Clinical Presentation and Therapy of Tricuspid Atresia and Univentricular Heart.

Although the terms "single ventricle" and "univentricular heart" are frequently used to describe a variety of complex congenital heart defects, in fact, nearly all hearts have two ventricles, although one of the two may be too small to be functional. A better term for these hearts would therefore be "functional single ventricle."

Long-term outcomes of atrioventricular septal defect and single ventricle: A multicenter study.

OBJECTIVE: The study objective was to analyze survival and incidence of Fontan completion of patients with single-ventricle and concomitant unbalanced atrioventricular septal defect. METHODS: Data from 4 Dutch and 3 Belgian institutional databases were retrospectively collected. A total of 151 patients with single-ventricle atrioventricular septal defect were selected; 36 patients underwent an atrioventricular valve procedure (valve surgery group). End points were survival, incidence of Fontan completion, and freedom from atrioventricular valve reoperation. RESULTS: Median follow-up was 13.4 years. Cumulative survival was 71.2%, 70%, and 68.5% at 10, 15, and 20 years, respectively. An atrioventricular valve procedure was not a risk factor for mortality. Patients with moderate-severe or severe atrioventricular valve regurgitation at echocardiographic follow-up had a significantly worse 15-year survival (58.3%) compared with patients with no or mild regurgitation (89.2%) and patients with moderate regurgitation (88.6%) (P = .033). Cumulative incidence of Fontan completion was 56.5%, 71%, and 77.6% at 5, 10, and 15 years, respectively. An atrioventricular valve procedure was not associated with the incidence of Fontan completion. In the valve surgery group, freedom from atrioventricular valve reoperation was 85.7% at 1 year and 52.6% at 5 years. CONCLUSIONS: The long-term survival and incidence of Fontan completion in our study were better than previously described for patients with single-ventricle atrioventricular septal defect. A concomitant atrioventricular valve procedure did not increase the mortality rate or decrease the incidence of Fontan completion, whereas patients with moderate-severe or severe valve regurgitation at follow-up had a worse survival. Therefore, in patients with single-ventricle atrioventricular septal defect when atrioventricular valve regurgitation exceeds a moderate degree, the atrioventricular valve should be repaired.

Assessment of pressure-volume relations in univentricular hearts: Comparison of obtainment by real-time 3D echocardiography and mini pressure-wire with conductance technology.

OBJECTIVES: The gold standard to obtain pressure-volume relations (PVR) of the heart, the conductance technology (PVRCond), is rarely used in children. PVR can also be obtained by 3D-echocardiography volume data combined with simultaneously measured pressure data by a mini pressure-wire (PVR3DE). We sought to investigate the feasibility of both methods in patients with univentricular hearts and to compare them, including hemodynamic changes. METHODS: We studied 19 patients (age 2-29 years). PVR3DE and PVRCond were assessed under baseline conditions and stimulation with dobutamine. RESULTS: Obtaining PVR3DE was successful in all patients. Obtaining PVRCond was possible in 15 patients during baseline (79%) and in 12 patients under dobutamine (63%). Both methods showed that end-systolic elastance (Ees) and arterial elastance (Ea) increased under dobutamine and that Tau showed a statistically significant decrease. Intraclass correlation (95% confidence interval) showed moderate to good agreement between methods: Ees: 0.873 (0.711-0.945), Ea: 0.709 (0.336-0.873), Tau: 0.867 (0.697-0.942). Bland-Altman analyses showed an acceptable bias with wider limits of agreement: Ees: 1.63 mmHg/ml (-3.83-7.08 mmHg/ml), Ea: 0.53 mmHg/ml (-5.23-6.28 mmHg/ml), Tau: -0,76 ms (-10.73-9.21 ms). CONCLUSION: Changes of PVR-specific parameters under dobutamine stimulation were reflected in the same way by both methods. However, the absolute values for these parameters could vary between methods and, therefore, methods are not interchangeable. Obtaining PVR3DE in a single ventricle was easier, faster and more successful than PVRCond. PVR3DE provides a promising and needed alternative to the conductance technology for the assessment of cardiac function in univentricular hearts.

Total vascular resistance increases during volume-unloading in asymptomatic single ventricle patients.

