New cardiologists join Herma Heart Center

Stuart Berger, MD, medical director, Cardiology, Herma Heart Center, Children's Hospital of Wisconsin; professor, Cardiology, Medical College of Wisconsin.

Peter Bartz, MD, and Margaret Samyn, MD, joined Herma Heart Center in August. Both are pediatric cardiologists at Children's Hospital of Wisconsin and assistant professors of Pediatrics (Cardiology) at the Medical College of Wisconsin.

Dr. Bartz received his medical degree from the Universtiy of Minnesota in Minneapolis. He completed a residency in Medicine and Pediatrics at Michigan State University in East Lansing and a fellowship in Pediatric Cardiology at Mayo Medical School in Rochester, Minn. He is board certified in Internal Medicine and Pediatrics and has a special interest in adults with congenital heart disease.

Dr. Samyn received her medical degree from Wayne State University in Michigan. She completed a residency in Pediatrics at the University of Michigan in Ann Arbor and a fellowship in Pediatric Cardiology at the University of Iowa in Iowa City. She is board certified in Pediatrics and Pediatric Cardiology and has a special interest in non-invasive diagnostics such as cardiac MRI.

Pediatric hypertension

Pamela S. Cava, DO, pediatric cardiologist, Herma Heart Center, Children's Hospital of Wisconsin; assistant professor of Pediatrics (Pediatric Cardiology), Medical College of Wisconsin.

The most accurate way to take a blood pressure is by auscultation with a standard mercury sphygmomanometer and an appropriately sized blood pressure cuff. An appropriate cuff size is one in which the cuff bladder width is equal to approximately 70 percent of the acromian-olecranon distance and should encircle the arm completely. Inappropriately small cuffs give falsely high readings; inappropriately large cuffs give falsely low readings. Measurements should be taken after 3 to 5 minutes of resting with the patient quiet and comfortable in a sitting position, with the arm at the level of the heart.

The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents published its fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents in Pediatrics 2004. This report includes tables for the 50th, 90th and 95th percentiles for blood pressure by sex, age and height. Hypertension in children is defined as systolic or diastolic pressure equal to or greater than the 95th percentile. Pre-hypertension is defined as that blood pressure between the 90th and 95th percentiles. Optimal blood pressure in children is less than the 90th percentile corrected for height, age and gender. The diagnosis of hypertension is made only after an elevated and properly measured blood pressure has been confirmed on at least three separate occasions. Once the diagnosis is made an evaluation should be performed to determine the extent of target organ damage, assess the patient's overall cardiovascular risk factors and to rule out identifiable secondary and often curable causes of hypertension. 

The workup for hypertension includes a detailed history and physical geared toward the possible causes and risk factors for hypertension. Laboratory assessment should be geared toward possible etiologies and may include: CBC, metabolic panel (renal functions, electrolyte abnormalities), lipid panel, thyroid functions, toxicology screen and urinalysis. Expanded laboratory tests may include creatinine clearance, urine catecholamines, C3, C4, ANA, plasma rennin and aldosterone levels. Other necessary studies include EKG, echocardiogram and renal ultrasound.

Causes of hypertension vary depending on age. For infants younger than 1 year of age, renal artery or vein thrombosis and congenital renal abnormalities are most common, followed by coarctation, bronchopulmonary dysplasia and maternal drug use. For children ages 1 to 6 years, renal artery stenosis is most common, followed by tumors, such as Wilms or neuroblastoma, and coarctation. For children and preadolescents ages 7 to 12 years, secondary causes still are common; however, essential hypertension becomes a significant etiology in this age group. In the adolescents, essential hypertension is the most common cause followed by renal parenchymal disease and endocrine abnormalities.

Any child with a blood pressure greater than or equal to the 95th percentile for age, gender and height should receive treatment. Hypertension related to secondary causes should involve specific therapies focused on treatment of that entity. Treatment of hypertension begins with nonpharmacologic therapy including dietary sodium restriction, weight reduction in the obese, avoidance of alcohol/smoking and regular aerobic exercise.

