Pedram Argani, M.D.

• Associate Director, Surgical Pathology
• Professor of Pathology

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0010788/pedram-argani

The current role of cardiac resynchronization therapy in reducing mortality and hospitalization in heart failure patients: a meta-analysis from clinical trials antibiotics keflex buy generic ceftin 500 mg on line. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association oral antibiotics for acne rosacea buy cheap ceftin. Indications for cardiac resynchronization therapy: 2011 Update from the Heart Failure Society of America Guideline Committee antibiotic resistance nursing implications discount ceftin 250 mg on-line. Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure antimicrobial uv light 500 mg ceftin purchase. Three-dimensional mapping of optimal left ventricular pacing site for cardiac resynchronization antimicrobial chemotherapy ceftin 500 mg order amex. Doppler myocardial imaging to evaluate the effectiveness of pacing sites in patients receiving biventricular pacing. Optimizing hemodynamics in heart failure patients by systematic screening of left ventricular pacing sites: the lateral left ventricular wall and the coronary sinus are rarely the best sites. Local electrogram delay recorded from left ventricular lead at implant predicts response to cardiac resynchronization therapy: retrospective study with 1 year follow up. Invasive acute hemodynamic response to guide left ventricular lead implantation predicts chronic remodeling in patients undergoing cardiac resynchronization therapy. Lead positioning strategies to enhance response to cardiac resynchronization therapy. Biventricular pacing and left ventricular pacing in heart failure: similar hemodynamic improvement despite marked electromechanical differences. Midterm benefits of left univentricular pacing in patients with congestive heart failure. Meta-analysis of randomized controlled trials comparing isolated left ventricular and biventricular pacing in patients with chronic heart failure. Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates. Resynchronization therapy in pediatric and congenital heart disease patients: an international multicenter study. Assessment of upgrading to biventricular pacing in patients with right ventricular pacing and congestive heart failure after atrioventricular junctional ablation for chronic atrial fibrillation. Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation: effect of upgrading to biventricular pacing after chronic right ventricular pacing. Left heart atrial and ventricular epicardial pacing through a left lateral thoracotomy in children: a safe approach with excellent functional and cosmetic results. Regional wall motion and abnormalities of electrical depolarization and repolarization in patients after surgical repair of tetralogy of Fallot. Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects. Acute hemodynamic benefit of multisite ventricular pacing after congenital heart surgery. Relation of right ventricular pacing in tetralogy of Fallot to electrical resynchronization. Biventricular stimulation improves right and left ventricular function after tetralogy of Fallot repair: acute animal and clinical studies. Biventricular pacing in patients with Tetralogy of Fallot: Non-invasive epicardial mapping and clinical impact. Long-term outcomes after the atrial switch for surgical correction of transposition: a meta-analysis comparing the Mustard and Senning procedures. Cardiac resynchronization therapy: a novel adjunct to the treatment and prevention of systemic right ventricular failure. Myocardial perfusion and function of the systemic right ventricle in patients after atrial switch procedure for complete transposition: long-term follow-up. Role of ischemia and infarction in late right ventricular dysfunction after atrial repair of transposition of the great arteries. Two-dimensional echocardiographic assessment of right ventricular function as a predictor of outcome in hypoplastic left heart syndrome. Results of Norwood stage I operation: comparison of hypoplastic left heart syndrome with other malformations. Ventricular resynchronization by multisite pacing improves myocardial performance in the postoperative single-ventricle patient. Cardiac resynchronization therapy for heart failure: biventricular pacing and beyond. Pediatric dilated cardiomyopathy patients do not meet traditional cardiac resynchronization criteria. Applying cardiac resynchronization criteria to pediatric patients: fitting a square peg into a round hole Noninvasive imaging of cardiac venous anatomy with 64-slice multi-slice computed tomography and noninvasive assessment of left ventricular dyssynchrony by 3-dimensional tissue synchronization imaging in patients with heart failure scheduled for cardiac resynchronization therapy. Cardiac resynchronization therapy in pediatric congenital heart disease: insights from noninvasive electrocardiographic imaging. Simultaneous electrical and mechanical mapping using 3D cardiac mapping system: novel approach for optimal cardiac resynchronization therapy. Non-contact left ventricular endocardial mapping in cardiac resynchronisation therapy. Classic-pattern dyssynchrony and electrical activation delays in pediatric dilated cardiomyopathy. This includes increasing the heart rate in times of physiologic demand and decreasing