OBJECTIVE: While the surgical stages of single ventricle (SV) palliation serve to separate pulmonary venous and systemic venous return, and to volume-unload the SV, staged palliation also results in transition from parallel to series circulation, increasing total vascular resistance. How this transition affects pressure loading of the SV is as yet unreported. METHODS: We performed a retrospective chart review of Stage I, II, and III cardiac catheterization (CC) and echocardiographic data from 2001-2017 in all SV pts, with focus on systemic, pulmonary, and total vascular resistance (SVR, PVR, TVR respectively). Longitudinal analyses were performed with log-transformed variables. Effects of SVR-lowering medications were analyzed using Wilcoxon rank-sum testing. RESULTS: There were 372 total patients who underwent CC at a Stage I (median age of 4.4 months, n=310), Stage II (median age 2.7 years, n = 244), and Stage III (median age 7.3 years, n = 113). Total volume loading decreases with progression to Stage III (P< 0.001). While PVR gradually increases from Stage II to Stage III, and SVR increases from Stage I to Stage III, TVR dramatically increases with progress towards series circulation. TVR was not affected by use of systemic vasodilator therapy. TVR, PVR, SVR, and CI did not correlate with indices of SV function at Stage III. CONCLUSIONS: TVR steadily increases with an increasing contribution from SVR over progressive stages. TVR was not affected by systemic vasodilator agents. TVR did not correlate with echo-based indices of SV function. Further studies are needed to see if modulating TVR can improve exercise tolerance and outcomes.

Assessing Single Ventricle Function in the Fontan Circulation using Wave Intensity Analysis.

Single ventricle hearts palliated with the Fontan operation present complications later in life as a result of increased venous pressures and abnormal ventricle function. Wave intensity analysis uses measurements of blood velocity and pressure to represent arterial hemodynamics as summations of energy waves. This methodology could potentially be a useful tool in assessment of Fontan patients. The clinical value of wave intensity parameters was utilized to evaluate the functional performance of the single ventricle in Fontan patients. A retrospective analysis of invasive hemodynamic data was retrospectively obtained from routine cardiac catheterization of patients with Fontan circulation (n = 20) and comparison to those with biventricular circulation (n = 10) who presented to the catheterization laboratory for closure of small patent ductus arteriosus (PDAs). Wave intensity analysis and wave energy flux was calculated using aortic pressure waveforms and echocardiography aortic Doppler measurements as previously described. Significant differences were seen in the peak forward compression wave (p = 0.013), early systolic energy flux (p = 0.005) and the systolic and diastolic ratio (p = 0.006) in Fontan patients versus controls. Within the Fontan group, there was a positive correlation (0.54, p = 0.02) between the wave speed and pulmonary vascular resistance. Early systolic energy flux was a potential individual indicator of a Fontan patients heart failure classification (AUC = 0.71). Wave intensity analysis could be a useful tool in screening Fontan patients and predicting clinical outcomes and Fontan failure. Future prospective analyses of Fontan hemodynamics and WIA are needed.

Predictive Models for Pulmonary Artery Size in Fontan Patients.

We developed models of pulmonary artery (PA) size in Fontan patients as a function of age and body surface area (BSA) using linear regression and breakpoint analyses based on data from 43 Fontan patients divided into two groups: the extracardiac conduit (ECC) group (n = 24) and the non-ECC group (n = 19). Model predictions were compared against those of a non-Fontan control group (n = 18) and published literature. We observed strong positive correlations of the mean PA diameter with BSA (r = 0.9, p < 0.05) and age (r = 0.88, p < 0.05) in the ECC group. The absolute percentage differences between our BSA and age model predictions against published literature were less than 16% and 20%, respectively. Predicted PA size for Fontan patients was consistently smaller than the control group. These models may serve as useful references for clinicians and be utilized to construct 3D anatomic models that correspond to patient body size or age.

The Influence of Atrial Strain on Functional Capacity in Patients with the Fontan Circulation.

Speckle-tracking echocardiography has been used to assess atrial function. This analysis is feasible in univentricular hearts. The aim of this study was to characterize the relationship between atrial strain and functional capacity in the Fontan circulation. Apical four-chamber echocardiographic loops of 39 Fontan patients were reviewed. The dominant atrium was assessed for active (εact), conduit (εcon), and reservoir (εres) strain and εact/εres ratio. Cardiopulmonary exercise test was performed on the same day and oxygen uptake (VO2) at ventilatory threshold (VT) and peak VO2 were chosen as the dependent variables. Statistical analysis was performed using SPSS® version 23. Unpaired t test was used for binomial and continuous variable correlation; single and multivariable linear regression were used for continuous variable correlation. Statistical significance was defined as p value < 0.05. VO2 at VT as a percentage of predicted VO2 was 36.8% (SD 10.7). Peak VO2 was 64.7% (SD 18.9) of the predicted value. In univariate analysis, both were associated with age, atrioventricular regurgitation, ejection fraction, εres, εcon, and εact/εres. In multivariate regression, higher VO2 at VT and peak VO2 were associated with younger age (p = 0.003 and p = 0.001, respectively) and higher εcon (p = 0.026 and p = 0.020). Evaluation of heart function is difficult in the Fontan circulation, hindered by complex ventricular morphology and lack of normative data. VO2 provides a good surrogate. Atrial strain parameters are compromised in these patients and associated with VO2. Therefore, whenever possible, atrial strain should be measured as it may provide a new method of risk stratification.

