Carlen A. Gomez

Creation of an Atrial Septal Defect In Utero for Fetuses With Hypoplastic Left Heart Syndrome and Intact or Highly Restrictive Atrial Septum

Background—Infants born with hypoplastic left heart syndrome and an intact or highly restrictive atrial septum face a neonatal mortality of at least 48% despite early postnatal left atrial decompression and palliative surgery. Prenatal left atrial decompression has been suggested as a means of improving these outcomes. This study reports the feasibility of fetal catheterization to create an interatrial communication and describes technical considerations. Methods and Results—Seven fetuses at 26 to 34 weeks’ gestation with hypoplastic left heart syndrome and intact or highly restrictive atrial septum underwent attempted prenatal intervention. Under ultrasound guidance, the atrial septum was approached with a needle introduced percutaneously from the maternal abdominal surface. In 6 of 7 fetuses, the atrial septum was successfully perforated, with balloon dilation of this iatrogenic defect resulting in a small but persistent interatrial communication. There were no maternal complications. One fetus died after the procedure. The remaining fetuses were liveborn at term, although 4 died as neonates. Conclusions—Ultrasound-guided fetal atrial septoplasty consisting of septal puncture and balloon dilation is feasible and can be performed percutaneously to minimize maternal risk. Although we have not demonstrated any positive clinical impact to date, it is our hope that further technical evolution will ultimately enable prenatal left atrial decompression and improvement of outcomes in fetuses with hypoplastic left heart syndrome and intact atrial septum.

In vivo acceleration of heart relaxation performance by parvalbumin gene delivery

Defective cardiac muscle relaxation plays a causal role in heart failure. Shown here is the new in vivo application of parvalbumin, a calcium-binding protein that facilitates ultrafast relaxation of specialized skeletal muscles. Parvalbumin is not naturally expressed in the heart. We show that parvalbumin gene transfer to the heart in vivo produces levels of parvalbumin characteristic of fast skeletal muscles, causes a physiologically relevant acceleration of heart relaxation performance in normal hearts, and enhances relaxation performance in an animal model of slowed cardiac muscle relaxation. Parvalbumin may offer the unique potential to correct defective relaxation in energetically compromised failing hearts because the relaxation-enhancement effect of parvalbumin arises from an ATP-independent mechanism. Additionally, parvalbumin gene transfer may provide a new therapeutic approach to correct cellular disturbances in calcium signaling pathways that cause abnormal growth or damage in the heart or other organs.

The Ross/Konno procedure in neonates and infants: intermediate-term survival and autograft function

BACKGROUND The Ross procedure has been increasingly applied to neonates and infants. Addition of a modified Konno-type enlargement of the aortic annulus allows the application of this procedure to neonates and infants with significant annular hypoplasia. The potential for growth and the proven durability make the autograft an ideal aortic valve replacement. METHODS Between March 1993 and December 2000, 10 patients under 1 year of age underwent a Ross/Konno procedure at our institution (range, 2 to 349 days; median 16). All patients had severe to critical aortic stenosis. All patients required aortic annulus enlargement for size mismatch between the aortic and pulmonary valves. RESULTS There were no deaths at a median follow-up of 48 months (range, 1 to 74 months). All patients had none to mild aortic stenosis on Doppler echocardiography. Eight patients had a 0 to 1+ aortic insufficiency, 1 patient had a 2+ aortic insufficiency, and 1 patient had a 3+ aortic insufficiency. Aortic annular dilatation was not observed. Aortic sinus dilatation occurred initially (mean change in z-value: 0 to 12 months, +2.1) and then stabilized (mean change in z-value: 12 to > 36 months, +0.6). No patient required additional procedures for aortic valve disease. Two patients required three pulmonary allograft replacements. CONCLUSIONS The Ross procedure with a modified Konno-type enlargement of the aortic annulus is an excellent approach to aortic valve disease in the neonate and infant. The procedure can be accomplished with low morbidity and mortality, and low rates of reoperation. The pulmonary autograft demonstrates durability without developing aortic stenosis, aortic insufficiency, or progressive dilatation. Enlargement of the aortic annulus parallels somatic growth.

Cardiac Dysfunction in Hypertrophic Cardiomyopathy Mutant Tropomyosin Mice Is Transgene-Dependent, Hypertrophy-Independent, and Improved by β-Blockade

Abstract— Familial hypertrophic cardiomyopathy (FHC) has been linked to mutations in proteins of the cardiac contractile apparatus, including &agr;-tropomyosin (Tm). Mice expressing &agr;Tm in the heart were developed to determine the effects of FHC mutant Tm on cardiac structure and function from single cardiac myocytes to whole organ function in vivo. Expression of E180G mutant Tm did not produce cardiac hypertrophy or detectable changes in cardiac muscle morphology. However, E180G mutant Tm expression increased the Ca2+ sensitivity of force production in single cardiac myocytes in a transgene expression–dependent manner. Contractile dysfunction in single myocytes manifested organ level dysfunction, as conductance-micromanometry showed E180G Tm mice had significantly slowed relaxation (diastolic dysfunction) under physiological conditions. The diastolic dysfunction in E180G Tm mice was no longer evident during &bgr;-blockade because propranolol eliminated the effect of E180G Tm to slow myocardial relaxation. Cellular and organ level dysfunction were evident in E180G Tm mice in the absence of significant cardiac structural abnormalities normally associated with FHC. These findings therefore suggest that diastolic dysfunction in FHC may be a direct consequence of FHC mutant protein expression. In addition, because diastolic dysfunction in E180G Tm mice is dependent on inotropic status, cardiovascular stress may play an important role in FHC pathogenesis.

