Post-ligation cardiac syndrome after surgical versus transcatheter closure of patent ductus arteriosus in low body weight premature infants: a multicenter retrospective cohort study.

Transcatheter patent ductus arteriosus (PDA) closure is a safe and effective alternative to surgical ligation in low-body-weight infants. Post-ligation cardiac syndrome (PLCS) is defined as severe hemodynamic and respiratory collapse within 24 h of PDA closure, requiring initiation or an increase of an inotropic agent by > 20% of preligation dosing and an absolute increase of at least 20% in ventilation parameters compared with the preoperative value. Whilst PLCS is routinely observed after surgery, its incidence remains poorly described following transcatheter closure. This study aimed to compare the incidence of PLCS after surgical versus transcatheter closure of PDA in low-body-weight premature infants. Propensity scores were used to compare surgical (N = 78) and transcatheter (N = 76) groups of preterm infants who underwent PDA closure at a procedural weight less than 2000 g in two tertiary institutions between 2009 and 2021. The primary outcome was the incidence of PLCS. Secondary outcomes included overall mortality before discharge, risk factors for PLCS, and post-procedural complications. Procedural success was 100% in both groups. After matching, transcatheter group experienced no PLCS vs 15% in the surgical group (p = 0.012). Furthermore, overall mortality (2% vs 17%; p = 0.03) and major complications (2% vs 23%; p = 0.002) were higher in the surgical group. Surgery (100% vs 47%; p < 0.01), gestation age (25 ± 1 vs 26 ± 2 weeks, p < 0.05) and inotropic support before closure (90% vs 29%; p < 0.001) were associated with PLCS occurrence.          Conclusion: Transcatheter PDA closure may be equally effective but safer than surgical PDA closure in low-body-weight premature infants. What is Known: • Post-ligation cardiac syndrome is a serious and common complication of surgical closure of the ductus arteriosus in preterm infants. • Transcatheter closure of preterm ductus arteriosus is a safe and effective technique that is becoming more and more common worldwide. What is New: • Device closure is safer than surgical ligation for patent ductus arteriosus closure in preterm infants and may be the first-line non-pharmacological therapeutic option in this indication in experienced teams. • Our findings should encourage neonatologists and pediatric cardiologists to start and/or strengthen a durable interventional program for transcatheter PDA closure in premature infants.

Bilateral ductal stenting in an infant with pulmonary atresia and ventricular septal defect, non-confluent pulmonary arteries, and bilateral arterial duct.

Pulmonary atresia with ventricular septal defect, non-confluent pulmonary arteries, and bilateral arterial duct is a rare and complex CHD. Physiologic ductal closure may lead to life-threatening hypoxia. We present a case of successful bilateral ductal stenting as a bridge to further lower-risk surgical repair.

Midline crossing right pulmonary veins with dual drainage to the left atrium.

We report the exceptional case of transcatheter treatment of a partial anomalous pulmonary venous drainage of the right lung to the innominate vein and dual drainage to the left atrium.

Fluoroscopy-free, echocardiography-guided hybrid stenting of native aortic coarctation in a 920-grams premature infant.

Therapeutic options are limited for the management of extremely low-birth-weight infants with critical aortic coarctation despite high doses of prostaglandin infusion. We report successful hybrid, fluoroscopy-free, echocardiography-guided primary stenting of native aortic coarctation in a 920-grams premature infant.

Late aortic obstruction due to ductal vasoconstriction on pulmonic end after transcatheter patent ductus arteriosus closure in an extremely low-birth-weight infant.

Device-induced aortic obstruction is a known rare complication following transcatheter closure of patent ductus arteriosus in extremely low-birth-weight infants. Various mechanisms have been proposed. We report the first description of late aortic obstruction due to ductal vasoconstriction on pulmonic end causing device to be gradually pushed out of aortic end in a 980-gram premature infant.

Isoproterenol Challenge Unmasking Dynamic Bulbo-Ventricular Foramen Restriction.

Isoproterenol stress test during cardiac catheterization unmasked dynamic bulbo-ventricular foramen restriction in a 5-year-old boy with bidirectional Glenn anastomosis for tricuspid atresia/transposed great arteries and unexplained syncope.

Edwards SAPIEN XT transcatheter pulmonary valve implantation: 5-year follow-up in a French Registry.