the heart rate during times of low energy requirements. The sinus node may become unable to meet these needs as a result of disease, pharmacologic alterations, or mechanical trauma such as following surgery for congenital heart disease. When the sinus node cannot adequately alter the heart rate to deliver appropriate blood flow to the peripheral tissues, symptoms such as fatigue, exercise intolerance, and syncope may result. While standard pacing will overcome limited cardiac output due to bradycardia induced by atrioventricular block, it does not address low cardiac output due to chronotropic incompetence of the sinus node. The goal of the rate response sensor is to adjust the heart rate based on the metabolic needs of the individual. The basic system involves a sensor and electronics to calculate a graded and appropriate output rate from the measured input. Currently, the most commonly used sensor responds to device motion, a simple and reasonable correlate of the heart rate during common activities. This is a surprisingly high proportion when compared to patients with coronary artery disease (11%) and adults with congestive heart failure or dilated cardiomyopathy (25%). This provides fuel (oxygen and glucose) to the muscles and removes metabolic waste while also maintaining an appropriate body temperature. During exercise, increased preload resulting from enhanced venous return combined with increased sympathetic stimulation leads to increased contractility, decreased peripheral vascular resistance, and as a result, an increase of up to 150% in the stroke volume. Heart rate tends to increase slightly prior to the onset of activity and increases rapidly after the initiation of exercise. The initial steep slope of heart rate acceleration is due to parasympathetic withdrawal while the continued heart rate acceleration results from sympathetic stimulation. Characteristics of an ideal rate-adaptive pacing system the goal of rate responsive pacemakers ­ to recreate the complex function of the sinus node ­ has proven to be a difficult task. There are limited data in adult patients regarding the ability of rate responsive devices to mimic the output from the sinus node, and even less is known in pediatric patients and those with congenital heart disease. In pediatric patients with congenital heart block, using the Medtronic (Medtronic Inc. In a closed loop system, the physiologic parameter being monitored effects a change in the heart rate. This change in the heart rate alters the physiologic parameter thereby creating a negative feedback loop. This system therefore should be fully "automatic" and not require any physician input. While this system seems ideal, the reality is that the normally functioning sinus node has multiple inputs influencing the heart rate. The overwhelming majority of commercially available rate sensors today use an open-loop system in which the change in the heart rate does not feed back on the parameter being measured. A normally functioning sinus node alters the heart rate in response to various physiologic stimuli. The heart rate response to other stimuli such as emotion or fever is more complex, however. It also remains unclear if reproducing the function of the normal sinus node is essential for all clinical conditions. The high level of function of many pediatric patients with nonphysiologic heart rates, such as unpaced school-aged children with congenital heart block, calls into question the necessity of the heart rate being tuned to metabolic need. The relationship of cardiac output and heart rate is particularly complex in patients with single ventricle physiology following staged surgical palliation. This is important as the incidence of late sinus node dysfunction after the Fontan operation has been reported to range between 9 and 60%. Sensors Sensor technology aims to approximate the normal changes in heart rate observed with physical activity and other physiologic perturbations, which may not involve body movement such as fever, stress, sleep, and emotion. A wide array of parameters has been identified as markers of changing metabolic need. While many have undergone clinical testing, only activity and respiration sensors have achieved broad clinical use. Reasons for this appear less evidence-based than due to manufacturing, regulatory, and logistical issues. In contrast, the accelerometer, despite obvious shortcomings, is the most widely available rate response sensor. A common design is a small flexible arm with a weight at one end, secured to a piezoelectric crystal, which produces a current when the arm is flexed. The current fluctuations are counted by the device computer, and a rate is computed in proportion to the number of counts. Its rapid response to common activities and durability make the accelerometer a useful system. Sensitive to vibrations within the torso, however, this modality may inappropriately elevate rates in the presence of passive movement, such as riding in a car on an uneven road, or even in the presence of loud sounds, such as in a movie theater. Additionally, it may fail to respond physiologically during certain forms of low-impact exercise such as riding a bicycle or swimming. Notable also is its ineffectiveness for the non-ambulatory patient or infant, in whom it will inadequately vary heart rate. Chest impedance or "minute ventilation" Impedance, or resistance