Challenges of healthcare administration: optimizing quality and value at an affordable cost in pediatric cardiology.

PURPOSE OF REVIEW: The purpose of this review is to explore the paradigm shift in healthcare delivery that will need to take place over the next few years away from an emphasis on supply-driven health care to better quality transparent-driven health care whose focus is on the consumer's best interest. RECENT FINDINGS: The current healthcare system is fragmented and costs continue to rise. The best way to contain costs is to improve quality to the consumer, the patient. Physicians and hospitals need to align in a team-based approach that allows physicians to understand current costs and how to strive toward a focus on healthcare outcomes. Pediatric cardiology is a unique discipline that cares for patients with complex congenital conditions that will span their lifetime and also involves not just cardiology but surgery, intensive care, anesthesia, nursing, and a host of inpatient and ambulatory services. Understanding what matters to the patient and his/her family and presenting quality outcomes in a transparent fashion will gradually allow a shift to take place away from physician visits, tests ordered, and procedures performed. This can only be achieved with physicians, given the appropriate tools to understand costs, value, and outcomes and models where the hospitals and physicians are aligned. SUMMARY: The transformation to a value-based healthcare system is beginning and pediatric cardiologists need to be educated, given the appropriate resources, receive appropriate feedback, and patients need to be part of the solution so that care providers can understand what matters most to them.

Outpatient echocardiography in the evaluation of innocent murmurs in children: utilisation benchmarking.

OBJECTIVES: We sought to benchmark the utilisation of echocardiography in the outpatient evaluation of heart murmurs by evaluating two large paediatric cardiology centres. BACKGROUND: Although criteria exist for appropriate use of echocardiography, there are no benchmarking data demonstrating its utilisation. METHODS: We performed a retrospective cohort study of outpatients aged between 0 and 18 years at the Sibley Heart Center Cardiology and the Children's Hospital of Philadelphia Division of Cardiology, given a sole diagnosis of "innocent murmur" from 1 July, 2007 to 31 October, 2010. Using internal claims data, we compared the utilisation of echocardiography according to centre, patient age, and physician years of service. RESULTS: Of 23,114 eligible patients (Sibley Heart Center Cardiology: 12,815, Children's Hospital of Philadelphia Division of Cardiology: 10,299), 43.1% (Sibley Heart Center Cardiology: 45.2%, Children's Hospital of Philadelphia Division of Cardiology: 40.4%; p1-5 years had the lowest utilisation (32.7%). CONCLUSIONS: In two large paediatric cardiology practices, the overall utilisation of echocardiography by physicians with a sole diagnosis of innocent murmur was similar. There was significant and similar variability in utilisation by provider at both centres. Although these data serve as initial benchmarking, the variability in utilisation highlights the importance of appropriate use criteria.

Supervised embedding of textual predictors with applications in clinical diagnostics for pediatric cardiology.

OBJECTIVE: Electronic health records possess critical predictive information for machine-learning-based diagnostic aids. However, many traditional machine learning methods fail to simultaneously integrate textual data into the prediction process because of its high dimensionality. In this paper, we present a supervised method using Laplacian Eigenmaps to enable existing machine learning methods to estimate both low-dimensional representations of textual data and accurate predictors based on these low-dimensional representations at the same time. MATERIALS AND METHODS: We present a supervised Laplacian Eigenmap method to enhance predictive models by embedding textual predictors into a low-dimensional latent space, which preserves the local similarities among textual data in high-dimensional space. The proposed implementation performs alternating optimization using gradient descent. For the evaluation, we applied our method to over 2000 patient records from a large single-center pediatric cardiology practice to predict if patients were diagnosed with cardiac disease. In our experiments, we consider relatively short textual descriptions because of data availability. We compared our method with latent semantic indexing, latent Dirichlet allocation, and local Fisher discriminant analysis. The results were assessed using four metrics: the area under the receiver operating characteristic curve (AUC), Matthews correlation coefficient (MCC), specificity, and sensitivity. RESULTS AND DISCUSSION: The results indicate that supervised Laplacian Eigenmaps was the highest performing method in our study, achieving 0.782 and 0.374 for AUC and MCC, respectively. Supervised Laplacian Eigenmaps showed an increase of 8.16% in AUC and 20.6% in MCC over the baseline that excluded textual data and a 2.69% and 5.35% increase in AUC and MCC, respectively, over unsupervised Laplacian Eigenmaps. CONCLUSIONS: As a solution, we present a supervised Laplacian Eigenmap method to embed textual predictors into a low-dimensional Euclidean space. This method allows many existing machine learning predictors to effectively and efficiently capture the potential of textual predictors, especially those based on short texts.

