Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

OBJECTIVE: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age. METHODS: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival. RESULTS: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo2 for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications. CONCLUSIONS: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo2, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT0245531.

Decreased erythrocyte aggregation in Glenn and Fontan: univentricular circulation as a rheologic disease model.

BACKGROUND: In the Fontan palliation for single ventricle heart disease (SVHD), pulmonary blood flow is non-pulsatile/passive, low velocity, and low shear, making viscous power loss a critical determinant of cardiac output. The rheologic properties of blood in SVHD patients are essential for understanding and modulating their limited cardiac output and they have not been systematically studied. We hypothesize that viscosity is decreased in single ventricle circulation. METHODS: We evaluated whole blood viscosity, red blood cell (RBC) aggregation, and RBC deformability to evaluate changes in healthy children and SVHD patients. We altered suspending media to understand cellular and plasma differences contributing to rheologic differences. RESULTS: Whole blood viscosity was similar between SVHD and healthy at their native hematocrits, while viscosity was lower at equivalent hematocrits for SVHD patients. RBC deformability is increased, and RBC aggregation is decreased in SVHD patients. Suspending SVHD RBCs in healthy plasma resulted in increased RBC aggregation and suspending healthy RBCs in SVHD plasma resulted in lower RBC aggregation. CONCLUSIONS: Hematocrit corrected blood viscosity is lower in SVHD vs. healthy due to decreased RBC aggregation and higher RBC deformability, a viscous adaptation of blood in patients whose cardiac output is dependent on minimizing viscous power loss. IMPACT: Patients with single ventricle circulation have decreased red blood cell aggregation and increased red blood cell deformability, both of which result in a decrease in blood viscosity across a large shear rate range. Since the unique Fontan circulation has very low-shear and low velocity flow in the pulmonary arteries, blood viscosity plays an increased role in vascular resistance, therefore this work is the first to describe a novel mechanism to target pulmonary vascular resistance as a modifiable risk factor. This is a novel, modifiable risk factor in this patient population.

Cardiac Magnetic Resonance Imaging to Determine Single Ventricle Function in a Pediatric Population is Feasible in a Large Trial Setting: Experience from the Single Ventricle Reconstruction Trial Longitudinal Follow up.

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function and flow quantification. There were 313 eligible SVRIII participants and 237 enrolled, ages ranging from 10 to 12.5 years. 177/237 (75%) participants underwent CMR. The most common reasons for not undergoing CMR exam were requirement for anesthesia (n = 14) or ICD/pacemaker (n = 11). A total of 168/177 (94%) CMR studies were diagnostic for RVEF. Median exam time was 54 [IQR 40-74] minutes, cine function exam time 20 [IQR 14-27] minutes, and flow quantification time 18 [IQR 12-25] minutes. There were 69/177 (39%) studies noted to have intra-thoracic artifacts, most common being susceptibility artifact from intra-thoracic metal. Not all artifacts resulted in non-diagnostic exams. These data describe the use and limitations of CMR for the assessment of cardiac function in a prospective trial setting in a grade-school-aged pediatric population with congenital heart disease. Many of the limitations are expected to decrease with the continued advancement of CMR technology.

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis.

The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.5 mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.

The prevalence of abnormal spirometry in children with CHD.

