Kevin K. Whitehead

Nonlinear Power Loss During Exercise in Single-Ventricle Patients After the Fontan Insights From Computational Fluid Dynamics

Background— We previously demonstrated that power loss (PL) through the total cavopulmonary connection (TCPC) in single-ventricle patients undergoing Fontan can be calculated by computational fluid dynamic analysis using 3-dimensional MRI anatomic reconstructions. PL through the TCPC may play a role in single-ventricle physiology and is a function of cardiac output. We hypothesized that PL through the TCPC increases significantly under exercise flow conditions. Methods and Results— MRI data of 10 patients with a TCPC were analyzed to obtain 3-dimensional geometry and flow rates through the superior vena cava, inferior vena cava, left pulmonary artery, and right pulmonary artery. Steady computational fluid dynamic simulations were performed at baseline conditions using MRI-derived flows. Simulated exercise conditions of twice (2×) and three times (3×) baseline flow were performed by increasing inferior vena cava flow. PL, head loss, and effective resistance through the TCPC were calculated for each condition. Each condition was repeated at left pulmonary artery/right pulmonary artery ratios of 30/70 and 70/30 to determine the effects of pulmonary flow splits on exercise PL. For each patient, PL increases dramatically in a nonlinear fashion with increasing cardiac output, even when normalized to calculate head loss or resistance. Flow splits had a significant effect on PL at exercise, with most geometries favoring right pulmonary artery flow. Conclusions— The relationship between cardiac output and PL is nonlinear and highly dependent on TCPC geometry and pulmonary flow splits. This study demonstrates the importance of studying the TCPC under exercise conditions, because baseline conditions may not adequately characterize TCPC efficiency.

The total cavopulmonary connection resistance: a significant impact on single ventricle hemodynamics at rest and exercise

Little is known about the impact of the total cavopulmonary connection (TCPC) on resting and exercise hemodynamics in a single ventricle (SV) circulation. The aim of this study was to elucidate this mechanism using a lumped parameter model of the SV circulation. Pulmonary vascular resistance (1.96+/-0.80 WU) and systemic vascular resistances (18.4+/-7.2 WU) were obtained from catheterization data on 40 patients with a TCPC. TCPC resistances (0.39+/-0.26 WU) were established using computational fluid dynamic simulations conducted on anatomically accurate three-dimensional models reconstructed from MRI (n=16). These parameters were used in a lumped parameter model of the SV circulation to investigate the impact of TCPC resistance on SV hemodynamics under resting and exercise conditions. A biventricular model was used for comparison. For a biventricular circulation, the cardiac output (CO) dependence on TCPC resistance was negligible (sensitivity=-0.064 l.min(-1).WU(-1)) but not for the SV circulation (sensitivity=-0.88 l.min(-1).WU(-1)). The capacity to increase CO with heart rate was also severely reduced for the SV. At a simulated heart rate of 150 beats/min, the SV patient with the highest resistance (1.08 WU) had a significantly lower increase in CO (20.5%) compared with the SV patient with the lowest resistance (50%) and normal circulation (119%). This was due to the increased afterload (+35%) and decreased preload (-12%) associated with the SV circulation. In conclusion, TCPC resistance has a significant impact on resting hemodynamics and the exercise capacity of patients with a SV physiology.

Noninvasive quantification of systemic-to-pulmonary collateral flow: a major source of inefficiency in patients with superior cavopulmonary connections.