Cryoablation therapy for atrioventricular nodal reentrant tachycardia in children: a multicenter experience of efficacy.

Atrioventricular nodal reentrant tachycardia (AVNRT), a common tachycardia in children, is routinely treated by catheter ablation using radiofrequency or cryothermal energy. Acute success rates of 95-97 % are reported for cryoablation, similar to those achieved with radiofrequency ablation (RFA). However, early studies reported higher recurrence rates after cryoablation for treatment of AVNRT than those reported for RFA. This study evaluated the success and recurrence rates for cryoablation in a current cohort of pediatric patients across several institutions. Patients 21 years old or younger with AVNRT who underwent cryoablation at five participating centers between 2004 and 2009 were retrospectively reviewed. Patient demographics and procedural data were extracted from patient records and analyzed. A total of 434 patients with AVNRT who underwent cryoablation were identified. Cryoablation was used as the exclusive ablation method for 379 patients. For 97 % (368/379) of these patients, cryoablation was acutely successful. A higher acute success rate was found with the 6-mm-tip catheter (99 %) than with the 4-mm-tip catheter (91 %) (p < 0.01). Recurrence was experienced by 7.3 % of the patients. Recurrence was more likely for those treated with the 4-mm-tip catheter (6/42, 14 %) than for those who had the larger catheters (12/204, 6 %) No patient experienced permanent heart block. Success and recurrence rates for this cohort of patients were similar to those reported for RFA used to treat AVNRT in pediatric patients. The findings show a higher success rate and a lower recurrence rate after cryoablation with a 6-mm-tip catheter than after use of the 4-mm-tip catheter, with an associated excellent safety profile.

Utility of a clinical support tool for outpatient evaluation of pediatric chest pain.

This study evaluates a clinical pathway currently being employed at a large single-center pediatric cardiology practice. The dataset includes 1,997 pediatric patients with the primary complaint of chest pain. A logistic regression model was developed to predict cardiac disease and identify strong indicators of cardiac pathology. The area under the ROC curve was 0.73 and the Matthews correlation coefficient was 0.23. Given the low incidence of pathology disease, this study was unable to identify strong predictors of major cardiac pathology. The analysis did support syncope, palpitations and the onset of chest pain in the past 2-7 days as predictors of minor cardiac disease. However, the model indicated exertional chest pain is negatively associated with cardiac disease. This data should be evaluated with caution as some of the results are contrary to most clinical cardiologists' views. The majority of the results support the cardiac disease predictors in the clinical pathway.

Does ablation of supraventricular tachycardia in children with a structurally normal heart improve quality of life?

INTRODUCTION: Ablation has become first-line therapy for managing many pediatric patients with atrioventicular accessory pathway or atrioventricular nodal-mediated supraventricular tachycardia (SVT). Studies to date have all focused on elimination of the SVT substrate; yet, there are no studies to document whether this results in improved quality of life (QoL) scores. OBJECTIVE: The objective of this study was to evaluate whether a successful catheter ablation improved QoL scores in pediatric patients. PATIENT AND METHODS: Pediatric patients between the age of 5 and 18 years with structurally normal hearts and re-entry SVT that were referred to the electrophysiology laboratory between October 2004 and June 2006 at the Children's Healthcare of Atlanta were eligible to be enrolled in the study. The Pediatric Quality of Life Inventory cardiac model questionnaire was administered to patients prior to and 6 months following catheter ablation. Areas evaluated were physical, emotional, social, school, and psychosocial function. The paired t-test was used to test the difference between pre- and post-time points for the study groups. P value <.05 was considered significant. RESULTS: Forty-three patients consented to initial enrollment and returned the initial questionnaires. Seven patients did not have ablations performed during the electrophysiology study and therefore were excluded from further analysis. Complete pre- and post-ablation data were available for 27 patients. Comparing pre-ablation data with post-ablation data, there was significant improvement in all measured areas following successful elimination of tachycardia substrate. Patients reported lowest social and physical functioning scores pre-ablation. The greatest reported improvement post-ablation was in physical functioning. CONCLUSION: Successful elimination of SVT substrate results in improved pediatric QoL scores as reported by patients.

