Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of pharmacological or nonpharmacological treatment to no treatment to improve patient-important outcomes. Statistical analyses were performed to determine the clinical significance of using various interventions to treat RLS and PLMD in adults and children. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. RESULTS: The literature search resulted in 3631 studies out of which 148 studies provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.

Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline.

INTRODUCTION: This guideline establishes clinical practice recommendations for Treatment of Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD) in adults and pediatric patients. METHODS: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. GOOD PRACTICE STATEMENT: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RLS.1. In all patients with clinically significant RLS, clinicians should regularly test serum iron studies including ferritin and transferrin saturation (calculated from iron and total iron binding capacity, TIBC). The test should ideally be administered in the morning avoiding all iron-containing supplements and foods at least 24 hours prior to blood draw. Analysis of iron studies greatly influences the decision to use oral or intravenous (IV) iron treatment. Consensus guidelines, which have not been empirically tested, suggest that supplementation of iron in adults with RLS should be instituted with oral or IV iron if serum ferritin ≤75 ng/mL or transferrin saturation < 20%, and only with IV iron if serum ferritin is between 75 ng/mL and 100 ng/mL. In children, supplementation of iron should be instituted for serum ferritin < 50 ng/mL with oral or IV formulations. These iron supplementation guidelines are different than for the general population.2. The first step in the management of RLS should be addressing exacerbating factors, such as alcohol, caffeine, antihistaminergic, serotonergic, anti-dopaminergic medications, and untreated obstructive sleep apnea (OSA).3. RLS is common in pregnancy; prescribers should consider the pregnancy-specific safety profile of each treatment being considered. RECOMMENDATIONS: The following recommendations are intended as a guide for clinicians in choosing a specific treatment for RLS and PLMD in adults and children. Each recommendation statement is assigned a strength ("Strong" or "Conditional"). A "Strong" recommendation (i.e., "We recommend…") is one that clinicians should follow under most circumstances. The recommendations listed below are ranked in the order of strength of recommendations and grouped by class of treatments within each PICO question. Some recommendations include remarks that provide additional context to guide clinicians with implementation of this recommendation.Adults with RLS.1. In adults with RLS, the AASM recommends the use of gabapentin enacarbil over no gabapentin enacarbil (Strong recommendation, moderate certainty of evidence).2. In adults with RLS, the AASM recommends the use of gabapentin over no gabapentin (Strong recommendation, moderate certainty of evidence).3. In adults with RLS, the AASM recommends the use of pregabalin over no pregabalin (Strong recommendation, moderate certainty of evidence).4. In adults with RLS, the AASM recommends the use of IV ferric carboxymaltose over no IV ferric carboxymaltose in patients with appropriate iron status (see good practice statement for iron parameters) (Strong recommendation, moderate certainty of evidence).5. In adults with RLS, the AASM suggests the use of IV low molecular weight (LMW) iron dextran over no IV LMW iron dextran in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, very low certainty of evidence).6. Recommendation 6: In adults with RLS, the AASM suggests the use of IV ferumoxytol over no IV ferumoxytol in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, very low certainty of evidence).7. In adults with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, moderate certainty of evidence).8. In adults with RLS, the AASM suggests the use of dipyridamole over no dipyridamole (Conditional recommendation, low certainty of evidence).9. In adults with RLS, the AASM suggests the use of extended-release oxycodone and other opioids over no opioids (Conditional recommendation, moderate certainty of evidence).10. In adults with RLS, the AASM suggests the use of bilateral high-frequency peroneal nerve stimulation over no peroneal nerve stimulation (Conditional recommendation, low certainty of evidence).11. In adults with RLS, the AASM suggests against the standard use of levodopa (Conditional recommendation, very low certainty of evidence). Remarks: Levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 12. In adults with RLS, the AASM suggests against the standard use of pramipexole (Conditional recommendation, moderate certainty of evidence). Remarks: Pramipexole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 13. In adults with RLS, the AASM suggests against the standard use of transdermal rotigotine (Conditional recommendation, low certainty of evidence). Remarks: Transdermal Rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 14. In adults with RLS, the AASM suggests against the standard use of ropinirole (Conditional recommendation, moderate certainty of evidence). Remarks: Ropinirole may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 15. In adults with RLS, the AASM suggests against the use of bupropion for the treatment of RLS (Conditional recommendation, moderate certainty of evidence).16. In adults with RLS, the AASM suggests against the use of carbamazepine (Conditional recommendation, low certainty of evidence).17. In adults with RLS, the AASM suggests against the use of clonazepam (Conditional recommendation, very low certainty of evidence).18. In adults with RLS, the AASM suggests against the use of valerian (Conditional recommendation, low certainty of evidence).19. In adults with RLS, the AASM suggests against the use of valproic acid (Conditional recommendation, low certainty of evidence).20. In adults with RLS, the AASM recommends against the use of cabergoline (Strong recommendation, moderate certainty of evidence).Special adult populations with RLS.21. In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of gabapentin over no gabapentin (conditional recommendation, very low certainty of evidence).22. In adults with RLS and ESRD, the AASM suggests the use of IV iron sucrose over no IV iron sucrose in patients with ferritin < 200 ng/mL and transferrin saturation < 20% (Conditional recommendation, moderate certainty of evidence).23. In adults with RLS and ESRD, the AASM suggests the use of vitamin C over no vitamin C (conditional recommendation, low certainty of evidence).24. In adults with RLS and ESRD, the AASM suggests against the standard use of levodopa (Conditional recommendation, low certainty of evidence). Remarks: Levodopa may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). 25. In adults with RLS and ESRD, the AASM suggests against the standard use of rotigotine (Conditional recommendation, very low certainty of evidence). Remarks: Rotigotine may be used to treat RLS in patients who place a higher value on the reduction of restless legs symptoms with short-term use and a lower value on adverse effects with long-term use (particularly augmentation). Adults with PLMD.26. In adults with PLMD, the AASM suggests against the use of triazolam (Conditional recommendation, very low certainty of evidence).27. In adults with PLMD, the AASM suggests against the use of valproic acid (Conditional recommendation, very low certainty of evidence).Children with RLS.28. In children with RLS, the AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (see good practice statement for iron parameters) (Conditional recommendation, very low certainty of evidence).

Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in children: guidance from the American Academy of Sleep Medicine.

The American Academy of Sleep Medicine commissioned a task force of clinical experts in pediatric sleep medicine to review published literature on performing the Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test for diagnosis and management of central disorders of hypersomnolence among children and adolescents. This paper follows a format similar to that of the paper "Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine" that was published in 2021. Since there is insufficient evidence to specify a recommended protocol for the Maintenance of Wakefulness Test in children and adolescents, this paper focuses only on the MSLT protocol. This protocol paper provides guidance to health care providers who order, sleep specialists who interpret, and technical staff who administer the MSLT to pediatric patients. Similar to the adult protocol paper, this document provides guidance based on pediatric expert consensus and evidence-based data when available. Topics include patient preparation, evaluation of medication and substance use, sleep needs before testing, scheduling considerations, optimal test conditions for youth, and documentation. Specific changes recommended for pediatric MSLT protocols include (1) provision of a minimum of 7 hours of sleep (with a minimum 8-hour recording time) on polysomnography the night before the MSLT, ideally meeting age-based needs; (2) use of clinical judgment to guide the need for sleep-disordered breathing treatments before polysomnography-MSLT testing; and (3) shared patient-health care provider decision-making regarding modifications in the protocol for children and adolescents with neurodevelopmental/neurological disorders, young age, and/or delayed sleep phase. CITATION: Maski KP, Amos LB, Carter JC, Koch EE, Kazmi U, Rosen CL. Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in children: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med. 2024;20(4):631-641.

Management of REM sleep behavior disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

This systematic review provides supporting evidence for a clinical practice guideline for the management of rapid eye movement (REM) sleep behavior disorder in adults and children. The American Academy of Sleep Medicine commissioned a task force of 7 experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials and observational studies that addressed interventions for the management of REM sleep behavior disorder in adults and children. Statistical analyses were performed to determine the clinical significance of critical and important outcomes. Finally, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. The literature search identified 4,690 studies; 148 studies provided data suitable for statistical analyses; evidence for 45 interventions is presented. The task force provided a detailed summary of the evidence assessing the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2023;19(4):769-810.

Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline.