BACKGROUND: The burden of pulmonary disease in children with CHD remains under-recognised. Studies have examined children with single ventricle and two ventricle heart disease and documented a decreased forced vital capacity. Our study sought to further explore the pulmonary function of children with CHD. METHODS: A retrospective review was performed of spirometry in CHD patients over a 3-year period. Spirometry data were corrected for size, age, and gender and analysed using z-scores. RESULTS: The spirometry of 260 patients was analysed. About 31% had single ventricle (n = 80, 13.6 years (interquartile range 11.5-16.8)) and 69% had two ventricle circulation (n = 180, 14.4 years (interquartile range 12.0-17.3)). Single ventricle patients were found to have a lower median forced vital capacity z-score compared to two ventricle patients (p = 0.0133). The prevalence of an abnormal forced vital capacity was 41% in single ventricle patients and 29% in two ventricle patients. Two ventricle patients with tetralogy of Fallot and truncus arteriosus had similar low forced vital capacity comparable to single ventricle patients. The number of cardiac surgeries predicted an abnormal forced vital capacity in two ventricle patients except tetralogy of Fallot patients. CONCLUSION: Pulmonary morbidity in patients with CHD is common with a decreased forced vital capacity noted in single ventricle and two ventricle patients. Forced vital capacity is lower in patients with single ventricle circulation; however, two ventricle patients with tetralogy of Fallot or truncus arteriosus have similar lung function in comparison to the single ventricle group. The number of surgical interventions was predictive of forced vital capacity z-score in some but not all two ventricle patients and not predictive in single ventricle patients suggesting a multifactorial to pulmonary disease in children with CHD.

The pediatric heart network's study on long-term outcomes of children with HLHS and the impact of Norwood Shunt type in the single ventricle reconstruction trial cohort (SVRIII): Design and adaptations.

BACKGROUND: The Single Ventricle Reconstruction (SVR) Trial was the first randomized clinical trial of a surgical approach for treatment of congenital heart disease. Infants with hypoplastic left heart syndrome (HLHS) and other single right ventricle (RV) anomalies were randomized to a modified Blalock Taussig Thomas shunt (mBTTS) or a right-ventricular-to-pulmonary-artery shunt (RVPAS) at the time of the Norwood procedure. The aim of the Long-term Outcomes of Children with HLHS and the Impact of Norwood Shunt Type (SVR III) study is to compare early adolescent outcomes including measures of cardiac function, transplant-free survival, and neurodevelopment, between those who received a mBTTS and those who received an RVPAS. METHODS: Transplant-free survivors of the SVR cohort were enrolled at 10 to 15 years of age for multifaceted in-person evaluation of cardiac function (cardiac magnetic resonance [CMR], echocardiogram and exercise test) and neurodevelopmental evaluation. Right ventricular ejection fraction measured by CMR served as the primary outcome. Development of arrhythmias, protein losing enteropathy, and other comorbidities were assessed through annual medical history interview. Through the course of SVR III, protocol modifications to engage SVR trial participants were designed to enhance recruitment and retention. CONCLUSIONS: Evaluation of long-term outcomes will provide important data to inform decisions about the shunt type placed at the Norwood operation and will improve the understanding of cardiovascular and neurodevelopmental outcomes for early adolescents with HLHS.

Progressive vasoconstriction with sequential thermal stimulation indicates vascular dysautonomia in sickle cell disease.

Persons with sickle cell disease (SCD) exhibit subjective hypersensitivity to cold and heat perception in experimental settings, and triggers such as cold exposure are known to precipitate vaso-occlusive crises by still unclear mechanisms. Decreased microvascular blood flow (MBF) increases the likelihood of vaso-occlusion by increasing entrapment of sickled red blood cells in the microvasculature. Because those with SCD have dysautonomia, we anticipated that thermal exposure would induce autonomic hypersensitivity of their microvasculature with an increased propensity toward vasoconstriction. We exposed 17 patients with SCD and 16 control participants to a sequence of predetermined threshold temperatures for cold and heat detection and cold and heat pain via a thermode placed on the right hand. MBF was measured on the contralateral hand by photoplethysmography, and cardiac autonomic balance was assessed by determining heart rate variability. Thermal stimuli at both detection and pain thresholds caused a significant decrease in MBF in the contralateral hand within seconds of stimulus application, with patients with SCD showing significantly stronger vasoconstriction (P = .019). Furthermore, patients with SCD showed a greater progressive decrease in blood flow than did the controls, with poor recovery between episodes of thermal stimulation (P = .042). They had faster vasoconstriction than the controls (P = .033), especially with cold detection stimulus. Individuals with higher anxiety also experienced more rapid vasoconstriction (P = .007). Augmented vasoconstriction responses and progressive decreases in perfusion with repeated thermal stimulation in SCD are indicative of autonomic hypersensitivity in the microvasculature. These effects are likely to increase red cell entrapment in response to clinical triggers such as cold or stress, which have been associated with vaso-occlusive crises in SCD.

