Anesthesia for Combined Heart-Liver Transplantation: A Narrative Review.

In 1984, 21 years after the first liver transplantation, Thomas Starzl achieved a milestone by performing the world's first combined heart-liver transplantation. While still uncommon, the practice of combined heart-liver transplants is on the rise globally. In this review, the authors delve into the current literature on this procedure, highlighting the evolving landscape and key considerations for anesthesiologists. Over the years, there has been a remarkable increase in the number of combined heart-liver transplantations conducted worldwide. This surge is largely attributed to the growing population of adult survivors with single-ventricle physiology, palliated with a Fontan procedure, who later present with late Fontan failure and Fontan-associated liver disease. Research indicates that combined heart-liver transplantation is an effective treatment option, with reported outcomes comparable with isolated heart or liver transplants. Managing anesthesia during a combined heart-liver transplant procedure is challenging, especially in the context of underlying Fontan physiology. International experience in this field remains somewhat limited, with most techniques derived from expert opinions or experiences with single-organ heart and liver transplants. These procedures are highly complex and performed infrequently. As the number of combined heart-liver transplants continues to rise globally, there is a growing need for clear guidance on periprocedural surgical and anesthetic management. Anesthesiologists overseeing these patients must consider multiple factors, balancing various comorbidities with significant hemodynamic and metabolic shifts. An increase in (multicenter) studies focusing on specific interventions to enhance patient and organ outcomes is anticipated in the coming years.

Preterm Birth Is Associated With Adverse Cardiac Remodeling and Worse Outcomes in Patients With a Functional Single Right Ventricle.

OBJECTIVE: To assess the effects of preterm birth on cardiac structure and function and transplant-free survival in patients with hypoplastic left heart syndrome and associated anomalies throughout the staged palliation process. STUDY DESIGN: Data from the Single Ventricle Reconstruction trial were used to assess the impact of prematurity on echocardiographic measures at birth, Norwood, Stage II, and 14 months in 549 patients with a single functional right ventricle. Medical history was recorded once a year using medical records or telephone interviews. Cox regression models were applied to analyze transplant-free survival to age 6 years. Causal mediation analysis was performed to estimate the mediating effect of birth weight within this relationship. RESULTS: Of the 549 participants, 64 (11.7%) were born preterm. Preterm-born participants had lower indexed right ventricle end-diastolic volumes at birth but higher volumes than term-born participants by age 14 months. Preterm-born participants had an increased risk of death or heart transplantation from birth to age 6 years, with an almost linear increase in the observed risk as gestational age decreased below 37 weeks. Of the total effect of preterm birth on transplant-free survival, 27.3% (95% CI 2.5-59.0%) was mediated through birth weight. CONCLUSIONS: Preterm birth is associated with adverse right ventricle remodeling and worse transplant-free survival throughout the palliation process, in part independently of low birth weight. Further investigation into this vulnerable group may allow development of strategies that mitigate the impact of prematurity on outcomes in patients with hypoplastic left heart syndrome.

Three-dimensional printing, holograms, computational modelling, and artificial intelligence for adult congenital heart disease care: an exciting future.

Congenital heart disease (CHD) is often comprised of complex three-dimensional (3D) anatomy that must be well understood to assess the pathophysiological consequences and guide therapy. Thus, detailed cardiac imaging for early detection and planning of interventional and/or surgical treatment is paramount. Advanced technologies have revolutionized diagnostic and therapeutic practice in CHD, thus playing an increasing role in its management. Traditional reliance on standard imaging modalities including echocardiography, cardiac computed tomography (CT) and magnetic resonance imaging (MRI) has been augmented by the use of recent technologies such as 3D printing, virtual reality, augmented reality, computational modelling, and artificial intelligence because of insufficient information available with these standard imaging techniques. This has created potential opportunities of incorporating these technologies into routine clinical practice to achieve the best outcomes through delivery of personalized medicine. In this review, we provide an overview of these evolving technologies and a new approach enabling physicians to better understand their real-world application in adult CHD as a prelude to clinical workflow implementation.

A new score for life-threatening ventricular arrhythmias and sudden cardiac death in adults with transposition of the great arteries and a systemic right ventricle.

