Fontan hemodynamics in adults with obesity compared to overweight and normal body mass index: a retrospective invasive exercise study.

AIMS: The effects of obesity on Fontan hemodynamics are poorly understood. Accordingly, we assessed its impact on exercise invasive hemodynamics and exercise capacity. METHODS: Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) were retrospectively identified using an institutional database and categorized according to the presence of obesity (body mass index [BMI] >30 kg/m2) and overweight/normal BMI (BMI≤30 kg/m2). RESULTS: There were 18 individuals with obesity (BMI 36.4±3 kg/m2) and 59 (BMI 24.1±3.6 kg/m2) with overweight/normal BMI. Peak oxygen consumption (VO2) on noninvasive cardiopulmonary exercise testing was lower in patients with obesity (15.6±3.5 vs 19.6±5.8 ml/kg/min, p=0.04). At rest, systemic flow (Qs) (7.0 [4.8; 8.3] vs 4.8 [3.9; 5.8] l/min, p=0.001), pulmonary artery (PA) pressure (16.3±3.5 vs 13.1±3.5 mmHg, p=0.002), and PA wedge pressure (PAWP) (11.7±4.4 vs 8.9±3.1 mmHg, p=0.01) were higher, while arterial O2 saturation was lower (89.5% [86.5; 92.3] vs 93% [90; 95]) in obesity compared to overweight/normal BMI. Similarly, patients with obesity had higher exercise PA pressure (29.7±6.5 vs 24.7±6.8 mmHg, p=0.01) and PAWP (23.0±6.5 vs 19.8±7.3 mmHg, p=0.047), but lower arterial O2 saturation (82.4±7.0% vs 89% [85; 92], p=0.003). CONCLUSION: Adults post-Fontan with obesity have worse aerobic capacity, increased Qs, higher filling pressures, and decreased arterial O2 saturation compared to those with overweight/normal BMI, both at rest and during exercise, mirroring the findings observed in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve hemodynamics and outcomes requires further study.

Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) at Mayo Clinic, MN were categorized according to according to the presence of obesity (body mass index [BMI] >30 kg/m2) and overweight/normal BMI (BMI≤30 kg/m2). Adults post-Fontan with obesity have worse aerobic capacity, increased cardiac output, higher filling pressures, decreased arterial O2 saturation, and lower systemic vascular resistance compared to individuals with overweight or normal BMI, both at rest and during exercise.These findings mirror the observations in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve hemodynamics and outcomes requires further study.

High-Performing Fontan Patients: A Fontan Outcome Registry by Cardiac Magnetic Resonance Imaging Study.

Background: Fontan patients exhibit decreased exercise capacity. However, there is a subset of high-performing Fontan (HPF) patients with excellent exercise capacity. Objectives: This study aims to: 1) create a Fontan-specific percent predicted peak VO2 tool using exercise data; 2) examine clinical factors associated with HPF patients; and 3) examine late outcomes in HPF patients. Methods: Patients in the multi-institutional Fontan Outcomes Registry Using CMR Examination above the age of 8 years who had a maximal exercise test were included. An HPF patient was defined as a patient in the upper Fontan-specific percent predicted peak VO2 quartile. Multivariable logistic regression was employed to investigate factors associated with the HPF and Cox regression was used to examine the association between HPF patients and late outcomes (composite of death or listing for cardiac transplant). Results: The study included 813 patients (mean age: 20.2 ± 8.7 years). An HPF patient was associated with left ventricular morphology (OR: 1.50, P = 0.04), mixed morphology (OR: 2.23, P < 0.001), and a higher ejection fraction (OR: 1.31 for 10% increase, P = 0.01). Patients with at least moderate atrioventricular valve regurgitation, protein-losing enteropathy, or who were using psychiatric medications, were less likely to be an HPF patient. After a mean follow-up of 3.7 years, 46 (5.7%) patients developed a composite endpoint. HPF had a lower risk of death or listing for cardiac transplant (HR: 0.06 [95% CI: 0.01-0.25]). Conclusions: Patients with HPF have more favorable outcomes when compared to patients with lower exercise capacity. This large registry data highlights the role of exercise testing in providing personalized care and surveillance post-Fontan.