INTRODUCTION: This guideline establishes clinical practice recommendations for the management of rapid eye movement sleep behavior disorder (RBD) in adults. METHODS: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. GOOD PRACTICE STATEMENT: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RBD: It is critically important to help patients maintain a safe sleeping environment to prevent potentially injurious nocturnal behaviors. In particular, the removal of bedside weapons, or objects that could inflict injury if thrown or wielded against a bed partner, is of paramount importance. Sharp furniture like nightstands should be moved away or their edges and headboard should be padded. To reduce the risk of injurious falls, a soft carpet, rug, or mat should be placed next to the bed. Patients with severe, uncontrolled RBD should be recommended to sleep separately from their partners, or at the minimum, to place a pillow between themselves and their partners. RECOMMENDATIONS: The following recommendations, with medications listed in alphabetical order, are a guide for clinicians in choosing a specific treatment for RBD in adults. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the patient's values and preferences to determine the best course of action.Adult patients with isolated RBD.1. The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).2. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).3. * The AASM suggests that clinicians use pramipexole (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).4. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of isolated RBD in adults with mild cognitive impairment. (CONDITIONAL).Adult patients with secondary RBD due to medical condition.5. * The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).6. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).7. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of secondary RBD due to medical condition (Parkinson disease) in adults. (CONDITIONAL).8. * The AASM suggests that clinicians not use deep brain stimulation (DBS; vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).Adult patients with drug-induced RBD.9. * The AASM suggests that clinicians use drug discontinuation (vs drug continuation) for the treatment of drug-induced RBD in adults. (CONDITIONAL).* The Recommendations section of this paper includes remarks that provide additional context to guide clinicians with implementation of this recommendation. CITATION: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2023;19(4):759-768.

Short to midterm follow-up of multi-system inflammatory syndrome in children with special reference to cardiac involvement.

OBJECTIVES: We aim to describe the early and upto 16 months follow-up of post-coronavirus disease (COVID), multi-system inflammatory syndrome in children (MIS-C), with special reference to cardiac involvement. STUDY DESIGN: This cohort non-interventional descriptive study included patients <18 years admitted between May, 2020 and April, 2021. Based on underlying similarities, children were classified as post-COVID MIS-C with overlapping Kawasaki Disease, MIS-C with no overlapping Kawasaki Disease, and MIS-C with shock. Post-discharge, patients were followed at 1, 3, 6, 12, and 16 months. RESULTS: Forty-one patients predominantly males (73%), at median age of 7 years (range 0.2-16 years) fulfilled the World Health Organisation criteria for MIS-C. Cardiac involvement was seen in 15 (36.5%); impaired left ventricle (LV) function in 5 (12.2%), coronary artery involvement in 10 (24.4%), pericardial effusion in 6 (14.6%) patients, and no arrhythmias. There were two hospital deaths (4.9%), both in MIS-C shock subgroup (2/10, 20%). At 1 month, there was persistent LV dysfunction in 2/5, coronary artery abnormalities in 7/10, and pericardial effusion resolved completely in all patients. By 6 months, LV function returned to normal in all but coronary abnormalities persisted in two patients. At last follow-up (median 9.8 months, interquartile range 2-16 months), in 36/38 (94.7%) patients, coronary artery dilatation was persistent in 2 (20%) patients. CONCLUSIONS: Children with MIS-C have a good early outcome, though MIS-C with shock can be life-threatening subgroup in a resource-constrained country setting. On midterm follow-up, there is normalisation of LV function in all and recovery of coronary abnormalities in 80% of patients.

Age and weight considerations for the use of continuous positive airway pressure therapy in pediatric populations: an American Academy of Sleep Medicine position statement.

This position statement provides guidance for age and weight considerations for using continuous positive airway pressure therapy in pediatric populations. The American Academy of Sleep Medicine commissioned a task force of experts in pediatric sleep medicine to review the medical literature and develop a position statement based on a thorough review of these studies and their clinical expertise. The American Academy of Sleep Medicine Board of Directors approved the final position statement. It is the position of the American Academy of Sleep Medicine that continuous positive airway pressure can be safe and effective for the treatment of obstructive sleep apnea for pediatric patients, even in children of younger ages and lower weights, when managed by a clinician with expertise in evaluating and treating pediatric obstructive sleep apnea. The clinician must make the ultimate judgment regarding any specific care in light of the individual circumstances presented by the patient, accessible treatment options, patient/parental preference, and resources. CITATION: Amos L, Afolabi-Brown O, Gault D, et al. Age and weight considerations for the use of continuous positive airway pressure therapy in pediatric populations: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2022;18(8):2041-2043.

Guiding principles for determining work shift duration and addressing the effects of work shift duration on performance, safety, and health: guidance from the American Academy of Sleep Medicine and the Sleep Research Society.

