From theory to practice: optimizing the efficiency of an inefficient circulation.
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Blood Circulation↗
Biomedical subjects
Doff B McElhinney
Publications and source records attributed to Doff B McElhinney.
Endovascular stenting of obstructed right ventricle-to-pulmonary artery conduits: a 15-year experience.
BACKGROUND: The optimal treatment for dysfunctional right ventricle-to-pulmonary artery (RV-PA) conduits is unknown. Limited follow-up data on stenting of RV-PA conduits have been reported. METHODS AND RESULTS: Between 1990 and 2004, deployment of balloon-expandable bare stents was attempted in 242 obstructed RV-PA conduits in 221 patients (median age, 6.7 years). Acute hemodynamic changes after stenting included significantly decreased RV systolic pressure (89+/-18 to 65+/-20 mm Hg, P<0.001) and peak RV-PA gradient (59+/-19 to 27+/-14 mm Hg, P<0.001). There were no deaths, and, aside from 5 malpositioned stents requiring surgical removal, there were no serious procedural complications. During follow-up of 4.0+/-3.2 years, 9 patients died and 2 underwent heart transplantation, none related to catheterization or stent malfunction. During 155 follow-up catheterizations in 126 patients, the stent was redilated in 83 patients and additional stents were placed in 41. Stent fractures were diagnosed in 56 patients (43%) and associated with stent compression and substernal location but did not cause acute hemodynamic consequences. By Kaplan-Meier analysis, median freedom from conduit surgery after stenting was 2.7 years (3.9 years in patients >5 years), with younger age, homograft conduit, conduit diameter < or =10 mm, diagnosis other than tetralogy of Fallot, Genesis stent, higher prestent RV:aortic pressure ratio, and stent malposition associated with shorter freedom from surgery. Tricuspid regurgitation and RV function did not change between stent implantation and subsequent surgery. CONCLUSIONS: Conduit stenting is an effective interim treatment for RV-PA conduit obstruction and prolongs conduit lifespan in most patients. Stent fractures were common but not associated with significant complications or earlier conduit reoperation.
Adolescent↗
Validation and re-evaluation of a discriminant model predicting anatomic suitability for biventricular repair in neonates with aortic stenosis.
OBJECTIVES: The purpose of this study was to validate and re-evaluate our previously reported scoring systems for predicting optimal management in neonates with aortic stenosis (AS). BACKGROUND: In 1991, we reported a multivariate discriminant equation and an ordinal scoring system for predicting which neonates with AS are suitable for biventricular repair and which are better served by single ventricle management. METHODS: Retrospective analysis was performed to: 1) validate our scoring systems in 89 additional neonates with AS and normal mitral valve area, 2) assess the effects of 5% measurement variation on predictive scores, 3) evaluate our cohort with the Congenital Heart Surgeons' Society scoring system, and 4) repeat the discriminant analysis on the basis of all 126 patients. RESULTS: The original scores each predicted outcome accurately in 68 patients (77%). Minor (5%) measurement variation changed the outcome predicted by the discriminant equation in 8 patients (9%) and by the threshold system in 13 patients (15%). The most accurate model for predicting survival with a biventricular circulation among the full cohort is: 10.98 (body surface area) + 0.56 (aortic annulus z-score) + 5.89 (left ventricular to heart long-axis ratio) - 0.79 (grade 2 or 3 endocardial fibroelastosis) - 6.78. With a cutoff of -0.65, outcome was predicted accurately in 90% of patients. CONCLUSIONS: Both of our original scoring systems are less accurate at predicting outcome than in our original analysis. Revised discriminant analysis yielded a model similar to our original equation that was 90% accurate at predicting survival with a biventricular circulation among neonates with AS and a mitral valve area z-score >-2.
Aortic Valve Stenosis↗
Fetal aortic valve stenosis and the evolution of hypoplastic left heart syndrome: patient selection for fetal intervention.
