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.

Fontan circulation and systemic disease - a retrospective cohort analysis over 35 years of follow-up: Fontan systemic disease at 35 years.

BACKGROUND: The Fontan operation provides lifesaving palliation for individuals with single ventricle (SV) physiology. Given recent concerns of systemic disease (SD) for patients with a Fontan circulation, we sought to 1) quantify the increase in SD incidence associated with the Fontan circulation; 2) identify the risk factor of SD; 3) assess the association between SD and mortality in patients with a Fontan circulation. METHODS: A matched retrospective cohort study design was adopted. From the Quebec Congenital Heart Disease (CHD) Database with up to 35 years of follow-up, patients who survived at least 30 days after the Fontan operation were identified. For each Fontan patient, patients with isolated ventricular septal defect (VSD) with the same sex and age were identified and 20 of them were randomly selected to form the control group. The presence of SD was defined as at least one hospitalization due to extra-cardiac complications including liver, respiratory, gastrointestinal or renal disease. Time-to-event analysis including Kaplan-Meier curve analysis and Cox proportional hazard models were conducted to assess the cumulative risk of SD, risk factors of SD, and the association between SD and 10-year mortality. RESULTS: A total of 533 patients with Fontan circulation were identified and matched with 10,280 VSD patients. The cumulative probabilities of SD at 10- and 35-years follow-up were 59.02% and 89.66% in patients with a Fontan circulation, 4-7 times of the probabilities in VSD patients (8.68% and 23.34%, respectively; LogRank tests p<0.0001). In Fontan patients, cardiovascular complications were associated with a 4.1-fold (95% CI: 3.52-4.88) higher risk of developing SD. Multisystem disease (>1 extra-cardiac organ affected) disease was associated with a 3.38-fold (95%CI: 1.73-6.60) increase in 10-year mortality risk when comparing to the absence of SD. CONCLUSIONS: This population-based study demonstrated that patients with a Fontan circulation had increased risk of SD, which in turn led to higher risk of mortality. These findings underscore the need for more systematic surveillance of cardiac and systemic disease for patients after Fontan operation.

Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial).

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241.

The prognostic role of liver volumetry in Fontan patients.

BACKGROUND AND HYPOTHESES: High venous pressures and associated hepatic congestion are important drivers for Fontan-associated liver disease. The prognostic significance of hepatomegaly as a marker of congestion however is not well defined and is further explored in this research study. METHODS: Fontan patients who have had liver ultrasound scans were identified from the Prince Sultan Cardiac Centre Fontan Database and had their anatomic, surgical, clinical histories abstracted from the electronic medical records following institutional ethics approval. Liver volumes were determined retrospectively from reviewing individual US images, and these, divided into tertiles, were analysed in the context of the predefined endpoints of (i) Primary - death or heart or liver transplantation, or (ii) Secondary - combined endpoint of death, transplantation, arrhythmia, or protein-losing enteropathy. RESULTS: Mean indexed liver volumes for the entire cohort (n = 199) were 1065.1 ± 312.1 ml/m2, range 387 to 2071 ml/m2. Patients with the largest liver volumes (highest tertile) were less likely to have a functioning fenestration compared to those in the lowest tertile 44% versus 56% p = 0.016 and experienced the highest burden of mortality and heart or heart-liver transplantation, p = 0.016, and were more likely to reach the composite endpoint of death, protein-losing enteropathy, arrhythmia, or transplantation, p = 0.010. Liver volumes had an overall predictive accuracy for the combined outcome of 61% (CI 53%, 67%, p = 0.009). CONCLUSIONS: Liver volumetry may serve as a potentially important congestion biomarker for adverse outcomes after the Fontan operation.

Developing an adolescent and adult Fontan Management Programme.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

Phenotypes of adults with congenital heart disease around the globe: a cluster analysis.

