The Child Opportunity Index 2.0 and Disparities in Pediatric Cardiorespiratory Fitness.

OBJECTIVE: To evaluate the effect of neighborhood-level characteristics on cardiorespiratory fitness (CRF) via peak oxygen consumption (VO2peak) for healthy pediatric patients. STUDY DESIGN: The institutional cardiopulmonary exercise testing (CPET) database was analyzed retrospectively. All patients aged ≤ 18 years without a diagnosis of cardiac disease and with a maximal effort CPET were included. Patients were divided into three self-identified racial categories: White, Black, and Latinx. The Child Opportunity Index (COI) 2.0 was used to analyze social determinants of health. CRF was evaluated based on COI quintiles and race. Assessment of the effect of COI on racial disparities in CRF was performed using ANCOVA. RESULTS: A total of 1753 CPETs met inclusion criteria. The mean VO2peak was 42.1 ± 9.8 mL/kg/min. The VO2peak increased from 39.1 ± 9.6 mL/kg/min for patients in the very low opportunity cohort to 43.9 ± 9.4 mL/kg/min for patients in the very high opportunity cohort. White patients had higher percent predicted VO2peak compared with both Black and Latinx patients (P < .01 for both comparisons). The racial differences in CRF were no longer significant when adjusting for COI. CONCLUSION: In a large pediatric cohort, COI was associated with CRF. Racial disparities in CRF are reduced when accounting for modifiable risk factors.

Reference Values for Cardiorespiratory Fitness in Patients Aged 6 to 18 Years.

OBJECTIVE: To develop reference values for cardiorespiratory fitness, as quantified by peak oxygen uptake (VO2peak) and treadmill time, in patients aged 6 through 18 years referred for cardiopulmonary exercise testing (CPET). STUDY DESIGN: We reviewed a clinical pediatric CPET database for fitness data in children aged 6-18 years with no underlying heart disease. CPET was obtained via the Bruce protocol utilizing objectively confirmed maximal effort via respiratory exchange ratio. Fitness data (VO2peak and treadmill test duration) were analyzed to determine age- and sex-specific reference values for this pediatric cohort. RESULTS: Data from 2025 pediatric CPETs (53.2% female) were included in the analyses. VO2peak increased with age in males, but not females. Treadmill test duration increased with age in both males and females. Fitness was generally higher in males when compared with females in the same age groups. CONCLUSIONS: Our study provides extensive reference values for both VO2peak and total treadmill test time via the Bruce protocol for a pediatric population without known cardiac disease. Furthermore, the inclusion of objectively confirmed maximal exercise effort increases confidence in these findings compared with prior studies in this area. Clinicians performing CPET in pediatric populations can utilize these reference values to characterize test results according to representative peer data.

Effect of body mass index on exercise capacity following pediatric heart transplantation.

BACKGROUND: Obesity and impaired exercise tolerance following heart transplantation increase the risk of post-transplant morbidity and mortality. The aim of this study was to evaluate the effect of body mass index on markers of exercise capacity in pediatric heart transplant recipients and compare this effect with a healthy pediatric cohort. METHODS: A retrospective analysis of cardiopulmonary exercise test data between 2004 and 2022 was performed. All patients exercised on a treadmill using the Bruce protocol. Inclusion criteria included patients aged 6-21 years, history of heart transplantation (transplant cohort) or no cardiac diagnosis (control cohort) at the time of testing, and a maximal effort test. Patients were further stratified within these two cohorts as underweight, normal, overweight, and obese based on body mass index groups. Two-way analyses of variance were performed with diagnosis and body mass index category as the independent variables. RESULTS: A total of 250 exercise tests following heart transplant and 1963 exercise tests of healthy patients were included. Heart transplant patients across all body mass index groups had higher resting heart rate and lower maximal heart rate, heart rate recovery at 1 min, exercise duration, and peak aerobic capacity (VO2peak). Heart transplant patients in the normal and overweight body mass index categories had higher VO2peak and exercise duration when compared to underweight and obese patients. CONCLUSION: Underweight status and obesity are strongly associated with lower VO2peak and exercise duration in heart transplant patients. Normal and overweight heart transplant patients had the best markers of exercise capacity.