Major aortopulmonary collateral arteries in a case of unrepaired tricuspid and pulmonary atresia with single ventricle physiology.

Tricuspid and pulmonary atresia with single ventricle physiology and major aortopulmonary collateral arteries (MAPCAs) is a complex cyanotic congenital heart disease with heterogeneous pulmonary artery morphology and arborization. The complex anatomy and physiology, coupled with a dearth of existing literature, pose imitable challenges to treatment. Although the exact surgical algorithm is still unclear, the goal is a well-developed, low-resistance pulmonary vascular bed. A precise understanding of the blood supply to each lung is a requisite for successful surgery, and a multimodality and multidisciplinary approach is compulsory. Herein, we describe a case of tricuspid and pulmonary atresia with single ventricle, MAPCAs and aortopulmonary collateral arteries.

GDF-15 (Growth Differentiation Factor 15) Is Associated With Hospitalization and Mortality in Patients With a Fontan Circulation.

Background We investigated serial serum levels of GDF-15 (growth differentiation factor 15) in Fontan patients and their relation to outcome. Methods and Results In this single-center prospective study of consecutive Fontan patients, serial serum GDF-15 measurement and clinical assessment was done at baseline (n=81) and after 2 years (n=51). The association between GDF-15 and the combined end point of all-cause mortality, heart transplant listing, and Fontan-related hospitalization was investigated. Median age at baseline was 21 years (interquartile range: 15-28 years). Median GDF-15 serum levels at baseline were 552 pg/mL (interquartile range: 453-729 pg/mL). GDF-15 serum levels correlated positively with age, age at Fontan initiation, New York Heart Association class, and serum levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and É£GT (γ-glutamyltransferase) and negatively with exercise capacity. During a median follow-up of 4.8 years (interquartile range: 3.3-5.5 years), the combined end point occurred in 30 patients (37%). Multivariate Cox regression showed that patients with the highest baseline GDF-15 (n=20, defined as the upper quartile) had a higher risk of hospitalization or death than the lowest 3 quartiles (hazard ratio [HR], 2.76; 95% CI, 1.27-6.00; P=0.011). After 2 years of follow-up, patients in whom serum level of GDF-15 increased to >70 pg/mL (n=13) had a higher risk of hospitalization or death than the lowest 3 quartiles (HR, 2.69; 95% CI, 1.03-6.99; P=0.043). Conclusions In Fontan patients, elevated serum levels of GDF-15 are associated with worse functional status and predict Fontan-related events. Furthermore, serial measurements showed that an increase in GDF-15 serum level was associated with increased risk for adverse outcome.

What have we learnt 50 years after the first Fontan procedure?

The Fontan procedure is often the only definitive palliative surgical option for patients with a variety of complex CHD sharing in common, a single, dominant ventricle. In recent decades, imaging and therapeutic improvement have played a crucial role in those patients in whom many complications can hamper their life. After 50 years from the first procedure, heart transplantation remains the only definitive treatment for those with a failing Fontan circulation.

Uncorrected Univentricular Heart in an Adult.

An 18-year-old male with an unknown medical history presented with palpitations and paroxysmal episodes of shortness of breath over a 7-year period. Transthoracic echocardiography displayed a univentricle with an ejection fraction of 45%. The patient refused treatment and was lost to follow-up.

Development of a validated risk score for interstage death or transplant after stage I palliation for single-ventricle heart disease.