across the chest, to a small electrical current, falls with the filling of the lungs with air. Just as respiratory rate can be estimated on bedside monitors by this principle, it can be measured between a pectoral generator and intracardiac lead, allowing sensing of exertion regardless of the degree of body movement. Its utility in the presence of rapid respiratory rates seen in small patients is debated,10 but probably acceptable. The instantaneous impedance measurement at the lead tip fluctuates in a pattern that differs significantly between times of low and elevated sympathetic tone. The slope of this change at a specific window after myocardial activation provides the measure from which physiological changes in heart rate are computed by this closed-loop system. Appropriate responses not only to exercise but also positional changes and mental stress can thereby be approximated. The most commonly used motion sensors will be ineffective in this patient who may effectively be left with fixed rate pacing. Another may be the small patient in whom it is desired to limit the amount of hardware implanted. Finally, for those patients with chronic atrial arrhythmias, rate responsive ventricular pacing may be the most practical pacing mode. Ensuring appropriate heart rate variability in these patients is a challenge to which attentive device choice and programming will be required. Influence of heart rate and atrioventricular synchronization on maximal work tolerance in patients treated with artificial pacemakers. The spectrum of long-term electrophysiologic abnormalities in patients with univentricular hearts. Can current minute ventilation rate adaptive pacemakers provide appropriate chronotropic response in pediatric patients Closed loop stimulation improves ejection fraction in pediatric patients with pacemaker and ventricular dysfunction. Heart rate changes during acute mental stress with closed loop stimulation: report on two single-blinded, pacemaker studies. Rate-adaptive pacing using intracardiac impedance shows no evidence for positive feedback during dobutamine stress test. Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. Most children and young adults requiring rate responsive pacing experience acceptable performance provided by an accelerometer based system, which will be durable and sensitive. Knowledge of the available sensor types, along with the other features of the devices which accompany them, allows the clinician to make reasonable patient-specific device selection and programming. Chronotropic incompetence in adolescents and adults with congenital heart disease after cardiac surgery. Exercise training prevents decline in stroke volume during exercise in young healthy subjects. Peripheral vasodilation determines cardiac output in exercising humans: Insight from atrial pacing. Implantable defibrillators are commonly used for secondary prevention, such as in patients resuscitated from cardiac arrest or those with documented ventricular arrhythmia. This chapter will focus on the initial evaluation of high energy output and ongoing assessment of the adequacy of programmed shock output. Fibrillation and defibrillation Ventricular fibrillation is an apparently chaotic rhythm that is frequently described as dependent on multiple eddy currents. Recent work has supported the theory that within this chaotic rhythm there exists a more organized underlying rhythm, described as a mother rotor, which drives the continuing fibrillation.

Syndromes

• Watery, red eyes
• Gastroesophageal reflux
• Normal variation
• Venous ultrasound of the arms and legs
• An itchy sore develops that is similar to an insect bite. This sore may blister and form a black ulcer (sore or eschar).
• Drug or alcohol levels (toxicology screen)
• You have a tick bite or a rash
• Diabetes
• Be given medications to prevent graft-versus-host disease

The typical 3 Mb deletion encompassing over 40 genes is mediated by meiotic nonallelic recombination events antibiotics for dogs for dog bites best order for ceftin. Inactivation of Tbx1 in mice causes hypoplasia/aplasia of the pharyngeal arch arteries and severe pathologies in tissues derived from the third and fourth pharyngeal pouches antibiotics for uti in infants 250 mg ceftin purchase fast delivery, including hypoplasia of the thymus and parathyroid glands [80­82] antibiotic eye drops for pink eye purchase discount ceftin on line, consistent with the human disease virus killing kids cheapest ceftin. The syndrome is recognizable with typical features of periorbital fullness prescribed antibiotics for sinus infection purchase ceftin 500 mg without a prescription, wide mouth, full cheeks, unique social personality, and hypercalcemia [83]. Peripheral pulmonary stenosis is also encountered at a higher frequency (60%), which usually improves over time [87]. Mild to moderate aortic dilatation has been reported in a number of individuals [91]. The ascending aorta is notably more commonly involved, while the aortic root and sinotubular junction are less affected. Developmental delay, expressive language delay, and hypotonia are other relevant features of the syndrome [92]. Cardiomyopathy, largely diagnosed as noncompaction cardiomyopathy is observed in about 23­27% of children [100]. Characteristic dysmorphic features, sensorineural hearing loss, seizures, intellectual disability, and brain abnormalities