Chronotropic Response to Exercise is Decreased in Patients With Congenital Heart Disease Compared to Cardiomyopathy Following Pediatric Heart Transplantation.

BACKGROUND: Two common indications for pediatric heart transplantation are congenital heart disease and cardiomyopathy. Prior studies suggest differences in chronotropy on cardiopulmonary exercise testing outcomes depending on indication for heart transplantation. We aimed to determine whether the number of pretransplant sternotomies is associated with differences in heart rate response during exercise testing. METHODS: A retrospective analysis of our institutional pediatric heart transplant data between 2004 and 2022 was performed. Patients were categorized by indication for transplantation into a cardiomyopathy (CM) group if they had a congenital or acquired cardiomyopathy or a congenital heart disease (CHD) group including all other forms of congenital cardiac anatomic abnormalities. RESULTS: CHD patients (n = 40) differed from CM patients (n = 53) by mean number of sternotomies prior to transplant (2.4 ± 1.8 vs. 0.5 ± 0.9, p < 0.001). There were no significant differences in echocardiographic function or catheterization hemodynamics. In cardiopulmonary exercise testing performance, the congenital heart disease group had a significantly higher resting heart rate (91.8 ± 11.2 vs. 86.4 ± 10.2 bpm, p = 0.019), lower percent predicted age-predicted maximal heart rate achieved (78.3 ± 8.5% vs. 83.2 ± 11.4%, p = 0.032), and lower heart rate reserve (68.6 ± 19.8 vs. 84.4 ± 24.0 bpm, p = 0.001) despite a similar age and average time from transplantation. Regression analysis confirmed number of pretransplant sternotomies as a main predictor of heart rate metrics. CONCLUSIONS: There is greater chronotropic incompetence in patients who underwent transplantation due to congenital heart disease compared to cardiomyopathy. The groups differ significantly by number of sternotomies, potentially supporting the hypothesis that prior surgical disruption of cardiac innervation may cause decreased chronotropic response to exercise following transplantation.

Indication for Pediatric Heart Transplant Affects Longitudinal Chronotropy on Cardiopulmonary Exercise Testing.

Studies have suggested that pediatric patients with heart transplants (HT) due to congenital heart disease (CHD) perform differently on cardiopulmonary exercise testing compared to pediatric patients with HT due to cardiomyopathy (CM). However, it is not known if this relationship changes over time. The aim of this study was to examine the differences in cardiopulmonary exercise test (CPET) parameters over time between patients with HT due to CHD versus CM. A large single-institution CPET database was used for this study. We conducted a retrospective cohort study of 250 total CPETs from 93 unique patients, examining how patients with HT due to CHD (109 CPETs, 40 unique patients) differed in CPET performance from patients with HT due to CM (141 CPETs, 53 unique patients) from < 2 years post-HT, 2 to < 6 years post-HT, and ≥ 6 years post-HT. There were no differences between patients with HT due to CHD compared to CM in CPETs performed < 2 years post-HT. In CPETs performed 2 to < 6 years post-HT, the CM group had higher maximal HR and percentage of age-predicted maximal heart rate (APMHR) achieved. At ≥ 6 years post-HT, the CM group continued to have higher maximal HR and percentage of APMHR achieved, but also improved HR recovery at one minute. Initial indication for transplant may affect performance on CPETs post-transplant. Patients with HT due to CM have improved chronotropic measures compared to patients with HT due to CHD and these differences are more pronounced with increased time post-HT.

Development of a Pediatric Cardiology Cardiopulmonary Exercise Testing Database.