Epicardial ablation of ventricular tachycardia in a child on venoarterial extracorporeal membrane oxygenation.

Epicardial catheter ablation has been demonstrated to be safe and effective in adults, but there are limited reports in the pediatric population. We report the epicardial ablation of an incessant, hemodynamically compromising ventricular tachycardia in a 13-month-old patient on venoarterial extracorporeal membrane oxygenation. The procedure resulted in elimination of tachycardia substrate with improved cardiac size and function at follow-up. Despite a reasonable long-term outcome in this child, epicardial ablation in young patients should be reserved for similarly dire circumstances.

Outcome of isolated bicuspid aortic valve in childhood.

OBJECTIVE: To evaluate the outcomes associated with isolated bicuspid aortic valve (BAV) during childhood and adolescence. STUDY DESIGN: Analysis of a large single institutional cohort of children (n=981) with isolated BAV was undertaken to determine the prevalence of significant ascending aortic dilation and risk of cardiac events. Subjects with known genetic disorders, critical aortic stenosis (intervention required in infancy), or additional lesions such as coarctation of the aorta were excluded. Aortic dimensions were derived from echocardiography, and values were plotted as Z scores. Clinical outcomes included death, aortic dissection, balloon aortic valvuloplasty, or cardiac surgery. RESULTS: The median age of the subjects at diagnosis was 8.3 years. At the time of the last pediatric follow-up, 7% of the subjects had moderate aortic regurgitation or greater, and the median Z score for the ascending aorta was +2.31. There were 9427 patient years of follow-up. Primary cardiac events occurred in 38 subjects, yielding an event rate of 0.004 per patient year. Eleven subjects (1.1%) underwent aortic valve surgery. Thirty subjects (3.0%) underwent balloon dilatation of the aortic valve. There was a single case of endocarditis. There were no cardiac-related deaths and no cases of aortic dissection. CONCLUSIONS: The incidence of primary cardiac events in children with BAV is relatively low, approximately 3-fold lower than in young adults, and is generally related to aortic stenosis amenable to balloon dilatation. Although mild ascending aortic dilation is common in children, the clinical course is relatively benign. In this series, aortic dissection did not occur. Whether elective surgery for the dilated aorta has a role in children remains unknown.

Early and delayed atrioventricular conduction block after routine surgery for congenital heart disease.

OBJECTIVES: Patients undergoing surgical closure of ventricular septal defects are at risk for immediate or delayed atrioventricular conduction block. Our goal was to better define the incidence of delayed atrioventricular conduction block. METHODS: A retrospective review was conducted of hospital records and pacemaker database for ventricular septal defect, atrioventricular canal, and tetralogy of Fallot repairs between 1999 and 2004. A total of 922 patients were identified (atrioventricular canal in 197, tetralogy of Fallot in 222, and ventricular septal defect in 503). Median follow-up was 4.1 years. RESULTS: There were 472 male and 450 female patients, median age 6 months (0-444 months) and median weight 5.8 kg (1.3-116 kg) at surgery. Postoperative atrioventricular conduction block developed in 21 (2.3%) of the 922, being transient, with return of conduction 3 days (1-14 days) after surgery, in 13 (1.4%) and permanent, with pacemakers implanted 10 days (6-20 days) after surgery, in 8 (0.9%). Of the 905 patients at risk for delayed atrioventricular conduction block, 3 (0.3%) had second- or third-degree block at 2, 8, and 16 months after surgery. Two of these 3 had transient postoperative block. For isolated ventricular septal defects, the incidence was 1 (0.2%) of 496. There were 8 late deaths at 31 months (7-45 months) after surgery. Five had normal conduction at death, but for 3 patients the conduction status at death could not be determined. Including these 3 patients as possible cases of delayed atrioventricular block yields an incidence of 0.3% to 0.7%. CONCLUSIONS: The incidence of early atrioventricular conduction block requiring a pacemaker was 0.9% and that of delayed atrioventricular conduction block was 0.3% to 0.7%. Transient atrioventricular conduction block may be a marker for increased risk of delayed block. These data may be useful for evaluation of new techniques.

