Burchill, Luke J.

Background: Artificial intelligence (AI) can be used to predict a person’s age from the electrocardiogram (ECG) (AI-ECG age) and has been proposed as a measurement of biological age. The difference between AI-ECG age and chronological age (defined as delta-age) is an independent predictor of mortality in the general population. This study assessed the relationship between AI ECG estimated age and mortality among adults living with congenital heart disease (CHD). Methods: A previously validated neural network to estimate AI-ECG age was used to analyze standard digital 12-lead ECGs in a cohort of subjects aged >18 years seen in the adult CHD (ACHD) clinic between 1992 to 2023. A single ECG, collected during the year of the first visit to the ACHD clinic was analyzed to compute the delta-age.. A positive delta-age indicates an AI ECG estimated age higher than the subject’s chronological age. The relationship between the delta-age and mortality was evaluated using Cox proportional hazard models adjusting for influential clinical factors including chronologic age, sex, ACHD severity, NYHA class and history of arrhythmia. Results: Of 5,780 subjects tested (50% females), the mean chronological age was 39.1 ± 15.0 years. AI ECG estimated age was 52.3 ± 16.6 years. Complexity of CHD was classified as mild, moderate, and severe in 7.4%, 73.9% and 18.7% of patients respectively. Patients with severe CHD had the highest delta-age of 17.1 (±18.2) years followed by moderate 12.7 (±13.6) y and simple 7.7 (±11.5) y. Patients with single ventricle had the highest deviation in AI estimated age [median delta-age 21.0 (IQR 28.6) y] followed by those with a systemic right ventricle [median delta-age of 16.3 (IQR 29.3) y]. During a median follow-up of 6.4 y (25th – 75th centile 1.58 – 13.7 y), mortality occurred in 839 (14.5%) patients. After adjusting for chronological age, CHD severity, and other clinical variables, delta-age gap was associated with increased mortality risk (HR 1.06 (1.03 – 1.09) per 5-year increment in delta-age, p<0.005), Table 1. Conclusion: The difference between AI ECG and chronological age is an independent predictor of all-cause mortality in ACHD patients.

INTRODUCTION: There is a significant shortage of specialized Adult Congenital Heart Disease (ACHD) cardiologists despite a rising prevalence of adults with this condition. AIM: Our study explores the specific motivations and deterrents that influence adult and pediatric cardiologists’ ACHD career decisions, which could serve as the basis for future solutions to overcome this shortage in each specific region. METHODS: An anonymous global survey was distributed to adult and pediatric cardiologists and trainees via email, social media, and medical society newsletters. The survey included demographics, ACHD exposure, career considerations, Likert scale ratings, and open-ended inquiries on ACHD career recommendations. Respondents included non-ACHD and ACHD cardiologists (defined as those caring for ACHD with or without formal training). The analysis covered regional variations across continents. Responses with less than 75% completion were excluded. RESULTS: A total of 811 valid responses were collected (53.5% female, 48.3% aged 31-40, and 43.3% White). ACHD cardiologists were 21%, mostly practicing in North America (44.1%) and Europe (32.9%). Almost all ACHD cardiologists (94.7%) recommended it as a career. Among the 641 non-ACHD cardiologists, 85.7% had been exposed to ACHD, however, only 35.1% considered pursuing it themselves. For ACHD cardiologists the top global motivators for pursuing an ACHD career were awareness of the field and its significance, mentor's influence, and sufficient clinical exposure during residency (Figure 1A). Factors that deterred non-ACHD cardiologists included a lack of compensation compared to other cardiology subspecialties, limited job opportunities, and the longer duration of training (Figure 1B). Absence of specialized training and educational programs emerged as a major deterrent in all continents except North America. The lack of mentorship or role models in ACHD was particularly pronounced in Africa and Central and South America. Limited exposure to ACHD during training was a significant issue in Europe and Africa. CONCLUSION: Most ACHD cardiologists recommend a career in ACHD. However, only a few non-ACHD cardiologists recommend it. Influential mentors, clinical exposure motivate; low compensation, lengthy training deter. Regional disparities require targeted interventions for better ACHD cardiologist recruitment.