Transcatheter occlusion of venovenous collaterals in the total cavopulmonary Fontan circulation.

BACKGROUND: Venovenous collaterals are abnormal connections between the systemic and pulmonary venous systems. They are commonly seen in the Fontan circulation and may lead to significant hypoxaemia. Transcatheter closure of venovenous collaterals is a potential but controversial treatment as the long-term benefits and outcomes are not well understood. METHODS: This retrospective cohort study utilised data from the Australian and New Zealand Fontan Registry. Patients who underwent transcatheter venovenous collateral occlusion for hypoxemia from the year 2000 onwards were included. Atriopulmonary and Kawashima-type Fontan circulations were excluded to reflect a more contemporary Fontan cohort. RESULTS: Nineteen patients (age 19.3 ± 7.8 years, 53% female) underwent transcatheter venovenous collateral occlusion. Compared to baseline, mean oxygen saturation was improved at latest follow-up (90.5% vs 87.0%; p = 0.003). Nine patients achieved a clinically significant response (defined as an increase of at least 5% to 90% or greater), and this was associated with lower baseline Fontan pressures (12.9 v 15.6 mmHg; p = 0.02). No heart failure hospitalisations, arrhythmia, transplant referrals, or mortality were observed during the median follow-up period of 4 years. Two patients experienced thromboembolic events and five patients underwent re-intervention. CONCLUSION: Transcatheter occlusion of venovenous collaterals in Fontan patients with chronic hypoxaemia resulted in a modest increase in oxygenation over a median follow-up of 4 years and longer-term prognosis did not appear to be adversely affected. Lower Fontan pressures at baseline were associated with a greater improvement in oxygenation.

Percentage Predicted Peak Oxygen Consumption in People With Fontan Circulation: A Rapid Systematic Scoping Review and Validation Study.

BACKGROUND: Peak oxygen consumption (peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$) is routinely measured in people who have congenital heart disease and is reported as a percentage of predicted value, based upon age- and sex-matched normative reference values (NRVs). This study aimed to identify which NRVs are being used, assess whether NRVs are being applied appropriately, and evaluate if recommended NRVs are valid when applied to people with congenital heart disease. METHODS AND RESULTS: A systematic scoping review identified studies that reported peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ percentage of predicted value in people with congenital heart disease. A modified risk of bias tool evaluated the included studies. Forty-five studies reported peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ percentage of predicted value, and only 21 (47%) studies described or provided a reference on how their percentage of predicted value was calculated. The most cited NRVs were from Wasserman (n=12) and Cooper and Weiler-Ravell (n=7). Risk of bias analysis judged 63% of studies as having some concerns. The NRVs recommended by the American Heart Association were applied to participants with a Fontan circulation (n=70; aged 26.5±6.4 years; 59% women) to examine validity. Predicted peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ values from the Wasserman NRV was not significantly associated to measured peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ values (men: b=0.31, R2≤0.01; women: b=0.07, R2=0.02). CONCLUSIONS: Numerous NRVs have been applied to individuals with congenital heart disease and are often poorly reported and inappropriately matched to participants. The Wasserman NRV was the most cited but showed poor validity when applied to a Fontan cohort.

Quality of Life and Well-Being in Adults With Fontan Physiology: Findings From the Australian and New Zealand Fontan Registry Quality of Life Study.