Pharmacologic therapy primarily includes angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin- receptor-antagonists (ARB), calcium channel blockers (CCB), diuretics and beta blockers. Treatment with an ACEI is warranted in patients with renal insufficiency, diabetes mellitus or heart failure and has been shown to slow the progression of the underlying disease. ACEI also are good for the hypertensive athlete because they do not affect performance. African-American patients are more sensitive to thiazide diuretics and calcium channel blockers than to monotherapy with ACEI, ARB or beta blockers. Beta blocker should be given to patients with evidence of ischemic heart disease.

Exercise recommendations include aerobic activity for 30 to 45 minutes per day. Isometric exercises, such as weight lifting and wrestling, should be discouraged. Athletes and children with hypertension (BP > 99th percentile) need to be restricted from competitive sports and isometric activities until the hypertension is under adequate control and they have no evidence of target organ damage. Diuretics and beta blockers should not be used in athletes; ace inhibitors or calcium channel blockers are preferred. Athletes with significant hypertension (< 99th percentile) without evidence of target organ damage should be allowed to participate in competitive activities but a resting BP should be checked every two months.
Hypertension and prehypertension are significant health issues in children due to the marked increase in the prevalence of obesity. Hypertension along with other risk factors – hyperuricemia, microalbuminuria, Body Mass Index (BMI) > 25th percentile, elevated triglycerides > 150 mg/dL, LDL > 100 mg/dL and HDL < 40 mg/dL are all components of metabolic disease and are markers for increased cardiovascular risk.    

The Preventative Cardiology Program in the Herma Heart Center at Children's Hospital of Wisconsin focuses on identification and treatment of children with these cardiovascular risk factors. The program uses a multidisciplinary approach with a physician, nurse practitioner and exercise physiologist to custom design a treatment program for the patient with or at risk for early coronary heart disease.

Pediatric heart transplantation: An update on outcomes and surveillance

Gail Stendahl, RN, MSN, CPNP, heart transplant coordinator, Herma Heart Center, Children's Hospital of Wisconsin.

Over the past two decades heart transplantation has become the treatment of choice for pediatric patients with end-stage heart disease. The increased number of heart transplants is credited to improvements in surgery, tissue preservation, immunology and infectious disease, which have resulted in enhanced short- and long-term survival. The improved outcomes also are due to highly specialized care provided by medical professionals with a strong commitment to heart transplantation and expertise in recipient selection, organ procurement, and medical follow-up before and after transplantation.

The most common indication for heart transplant in infants is congenital heart disease followed by cardiomyopathy. In older children, the percent of patients transplanted with congenital heart disease and cardiomyopathy is closely balanced, while cardiomyopathy is the most common indication in adolescents. Since 1991, Children's Hospital of Wisconsin has performed a total of 51 heart transplants. Our transplant volume has increased over the past two years with a total of 19 cases including three ABO-incompatible transplants and one multi-organ transplant. Nationally, survival rates for heart transplantation have been improving with time. Figure 1 shows the era related survival for pediatric recipients. For the most recent cohort (1995-1999), 5-year survival is approximately 75 percent and the predicated 10-year survival 60 percent. While these statistics are valid for the transplant population as a whole, there is no specific limit to the potential lifespan of any given transplant patient. There are increasing numbers of patients who are thriving more than 15 years out from heart transplantation.

Overall survival rates for cardiac transplant recipients continue to improve; yet there remain important differences based on recipient age. Specifically, transplant in infancy carries a higher risk for early mortality. Figure 2 shows survival after orthotopic heart transplant stratified by recipient age. Additional risk factors associated with increased mortality include congenital heart disease or the need for mechanical support, previous sternotomy or thoracotomy, history of malignancy, elevated pulmonary vascular resistance and small transplant center volumes. Children who are sicker at the time of listing face greater risks, thus hospitalization and ventilator support are identified risk factors along with retransplantation and antibody sensitization.