Background Adults with congenital heart disease (CHD) are at increased risk of stroke but high‐quality population level data on stroke incidence in these patients are scant. Methods and Results A retrospective whole‐population Western Australian cohort of adult patients with CHD aged 18 to 64 years was created and followed from January 2000 to December 2017 using linked hospital data. Stroke incidence rates within the adult cohort with CHD were calculated and compared with the general population via direct standardization. A nested case–control design assessed predictors of ischemic and hemorrhagic stroke within the cohort. Among 7916 adults with CHD, 249 (3.1%) incident strokes occurred at a median age of 47 years; 186 (2.3%) ischemic, 33 (0.4%) hemorrhagic and 30 (0.4%) unspecified strokes. Ischemic and hemorrhagic stroke incidence was, respectively, 9 and 3 times higher in adults with CHD than the general population. Absolute risk was low with annual rates of 0.26% (ischemic) and 0.05% (hemorrhagic). Highest rates were observed in adults with shunt and left‐sided lesions. Predictors of ischemic stroke in adults with CHD included recent cardiac surgery, left‐sided valve repair/replacements, shunt lesions, and traditional risk factors (hypertension, infective endocarditis, peripheral vascular disease, and tobacco use). Mental health disorders and increasing Charlson's comorbidity scores were strongly associated with higher risk of ischemic and hemorrhagic stroke. The CHA 2 DS 2 VASc score was associated with ischemic stroke incidence. Conclusions This study provides the first population‐based stroke incidence estimates for adults with CHD in Australia, showing elevated stroke risk across different CHD lesions. It highlights the potential clinical importance of managing comorbidities, especially mental health.

Abstract Aims Women with congenital heart disease (CHD) are at risk of pregnancy-related adverse outcomes (PRAO). The purpose of this study was to assess temporal changes in cardiac structure and function (cardiac remodelling) during pregnancy, and the association with PRAO in women with CHD. Methods and results Retrospective study of pregnant women with CHD and serial echocardiograms (2003–2021). Cardiac structure and function were assessed at pre-specified time points: prepregnancy, early pregnancy, late pregnancy, and postnatal period. PRAO was defined as the composite of maternal cardiovascular, obstetric, and neonatal complications. The study comprised 81 women with CHD (age, 29 ± 5 years). Compared to the baseline echocardiogram, there was a relative increase in right ventricular systolic pressure (RVSP) (relative change 13 ± 5%, P &lt; 0.001, in early pregnancy; and 18 ± 5%, P &lt; 0.001, in late pregnancy). There was a relative decrease in right ventricle free wall strain (RVFWS) (relative change −11 ± 3%, P &lt; 0.001, in late pregnancy; and −11 ± 4%, P = 0.003, in postnatal period), and a relative decrease in RVFWS/RVSP (relative change, −10 ± 5%, P = 0.02 in early pregnancy, −26 ± 7%, P &lt; 0.001, in late pregnancy, and −14 ± 5%, P &lt; 0.001, in postnatal period). Baseline right ventricular to pulmonary arterial (RV–PA) coupling, and temporal change in RV–PA coupling were associated with PRAO, after adjustment for maternal age and severity of cardiovascular disease. Conclusion Women with CHD had a temporal decrease in RV systolic function and RV–PA coupling, and these changes were associated with PRAO. Further studies are required to delineate the aetiology of deterioration in RV–PA coupling during pregnancy, and the long-term implications of right heart dysfunction observed in the postnatal period.

Background There are limited data about the impact of timing of pulmonary valve replacement (PVR) on right heart reverse remodeling in patients with pulmonary regurgitation following intervention for isolated pulmonary valve stenosis (PS). This study compared differences in postprocedural right heart reverse remodeling after early versus late PVR (defined as PVR before versus after attainment of the conservative consensus criteria proposed by Bokma et al, 2018) in patients with prior intervention for PS, using patients with tetralogy of Fallot as the reference group. Method and Results Right atrial reservoir strain and right ventricular free wall strain was measured at baseline, 1 and 3 years after PVR. There were 114 patients with PS (early PVR, 87 [76%]; late PVR, 27 [24%]) and 291 patients with tetralogy of Fallot (early PVR, 197 [67%]; late PVR, 96 [33%]). The PS group had greater improvement in right atrial reservoir strain at 1 year (12%±4% versus 8%±4%; P <0.001) and 3 years (15%±6% versus 9%±6%; P <0.001), and a greater improvement in right ventricular free wall strain at 1 year (12%±4% versus 7%±3%, P =0.008) and 3‐years (16%±6% versus 12%±5%; P =0.01) after PVR compared with the tetralogy of Fallot group. There was no difference in right heart reverse remodeling between patients who underwent early versus later PVR within the PS group. In contrast, late PVR was associated with less right heart reverse remodeling within the tetralogy of Fallot group. Conclusions These data suggest that patients with palliated PS presenting pulmonary regurgitation have a more benign clinical course, and hence delaying PVR in this population may be appropriate.