BACKGROUND: To characterize global and health-related quality of life (QOL) among adults with Fontan physiology enrolled in the Australian and New Zealand Fontan Registry (ANZFR), and identify sociodemographic, clinical, psychological, and relational factors associated with outcomes. METHODS AND RESULTS: Using a cross-sectional survey design, 66 adults with Fontan physiology (58% women; mean age, 29.6±7.7 years; range, 18-50 years) completed validated self-report measures. Health-related QOL was assessed using the Pediatric Quality of Life Inventory, and global QOL was assessed using a visual analog scale (0-10). Participants reported lower total health-related QOL (P<0.001), as well as lower physical (P<0.001) and social (P=0.002) functioning compared with normative data. Median global QOL was 7.0 (interquartile range: 5.0-8.0) and most participants (71%) rated their QOL ≥6. For health-related QOL, age, sex, university education, and length of hospital stay in the past 12 months explained 27% of the variance in scores, while general psychological stress, medical traumatic stress, communication problems, and access to emotional support explained a further 44% of variance (final model: 71% of variance explained). For global QOL, sociodemographic and clinical factors explained 20% of the variance in scores, while psychological stress and sense of coherence explained a further 24% (final model: 44% of variance explained). CONCLUSIONS: Adults with Fontan physiology reported lower overall health-related QOL compared with community-based norms. Variance in QOL outcomes were predominantly attributable to psychological and relational factors. Tailored screening and assessment to identify Fontan patients at greatest risk of lower QOL, and a proactive approach to supportive care, are needed.

Wellbeing in Children and Adolescents with Fontan Physiology.

OBJECTIVE: To assess health-related quality of life (HRQOL) and global quality of life (QOL) in children and adolescents with Fontan physiology and identify key predictors influencing these outcomes. STUDY DESIGN: Cross-sectional analysis of 73 children and adolescents enrolled in the Australia and New Zealand Fontan Registry aged 6-17 years, at least 12 months post-Fontan operation. Assessments included the Pediatric Quality of Life Inventory (PedsQL) for HRQOL and a developmentally-tailored visual analogue scale (0-10) for global QOL, along with validated sociodemographic, clinical, psychological, relational, and parental measures. Clinical data were provided by the Australia and New Zealand Fontan Registry. RESULTS: Participants (mean age: 11.5 ± 2.6 years, 62% male) reported lower overall HRQOL (P < .001), and lower scores across all HRQOL domains (all P < .0001), compared with normative data. Median global QOL score was 7.0 (IQR 5.8-8.0), with most participants (79%) rating their global QOL ≥6. Anxiety and depressive symptoms requiring clinical assessment were reported by 21% and 26% of participants, respectively. Age, sex, and perceived seriousness of congenital heart disease explained 15% of the variation in HRQOL scores, while depressive symptoms and treatment-related anxiety explained an additional 37% (final model: 52% of variance explained). For global QOL, sociodemographic and clinical factors explained 13% of the variance in scores, while depressive symptoms explained a further 25% (final model: 38% of variance explained). Parental factors were not associated with child QOL outcomes. CONCLUSIONS: Children and adolescents with Fontan physiology experience lower HRQOL than community-based norms, despite reporting fair overall QOL. Psychological factors predominantly influenced QOL outcomes, indicating strategies to bolster psychological health could improve QOL in this population.

The effects of telerehabilitation in adults with complex biventricular congenital heart conditions: protocol for a multi-centre, randomised controlled trial-CH-FIT.

BACKGROUND: Accumulated evidence suggests that exercise training exerts beneficial effects on people with congenital heart conditions. These findings are predominantly derived from small, single-centre exercise trials conducted in outpatient rehabilitation facilities. In recent years, the delivery of exercise interventions remotely has increased through digital communications technology (telerehabilitation). However, very little research to date has been conducted into the efficacy of telerehabilitation in people with a congenital heart condition. AIMS: To evaluate the effects of a telehealth-delivered exercise intervention in people with a history of a surgical biventricular repair due to a congenital heart condition. METHODS: One hundred eligible adolescent (≥ 16 years) and adult participants living with a complex biventricular congenital heart condition will be recruited from four Australian sites and randomised to either (1) a 16-week telehealth-delivered combined (aerobic and resistance) exercise training programme of moderate-to-vigorous intensity or (2) usual care (control group), in a 1:1 allocation, with an 8-month follow-up. OUTCOMES OF INTEREST: The primary outcome will be the change in aerobic capacity expressed as peak oxygen uptake (VO2peak). Secondary outcomes will include changes in vascular function, muscle oxygenation, metabolic profile, body composition and musculoskeletal fitness, neurohormonal activation, neurocognitive function, physical activity levels, dietary and nutritional status, and quality of life. Outcomes will be assessed at baseline, 16 weeks, and 12 months (to determine longer-term maintenance potential). DISCUSSION: If found to be efficacious, telerehabilitation may be an alternative option for delivering exercise, improving health outcomes, and increasing accessibility to exercise programmes. Efficacy data is required to quantify the clinical significance of this delivery mode of exercise. TRIAL REGISTRATION: ACTRN12622000050752 Trial registration date: 17 January 2022 Trial registration URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382635&showOriginal=true&isReview=true Trial registry name: Australian and New Zealand Clinical Trials Registry.

