Jeffrey A. Feinstein

Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge A Scientific Statement From the American Heart Association Council on Cardiovascular Disease in the Young: Endorsed by the American Academy of Pediatrics

Prevention of congenital cardiovascular defects has been hampered by a lack of information about modifiable risk factors for abnormalities in cardiac development. Over the past decade, there have been major breakthroughs in the understanding of inherited causes of congenital heart disease, including the identification of specific genetic abnormalities for some types of malformations. Although relatively less information has been available on noninherited modifiable factors that may have an adverse effect on the fetal heart, there is a growing body of epidemiological literature on this topic. This statement summarizes the currently available literature on potential fetal exposures that might alter risk for cardiovascular defects. Information is summarized for periconceptional multivitamin or folic acid intake, which may reduce the risk of cardiac disease in the fetus, and for additional types of potential exposures that may increase the risk, including maternal illnesses, maternal therapeutic and nontherapeutic drug exposures, environmental exposures, and paternal exposures. Information is highlighted regarding definitive risk factors such as maternal rubella; phenylketonuria; pregestational diabetes; exposure to thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis. Caveats regarding interpretation of possible exposure-outcome relationships from case-control studies are given because this type of study has provided most of the available information. Guidelines for prospective parents that could reduce the likelihood that their child will have a major cardiac malformation are given. Issues related to pregnancy monitoring are discussed. Knowledge gaps and future sources of new information on risk factors are described.

Hypoplastic Left Heart Syndrome : Current Considerations and Expectations

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients.

Balloon Pulmonary Angioplasty for Treatment of Chronic Thromboembolic Pulmonary Hypertension

Background—Although pulmonary thromboendarterectomy is increasingly successful for the definitive treatment of chronic thromboembolic pulmonary hypertension (CTEPH), not all patients have surgically accessible disease. Others are poor surgical candidates because of comorbid illness. Therefore, for selected patients, we defined and implemented an alternative interventional strategy of balloon pulmonary angioplasty (BPA). Methods and Results—Eighteen patients (mean age, 51.8 years; range, 14 to 75 years) with CTEPH underwent BPA; they averaged 2.6 procedures (range, 1 to 5) and 6 dilations (range, 1 to 12). Selection of pulmonary artery segments for dilation required (1) complete occlusion, (2) filling defects, or (3) signs of intravascular webs. After an average of 36 months of follow-up (range, 0.5 to 66 months), the average New York Heart Association class improved from 3.3 to 1.8 (P <0.001), and 6-minute walking distances increased from 209 to 497 yards (P <0.0001). Pulmonary artery mean pressures decreased from 43.0±12.1 to 33.7±10.2 mm Hg (P =0.007). Eleven patients developed reperfusion pulmonary edema; 3 required mechanical ventilation. Conclusions—BPA reduces pulmonary artery hypertension in patients with CTEPH and is associated with long-term improvement in New York Heart Association class and 6-minute walking distances. BPA is a promising interventional technique that warrants randomized comparison with medical therapy in CTEPH patients who are not surgical candidates.

Electrical Resynchronization A Novel Therapy for the Failing Right Ventricle

Background—Many patients with congenital heart disease develop right ventricular (RV) failure due to anatomy and prior therapy. RV problems may include right bundle-branch block (RBBB), volume loading, and chamber enlargement. Because the failing RV may have regional dyskinesis, we hypothesized that resynchronization therapy might augment its performance. Methods and Results—We studied 7 patients with RV dysfunction and RBBB, using a predefined pacing protocol. QRS duration, cardiac index (CI), and RV dP/dt were measured in 4 different pacing states. Atrioventricular pacing improved CI and RV dP/dtmax and decreased QRS duration as compared with atrial pacing or sinus rhythm. Conclusions—Atrioventricular pacing in patients with RBBB and RV dysfunction augments RV and systemic performance. RV resynchronization is a promising novel therapy for patients with RV failure.

On Coupling a Lumped Parameter Heart Model and a Three-Dimensional Finite Element Aorta Model

Aortic flow and pressure result from the interactions between the heart and arterial system. In this work, we considered these interactions by utilizing a lumped parameter heart model as an inflow boundary condition for three-dimensional finite element simulations of aortic blood flow and vessel wall dynamics. The ventricular pressure–volume behavior of the lumped parameter heart model is approximated using a time varying elastance function scaled from a normalized elastance function. When the aortic valve is open, the coupled multidomain method is used to strongly couple the lumped parameter heart model and three-dimensional arterial models and compute ventricular volume, ventricular pressure, aortic flow, and aortic pressure. The shape of the velocity profiles of the inlet boundary and the outlet boundaries that experience retrograde flow are constrained to achieve a robust algorithm. When the aortic valve is closed, the inflow boundary condition is switched to a zero velocity Dirichlet condition. With this method, we obtain physiologically realistic aortic flow and pressure waveforms. We demonstrate this method in a patient-specific model of a normal human thoracic aorta under rest and exercise conditions and an aortic coarctation model under pre- and post-interventions.