Long-term success after heart transplant requires constant and careful attention. Transplant recipients need ongoing evaluation of heart allograft function, rejection surveillance and titration of immunosuppression. Patients must remain on immunosuppressant medication indefinitely, and it is not unusual for a transplant patient to require up to 10 medications daily. Some of these medications can have significant side effects including increased risk for the development of lymphoproliferative disorders, infection, hypertension, etc. It is critical the patient adheres strictly to prescribed regimens to avoid potential complications. Medicines are adjusted based on blood levels, evidence of infection, rejection or coronary disease documented through surveillance testing during frequent evaluations.

Rejection occurs when the recipient immune system recognizes the new heart as foreign. Immunosuppressant drugs prevent this from happening and therein lies the critical balance at the core of post transplant care: finding the right balance of medications to prevent rejection while limiting side effects. Clinical manifestations of acute rejection can be variable. Rejection may be identified by routine surveillance myocardial biopsy before symptoms become evident. Occasionally, acute rejection will present with malaise, reduced exercise tolerance, low-grade fever or heart failure. Physical examination may reveal arrhythmias or the onset of a third heart sound. Although noninvasive techniques for diagnosis of rejection have been proposed, endomyocardial biopsy remains the procedure of choice to confirm cardiac rejection.

Cardiac allograft vasculopathy, a form of coronary artery disease specific to transplant patients, is the major factor limiting long-term survival of pediatric heart transplant recipients. It is a diffuse form of coronary disease involving the epicardial, myocardial and microscopic vessels. Patients with cardiac allograft vasculopathy often do not experience angina due to denervation of the transplanted heart. As a result, the presenting symptoms may be congestive heart failure or sudden death due to ischemia or infarction. Noninvasive screening using exercise stress testing can help detect early disease. Coronary angiography remains the gold standard for the diagnosis of cardiac allograft vasculopathy and is performed annually or when cardiac symptoms occur in the absence of histopathological rejection. Newer technologies such as intravascular ultrasound may add in earlier detection of developing vasculopathy allowing more aggressive treatment to prevent rapid progression.

Pediatric heart transplantation remains an important therapy for the growing number of pediatric patients with end-stage heart failure. This palliative therapy allows most patients to return to a functionally normal status. The length of time a child can live after a heart transplant is uncertain, as every child and every transplant is unique. Long-term survival rates continue to improve with experience, innovative surgical techniques, new medications, ongoing surveillance and a close relationship between the patient and the transplant team.

Figures are from the Registry of the International Society for Heart and Lung Transplantation: Ninth Official Pediatric Heart Transplant Report - 2006, Authors: Boucek, M et al, JHLT 2006;25:893-903.

Non-invasive assessment of cardiac output with near-infrared spectroscopy

George Hoffman, MD, medical director, Anesthesiology, Children's Hospital of Wisconsin, and professor, Pediatrics (Anesthesiology), Medical College of Wisconsin; and Nancy Ghanayem, MD, pediatric intensivist, Children's Hospital of Wisconsin, and assistant professor, Pediatrics, Medical College of Wisconsin.

The cardiovascular system functions to distribute substrate adequate to meet tissue demands under a wide range of physiologic conditions. Maintenance of adequate oxygen delivery is important to reverse or prevent ischemic injury, which can result in multisystem organ dysfunction, prolonged morbidity and mortality. Because interventions targeting early treatment of inadequate whole body or regional oxygen supply-demand relationships (shock) have improved outcome in critical illness, detection of inadequate oxygen delivery is important for preventative or therapeutic interventions. Non-invasive monitors are increasingly useful in children for assessment of oxygen delivery, avoiding the technical challenges and risks associated with invasive devices, and allowing early and extended duration of assessment.