Background—Systemic-to-pulmonary collateral flow (SPCF) is common in single-ventricle patients with superior cavopulmonary connections (SCPC). Because no validated method to quantify that SPCF exists, neither its hemodynamic burden nor its clinical impact can be systematically evaluated. We hypothesize that (1) the difference in total ascending aortic (Ao) and caval flow (superior vena cava [SVC]+inferior vena cava [IVC]) and (2) the difference between pulmonary vein and pulmonary artery flow (PV−PA) provide 2 independent estimators of SPCF. Methods and Results—We measured Ao, SVC, IVC, right (RPA) and left (LPA) PA, and left (LPV) and right (RPV) PV flows in 17 patients with SCPC during routine cardiac MRI studies using through-plane phase-contrast velocity mapping. Two independent measures of SPCF were obtained: model 1, Ao−(SVC+IVC); and model 2, (LPV−LPA)+(RPV−RPA). Values were normalized to body surface area, Ao, and PV, and comparisons were made using linear regression and Bland-Altman analysis. SPCF ranged from 0.2 to 1.4 L/min for model 1 and 0.2 to 1.6 L/min for model 2, for an average indexed SPCF of 0.5 to 2.8 L/min/m2: 11% to 53% (mean, 37%) of Ao and 19% to 77% (mean, 54%) of PV. The mean difference between model 1 and model 2 was 0.01 L/min (P=0.40; 2-SD range, −0.45 to 0.47 L/min). Conclusions—We present a noninvasive method for SPCF quantification in patients with SCPC. It should provide an important clinical tool in treating these patients. Furthermore, we show that SPCF is a significant hemodynamic burden in many patients with bidirectional Glenn shunt physiology. Future investigations will allow objective study of the impact of collateral flow on outcome.Background— Systemic-to-pulmonary collateral flow (SPCF) is common in single-ventricle patients with superior cavopulmonary connections (SCPC). Because no validated method to quantify SPCF exists, neither its hemodynamic burden nor its clinical impact can be systematically evaluated. We hypothesize that (1) the difference in total ascending aortic (Ao) and caval flow (superior vena cava [SVC]+inferior vena cava [IVC]) and (2) the difference between pulmonary vein and pulmonary artery flow (PV−PA) provide 2 independent estimators of SPCF. Methods and Results— We measured Ao, SVC, IVC, right (RPA) and left (LPA) PA, and left (LPV) and right (RPV) PV flows in 17 patients with SCPC during routine cardiac MRI studies using through-plane phase-contrast velocity mapping. Two independent measures of SPCF were obtained: model 1, Ao−(SVC+IVC); and model 2, (LPV−LPA)+(RPV−RPA). Values were normalized to body surface area, Ao, and PV, and comparisons were made using linear regression and Bland-Altman analysis. SPCF ranged from 0.2 to 1.4 L/min for model 1 and 0.2 to 1.6 L/min for model 2, for an average indexed SPCF of 0.5 to 2.8 L/min/m2: 11% to 53% (mean, 37%) of Ao and 19% to 77% (mean, 54%) of PV. The mean difference between model 1 and model 2 was 0.01 L/min ( P =0.40; 2-SD range, −0.45 to 0.47 L/min). Conclusions— We present a noninvasive method for SPCF quantification in patients with SCPC. It should provide an important clinical tool in treating these patients. Furthermore, we show that SPCF is a significant hemodynamic burden in many patients with bidirectional Glenn shunt physiology. Future investigations will allow objective study of the impact of collateral flow on outcome. Received November 10, 2008; accepted July 7, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Fontan hemodynamics: Importance of pulmonary artery diameter

OBJECTIVE We quantify the geometric and hemodynamic characteristics of extracardiac and lateral tunnel Fontan surgical options and correlate certain anatomic characteristics with their hemodynamic efficiency and patient cardiac index. METHODS AND RESULTS The study was conducted retrospectively on 22 patients undergoing Fontan operations (11 extracardiac and 11 lateral tunnel operations). Total cavopulmonary connection geometric parameters such as vessel areas, curvature, and offsets were quantified using a skeletonization method. Energy loss at the total cavopulmonary connection junction was available from previous in vitro experiments and computational fluid dynamic simulations for 5 and 9 patients, respectively. Cardiac index data were available for all patients. There was no significant difference in the mean and minimum cross-sectional vessel areas of the pulmonary artery between the extracardiac and lateral tunnel groups. The indexed energy dissipation within the total cavopulmonary connection was strongly correlated to minimum cross-sectional area of the pulmonary arteries (R(2) value of 0.90 and P < .0002), whereas all other geometric features, including shape characteristics, had no significant correlation. Finally, cardiac index significantly correlated with the minimum pulmonary artery area (P = .006), suggesting that total cavopulmonary connection energy losses significantly affect resting cardiac output. CONCLUSIONS The minimum outlet size of the total cavopulmonary connection (ie, minimum cross section of pulmonary artery) governs the energy loss characteristics of the total cavopulmonary connection more strongly than variations in the shapes corresponding to extracardiac and lateral tunnel configurations. Differences in pulmonary artery sizes must be accounted for when comparing energy losses between extracardiac and lateral tunnel geometries.

Exercise capacity in single-ventricle patients after Fontan correlates with haemodynamic energy loss in TCPC

Objective Elevated energy loss in the total cavopulmonary connection (TCPC) is hypothesised to have a detrimental effect on clinical outcomes in single-ventricle physiology, which may be magnified with exercise. This study investigates the relationship between TCPC haemodynamic energy dissipation and exercise performance in single-ventricle patients. Methods Thirty consecutive Fontan patients with TCPC and standard metabolic exercise testing were included. Specific anatomies and flow rates at rest and exercise were obtained from cardiac MR (CMR) and phase-encoded velocity mapping. Exercise CMR images were acquired immediately following supine lower limb exercise using a CMR-compatible cycle ergometer. Computational fluid dynamics simulations were performed to determine power loss of the TCPC anatomies using in vivo anatomies and measured flows. Results A significant negative linear correlation was observed between indexed power loss at exercise and (a) minute oxygen consumption (r=−0.60, p<0.0005) and (b) work (r=−0.62, p<0.0005) at anaerobic threshold. As cardiac output increased during exercise, indexed power loss increased in an exponential fashion (y=0.9671x3.0263, p<0.0001). Conclusions This is the first study to demonstrate the relationship between power loss and exercise performance with the TCPC being one of the few modifiable factors to allow for improved quality of life. These results suggest that aerobic exercise tolerance in Fontan patients may, in part, be a consequence of TCPC power loss.