OBJECTIVES: This study sought to investigate patient intermediate-term outcomes after transcatheter pulmonary valve replacement (TPVR) with Edwards SAPIEN valve. BACKGROUND: The Edwards SAPIEN valve, initially designed for percutaneous aortic valve replacement, has been approved for TPVR in patients with dysfunctional right ventricular outflow tracts (RVOT), but only short-term follow-up has been reported. METHODS: From 2011 to 2016, 62 patients undergoing successful TPVR using the SAPIEN XT valve were consecutively included into the study. Primary efficacy and safety endpoints were defined as freedom from valve-reintervention and freedom from infective endocarditis at last follow-up, respectively. RESULTS: The primary efficacy outcome was met for 87.1% patients after a mean follow-up of 4.6 ± 1.8 years, corresponding to a freedom of reintervention at 5 years of 89% (95% CI 74.8-95.6%). Reinterventions were exclusively due to recurrent obstruction, no significant valvular regurgitation was observed. One case of infective endocarditis was reported, corresponding to a rate of 0.35% per patient-year (95% CI 0.01-2.00%). At 5 years, freedom from infective endocarditis was 98.4% (95% CI 89.1-99.8%). Six patients died or were transplanted due to advanced cardiac failure, without relationship with TPVR. In univariate analysis, reintervention was associated with young age, a smaller tube-graft, a higher pulmonary valve gradient after the procedure and a ratio of largest implanted stent diameter to invasive balloon conduit diameter over 1.35. CONCLUSIONS: This study documents the mid-term safety and efficacy of the Edwards SAPIEN XT valve in patients with dysfunctional RVOT, and identifies a patient profile associated with an uncertain benefit-risk balance.

Health-related quality of life and physical activity in children with inherited cardiac arrhythmia or inherited cardiomyopathy: the prospective multicentre controlled QUALIMYORYTHM study rationale, design and methods.

BACKGROUND: Advances in paediatric cardiology have improved the prognosis of children with inherited cardiac disorders. However, health-related quality of life (QoL) and physical activity have been scarcely analysed in children with inherited cardiac arrhythmia or inherited cardiomyopathy. Moreover, current guidelines on the eligibility of young athletes with inherited cardiac disorders for sports participation mainly rely on expert opinions and remain controversial. METHODS: The QUALIMYORYTHM trial is a multicentre observational controlled study. The main objective is to compare the QoL of children aged 6 to 17 years old with inherited cardiac arrhythmia (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, or arrhythmogenic right ventricular dysplasia), or inherited cardiomyopathy (hypertrophic, dilated, or restrictive cardiomyopathy), to that of age and gender-matched healthy subjects. The secondary objective is to assess their QoL according to the disease's clinical and genetic characteristics, the level of physical activity and motivation for sports, the exercise capacity, and the socio-demographic data. Participants will wear a fitness tracker (ActiGraph GT3X accelerometer) for 2 weeks. A total of 214 children are required to observe a significant difference of 7 ± 15 points in the PedsQL, with a power of 90% and an alpha risk of 5%. DISCUSSION: After focusing on the survival in children with inherited cardiac disorders, current research is expanding to patient-reported outcomes and secondary prevention. The QUALIMYORYTHM trial intends to improve the level of evidence for future guidelines on sports eligibility in this population. Trial registration ClinicalTrials.gov Identifier: NCT04712136, registered on January 15th, 2021 ( https://clinicaltrials.gov/ct2/show/NCT04712136 ).

Frequency of Extracorporeal Membrane Oxygenation Support and Outcomes After Implementation of a Structured PICU Network in Neonates and Children: A Prospective Population-Based Study in the West of France.

OBJECTIVES: To describe the frequency and outcomes on the use of extracorporeal membrane oxygenation (ECMO) among critically ill neonates and children within a structured pediatric critical care network in the West of France. To assess the optimality of decision-making process for patients primarily admitted in non-ECMO centers. DESIGN: Observational prospective population-based study from January 2015 to December 2019. PATIENTS: Neonates over 34 weeks of gestational age, weighing more than 2,000 g and children under 15 years and 3 months old admitted in one of the 10 units belonging to a Regional Pediatric Critical Care Network. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight-thousand one hundred eighty-nine children and 3,947 newborns were admitted within one of the 10 units of the network over the study period. Sixty-five children (8.1% [95% CI, 6.2-10‰]) and 35 newborns (9.4% [95% CI, 6.4-12%]) required ECMO support. Of these patients, 31 were first admitted to a non-ECMO center, where 20 were cannulated in situ (outside the regional ECMO center) and 11 after transfer to the ECMO regional center. Cardiogenic shock, highest serum lactate level, and cardiac arrest prior to first phone call with the regional ECMO center were associated with higher rate of in situ cannulation. During the study period, most of the patients were cannulated for underlying cardiac issue (42/100), postoperative cardiac surgery instability (38/100), and pediatric (10/100) and neonatal (10/100) respiratory distress syndrome. Patients primarily admitted in non-ECMO centers or not had similar 28-day post-ICU survival rates compared with those admitted in the referral ECMO center (58% vs 51%; p = 0.332). Pre-ECMO cardiac arrest, ECMO, and lower pH at ECMO onset were associated with lower 28-day post-ICU survival. CONCLUSIONS: Our local results suggest that a structured referral network for neonatal and pediatric ECMO in the region of Western France facilitated escalation of care with noninferior (or similar) early mortality outcome. Our data support establishing referral networks in other equivalent regions.

Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO).

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present. BACKGROUND: The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. METHODS: The Filiale de Cardiologie Pediatrique et Congénitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018­2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. CONCLUSIONS: The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.

AIMS: Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1-3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome. METHODS AND RESULTS: A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1-5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0-8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively. CONCLUSION: Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.

Noncardiac genetic predisposition in sudden infant death syndrome.

PURPOSE: Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls. METHODS: Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis. RESULTS: Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS. CONCLUSIONS: A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible.

SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Aims: To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. Methods and results: A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE. Conclusion: In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function.

Differential calcium sensitivity in NaV 1.5 mixed syndrome mutants.

KEY POINTS: SCN5a mutations may express gain-of-function (Long QT Syndrome-3), loss-of-function (Brugada Syndrome 1) or both (mixed syndromes), depending on the mutation and environmental triggers. One such trigger may be an increase in cytosolic calcium, accompanying exercise. Many mixed syndromes mutants, including ∆KPQ, E1784K, 1795insD and Q1909R, are found in calcium-sensitive regions. Elevated cytosolic calcium attenuates gain-of-function properties in ∆KPQ, 1795insD and Q1909R, but not in E1784K. By contrast, elevated cytosolic calcium further exacerbates gain-of-function in E1784K by destabilizing slow inactivation. Action potential modelling, using a modified O'Hara Rudy model, suggests that elevated heart rate rescues action potential duration in ∆KPQ, 1795insD and Q1909R, but not in E1784K. Action potential simulations suggest that E1784K carriers have an increased intracellular sodium-to-calcium ratio under bradycardia and tachycardia conditions. Elevated cytosolic calcium, which is common during high heart rates, ameliorates or exacerbates the mixed syndrome phenotype depending on the genetic signature. ABSTRACT: Inherited arrhythmias may arise from mutations in the gene for SCN5a, which encodes the cardiac voltage-gated sodium channel, NaV 1.5. Mutants in NaV 1.5 result in Brugada Syndrome (BrS1), Long-QT Syndrome (LQT3) or mixed syndromes (an overlap of BrS1/LQT3). Exercise is a potential arrhythmogenic trigger in mixed syndromes. We aimed to determine the effects of elevated cytosolic calcium, which is common during exercise, in mixed syndrome NaV 1.5 mutants. We used whole-cell patch clamp to assess the biophysical properties of NaV 1.5 wild-type (WT), ∆KPQ, E1784K, 1795insD and Q1909R mutants in human embryonic kidney 293 cells transiently transfected with the NaV 1.5 α subunit (WT or mutants), ß1 subunit and enhanced green fluorescent protein. Voltage-dependence and kinetics were measured at cytosolic calcium levels of approximately 0, 500 and 2500 nm. In silico, action potential (AP) model simulations were performed using a modified O'Hara Rudy model. Elevated cytosolic calcium attenuates the late sodium current in ∆KPQ, 1795insD and Q1909R, but not in E1784K. Elevated cytosolic calcium restores steady-state slow inactivation (SSSI) to the WT-form in Q1909R, but depolarized SSSI in E1784K. Our AP simulations showed a frequency-dependent reduction of AP duration in ∆KPQ, 1795insD and Q1909R carriers. In E1784K, AP duration is relatively prolonged at both low and high heart rates, resulting in a sodium overload. Cellular perturbations during exercise may affect BrS1/LQT3 patients differently depending on their individual genetic signature. Thus, exercise may be therapeutic or may be an arrhythmogenic trigger in some SCN5a patients.

Transcatheter closure of coronary artery fistulas in infants and children: A French multicenter study.

