Measurement of the mechanical PR interval in the fetus at risk for congenital complete heart block

Michele A. Frommelt, MD, pediatric cardiologist, Children's Hospital of Wisconsin; assistant professor, Pediatrics, Medical College of Wisconsin.

Over three decades ago it was noted that mothers who gave birth to children with complete heart block often had autoimmune diseases. It now is well established that heart block detected before or at birth, in the absence of structural cardiac abnormalities, is strongly associated with maternal autoantibodies to SSA/Ro and/or SSB/La ribonucleproteins, regardless of whether the mother has systemic lupus erythematosus (SLE), Sjögren's syndrome or is totally asymptomatic. Complete heart block is the most serious manifestation of the transplacental passage of these antibodies which seem to have a particular affinity for the fetal conduction system. In some cases, there also may be valvular injury and/or an associated myocarditis. Congenital complete heart block carries a substantial mortality (about 20 percent) and morbidity, with more than 60 percent of affected children requiring lifelong pacemakers. In recent literature, there have been several reports of these children requiring cardiac transplantation secondary to the development of a chronic, severe dilated cardiomyopathy.

To date, autoimmune associated complete heart block is irreversible. However, several case reports have suggested that less severe forms of heart block might be reversible with maternal steroid therapy. From an immunologic standpoint, it makes sense that elimination of maternal autoantibodies should reduce the overall inflammatory response. There may be a therapeutic window during which reversibility still is achievable.

Well then, how do we diagnose heart block in the fetus? Transabdominal fetal electrocardiography (ECG) has several limitations. First of all, only ventricular depolarization can be well recorded; thus no information is provided concerning the atrial rate or the sequence of atrioventricular activation. One would not be able to distinguish between sinus bradycardia (ventricular rate 80 bpm) and complete heart block (ventricular rate 80 bpm) with a transabdominal fetal ECG. Also, transabdominal fetal ECG can only be obtained from 18 to 28 weeks' gestation. The electrical signals are too weak to be recorded prior to 18 weeks; after 28 weeks, it is believed that electrical signals cannot be recorded because of the insulating effect of the vernix caseosa. Lastly, transabdominal fetal ECG provides no information on the fetal cardiac structure or function.

Fetal echocardiography has become the most useful means for the detection, diagnosis and monitoring of fetal arrhythmias. M-mode echocardiography looks at motion of a defined area of the heart over time; atrial systole is defined as the onset of atrial wall motion and ventricular systole is defined as the onset of ventricular wall motion. In a fetus with complete heart block, M-mode echocardiography will reveal that atrial systole has no fixed relationship with ventricular systole; the atrial rate is faster than the ventricular rate and can be easily computed (Figure 1).

Pulsed Doppler echocardiography records the sequence of forward blood flow velocities in the heart; the atrioventricular contraction sequence is determined by sampling in the area between the aortic and mitral valves in an apical five-chamber view. In a fetus with normal sinus rhythm, pulsed Doppler will reveal one ventricular outflow signal for every ventricular inflow signal (Figure 2).

Recently, we also have been able to estimate the PR interval using Doppler echocardiography. The Doppler is again positioned in the area between the aortic and mitral valves, and ventricular inflow and outflow signals are recorded. We can then measure the interval from the onset of atrial contraction (A wave) to the onset of ventricular outflow; this has been termed the "mechanical" PR interval. Several studies in the normal fetus suggest that this interval should not be longer than 0.15 seconds. If it is longer than 0.15 seconds, that suggests first degree heart block.

The recent establishment of normative values for the in utero mechanical PR interval now allows us to potentially search for the earliest non-invasive marker of AV nodal injury. If the heart block seen in this disease progresses in a stepwise fashion from first degree block to third degree block, it makes sense that the maximal chance for reversal occurs when the block is early and incomplete. This has prompted a multi-center study titled "Identification of the earliest non-invasive echocardiographic marker of atrioventricular nodal dysfunction and/or myocardial injury in fetuses at risk for congenital heart block." Mothers considered at high risk for having a child with complete heart block (for example, mothers with SLE and positive antibodies) will be followed by weekly echocardiograms from 16 weeks gestation with special attention to the mechanical PR interval. If the fetus develops any degree of heart block, that mother will be randomized to receive either dexamethasone or placebo. Again, it is postulated that the detection of AV nodal dysfunction at a time when the block is incomplete will offer the maximal chance for reversal with steroids.

In summary, recent advances in echocardiography have led to the ability to detect and monitor fetal arrhythmias. Congenital complete heart block associated with maternal autoimmune disease is a cause of significant morbidity and mortality in the fetus and young child and has not been reversible with any therapies. With the ability to now measure the mechanical PR interval, we are hoping to be able to intervene in these patients prior to the development of permanent disease. For any questions regarding the study, please contact me at (414) 266-2380.