Systemic-to-Pulmonary Collateral Flow, as Measured by Cardiac Magnetic Resonance Imaging, Is Associated With Acute Post-Fontan Clinical Outcomes

Background— Systemic-pulmonary collateral (SPC) flow occurs commonly in single ventricle patients after superior cavo-pulmonary connection, with unclear clinical significance. We sought to evaluate the association between SPC flow and acute post-Fontan clinical outcomes using a novel method of quantifying SPC flow by cardiac magnetic resonance (CMR) imaging. Methods and Results— All patients who had SPC flow quantified by CMR imaging before Fontan were retrospectively reviewed to assess for acute clinical outcomes after Fontan completion. Forty-four subjects were included who had Fontan completion between May 2008 and September 2010. SPC flow prior to Fontan measured 1.5±0.9 L/min/m2, accounting for 31±11% of total aortic flow and 44±15% of total pulmonary venous flow. There was a significant linear association between natural log-transformed duration of hospitalization and SPC flow as a proportion of total aortic (rho=0.31, P=0.04) and total pulmonary venous flow (rho=0.29, P=0.05). After adjustment for Fontan type and presence of a fenestration, absolute SPC flow was significantly associated with hospital duration ≥7 days (odds ratio [OR]=9.2, P=0.02) and chest tube duration ≥10 days (OR=22.7, P=0.009). Similar associations exist for SPC flow as a percentage of total aortic (OR=1.09, P=0.048 for hospitalization ≥7 days; OR=1.24, P=0.007 for chest tube duration ≥10 days) and total pulmonary venous flow (OR=1.07, P=0.048 for hospitalization ≥7 days; OR=1.18, P=0.006 for chest tube duration ≥10 days). Conclusions— Increasing SPC flow before Fontan, as measured by CMR imaging, is associated with increased duration of hospitalization and chest tube following Fontan completion.

Blood flow distribution in a large series of patients having the Fontan operation: A cardiac magnetic resonance velocity mapping study

OBJECTIVES Our goal was to determine flow distribution in the cavopulmonary connections of patients with and without bilateral superior venae cavae who had the Fontan procedure. No large series exists that establishes the flow distributions in Fontan patients, which would be an important resource for everyday clinical use and may affect future surgical reconstruction. METHODS We studied 105 Fontan patients (aged 2-24 years) with through-plane phase contrast velocity mapping to determine flow rates in the inferior and superior venae cavae and left and right pulmonary arteries. Superior caval anastomosis type included 40 bidirectional Glenn shunts (of which 15 were bilateral) and 53 hemi-Fontan anastomoses; Fontan type included 69 intra-atrial baffles, 28 extracardiac conduits, and 4 atriopulmonary connections. RESULTS Total caval flow was 2.9 +/- 1.0 L x min(-1) x m(-2), with an inferior vena cava contribution of 59% +/- 15%. Total pulmonary flow was 2.5 +/- 0.8 L x min(-1) x m(-2), statistically less than caval flow and not explained by fenestration presence. The right pulmonary artery contribution (55% +/- 13%) was statistically greater than the left. In patients with bilateral superior cavae, the right cava accounted for 52% +/- 14% of the flow, with no difference in pulmonary flow splits (50% +/- 16% to the right). Age and body surface area correlated with percent inferior caval contribution (r = 0.60 and 0.74, respectively). Superior vena cava anastomosis and Fontan type did not significantly affect pulmonary flow splits. CONCLUSIONS Total Fontan cardiac index was 2.9 L x min(-1) x m(-2), with normal pulmonary flow splits (55% to the right lung). Inferior vena caval contribution to total flow increases with body surface area and age, consistent with data from healthy children.