OBJECTIVE: To develop a risk score to predict mortality or transplant in the interstage period. BACKGROUND: The "interstage" period between the stage 1 and stage 2 palliation is a time of high morbidity and mortality for infants with single-ventricle congenital heart disease. METHODS: This was an analysis of patients with single-ventricle congenital heart disease requiring arch reconstruction who were enrolled in the National Pediatric Cardiology Quality Improvement Collaborative registry from 2008 to 2015. The primary composite endpoint was interstage mortality or transplant. Multivariable logistic regression and classification and regression tree analysis were performed on two-thirds of the patients ("learning cohort") to build a risk score for the composite endpoint, that was validated in the remaining patients ("validation cohort"). RESULTS: In the 2128 patients analyzed in the registry, the overall event rate was 9% (153 [7%] deaths, 42 [2%] transplants). In the learning cohort, factors independently associated with the composite endpoint were (1) type of Norwood; (2) postoperative ECMO; (3) discharge with Opiates; (4) No Digoxin at discharge; (5) postoperative Arch obstruction, (6) moderate-to-severe Tricuspid regurgitation without an oxygen requirement, and (7) Extra Oxygen required at discharge in patients with moderate-to-severe tricuspid regurgitation. This model was used to create a weighted risk score ("NEONATE" score; 0-76 points), with >75% accuracy in the learning and validation cohorts. In the validation cohort, the event rate in patients with a score >17 was nearly three times those with a score ≤17. CONCLUSIONS: We introduce a risk score that can be used post-stage 1 palliation to predict freedom from interstage mortality or transplant.

Outcomes of Multistage Palliation of Infants With Single Ventricle and Atrioventricular Septal Defect.

BACKGROUND: Published palliation outcomes of infants with functional single ventricle (SV) and common atrioventricular septal defect (AVSD) are poor due to associated cardiac and extracardiac anomalies and development of atrioventricular valve (AVV) regurgitation. We report current palliation results. METHODS: From 2002 to 2012, 80 infants with functional SV with AVSD underwent multistage palliation. Competing-risks analyses modeled events after first-stage surgery and Glenn (death/transplantation vs next palliation surgery) and examined factors associated with survival and AVV intervention. RESULTS: Sixty-eight (80%) patients received neonatal palliation: modified Blalock-Taussig shunt (n = 33, 41%), Norwood (n = 20, 25%), and pulmonary artery band (n = 15, 19%), whereas 12 (15%) received primary Glenn. On competing-risks analysis, one-year following first-stage surgery, 29% of patients had died or received transplantation and 62% had undergone Glenn. Five years following Glenn, 9% of patients had died or received transplantation and 68% had undergone Fontan. Overall eight-year survival was 64% and was lower in patients with genetic syndromes (53% vs 82%), patients requiring concomitant total anomalous pulmonary venous connection repair (53% vs 69%), and those requiring neonatal palliation (48% vs 100%). Factors associated with mortality were unplanned reoperation (hazard ratio [HR]: 3.7 [1.7-8.0], P = .001) and extracorporeal membrane oxygenation use (HR: 7.1 [3.0-16.6], P < .001). Initial AVV regurgitation ≥ moderate was associated with AVV intervention (HR: 6.2 [2.4-16.1], P = .002) with eight-year freedom from death or AVV intervention of 25% in those patients. CONCLUSIONS: Patients with SV with AVSD are a distinct group and commonly have associated cardiac and extracardiac malformations that complicate care and affect survival. The development of AVV regurgitation requiring intervention is common but does not affect survival.

Prediction of pulmonary pressure after Glenn shunts by computed tomography-based machine learning models.

OBJECTIVES: This study aimed to develop non-invasive machine learning classifiers for predicting post-Glenn shunt patients with low and high risks of a mean pulmonary arterial pressure (mPAP) > 15 mmHg based on preoperative cardiac computed tomography (CT). METHODS: This retrospective study included 96 patients with functional single ventricle who underwent a bidirectional Glenn procedure between November 1, 2009, and July, 31, 2017. All patients underwent post-procedure CT, followed by cardiac catheterization. Overall, 23 morphologic parameters were manually extracted from cardiac CT images for each patient. The Mann-Whitney U or chi-square test was applied to select the most significant predictors. Six machine learning algorithms including logistic regression, Naive Bayes, random forest (RF), linear discriminant analysis, support vector machine, and K-nearest neighbor were used for modeling. These algorithms were independently trained on 100 train-validation random splits with a 3:1 ratio. Their average performance was evaluated by area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: Seven CT morphologic parameters were selected for modeling. RF obtained the best performance, with mean AUC of 0.840 (confidence interval [CI] 0.832-0.850) and 0.787 (95% CI 0.780-0.794); sensitivity of 0.815 (95% CI 0.797-0.833) and 0.778 (95% CI 0.767-0.788), specificity of 0.766 (95% CI 0.748-0.785) and 0.746 (95% CI 0.735-0.757); and accuracy of 0.782 (95% CI 0.771-0.793) and 0.756 (95% CI 0.748-0.764) in the training and validation cohorts, respectively. CONCLUSIONS: The CT-based RF model demonstrates a good performance in the prediction of mPAP, which may reduce the need for right heart catheterization in post-Glenn shunt patients with suspected mPAP > 15 mmHg. KEY POINTS: • Twenty-three candidate descriptors were manually extracted from cardiac computed tomography images, and seven of them were selected for subsequent modeling. • The random forest model presents the best predictive performance for pulmonary pressure among all methods. • The computed tomography-based machine learning model could predict post-Glenn shunt pulmonary pressure non-invasively.