OBJECTIVE: To derive cluster analysis-based groupings for adults with congenital heart disease (ACHD) when it comes to perceived health, psychological functioning, health behaviours and quality of life (QoL). METHODS: This study was part of a larger worldwide multicentre study called APPROACH-IS; a cross sectional study which recruited 4028 patients (2013-2015) from 15 participating countries. A hierarchical cluster analysis was performed using Ward's method in order to group patients with similar psychological characteristics, which were defined by taking into consideration the scores of the following tests: Sense Of Coherence, Health Behavior Scale (physical exercise score), Hospital Anxiety Depression Scale, Illness Perception Questionnaire, Satisfaction with Life Scale and the Visual Analogue Scale scores of the EQ-5D perceived health scale and a linear analogue scale (0-100) measuring QoL. RESULTS: 3768 patients with complete data were divided into 3 clusters. The first and second clusters represented 89.6% of patients in the analysis who reported a good health perception, QoL, psychological functioning and the greatest amount of exercise. Patients in the third cluster reported substantially lower scores in all PROs. This cluster was characterised by a significantly higher proportion of females, a higher average age the lowest education level, more complex forms of congenital heart disease and more medical comorbidities. CONCLUSIONS: This study suggests that certain demographic and clinical characteristics may be linked to less favourable health perception, quality of life, psychological functioning, and health behaviours in ACHD. This information may be used to improve psychosocial screening and the timely provision of psychosocial care.

Smoking among adult congenital heart disease survivors in the United States: Prevalence and relationship with illness perceptions.

The relationship between smoking and illness perceptions among congenital heart disease (CHD) survivors is unknown. The primary aims of the present study were to compare the smoking prevalence among CHD survivors to a nationally representative U.S. sample and examine the relationship between smoking and illness perceptions. CHD survivors (N = 744) from six U.S. sites participated in the study. The smoking prevalence among CHD survivors (9.3%) was lower than the general population (15.3%). However, 23.3% of CHD survivors with severe functional limitations smoked. Smoking prevalence differed by U.S. region, with a greater proportion of those attending CHD care in the Midwest reporting smoking (11.8%). The illness perception dimensions of Concern and Emotional Response were independently associated with smoking. Differences in illness perceptions enhance our understanding of smoking among CHD survivors and may guide interventions promoting positive health behaviors. The protocol for the study from which the present analyses were conducted was recorded at ClinicalTrials.gov: NCT02150603.

The pulmonary vascular bed in patients with functionally univentricular physiology and a Fontan circulation.

Fontan palliation represents one of the most remarkable surgical advances in the management of individuals born with functionally univentricular physiology. The operation secures adult survival for all but a few with unfavourable anatomy and/or physiology. Inherent to the physiology is passive transpulmonary blood flow, which produces a vulnerability to adequate filling of the systemic ventricle at rest and during exertion. Similarly, the upstream effects of passive flow in the lungs are venous congestion and venous hypertension, especially marked during physical activity. The pulmonary vascular bed has emerged as a defining character on the stage of Fontan circulatory behaviour and clinical outcomes. Its pharmacologic regulation and anatomic rehabilitation therefore seem important strategic therapeutic targets. This review seeks to delineate the important aspects of pulmonary artery development and maturation in functionally univentricular physiology patients, pulmonary artery biology, pulmonary vascular reserve with exercise, and pulmonary artery morphologic and pharmacologic rehabilitation.

Lessons learnt from COVID-19 in adult congenital heart patient in Tehran: a survey-based study of prevention, exposure, susceptibility, and outcomes.

BACKGROUND: COVD-19 pandemic has overwhelmed many healthcare systems worldwide. Underlying cardiovascular disease predisposes to greater disease susceptibility and more complications including mortality. Such data is unverified in adults with congenital heart disease (ACHD). The aim of the study is to report the Tehran experience with respect to preventative self-care measures, disease exposure, susceptibility, and outcomes after COVD-19 infection in ACHD patients. METHODS: A telephone-based survey was conducted in ACHD patients, focusing on new-onset symptoms that might indicate COVID-19 infection, prevention measures, confirmed infection rates, and outcomes. RESULTS: Three-hundred and nine ACHD patients, with a mean age of 29.13 years (range from 14 to 72 years, SD = 10.64), and 170 (55%) women were assessed. The majority (86.7%) had moderate or complex ACHD. Two-thirds (67.3%) of the patients practiced high-level preventative self-care measures. After community exposure, 33.3% developed COVID-19, and after household exposure, 43.7% developed COVID-19. There was only one mortality in a post-operative patient. Thirty-seven patients (12%) reported new symptoms including cough (10%), fatigue (8%), fever (7%), and new dyspnoea (6.5%). Amongst 18 (6%) with confirmed COVID-19, there was only 1 mortality in a post-operative patient. Age (adjusted OR = 1.19, 95% CI: 1.07-1.31, p = 0.001), contact with confirmed COVID-19 cases (adjusted OR = 59.34, 95% CI: 3.68-955.10, p = 0.004) were independently associated with COVID-19 infection. CONCLUSIONS: Mortality risk associated with COVID-19 infection in ACHD patients with moderate or severe disease appears to be relatively low, similar to the general population. Such risk appears to act through conventional risk factors, and in this cohort, we demonstrated age as a significant risk factor in addition to exposure to the development of COVID-19 infection. Preventative self-care measures are a potentially significant and impactful intervention target for intervention and for improving outcomes.