The Influence of a Restrictive Atrial Septal Defect on Pulmonary Vascular Morphology in Patients with Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) with a restrictive atrial septal defect (ASD) is a form of congenital heart disease with considerable morbidity and mortality. This morphologic analysis assesses the pulmonary vasculature in this patient population. Pulmonary arteries, the persistence of high-resistance fetal arterioles, pulmonary veins, and lymphatics from multiple lung sections from each of five patients with HLHS and a restrictive ASD were compared to those of five patients with HLHS and nonrestrictive ASD. Lung sections from each patient were qualitatively graded in severity of pathology from 0 to 3 for each of the structures described previously, with the pathologist blinded to the status of the ASD. Patients with a restrictive ASD exhibited more significant pulmonary venous thickening and lymphatic dilatation (p = 0.02), with a tendency toward persistence of high-resistance fetal vessels (p = 0.2), compared to patients with a nonrestrictive ASD. These findings imply that patients with HLHS and a restrictive ASD possess pulmonary vascular abnormalities that place them at higher risk for the current surgical interventions available compared to patients with a nonrestrictive ASD.

Hypoplastic left heart syndrome: new developments and current controversies

Prior to 1980, the diagnosis of hypoplastic left heart syndrome (HLHS) was almost uniformly lethal. Over the past 25 years, the development of operative options, including staged surgical palliation and infant heart transplant, have resulted in major improvements in survival and quality-of-life outcomes. Throughout this period, the optimal treatment strategy for children with HLHS has continued to be controversial. Current advances include fetal diagnosis, medical management, catheter intervention and operative techniques, and hold great promise for further improvements. However, as new techniques continue to evolve, controversies will continue to arise. This article will explore the treatment strategies for children with HLHS and review current controversies surrounding this complex congenital cardiac disease.

Large fetal pulmonary arteriovenous fistula: Impact on pulmonary development

AbstractA case report of a patient with a large pulmonary arteriovenous fistula and valvar pulmonary stenosis is presented. The fistula was diagnosed prenatally and its effect on in utero cardiovascular growth and development documented. Due to concerns about massive intrapulmonary shunting potentially causing profound cyanosis after delivery, an EXIT (EX-utero Intrapartum Treatment) procedure was used to transfer the infant from placental to extracorporeal membrane oxygenation (ECMO) support. Severe pulmonary microvascular disease resulted in prohibitive pulmonary hypertension despite surgical ligation of the fistula. Prenatal and postnatal hemodynamic assessments of the fistula are presented and are compared to the pathologic findings.

Peritoneal Migration of an Abdominally Implanted Epicardial Pacemaker: A Cause of Intestinal Obstruction

We report the case of a 10‐year‐old child with an abdominally implanted epicardial pacemaker that eroded through the peritoneum and migrated to an intraperitoneal location, resulting in partial and then complete intestinal obstruction. This potentially life‐threatening complication should be considered when a patient with an abdominally implanted pacemaker presents with abdominal pain.

Fontan fenestration closure in the catheterization laboratory—Echocardiographic evaluation of residual right to left shunts

This study is a retrospective review using transthoracic echocardiography to assess the success of fenestration closure as well as residual right to left shunts in 35 patients who underwent Fontan fenestration closure in the catheterization laboratory. There is a high rate of closure of the Fontan fenestration; however, other residual right to left shunts are common.

Effect of arginine on cyclosporine-induced systemic hypertension after cardiac transplantation in the young

R publications support many different etiologies for cyclosporine-induced hypertension, but none have been definitive. Several studies have demonstrated impaired endothelium-dependent vasodilation in arteries isolated from cyclosporine-treated animals,1,2 and in human peripheral arteries exposed to cyclosporine in vitro.3 Furthermore, studies suggest that long-term cyclosporine treatment suppresses synthesis of nitric oxide (NO), a potent endogenous vasodilator.4–6 Pretreatment with L-arginine, the amino acid precursor for NO, preserves endothelium-dependent vascular relaxation and prevents systemic hypertension in cyclosporine-treated animals.7,8 Therefore, we hypothesized that cyclosporine-induced hypertension is associated with an altered L-arginine/NO pathway in vivo. To evaluate this hypothesis, we studied the acute effects of intravenous L-arginine infusion on blood pressure (BP), heart rate, left ventricular (LV) function, and NO production in young heart transplant patients receiving cyclosporine. • • • The study population consisted of 9 young cardiac transplant patients and 5 healthy volunteers. All patients were receiving cyclosporine as part of their immunosuppressive regimen, in addition to an antihypertensive medication (either a calcium channel antagonist or an angiotensin-converting enzyme inhibitor). No control subject was taking any medications at the time of the study. Patient and parental permission were obtained for inclusion in the study. The research protocol was approved by The University of Michigan Medical School Institutional Review Board for Human Subject Research. Heart transplant patients were studied in the cardiac catheterization laboratory after routine cardiac catheterization and endomyocardial biopsy (Figure 1). All patients were awake and alert; only local anesthetic was used for the catheterization. Control subjects were also studied in the cardiac catheterization laboratory. All subjects fasted for