The Future of Adult Congenital Heart Disease Research: Precision Health Services Delivery for the Next Decade

Abstract

Contributions to the field of congenital heart disease (CHD) by Canadians are well known. Much has been written about Maude E. Abbott of Qu ebec: Prevented from practicing medicine in Montr eal, she took on the task of running McGill University's pathology museum, producing the first atlas of CHD. 1 The description of an absent sinus (inflow tract) of the morphologically right ventricle with a single morphologically double-inlet LV, infundibular outlet chamber with normally related great arteries, the Holmes heart, so named for the first Dean of McGill's Faculty of Medicine, was published by Maude Abbott in 1901 at the recommendation of William Osler. 2,3 The Holmes heart was subsequently imaged with the use of magnetic resonance imaging and used for the cover of the 6th edition of Perloff's Clinical Recognition of Congenital Heart Disease in 2012. 4 Abbott's meticulous recording of both anatomy and first-time documentation of longevity and death makes her possibly the first CHD epidemiologist of the 20th century. Modern techniques in surgical repair, resulting in first-time survival of children born with complete transposition of the great arteries were led in Canada by William T. Mustard at the Hospital for Sick Children in Toronto. Mustard used a pericardial patch to simplify the lifesaving procedure originally described in 1959 by Ake Senning in Stockholm, 5 publishing his results in 1964. 6 To this day, that hospital remains a leading Canadian and international pediatric institution. Emerging from one of the largest pioneering adult-CHD (ACHD) programs in North America, Gary Webb of Toronto, led first-time efforts to establish a regional, provincial, and national care plan for ACHD patients and training of emerging ACHD specialists. Webb launched the first network dedicated to ACHD professionals, the Canadian Adult Congenital Heart (CACH) Network, 7 securing a position as a recognized affiliate of the Canadian Cardiovascular Society in 2010. In an initiative that brought together international leaders in CHD, the first consensus conference on the care of ACHD patients was held in Canada in 1996, with proceedings published in l998. 8 Robust scientific inquiry is new to ACHD compared with other cardiovascular diseases. "Adult congenital heart disease" was coined as a new subspecialty by J.K. Perloff in 1991. 9 The following 10-15 years were dominated by single-centre studies reporting postoperative longevity for up to 200 or 300 patients with increasingly well characterized anatomic substratesdfrom Toronto, the Mayo Clinic, the University of California in Los Angeles, and the Royal Brompton in England. As a field, we began our journey first by marvelling that in patients with repaired atrial septal defect, tetralogy of Fallot, atrioventricular septal defects, and baffle procedures for complete transposition of the great arteries, long-term survival was possible, as reported in single-centre studies with strong surgical teams. 10-14 We soon realized that the road ahead would be marked by emerging complications;...

The TRIVIA Cohort for Surgical Management of Tetralogy of Fallot: Merging Population and Clinical Data for Real-World Scientific Evidence

“…Recent reviews have highlighted the paucity of high-quality scientific evidence for PVR's efficacy and timing in patients with repaired TOF. 2,[22][23][24] With the lack of frequent hard outcomes and heterogeneity of cardiac native anatomy, the amount of resources required to conduct adequately powered prospective trials with sufficient follow-up is often insurmountable. Hence, published guidelines for PVR mostly rely on lowquality evidence.…”

Use of Serial High-Sensitive Troponin T in Patients With Adult Congenital Heart Disease: Enhancing the Detection of Major Adverse Cardiac Events

“…As patients with congenital heart disease transition into adulthood, they are at greater risk of adverse clinical outcomes. 6 Furthermore, because of the risk of heart failure (HF) in this aging population, 7 our ability for risk stratification and proper surveillance using cardiac biomarkers in this patient cohort deserves further investigation. N-terminal probrain natriuretic peptide (NT-proBNP) has important prognostic value in ACHD patients; increasing levels are indicative of adverse cardiac remodelling.…”

Lifespan Perspective on Congenital Heart Disease Research

“…Thus, a substantive data-to-evidence gap exists in lifespan CHD research. Although surgical and medical innovation in CHD conveys impressive reductions in morbidity and mortality during childhood, the quality of evidence guiding life-long care in adults, across the spectrum of CHD, lags far behind other fields of cardiovascular medicine (10). Current clinical practice guidelines of the American Heart Association/American College of Cardiology (AHA/ACC 2018) (11) and the European Society of Cardiology (ESC 2020) (12) are primarily based on expert opinion (Level of evidence C) and supported by non-randomized or observational studies and multicenter registries (Level of Evidence B).…”

“…In this review, we turn our attention to the healthcare transformation and precision health initiative catalyzed by the changing research landscape (10,13). The vision for the framework proposed in this state-of-the-art review grew out of novel constructs proposed in our field including the idea of precision delivery of health services, trajectories of disease progression that start in the womb and a lifecourse epidemiology approach (5,10). We amplified this with the first papers published using machine learning in CHD, applied to risk scores and modeled trajectories of care (14,15).…”

“…Thus, we present an integrated understanding of CHD substrate, reviewing where we are as a field, in our ability to integrate genome, phenome and environome to move towards a precision health framework. We review emerging research methodologies relvant to the lifespan investigation of CHD (10). Figure 1 illustrates the interaction of the genome and the environome that governs the expression of the phenome and the impact of medical interventions and the hypothesized impact on patients' lifespan trajectory (5).…”