Recurrent immunosuppressive-responsive myocarditis in a patient with desmoplakin cardiomyopathy: a case report.

Background: Desmoplakin (DSP) cardiomyopathy is a rare genetic condition characterized by repeated inflammatory myocardial injury and is associated with ventricular arrhythmia and sudden cardiac death. Diagnosis is challenging and requires a combination of genetic testing and advanced imaging techniques. Case summary: We present the case of a 38-year-old woman with recurrent episodes of subclinical myocarditis. Investigation using cardiac magnetic resonance imaging (cMRI) and genetic testing revealed a diagnosis of DSP cardiomyopathy. Her disease was initially responsive to corticosteroid therapy but quickly relapsed when treatment was tapered. Management of her condition required significant immunosuppression and the subsequent insertion of an implantable cardiac defibrillator due to her risk of sudden cardiac death. Discussion: Cardiac MRI and genetic testing are key diagnostic techniques in the assessment of patients with recurrent myocarditis and cardiomyopathy. The management of cardiomyopathies with an inflammatory component is not completely understood; however, there is likely a key role for immune suppression therapies. Furthermore, there are several cardiomyopathy genetic variants including DSP which require careful risk stratification due to an increased risk of sudden cardiac death.

Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards). 1st Edition.

These first Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards) have been developed to inform the healthcare requirements for CoHD services and enable all Australian patients, families and carers impacted by CoHD (paediatric CoHD and adult congenital heart disease [ACHD]) to live their best and healthiest lives. The CoHD Standards are designed to provide the clarity and certainty required for healthcare services to deliver excellent, comprehensive, inclusive, and equitable CoHD care across Australia for patients, families and carers, and offer an iterative roadmap to the future of these services. The CoHD Standards provide a framework for excellent CoHD care, encompassing key requirements and expectations for whole-of-life, holistic and connected healthcare service delivery. The CoHD Standards should be implemented in health services in conjunction with the National Safety and Quality Health Service Standards developed by the Australian Commission on Safety and Quality in Health Care. All healthcare services should comply with the CoHD Standards, as well as working to their organisation's or jurisdiction's agreed clinical governance framework, to guide the implementation of structures and processes that support safe care.

Cognitive Functioning and Psychosocial Outcomes in Adults with Complex Congenital Heart Disease: A Cross-sectional Pilot Study.

Adults with complex congenital heart disease (CHD) are at risk for cognitive dysfunction. However, associations between cognitive dysfunction and psychosocial outcomes are poorly defined. Between June and November 2022, we prospectively recruited 39 adults with complex CHD who completed a computerized cognitive assessment (Cogstate) and validated psychosocial scales measuring psychological distress, health-related quality of life (HRQOL), and resilience. Participants had a mean age of 36.4 ± 11.2 years. Over half (62%) were women, most (79%) had complex biventricular CHD, and 21% had Fontan physiology. Prevalence of cognitive dysfunction was greatest in the domains of attention (29%), working memory (25%), and psychomotor speed (21%). Adjusting for age and sex, Pearson partial correlations between Cogstate z-scores and self-reported cognitive problems were small. Participants who lived in the most disadvantaged areas and those with a below-average annual household income had lower global cognitive z-scores (p = 0.02 and p = 0.03, respectively). Two-thirds (64%) reported elevated symptoms of depression, anxiety, and/or stress. Small correlations were observed between psychological distress and cognitive performance. Greater resilience was associated with lower psychological distress (r ≥ -0.5, p < 0.001) and higher HRQOL (r = 0.33, p = 0.02). Our findings demonstrate that adults with complex CHD have a high risk of cognitive dysfunction, though may not recognize or report their cognitive challenges. Lower socioeconomic status may be an indicator for those at risk of poorer cognitive functioning. Psychological distress is common though may not be a strong correlate of performance-based cognitive functioning. Formal cognitive evaluation in this patient population is essential. Optimizing resilience may be a protective strategy to minimize psychological distress and bolster HRQOL.