are extracardiac abnormalities frequently seen with 1p36 deletion [101]. Several more genes within the 1p36 region may be responsible for structural and functional abnormalities of heart, as shown by extensive fine-mapping studies in 1p36 monosomy. It is important to note that several healthy carrier parents and unaffected individuals have been reported with genomic rearrangements of 1q21. The disorder is caused either by a submicroscopic deletion in the terminal region of chromosomal region 9q34. In the mutant mice, the sinus venosus and atria fail to develop past the primitive tube stage [132]. It is plausible that there are other dosage-sensitive genes within this region important for human cardiac morphogenesis. Distinctive facial features include long face, upslanting palpebral fissures, epicanthic folds, tubular nose, and large prominent ears. Cardiac septal defects are noted in between 30% and 40% of the affected individuals [136]. The carriers of the H2 ancestral haplotype are predisposed to having offspring with 17q21. Congenital heart defects: 15 years of experience of the Emilia-Romagna Registry (Italy). The epidemiology of cardiovascular defects, Part I: a study based on data from three large registries of congenital malformations. The contribution of chromosomal abnormalities to congenital heart defects: a population-based study. Long-term survival in children with atrioventricular septal defect and common atrioventricular valvar orifice in Sweden. Adults with genetic syndromes and cardiovascular abnormalities: clinical history and management. Prevalence of congenital heart defects and persistent pulmonary hypertension of the neonate with Down syndrome. The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. The impact of cardiac surgery in patients with trisomy 18 and trisomy 13 in Japan. Cardiovascular anomalies in children and young adults with Ullrich-Turner syndrome the Erlangen experience. Heart disease and stroke statistics­2011 update: a report from the American Heart Association. Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature. Cri du chat syndrome and congenital heart disease: a review of previously reported cases and presentation of an additional 21 cases from the Pediatric Cardiac Care Consortium. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision. A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region. Cardioskeletal Muscle Disease Associated With Chromosomal Disorders Chapter 16 341 [50] Catela C, Bilbao-Cortes D, Slonimsky E, Kratsios P, Rosenthal N, The Welscher P. Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated in Fgfrl1 null mice. Ets1 is required for proper migration and differentiation of the cardiac neural crest. Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia. Partial trisomy of chromosome 22 resulting from an interstitial duplication of 22q11. Assessment of the role of copy-number variants in 150 patients with congenital heart defects. Challenges of interpreting copy number variation in syndromic and non-syndromic congenital heart defects. De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning. Identification of de novo mutations and rare variants in hypoplastic left heart syndrome. Effect of copy number variants on outcomes for infants with single ventricle heart defects. Rare copy number variants in isolated sporadic and syndromic atrioventricular septal defects. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Long-term outcomes of patients with cardiovascular abnormalities and Williams syndrome. Presenting phenotype and clinical evaluation in a cohort of 22 WilliamsBeuren syndrome patients. Refinement of causative genes in monosomy 1p36 through clinical and molecular cytogenetic characterization of small interstitial deletions. Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome. Further delineation of deletion 1p36 syndrome in 60 patients: a recognizable phenotype and common cause of developmental delay and mental retardation. Reciprocal crossovers and a positional preference for strand exchange in recombination events resulting in deletion or duplication of chromosome 17p11. The severe end of the spectrum: hypoplastic left heart in Potocki-Lupski syndrome. Congenital heart defects associated with Smith-Magenis syndrome: two cases of total anomalous pulmonary venous return. Ventriculomegaly, intrauterine growth restriction, and congenital heart defects as salient prenatal sonographic findings of Miller-Dieker lissencephaly syndrome associated with monosomy 17p (17p13. Novel deletion on the short arm of chromosome 17 in a patient with multiple cardiac anomalies. Array based characterization of a terminal deletion involving chromosome subband 15q26. Genome-wide oligonucleotide-based array comparative genome hybridization analysis of non-isolated congenital diaphragmatic hernia. Molecular cytogenetic characterization of ring chromosome 15 in three unrelated patients. Indeed, even those patients described as asymptomatic exhibit significantly reduced aerobic exercise capacity by comparison to their healthy, age-matched, peers [19]. Even patients with simple lesions exhibit decreased exercise performance by comparison to age-matched controls in this cross-sectional sample, though those with more complex and particularly cyanotic lesions, demonstrated the poorest exercise performance. Comprehensive use of cardiopulmonary exercise