BACKGROUND: Fetal aortic valvuloplasty may prevent progression of aortic stenosis (AS) to hypoplastic left heart syndrome (HLHS). Predicting which fetuses with AS will develop HLHS is essential to optimize patient selection for fetal intervention. The aim of this study was to define echocardiographic features associated with progression of midgestation fetal AS to HLHS. METHODS AND RESULTS: Fetal echocardiograms were reviewed from 43 fetuses diagnosed with AS and normal left ventricular (LV) length at < or =30 weeks' gestation. Of 23 live-born patients with available follow-up data, 17 had HLHS and 6 had a biventricular circulation. At the time of diagnosis, LV length, mitral valve, aortic valve, and ascending aortic diameter Z-scores did not differ between fetuses that ultimately developed HLHS and those that maintained a biventricular circulation postnatally. However, all of the fetuses that progressed to HLHS had retrograde flow in the transverse aortic arch (TAA), 88% had left-to-right flow across the foramen ovale, 91% had monophasic mitral inflow, and 94% had significant LV dysfunction. In contrast, all 6 fetuses with a biventricular circulation postnatally had antegrade flow in the TAA, biphasic mitral inflow, and normal LV function. With advancing gestation, growth arrest of left heart structures became evident in fetuses developing HLHS. CONCLUSIONS: In midgestation fetuses with AS and normal LV length, reversed flow in the TAA and foramen ovale, monophasic mitral inflow, and LV dysfunction are predictive of progression to HLHS. These physiological features may help refine patient selection for fetal intervention to prevent the progression of AS to HLHS.
Abortion, Therapeutic↗
Neo-aortic valvar function after the arterial switch.
OBJECTIVES: The purpose of our study was to assess the prevalence and progression, during childhood and adolescence, of dilation of the neo-aortic root, and neo-aortic valvar regurgitation, and to identify risk factors for such dilation and regurgitation, after the arterial switch operation. METHODS: We included all patients who had undergone an arterial switch operation at The Children's Hospital of Philadelphia, and had been followed for a minimum of 4 years, and had at least 2 postoperative echocardiograms. Neo-aortic valvar regurgitation was quantitatively assessed, and measurements were made of the neo-aortic root at the level of the basal attachment of the leaflets, mid-sinusal level, and the sinutubular junction. RESULTS: We found 82 patients who satisfied the criterions for inclusion, of whom 52 patients had transposition with an intact ventricular septum, and 30 had either an associated ventricular septal defect or double outlet right ventricle. The median follow-up time was 8.8 years (4.1 to 16.4 years). The neo-aortic valve had been replaced in 1 patient. Of the patients, 3 had moderate, 66 had trivial to mild, and 12 had no neo-aortic valvar regurgitation at their most recent follow-up. The regurgitation had progressed by at least 1 grade in 38 of the 82 patients (46.4%). Neo-aortic dilation was noted at the basal attachment of the leaflets, and at mid-sinusal level, which was out of proportion to somatic growth. CONCLUSIONS: At mid-term follow-up, significant neo-aortic valve regurgitation is present in 3.7%, and trivial to mild regurgitation in 81.4% of patients. The regurgitation progressed in almost half of the patients over time. We also noted progressive dilation of the neo-aortic root out of proportion to somatic growth.
Aortic Valve Insufficiency↗
Fetal tricuspid valve size and growth as predictors of outcome in pulmonary atresia with intact ventricular septum.
OBJECTIVE: Pulmonary atresia with intact ventricular septum is a complex congenital cardiovascular anomaly that frequently requires single ventricle palliation. Fetal diagnosis of pulmonary atresia with intact ventricular septum is common, but the natural history of pulmonary atresia with intact ventricular septum diagnosed in midgestation, predictors of neonatal anatomy, and predictors of biventricular repair have not been determined. The objective of this study was to determine whether the size and rate of growth of the fetal tricuspid valve predict neonatal anatomy and biventricular repair. DESIGN AND RESULTS: Twenty-three fetuses diagnosed with pulmonary atresia with intact ventricular septum between 1990 and 2004 were studied. Of 13 fetuses with a midgestation fetal tricuspid valve z score < or = -3, 1 achieved biventricular repair, compared with 5 of 5 with a tricuspid valve z score > -3. Of 13 fetuses with a midgestation fetal tricuspid valve z score < or = -3, 8 were diagnosed postnatally with a right ventricular dependent coronary circulation, compared with none with a tricuspid valve z score > -3. Midgestation and late gestation fetal tricuspid valve z scores correlated with neonatal tricuspid valve z score. The average rate of tricuspid valve growth between mid- and late fetal echocardiograms was significantly lower in patients who did not achieve biventricular repair than in those who did (0.012 +/- 0.008 cm per week vs 0.028 +/- 0.014 cm per week). CONCLUSIONS: Fetal tricuspid valve z score and rate of growth predict postnatal outcome in pulmonary atresia with intact ventricular septum. These findings may have important implications for prenatal counseling and selection of patients for fetal pulmonary valve dilation.