Pulmonary arteriovenous malformations in a patient with single ventricle and polysplenia syndrome.

A 5-month-old girl with single ventricle, interrupted inferior vena cava and polysplenia syndrome palliated with bilateral Blalock-Taussig shunts developed severe cyanosis despite apparently increased pulmonary blood flow. Angiography revealed diffuse pulmonary arteriolar capillary dilatation and early pulmonary venous filling, suggesting the presence of pulmonary arteriovenous malformations. Abdominal angiography at 6 months demonstrated a large extrahepatic portosystemic shunt, which was percutaneously closed with a vascular plug. Kawashima operation was performed 2 weeks after portosystemic shunt closure. Although cyanosis improved temporarily, the patient suffered from deteriorating cyanosis at 9 months of age and underwent Fontan completion. Thereafter, her oxygen saturation gradually improved to 95% over the course of 3 weeks. Both the congenital extrahepatic portosystemic shunt and Kawashima operation contributed to the development of pulmonary arteriovenous malformations.

Concurrent right atrial isomerism, complete atrioventricular septal defect, and single ventricle in an L-transposition of great arteries patient complicated by brain abscess.

We present a case of an 11-year-old Indonesian female who was referred to our facility after surgical excision of brain abscess. The patient has been previously diagnosed with right atrial isomerism, complete atrioventricular septal defect, and L-Transposition of great arteries. Multiple staged surgeries are required for the management of this condition.

Successful biventricular cardiac resynchronization therapy in a failing Fontan patient: Implications of ventriculo-ventricular interdependency in single ventricle physiology.

We describe a Fontan patient with severe heart failure who was successfully treated with biventricular cardiac resynchronization therapy (CRT). Our case shows that strain imaging might play a crucial role in guiding placement of pacing leads and in characterizing the electromechanical substrate associated with a favorable CRT response. Furthermore, we demonstrate for the first time that ventriculo-ventricular interdependency seems an important mechanical concept, which can be utilized to augment cardiac performance in failing Fontan patients with a functional hypoplastic ventricle.

Patient-Specific Multiscale Modeling of the Assisted Bidirectional Glenn.

BACKGROUND: First-stage palliation of neonates with single-ventricle physiology is associated with poor outcomes and challenging clinical management. Prior computational modeling and in vitro experiments introduced the assisted bidirectional Glenn (ABG), which increased pulmonary flow and oxygenation over the bidirectional Glenn (BDG) and the systemic-to-pulmonary shunt in idealized models. In this study, we demonstrate that the ABG achieves similar performance in patient-specific models and assess the influence of varying shunt geometry. METHODS: In a small cohort of single-ventricle prestage 2 patients, we constructed three-dimensional in silico models and tuned lumped parameter networks to match clinical measurements. Each model was modified to produce virtual BDG and ABG surgeries. We simulated the hemodynamics of the stage 1 procedure, BDG, and ABG by using multiscale computational modeling, coupling a finite-element flow solver to the lumped parameter network. Two levels of pulmonary vascular resistances (PVRs) were investigated: baseline (low) PVR of the patients and doubled (high) PVR. The shunt nozzle diameter, anastomosis location, and shape were also manipulated. RESULTS: The ABG increased the pulmonary flow rate and pressure by 15% to 20%, which was accompanied by a rise in superior vena caval pressure (2 to 3 mm Hg) at both PVR values. Pulmonary flow rate and superior vena caval pressures were most sensitive to the shunt nozzle diameter. CONCLUSIONS: Patient-specific ABG performance was similar to prior idealized simulations and experiments, with good performance at lower PVR values in the range of measured clinical data. Larger shunt outlet diameters and lower PVR led to improved ABG performance.