Inappropriate ICD discharges in single-chamber versus dual-chamber devices in the pediatric and young adult population.

BACKGROUND: Implantable cardioverter defibrillator (ICD) use is increasing in young patients and is frequently complicated by inappropriate device discharges (IDs), leading to discomfort, anxiety and, potentially, proarrhythmia. Dual-chamber (DC) ICDs may decrease IDs by improving rhythm discrimination, but are associated with increased size, expense, and implant complications. We examined whether the frequency of IDs was the same in dual- and single-chamber (SC) ICDs in young patients. METHODS: A multicenter review of patients

Long-term risk of fatal malignancy following pediatric radiofrequency ablation.

Children undergoing radiofrequency ablation (RFA) are believed to be at increased risk of developing malignancy caused by radiation, although the magnitude of this risk is incompletely understood. We previously reported a strategy to reduce radiation exposure during pediatric RFA. In a cohort of 15 subjects (median age 12 years, range 9 to 17), radiation was measured using dosimeters at 5 sites. The risk of malignancy using measured radiation absorbed dose was calculated. International Council for Radiation Protection 60 risk estimates were applied to calculate absorbed organ doses. Median duration of combined biplane fluoroscopy was 14.4 minutes. Of the 5 dosimeter locations, the right scapular location had the highest median radiation exposure (43 mGy). Incorporating data from the 5 dosimeters, the risk model calculated that the organ with the greatest absorbed dose and at greatest risk of malignancy was the lung, followed by bone marrow, then breast. Thyroid and ovary exposures were negligible. The increased lifetime risk of fatal malignancy was 0.02% per single RFA procedure. In conclusion, with appropriate measures to reduce radiation exposure, the increased risk of malignancy after a single RFA procedure in children is low. These data should be of help counseling families and will contribute to analysis of the relative risk reduction benefits of such novel imaging approaches as a magnetic resonance imaging-based catheterization laboratory.

Acute pacing-induced dyssynchronous activation of the left ventricle creates systolic dyssynchrony with preserved diastolic synchrony.

INTRODUCTION: Patients with heart block have conventionally received a pacemaker that stimulates the right ventricular apex (RVA) to restore heart rate control. While RVA pacing has been shown to create systolic dyssynchrony acutely, dyssynchrony can also occur in diastole. The effects of acute RVA pacing on diastolic synchrony have not been investigated. RVA pacing acutely impairs diastolic function by increasing the time constant of relaxation, decreasing the peak lengthening rate and decreasing peak negative dP/dt. We therefore hypothesized that acute RVA pacing would cause diastolic dyssynchrony in addition to creating systolic dyssynchrony. METHODS AND RESULTS: Fourteen patients (13 +/- 4 years old) with non-preexcited supraventricular tachycardia underwent ablation therapy with subsequent testing to confirm elimination of the tachycardia substrate. Normal cardiac structure and function were then documented on two-dimensional echocardiography and 12-lead electrocardiography prior to enrollment. Tissue Doppler images were collected during normal sinus rhythm (NSR), right atrial appendage pacing (AAI), and VVI-RVA pacing during the postablation waiting interval. Systolic and diastolic dyssynchrony were quantified using cross-correlation analysis of tissue Doppler velocity curves. Systolic dyssynchrony increased 81% during RVA pacing relative to AAI and NSR (P < 0.01). Diastolic synchrony was not affected by the different pacing modes (P = 0.375). CONCLUSION: Acute dyssynchronous activation of the LV created by RVA pacing resulted in systolic dyssynchrony with preserved diastolic synchrony in pediatric patients following catheter ablation for treatment of supraventricular tachycardia. Our results suggest that systolic and diastolic dyssynchrony are not tightly coupled and may develop through separate mechanisms.

Outcomes following electroanatomic mapping and ablation for the treatment of ectopic atrial tachycardia in the pediatric population.