AbstractObjectiveWe performed a pilot stroke incidence study, focused on feasibility and inclusion of the CONSIDER reporting guidelines, to model the design of a future population‐based study aiming to definitively determine stroke incidence, antecedents, treatment, and outcomes.Study designProspective stroke incidence study (pilot study).Setting, participantsAll people aged 15 years or older who lived in postcode‐defined areas of South Australia and Northern Territory (885 472 people, including 45 127 Aboriginal people [5.1%]) diagnosed with stroke for the first time during 1 October – 31 December 2015 and admitted to public hospitals or stroke and transient ischaemic attack clinics.Main outcome measuresFeasibility of a prospective population‐based stroke incidence study.ResultsOf the 123 participants with first strokes, ten were Aboriginal (8%); the median age of Aboriginal people was 45 years (interquartile range [IQR], 33–55 years), of non‐Indigenous people 73 years (IQR, 62–84 years). For Aboriginal people, the age‐standardised incidence of stroke was 104 (95% confidence interval [CI], 84–124) per 100 000 person‐years, for non‐Indigenous people 33 (95% CI, 22–44) per 100 000 person‐years. We found that a prospective population‐based stroke incidence study in Aboriginal people was feasible, including with respect to establishing an adequate sample size, diagnostic confirmation, identification of incident stroke, confirming stroke subtypes, establishing a stable statistical population, standardising data reporting for comparison with other stroke incidence studies, and ethical research reporting that conforms to CONSIDER guidelines.ConclusionsA larger, population‐based study of the incidence of stroke in Aboriginal people is both feasible and needed to provide robust estimates of stroke incidence, antecedents, treatments and outcomes to help guide strategies for reducing the risk of and outcomes of stroke in Aboriginal people.

Abstract Aim The normal (i.e. expected) haemodynamics in adults post-Fontan remain poorly delineated. Moreover, the definitions of elevated exercise pulmonary artery (PA) and PA wedge pressure (PAWP) for this population have not been described. Methods and results Seventy-two adults post-Fontan undergoing exercise catheterization were categorized into abnormal (Group I, n = 59; defined as resting mean PA ≥14 mmHg and/or PAWP ≥12 mmHg, ΔPAWP/Δsystemic flow [Qs] &gt;2 mmHg/L/min, and/or ΔPA/Δpulmonary flow &gt;3 mmHg/L/min) and normal (Group II, n = 13) haemodynamics. Thirty-nine patients with non-cardiac dyspnoea (NCD) were included as controls. There was no difference in exercise arterial oxygen saturation (87% [81–92] vs. 89% [85–93], p = 0.29), while exercise PA pressure (27 [23–31] vs. 16 [14.5–19.5] mmHg, p &lt; 0.001) and PAWP were higher (21 [18–28] vs. 12 [8–14] mmHg, p &lt; 0.001) in Group I. At peak exercise, Group I had lower heart rate (97 [81–120] vs. 133 [112.5–147.5] bpm, p &lt; 0.001) and Qs response (67.3 [43.8–93.1] vs. 105.9 (82–118.5) % predicted, p &lt; 0.001) than Group II. Exercise superior vena cava pressures were higher (16 [14–22.5] vs. 5.5 [3–7.3] mmHg, p &lt; 0.001) and arterial oxygen saturation lower (89% [85–93] vs. 97% [96–98], p &lt; 0.001) in Group II compared to NCD, while no differences in PAWP, stroke volume index, heart rate, or Qs response were seen. If defined as two standard deviations above mean values for Group II, elevated PAWP and mean PA pressure post-Fontan would correspond to 20.6 mmHg and 25.8 mmHg, respectively. Conclusion PAWP &gt;20 mmHg and mean PA pressure &gt;25 mmHg could be used to define elevated values during exercise in adults post-Fontan. The major discrepancy in exercise haemodynamics among Group II compared to controls appears to be the degree of systemic venous hypertension and arterial desaturation.