Cardiopulmonary exercise testing (CPET) provides clinicians with information vital to the management of pediatric cardiology patients. CPET can also be used to measure cardiorespiratory fitness (CRF) in these patients. CRF is a robust marker of overall health in children. However, a complete understanding of CRF in pediatric cardiology patients is limited by lack of large, standardized CPET databases. Our purpose was to develop a standardized CPET database, describe available data at our institution, and discuss challenges and opportunities associated with this project. CPETs performed from 1993 to present in an urban pediatric hospital were collected and compiled into a research database. Historical data included demographic and clinical variables and CPET outcomes, and additional variables were calculated and coded to facilitate analyses in these cohorts. Patient diagnoses were coded to facilitate sub-analyses of specific cohorts. Quality assurance protocols were established to ensure future database contributions and promote inter-institutional collaborations. This database includes 10,319 CPETs (56.1% male), predominantly using the Bruce Protocol. Patients ranging from ages 6 to 18 years comprise 86.8% of available CPETs. Diagnosis classification scheme includes patients with structurally normal hearts (n = 3,454), congenital heart disease (n = 3,614), electrophysiological abnormalities (n = 2,082), heart transplant or cardiomyopathy (n = 833), and other diagnoses (n = 336). Historically, clinicians were provided with suboptimal interpretive resources for CPET, often generalizing inferences from these resources to non-representative clinical populations. This database supports representative CRF comparisons and establishes a framework for future CRF-based registries in pediatric patients referred for CPET, ultimately improving clinical decision-making regarding fitness in these populations.

Multisystem Inflammatory Syndrome in Children (MIS-C): Reduced Exercise Duration and Capacity at Six Month Follow-Up.

Myocarditis is common in Multisystem Inflammatory Syndrome in Children (MIS-C), and the mechanism may differ from idiopathic/viral myocarditis as MIS-C involves a hyper-inflammatory state weeks after COVID-19. We sought to evaluate exercise stress testing (EST) in these patients as EST may help guide return-to-play recommendations. Retrospective cohort study evaluating ESTs (standard Bruce treadmill protocol) from MIS-C patients from 2020 to 2022, compared to myocarditis patients and age, sex, and weight matched controls from 2005 to 2019. ESTs included 22 MIS-C patients (mean age 11.9 years) with 14 cardiopulmonary and 8 cardiovascular tests, 33 myocarditis (15.5 years), and 44 controls (12.0 years). Percent-predicted peak VO2 was abnormal (< 80% predicted) in 11/14 (79%) MIS-C patients, 13/33 (39%) myocarditis, and 17/44 (39%) controls (p = 0.04). Exercise duration was shorter in MIS-C than myocarditis or control cohorts (p = 0.01). Isolated atrial or ventricular ectopy was seen in 8/22 (36%) MIS-C, 9/33 (27%) myocarditis, and 5/44 (11%) controls (p = 0.049). No arrhythmias/complex ectopy or evidence of ischemia were noted, though non-specific ST/T wave abnormalities occurred in 4/22 (18%) MIS-C, 5/33 (15%) myocarditis, and 3/44 (7%) controls. Exercise duration and percent-predicted peak VO2 were significantly reduced in MIS-C at mean 6-month follow-up compared to pre-COVID era idiopathic/viral myocarditis and control cohorts. This may be secondary to deconditioning during the pandemic and/or chronic cardiopulmonary or autonomic effects of COVID/MIS-C. Although there were no exercise-induced arrhythmias in our MIS-C patients, larger cohort studies are warranted. EST in MIS-C follow-up may help evaluate safety and timing of return to play and potentially mitigate further deconditioning.

Limited utility of repeated vital sign monitoring during initiation of oral propranolol for complicated infantile hemangioma.