Nutritional considerations for people living with a Fontan circulation: a narrative review.

The population of people living with a Fontan circulation are highly heterogenous, including both children and adults, who have complex health issues and comorbidities associated with their unique physiology throughout life. Research focused on nutritional considerations and interventions in the Fontan population is extremely limited beyond childhood. This review article discusses the current literature examining nutritional considerations in the setting of Fontan physiology and provides an overview of the available evidence to support nutritional management strategies and future research directions. Protein-losing enteropathy, growth deficits, bone mineral loss, and malabsorption are well-recognised nutritional concerns within this population, but increased adiposity, altered glucose metabolism, and skeletal muscle deficiency are also more recently identified issues. Emergencing evidence suggets that abnormal body composition is associated with poor circulatory function and health outcomes. Many nutrition-related issues, including the impact of congenital heart disease on nutritional status, factors contributing to altered body composition and comorbidities, as well as the role of the microbiome and metabolomics, remain poodly understood.

Impact of Left Heart Disease Risk Factors on Outcomes in Pulmonary Arterial Hypertension Therapy.

BACKGROUND: Current guidelines recommend initial monotherapy for pulmonary arterial hypertension (PAH) with cardiopulmonary comorbidities, despite limited available evidence to guide management. RESEARCH QUESTION: Do left heart disease (LHD) risk factors have an impact on treatment response and influence applicability of risk assessment in a real-world cohort of patients with PAH? STUDY DESIGN AND METHODS: The Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) trial criteria was used to define the phenotype of patients with PAH with risk factors for LHD. Treatment strategy, functional outcome, long-term survival, and risk discrimination were compared with a reference PAH cohort using the Pulmonary Hypertension Society of Australia and New Zealand Registry. RESULTS: A total of 487 incident patients with PAH diagnosed between 2011 and 2020 were included. Of these, 103 (21.1%) fulfilled the definition of PAH with LHD risk factors, with 384 (78.9%) remaining as the reference group. Patients in the PAH with LHD risk factors group were older (66 ± 13 vs 58 ± 19 years; P < .001), had lower pulmonary vascular resistance (393 ± 266 vs 708 ± 391 dyn.s/cm5; P = .031), and had worse 6-min walk distance (286 ± 130 vs 327 ± 136 m; P = .005) at diagnosis. The PAH with LHD risk factors group was less likely to receive initial combination therapy (27% vs 44%; P = .02). Changes in 6-min walk distance at 12 months were similar in both groups (43 ± 77 m in the PAH with LHD risk factors group and 50 ± 90 m in the reference group; P = .50), including when stratified by initial treatment strategy (PAH with LHD risk factors group vs reference PAH group: monotherapy: 40 ± 81 vs 38 ± 95 m, P = .87; combination therapy: 53 ± 78 vs 64 ± 106 m, P = .511). Functional class improvements were also similar in both groups. REVEAL Registry 2.0 risk score effectively discriminated risk in both populations (C statistic = 0.756 for the PAH with LHD risk factors group and C statistic = 0.750 for the reference PAH group). There was no difference in survival between the two groups (log-rank test, P = .29). INTERPRETATION: In a real-world cohort, patients with PAH with LHD risk factors were less likely to be exposed to initial combination therapy. Nevertheless, selected patients with PAH with LHD risk factors who were treated with initial combination therapy derived similar functional response compared with the reference group. Further studies are needed to phenotype patients with PAH with cardiopulmonary comorbidities who may benefit from initial combination therapy.

O2 pulse slope correlates with stroke volume during exercise in patients with a Fontan circulation.