Dynamic exercise changes in venous pressure and liver stiffness in Fontan patients: effects of Treprostinil.

BACKGROUND: Systemic venous hypertension and low cardiac output are believed to be important mediators of liver injury after the Fontan procedure. Pulmonary vasodilators have the potential to improve such haemodynamics. The aim of this study was to assess the acute effects of exercise on liver stiffness and venous pressures and to assess the impact of inhaled Treprostinil on this response. METHODS: In this prospective, double-blind, placebo-controlled, crossover trial, 14 patients with a Fontan circulation were randomised to inhalation of placebo and Treprostinil. Incremental and constant work rate exercise tests were performed to assess the effect of Treprostinil on exercise tolerance. Venous pressures were measured throughout and liver stiffness at rest and immediately after peak exercise. RESULTS: Mean age was 27.8 ± 7.9 years and 66% were females. Exercise acutely increased liver stiffness by 30% (mean shear wave speed: 2.38 ± 0.71 versus 2.89 ± 0.51 ms, p = 0.02). Peripheral venous pressures increased acutely during both incremental (12.1 ± 2.4 versus 22.6 ± 8.0 mmHg, p < 0.001) and constant work rate exercise (12.5 ± 2.5 versus 23.4 ± 5.2 mmHg, p < 0.001). Overall, Treprostinil failed to attenuate exercise-induced increases in liver stiffness. Compared with placebo, Treprostinil did not significantly impact venous pressure responses, VO2peak, nor exercise endurance times. CONCLUSIONS: Peripheral venous pressure increased acutely during exercise by an average of 88% above baseline and was not altered by administration of inhaled Treprostinil. Liver stiffness measured immediately post-exercise increased acutely by an average of 30%, with no attenuation following Treprostinil inhalation.

Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association.

It has been 50 years since Francis Fontan pioneered the operation that today bears his name. Initially designed for patients with tricuspid atresia, this procedure is now offered for a vast array of congenital cardiac lesions when a circulation with 2 ventricles cannot be achieved. As a result of technical advances and improvements in patient selection and perioperative management, survival has steadily increased, and it is estimated that patients operated on today may hope for a 30-year survival of >80%. Up to 70 000 patients may be alive worldwide today with Fontan circulation, and this population is expected to double in the next 20 years. In the absence of a subpulmonary ventricle, Fontan circulation is characterized by chronically elevated systemic venous pressures and decreased cardiac output. The addition of this acquired abnormal circulation to innate abnormalities associated with single-ventricle congenital heart disease exposes these patients to a variety of complications. Circulatory failure, ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia, protein-losing enteropathy, and plastic bronchitis are potential complications of the Fontan circulation. Abnormalities in body composition, bone structure, and growth have been detected. Liver fibrosis and renal dysfunction are common and may progress over time. Cognitive, neuropsychological, and behavioral deficits are highly prevalent. As a testimony to the success of the current strategy of care, the proportion of adults with Fontan circulation is increasing. Healthcare providers are ill-prepared to tackle these challenges, as well as specific needs such as contraception and pregnancy in female patients. The role of therapies such as cardiovascular drugs to prevent and treat complications, heart transplantation, and mechanical circulatory support remains undetermined. There is a clear need for consensus on how best to follow up patients with Fontan circulation and to treat their complications. This American Heart Association statement summarizes the current state of knowledge on the Fontan circulation and its consequences. A proposed surveillance testing toolkit provides recommendations for a range of acceptable approaches to follow-up care for the patient with Fontan circulation. Gaps in knowledge and areas for future focus of investigation are highlighted, with the objective of laying the groundwork for creating a normal quality and duration of life for these unique individuals.

Effect of Viscoelasticity on Arterial-Like Pulsatile Flow Dynamics and Energy.