Ectopic atrial tachycardia (EAT) is often resistant to medical therapy, with radiofrequency ablation (RFA) being a preferred treatment option. Three-dimensional (3-D) electroanatomic mapping was introduced as a tool for improved substrate localization, although there are no published data with this technology in pediatric patients with EAT. The objective of this study was to examine our experience with 3-D mapping and standard mapping in this patient population. We used retrospective chart review of pediatric patients with EAT requiring RFA from 1993 to 2004. We analyzed the method of ablation, acute success and recurrence rates, procedure and fluoroscopy times, and cardiac function. Twenty-five patients underwent 31 RFA procedures. All patients had been followed for >6 months (6 months to 7 years). Standard mapping (Group 1) was used in 11 patients (5F/6M, 1.4-11.8 years) who underwent 13 RFA procedures; 3-D mapping (Group 2, October 2000-2004) was used in 16 patients (8 F/8M, 2.7-17 years) who underwent 18 RFA procedures. Left-sided focus was present in 6/13 in Group 1 and 7/18 in Group 2 (all transeptal, NS). There was a trend toward fewer lesions with 3-D mapping (15 +/- 14, median 9.5 in Group 1; 8 +/- 6, median 6.5 in Group 2, NS). Acute success was more likely for patients in which 3-D mapping was utilized (10/13 Group 1 vs. 18/18 Group 2, p < 0.04). Recurrence or persistence of tachycardia at follow-up (2 weeks to 1 year) was documented in 7/13 cases in Group 1, compared to only 2/18 cases in Group 2 (p = 0.01). Six patients underwent repeat RFA: two patients using standard mapping (one failure, one success) and four patients using 3-D mapping [all acute and long-term (>1 year) success]. Procedure times (232 +/- 84 vs. 268 +/- 72 min, skin-to-skin) and fluoroscopy times (47 +/- 24 vs. 40 +/- 20 min) were similar (NS). Of the 25 pts, 17 (7 in Group 1, 10 in Group 2, NS) presented with cardiomyopathy [Ejection fraction (EF), 38.6 +/- 12.1%]. Successful RFA resulted in improved EF (61.1 +/- 11.6%, p < 0.0001) in the 14 patients in whom pre-RFA and post-RFA echocardiograms were available. Compared to standard techniques, 3-D electroanatomic mapping has resulted in no acute failures, statistically reduced recurrence rates, and improved overall success in the management of EAT.

Infrequently studied congenital anomalies as clues to the diagnosis of maternal diabetes mellitus.

The aim of this study was to identify congenital anomalies (CA) among infants of women with diabetes mellitus (DM) that, even though infrequent or infrequently reported, may suggest diabetic teratogenesis. Using 1976-2005 data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we compared the frequency of selected CA among 130 infants with CA born to women with pregestational DM (PGDM) and 30,009 infants with CA whose mothers had normal glucose tolerance (NGT). To identify which CA were not only significantly more frequent among infants of mothers with PGDM, but also more specific, we calculated the quotient of their frequencies (frequency ratio: FR). The same analysis was made using data from 927 infants of mothers with gestational DM (GDM). Among the studied defects, several were statistically significantly more frequent among infants of PGDM mothers than among infants of mothers with NGT, although the specificity of their association with DM varied, as indicated by the values of the FR. These included: anorectal atresia/stenosis (FR = 2.81; P = 0.03), hallucal polydactyly (FR = 3.62; P = 0.002), heterotaxy (FR = 5.70; P = 0.049), hypertrophic cardiomyopathy (HCM) (FR = 61.60; P = 0.000000), multicystic dysplastic kidneys (MDK) (FR = 5.13; P = 0.0002), and thymus aplasia/hypoplasia (FR = 29.62; P = 0.000001). The only CA significantly more frequent among infants of women with GDM were HCM (FR = 8.60; P = 0.002) and MDK (FR = 1.80; P = 0.01). Our results suggest that maternal PGDM should be suspected in children with hallucal polydactyly, anorectal atresia/stenosis, heterotaxy, or aplasia/hypoplasia of the thymus. The presence of transient HCM or MDK in a newborn suggests maternal PGDM or GDM. These observations are important in view of the increasing worldwide frequency of DM and the high proportion of individuals with DM in whom the condition remains undiagnosed. (c) 2007 Wiley-Liss, Inc.

Natural history and current therapy for complete heart block in children and patients with congenital heart disease.