OBJECTIVES: The short-term efficacy and safety of transcatheter closure (TCC) for the management of coronary artery fistulas (CAFs) was investigated in pediatric patients. BACKGROUND: CAFS are rare with potentially severe complications and their management is still a matter of debate. Percutaneous closure appears to be the treatment of choice in anatomically suitable vessels but limited data are available in the pediatric population. METHODS: This retrospective, observational, multicenter, national study included patients under 16 years of age who underwent TCC of a congenital CAF. Patients with additional congenital heart defect were excluded. RESULTS: 61 patients (36 girls, 25 boys) with a median age of 0.6 year [0-15.4] at diagnosis and 3.9 years [0-16] at procedure were included. The CAF was large in 48 patients (79%); it was distal in 23 (38%) and proximal in 22 (36%). Most patients (77%) were asymptomatic at diagnosis. Clinical signs of congestive heart failure were present in seven patients (11%). Perioperative complications included three cases of ST elevation myocardial infarction (exclusively during attempted closure of a distal CAF), three devices migrations, and one case of leg ischemia. One patient died after surgical closure of a large distal CAF that could not be closed by TCC. Follow-up data were collected for 43 patients (70%) for a median of 91 days [0-4,824]. The Kaplan-Meyer estimate for complete occlusion at 2 years was 73 ± 7.6%. CONCLUSION: TCC in the pediatric population appears to be effective and associated with few complications.

Evaluation and management of bradycardia in neonates and children.

Heart rate is commonly used in pediatric early warning scores. Age-related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Bradycardia is defined as a heart rate below the lowest normal value for age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. As a result of several different etiologies, it may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited sinus node dysfunction or progressive cardiac conduction disorders. Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. The simplest aspect of severe bradycardia management is reflected in the Pediatric and Advanced Life Support (PALS) guidelines. CONCLUSION: Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current practice for evaluation and management of bradycardia in neonates and children. WHAT IS KNOWN: Bradycardia is defined as a heart rate below the lowest normal value for age. Age related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. WHAT IS NEW: Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Bradycardia may occur in a structurally normal heart or in association with congenital heart disease. Genetic variants in multiple genes have been described. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. Early diagnosis and appropriate management are critical in order to prevent sudden death.

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management.

UNLABELLED: Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities. CONCLUSION: Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. WHAT IS KNOWN: • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for biological pacing are promising research fields. In utero percutaneous pacing appears to be at high risk and needs further development before it can be adopted into routine clinical practice. Cardiac resynchronization therapy is of proven value in case of pacing-induced cardiomyopathy.

Inherited progressive cardiac conduction disorders.

PURPOSE OF REVIEW: Progressive cardiac conduction disorder (PCCD) is an inherited cardiac disease that may present as a primary electrical disease or be associated with structural heart disease. In this brief review, we present recent clinical, genetic, and molecular findings relating to PCCD. RECENT FINDINGS: Inherited PCCD in structurally normal hearts has been found to be linked to genetic variants in the ion channel genes SCN5A, SCN1B, SCN10A, TRPM4, and KCNK17, as well as in genes coding for cardiac connexin proteins. In addition, several SCN5A mutations lead to 'cardiac sodium channelopathy overlap syndrome'. Other genes coding for cardiac transcription factors, such as NKX2.5 and TBX5, are involved in the development of the cardiac conduction system and in the morphogenesis of the heart. Mutations in these two genes have been shown to cause cardiac conduction disorders associated with various congenital heart defects. SUMMARY: PCCD is a hereditary syndrome, and genetic variants in multiple genes have been described to date. Genetic screening and identification of the causal mutation are crucial for risk stratification and family counselling.

Closure of Isolated Congenital Coronary Artery Fistula: Long-Term Outcomes and Rate of Re-intervention.

Long-term outcome after closure of isolated congenital coronary artery fistula (ICCAF) is poorly documented. To assess late outcome after ICCAF closure, a 1983-2013 retrospective study included all patients who attempted an ICCAF closure and whose follow-up was ≥1 year. ICCAF was diagnosed in 23 patients [median age 6.9 years (0.1-70.5 years), 13 children]. ICCAF was symptomatic in 12 patients (52.2 %). First intervention was either a transcatheter embolization (n = 19 patients, 82.6 %) or a surgical ligation (n = 4 patients, 17.4 %). After a follow-up of 9.0 years (2.8-33.5), neither death nor late ischemic event occurred but one patient was transplanted, because of postoperative myocardial infarction. Late ICCAF recanalization occurred in eight patients, leading to successful embolization of the shunt in all patients after a delay of 9.8 years (5.7-13.8 years) from the first intervention. Re-intervention occurred later in children (p = 0.0027), with a 50 and 37.5 % freedom from re-intervention in adults compared to a 100 and 89.0 % in children, respectively, at 1 and 6 years of follow-up. At last follow-up, coronary artery diameter had decreased from a mean z score of 12.0 ± 7.7 to a mean z score of 6.0 ± 6.0 (p = 0.002). Long-term outcome after ICCAF closure is excellent, with neither death nor late ischemic event, and a significant decrease in coronary artery diameter with time. Late follow-up is of paramount importance, as one-third of patients will require a re-intervention for late shunt recanalization.