Fontan Geometry and Hemodynamics Are Associated With Quality of Life in Adolescents and Young Adults.

BACKGROUND: Despite favorable short-term outcomes, Fontan palliation is associated with comorbidities and diminished quality of life (QOL) in the years after completion. We hypothesized that poor Fontan hemodynamics and ventricular function are associated with worse QOL. METHODS: This was a single-center study of Fontan survivors aged more than 12 years. Subjects completed a cardiac magnetic resonance scan and QOL questionnaire. Cardiac magnetic resonance-derived variables included Fontan geometry, and hemodynamics. Computational fluid dynamics simulations quantified power loss, pressure drop, and total cavopulmonary connection resistance across the Fontan. Quality of life was assessed by completion of the Pediatric Quality of Life Inventory. Longitudinal and cross-sectional comparisons were made between cardiac magnetic resonance and computational fluid dynamics parameters with patient-reported QOL. RESULTS: We studied 77 Fontan patients, median age 19.7 years (interquartile range, 17.1 to 23.6), median time from Fontan completion 16 years (interquartile range, 13 to 20). Longitudinal data were available for 48 patients; median time between cardiac magnetic resonance and QOL was 8.1 years (interquartile range, 7 to 9.4). Median patient-reported Pediatric Quality of Life Inventory total score was 80 (interquartile range, 67.4 to 88). Greater power loss and smaller left pulmonary artery diameter at baseline were associated with worse QOL at follow-up. Greater pressure drop was associated with worse QOL at the same time point. CONCLUSIONS: For Fontan survivors, measures of computational fluid dynamics hemodynamics and geometry are associated with worse QOL. Interventional strategies targeted at optimizing the Fontan may improve QOL.

Impact of Free-Breathing Phase-Contrast MRI on Decision-Making in Fontan Surgical Planning.

Fontan surgical planning ranks proposed surgical options according to their hemodynamics assessed by computational fluid dynamic (CFD) modeling. CFD commonly utilizes blood flow acquired under breath-holding (BH) conditions. Ignoring the free-breathing (FB) effect on blood flow waveforms may impact the ranking of surgical options. This study investigates such a potential impact by including ten Fontan patients who had blood flow acquisitions under both BH and FB conditions. A virtual surgery platform was used to generate two surgical options for each patient: (1) a traditional Fontan conduit and (2) a Y-graft. These options were ranked based on clinically relevant hemodynamic metrics: power loss (PL) and hepatic flow distribution (HFD). No difference was found in the ranking of options between using FB and BH flow acquisitions. The findings indicated that decision-making is not affected by the types of flow acquisition for Fontan surgical planning.

High Prevalence of Cirrhosis at Initial Presentation Among Safety-Net Adults with Chronic Hepatitis B Virus Infection.

BACKGROUND AND AIMS: Delays in diagnosis of chronic hepatitis B virus infection (HBV) may be more common among underserved safety-net populations, contributing to more advanced disease at presentation. We aim to evaluate rates of and predictors of cirrhosis and cirrhosis-related complications among adults with chronic HBV. METHODS: We retrospectively evaluated consecutive chronic HBV adults from gastroenterology clinics from July 2014 to May 2016 at a community-based safety-net hospital. Prevalence of cirrhosis or cirrhosis-related complications (ascites, variceal bleeding, hepatic encephalopathy (HE), hepatocellular carcinoma (HCC)) at initial presentation was stratified by sex and race/ethnicity. Predictors of cirrhosis or cirrhosis-related complications at presentation were evaluated with multivariate logistic regression. RESULTS: Among 329 chronic HBV patients (mean age 49.1 years, 55.3% male, 66.5% Asian, 18.6% HBeAg positive) 27.7% had cirrhosis at presentation, 4.3% ascites, 3.7% variceal bleeding, 4.9% HE, and 4.0% HCC. Compared to women, men were more likely to have cirrhosis (34.6% vs. 19.1%, P < 0.01) and variceal bleeding (5.6% vs. 1.4%, P < 0.05) at presentation. On multivariate regression, older age at presentation (OR, 1.04; 95% CI, 1.01-1.07; P = 0.003) and positive HBeAg (OR, 2.57; 95% CI, 1.20-5.51; P = 0.015) were associated with higher odds of cirrhosis at presentation, whereas men had a non-significant trend toward higher odds of cirrhosis (OR, 1.88; 95% CI, 0.99-3.58; P = 0.055). CONCLUSION: Among adults with chronic HBV at an ethnically diverse safety-net hospital system, nearly 30% of patients had cirrhosis at initial presentation, with the greatest risk seen among patients of male sex, older age, and with positive HBeAg.

The macula densa prorenin receptor is essential in renin release and blood pressure control.