CITATION: Risks associated with fatigue that accumulates during work shifts have historically been managed through working time arrangements that specify fixed maximum durations of work shifts and minimum durations of time off. By themselves, such arrangements are not sufficient to curb risks to performance, safety, and health caused by misalignment between work schedules and the biological regulation of waking alertness and sleep. Science-based approaches for determining shift duration and mitigating associated risks, while addressing operational needs, require: (1) a recognition of the factors contributing to fatigue and fatigue-related risks; (2) an understanding of evidence-based countermeasures that may reduce fatigue and/or fatigue-related risks; and (3) an informed approach to selecting workplace-specific strategies for managing work hours. We propose a series of guiding principles to assist stakeholders with designing a shift duration decision-making process that effectively balances the need to meet operational demands with the need to manage fatigue-related risks.

Guiding principles for determining work shift duration and addressing the effects of work shift duration on performance, safety, and health: guidance from the American Academy of Sleep Medicine and the Sleep Research Society.

Risks associated with fatigue that accumulates during work shifts have historically been managed through working time arrangements that specify fixed maximum durations of work shifts and minimum durations of time off. By themselves, such arrangements are not sufficient to curb risks to performance, safety, and health caused by misalignment between work schedules and the biological regulation of waking alertness and sleep. Science-based approaches for determining shift duration and mitigating associated risks, while addressing operational needs, require: (1) a recognition of the factors contributing to fatigue and fatigue-related risks; (2) an understanding of evidence-based countermeasures that may reduce fatigue and/or fatigue-related risks; and (3) an informed approach to selecting workplace-specific strategies for managing work hours. We propose a series of guiding principles to assist stakeholders with designing a shift duration decision-making process that effectively balances the need to meet operational demands with the need to manage fatigue-related risks.

Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

INTRODUCTION: The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on the use of behavioral and psychological treatments for chronic insomnia disorder in adult populations. METHODS: The American Academy of Sleep Medicine commissioned a task force of 9 experts in sleep medicine and sleep psychology. A systematic review was conducted to identify randomized controlled trials that addressed behavioral and psychological interventions for the treatment of chronic insomnia disorder in adults. Statistical analyses were performed to determine if the treatments produced clinically significant improvements in a range of critical and important outcomes. Finally, the Grading of Recommendations Assessment, Development, and Evaluation process was used to evaluate the evidence for making specific treatment recommendations. RESULTS: The literature search identified 1,244 studies; 124 studies met the inclusion criteria, and 89 studies provided data suitable for statistical analyses. Evidence for the following interventions is presented in this review: cognitive-behavioral therapy for insomnia, brief therapies for insomnia, stimulus control, sleep restriction therapy, relaxation training, sleep hygiene, biofeedback, paradoxical intention, intensive sleep retraining, and mindfulness. This review provides a detailed summary of the evidence along with the quality of evidence, the balance of benefits vs harms, patient values and preferences, and resource use considerations.

Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline.

INTRODUCTION: This guideline establishes clinical practice recommendations for the use of behavioral and psychological treatments for chronic insomnia disorder in adults. METHODS: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine and sleep psychology to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The task force evaluated a summary of the relevant literature and the quality of evidence, the balance of clinically relevant benefits and harms, patient values and preferences, and resource use considerations that underpin the recommendations. The AASM Board of Directors approved the final recommendations. RECOMMENDATIONS: The following recommendations are intended as a guide for clinicians in choosing a specific behavioral and psychological therapy for the treatment of chronic insomnia disorder in adult patients. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation is one that requires that the clinician use clinical knowledge and experience, and to strongly consider the patient's values and preferences to determine the best course of action. 1. We recommend that clinicians use multicomponent cognitive behavioral therapy for insomnia for the treatment of chronic insomnia disorder in adults. (STRONG). 2. We suggest that clinicians use multicomponent brief therapies for insomnia for the treatment of chronic insomnia disorder in adults. (CONDITIONAL). 3. We suggest that clinicians use stimulus control as a single-component therapy for the treatment of chronic insomnia disorder in adults. (CONDITIONAL). 4. We suggest that clinicians use sleep restriction therapy as a single-component therapy for the treatment of chronic insomnia disorder in adults. (CONDITIONAL). 5. We suggest that clinicians use relaxation therapy as a single-component therapy for the treatment of chronic insomnia disorder in adults. (CONDITIONAL). 6. We suggest that clinicians not use sleep hygiene as a single-component therapy for the treatment of chronic insomnia disorder in adults. (CONDITIONAL).