BACKGROUND: Initial propranolol recommendations for infantile hemangioma published in 2013 were intended as provisional best practices to be updated as evidence-based data emerged. METHODS: A retrospective multicenter study was performed to evaluate utility of prolonged monitoring after first propranolol dose and escalation(s). Inclusion criteria included diagnosis of hemangioma requiring propranolol of greater than or equal to 0.3 mg/kg per dose, younger than 2 years, and heart rate monitoring for greater than or equal to 1 hour. Data collected included demographics, dose, vital signs, and adverse events. RESULTS: A total of 783 subjects met inclusion criteria; median age at initiation was 112 days. None of the 1148 episodes of prolonged monitoring warranted immediate intervention or drug discontinuation. No symptomatic bradycardia or hypotension occurred during monitoring. Mean heart rate change from baseline to 1 hour was -8.19/min (±15.54/min) and baseline to 2 hours was -9.24/min (±15.84/min). Three preterm subjects had dose adjustments because of prescriber concerns about asymptomatic vital sign changes. No significant difference existed in pretreatment heart rate or in heart rate change between individuals with later adverse events during treatment and those without. CONCLUSION: Prolonged monitoring for initiation and escalation of oral propranolol rarely changed management and did not predict future adverse events. Few serious adverse events occurred during therapy; none were cardiovascular.

Pediatric Cardiology Fellowship Training in Exercise Medicine: A General Needs Assessment.

The aim of this study was to improve understanding of exercise medicine training needs for pediatric cardiology fellows. A survey was sent via email to all (N = 63) pediatric cardiology training program directors in the United States to evaluate the perceived exercise training needs of pediatric cardiology fellows. The survey consisted of multiple-choice responses as well as a few open-ended responses. A 60% response rate was achieved. 74% of programs did not have a pre-existing exercise core program. This type of training was felt to be important or very important in 84%. A wide variability of time allotted for exercise training exists amongst programs from < 1 week to > 4 weeks, with 2 weeks being most common. There was no consensus on a target number of total exercise tests nor types of tests in which fellows should participate. Preferred methods in training consisted of lectures and online media. Less preferred methods of teaching methods included dedicated reading of a handbook, a dedicated rotation, or live webinars. There was general support to develop exercise training competencies as well as the associated online learning materials with a focus on competency rather than target numbers. There is a need for educational recommendations for exercise training in pediatric cardiology fellowships as well as a unified method of achieving competencies.

Persistence of Palpitations After Slow Pathway Modification for AVNRT in Young People.

Symptoms are the most common indication for ablation in children with atrioventricular nodal reentrant tachycardia (AVNRT). After the procedure, patients may continue to report palpitations. The objective of this study was to quantify the risk and duration of palpitations after pediatric slow pathway modification as well as demographic and technical associations. This was a retrospective review of consecutive patients at a pediatric center who underwent slow pathway modification for AVNRT from 2012 to 2018. Patients with a prior ablation attempt or congenital heart disease were excluded. Palpitations were documented in 35% of patients after ablation. Neither post-ablation echo beats nor other evidence of residual dual AV nodal physiology were associated with a higher risk of post-ablation palpitations. Of the 35 patients with post-ablation palpitations, the median time to resolution of palpitations was 48 months. Acute procedural success was achieved in all 100 cases. There were two recurrences of AVNRT during long-term follow-up and one instance of ectopic atrial tachycardia (3% SVT recurrence). Palpitations after AVNRT ablation occurred in approximately one-third of cases, despite a low recurrence of true arrhythmia. Prior to ablation, patients and families should be counseled that post-ablation palpitations are common and AVNRT recurrence is rare.

A survey of paediatricians on the use of electrocardiogram for pre-participation sports screening.