testing identifies adults with congenital heart disease at increased mortality risk in the medium Term. These parameters offer independent and additive prognostic information, as is the case for the more familiar scenario of patients with acquired heart failure in the setting of a systemic left ventricle. Ventilatory efficiency and aerobic capacity predict event-free survival in adults with atrial repair for complete transposition of the great arteries. This response is a significant determinant of symptoms during exercise [24] and yet does not appear to be predictive of mortality in this subgroup [22]. This is likely because the driver of this response is systemic hypoxemia due to right-to-left shunting, via surgical fenestrations, pulmonary arteriovenous malformations, and systemic to pulmonary venovenous malformations. Such shunting permits venous blood to bypass the lungs and diminishes respiratory regulation of carbon dioxide and acid base status. Abnormal conduit vascular function, as reflected in diminished flow-mediated dilatation also likely has a role in limiting skeletal muscle perfusion during exercise [44­46]. These various processes result in rapid depletion of high-energy phosphates and early onset of intracellular acidosis [47­49], with increased lactate production [50,51] and diminished fatigue resistance during both isometric and isotonic exercise [52]. Similarly diminished fatigue resistance during knee extensor exercise is not mediated by diminished total limb perfusion [41,53]. This suggests that the abnormal conduit vascular function described above, might affect flow distribution to metabolically active muscle rather than limiting total limb blood flow. Several small studies suggest altered skeletal muscle function, with increased fatigability during isotonic exercise being the most consistently described abnormality. Brassard assessed a small series of adolescent Fontan patients and did not find a difference in quadriceps and forearm strength between patients and age matched controls. Fontan patients, however, exhibited greater fatigability of nondominant forearm muscles during dynamic handgrip exercise. Skeletal muscle performance during isotonic exercise was not assessed in this study. In addition to these functional myopathic changes, Cordina recently described a reduction in limb skeletal muscle mass as measured by dual X-ray absorptiometry in a series of 16 Fontan patients: a quarter fell into the sarcopenic range. Cordina also studied 31P nuclear magnetic resonance to assess the kinetics of skeletal muscular phosphocreatine resynthesis in calf muscle, demonstrating a reduction in muscle aerobic capacity in Fontan patients [60]. Maximal dilatation with nitroglycerin was comparable between subjects and controls, implying a failure of endothelium-dependent vasodilatation of conduit arteries [61]. Again, endothelium-independent vasodilatation in response to nitroglycerin appeared to be preserved. Activation of the sympathetic nervous system is reflected in increased resting spillover of norepinephrine, which correlates with prognosis [63], and increased -adrenergic stimulation may mediate the blunted vasodilatory responses to exercise [64]. Activation of the central chemoreflex produces a hemodynamic and ventilatory response, which is associated with increased muscle sympathetic nerve activity [94,95] and may partially explain the abnormal ventilatory Cardioskeletal Myopathies in Congenital Heart Diseases Chapter 17 351 response to exercise [92]. A third group of reflexes, collectively referred to as the ergoreflex, respond to incompletely defined metabolic changes within skeletal muscle and mediate the cardiovascular and ventilatory response to physical activity [96]. Further ergoreflex activation is a strong predictor of aerobic exercise capacity and ventilatory response to exercise in these patients [99]. Exercise therapy also normalizes exaggerated neurocardiac and neurorespiratory reflexes. Given the previously mentioned involvement of respiratory musculature, it is interesting to note that selective inspiratory muscle training has been associated with an improvement in inspiratory and expiratory respiratory muscle strength, exercise performance, and quality of life scores [116­118]. These benefits appear to be additive to those of a 12-week aerobic exercise training program [118]. In the absence of a subpulmonary ventricle, venous return and hence preloading of the systemic ventricle is critically dependent on the function of the skeletal muscle and respiratory "pumps. An increase in oxygen pulse, but not peak heart rate was seen, implying that some of the improvement relates to some combination of increased stroke volume and more efficient peripheral oxygen extraction at peak exercise. The authors attributed this to intrinsic changes in cardiac function and improved venous return due to a more efficient skeletal muscle pump, though this was not directly confirmed. In the context of a predominantly Fontan population, this may plausibly reflect a strengthening effect of training on respiratory musculature, which sustains improved ventricular filling during exercise, via the known cardiorespiratory dependence of cardiac output on the work of breathing [131]. Further support comes from another paper by Cordina, in which six Fontan patients were submitted to a 20-week resistance exercise