Mediastinal infantile hemangioma with spinal canal extension and extensive gastrointestinal involvement complicated by respiratory failure.

Infantile hemangioma is the most common soft tissue tumor of infancy. Extensive organ involvement is rare. This report describes an infant with biopsy confirmed infantile hemangioma with diffuse organ involvement causing anemia and failure to thrive. Treatment was initiated with propranolol and led to initial improvement; however, course was complicated by several episodes of respiratory failure secondary to pulmonary edema. Propranolol therapy was interrupted for several months while patient was maintained on a diuretic regimen and treated with vincristine and high-dose corticosteroids. Patient was transitioned back to propranolol and is clinically thriving with objective improvement on radiographic imaging.

Considerations for Biventricular Conversion of Fontan Circulation.

Despite significant improvements in the management of Fontan circulation in patients with single ventricle physiology, long-term outcomes continue to be suboptimal. Conversion to biventricular circulation is increasingly gaining popularity, particularly in the subset of patients who are not ideal Fontan candidates. Meticulous image-guided planning, extensive preoperative discussions, and a team-based approach are required for successful execution of complex biventricular conversion. A segmental approach to the anatomy of the heart defect allows methodical planning of the technique of biventricular conversion. Ventricular size and function continue to be the Achilles heel of successful biventricular repair. Long-term studies comparing outcomes in patients converted to biventricular circulation to those in patients with Fontan physiology are required to appropriately tailor management approaches to an individual patient.

Reduced Forced Vital Capacity and the Number of Chest Wall Surgeries are Associated with Decreased Exercise Capacity in Children with Congenital Heart Disease.

Low forced vital capacity (FVC) is associated with decreased exercise capacity in CHD. Multiple prior cardiac surgeries have been associated with low FVC. We seek to understand the relationship between low FVC, number of cardiac surgeries and cardiopulmonary response leading to decreased exercise capacity. Retrospective chart review of demographics, surgical history and exercise testing including spirometry was performed in patients with CHD. Single ventricle patients were excluded. Low FVC was defined as a Z-score below the lower limit of normal. Exercise parameters were expressed as a percent of predicted. There were 93 patients with 2 ventricle CHD identified over 34 months with cardiopulmonary exercise testing. The FVC Z-score directly correlated with peak V̇O2% (R2 = 0.07, p < 0.05), and the O2 pulse% (R2 = 0.25, p < 0.0001). The VE/VCO2 was inversely related to the FVC Z-score (R2 = 0.11, p < 0.01). Patients with minimum three prior surgeries had decreased peak VO2% (63.7 vs. 72.8, p < 0.05), decreased peak O2 pulse% (80.8 vs. 97.9, p < 0.01) and a lower mean FVC Z-score (- 1.9 vs - 0.38, p < 0.01). The FVC Z-score and number of surgeries both predicted peak V̇O2% in multivariate analysis. Our study demonstrated that low FVC and three or more prior cardiac surgeries were associated with lower exercise capacity and lower stroke volume response. More cardiac surgeries were also associated with low FVC. However, both low FVC and the number of surgeries were independent predictors of exercise capacity.

Kidney iron deposition by R2* is associated with haemolysis and urinary iron.