Aim The aim of the present study was to determine general paediatrician knowledge, practices, and attitudes towards electrocardiogram (ECG) screening in school athletes during pre-participation screening exam (PPSE). METHODS: Paediatricians affiliated with a tertiary children's hospital completed a survey about ECGs for PPSE. RESULTS: In total, 205/498 (41%) responded; 92% of the paediatricians did not include an ECG as part of PPSE; 56% were aware of a case in which a student athlete in their own community had died of sudden unexplained death; 4% had an athlete in their practice die. Only 16% of paediatricians perform all 12 American Heart Association recommended elements of the PPSE. If any of these screening elements are abnormal, 69% obtain an ECG, 36% an echocardiogram, and 30% restrict patients from sports activity; 73% of them refer the patient to a cardiologist. CONCLUSION: Most of the general paediatricians surveyed did not currently perform ECGs for PPSE. In addition, there was a low rate of adherence to performing the 12 screening elements recommended by the American Heart Association. They have trouble obtaining timely, accurate ECG interpretations, worry about potential unnecessary exercise restrictions, and cost-effectiveness. The practical hurdles to ECG implementation emphasise the need for a fresh look at PPSE, and not just ECG screening. Improvements in ECG performance/interpretation would be necessary for ECGs to be a useful part of PPSE.

Heart rate recovery is impaired after maximal exercise testing in children with sickle cell anemia.

OBJECTIVE: To examine heart rate recovery (HRR) as an indicator of autonomic nervous system dysfunction after maximal exercise testing in children and young adults with sickle cell anemia (SCA). STUDY DESIGN: Recovery phase heart rate (HR) in the first 5 minutes after maximal exercise testing in 60 subjects with SCA and 30 matched controls without SCA was assessed. The difference between peak HR and HR at both 1-minute (ΔHR1min) and 2-minutes recovery was our primary outcome. RESULTS: Compared with controls, subjects with SCA demonstrated significantly smaller mean ΔHR1min (23 beats per minute [bpm], 95% CI 20-26 vs 32 bpm, 95% CI 26-37, P = .006) and the difference between maximal HR and HR at 2 minutes (39 bpm, 95% CI 36-43 vs 48 bpm, 95% CI 42-53, P = .011). Subjects with SCA also showed smaller mean changes in HR from peak HR to 1 minute, from 1 minute to 2 minutes, and from 2 through 5 minutes of recovery by repeated-measures testing. In a multivariable regression model, older age was independently associated with smaller ΔHR1min in subjects with SCA. Cardiopulmonary fitness and hydroxyurea use, however, were not independent predictors of ΔHR1min. CONCLUSIONS: Children with SCA demonstrate impaired HRR after maximal exercise. Reduced postexercise HRR in SCA suggests impaired parasympathetic function, which may become progressively worse with age, in this population.

A Reference Equation for Peak Oxygen Uptake for Pediatric Patients Who Undergo Treadmill Cardiopulmonary Exercise Testing.

Pediatric patients are often referred to cardiopulmonary exercise testing (CPET) laboratories for assessment of exercise-related symptoms. For clinicians to understand results in the context of performance relative to peers, adequate fitness-based prediction equations must be available. However, reference equations for prediction of peak oxygen uptake (VO2peak) in pediatrics are largely developed from field-based testing, and equations derived from CPET are primarily developed using adult data. Our objective was to develop a pediatric reference equation for VO2peak. Clinical CPET data from a validation cohort of 1,383 pediatric patients aged 6 to 18 years who achieved a peak respiratory exchange ratio ≥1.00 were analyzed to identify clinical and exercise testing factors that contributed to the prediction of VO2peak from tests performed using the Bruce protocol. The resultant prediction equation was applied to a cross-validation cohort of 1,367 pediatric patients. Exercise duration, gender, weight, and age contributed to the prediction of VO2peak, generating the following prediction equation: (R2 = 0.645, p <0.001, standard error of the estimate = 6.19 ml/kg/min): VO2peak (ml/kg/min) =16.411+ 3.423 (exercise duration [minutes]) - 5.145 (gender [0 = male, 1 = female]) - 0.121 (weight [kg]) + 0.179 (age [years]). This equation was stable across the age range included in the present study, with differences ≤0.5 ml/kg/min between mean measured and predicted VO2peak in all age groups. In conclusion, this study represents what we believe is the largest pediatric CPET-derived VO2peak prediction effort to date, and this VO2peak prediction equation provides clinicians who perform and interpret exercise tests in pediatric patients with a resource with which to better quantify fitness when CPET is not available.

ehealth technology in cardiac exercise therapeutics for pediatric patients with congenital and acquired heart conditions: a summary of evidence and future directions.