training program, resulting in a mean 1. Four trained subjects were then subjected to a 12-month detraining protocol following which total body lean mass decreased (3. Importantly, stroke volume during exercise decreased by 17% thus accounting for the decrease in oxygen pulse. However, following resistance-training patients exhibited diminished respiratory dependence, both at rest and during exercise, as a result of increased forward flow during expiration. This, together with the observed lessened impact of continuous positive airway pressure on pulmonary blood flow is compatible with a more efficient appendicular muscle pump [132]. Assessment over a much longer timeframe will be required to answer this important question. Further, these changes appear to be at least partly reversible during both aerobic and resistance-training programs, with beneficial impacts on exercise capacity and symptoms. Encouragingly, participation in time-limited exercise training, together with the use of motivational techniques, may result in persistent increase in activity [127], and the benefits of exercise therapy appear to be sustained beyond the treatment period [135,136]. Each of these highly variable phenotypic features may, in turn, be further susceptible to modification by underlying genetic influences. The relative importance of each of these factors and the degree to which they overlap and interact is unclear. The published studies of exercise rehabilitation could be extended with larger numbers, more systematic phenotyping, and longer follow-up. A molecular basis for familial hypertrophic cardiomyopathy: a cardiac myosin heavy chain gene missense mutation. Pediatric restrictive cardiomyopathy associated with a mutation in -myosin heavy chain. Mutation screening in dilated cardiomyopathy: prominent role of the beta myosin heavy chain gene.

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Future studies will likely investigate the potential for 3D echocardiography as a tool for optimization antibiotic resistant virus in hospitals order ceftin on line. Electrophysiology and echocardiography practitioners should focus on two or three of these techniques antibiotic resistance animation ks4 generic ceftin 500 mg with visa, based on the equipment and technology available at their center antibiotics variceal bleed purchase ceftin 500 mg otc, and gain expertise as optimization is applied to their patients bacteria 80s order ceftin overnight delivery. Optimization in pediatrics and congenital heart disease Optimization techniques have been applied with success in pediatric case reports antibiotics for mrsa buy ceftin 250 mg mastercard. Systemic right and single ventricles pose a unique challenge for pediatric and adult congenital heart disease resynchronization. Since no universal optimization technique exists it is important for the practitioner to familiarize him/herself with a few methods, apply them to the patients, and monitor their response. The effect of cardiac resynchronization on morbidity and mortality in heart failure. Cardiac resynchronization therapy (and multisite pacing) in pediatrics and congenital heart disease: five years experience in a single institution. Echocardiographic tools for pacemaker optimization of ventricular function in an infant following surgical repair for double outlet right ventricle. Optimization of myocardial strain imaging and speckle tracking for resynchronization after congenital heart surgery in children. Resynchronization therapy after congenital heart surgery to improve left ventricular function. Three-dimensional echocardiographic assessment of right ventricular volume and function in adult patients with congenital heart disease: comparison with magnetic resonance imaging. Optimisation of atrioventricular delay during exercise improves cardiac output in patients stabilised with cardiac resynchronisation therapy. Electrocardiographic versus echocardiographic optimization of the interventricular pacing delay in patients undergoing cardiac resynchronization therapy. Unlike in the adult population, large scale, randomized, prospective studies are few in pediatrics. Through innovation and experience, pediatric cardiologists translate and mold adult practices to benefit the children they care for. In this way, implantable syncope and arrhythmia monitors, and automated external defibrillators have been added to the armamentarium of diagnostic and treatment options for children with arrhythmias. In this chapter, the utility of implantable syncope and arrhythmia monitors and automated external defibrillators will be discussed. Implantable loop recorders Indications for implantable loop recorders Syncope and palpitations occur frequently in young patients and are a common reason for referral to pediatric cardiologists,1­3 yet, syncope and palpitations are symptoms rather than diagnoses. Syncope is a transient, self-limited loss of consciousness and voluntary muscle tone. Determining the etiology of these symptoms is often challenging and perplexing, particularly in the pediatric population where obtaining a history may be difficult. Although these symptoms are frequently benign, they are a source of anxiety for patients and their parents and may herald significant heart disease or potentially lethal problems. Studies have shown that patients with congenital heart disease have an increased incidence