Kidney iron deposition measured by R2* (magnetic resonance imaging) MRI is posited to result from tubular reabsorption of filtered haemoglobin due to intravascular haemolysis. In chronically transfused sickle cell disease (SCD), R2* is elevated and positively correlated with lactate dehydrogenase (LDH). To account for contributions to renal iron from systemic iron overload, we evaluated kidney R2*, urinary iron and haemolysis markers in 62 non-transfused SCD patients. On multivariate analysis, kidney R2* was associated with urinary iron and LDH (R2  = 0·55, P < 0·0001). Our study confirms that kidney R2* is associated with intravascular haemolysis and raises important questions regarding the role of iron in SCD nephropathy.

Loss of alpha-globin genes in human subjects is associated with improved nitric oxide-mediated vascular perfusion.

Alpha thalassemia is a hemoglobinopathy due to decreased production of the α-globin protein from loss of up to four α-globin genes, with one or two missing in the trait phenotype. Individuals with sickle cell disease who co-inherit the loss of one or two α-globin genes have been known to have reduced risk of morbid outcomes, but the underlying mechanism is unknown. While α-globin gene deletions affect sickle red cell deformability, the α-globin genes and protein are also present in the endothelial wall of human arterioles and participate in nitric oxide scavenging during vasoconstriction. Decreased production of α-globin due to α-thalassemia trait may thereby limit nitric oxide scavenging and promote vasodilation. To evaluate this potential mechanism, we performed flow-mediated dilation and microvascular post-occlusive reactive hyperemia in 27 human subjects (15 missing one or two α-globin genes and 12 healthy controls). Flow-mediated dilation was significantly higher in subjects with α-trait after controlling for age (P = .0357), but microvascular perfusion was not different between groups. As none of the subjects had anemia or hemolysis, the improvement in vascular function could be attributed to the difference in α-globin gene status. This may explain the beneficial effect of α-globin gene loss in sickle cell disease and suggests that α-globin gene status may play a role in other vascular diseases.

Tricuspid regurgitant jet velocity and myocardial tissue Doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups - revisiting this controversial concept after 16 years of additional evidence.

Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death are the reasons for the majority of young adult mortality in SCD. To better understand the clinical importance of multi-level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S') and diastole (E'), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD. With up to 9 years of follow up, we determined survival in 95 children, adolescents and adults with SCD. Thirty-eight patients (40%) were less than 21 years old at initial evaluation. Survival and Cox proportional-hazards analysis were performed. There was 19% mortality in our cohort, with median age at death of 35 years. In the pediatric subset, there was 11% mortality during the follow up period. The causes of death included cardiovascular and pulmonary complications in addition to other end-organ failure. On Cox proportional-hazards analysis, our model predicts that a 0.1 m/s increase in TRV increases risk of mortality 3%, 1 cm/s increase in S' results in a 91% increase, and 1 cm/s decrease in E' results in a 43% increase in mortality. While excluding cardiac parameters, higher plasma free hemoglobin was significantly associated with risk of mortality (p=.049). In conclusion, elevated TRV and altered markers of cardiac systolic and diastolic function predict mortality in a cohort of adolescents and young adult patients with SCD. These predictors should be considered when counseling cardiovascular risk and therapeutic optimization at transition to adult providers.

Extracardiac Doppler indices predict perinatal mortality in fetuses with Ebstein anomaly and tricuspid valve dysplasia.

OBJECTIVES: Ebstein anomaly and tricuspid valve dysplasia (EA/TVD) carry high perinatal mortality. Past studies have focused on cardiac predictors of mortality; we sought to describe the fetal echo (FE) extracardiac Dopplers in this cohort and determine their association with perinatal mortality. METHOD: Fetuses with EA/TVD at 23 centers from 2005-2011 were included for retrospective study. Doppler pattern and velocity of the umbilical artery (UA), umbilical vein (UV), ductus venosus (DV), and middle cerebral artery (MCA) were collected. Bivariate and multivariate analyzes were performed. The primary outcome measure was perinatal mortality, defined as fetal demise or neonatal death. RESULTS: Of 190 cases that met eligibility criteria, alterations were seen in 50% of UA, 16% of UV, 48% of DV, and 8% of MCA Doppler indices on the last FE (median 27.4 weeks). Independent predictors of perinatal mortality included abnormal UA Doppler pattern of absence or reversed end diastolic flow (OR 9.7) and UV velocity z score <1 (OR 2.5), in addition to diagnosis <32 weeks (OR 4.2) and tricuspid valve (TV) annulus z score ≥6 (OR 5.3). CONCLUSION: Abnormal UA Doppler pattern and decreased UV velocity are independent predictors of perinatal mortality in EA/TVD fetuses and should be used to refine mortality risk and guide perinatal management.