Time-dependent arterial wall property is an important but difficult topic in vascular mechanics. Hysteresis, which appears during the measurement of arterial pressure-diameter relationship through a cardiac cycle, has been used to indicate time-dependent mechanics of arteries. However, the cause-effect relationship between viscoelastic (VE) properties of the arterial wall and hemodynamics, particularly the viscous contribution to hemodynamics, remains challenging. Herein, we show direct comparisons between elastic (E) (loss/storage < 0.1) and highly viscoelastic (loss/storage > 0.45) conduit structures with arterial-like compliance, in terms of their capability of altering pulsatile flow, wall shear, and energy level. Conduits were made from varying ratio of vinyl- and methyl-terminated poly(dimethylsiloxane) and were fit in a mimetic circulatory system measuring volumetric flow, pressure, and strain. Results indicated that when compared to elastic conduits, viscoelastic conduits attenuated lumen distension waveforms, producing an average of 11% greater cross-sectional area throughout a mimetic cardiac cycle. In response to such changes in lumen diameter strain, pressure and volumetric flow waves in viscoelastic conduits decreased by 3.9% and 6%, respectively, in the peak-to-peak amplitude. Importantly, the pulsatile waveforms for both diameter strain and volumetric flow demonstrated greater temporal alignment in viscoelastic conduits due to pulsation attenuation, resulting in 25% decrease in the oscillation of wall shear stress (WSS). We hope these findings may be used to further examine time-dependent arterial properties in disease prognosis and progression, as well as their use in vascular graft design.

Healthcare system inputs and patient-reported outcomes: a study in adults with congenital heart defect from 15 countries.

BACKGROUND: The relationship between healthcare system inputs (e.g., human resources and infrastructure) and mortality has been extensively studied. However, the association between healthcare system inputs and patient-reported outcomes remains unclear. Hence, we explored the predictive value of human resources and infrastructures of the countries' healthcare system on patient-reported outcomes in adults with congenital heart disease. METHODS: This cross-sectional study included 3588 patients with congenital heart disease (median age = 31y; IQR = 16.0; 52% women; 26% simple, 49% moderate, and 25% complex defects) from 15 countries. The following patient-reported outcomes were measured: perceived physical and mental health, psychological distress, health behaviors, and quality of life. The assessed inputs of the healthcare system were: (i) human resources (i.e., density of physicians and nurses, both per 1000 people) and (ii) infrastructure (i.e., density of hospital beds per 10,000 people). Univariable, multivariable, and sensitivity analyses using general linear mixed models were conducted, adjusting for patient-specific variables and unmeasured country differences. RESULTS: Sensitivity analyses showed that higher density of physicians was significantly associated with better self-reported physical and mental health, less psychological distress, and better quality of life. A greater number of nurses was significantly associated with better self-reported physical health, less psychological distress, and less risky health behavior. No associations between a higher density of hospital beds and patient-reported outcomes were observed. CONCLUSIONS: This explorative study suggests that density of human resources for health, measured on country level, are associated with patient-reported outcomes in adults with congenital heart disease. More research needs to be conducted before firm conclusions about the relationships observed can be drawn. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02150603. Registered 30 May 2014.

Probenecid Improves Cardiac Function in Subjects with a Fontan Circulation and Augments Cardiomyocyte Calcium Homeostasis.

Subjects with functionally univentricular circulation who have completed staged single ventricle palliation, with the final stage culminating in the Fontan procedure, are often living into adulthood. However, high morbidity and mortality remain prevalent in these patients, as diastolic and systolic dysfunction of the single systemic ventricle are linked to Fontan circulatory failure. We presently investigated the effects of probenecid in post-Fontan patients. Used for decades for the treatment of gout, probenecid has been shown in recent years to positively influence cardiac function via effects on the Transient Receptor Potential Vanilloid 2 (TRPV2) channel in cardiomyocytes. Indeed, we observed that probenecid improved cardiac function and exercise performance in patients with a functionally univentricular circulation. This was consistent with our findings from a retrospective cohort of patients with single ventricle physiology where TRPV2 expression was increased. Experiments in isolated cardiomyocytes associated these positive actions to augmentation of diastolic calcium homeostasis.

Advance care planning and palliative care in ACHD: the healthcare providers' perspective.

BACKGROUND: Advance care planning and palliative care are gaining recognition as critical care components for adults with CHD, yet these often do not occur. Study objectives were to evaluate ACHD providers' 1) comfort managing patients' physical symptoms and psychosocial needs and 2) perspectives on the decision/timing of advance care planning initiation and palliative care referral. METHODS: Cross-sectional study of ACHD providers. Six hypothetical patients were described in case format, followed by questions regarding provider comfort managing symptoms, initiating advance care planning, and palliative care referral. RESULTS: Fifty providers (72% physicians) completed surveys. Participants reported low levels of personal palliative care knowledge, without variation by gender, years in practice, or prior palliative care training. Providers appeared more comfortable managing physical symptoms and discussing prognosis than addressing psychosocial needs. Providers recognised advance directives as important, although the percentage who would initiate advance care planning ranged from 18 to 67% and referral to palliative care from 14 to 32%. Barriers and facilitators to discussing advance care planning with patients were identified. Over 20% indicated that advance care planning and end-of-life discussions are best initiated with the development of at least one life-threatening complication/hospitalisation. CONCLUSIONS: Providers noted high value in advance directives yet were themselves less likely to initiate advance care planning or refer to palliative care. This raises the critical questions of when, how, and by whom discussion of these important matters should be initiated and how best to support ACHD providers in these endeavours.