of malignant arrhythmias, including atrioventricular conduction disturbances, ventricular tachycardia, and rapid conduction of atrial arrhythmias. Substrates for malignant arrhythmias may often be diagnosed by patient history, family history, and physical examination alone. Electrocardiography Cardiac Pacing and Defibrillation in Pediatric and Congenital Heart Disease, First Edition. Continuous rhythm assessment with ambulatory Holter monitors are useful in correlating symptoms with the heart rhythm only if the patient is symptomatic during the monitoring period. Studies show the diagnostic yield of external loop recorders ranging from 24­47% with the highest yield in patients with frequent events. However, symptoms can be induced in a large number of asymptomatic adolescents, thus decreasing the specificity of the test while failing to conclusively exclude a malignant etiology. Previous work-up was negative or unable to be performed secondary to lack of patient cooperation. Devices are implanted subcutaneously in the chest wall typically to the right or left of the sternum. Abdominal, submammary, and subaxillary implantation have been described in small children. Prior to implantation, cutaneous mapping with the device is advised to optimize the sensed signal and decrease T-wave oversensing that may be falsely interpreted as a high rate episode. The duration of recording prior to and after an event is programmable with a total recording time of 48­50 min. The population was 16 adult patients who were highly symptomatic with recurrent unexplained syncope. All patients had a negative work-up, including ambulatory Holter monitoring, tilt table testing, and electrophysiological studies. After undergoing device implantation, 15 of 16 patients (94%) had recurrent syncope during a mean of 13 ± 8. For those 15 patients, a diagnosis was obtained in all with symptom-rhythm correlation in 9 patients (60%). Treatment was initiated in all with no recurrence of syncope at the time the study was terminated. If the original evaluation did not yield a diagnosis, the patients were offered the option of crossover to the alternative strategy. One of the first pediatric studies retrospectively evaluated 21 patients from three pediatric centers. All 14 patients who continued to have symptoms were able to achieve symptom-rhythm correlation, including supraventricular tachycardia in 4 patients, ventricular tachycardia in 2 patients, torsades de pointes in 1 patient, asystole in 1 patient, junctional bradycardia in 1 patient, and sinus rhythm in 5 patients. Also, secondary to continuous overwriting by the auto-detection, genuine arrhythmias may be over-recorded by artifact. These newer detection algorithms may be particularly helpful in the growing population of adult congenital heart disease patients who are at risk for such arrhythmias. Newer sensing and detection schemes have been introduced, employing an automatically adjusted R-wave sensing threshold, enhanced noise rejection, and algorithms to detect asystole, bradyarrhythmia, and tachyarrhythmia. It consists of software that can be downloaded to a smart phone and a phone cover with two large electrodes on the back which serve as electrodes analogous to a lead I. Automated external defibrillators the importance of early defibrillation to treat sudden cardiac arrest is based on the principles that (1) ventricular fibrillation is the most common initial rhythm in witnessed sudden cardiac arrest; (2) electrical defibrillation is the most effective treatment of ventricular fibrillation; and (3) the probability of successful defibrillation diminishes rapidly over time. In 1900, Prevost and Batelli conducted research on ventricular fibrillation in dogs. Patient had negative work-up including Holter monitor, exercise stress test, and external transtelephonic monitor. They noted that weaker currents were needed to fibrillate the ventricle compared to the stronger currents needed to defibrillate (or what they called "countershocking") ventricular fibrillation. Claude Beck put this information into clinical practice and performed the first successful human defibrillation using internal cardiac paddles on a 14-year-old boy who developed pulseless ventricular fibrillation during elective chest surgery. In 1956, Paul Zoll used a more powerful unit to perform the first closed-chest defibrillation of a human. Since then, these devices have advanced significantly with regard to ease of rescuer use, accuracy of rhythm analysis and efficacy of charge delivery. The devices consist of essentially two components: the electrode pads and the device itself. Semi-automated devices alert the rescuer that a shock is advised and then the rescuer must deliver the shock by pressing a button. Fully automated devices alert the rescuer that a shock is advised, asks rescuers to clear away from the victim and then automatically delivers a shock. This is an important distinction because the comfort of the rescuer influences the time to delivery of a therapy in a semi-automated device. Placement location of the defibrillator pads is uniform for all devices with one pad being placed at the right sternal border and the other at the cardiac apex. The pads themselves are marked with a picture depicting where to place the pads on the chest. In general, analysis consists of filtering the electrocardiographic signal to reduce