Cardiovascular reflexes and physiology of shock

Global and regional mechanisms operate both independently and with complex interactions to mediate efficient oxygen delivery with reserve in total cardiac output and in the distribution thereof. Global cardiac output is affected by preload, afterload, rate, rhythm, contractility and the presence of shunt. Assessment of those parameters may be helpful in determining the appropriate intervention to alter cardiac output. Regional resistance is determined by the interaction of neurohumoral factors related to inflammation and the sympathetic nervous system, and local factors related to autoregulation. The total systemic vascular resistance is thus determined by the net effect of regional resistances, through the overall effects of autokines, cytokines and neurohumoral autonomic activity. Oxygen delivery (DO2) is a function of systemic cardiac output times arterial oxygen content (CaO2), which is determined by the hemoglobin concentration, oxygen saturation and tension (CaO2 = 1.34*Hgb*SaO2 + 0.003*PaO2).

he sympathetic stress response evolved to deal with hypovolemic-septic shock, yet it is activated in all shock states to redistribute blood flow to brain and heart. The distribution of cardiac output can be altered significantly by stress responses, with the mesenteric and splanchnic circulations being at risk for silent ischemia during "compensated" shock. Circulatory reflexes to hemorrhage or hypotension will increase baroreflex gain to raise contractility, heart rate and systemic vascular resistance, and decrease venous capacitance. These responses may be immediately protective in the face of hemorrhagic shock but often impair systemic flow in the face of myocardial dysfunction. These responses also are activated by cold, stress, pain and anxiety, and thus are not specific to low cardiac output syndrome.

Assessment of cardiac output

Clinical examination

The clinical exam and standard noninvasive devices can relatively accurately measure heart rate, blood pressure and arterial oxygen saturation. Cardiac output is perfusion pressure (MABP - CVP) divided by SVR, and SVR often changes inversely with blood pressure. Oxygen delivery is CO x CaO2, which is a function of SaO2 and the hemoglobin concentration. Thus approximation of DO2 by the usual noninvasive parameters is limited by three unmeasured unknowns.

Subjective assessment of pulse amplitude, extremity temperature and capillary refill time commonly are used in attempts to assess cardiac output. The signs of elevated sympathetic tone – tachycardia, pallor, cool extremities, poor pulse amplitude – usually are inferred to result from the reflex responses to low cardiac out, yet these same responses may elevate blood pressure and thereby be misleading in global assessment. The pattern recognition of the experienced clinician frequently is discordant with objective data, and cardiac output is often poorly estimated in critically ill infants and children using commonly measured parameters.

Regional SvO2: Near-infrared spectroscopy

A technology that addresses a number of the limitations of conventional invasive and noninvasive monitoring is near-infrared spectroscopy. NIRS devices rely on the change in differential light signal based upon the changing absorption spectrum of hemoglobin depending upon its oxygen saturation. Because most blood is not in arteries but in capillaries and veins, quantitatively the greatest contribution to the absorption spectrum of hemoglobin is venous-weighted capillary blood. An FDA-approved NIRS device (INVOS, Somanetics) uses a dual-detector system to subtract a shallow light path from a deep light path, theoretically allowing the derivation of the average oxyhemoglobin saturation (rSO2) in a volume of tissue about 2.5 to 3.0 cm deep to the skin and is displayed as a relative number from 0 to 100 percent.
The use of NIRS technology to monitor oxygenation in the brain, muscle, liver and kidney has been extensively described. Changes in rSO2 monitored by NIRS are sensitive indicators of perfusion-metabolism coupling, and regional NIRS can guide resuscitation from shock. The initial FDA-approved indication for the Somanetics device is for trend monitoring of rSO2 in the cerebral circulation, which has been widely modeled as a compartment with 75 percent venous blood, thus allowing validation of the device in an accepted clinical model. In animal models, brain rSO2 < 40 percent is associated with intracellular anaerobic metabolism and depletion of high energy phosphates. Clinical data in children and adults supports the hypothesis that cerebral rSO2 < 40 to 50 percent, or a change in baseline of > 20 percent, is associated with hypoxic-ischemic neural injury.