Lymphopenia in adults after the Fontan operation: prevalence and associations.

Lymphopenia is common in adults who have had a Fontan operation although its aetiology and clinical implications remain unknown. Previous work suggests an association between lymphopenia and both liver disease and splenomegaly. The objective of this study was to assess the prevalence of lymphopenia in adults with a Fontan circulation and evaluate its associations with risk factors and clinical outcomes. Using a retrospective cohort study design, we studied 73 adult Fontan patients (age 25.0 ± 8.4 years) who had a complete blood count and abdominal imaging performed. Patients with protein-losing enteropathy were excluded. Clinical data were extracted from hospital records. The mean white blood cell count was 6580 ± 220/ml with a mean lymphocyte count of 1223 ± 508/ml. Lymphopenia, defined as lymphocyte count <1000/ml, was present in 23 (32%) patients. Patients with lymphopenia had a lower total white blood cell count (5556 ± 2517 versus 7136 ± 1924/ml, p = 0.009) and a lower platelet count (162 ± 69 versus 208 ± 69 k/ml, p = 0.008). Lymphopenia was also associated with findings of portal hypertension, including splenomegaly (36 versus 14%, p = 0.04), varices (22 versus 6%, p = 0.04), and ascites (39 versus 14%, p = 0.02). Lymphopenia did not correlate with any cardiac imaging, haemodynamic or exercise testing variables. In conclusion, lymphopenia is common in adult Fontan patients and is associated with markers of portal hypertension. Larger studies are needed to better define the relationship between lymphopenia and clinical outcomes.

Creatinine versus cystatin C to estimate glomerular filtration rate in adults with congenital heart disease: Results of the Boston Adult Congenital Heart Disease Biobank.

BACKGROUND: Glomerular filtration rate is a key physiologic variable with a central role in clinical decision making and a strong association with prognosis in diverse populations. Reduced estimated glomerular filtration rate (eGFR) is common among adults with congenital heart disease (ACHD). METHODS: We conducted a prospective cohort study of outpatient ACHD ≥18 years old seen in 2012-2017. Creatinine and cystatin C were measured; eGFR was calculated using either the creatinine or cystatin C Chronic Kidney Disease-Epidemiology Collaboration equation (CKD-EPICr and CKD-EPICysC, respectively). Survival analysis was performed to define the relationship between eGFR and both all-cause mortality and a composite outcome of death or nonelective cardiovascular hospitalization. RESULTS: Our cohort included 911 ACHD (39 ±â€¯14 years old, 49% female). Mean CKD-EPICr and CKD-EPICysC were similar (101 ±â€¯20 vs 100 ±â€¯23 mL/min/1.73 m2), but CKD-EPICr estimates were higher for patients with a Fontan circulation (n = 131, +10 ±â€¯19 mL/min/1.73 m2). After mean follow-up of 659 days, 128 patients (14.1%) experienced the composite outcome and 31 (3.4%) died. CKD-EPICysC more strongly predicted all-cause mortality (eGFR <60 vs >90 mL/min/1.73 m2: CKD-EPICysC unadjusted HR = 20.2 [95% CI 7.6-53.1], C-statistic = 0.797; CKD-EPICr unadjusted HR = 4.6 [1.7-12.7], C-statistic = 0.620). CKD-EPICysC independently predicted the composite outcome, whereas CKD-EPICr did not (CKD-EPICysC adjusted HR = 3.0 [1.7-5.3]; CKD-EPICr adjusted HR = 1.5 [0.8-3.1]). Patients reclassified to a lower eGFR category by CKD-EPICysC, compared with CKD-EPICr, were at increased risk for the composite outcome (HR = 2.9 [2.0-4.3], P < .0001); those reclassified to a higher eGFR class were at lower risk (HR = 0.5 [0.3-0.9], P = .03). CONCLUSIONS: Cystatin C-based eGFR more strongly predicts clinical events than creatinine-based eGFR in ACHD. Creatinine-based methods appear particularly questionable in the Fontan circulation.