Mental stress causes vasoconstriction in subjects with sickle cell disease and in normal controls.

Vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD) and occurs when deoxygenated sickled red blood cells occlude the microvasculature. Any stimulus, such as mental stress, which decreases microvascular blood flow will increase the likelihood of red cell entrapment resulting in local vaso-occlusion and progression to VOC. Neurally mediated vasoconstriction might be the physiological link between crisis triggers and vaso-occlusion. In this study, we determined the effect of mental stress on microvascular blood flow and autonomic nervous system reactivity. Sickle cell patients and controls performed mentally stressful tasks, including a memory task, conflict test and pain anticipation test. Blood flow was measured using photoplethysmography, autonomic reactivity was derived from electrocardiography and perceived stress was measured by the State-Trait Anxiety Inventory questionnaire. Stress tasks induced a significant decrease in microvascular blood flow, parasympathetic withdrawal and sympathetic activation in all subjects. Of the various tests, pain anticipation caused the highest degree of vasoconstriction. The magnitude of vasoconstriction, sympathetic activation and perceived stress was greater during the Stroop conflict test than during the N-back memory test, indicating the relationship between magnitude of experimental stress and degree of regional vasoconstriction. Baseline anxiety had a significant effect on the vasoconstrictive response in sickle cell subjects but not in controls. In conclusion, mental stress caused vasoconstriction and autonomic nervous system reactivity in all subjects. Although the pattern of responses was not significantly different between the two groups, the consequences of vasoconstriction can be quite significant in SCD because of the resultant entrapment of sickle cells in the microvasculature. This suggests that mental stress can precipitate a VOC in SCD by causing neural-mediated vasoconstriction.

Procedural, pregnancy, and short-term outcomes after fetal aortic valvuloplasty.

OBJECTIVES: We aimed to evaluate the effect of technical aspects of fetal aortic valvuloplasty (FAV) on procedural risks and pregnancy outcomes. BACKGROUND: FAV is performed in cases of severe mid-gestation aortic stenosis with the goal of preventing hypoplastic left heart syndrome (HLHS). METHODS: The International Fetal Cardiac Intervention Registry was queried for fetuses who underwent FAV from 2002 to 2018, excluding one high-volume center. RESULTS: The 108 fetuses had an attempted cardiac puncture (mean gestational age [GA] 26.1 ± 3.3 weeks). 83.3% of attempted interventions were technically successful (increased forward flow/new aortic insufficiency). The interventional cannula was larger than 19 g in 70.4%. More than one cardiac puncture was performed in 25.0%. Intraprocedural complications occurred in 48.1%, including bradycardia (34.1%), pericardial (22.2%) or pleural effusion (2.7%) requiring drainage, and balloon rupture (5.6%). Death within 48 hr occurred in 16.7% of fetuses. Of the 81 patients born alive, 59 were discharged home, 34 of whom had biventricular circulation. More than one cardiac puncture was associated with higher complication rates (p < .001). Larger cannula size was associated with higher pericardial effusion rates (p = .044). On multivariate analysis, technical success (odds ratio [OR] = 10.9, 95% confidence interval [CI] = 2.2-53.5, p = .003) and later GA at intervention (OR = 1.5, 95% CI = 1.2-1.9, p = .002) were associated with increased odds of live birth. CONCLUSIONS: FAV is an often successful but high-risk procedure. Multiple cardiac punctures are associated with increased complication and fetal mortality rates. Later GA at intervention and technical success were independently associated with increased odds of live birth. However, performing the procedure later in gestation may miss the window to prevent progression to HLHS.