noise artifact, detecting and evaluating electrocardiographic characteristics including amplitude, frequency, and slope and calculating average heart rate. From this information, a decision to advise the delivery of a shock, or not, is recommended by the device. This means that the charge is delivered in one direction for half the shock and the electrically opposite direction for the second half. This form of defibrillation uses less energy with the same or superior effectiveness compared to a monophasic therapy. Pediatric pads that attenuate energy output or adapters to reduce energy are available for use in victims less than 8 years of age or under 25 kg (55 lb). These pads deliver approximately 50 J of energy and have been shown to be effective and safe. By the age of 18 years, a person is estimated to have spent 35% of their days in school, about 18% of their waking hours. In a large cross-sectional national survey of over 1700 high schools across the country, Drezner et al showed improved survival in high school student athletes and nonstudents who suffer sudden cardiac arrest. The annual incidence of sudden cardiac arrest in high school athletes was found to be 4. Yet, data shows that most schools obtain devices through donations or grants, with a minority actually using school funds. Perhaps most impressive is the ability of parents struck by the tragedy of a child with sudden death to implement change and policy. Parents have spearheaded change in state legislature, and parental and community programs provide material, information, and funds to aid interested groups in obtaining devices for their schools. This creates a conundrum for the practitioner with regard to treatment recommendations, exercise restrictions, and sudden death risk stratification. Patients most at risk are those with massive left ventricular hypertrophy (wall thickness >45 mm) and/or concomitant amiodarone use. His left ventricular lateral free wall measured 40 mm, the left ventricular posterior wall measured 37 mm, the ventricular septum measured 44 mm, and the apical wall measured 40 mm. An additional azygous vein defibrillation coil was added but again did not provide successful defibrillation thresholds. Using a combination of energy vectors from the array and transvenous system, adequate defibrillation thresholds were not attained. It is worth noting that a wearable defibrillator is available that has been shown to be an effective bridge to implantable defibrillation therapy or cardiac transplant and provides patients around-the-clock rhythm analysis and treatment of malignant arrhythmias. The chest does not need to be shaved but should be dried prior to placing the pads. Individual manufacturer recommendations for scheduled maintenance should be followed. Most models perform scheduled self-tests to detect issues with the device and sound audible warnings to notify the owner of possible problems with the device. Conclusion Advances in medical technology include the advent of implantable syncope and arrhythmia devices and automated external defibrillators. In the realm of pediatric medicine, practitioners have developed innovative applications of these technologies to aid in the diagnosis and treatment of arrhythmias in the young and those with congenital heart disease. Conditions leading to pediatric cardiology consultation in a tertiary academic hospital. Cardiac rhythm after the Mustard operation for complete transposition of the great arteries. Digital implantable loop recorders in the investigation of syncope in children: benefits and limitations. Incremental diagnostic yield of loop electrocardiographic recorder in unexplained syncope. Detection of arrhythmias: use of a patient-activated ambulatory electrocardiogram device with solid-state memory loop. Specificity of head-up tilt testing in adolescents: effect of various degrees of tilt challenge in normal control subjects. Efficacy of implantable loop recorders in establishing symptom-rhythm correlation in young patients with syncope and palpitations. Implantable loop recorders in the investigation of unexplained syncope: a state of the art review. The etiology of syncope in patients with negative tilt table and electrophysiological testing. Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy. A randomized prospective comparison of three protocols for head-up tilt testing and carotid sinus massage. Mechanism of syncope in patients with isolated syncope and in patients with tilt-positive syncope. Mechanism of syncope in patients with heart disease and negative electrophysiologic test. Proposed electrocardiographic classification of spontaneous syncope documented by an implantable loop recorder. Are implantable loop recorders useful in detecting arrhythmias in children with unexplained syncope Single-centre use of implantable loop recorders in patients with congenital heart disease. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Termination of ventricular fibrillation in man by externally applied electric countershock. Initial clinical experience with a fully automatic in-hospital external cardioverter defibrillator.

Diseases

• Optic neuritis
• Parry-Romberg syndrome
• Quebec platelet disorder
• Myoclonus cerebellar ataxia deafness
• Cervical vertebral fusion
• Brachyolmia recessive Hobaek type
• Lowe syndrome

References

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