AIMS: To investigate the incidence of major adverse ventricular arrhythmias and related events (MAREs) and to develop a stratification tool predicting MAREs in adults with a systemic right ventricle (sRV). METHODS AND RESULTS: In a multicentre approach, all adults (≥16 years old) with a sRV undergoing follow-up between 2000 and 2018 were identified. The incidence of MAREs, defined as sudden cardiac death, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator (ICD) therapy, was analysed. The association of MAREs with clinical, electrical, and echocardiographic parameters was evaluated. A total of 1184 patients (median age 27.1 years; interquartile range 19.9-34.9 years; 59% male; 70% with atrial switch repair for D-transposition of the great arteries) were included. The incidence of MAREs was 6.3 per 1000 patient-years. On multivariate analysis, age, history of heart failure, syncope, QRS duration, severe sRV dysfunction and at least moderate left ventricular outflow tract obstruction were retained in the final model with a C-index of 0.78 [95% confidence interval (CI) 0.72-0.83] and a calibration slope of 0.93 (95% CI 0.64-1.21). For every five ICDs implanted in patients with a 5-year MARE risk >10%, one patient may potentially be spared from a MARE. CONCLUSION: Sudden cardiac death remains a devastating cause of death in a contemporary adult cohort with a sRV. A prediction model based on clinical, electrocardiographic, and echocardiographic parameters was devised to estimate MARE risk and to identify high-risk patients who may benefit from primary prevention ICD implantation.

Sudden cardiac death in congenital heart disease.

Sudden cardiac death (SCD) accounts for up to 25% of deaths in patients with congenital heart disease (CHD). To date, research has largely been driven by observational studies and real-world experience. Drawbacks include varying definitions, incomplete taxonomy that considers SCD as a unitary diagnosis as opposed to a terminal event with diverse causes, inconsistent outcome ascertainment, and limited data granularity. Notwithstanding these constraints, identified higher-risk substrates include tetralogy of Fallot, transposition of the great arteries, cyanotic heart disease, Ebstein anomaly, and Fontan circulation. Without autopsies, it is often impossible to distinguish SCD from non-cardiac sudden deaths. Asystole and pulseless electrical activity account for a high proportion of SCDs, particularly in patients with heart failure. High-quality cardiopulmonary resuscitation is essential to improve outcomes. Pulmonary hypertension and CHD complexity are associated with lower likelihood of successful resuscitation. Risk stratification for primary prevention implantable cardioverter-defibrillators (ICDs) should consider the probability of SCD due to a shockable rhythm, competing causes of mortality, complications of ICD therapy, and associated costs. Risk scores to better estimate probabilities of SCD and CHD-specific guidelines and consensus-based recommendations have been proposed. The subcutaneous ICD has emerged as an attractive alternative to transvenous systems in those with vascular access limitations, prior device infections, intra-cardiac shunts, or a Fontan circulation. Further improving SCD-related outcomes will require a multidimensional approach to research that addresses disease processes and triggers, taxonomy to better reflect underlying pathophysiology, high-risk features, early warning signs, access to high-quality cardiopulmonary resuscitation and specialized care, and preventive therapies tailored to underlying mechanisms.

Gothenburg Empowerment Scale (GES): psychometric properties and measurement invariance in adults with congenital heart disease from Belgium, Norway and South Korea.

BACKGROUND: Patient empowerment is associated with improvements in different patient-reported and clinical outcomes. However, despite being widely researched, high quality and theoretically substantiated disease-generic measures of patient empowerment are lacking. The few good instruments that are available have not reported important psychometric properties, including measurement invariance. The aim of this study was to assess the psychometric properties of the 15-item Gothenburg Empowerment Scale (GES), with a particular focus on measurement invariance of the GES across individuals from three countries. METHODS: Adults with congenital heart disease from Belgium, Norway and South Korea completed the GES and other patient-reported outcomes as part of an international, cross-sectional, descriptive study called APPROACH-IS II. The scale's content (missing data) and factorial validity (confirmatory factor analyses), measurement invariance (multi-group confirmatory factor analyses), responsiveness (floor and ceiling effects) and reliability (internal consistency) were assessed. RESULTS: Content validity, responsiveness and reliability were confirmed. Nonetheless, metric but not scalar measurement invariance was supported when including the three countries, possibly because the scale performed differently in the sample from South Korea. A second set of analyses supported partial scalar invariance for a sample that was limited to Norway and Belgium. CONCLUSION: Our study offers preliminary evidence that GES is a valid and reliable measure of patient empowerment in adults with congenital heart disease. However, cross-country comparisons must be made with caution, given the scale did not perform equivalently across the three countries.

Iron Deficiency Is Associated With Impaired Biventricular Reserve and Reduced Exercise Capacity in Patients With Unexplained Dyspnea.