Design of the patient navigator to Reduce Readmissions (PArTNER) study: A pragmatic clinical effectiveness trial.

Previous work indicates the potential for community health workers and peer coaches serving as patient navigators to improve processes of care and health outcomes during care transitions, but have not been sufficiently tested to determine if such programs improve measures of patient experience in minority serving institutions. The objectives of the Patient Navigator to Reduce Readmissions (PArTNER) study was to: 1) conduct a pragmatic clinical effectiveness trial comparing a multi-faceted, stakeholder-supported Navigator intervention (in-person CHW visits in the hospital and after hospital discharge, plus telephone-based peer coaching) versus usual care on the experience of hospital-to-home care transitions in patients hospitalized with heart failure, pneumonia, chronic obstructive pulmonary disease, myocardial infarction, or sickle cell disease; 2) examine the effectiveness of the Navigator intervention in patient subgroups; and 3) understand the barriers and facilitators of successfully implementing the Navigator intervention across patient populations. The co-primary outcomes are the 30-day changes in: 1) Patient Reported Outcomes Measurement Information System (PROMIS) emotional distress-anxiety, and 2) PROMIS informational support. Secondary outcomes at 30 and 60 days include other PROMIS health measures and hospital readmissions. Innovative features of the PArTNER study include early and continuous engagement of patients, their caregivers, clinicians, health system administrators, and other stakeholders to inform the design and implementation of the Navigator intervention. In this report, we describe the design of the PArTNER study.

Balloon valvuloplasty in dysplastic pulmonary valve stenosis: immediate and intermediate outcomes.

OBJECTIVE: To determine the immediate and intermediate outcome in dysplastic and doming pulmonary valve stenosis in children and to determine various factors associated with unsuccessful outcome. STUDY DESIGN: An interventional study. PLACE AND DURATION OF STUDY: The Children's Hospital, Lahore, Pakistan, from June 2006 to December 2012. METHODOLOGY: All patients presenting with severe pulmonary valve stenosis were enrolled in the study. Balloon valvuloplasty was performed on all patients. Successful outcome (residual gradient < 36 mmHg) was compared with matched doming pulmonary valve stenosis control group valvuloplasty. Difference in various quantitative variables was calculated using independent t-test and Mann Whitney U test. Categorical variables were compared using Chi square and Kruskal-Wallis test. Multivariate analysis was performed to determine various factors associated with outcome. Kaplan- Meier survival table was used to determine freedom from re-intervention proportions. RESULTS: One hundred and fifty two patients (Dysplastic group A, n=73; Doming group B, n=79) with median age of 24 months (range 3 - 192 months) and M:F; 2:1 were included in the study. Mean gradient decreased from 96 ± 33 mmHg to 29 ± 20 mmHg. Group A had significantly higher number of patients with unsuccessful outcome (9.6%, p=0.02). Preprocedure gradient > 75 mmHg was the most significant factor associated with unsuccessful outcome (p < 0.001). Median follow-up duration was 3 years (range 1 - 6 years). Freedom from re-intervention proportion at 1, 3 and 6 years was 91.3%, 86.7% and 78.9% respectively in group A compared to 100%, 96.5% and 96.5% respectively in group B. Immediate postprocedure gradient > 60 mmHg was the only significant factor associated with re-intervention in group A (p=0.001). CONCLUSION: The results from balloon valvuloplasty in dysplastic pulmonary valve were suboptimal when compared to doming valves. However, it provides a high freedom from re-intervention rate in intermediate follow-up. Intervention at moderate severity can result in better outcome.

Variations of pulmonary arteries and other associated defects in Tetralogy of Fallot.