The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS); however, recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry-localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys. MD cell PRR activation led to MAP kinase ERK1/2 signaling and stimulation of PGE2 release, the classic pathway of MD-mediated renin release. Exogenous renin or prorenin added to the in vitro microperfused JGA-induced acute renin release, which was inhibited by removing the MD or by the administration of a PRR decoy peptide. To test the function of MD PRR in vivo, we established a new mouse model with inducible conditional knockout (cKO) of the PRR in MD cells based on neural nitric oxide synthase-driven Cre-lox recombination. Deletion of the MD PRR significantly reduced blood pressure and plasma renin. Challenging the RAS by low-salt diet + captopril treatment caused further significant reductions in blood pressure, renal renin, cyclooxygenase-2, and microsomal PGE synthase expression in cKO vs. wild-type mice. These results suggest that the MD PRR is essential in a novel JGA short-loop feedback mechanism, which is integrated within the classic MD mechanism to control renin synthesis and release and to maintain blood pressure.

Respiratory Effects on Fontan Circulation During Rest and Exercise Using Real-Time Cardiac Magnetic Resonance Imaging.

BACKGROUND: It is known that respiration modulates cavopulmonary flows, but little data compare mean flows under breath-holding and free-breathing conditions to isolate the respiratory effects and effects of exercise on the respiratory modulation. METHODS: Real-time phase-contrast magnetic resonance combined with a novel method to track respiration on the same image acquisition was used to investigate respiratory effects on Fontan caval and aortic flows under breath-holding, free-breathing, and exercise conditions. Respiratory phasicity indices that were based on beat-averaged flow were used to quantify the respiratory effect. RESULTS: Flow during inspiration was substantially higher than expiration under the free-breathing and exercise conditions for both inferior vena cava (inspiration/expiration: 1.6 ± 0.5 and 1.8 ± 0.5, respectively) and superior vena cava (inspiration/expiration: 1.9 ± 0.6 and 2.6 ± 2.0, respectively). Changes from rest to exercise in the respiratory phasicity index for these vessels further showed the impact of respiration. Total systemic venous flow showed no significant statistical difference between the breath-holding and free-breathing conditions. In addition, no substantial difference was found between the descending aorta and inferior vena cava mean flows under either resting or exercise conditions. CONCLUSIONS: This study demonstrated that inferior vena cava and superior vena cava flow time variance is dominated by respiratory effects, which can be detected by the respiratory phasicity index. However, the minimal respiration influence on net flow validates the routine use of breath-holding techniques to measure mean flows in Fontan patients. Moreover, the mean flows in the inferior vena cava and descending aorta are interchangeable.

Durability and survival are similar after elective endovascular and open repair of abdominal aortic aneurysms in younger patients.

OBJECTIVE: The role of endovascular repair (EVAR) of aortic aneurysms in young patients is controversial. The purpose of this study was to determine the long-term outcomes and reintervention rates in patients 60 years of age or younger who underwent elective open or endovascular repair of an abdominal aortic aneurysm. METHODS: Retrospective review of a prospectively collected vascular surgery database at a university-affiliated medical center was performed to identify all patients who underwent elective repair of an abdominal aortic aneurysm between 2000 and 2013 and were 60 years of age or younger at the time of the repair. Preoperative anatomic measurements were performed and compared with instructions for use (IFU) criteria for the endografts. RESULTS: The study cohort comprised 169 patients 60 years of age or younger (mean age, 56.7 ± 2.8 years) who underwent elective repair (119 open repair, 50 EVAR). Patients treated with open repair and EVAR had similar comorbidities, except that EVAR patients were more likely to have hypertension (P = .03) and poor left ventricular function (P = .04). The open repair group had significantly larger suprarenal (P = .004) and infrarenal (P = .005) neck angles, shorter neck lengths (P < .001), and larger maximum aneurysm diameter (P = .02) compared with the EVAR group. Only five patients (13%) in the EVAR group did not meet all IFU criteria. The overall in-hospital mortality rate was 1.8% (0% EVAR, 2.5% open repair; P = .56). Overall mean life expectancy was 11.5 years (9.8 years EVAR, 11.9 years open repair; P = .09). The 1-year (98% EVAR, 96% open repair), 5-year (86% EVAR, 88% open repair), and 10-year (54% EVAR, 75% open repair) survival did not differ between EVAR and open repair (P = .16). Long-term survival (78% EVAR, 85% open repair; P = .09) and reintervention rates (12% EVAR, 16% open repair; P = .80) did not differ. No late aneurysm rupture or aneurysm-related deaths were observed. The most common causes of long-term mortality were malignant disease and cardiovascular events. Reinterventions in the open repair group were exclusively laparotomy related (incisional hernia repairs), whereas all reinterventions in the EVAR group were aortic related, including one conversion to open repair. CONCLUSIONS: After elective aneurysm repair, younger patients have a moderate life expectancy related to malignant disease and cardiovascular health. EVAR offers durability and long-term survival similar to those with open repair in these younger patients as long as aneurysm anatomy and IFU are adhered to.