BACKGROUND: Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear. METHODS AND RESULTS: Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography in a tertiary care dyspnea clinic. ID was defined as ferritin of <300 µg/L and a transferrin saturation of <20% and its impact on peak oxygen uptake (peakVO2), biventricular response to exercise, and peripheral oxygen extraction was assessed. Of 272 patients who underwent cardiopulmonary exercise testing with echocardiography, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO2 (14.6 ± 7.6 mL/kg/minvs 17.8 ± 8.8 mL/kg/min; P = .009) and maximal workload (89 ± 50 watt vs 108 ± 56 watt P = .047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (P < .05) and depressed RV function by tricuspid s' (P = .004), tricuspid annular plane systolic excursion (P = .034), and RV end-systolic pressure-area ratio (P = .038), with more RV-pulmonary artery uncoupling measured by tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure ratio (P = .023). RV end-systolic pressure-area ratio change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09 ± 0.72 mm Hg/cm2 vs 2.58 ± 1.14 mm Hg/cm2; P < .001). ID was associated with impaired peripheral oxygen extraction (peakVO2/peak cardiac output; P = .036). Cardiopulmonary exercise testing with echocardiography resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio of >14, with equal distribution in patients with (28.6%) or without ID (25.4%, P = .611). None of these findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea. CONCLUSIONS: In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with decreased exercise capacity, diminished biventricular contractile reserve, and decreased peripheral oxygen extraction.

Assessment of long-term cardiac adaptation in adult patients with type II atrial septal defect : A cardiovascular magnetic resonance (CMR) study.

OBJECTIVES: In type II atrial septal defect (ASD) patients, the left-to-right (LR) shunt causes adaptation of the heart and circulation. The study objective was to evaluate with cardiovascular magnetic resonance imaging (CMR) the impact of LR shunt on left (LV) and right ventricular (RV) volumes, function, and myocardial strain. METHODS: Thirty-five patients (42 ± 17 years, 17 male) were compared to a control group (n = 40). Cine imaging was used to calculate ventricular volumes and ejection fraction (EF), global longitudinal (GLS) and circumferential strain (GCS), and longitudinal free wall (FWS) and interventricular septal (IVS) strain. Phase-contrast imaging was used to calculate pulmonary flow to systemic flow ratio (Qp/Qs). RESULTS: The LR shunt (Qp/Qs 2.2 ± 0.6) resulted in larger RV end-diastolic volume (EDVi) (152 ± 42 vs 82 ± 11 ml/m2), lower LV EDVi (72 ± 16 vs 83 ± 9 ml/m2), and higher RV/LV EDVi ratio (2.2 ± 0.5 vs 1.0 ± 0.1) than controls (all p < 0.001). Functionally, stroke volumes were larger in RV and lower in LV (both p < 0.001) with a strong trend toward lower RV EF in patients (p = 0.08). The LR shunt negatively impacted RV GLS (p = 0.03) but not RV GCS. Longitudinal IVS but not RV FWS were significantly lower in patients, i.e., p < 0.001, of longitudinal IVS. Shunt severity correlated with RV size and stroke volume, right atrial size, and pulmonary trunk diameter (all p < 0.001), but not with functional nor strain parameters. CONCLUSION: Long-term cardiac adaptation in ASD patients, with RV overfilling and LV underfilling, has a negative impact on systolic RV performance, a phenomenon which likely can be attributed to longitudinal dysfunction of the interventricular septum. KEY POINTS: • An LR shunt in type II ASD patients causes cardiac remodeling characterized by RV overfilling and conversely underfilling of the left ventricle. • At the long term, there is evidence of systolic dysfunction of the right ventricle in this group of patients. • Septal dysfunction underlies the observed impairment in RV function.

Providing a framework of principles for conceptualising the Fontan circulation.

The Fontan operation remains the final palliation for thousands of patients with complex congenital heart disease. By creating a Fontan circuit, control of cardiac output and congestion is wrested away from the ventricle and new haemodynamic forces take control. Understanding how to control the flow in the Fontan circuit will enable clinicians to improve patient management and possibly prevent future complications. CONCLUSION: This review proposes a framework of principles to conceptualise the functionality and limitations of a Fontan circulation.

Management of acute heart failure in adult patients with congenital heart disease.