Extended role for nurse practitioners

Gen Ownes, CPNP; Nancy Rudd, CPNP; and Michelle Steltzer, CPNP; Children's Hospital of Wisconsin

In spring 1999, two pediatric nurse practitioners (PNPs) joined the Heart Center physicians and staff caring for cardiac medical and cardiothoracic surgery patients at Children's Hospital. Since then, the role of the cardiology PNP mainly focused on meeting the needs of cardiac inpatients on 4 West, the hospital's Intermediate Care Unit. This past August, a third PNP was hired and, with this addition, the role of the PNP expanded to include inpatient cardiology patients in the Pediatric and Neonatal Intensive Care Units.

Currently, the cardiology PNPs have diverse job responsibilities. They include patient assessment and evaluation, participation in rounds and completion of daily progress notes for all inpatient cardiac and cardiothoracic (CT) surgery patients followed by the cardiologists. The cardiology PNPs participate in the patient admission process from the emergency room, cardiology clinic and referring hospitals. Daily activities include collaboration with the discharge planner, involvement in patient and parent education, and ongoing coordination of care with medical staff, nursing personnel, CT surgery providers and other ancillary staff. In addition, PNPs assist with unit-based educational offerings as well as critical care orientation for newly hired nurses on intermediate and intensive care units.

Ongoing projects the PNPs are actively involved in include establishing practice protocols, such as Anticoagulation in the Single Ventricle Patient, Management of Post Operative Chest Tube Drainage in the Fontan Patient, and Carvedilol Therapy in Patients with Dilated Cardiomyopathy. Current research projects include nutrition and growth issues in infants with congenital heart disease, home monitoring of Norwood patients, and management of persistent chest tube drainage in the Fontan population.

Mechanical pumps for extracorporeal circulation

Christopher Brabant, perfusionist, Children's Hospital of Wisconsin

Developing a mechanical blood pump to temporarily replace the function of the human heart has been the focus of physiologic and engineering research since the early 1900s. The ideal blood pump would have a controllable stroke volume and would be capable of producing a wide range of outputs. The output would be relatively independent of the resistance to fluid flow in the perfusion circuit and patient. Furthermore, the pumping motion would not damage the cellular or acellular components of the blood. All parts of the blood pump circuit in contact with the bloodstream would be disposable. It would have a smooth, continuous surface with negligible dead spaces so that stagnation and turbulence are kept to a minimum. Calibration of the pump flow would be exact and reproducible so that blood flow could be accurately monitored. Finally, the ideal pump would be manually operable in the event of a power failure.

Although no ideal exists, there are four types of pumps available. The two most commonly used are the roller and centrifugal pump. Both are used at Children's Hospital of Wisconsin for cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO).

Both roller pumps and centrifugal pumps have advantages and disadvantages.

Roller pumps contain mechanical parts that trap a portion of the fluid and propel it forward. The design of this pump combines a 210º semicircular backing plate and twin rollers that are 180º out of phase with one another. A length of tubing is placed inside the curved backing plate at the perimeter of travel of the rollers. The 180º arrangement of the rollers assures that one roller is in contact with the tubing at all times. Blood flow is induced by compressing the tubing, thereby pushing the blood ahead of the moving roller. As one roller ends its compressive phase, the other has already begun its compressive phase. Since the length of tubing in the curved backing plate remains constant, flow rate depends upon the size of the tubing and the rotation rate of the rollers.

The degree of compression ("occlusiveness") of the tubing in a roller head pump is critical for extracorporeal circulation. Excessive compression exacerbates hemolysis and tubing wear, while an under occlusive roller head causes turbulence and compromises forward output. Therefore adjusting tubing compression to be barely nonocclusive results in the least amount of damage to blood components.

One of the main complications associated with roller pumps is spallation. Spallation refers to the release of micro-particles of plastic from the inner walls of the tubing in the curved backing plate, due to compression by the rollers. An optimal occlusion setting attenuates this problem. Other complications include malocclusion, miscalibration and obstruction of flow through the pump. Should the outflow of the pump become occluded, pressure in the line will progressively increase resulting in an uncontrolled, catastrophic rupture of the pump circuit. If the inflow of the pump becomes occluded, the resulting build up of negative pressure will cause cavitation and the creation of air bubbles in the pump circuit.

The centrifugal blood pump used at Children's Hospital consists of a nest of smooth plastic cones that sit inside a plastic housing. The cones are magnetically coupled with an electric motor. This magnetic coupling results in the rotational speed of the pump equaling the rotational speed of the driver magnet inside the centrifugal pump console. Rotation of the parallel cones induces centrifugal force and radial flow to the blood that passes between the cones. The spinning cones create a negative pressure that pulls blood into the pump. Once the blood is inside the pump head, energy is imparted to the blood by the spinning cones, forming a vortex. The vortex is then constrained by the outside plastic housing, generating pressure to pump the blood forward. There are no occlusive devices between the inlet and the outlet of the centrifugal pump. If the cones are not spinning, fluid can flow through the pump head in either direction.