BACKGROUND: The objective of study was to determine pulmonary artery variations and other associated cardiac defects in patients with Tetralogy of Fallot. This cross-sectional, descriptive study was carried out at The Children's Hospital and the Institute of Child Health, Lahore, from January 2006 to December 2012. All patients with Tetralogy of Fallot, who underwent cardiac catheterization during this period, were included. Standard cine-angiograms were done to record the pulmonary artery sizes and associated cardiac defects. DESCRIPTION: A total of 576 patients with Tetralogy of Fallot were catheterized. Pulmonary Artery abnormalities were present in 109 (18.92%) patients. The commonest abnormality was isolated Left Pulmonary Artery stenosis (n = 60, 10.4%) followed by supra-valvular stenosis (n = 9, 1.6%). Left Pulmonary Artery was absent in seven patients(1.2%), while 1 patient (0.2%) had both absent right and left Pulmonary Arteries with segmental branch pulmonary arteries originating directly from Main Pulmonary Artery. Associated cardiac lesions included right aortic arch in 72 (12.5%), additional muscular Ventricular Septal Defect in 31 (5.4%), Patent Ductus Arteriosus in 31 (5.4%), bilateral Superior Vena Cava 36(6.2%), Atrial Septal Defect 4(0.7%) and Major Aortopulmonary Collateral Arteries in 75(13%) patients. Significant coronary artery abnormalities were present in 28(4.9%) children. CONCLUSION: Pulmonary artery abnormalities were present in 18.92% of patients with Tetralogy of Fallot. Isolated Left Pulmonary Artery origin stenosis was the most common abnormality. Significant associated cardiac lesions including Patent Ductus Arteriosus , additional muscular Ventricular Septal Defect, coronary artery abnormalities, bilateral Superior Vena Cava, Atrial Septal Defect and Major Aortopulmonary Collateral Arteries were present in one-third of the patients.

Congenital heart defects associated with atrial heterotaxy.

OBJECTIVE: To determine the frequency of various congenital cardiac defects associated with atrial heterotaxy and the difference between spectrum of cardiac defects in right atrial isomerism (RAI) and left atrial isomerism (LAI) in these patients. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Department of Cardiology, The Children's Hospital and Institute of Child Health, Lahore, from July 2006 to June 2011. METHODOLOGY: All children presenting to the hospital with suspected congenital heart defect were included in the study. Echocardiography based sequential segmental analysis was used, taking atrial symmetry, interrupted inferior vena cava (IVC) and juxtaposed aorta to IVC relation into account for identifying atrial heterotaxy. Various segmental defects were noted for RAI and LAI. RESULTS: Children had atrial heterotaxy (M:F; 1.7:1) with 61.6% (n=82) having LAI. Most common lesions associated with RAI included complete atrioventricular (AV) septal defect (n=48, 94.1%), single AV valve (n=45, 88.2%) and pulmonary outflow tract obstruction (n=41, 80.4%). LAI was associated with ventricular septal defect (n=68, 82.9%), atrial septal defect (n=63, 76.8%, mostly secundum variety), and miscellaneous left sided obstructive lesions. CONCLUSION: Atrial heterotaxy encompasses a wide spectrum of congenital cardiac defects. The frequency of various defects associated with RAI or LAI in local South Asian population of Lahore, Pakistan is similar to those as reported in the Western literature.

Pattern of ventricular septal defects and associated complications.

OBJECTIVE: To determine the frequency of various types of Ventricular Septal Defect (VSD) in local population and their complications. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: The Paediatric Cardiac Unit of the Children Hospital and Institute of Child Health, Lahore, from January 2006 to December 2007. METHODOLOGY: All patients aged between one day to 18 years presenting to the unit with isolated VSD during the study period were evaluated using 2-D, continuous wave Doppler and colour Doppler techniques on transthoracic echocardiography. Where necessary, transesophageal echocardiography and/or angiography data was used to further clarify the anatomy. RESULTS: Of the 854 patients with isolated VSD, 710 were of perimembranous type (83.1%), 100 were muscular type (11.7%), 25 were doubly committed subarterial (DCSA) type (2.9%) and 19 patients were having inlet VSD (2.2%). The mean age was 2.1+3 years. Females were 332 (38.8%) and males were 522 (61.1%). Aortic Valve Prolapse (AVP) was seen in 77 patients (10.8%). The mean age for this subgroup was 5.8+4 years with 54 (70.1%) males and 23 (29.9%) females. Of those, 36 (47.3%) had various degree of aortic regurgitation. Right ventricular outflow tract obstruction of variable severity was found in 4 patients. Two of these patients had echocardiographic evidence of subacute bacterial endocarditis. CONCLUSION: Perimembranous (PM) VSD is the commonest type of ventricular septal defect presenting to a tertiary care hospital. The incidence of AVP and AR is high (10.8%) and was found almost entirely in perimembranous outlet VSDs rather than DCSA. This observation has special implication in Pakistan where pool of unoperated VSDs is large.