Anastomosis, Surgical↗
Improving outcomes in fetuses and neonates with congenital displacement (Ebstein's malformation) or dysplasia of the tricuspid valve.
From 1984 to 2004, 66 patients were diagnosed with Ebstein's malformation (n = 61) or congenital tricuspid valve (TV) dysplasia (n = 5) in utero or during the first month of life. Of these, 33 were diagnosed by fetal echocardiography at a median gestational age of 22 weeks, and 33 were diagnosed postnatally at a median age of 1 day (range 1 to 27). In 8 of the 33 prenatally diagnosed patients (24%), the pregnancies were terminated; in 9 (27%), the fetuses died in utero, and in 16 (49%), the fetuses survived to birth. Seven prenatally diagnosed patients survived beyond the neonatal period (21% of 33). Of the 49 neonates, 35 (71%) survived to hospital discharge and beyond 1 month of age. Independent predictors of death by multivariable logistic regression analysis included right atrial area index >1, the absence of anterograde flow across the pulmonary valve, and diagnosis before 1997. Although outcomes in fetuses and neonates with congenital anomalies of the TV have improved in more recent experience, survival in patients at the severe end of the spectrum remains poor. To improve outcomes in this group of high-risk patients, novel approaches to management may be indicated.
Adult↗
Current management of severe congenital mitral stenosis: outcomes of transcatheter and surgical therapy in 108 infants and children.
BACKGROUND: Severe congenital mitral stenosis (MS) is a rare anomaly that is frequently associated with additional left heart obstructions. Anatomic treatments for congenital MS include balloon mitral valvuloplasty (BMVP), surgical mitral valvuloplasty (SMVP), and mitral valve replacement (MVR), although the optimal therapeutic strategy is unclear. METHODS AND RESULTS: Between 1985 and 2003, 108 patients with severe congenital MS underwent BMVP or surgical intervention at a median age of 18 months (range 1 month to 17.9 years). Anatomic subtypes of MS were "typical" congenital MS in 78 patients, supravalvar mitral ring in 46, parachute mitral valve in 28, and double-orifice mitral valve in 11, with multiple types in approximately 50% of patients. Additional left heart anomalies were present in 82 patients (76%). The first MS intervention was BMVP in 64 patients, SMVP in 33, and MVR in 11. BMVP decreased peak and mean MS gradients by a median of 33% and 38%, respectively (P<0.001), but was complicated by significant mitral regurgitation in 28%. Cross-sectional follow-up was obtained at 4.8+/-4.2 years. Overall, Kaplan-Meier survival was 92% at 1 month, 84% at 1 year, and 77% at 5 years, with 69% 5-year survival during the first decade of our experience and 87% since (P=0.09). Initial MVR and younger age were associated with worse survival. Survival free from failure of biventricular repair or mitral valve reintervention was 55% at 1 year among patients who underwent BMVP and 69% among patients who underwent supravalvar mitral ring resection initially. Among patients who underwent BMVP, survival free from failure of biventricular repair or MVR was 79% at 1 month and 55% at 5 years, with worse outcome in younger patients and those who developed significant postdilation mitral regurgitation. CONCLUSIONS: BMVP effectively relieves left ventricular inflow obstruction in most infants and children with severe congenital MS who require intervention. However, surgical resection is preferable in patients with MS due to a supravalvar mitral ring. Five-year survival is relatively poor in patients with severe congenital MS, with worse outcomes in infants and patients undergoing MVR, but has improved in our more recent experience. Many patients have undergone second procedures for either recurrent/residual MS or mitral regurgitation resulting from dilation-related disruption of the mitral valve apparatus.
Adolescent↗
Left heart growth, function, and reintervention after balloon aortic valvuloplasty for neonatal aortic stenosis.