Heart failure is an increasing reason for hospitalization and the leading cause of death in patients with adult congenital heart disease (ACHD). Recently, the European Society of Cardiology and the American Heart Association published consensus documents on the management of chronic heart failure in ACHD patients. However, little data and/or guidelines are available for the management of (sub)acute heart failure. The ACHD population is heterogeneous by definition and often has complex underlying anatomy, which could pose a challenge to the physician confronted with the ACHD patient in (sub)acute heart failure. Recognizing the underlying anatomy and awareness of the possible complications related would result in better treatment, avoid unnecessary delays, and improve outcomes of the ACHD patient with (sub)acute heart failure. This review focuses on the management of (sub)acute heart failure in ACHD with specific attention to lesion-specific issues.

Long-Term Outcome of Patients with Perimembranous Ventricular Septal Defect: Results from the Belgian Registry on Adult Congenital Heart Disease.

OBJECTIVES: Studies evaluating the long-term outcome of adults with ventricular septal defect (VSD) are important to inform patients about prognosis. This study investigated the long-term outcome of patients with perimembranous VSD (pmVSD) followed in the Belgian Registry on Adult Congenital Heart Disease. METHODS: All pmVSD patients in the registry were analyzed. RESULTS: Two hundred and sixty-six patients were studied. Fifteen patients had Eisenmenger syndrome. One hundred and seventy-three had isolated pmVSD and 78 had pmVSD with concomitant lesions. Of the patients with isolated pmVSD, 52% were male, median age was 29 years (IQR 24-35 years) and median follow-up duration was 18 years (IQR 10-25 years). Fifty-three (31%) patients underwent VSD closure and 10 (19%) had a residual shunt. Most (93%) patients were in NYHA class I. No patients died. Two (4%) patients developed atrial arrhythmia and 2 (4%) required pacemaker implantation. Seven (14%) developed left ventricular outflow tract obstruction (LVOTO). In the unrepaired pmVSD group, 4 developed endocarditis. In the entire group, moderate or severe aortic regurgitation (AR) occurred in 9 (5%) patients. CONCLUSIONS: Long-term survival in patients with isolated pmVSD was not uneventful. Moderate or severe AR might develop and endocarditis occurred in patients without VSD repair. Complications after VSD closure included atrial arrhythmia, pacemaker implantation and LVOTO.

Prognostic significance of improvement in right ventricular systolic function during cardiac resynchronization therapy.

Objectives There is conflicting evidence concerning the role of right ventricular (RV) systolic dysfunction in the long-term clinical outcome after cardiac resynchronization therapy (CRT). Therefore we aimed to assess evolution of RV systolic function during CRT, covariates associated with its improvement, and its impact on outcome. Methods and results All CRT device implantations (Jan 2009-Dec 2011) in our institution were reviewed. Records of 69 patients (25% female, mean age 62.8 ± 9.2 years, mean left ventricular (LV) ejection fraction 27 ± 8%) were analyzed. Baseline RV fractional area change (FAC) < 35% was present in 37 patients (54%). At one year, 24 of them (65%) improved in RV FAC. LV remodeling and mitral regurgitation were significantly associated with the likelihood of RV FAC improvement (OR 4.80, 95% CI 1.13-20.46, P = 0.034 and OR 0.32, 95% CI 0.12-0.89, P = 0.029, respectively). The composite endpoint of death or heart transplantation occurred in 23 patients (33%) over a mean follow-up of 2.8 ± 1.4 years. RV FAC at one year (HR 0.90, 95% CI 0.86-0.94, P < .001) was, independently of NYHA class and LV remodeling, associated with clinical outcome. Conclusions RV systolic function might improve during CRT. This seems mainly due to changed left-sided hemodynamics and LV remodeling. Good RV systolic function is independently related with better outcome.

Long-Term Follow-Up of Children with Heart Block Born from Mothers with Systemic Lupus Erythematosus: A Retrospective Study from the Database Pediatric and Congenital Heart Disease in University Hospitals Leuven.

BACKGROUND: Children from mothers with systemic lupus erythematosus are frequently born with congenital heart block. This study aimed at evaluating long-term outcome because long-term data are scarce. METHODS: In the database of pediatric and congenital heart disease (University Hospitals Leuven), 19 children from systemic lupus erythematosus mothers and who were born with or developed atrioventricular block were identified. All records were reviewed for disease course and outcome. RESULTS: Median follow-up time was 7 years (interquartile ranges [IQR] 4.5-13 years). One child had no heart block at birth and developed only a first-degree block during follow-up. One had a second-degree heart block and developed a complete heart block. Seventeen patients (89%) were born with a complete heart block. Seventeen patients (89%) needed a definitive pacemaker. In all, epicardial leads were used at first implantation. Eighty-two percent received their pacemaker in the first year of life. The first battery had a median lifetime of 5 years (IQR 3.5-5 years), the second 6 years (IQR 4.5-6.3 years), and the third 5 years (IQR 5-6 years). Note that 47% of patients needed a lead replacement due to lead problems. Only one pericardial tamponade after pacemaker implantation. No device or lead infections occurred. The left ventricular systolic function at latest follow-up was normal for all. No patients died. CONCLUSION: In children with heart block born from systemic lupus erythematosus mothers, an early need for pacemaker implantation was documented. The overall battery life was acceptable, but there was a high need for lead replacement. Complication rate was low. Late outcome was good.