Background Little is known about outcomes following heart failure (HF) hospitalization among adults with congenital heart disease (CHD) in the United States. We aim to compare the outcomes of HF versus non‐HF hospitalizations in adults with CHD. Methods and Results Using a national deidentified administrative claims data set, patients with adult congenital heart disease (ACHD) hospitalized with and without HF (ACHDHF+, ACHDHF−) were characterized to determine the predictors of 90‐day and 1‐year mortality and quantify the risk of mortality, major adverse cardiac and cerebrovascular events, and health resource use. Cox proportional hazard regression was used to compare ACHDHF+ versus ACHDHF− for risk of events and health resource use. Of 26 454 unique ACHD admissions between January 1, 2010 and December 31, 2020, 5826 (22%) were ACHDHF+ and 20 628 (78%) were ACHDHF−. The ACHD HF+ hospitalizations increased from 6.6% to 14.0% ( P <0.0001). Over a mean follow‐up period of 2.23 ± 2.19 years, patients with ACHDHF+ had a higher risk of mortality (hazard ratio [HR], 1.86 [95% CI, 1.67–2.07], P <0.001), major adverse cardiac and cerebrovascular events (HR, 1.73 [95% CI, 1.63–1.83], P <0.001) and health resource use including rehospitalization (HR, 1.09 [95% CI, 1.05–1.14], P <0.001) and increased postacute care service use (HR, 1.56 [95% CI, 1.32–1.85], P <0.001). Cardiology clinic visits within 30 days of hospital admission were associated with lower 90‐day and 1‐year all‐cause mortality (odds ratio [OR], 0.62 [95% CI, 0.49–0.78], P <0.001; OR, 0.69 [95% CI, 0.58–0.83], P <0.001, respectively). Conclusions HF hospitalization is associated with increased risk of mortality and morbidity with high health resource use in patients with ACHD. Recent cardiology clinic attendance appears to mitigate these risks.

AbstractBackgroundObservational reports suggest that supplementation that increases citric acid cycle intermediates via anaplerosis may have therapeutic advantages over traditional medium‐chain triglyceride (MCT) treatment of long‐chain fatty acid oxidation disorders (LC‐FAODs) but controlled trials have not been reported. The goal of our study was to compare the effects of triheptanoin (C7), an anaplerotic seven‐carbon fatty acid triglyceride, to trioctanoin (C8), an eight‐carbon fatty acid triglyceride, in patients with LC‐FAODs.MethodsA double blinded, randomized controlled trial of 32 subjects with LC‐FAODs (carnitine palmitoyltransferase‐2, very long‐chain acylCoA dehydrogenase, trifunctional protein or long‐chain 3‐hydroxy acylCoA dehydrogenase deficiencies) who were randomly assigned a diet containing 20% of their total daily energy from either C7 or C8 for 4 months was conducted. Primary outcomes included changes in total energy expenditure (TEE), cardiac function by echocardiogram, exercise tolerance, and phosphocreatine recovery following acute exercise. Secondary outcomes included body composition, blood biomarkers, and adverse events, including incidence of rhabdomyolysis.ResultsPatients in the C7 group increased left ventricular (LV) ejection fraction by 7.4% (p = 0.046) while experiencing a 20% (p = 0.041) decrease in LV wall mass on their resting echocardiogram. They also required a lower heart rate for the same amount of work during a moderate‐intensity exercise stress test when compared to patients taking C8. There was no difference in TEE, phosphocreatine recovery, body composition, incidence of rhabdomyolysis, or any secondary outcome measures between the groups.ConclusionsC7 improved LV ejection fraction and reduced LV mass at rest, as well as lowering heart rate during exercise among patients with LC‐FAODs.Clinical Trial Registration: Clinicaltrials.gov NCT01379625.