BACKGROUND: Peak oxygen pulse (O2pulse=oxygen consumption/heart rate) is calculated by the product of stroke volume (SV) and oxygen extraction. It has been shown to be reduced in patients with a Fontan circulation. However, in the Fontan population, it may be a poor marker of SV. We propose that the slope of the O2 pulse curve may be more reflective of SV during exercise. METHODS: We analysed cardiopulmonary exercise test data in 22 subjects with a Fontan circulation (cohort A) and examined the association between peak SV during exercise (aortic flow measured on exercise cardiac MRI), and O2 pulse parameters (absolute O2 pulse and O2 pulse slopes up to anaerobic threshold (AT) and peak exercise). In a separate Fontan cohort (cohort B, n=131), associations between clinical characteristics and O2 pulse kinetics were examined. RESULTS: In cohort A, peak aortic flow was moderately and significantly associated with O2pulseslopePEAK (r=0.47, p=0.02). However, neither absolute O2pulseAT nor O2pulsePEAK was significantly associated with peak aortic flow. In cohort B, O2pulseslopePEAK and O2pulseslopeAT were not significantly associated with clinical parameters, apart from a weak association with forced vital capacity. CONCLUSION: The slope of the O2 pulse curve to peak exercise may be more reflective of peak SV in the Fontan population than a single peak O2 pulse value.

Cluster Sets to Prescribe Interval Resistance Training: A Potential Method to Optimise Resistance Training Safety, Feasibility and Efficacy in Cardiac Patients.

The integration of resistance training for cardiac patients leads to important health outcomes that are not optimally obtained with aerobic exercise; these include an increase in muscle mass, maintenance of bone mineral density, and improvements in muscular fitness parameters. Despite the proliferation of evidence supporting resistance exercise in recent decades, the implementation of resistance training is underutilised, and prescription is often sub-optimal in cardiac patients. This is frequently associated with safety concerns and inadequate methods of practical exercise prescription. This review discusses the potential application of cluster sets to prescribe interval resistance training in cardiac populations. The addition of planned, regular passive intra-set rest periods (cluster sets) in resistance training (i.e., interval resistance training) may be a practical solution for reducing the magnitude of haemodynamic responses observed with traditional resistance training. This interval resistance training approach may be a more suitable option for cardiac patients. Additionally, many cardiac patients present with impaired exercise tolerance; this model of interval resistance training may be a more suitable option to reduce fatigue, increase patient tolerance and enhance performance to these workloads. Practical strategies to implement interval resistance training for cardiac patients are also discussed. Preliminary evidence suggests that interval resistance training may lead to safer acute haemodynamic responses in cardiac patients. Future research is needed to determine the efficacy and feasibility of interval resistance training for health outcomes in this population.

Exercise as therapy for neurodevelopmental and cognitive dysfunction in people with a Fontan circulation: A narrative review.

People with a Fontan circulation are at risk of neurodevelopmental delay and disability, and cognitive dysfunction, that has significant implications for academic and occupational attainment, psychosocial functioning, and overall quality of life. Interventions for improving these outcomes are lacking. This review article discusses current intervention practices and explores the evidence supporting exercise as a potential intervention for improving cognitive functioning in people living with a Fontan circulation. Proposed pathophysiological mechanisms underpinning these associations are discussed in the context of Fontan physiology and avenues for future research are recommended.

Cardiovascular Complications of Down Syndrome: Scoping Review and Expert Consensus.

Cardiovascular disease is a leading cause of morbidity and mortality in individuals with Down syndrome. Congenital heart disease is the most common cardiovascular condition in this group, present in up to 50% of people with Down syndrome and contributing to poor outcomes. Additional factors contributing to cardiovascular outcomes include pulmonary hypertension; coexistent pulmonary, endocrine, and metabolic diseases; and risk factors for atherosclerotic disease. Moreover, disparities in the cardiovascular care of people with Down syndrome compared with the general population, which vary across different geographies and health care systems, further contribute to cardiovascular mortality; this issue is often overlooked by the wider medical community. This review focuses on the diagnosis, prevalence, and management of cardiovascular disease encountered in people with Down syndrome and summarizes available evidence in 10 key areas relating to Down syndrome and cardiac disease, from prenatal diagnosis to disparities in care in areas of differing resource availability. All specialists and nonspecialist clinicians providing care for people with Down syndrome should be aware of best clinical practice in all aspects of care of this distinct population.