During centrifugal pump operation, the flow generated by this device is affected both by preload and afterload. Flow increases when the preload increases or when the afterload decreases. Conversely, a decreased preload or an increased afterload will decrease pump flow. Because centrifugal pumps are pressure sensitive, they require a flow meter to monitor blood flow out of the pump. Ideally, it should be placed distal to any intra-circuit shunts so that an accurate assessment of flow to the patient can be made. The electromagnetic flow meter is not susceptible to inaccuracy from turbulence, hematocrit levels or temperature.

The main difficulty associated with centrifugal pumps is their inability to pump at low flow rates, especially in a patient who is labile. Should the patient's pressure get too high, blood could potentially flow retrograde across the pump head. Diligently attending to the pump console and maintaining a minimum flow rate of approximately 200 cc/min should eliminate the occurrence of retrograde flow.

Centrifugal pumps have several potential advantages over roller pumps. Because centrifugal pumps are sensitive to afterload pressure, a catastrophic pressure buildup in the arterial line cannot occur because flow will decrease through the pump as pressure increases. The maximum amount of pressure that a centrifugal pump can generate is in the order of 700 to 900 mmHg. Conversely, a centrifugal pump only will generate a maximum negative pressure of roughly 500 mmHg if the inflow to the pump is occluded, thereby reducing the risk of cavitation and microembolus as compared with roller pumps. Another advantage is that centrifugal pumps have better air handling characteristics should air be inadvertently introduced into the inlet side of the circuit. In a constrained vortex pump, there is high pressure at the periphery and low pressure at the center of the pump head. Because of this pressure difference, air tends to remain at the center of the pump head and not be expelled from the pump. In the event of a massive introduction of air, the pump will de-prime and the forward flow will stop. Unless a roller head is connected to a servo-controlled bubble detector that stops the pump when air is detected, the roller head would continue to pump after it is filled with air.

Colloquially speaking, centrifugal pumps are associated with greater preservation of platelets and leukocytes, decreased complement activation, reduced micro-bubble transmission and less hemolysis when compared to conventional roller pumps. However, reproduction of this data is not consistent.

On the other hand, the design of roller pumps is mechanically more simple, they are less expensive and have a lower prime volume than centrifugal pumps. Roller pumps are easier to prime and de-air and they produce a predictable output that is independent of afterload.

Although physicians and perfusionists have their preferences about which pumps should be used for surgery requiring cardiopulmonary bypass, clinical outcome studies attempting to prove that one pump type is better than another have been insufficient and inconsistent.

However, the theoretic advantages of centrifugal pumps over roller pumps become more persuasive for prolonged applications such as circulatory support.

The first centrifugal ECMO system was used at Children's Hospital in March 2001. Since then, two more centrifugal pump ECMO circuits have been used. All three patients were successfully weaned from this system.

The common denominator among these children was they were older and therefore larger than most patients who require ECMO support. In a conventional arrangement, the patient's volume is drained by gravity into the ECMO circuit and then actively pumped by the roller head through the oxygenator and back to the patient. For neonatal patients and pediatric patients who weigh less than 10 kg, gravity venous return into the ECMO circuit is adequate enough to empty the heart and maintain a flow rate that sustains their metabolic requirements. The reason that venous return is maintained in this group of patients is because of the moderately large height differential between the patient and the pump, and because the tubing lengths are relatively short.

Once a child's weight exceeds approximately 10 kg, they become progressively more difficult to drain with a conventional roller head system. Because of the decreasing height differential between the patient and the pump, the longer tubing lengths and the higher flow requirements of larger patients, gravity drainage becomes increasingly inadequate. The major resulting consequence is that their failing heart remains distended and forward flow is markedly compromised because of lack of volume. An ECMO system utilizing a centrifugal pump actively drains venous return out of the patient. The "siphon" effect of the centrifugal pump results in better drainage of the heart with a concomitant increase in forward flow to the patient.

Patient size, pathology, vascular access, cannula size and physician preference are just a few of the many factors taken into consideration when deciding on the best medium of ECMO therapy. Even though great success has been achieved for weaning patients from centrifugal ECMO at Children's Hospital, additional clinical evaluation will be necessary in order to establish its clinical application and significance.

Heart Center loses physician and friend

Stuart Berger, MD, medical director of the Heart Center, Children's Hospital of Wisconsin; associate professor, Pediatrics, Medical College of Wisconsin; David Petasnick, manager of the Heart Center, Children's Hospital of Wisconsin

David Lewis, MD

The week of Sept. 10 was especially difficult for the staff and patients of the Heart Center, Children's Hospital and the Medical College. A day after terrorists attacked our nation, we received word David Lewis, MD, one of our pediatric cardiologists, had died while on a medical mission to Ecuador.

Although only 43, he died of natural causes.

Lewis worked in the Heart Center for seven years. He also was the director of Medical Education at Children's Hospital and an associate professor of Pediatrics at the Medical College of Wisconsin.

This was Lewis' fifth medical mission to provide charity care for children in less fortunate countries.

He will be greatly missed by those he leaves behind - his wife, three children and many, many friends and colleagues.