BACKGROUND: Transcatheter balloon aortic valvuloplasty (BAVP) has become the first-line treatment for critical aortic stenosis (AS) in neonates. However, little is known about the growth and function of left heart structures or about patterns of reintervention on the left heart after neonatal BAVP. METHODS AND RESULTS: Between 1985 and 2002, 113 patients underwent neonatal BAVP at < or =60 days of age. There were 16 early deaths (14%), with a significant decrease from 1985 to 1993 (22%) to 1994 to 2002 (4%), and 6 patients had successful early conversion to a univentricular circulation. In the short term, the mean relative gradient reduction was 54+/-26%, and significant aortic regurgitation (AR) developed in 15% of patients. The 91 early survivors with a biventricular circulation were followed up for 6.3+/-5.3 years, during which time there was a steady increase in the frequency of significant AR. Freedom from moderate or severe AR was 65% at 5 years. In almost all patients with a baseline aortic annulus z score less than -1, the annulus diameter increased to within the normal range within 1 to 2 years. Similarly, left ventricular (LV) end-diastolic dimension z scores, which ranged from -5 to 7.5 before BAVP, normalized within 1 to 2 years in nearly all patients with a predilation z score less than -1. Among early survivors with a biventricular circulation, reintervention-free survival on the LV outflow tract was 65% at 1 year and 48% at 5 years, with younger age, higher pre- and post-BAVP gradients, and a larger balloon-annulus diameter ratio associated with decreased reintervention-free survival (P<0.01). Seventeen surgical interventions were performed on the aortic valve in 15 patients, including replacement in 7. Survival free from aortic valve replacement was 84% at 5 years. CONCLUSIONS: BAVP for AS during the first 60 days of life results in short-term relief of AS in the majority of patients. Among early survivors, initially small left heart structures may be associated with worse subacute outcomes but typically normalize within 1 year. Reintervention for residual/recurrent AS or iatrogenic AR is relatively common, particularly during the first year after BAVP, but aortic valve replacement during early childhood is seldom necessary.
Aortic Valve↗
Creation of a brachial arteriovenous fistula for treatment of pulmonary arteriovenous malformations after cavopulmonary anastomosis.
BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) occur in approximately 20% of patients after unidirectional superior cavopulmonary anastomosis (CPA), and frequently after bidirectional CPA in patients with polysplenia syndrome. It is hypothesized that exclusion of a growth-modulating factor produced in the liver may predispose to PAVM formation. Resolution of PAVMs after inclusion of hepatic venous effluent into the cavopulmonary circulation has been reported. An upper extremity systemic arteriovenous (AV) fistula may be created to augment pulmonary blood flow and improve oxygenation in hypoxemic patients with CPA, but there has been no systematic investigation of the effects of such fistulas on PAVMs after CPA. METHODS: We studied 11 patients with PAVMs who underwent creation of a brachial AV fistula a median of 11 years after CPA. RESULTS: Eight patients had discontinuous pulmonary arteries or unilateral flow of a bidirectional CPA and were not considered good candidates for Fontan completion; the other 3 patients had polysplenia and unilateral hepatic venous streaming after Fontan completion. Three patients died of progressive complications of their heart disease 4 to 18 months after AV fistula creation. Pulmonary arteriovenous malformations resolved after creation of a brachial AV fistula in 4 of 5 surviving patients with unilateral flow of a superior CPA, but in none of 3 patients with polysplenia who had unilateral hepatic venous streaming after Fontan completion and PAVMs in the contralateral lung. CONCLUSIONS: These findings are consistent with the "hepatic factor" hypothesis, according to which the development of PAVMs is facilitated when an unidentified factor produced or metabolized in the liver does not reach the pulmonary circulation before traversing another capillary bed. Patients with unilateral superior CPA flow and PAVMs who are not considered candidates for Fontan completion may benefit from a brachial AV fistula.
Adolescent↗
Incorporation of the hepatic veins into the cavopulmonary circulation in patients with heterotaxy and pulmonary arteriovenous malformations after a Kawashima procedure.