Sickle cell microvascular paradox-oxygen supply-demand mismatch.

We have previously demonstrated that sickle cell disease (SCD) patients maintain normal global systemic and cerebral oxygen delivery by increasing cardiac output. However, ischemic end-organ injury remains common suggesting that tissue oxygen delivery may be impaired by microvascular dysregulation or damage. To test this hypothesis, we performed fingertip laser Doppler flowmetry measurements at the base of the nailbed and regional oxygen saturation (rSO2 ) on the dorsal surface of the same hand. This was done during flow mediated dilation (FMD) studies in 26 chronically transfused SCD, 75 non-transfused SCD, and 18 control subjects. Chronically transfused SCD patients were studied prior to and following a single transfusion and there was no acute change in rSO2 or perfusion. Laser Doppler estimates of resting perfusion were 76% higher in non-transfused and 110% higher in transfused SCD patients, compared to control subjects. In contrast, rSO2 was 12 saturation points lower in non-transfused SCD patients, but normal in the transfused SCD patients. During cuff occlusion, rSO2 declined at the same rate in all subjects suggesting similar intrinsic oxygen consumption rates. Upon cuff release, laser doppler post occlusive hyperemia was blunted in SCD patients in proportion to their resting perfusion values. Transfusion therapy did not improve the hyperemia response. FMD was impaired in SCD subjects but partially ameliorated in transfused SCD subjects. Taken together, non-transfused SCD subjects demonstrate impaired conduit artery FMD, impaired microcirculatory post-occlusive hyperemia, and resting hypoxia in the hand despite compensated oxygen delivery, suggesting impaired oxygen supply-demand matching. Transfusion improves FMD and oxygen supply-demand matching but not microcirculation hyperemic response.

Differences in Right Ventricular Physiologic Response to Chronic Volume Load in Patients with Repaired Pulmonary Atresia Intact Ventricular Septum/Critical Pulmonary Stenosis Versus Tetralogy of Fallot.

BACKGROUND: Patients with pulmonary atresia with intact ventricular septum and critical pulmonary stenosis (PAIVS/CPS) have wide variation in right ventricle (RV) size, systolic function, and diastolic function at birth. Establishment of antegrade pulmonary blood flow creates the potential for RV dilation from chronic pulmonary insufficiency. Future surgical decisions are based on RV size and function, largely supported by longitudinal studies of patients with Tetralogy of Fallot (TOF). Given potential differences in RV physiology and lack of similar data in PAIVS/CPS, the objective of this study was to determine differences in RV size, systolic function, and diastolic function between patients with PAIVS/CPS versus TOF. METHODS: We retrospectively collected cardiovascular magnetic resonance (CMR) data in 27 patients with PAIVS/CPS (ages 13.3 ± 8.8 years) and 78 with TOF (11.4 ± 5.4 years). RV volumes, ejection fraction (EF), regurgitant fraction, end-diastolic forward flow across the pulmonary valve, and right atrial cross-sectional area were calculated. RESULTS: There was no difference between the groups in RV end-diastolic volume (RVEDVi), RVEF, or pulmonary regurgitation. RVEF tended to decrease in TOF when RVEDVi exceeded 164 ml/m2. In PAIVS/CPS, RVEDVi less frequently reached 164 ml/m2 and was not associated with RVEF. There was worse RV diastolic dysfunction in PAIVS/CPS, with 1.5 times larger right atrial area and two times higher pulmonary end-diastolic forward flow (p < 0.0001). CONCLUSIONS: Patients with PAIVS/CPS have similar RV size, systolic function, and pulmonary regurgitation as TOF. However, impaired RV diastolic function may limit extremes of RV dilatation and impact long-term management of PAIVS/CPS.