We have been using two simultaneous probe sites (cerebral and T10-L2 somatic-renal) to monitor regional saturation. The two-site approach reveals the profound differences in tissue oxygenation in different organ beds. Brain oxygen extraction is relatively high and is achieved by autoregulatory mechanisms to meet high metabolic demand resulting in minimal change in cerebral blood flow related to sympathetic tone. The kidney normally is a high-flow, low-extraction organ with high vein saturation, but renovascular resistance is under intense sympathetic control. Because brain circulation is maintained at the expense of somatic-renal perfusion with stress, we hypothesized that two-site monitoring would provide information about the distribution of vascular resistance, which is the point of clinical assessments of perfusion. Normally, renal rSO2 is higher than brain rSO2 by 15 to 20 percent absolute. We recently have demonstrated that circulatory impairment, as detected by falling somatic-renal rSO2 from NIRS, is associated with a high risk of anaerobic metabolism. The decrease in somatic perfusion that attends reflex responses to falling cardiac output is easily visualized, allowing for individualization and titration of therapeutic interventions.

This technology has allowed extended non-invasive monitoring to occur in both critical care and step-down environments. Because rSO2 represents a regional venous-weighted value, it parallels the regional SvO2. (Figure 1)  

In neonates following the Norwood operation, we found a similar parallel trend, particularly between cerebral rSO2 and SvO2. We currently consider two-site NIRS to be an indispensable non-invasive modality to monitor global and regional perfusion in high-risk patients.

Pulmonary hypertension in children

Stuart Berger, MD, medical director, Cardiology, Herma Heart Center at Children's Hospital of Wisconsin, and professor, Pediatrics (Cardiology), Medical College of Wisconsin; and Amy Zahn, MSN, NP-C, Herma Heart Center, Children's Hospital of Wisconsin.

Pulmonary hypertension (PAH) is an elevation in pulmonary artery pressure and is defined as a mean pulmonary artery pressure greater than 25 mm Hg at rest. It is associated with a wide spectrum of diseases and etiologies, and its clinical severity and presentation is widely variable. Regardless of its origin, PAH can be progressive, severe and can lead to right ventricular failure, arrhythmias and sudden death.

The presenting symptoms of PAH vary with severity of the hypertension and the age at presentation. Infants can present with poor appetite, poor growth and irritability. Older children present with nausea, activity intolerance, lethargy and diaphoresis. With severe PAH, syncope or sudden cardiac death may be a presenting symptom.
Physical examination findings include manifestations of low cardiac output such as tachypnea and tachycardia. The pulmonic component of the second heart sound is accentuated; there may be a right ventricular heave, which is associated with right ventricular hypertrophy and/or dysfunction. Tricuspid and pulmonary insufficiency may be audible. Signs of right heart failure, including hepatomegaly, ascites and peripheral edema may be present.

The details of the pathophysiology of pulmonary vascular tone are complex and represent a balance between dilator and constrictor stimuli. In PAH the vascular tone is shifted toward vasoconstriction, regardless of the initiating event. The nitric oxide-cyclic GMP system and prostacyclin-cAMP system are active in the pulmonary circulation, and alterations in these systems are important causes of PAH. Current drug therapy is targeted toward these two systems.

A new classification system for PAH was proposed based upon the World Health Organization 2003 recommendations outlined in Table 1. Patients who present with PAH should be assessed carefully in order to rule out associated abnormalities. The workup is outlined in Table 2. Cardiac catheterization and acute drug testing are important in determining optimal pulmonary vasodilator therapy. Once baseline pulmonary artery pressures, resistance and cardiac output are determined, measurements are obtained with the use of various medications in order to determine pulmonary vascular reactivity. Medications used for acute drug testing include inhaled nitric oxide, calcium channel blockers and/or prostacyclin. An acute responder is defined as a patient who has a 20 percent decrease in pulmonary resistance with unchanged or increased cardiac output. 

General measures are important for the treatment of children with PAH. Childhood illnesses that are relatively benign for most children can be devastating for those with PAH. Thus, annual influenza and respiratory syncytial virus vaccination are administered. Anticoagulation with warfarin is recommended. Digoxin tends to be used in patients with right ventricular dysfunction. Diuretics can be beneficial in patients with edema and ascites, but hypovolemia must be prevented due to its detrimental effect on cardiac output. Calcium channel blocker therapy is recommended for patients who experience an acute response in the catheterization laboratory. 