BACKGROUND: In patients with polysplenia syndrome and azygous continuation of an interrupted inferior vena cava (IVC), pulmonary arteriovenous malformations (PAVMs) are relatively common after bidirectional cavopulmonary anastomosis (BCPA, Kawashima procedure). Resolution of PAVMs after hepatic vein (HV) inclusion into the cavopulmonary circulation has been reported, but there has been no systematic investigation of the effects of this therapy in a population of more than 3 patients. METHODS: We studied 16 patients with heterotaxy, univentricular congenital heart disease, and azygous continuation of the IVC who underwent incorporation of the HV into the cavopulmonary circuit for treatment of significant PAVMs after a Kawashima procedure. RESULTS: The median preoperative systemic arterial oxygen saturation (SsaO2) was 76% (65%-85%), compared with 89% (85% to 92%) early after BCPA. Among 15 early survivors, the median early postoperative SsaO2 was 76% (56%-85%). In 11 of the 15 survivors, SsaO2 rose to 90% or greater within a year and remained at 93% or greater at follow-up of 2.8 to 10 years. Four patients had persistent hypoxemia and residual PAVMs at follow-up catheterization 1.5 to 8 years postoperatively; these patients had the most severe hypoxemia prior to HV inclusion, and in 2 the residual PAVMs were unilateral, with HV flow streaming to the contralateral lung, in which PAVMs had resolved. CONCLUSIONS: Hypoxemia resolved after cavopulmonary incorporation of the HV in the majority of our patients with PAVMs after the Kawashima operation, presumably due to a combination of PAVM resolution and elimination of hepatic venoatrial right-to-left shunting. These findings support the theory that development of PAVMs is facilitated by exclusion of HV effluent from the pulmonary circulation.
Adolescent↗
Aortic valvuloplasty in the fetus: technical characteristics of successful balloon dilation.
OBJECTIVES: To describe technical aspects of successful fetal aortic valvuloplasty, with particular attention to balloon size. STUDY DESIGN: We retrospectively reviewed all procedural records and echocardiograms pertaining to 26 attempts at fetal aortic valve dilation performed at a single center over a period of 4 years. We assessed the effect of valvuloplasty as determined by echocardiographic appearance at the time of intervention and in follow-up. RESULTS: In 20 of 26 fetuses who had technically successful aortic valve dilation (median balloon:annulus ratio=1.1), all had improved antegrade flow and 12 had at least mild regurgitation after dilation. Use of an oversized balloon was associated with the onset of moderate or severe aortic regurgitation, seen in 5 fetuses. This aortic regurgitation was well tolerated and improved through the remainder of gestation. CONCLUSIONS: These data imply that fetal aortic valves can be dilated safely with larger balloons than are commonly used for postnatal dilation. The observation of spontaneous improvement in postdilation aortic regurgitation further suggests that fetal valve tissue behaves uniquely.
Aortic Valve Insufficiency↗
Transcatheter device closure of congenital and postoperative residual ventricular septal defects.
BACKGROUND: Our purpose was to describe a 13-year experience with patients undergoing transcatheter device closure of unrepaired congenital or postoperative residual ventricular septal defects (VSDs). METHODS AND RESULTS: Since 1989, 170 patients (median age, 3.9 years) have undergone catheterization for closure of 1 or more congenital (n=92) or postoperative (n=78) residual VSDs using successive generations of STARFlex-type devices. Outcomes included echocardiographic assessment of residual flow and device position, assessment of VSD shunt/severity, and adverse events. Among 168 patients in whom device implantation was performed, between 1 and 7 devices were placed per patient (median, 1), with multiple devices placed in 40%. There was a significant decrease in left-to-right shunting after device implantation (P<0.001) and significant improvement in VSD size/severity, and device position proved stable. Of 332 adverse events, 39 were related to the device and 261 were related to the catheterization; all but 5 occurred in the periprocedural period. At a median follow-up of 24 months (0 to 154 months), 14 patients had died and 18 had device(s) explanted. CONCLUSIONS: Congenital and postoperative VSD closure using STARFlex-type devices resulted in stable improvement in clinical status and decreased interventricular shunting. Although periprocedural events occurred frequently, late events caused by the device were rare. Transcatheter device closure is an effective management option for patients with complex muscular VSDs that are difficult to approach surgically and for postoperative residual VSDs.
Cardiac Catheterization↗
Hypoplastic left heart syndrome with intact or highly restrictive atrial septum: outcome after neonatal transcatheter atrial septostomy.