Pediatric Pulmonary Hypertension Guidelines From the American Heart Association and American Thoracic Society

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.

Transcatheter closure of postinfarction ventricular septal defects using the new Amplatzer muscular VSD occluder: Results of a U.S. Registry.

The objective of this study was to assess the immediate and mid‐term results of transcatheter closure of postinfarct muscular ventricular septal defects (VSDs) using the new Amplatzer postinfarct muscular VSD device (PIMVSD). Ventricular septal rupture occurs in 0.2% of myocardial infarcts and remains associated with very high morbidity and mortality. Data were prospectively collected for 18 patients who underwent attempted device closure of postinfarction VSDs between 2000 and 2003. Five patients underwent the closure in the acute phase (within 6 days from the infarct); the remaining patients underwent closure on day 14–95 after the diagnosis of the infarct. Outcome parameters included procedural success, evidence of residual shunts on echocardiography, and occurrence of procedure‐related complications. The procedure was successful in deploying a device across the VSD in 16 of 18 patients. The 30‐day mortality was 28%. Eleven patients are still alive and have been followed up for a median of 332 days. Two patients required a second procedure to close a residual VSD. At the most recent outpatient follow‐up, the VSD was completely closed in two patients, six patients had a trivial or small residual shunt, and two patients had a moderate residual shunt. We conclude that percutaneous device closure of postinfarction VSDs using the Amplatzer PIMVSD occluder appears to be safe and effective. Further trials are required to assess long‐term efficacy and compare the results with those of surgical closure. Catheter Cardiovasc Interv 2004;61:196–201.

Effects of Exercise and Respiration on Hemodynamic Efficiency in CFD Simulations of the Total Cavopulmonary Connection

Congenital heart defects with a single functional ventricle, such as hypoplastic left heart syndrome and tricuspid atresia, require a staged surgical approach to separate the systemic and pulmonary circulations. Ultimately, the venous or pulmonary side of the heart is bypassed by directly connecting the vena cava to the pulmonary arteries with a modified t-shaped junction. The Fontan procedure (total cavopulmonary connection, TCPC) completes this process of separation. To date, computational fluid dynamics (CFD) simulations in this low pressure, passive flow, intrathoracic system have neglected the presumed important effects of respiration on physiology and higher “stress” states such as with exercise have never been considered. We hypothesize that incorporating effects of respiration and exercise would provide more realistic estimates of TCPC performance. Time-dependent, 3D blood flow simulations are performed by a custom finite element solver for two patient-specific Fontan models with a novel respiration model, developed to generate physiologic time-varying flow conditions. Blood flow features, pressure, and energy efficiency are analyzed at rest and with increasing flow rates to simulate exercise conditions. The simulations produce realistic pressure and flow data, comparable to that measured by catheterization and echocardiography, and demonstrate substantial increases in energy dissipation (i.e. decreased performance) with exercise and respiration due to increasing intensity of small scale vortices in the flow. As would be expected, these changes are highly dependent on patient-specific anatomy and Fontan geometry. We propose that respiration and exercise should be incorporated into TCPC CFD simulations to provide increasingly realistic evaluations of TCPC performance.

Usefulness of epoprostenol therapy in the severely ill adolescent/adult with Eisenmenger physiology

We showed that in selected severely impaired and symptomatic patients with Eisenmenger physiology, IV-PGI 2 therapy can significantly improve functional capacity, oxygen saturation, and cardiopulmonary hemodynamics. The long-term effects of this agent on morbidity and survival for this population, as well as its complications, remain unknown. A larger controlled prospective multicentered trial should be performed for patients with Eisenmenger physiology who fail conventional therapy and are at the highest risk for significant morbidity and early mortality.

Morphometry-Based Impedance Boundary Conditions for Patient-Specific Modeling of Blood Flow in Pulmonary Arteries

Patient-specific computational models could aid in planning interventions to relieve pulmonary arterial stenoses common in many forms of congenital heart disease. We describe a new approach to simulate blood flow in subject-specific models of the pulmonary arteries that consists of a numerical model of the proximal pulmonary arteries created from three-dimensional medical imaging data with terminal impedance boundary conditions derived from linear wave propagation theory applied to morphometric models of distal vessels. A tuning method, employing numerical solution methods for nonlinear systems of equations, was developed to modify the distal vasculature to match measured pressure and flow distribution data. One-dimensional blood flow equations were solved with a finite element method in image-based pulmonary arterial models using prescribed inlet flow and morphometry-based impedance at the outlets. Application of these methods in a pilot study of the effect of removal of unilateral pulmonary arterial stenosis induced in a pig showed good agreement with experimental measurements for flow redistribution and main pulmonary arterial pressure. Next, these methods were applied to a patient with repaired tetralogy of Fallot and predicted insignificant hemodynamic improvement with relief of the stenosis. This method of coupling image-based and morphometry-based models could enable increased fidelity in pulmonary hemodynamic simulation.