Percutaneous closure of inter-atrial communications (atrial septal defect and patent foramen ovale): single-centre experience and mid-term follow-up.

BACKGROUND: Percutaneous closure of atrial septal defect (ASD) and patent foramen ovale (PFO) are increasingly being performed. Effective closure rate depends on the anatomy of the interatrial septum and the device used, but its relationship with outcome is poorly described. This study aimed at evaluating: (1) effective ASD and PFO closure rate, (2) factors related with effective closure rate, and (3) factors related with mid-term outcome. METHODS: All patients who underwent percutaneous ASD or PFO closure at Jessa Hospital Hasselt between April 2002 and February 2014 were enrolled. Closure rate was evaluated using consecutive contrast echocardiography studies. Adverse events were defined as a composite of all-cause mortality, hospitalization for heart failure, atrial arrhythmias and thrombo-embolic event. RESULTS: One-hundred and two patients (52 +/- 12 y, 42% male, 75 PFO and 27 ASD) were included in the study. Moderate residual shunt was present in 6% and 10% 6 years after ASD and PFO closure, respectively. The presence of an aneurysmatic interatrial septum was associated with residual shunt after PFO closure (HR 0.57 95% CI 0.33-0.96; P=0.031). Pulmonary hypertension (HR 1.09 95% CI 1.01-1.17; P=0.017) and a history of atrial arrhythmias in ASD (HR 4.28 95% CI 1.06-17.40; P=0.046) and age at closure (HR 1.09 95% CI 1.02-1.16; P=0.012) in PFO patients were related with adverse events. The highest rate of adverse events was observed after placement of a Helex Septal Occluder. Amplatzer and Occlutech devices yielded higher effective closure rates. CONCLUSIONS: Effective closure rates were acceptable 6 years after ASD and PFO closure. The presence of an aneurysmatic septum is associated with residual shunting after PFO closure. Pulmonary hypertension in ASD and older age at closure in PFO are associated with adverse outcome. Adverse events are more frequent with the Helex occluder and effective closure rate depends on the device used.

Right heart morphology in elevated pulmonary artery pressure: relationship between echocardiographic and right heart catheterization data.

BACKGROUND: When elevated pulmonary artery pressure (PAP) is assessed by echocardiography, right heart morphology is always considered. The goal of this study was to evaluate how right heart geometry changes with increasing right ventricular pressure load. SUBJECTS AND METHODS: Data from patients undergoing transthoracic echocardiography with subsequent right heart catheterization within a time period of 6 months were retrospectively analysed. First, Spearman-rho coefficients between mean PAP and right heart parameters were calculated. Second, the population was divided into tertiles according to mean PAP and Kruskal-Wallis variance analysis between variables was performed. RESULTS: Fifty-four patients (23 female, median age 77 years, IQ range 63-83) were selected. Mean PAP (median 27 mmHg, IQ range 24-36), right atrial (RA) dilatation (median 1, IQ range 0-2), tricuspid insufficiency (TI) severity (median 1.5, IQ range 0-2) and right ventricular (RV) dilatation (median 0, IQ range 0) were included. Significant correlations with mean PAP were found for RA dilatation (rho = 0.380; P = 0.005) and TI severity (rho = 0.294; P = 0.032). No correlation with RV dilatation could be shown (rho = 0.241; P = 0.081). Across the tertiles [(1) mean PAP 25 mmHg; (2) mean PAP 26-30 mmHg; (3) mean PAP > or = 31 mmHg)], variance analysis showed a significant increase in RA dilatation (P = 0.009) and TI severity (P = 0.040). No change in RV dilatation across groups was observed (P = 0.216). CONCLUSIONS: RA dilatation and TI severity significantly increase with increasing RV pressure load. No increase in RV dilatation was observed in the studied population. Hence, absence of RV dilatation does not exclude the presence of elevated PAP.