Energetic implications of vessel growth and flow changes over time in Fontan patients.

BACKGROUND: As patients with a single-ventricle physiology age, long-term complications inherent to this population become more evident. Previous studies have focused on correlating anatomic and hemodynamic performance, but there is little information of how these variables change with time. Vessel growth and flow rate changes were quantified using cardiac magnetic resonance and their effects on hemodynamics were assessed, which could affect the long-term outcome. METHODS: Forty-eight patients with a lateral tunnel or extracardiac conduit Fontan who underwent two cardiac magnetic resonance scans (average interval, 5.1 ± 2.3 years) were studied. Total cavopulmonary connection anatomic and flow variables were reconstructed and normalized to body surface area(1/2). Total cavopulmonary connection hemodynamic efficiency (indexed power loss) was obtained through computational fluid dynamic modeling. RESULTS: Absolute vessel diameters increased with time, normalized diameters decreased, and vessel mean flow rates remained unchanged. Indexed power loss changed significantly in the cohort, as well as in patients in whom the minimum normalized left pulmonary artery decreased. Age at first scan and connection type (lateral tunnel or extracardiac conduit) were not associated with changes in indexed power loss. CONCLUSIONS: We present the largest serial cardiac magnetic resonance Fontan cohort to date. Although flow rates increased proportionally to body surface area, vessel diameters did not match somatic growth. As a result, energy losses increased significantly with time in the cohort analyzed.

Fontan hemodynamics from 100 patient-specific cardiac magnetic resonance studies: a computational fluid dynamics analysis.

OBJECTIVES: This study sought to quantify average hemodynamic metrics of the Fontan connection as reference for future investigations, compare connection types (intra-atrial vs extracardiac), and identify functional correlates using computational fluid dynamics in a large patient-specific cohort. Fontan hemodynamics, particularly power losses, are hypothesized to vary considerably among patients with a single ventricle and adversely affect systemic hemodynamics and ventricular function if suboptimal. METHODS: Fontan connection models were created from cardiac magnetic resonance scans for 100 patients. Phase velocity cardiac magnetic resonance in the aorta, vena cavae, and pulmonary arteries was used to prescribe patient-specific time-averaged flow boundary conditions for computational fluid dynamics with a customized, validated solver. Comparison with 4-dimensional cardiac magnetic resonance velocity data from selected patients was used to provide additional verification of simulations. Indexed Fontan power loss, connection resistance, and hepatic flow distribution were quantified and correlated with systemic patient characteristics. RESULTS: Indexed power loss varied by 2 orders of magnitude, whereas, on average, Fontan resistance was 15% to 20% of published values of pulmonary vascular resistance in single ventricles. A significant inverse relationship was observed between indexed power loss and both systemic venous flow and cardiac index. Comparison by connection type showed no differences between intra-atrial and extracardiac connections. Instead, the least efficient connections revealed adverse consequences from localized Fontan pathway stenosis. CONCLUSIONS: Fontan power loss varies from patient to patient, and elevated levels are correlated with lower systemic flow and cardiac index. Fontan connection type does not influence hemodynamic efficiency, but an undersized or stenosed Fontan pathway or pulmonary arteries can be highly dissipative.

Fontan pathway growth: a quantitative evaluation of lateral tunnel and extracardiac cavopulmonary connections using serial cardiac magnetic resonance.

BACKGROUND: Typically, a Fontan connection is constructed as either a lateral tunnel (LT) pathway or an extracardiac (EC) conduit. The LT is formed partially by atrial wall and is assumed to have growth potential, but the extent and nature of LT pathway growth have not been well characterized. A quantitative analysis was performed to evaluate this issue. METHODS: Retrospective serial cardiac magnetic resonance data were obtained for 16 LT and 9 EC patients at 2 time points (mean time between studies, 4.2 ± 1.6 years). Patient-specific anatomies and flows were reconstructed. Geometric parameters of Fontan pathway vessels and the descending aorta were quantified, normalized to body surface area (BSA), and compared between time points and Fontan pathway types. RESULTS: Absolute LT pathway mean diameters increased over time for all but 2 patients; EC pathway size did not change (2.4 ± 2.2 mm vs 0.02 ± 2.1 mm, p < 0.05). Normalized LT and EC diameters decreased, while the size of the descending aorta increased proportionally to BSA. Growth of other cavopulmonary vessels varied. The patterns and extent of LT pathway growth were heterogeneous. Absolute flows for all vessels analyzed, except for the superior vena cava, proportionally to BSA. CONCLUSIONS: Fontan pathway vessel diameter changes over time were not proportional to somatic growth but increases in pathway flows were; LT pathway diameter changes were highly variable. These factors may impact Fontan pathway resistance and hemodynamic efficiency. These findings provide further understanding of the different characteristics of LT and EC Fontan connections and set the stage for further investigation.