Noninvasive Imaging in Adult Congenital Heart Disease.

Multimodality cardiovascular imaging plays a central role in caring for patients with congenital heart disease (CHD). CHD clinicians and scientists are interested not only in cardiac morphology but also in the maladaptive ventricular responses and extracellular changes predisposing to adverse outcomes in this population. Expertise in the applications, strengths, and pitfalls of these cardiovascular imaging techniques as they relate to CHD is essential. The purpose of this article is to provide an overview of cardiovascular imaging in CHD. We focus on the role of 3 widely used noninvasive imaging techniques in CHD-echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography. Consideration is given to the common goals of cardiac imaging in CHD, including assessment of structural and residual heart disease before and after surgery, quantification of ventricular volume and function, stress imaging, shunt quantification, and tissue characterization. Extracardiac imaging is highlighted as an increasingly important aspect of CHD care.

MRI measured liver stiffness does not predict focal liver lesions after the Fontan operation.

BACKGROUND: Focal liver lesions are common in children and adults after Fontan procedures. OBJECTIVE: To explore the relationship between liver shear stiffness, using magnetic resonance (MR) elastography, and the presence of focal liver lesions in patients after Fontan procedures (total cavopulmonary anastomosis). MATERIALS AND METHODS: The retrospective study was approved by the institutional review board and the requirement for informed consent was waived. By searching institutional electronic medical records, we identified all patients with a history of Fontan palliation of congenital heart disease who had undergone same-day liver MR elastography and liver MRI without and with intravenous contrast material between January 2012 and December 2017. Using imaging reports, patients were placed into two groups: 1) no focal liver lesions and 2) one or more focal liver lesions. Patient age, sex, mean liver shear stiffness (kPa) and maximum single anatomical level liver shear stiffness (kPa) were recorded. The Mann-Whitney U test was used to compare age and liver stiffness between groups, while the Fisher exact test was used to assess the impact of gender on liver lesions. RESULTS: Forty-eight patients met study inclusion criteria; 33 (69%) had one or more focal liver lesions. The median age was 20.0 years (IQR [interquartile range]: 10.8-29.1 years) for patients without liver lesions and 19.9 years (IQR: 17.2-27.0 years) for patients with liver lesions (P=0.49). Eleven of 21 male patients (52.4%) had liver lesions compared to 22 of 27 female patients (81.5%) (P=0.058). Mean (4.62 kPa [IQR: 4.10-5.59 kPa] vs. 4.10 kPa [IQR: 3.44-4.80 kPa]; P=0.02) and maximum (5.53 kPa [IQR: 4.64-6.56 kPa] vs. 4.50 kPa [IQR: 3.82-5.35 kPa]; P=0.009) liver stiffness were significantly higher in patients without liver lesions as compared to patients with liver lesions. CONCLUSION: Our study demonstrated a significant negative association between focal liver lesions and increased liver stiffness in patients following Fontan procedures.

Surveillance Testing and Preventive Care After Fontan Operation: A Multi-Institutional Survey.

More children with single ventricle heart disease are surviving after Fontan surgery. This circulation has pervasive effects on multiple organ systems and has unique modes of failure. Many centers have created multidisciplinary programs to care for these patients. Our aim was to survey such programs to better understand current approaches to care. We hypothesized that significant variability in surveillance testing strategy would be present. Eleven academic institutions with established Fontan care programs performing a combined estimated 300 Fontan surgeries per year, with a total population of 1500-2000 Fontan patients, were surveyed using a REDCap survey regarding surveillance testing and basic practice philosophies. Fontan care programs were structured both as consultative services (64%) and as the primary clinical team (9%). Electrocardiograms (73%) and echocardiograms (64%) were most commonly obtained annually. Serum studies, including complete blood count (73%), complete metabolic panel (73%), and Brain-type natriuretic peptide (54%), were most commonly obtained annually. Hepatic testing consisted of liver ultrasound in most centers, obtained biennially (45%) or > every 2 years (45%). Liver biopsy was not routinely recommended (54%). Neurodevelopmental outcomes were assessed at most institutions (54%), with a median frequency of every 3-4 years. There is considerable variability in the surveillance testing regimen and management strategy after a Fontan procedure at surveyed programs. There is an urgent need for surveillance guidelines to reduce variability, define quality metrics, streamline collaborative practice, and prospective research to better understand the complex adaptations of the body to Fontan physiology.