Predicting outcome after Fontan palliation: a single-centre experience, using simple clinical variables.

BACKGROUND: The Fontan procedure has become the procedure of choice for patients with one functional ventricle. Although perioperative mortality has decreased, late failure of the Fontan circulation remains a major concern. We aimed at (i) describing Fontan patient characteristics and (ii) identifying simple risk factors for outcome. METHODS: Seventy-three patients (median age 23 y (IQR 19-29 y), 60.3% male) were selected from the database of congenital heart defects. Followup data were collected. The primary end point was composed by death, resuscitation, or heart transplantation. RESULTS: The most frequently occurring defect was tricuspid atresia (41.1%). Twenty-five (34.2%) and 48 (65.8%) patients received an intra- and extracardiac conduit, respectively. Ten patients reached the primary end point (13.7%) after a median follow-up time of 16 years (IQR 14-19 y). NYHA classification (OR 63.0; 95% Cl 6.7-592.4; P < or =0.001), atrioventricular-valve regurgitation (OR 10.6; 95% Cl: 1.2-94.1; P = 0.034), ventricular function (OR 4.8; 95% Cl 1.7-13.7; P = 0.003), oxygen saturation (OR 0.7; 95% Cl 0.1-1.0; P = 0.002) and the presence (OR 8.6; 95% Cl 1.6-45.2; P = 0.011) or history of supraventricular arrhythmia (OR 6.7; 95% CI: 1.3-35.0; P = 0.025), all parameters gathered at the latest follow-up, were associated with outcome. An association was also found with the presence of an intracardiac conduit (OR 5.8; 95% Cl 1.4-25.1; P = 0.018), higher age at Fontan procedure (OR 1.2; 95% Cl 1.0-1.3; P = 0.007) and male gender (OR 0.2; 95% Cl 0.1-1.0; P = 0.047). CONCLUSIONS: Complications were not uncommon later after Fontan surgery. Several demographic and procedure-related data were associated with adverse outcome. Interestingly, the strongest correlation was found with clinical and basic echocardiographic characteristics at the latest follow-up.

Exercise catheterization in adults post-Fontan with normal and abnormal haemodynamic criteria: Insights into normal Fontan physiology.

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] >2 mmHg/L/min, and/or ΔPA/Δpulmonary flow >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 < 0.001) and PAWP were higher (21 [18-28] vs. 12 [8-14] mmHg, p < 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 < 0.001) and Qs response (67.3 [43.8-93.1] vs. 105.9 (82-118.5) % predicted, p < 0.001) than Group II. Exercise superior vena cava pressures were higher (16 [14-22.5] vs. 5.5 [3-7.3] mmHg, p < 0.001) and arterial oxygen saturation lower (89% [85-93] vs. 97% [96-98], p < 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 >20 mmHg and mean PA pressure >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.

Biomarkers in transposition of the great arteries after arterial switch operation: A pilot trial with deep phenotyping.

INTRODUCTION: Transposition of the great arteries (TGA) is a cyanotic congenital heart defect for which the arterial switch operation (ASO) is the preferred surgical repair. This study wanted to investigate whether a panel of biomarkers could identify morphologic as well as hemodynamic changes obtained by cardiac magnetic resonance (CMR). METHODS: Forty-four adult patients were included. Blood samples were collected to measure a broad range of biomarkers (galectin-3, ST2, GDF-15, PINP, ICTP, PIIINP, IGF-1, NT-proBNP, and hs-Tn). CMR was performed at rest and during exercise to assess cardiac function and morphology. Explorative statistics were performed between biomarker levels and CMR findings. RESULTS: All patients were asymptomatic. While galectin-3, GDF-15, and NT-proBNP levels were within normal ranges, increased ST2, PINP, PIIINP, and ICTP levels were found in 20.5%, 34.1%, 45.5%, and 27.3% of patients, respectively. Moreover, 3 and 2 patients, respectively, showed elevated IGF-1 and hs-Tn levels. Although the ejection fraction of both ventricles was within normal limits, impaired cardiac reserve was found in 20 and 25% of patients for left and right ventricle, respectively. CMR revealed no evidence of diffuse interstitial fibrosis, while 4 patients showed focal ischemic scarring. However, no significant associations between serum biomarkers and CMR data could be detected. CONCLUSION: The results suggest that in asymptomatic ASO-repaired TGA patients serum level biomarkers are elevated and that this increase is not associated with morphological changes nor with a decreased cardiac reserve. Further study with larger sample sizes is required to draw conclusions with greater confidence.