X-Ray Magnetic Resonance Fusion to Internal Markers and Utility in Congenital Heart Disease Catheterization

Background—X-ray magnetic resonance fusion (XMRF) allows for use of 3D data during cardiac catheterization. However, to date, technical requirements have limited the use of this modality in clinical practice. We report on a new internal-marker XMRF method that we have developed and describe how we used XMRF during cardiac catheterization in congenital heart disease. Methods and Results—XMRF was performed in a phantom and in 23 patients presenting for cardiac catheterization who also needed cardiac MRI for clinical reasons. The registration process was performed in <5 minutes per patient, with minimal radiation (0.004 to 0.024 mSv) and without contrast. Registration error was calculated in a phantom and in 8 patients using the maximum distance between angiographic and 3D model boundaries. In the phantom, the measured error in the anteroposterior projection had a mean of 1.15 mm (standard deviation, 0.73). The measured error in patients had a median of 2.15 mm (interquartile range, 1.65 to 2.56 mm). Internal markers included bones, airway, image artifact, calcifications, and the heart and vessel borders. The MRI data were used for road mapping in 17 of 23 (74%) cases and camera angle selection in 11 of 23 (48%) cases. Conclusions—Internal marker–based registration can be performed quickly, with minimal radiation, without the need for contrast, and with clinically acceptable accuracy using commercially available software. We have also demonstrated several potential uses for XMRF in routine clinical practice. This modality has the potential to reduce radiation exposure and improve catheterization outcomes.

MRI of Lymphatic Abnormalities After Functional Single-Ventricle Palliation Surgery

OBJECTIVE Protein-losing enteropathy (PLE) and plastic bronchitis are serious complications that occur after single-ventricle surgery. A lymphatic cause for these conditions has been proposed, but imaging correlation has not been reported. The objective of this study was to evaluate lymphatic abnormalities in patients after functional single-ventricle palliation compared with patients with non-single-ventricle congenital heart conditions using T2-weighted MR lymphangiography. MATERIALS AND METHODS We retrospectively reviewed imaging data from 48 patients who underwent T2-weighted MR lymphangiography in our institution between May 1, 2012, and October 24, 2012. The patients were divided into four groups: patients who underwent superior cavopulmonary connection, patients who underwent total cavopulmonary connection, patients with total cavopulmonary connection and lymphatic complications, and patients with non-single-ventricle cardiac anomalies. RESULTS There were 38 patients with single ventricles in this study. The lymphatic abnormalities observed in these patients included thoracic duct dilation greater than 3 mm (31%), lymphangiectasia and lymphatic collateralization (78%), and tissue edema (86%). There were five patients with PLE, one patient with plastic bronchitis, and one patient with chronic chylous effusions and superior cavopulmonary connection. The patients with PLE and plastic bronchitis had statistically significant larger thoracic duct maximal diameters (median, 3.9 mm; range, 3-7.2 mm) than did the other patients with total cavopulmonary connection (p < 0.01). In the two-ventricle patient group, there were no abnormal lymphatic findings. CONCLUSION Lymphatic abnormalities are found in many patients after functional single-ventricle palliation. T2-weighted unenhanced MRI is capable of anatomic assessment of the lymphatic system in this patient population and has promise for guiding treatment in the future.

Pulmonary hepatic flow distribution in total cavopulmonary connections: extracardiac versus intracardiac.

OBJECTIVE Pulmonary arteriovenous malformations can occur after the Fontan procedure and are believed to be associated with disproportionate pulmonary distribution of hepatic venous effluent. We studied the effect of total cavopulmonary connection geometry and the effect of increased cardiac output on distribution of inferior vena caval return to the lungs. METHODS Ten patients undergoing the Fontan procedure, 5 with extracardiac and 5 with intracardiac configurations of the total cavopulmonary connection, previously analyzed for power loss were processed for calculating the distribution of inferior vena caval return to the lungs (second-order accuracy). One idealized total cavopulmonary connection was similarly analyzed under parametric variation of inferior vena caval offset and cardiac output flow split. RESULTS Streaming of the inferior vena caval return in the idealized total cavopulmonary connection model was dependent on both inferior vena caval offset magnitude and cardiac output flow-split ratio. For patient-specific total cavopulmonary connections, preferential streaming of the inferior vena caval return was directly proportional to the cardiac output flow-split ratio in the intracardiac total cavopulmonary connections (P < .0001). Preferential streaming in extracardiac total cavopulmonary connections correlated to the inferior vena caval offset (P < .05) and did not correlate to cardiac output flow split. Enhanced mixing in intracardiac total cavopulmonary connections is speculated to explain the contrasting results. Exercising tends to reduce streaming toward the left pulmonary artery in intracardiac total cavopulmonary connections, whereas for extracardiac total cavopulmonary connections, exercising tends to equalize the streaming. CONCLUSIONS Extracardiac and intracardiac total cavopulmonary connections have inherently different streaming characteristics because of contrasting mixing characteristics caused by their geometric differences. Pulmonary artery diameters and inferior vena caval offsets might together determine hepatic flow streaming.