Prolonged Enteral Tube Feeding in Infants With a Functional Single Ventricle Is Associated With Adverse Outcomes After Fontan Completion.

OBJECTIVES: To define the baseline characteristics of long-term tube-fed (TF) single ventricle patients, investigate associations between long-term enteral tube feeding and growth, and determine associations with long-term outcomes after Fontan procedure. STUDY DESIGN: We performed a retrospective cohort study of patients in the Australia and New Zealand Fontan Registry undergoing treatment at the Royal Children's Hospital, the Children's Hospital at Westmead, Royal Melbourne Hospital, and Royal Prince Alfred Hospital from 1981 to 2018. Patients were defined as TF or non-tube-fed (NTF) based on enteral tube feeding at the age of 90 days. Feeding groups were compared regarding body mass index (BMI) trajectory, BMI at last follow-up, and long-term incidence of severe Fontan failure. RESULTS: Of 390 patients (56 [14%] TF, 334 [86%] NTF), TF was associated with right ventricular dominance, hypoplastic left heart syndrome, Norwood procedure, increased procedures prior to Fontan, extracardiac conduit Fontan, Fontan fenestration, and atrioventricular valve repair/replacement. TF patients were less likely to be in the higher compared with lowest 0-6 month BMI trajectory (P < .01; P = .03), had lower 6 month weight-for-age z-scores (P < .01) and length-for-age z-scores (P = .01). TF were less likely to be overweight/obese at pediatric follow-up (hazard ratio [HR] = 0.31, 95% CI: 0.12-0.80; P = .02) and more likely to be underweight at adult follow-up (HR = 16.51; 5% CI: 2.70-101.10; P < .01). TF compared with NTF was associated with increased risk of severe Fontan failure (HR = 4.13; 95% CI = 1.65-10.31; P < .01). CONCLUSIONS: Prolonged infant enteral tube feeding is an independent marker of poor growth and adverse clinical outcomes extending long-term post-Fontan procedure.

ß3 adrenergic agonism: A novel pathway which improves right ventricular-pulmonary arterial hemodynamics in pulmonary arterial hypertension.

Efficacy of therapies that target the downstream nitric oxide (NO) pathway in pulmonary arterial hypertension (PAH) depends on the bioavailability of NO. Reduced NO level in PAH is secondary to "uncoupling" of endothelial nitric oxide synthase (eNOS). Stimulation of ß3 adrenergic receptors (ß3 ARs) may lead to the recoupling of NOS and therefore be beneficial in PAH. We aimed to examine the efficacy of ß3 AR agonism as a novel pathway in experimental PAH. In hypoxia (5 weeks) and Sugen hypoxia (hypoxia for 5 weeks + SU5416 injection) models of PAH, we examined the effects of the selective ß3 AR agonist CL316243. We measured echocardiographic indices and invasive right ventricular (RV)-pulmonary arterial (PA) hemodynamics and compared CL316243 with riociguat and sildenafil. We assessed treatment effects on RV-PA remodeling, oxidative stress, and eNOS glutathionylation, an oxidative modification that uncouples eNOS. Compared with normoxic mice, RV systolic pressure was increased in the control hypoxic mice (p < 0.0001) and Sugen hypoxic mice (p < 0.0001). CL316243 reduced RV systolic pressure, to a similar degree to riociguat and sildenafil, in both hypoxia (p < 0.0001) and Sugen hypoxia models (p < 0.03). CL316243 reversed pulmonary vascular remodeling, decreased RV afterload, improved RV-PA coupling efficiency and reduced RV stiffness, hypertrophy, and fibrosis. Although all treatments decreased oxidative stress, CL316243 significantly reduced eNOS glutathionylation. ß3 AR stimulation improved RV hemodynamics and led to beneficial RV-PA remodeling in experimental models of PAH. ß3 AR agonists may be effective therapies in PAH.