Many children and adolescents with congenital and acquired heart disease (CHD) are physically inactive and participate in an insufficient amount of moderate-to-vigorous intensity exercise. Although physical activity (PA) and exercise interventions are effective at improving short- and long-term physiological and psychosocial outcomes in youth with CHD, several barriers including resource limitations, financial costs, and knowledge inhibit widespread implementation and dissemination of these beneficial programs. New and developing eHealth, mHealth, and remote monitoring technologies offer a potentially transformative and cost-effective solution to increase access to PA and exercise programs for youth with CHD, yet little has been written on this topic. In this review, a cardiac exercise therapeutics (CET) model is presented as a systematic approach to PA and exercise, with assessment and testing guiding three sequential PA and exercise intervention approaches of progressive intensity and resource requirements: (1) PA and exercise promotion within a clinical setting; (2) unsupervised exercise prescription; and (3) medically supervised fitness training intervention (i.e., cardiac rehabilitation). Using the CET model, the goal of this review is to summarize the current evidence describing the application of novel technologies within CET in populations of children and adolescents with CHD and introduce potential future applications of these technologies with an emphasis on improving equity and access to patients in low-resource settings and underserved communities.

The Role of Exercise Prescription in Pediatric Preventive Cardiology Programs.

Lifestyle changes such as exercise and dietary change are recommended first-line therapy for children with dyslipidemia, hypertension, and obesity. Although most clinicians recommend exercise, specific exercise prescriptions are not usually provided. The optimal type, duration, and intensity of activity to achieve a meaningful outcome is not definitively defined. As the pediatric population becomes more sedentary and morbidity accumulates from this lifestyle, understanding how targeted exercise prescriptions can benefit patients will be critical to effectively manage this group of patients. This review focuses on the role of exercise for the treatment of pediatric patients with dyslipidemia, hypertension, and obesity and describes additional factors that require future research to achieve desired outcomes in this at-risk population. [Pediatr Ann. 2018;47(12):e494-e498.].

Evolving anatomic and electrophysiologic considerations associated with Fontan conversion.

The principles of Fontan conversion with arrhythmia surgery are to restore the cardiac anatomy by converting the original atriopulmonary connection to a total cavopulmonary artery extracardiac connection and treat the underlying atrial arrhythmias. Successful outcomes of this procedure are dependent on a thorough understanding of several factors: the patient's fundamental diagnosis of single-ventricle anatomy, the resultant cardiac configuration from the original atriopulmonary Fontan connection, right atrial dilatation that leads to atrial flutter or fibrillation, and associated congenital cardiac anomalies. The purpose of this article is to present some of the more challenging anatomic and electrophysiologic problems we have encountered with Fontan conversion and arrhythmia surgery and the innovative solutions we have used to treat them. The cases reviewed herein include: takedown of a Bjork-Fontan modification, right ventricular hypertension and tricuspid regurgitation after atriopulmonary Fontan for pulmonary atresia and intact ventricular septum, takedown of atrioventricular valve isolation patch for right-sided maze procedure, resultant hemodynamic considerations leading to intraoperative pulmonary vein stenosis after Fontan conversion, unwanted inferior vena cava retraction during the extracardiac connection, right atrial cannulation in the presence of a right atrial clot, distended left superior vena cava causing left pulmonary vein stenosis, dropped atrial septum, and the modified right-sided maze procedure for various single-ventricle pathology. Since 1994 we have performed Fontan conversion with arrhythmia surgery on 109 patients with a 0.9% mortality rate. We attribute our program's success in no small measure to the strong collaborative efforts of the cardiothoracic surgery and cardiology teams.