BACKGROUND: Hypoplastic left heart syndrome (HLHS) with intact or very restrictive atrial septum is a highly lethal combination. We review our 13-year institutional experience treating this high-risk subgroup of patients with emergent catheter therapy. METHODS AND RESULTS: Infants with HLHS requiring catheter septostomy within the first 2 days of life were compared with a matched control group with adequate interatrial communication. Preoperative, early postoperative, and medium-term survival were evaluated. Earlier experience was compared with recent results to assess the effect of changes in catheterization and surgical and intensive care unit management strategies over the study period. From 1990 to 2002, 33 newborns with HLHS (11% of newborns with HLHS managed during this period) underwent urgent/semiurgent catheterization to create or enlarge an interatrial communication before surgical palliation. Preoperative and early postoperative mortality were high (48%) compared with control HLHS patients, regardless of prenatal diagnosis and despite successful catheter-based atrial septostomy with clinical stabilization. Mortality trended down during the later part of the study period. Those who survived the neonatal period had late survival, pulmonary artery pressure, and resistance similar to those of control subjects. CONCLUSIONS: Neonatal mortality in the subgroup of HLHS patients with intact or highly restrictive atrial septum remains high despite successful urgent septostomy. Persistently poor outcomes for these patients have prompted efforts at our center to develop techniques for fetal intervention for this condition, in the hope that prenatal relief of left atrial and pulmonary venous hypertension may promote normal pulmonary vascular and parenchymal development and improve both short- and long-term outcomes.
Cardiac Catheterization↗
Recombinant human growth hormone treatment for dilated cardiomyopathy in children.
OBJECTIVE: Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure among children and is often progressive despite maximal medical therapy. Heart failure is characterized by a number of neurohormonal abnormalities, including derangements in the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) signaling axis. Decreased serum levels of GH, which acts on cardiac myocytes primarily through IGF-1, are associated with impaired myocardial growth and function, which can be improved with restoration of GH/IGF-1 homeostasis. In animal models and among human adults with heart failure attributable to DCM, treatment with GH results in acquisition of left ventricular (LV) mass and improved LV function, through a combination of mechanisms. We undertook this study to determine the effects of recombinant human GH on LV function and mass among children with stable LV dysfunction attributable to DCM. METHODS: We performed a prospective, single-center, randomized, partially blinded, crossover trial among children 1 to 19 years of age with DCM and cardiac dysfunction of > or =6-month duration. After enrollment, patients were randomly assigned to receive treatment for 6 months with either conventional therapy (determined by the patient's primary cardiologist) plus recombinant human GH (0.025-0.04 mg/kg per day), administered as daily subcutaneous injections, or conventional therapy alone. Patients were then crossed over to the other treatment strategy for 6 months. The primary outcome measure was change in LV shortening fraction (SF). Other echocardiographic indices of LV function, somatic growth, and somatotropic/thyroid hormone levels were also monitored. RESULTS: Only 8 of an intended 15 patients were enrolled, because of a combination of factors. Two patients withdrew during the study as a result of declining LV function requiring transplantation. LV SF did not change significantly during GH treatment, although both LV SF and LV SF z score were higher 6 months after cessation of GH treatment than at baseline. LV ejection fraction increased during GH therapy to a degree that approached significance. Height and weight percentiles for age increased significantly during GH therapy and remained higher 6 months after treatment. Annualized height velocity during GH treatment (13.7 +/- 3.3 cm/year, >97th percentile for all patients) was significantly higher than that after GH discontinuation (3.2 +/- 3.5 cm/year). Serum levels of IGF-1 and IGF-binding protein-3 were significantly higher after 6 months of GH treatment and 6 months after discontinuation of GH treatment than at baseline. There were no adverse events related to GH treatment. DISCUSSION: In this prospective, single-center, randomized, partially blinded, crossover trial, recombinant human GH was administered to 8 pediatric patients with stable chronic heart failure secondary to DCM. Because of unanticipated difficulty enrolling eligible patients, the study was underpowered to detect changes in our primary outcome measure of the magnitude we projected. Nevertheless, we did observe several notable cardiovascular effects of GH treatment, including a trend toward improved LV ejection fraction during the course of GH treatment and significantly improved LV SF, SF z score, and LV end systolic stress z score 6 months after discontinuation of GH treatment (relative to baseline values). Given the fact that levels of IGF-1, the primary myocardial effector of GH signaling, remained significantly higher 6 months after GH treatment than at baseline, the improvement in LV functional indices 6 months after discontinuation of therapy may represent progression or perpetuation of a GH treatment effect. In addition to its cardiovascular effects, GH therapy was associated with significant acceleration of somatic growth. The benefits of GH were not associated with significant attributable side effects, although 2 patients developed progressive LV dysfunction during the study and underwent cardiac transplantation.