Complete heart block, either congenital or acquired, in children and patients with congenital heart disease is a relatively frequent occurrence requiring therapy. The natural history of this condition has been distorted by the advent of new diagnostic and therapeutic modalities. The therapy of complete heart block is evolving with new data suggesting that traditional treatment strategies utilizing right ventricular apical pacing may have inadvertent deleterious effects on cardiac function. In the following manuscript, the natural history of complete heart block is reviewed and the current therapy examined.

Effects of single-site versus biventricular epicardial pacing on myocardial performance in an immature animal model of atrioventricular block.

INTRODUCTION: Single-site ventricular pacing results in dyssynchronous ventricular activation and may contribute to ventricular dysfunction. We evaluated epicardial biventricular (BiV) pacing as a means of maintaining synchronous ventricular activation in an acute piglet model of AV block with normal ventricular anatomy and function. METHODS AND RESULTS: We used left ventricular (LV) impedance catheters and tissue Doppler imaging to assess the cardiodynamics of immature piglets (n = 6, 33-78 days, 9.35 +/- 0.85 kg). Following catheter ablation of the AV node, a pacemaker was programmed 20 beats per minute above the intrinsic atrial rate. The animals were paced at 5-minute intervals via the following AV sequential configurations: Right atrial appendage (RA)-RV apex (RVA), RA-LV apex (LVA), and RA-biventricular (RVA/LVA). RA-RVA was the experimental control. LV systolic mechanics, measured by the slope of the end-systolic pressure-volume relationship (E(es)), increased with BiV pacing (12.8 +/- 3.4 mmHg/mL, P < 0.02) or single-site LVA pacing (10.6 +/- 3.4 mmHg/mL, P < 0.05) compared with single-site RVA pacing (8.3 +/- 1.4 mmHg/mL). QRS duration lengthened compared with sinus rhythm (42 +/- 8 msec) with either RVA (56 +/- 9 msec, P < 0.02) or LVA (54 +/- 7 msec, P < 0.03), but not with BiV (48 +/- 7 msec, P = 0.08) pacing. Tissue Doppler imaging showed LV dyssynchrony with RVA (septal-to-lateral delay 46.0 +/- 51.7 msec), with return toward normal with LVA (-9.6 +/- 33.6 msec, P < 0.04) or BiV (-4.1 +/- 33.8 msec, P < 0.04) pacing. CONCLUSIONS: In this acute immature piglet model of AV block, LV performance improved with single-site pacing from the LVA and BiV pacing (RVA/LVA), as compared with single-site pacing from the RVA. These changes correlated with tissue Doppler indices of mechanical synchrony, though not necessarily with QRS duration.

Hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia in young patients.

The annual incidence of sudden cardiac death in young athletes is approximately 1 in 200,000. The most common causes include hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia/cardiomyopathy. These genetic disorders typically manifest in the second decade of life and have the potential for sudden death as the first symptom. Medical care providers must be aware of these disease entities when evaluating patients with seizures, syncope, and/or palpitations. The purpose of this article is to describe their genetics, clinical presentation, and diagnosis.

Atrial fibrillation in KCNE1-null mice.

Although atrial fibrillation is the most common serious cardiac arrhythmia, the fundamental molecular pathways remain undefined. Mutations in KCNQ1, one component of a sympathetically activated cardiac potassium channel complex, cause familial atrial fibrillation, although the mechanisms in vivo are unknown. We show here that mice with deletion of the KCNQ1 protein partner KCNE1 have spontaneous episodes of atrial fibrillation despite normal atrial size and structure. Isoproterenol abolishes these abnormalities, but vagomimetic interventions have no effect. Whereas loss of KCNE1 function prolongs ventricular action potentials in humans, KCNE1-/- mice displayed unexpectedly shortened atrial action potentials, and multiple potential mechanisms were identified: (1) K+ currents (total and those sensitive to the KCNQ1 blocker chromanol 293B) were significantly increased in atrial cells from KCNE1-/- mice compared with controls, and (2) when CHO cells expressing KCNQ1 and KCNE1 were pulsed very rapidly (at rates comparable to the normal mouse heart and to human atrial fibrillation), the sigmoidicity of IKs activation prevented current accumulation, whereas cells expressing KCNQ1 alone displayed marked current accumulation at these very rapid rates. Thus, KCNE1 deletion in mice unexpectedly leads to increased outward current in atrial myocytes, shortens atrial action potentials, and enhances susceptibility to atrial fibrillation.