Prevalence and determinants of tricuspid regurgitation after repair of tetralogy of Fallot.

BACKGROUND: The prevalence and determinants of tricuspid regurgitation (TR) in patients with repaired Tetralogy of Fallot (rTOF) remain incompletely understood. OBJECTIVES: To explore the prevalence of and factors associated with TR in patients with rTOF, specifically, the relationship of right ventricular (RV) dilatation with TR severity. METHODS: Patients (≥17 yrs) with rTOF referred to our service (2000-2019) were identified. Those with severe pulmonary stenosis, significant shunt, or previous tricuspid valve surgery were excluded. Using standard cardiac MRI protocols, RV, right atrial (RA) and tricuspid valve (TV) parameters were measured and compared. RESULTS: 68 consecutively eligible patients with rTOF were included in the study (27 ± 9 yrs., 35% female). Despite substantial RV volume overload (mean RVEDVi 153 mL/m2), the majority of the cohort (78%) had no or only mild TR. RA volumes, tenting height/area and annular diameter were normal (4.9 ± 2.0 mm, 1.1 ± 1.0 cm2 and 32.4 ± 6.2 mm, respectively). There was no significant correlation of TR fraction with RVEDVi (r = 0.13; p = 0.30), RVEF (r = 0.09; p = 0.44) or tricuspid annular diameter (r = 0.07; p = 0.62). Only RAVi showed a weak but significant correlation with TR fraction (0.29; p = 0.03). In a pooled cohort analysis, including both rTOF patients and adults with a dilated RV from pre-tricuspid shunt lesions, only rTOF was independently associated with higher TR fraction (p = 0.017). CONCLUSION: Despite substantial RV dilatation in a cohort with rTOF, there was surprisingly little TR. We found poor correlation between RVEDVi, RA volumes, tricuspid annular dilatation and the presence of significant TR. These findings question commonly held notions regarding the pathophysiology of functional TR in these patients.

Impact of Aortic Atresia After Fontan Operation in Patients With Hypoplastic Left Heart Syndrome.

BACKGROUND: Patients with aortic atresia have the worst prognosis in the spectrum of hypoplastic left heart syndrome. It remains unknown whether patients with aortic atresia continue to do poorly after Fontan operation. This study aimed to determine the association between aortic atresia and atrioventricular valve (AVV) function and clinical outcomes after Fontan operation in patients with hypoplastic left heart syndrome. METHODS: We performed a retrospective study of 1731 patients who survived the Fontan operation from the Australia and New Zealand Fontan Registry between 1975 and 2020. RESULTS: We identified 188 patients with hypoplastic left heart syndrome, including 99 (53%) with aortic atresia. Overall transplant-free survival and freedom from failure of Fontan circulation at 15 years was 91% (95% CI, 86%-96%) and 79% (95% CI, 71%-88%), respectively. The cumulative incidence of AVV operation at 15 years of age for patients with aortic atresia and aortic stenosis was 28% (95% CI, 19%-38%) and 14% (95% CI, 7%-22%; P = .03), respectively. The cumulative incidence of AVV failure (moderate or greater regurgitation or AVV operation) at 15 years of age for patients with aortic atresia and aortic stenosis was 50% (95% CI, 37%-61%) and 30% (95% CI, 19%-42%; P = .01). Patients with AVV failure were at increased risk of having moderately, or worse, decreased systolic ventricular function (odds ratio 6.7; 95% CI, 1.7-33; P = .01) and failure of Fontan circulation (hazard ratio 3.7; 95% CI, 1.5-9.1; P < .01). CONCLUSIONS: In patients with hypoplastic left heart syndrome, there is no significant difference in transplant-free survival after Fontan operation between patients with aortic atresia and patients with aortic stenosis. However, patients with aortic atresia have a much higher burden of AVV failure than patients with aortic stenosis. Atrioventricular valve failure is associated with failure of Fontan circulation.