Adolescent↗
NKX2.5 mutations in patients with congenital heart disease.
OBJECTIVES: The purpose of this study was to estimate the frequency of NKX2.5 mutations in specific cardiovascular anomalies and investigate genotype-phenotype correlations in individuals with NKX2.5 mutations. BACKGROUND: Recent reports have implicated mutations in the transcription factor NKX2.5 as a cause of various congenital heart defects (CHD). METHODS: We tested genomic deoxyribonucleic acid from 608 prospectively recruited patients with conotruncal anomalies (n = 370), left-sided lesions (n = 160), secundum atrial septal defect (ASD) (n = 71), and Ebstein's malformation (n = 7) for NKX2.5 mutations. RESULTS: Twelve distinct mutations in the NKX2.5 coding region were identified in 18 of 608 patients (3%), including 9 of 201 (4%) with tetralogy of Fallot, 3 of 71 (4%) with a secundum ASD, one each with truncus arteriosus, double-outlet right ventricle, L-transposition of the great arteries, interrupted aortic arch, hypoplastic left heart syndrome, and aortic coarctation, but in no patients with D-transposition of the great arteries (n = 86) or valvar aortic stenosis (n = 21). Eleven of the mutations were amino acid-altering missense nucleotide substitutions or deletions, and one was predicted to cause premature termination of translation. None of the mutations were in the homeodomain. Sixteen of the 18 individuals with NKX2.5 mutations in this study had no family history of congenital cardiovascular anomalies, and one had first-degree atrioventricular (AV) block. CONCLUSIONS: NKX2.5 mutations occur in a small percentage of patients with various CHD. Most of the mutations identified in this study were missense, outside the homeodomain, and not associated with AV block. These findings suggest that NKX2.5 mutations in non-homeodomain regions may be important in the development of human structural cardiac defects.
Genotype↗
Association between cardiac tumors and tuberous sclerosis in the fetus and neonate.
A retrospective review was performed in 94 patients with > or =1 cardiac tumors seen on prenatal or neonatal echocardiography at 5 major referral centers. Tuberous sclerosis was present in 68 patients diagnosed with a cardiac tumor in utero or during the neonatal period, including 61 of 64 with multiple tumors.
Fetal Diseases↗
Neo-aortic root dilation and valve regurgitation up to 21 years after staged reconstruction for hypoplastic left heart syndrome.
OBJECTIVES: We sought to assess the prevalence and progression of neo-aortic root dilation and valvar regurgitation after staged reconstruction for hypoplastic left heart syndrome (HLHS). BACKGROUND: In HLHS, the pulmonary valve functions as the neo-aortic valve. Neo-aortic valve dysfunction has been observed after arterial switch operation and the Ross procedure. METHODS: Patients with HLHS born before January 1995 who had the Fontan operation and had serial echocardiograms were included. Echocardiograms were reviewed preoperatively, after each surgical reconstruction, and at most recent follow-up for neo-aortic root size and severity of neo-aortic regurgitation (AR). Potential risk factors for neo-aortic valve dysfunction were assessed. RESULTS: Fifty-three patients met inclusion criteria. Bidirectional superior cavopulmonary anastomosis as an interim procedure was performed in 39 patients (74%). Median duration of follow-up was 9.2 (range 5.1 to 21) years. During follow-up, the neo-aortic root progressively dilated out of proportion to body size over time, with 52 patients (98%) having a Z-score >2 at most recent follow-up. Neo-AR was present in 61% of patients at most recent follow-up, with progression over time in 26 patients (49%). However, neo-AR was more than mild in only three patients. Significantly larger neo-aortic root Z-scores were observed in patients with any degree of neo-AR at most recent follow-up. No other anatomic or clinical variables correlated with severity of neo-AR or root dilation. CONCLUSIONS: After staged reconstruction for HLHS, neo-aortic root dilation and neo-AR progress over time. Early volume unloading does not have a beneficial impact on dilation of the neo-aortic root. These findings raise concerns about neo-aortic valve function into adulthood.
Aortic Valve Insufficiency↗