lesion and its heterogeneity,” said Eckerström and colleagues. “Further studies (both epidemiologic and clinical longitudinal follow-up studies) are warranted with focus on the functional status at rest and during exercise, symptoms, and cardiac function in relation to lesion severity and associated cardiac malformations.” A step toward better understanding Writing in an accompanying editorial, Heidi M. Connolly, MD, Joseph A. Dearani, MD, and William R. Miranda, MD – all from the Mayo Clinic, Rochester, Minnesota – noted that in addition to low prevalence, the challenges in managing EA are further deepened by the heterogeneity of anatomic abnormalities and clinical presentation, ranging from the symptomatic neonate requiring urgent surgery to the asymptomatic adult. “Before this publication, there were no population-based studies describing EA patients in the modern era. Current evidence is largely dependent on single-institution quaternary-care center data,” they said, noting that the authors should be congratulated for their work, “as it represents a step toward a better understanding of EA.” The editorialists added that the registry data “provides important lessons” that will help cardiologists to refine care for patients with EA: “First, the proposed dogma about early age at presentation/intervention suggesting adverse outcomes holds true. Second, those at highest risk are the youngest patients and those with severe disease,” they said. “Third, operative mortality is exceptionally low in patients beyond infancy. Fourth, the most common cause of late death was cardiac related.” “Nowadays, we have the unique opportunity to identify EA early (often before birth), provide timely intervention, and hopefully improve future survival and outcomes,” stated the expert commentators. “Based on these data, EA patients require life-long coordinated care at specialty centers to identify optimal treatment options.” Sources: Eckerström F, Dellborg M, Hjortdal VE, et al. Mortality in Patients With Ebstein Anomaly. J Am Coll Cardiol 2023;81:2420-2430. Connolly HM, Dearani JA, Miranda WR. Ebstein Anomaly. We Should Do Better. J Am Coll Cardiol 2023;81:2431-2433. Image Credit: ibreakstock – stock.adobe.com