Adaptation of Radiology Software to Improve Cardiology Results Reporting.

OBJECTIVE: Twenty-four hour ambulatory electrocardiograms ("Holter" monitors) are a key diagnostic test in cardiology. Commercial electronic medical record (EMR) tools have not been designed for pediatric Holter monitor reporting and paper-based methods are inefficient. METHODS: Our tertiary pediatric hospital adapted a radiology EMR tool to a cardiology workflow in order to report Holter monitor results. A retrospective review was performed at 4 time points: prior to intervention, immediately post-intervention, at 6 months and at 12 months post-intervention. The primary outcome variable was time to reporting of Holter findings. RESULTS: Holter reports were reviewed on 527 studies (patient ages: 1 day to 42 years). The time between the date the patient returned the Holter monitor until the date the referring physician received a final report improved from 19.8 days to 1.5 days (p<0.001). This result was durable over the next 12 months of follow-up. Physician interpretation time improved from 2.1 days to 0.6 days (p=0.01). Transcriptionist time and result scanning time were eliminated (removing 1.9 days and 14 days from the workflow, respectively). CONCLUSION: EMR systems are not typically designed for pediatric cardiology, but existing systems can be adapted, yielding important gains for patient care. In specialties like pediatric cardiology, there is insufficient volume nationally to drive development of commercial systems. This study demonstrates the general principle that creative adaptation of EMR systems can improve result reporting in pediatric cardiology and likely in other cardiology practices.Citation: Webster G, Ward K, Deal BJ, Anderson JB, Tsao S. Adaptation of Radiology Software to Improve Cardiology Results Reporting. Appl Clin Inform 2017; 8: 936-944 https://doi.org/10.4338/ACI-2017-03-RA-0051.

Bimodal regulation of an Elk subfamily K+ channel by phosphatidylinositol 4,5-bisphosphate.

Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates Shaker K+ channels and voltage-gated Ca2+ channels in a bimodal fashion by inhibiting voltage activation while stabilizing open channels. Bimodal regulation is conserved in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, but voltage activation is enhanced while the open channel state is destabilized. The proposed sites of PIP2 regulation in these channels include the voltage-sensor domain (VSD) and conserved regions of the proximal cytoplasmic C terminus. Relatively little is known about PIP2 regulation of Ether-á-go-go (EAG) channels, a metazoan-specific family of K+ channels that includes three gene subfamilies, Eag (Kv10), Erg (Kv11), and Elk (Kv12). We examined PIP2 regulation of the Elk subfamily potassium channel human Elk1 to determine whether bimodal regulation is conserved within the EAG K+ channel family. Open-state stabilization by PIP2 has been observed in human Erg1, but the proposed site of regulation in the distal C terminus is not conserved among EAG family channels. We show that PIP2 strongly inhibits voltage activation of Elk1 but also stabilizes the open state. This stabilization produces slow deactivation and a mode shift in voltage gating after activation. However, removal of PIP2 has the net effect of enhancing Elk1 activation. R347 in the linker between the VSD and pore (S4-S5 linker) and R479 near the S6 activation gate are required for PIP2 to inhibit voltage activation. The ability of PIP2 to stabilize the open state also requires these residues, suggesting an overlap in sites central to the opposing effects of PIP2 on channel gating. Open-state stabilization in Elk1 requires the N-terminal eag domain (PAS domain + Cap), and PIP2-dependent stabilization is enhanced by a conserved basic residue (K5) in the Cap. Our data shows that PIP2 can bimodally regulate voltage gating in EAG family channels, as has been proposed for Shaker and HCN channels. PIP2 regulation appears fundamentally different for Elk and KCNQ channels, suggesting that, although both channel types can regulate action potential threshold in neurons, they are not functionally redundant.