Long-term continuous intravenous prostacyclin therapy with epoprostenol (Flolan) has been shown to be efficacious in both children and adults with PAH. Its effects are based on the postulated imbalance of thromboxane A2 and prostacyclin. Interruption of the medication can cause acute decompensation in some patients as a result of a severe rebound PAH. Alternative routes of delivery of prostacylin analogues exist, the advantages are obvious though the efficacy is not as well-established.  Treprostinil (remodulin) is delivered via continuous subcutaneous drip delivered via an in-dwelling catheter. Iloprost is an inhaled prostacyclin analogue that has the advantage of selectivity on the pulmonary vasculature because of its delivery via the inhaled route. It has a short half-life (25 minutes) and therefore requires six to nine inhalations per day. 

The endothelin system plays a key role in the development of PAH. Endothelin is a potent vasoconstrictor peptide, and its expression is increased in the pulmonary arteries of patients with PAH; therefore, inhibition of endothelin production may be beneficial. Bosentan, a dual endothelin receptor antagonist, lowers pulmonary pressures and has improved exercise tolerance and lengthened the time to clinical deterioration in adults with idiopathic PAH. In addition, children with idiopathic PAH and PAH secondary to congenital heart disease have gained benefit from bosentan.
Sildenafil, a phosphodiesterase-5 inhibitor, is a pulmonary vasodilator agent that causes an increase in cGMP levels that has pulmonary vasodilatory properties and is as effective as, and may be an oral analogue of, inhaled nitric oxide. Sildenafil also has been noted to facilitate the weaning of INO in the post-operative setting of PAH. 
We suggest a vasodilator treatment strategy as proposed by Rashid and Ivy (Figure 1) based on the results of acute drug testing in the catheterization laboratory.  Balloon atrial septostomy is reserved for the patient with severe PAH and symptoms of right heart failure accompanied by syncope. Creation of an atrial level communication will decompress the pressure overloaded right heart and preserve cardiac output at the expense of right-to-left shunting and desaturation. Finally, lung transplantation is reserved for patients with severe PAH and symptoms of right heart failure that do not respond to therapy.

The modern era of drug therapy has resulted in major improvements in the prognosis of children with PAH. The five-year survival in children with idiopathic PAH who are acute responders is as high as 97 percent. The five-year survival in patients with idiopathic PAH who are non-responders may be as high as 80 percent. Though survival is lower for the latter group, there is the potential for "vascular remodeling" with chronic prostacyclin therapy.

We have gained a great deal of knowledge about PAH over the last several years. A more succinct understanding of pathophysiology has elucidated its mechanisms and facilitated a rational approach to therapy. Medications continue to evolve and provide patients with an improved outlook. Finally, the genomic approach to the study of PAH including the identification of candidate genes may allow for future gene manipulation and prevention.

ECMO program designated a Center of Excellence

Richard Berens, MD, pediatric anesthesiologist and intensivist, Children's Hospital of Wisconsin; associate professor, Pediatrics, Medical College of Wisconsin.

The Extracorporeal Life Support Organization has named the ECMO program at Children's Hospital of Wisconsin a Designated Center of Excellence. The Children's Hospital program is one of only six programs in the U.S. to receive the ELSO Award for Excellence in Life Support for 2006-2008.

ECMO, or extracorporeal membrane oxygenation, is a machine that acts like an artificial heart and lung. The machine puts oxygen in and takes carbon dioxide out of the blood and circulates the blood throughout the body, giving the patient's organs time to rest and heal. About 20 to 25 patients are placed on ECMO each year at Children's Hospital, which has been using ECMO therapy since 1986.

A panel of three experts judged each award application on criteria including facilities and equipment; staffing; education, training and mentoring; evidence-based practice and research; patient outcomes; and family education and participation. The Children's Hospital program was particularly praised for its accomplishments in the education, training and mentoring category.

ELSO encourages and supports excellence in ECMO practice, research and education. Its membership includes more than 115 hospitals and institutions around the world. ELSO established the award to "recognize and honor ECMO programs internationally who reach the highest level of performance, innovation, satisfaction and quality."