Percutaneous Device Closure of Congenital Isolated Ventricular Septal Defects: A Single-Center Retrospective Database Study Amongst 412 Cases.

To identify suitable cases and reduce failure/complication rates for percutaneous ventricular septal defect (VSD) closure, we aimed to (1) study causes of device failure and (2) compare outcomes with different VSD types and devices in a high-volume single center with limited resources. Retrospective data of 412 elective percutaneous VSD closure of isolated congenital VSDs between 2003 and 2017 were analyzed. Out of 412, 363 were successfully implanted, in 30 device implantation failed, and in 19 the procedure was abandoned. Outcome was assessed using echocardiography, electrocardiography, and catheterization data (before procedure, immediately after and during follow-up). Logistic regression analyses were performed to assess effects of age, VSD type, and device type and size on procedural outcome. Median [interquartile range] age and body surface area were 6.6 [4.1-10.9] years and 0.7 [0.5-1.0] m2, respectively. Device failure was not associated with age (p = 0.08), type of VSD (p = 0.5), device type (p = 0.2), or device size (p = 0.1). Device failure occurred in 7.6% of patients. As device type is not related to failure rate and device failure and complication risk was not associated with age, it is justifiable to use financially beneficial ductal devices in VSD position and to consider closure of VSD with device in clinically indicated children.

ECTOPIC trial: The efficacy of flEcainide Compared To metOprolol in reducing Premature ventrIcular Contractions: A randomized open-label crossover study in pediatric patients.

BACKGROUND: Frequent premature ventricular contractions (PVCs) in children are usually considered benign. Symptoms and left ventricular dysfunction are indications for treatment with antiarrhythmic drugs. OBJECTIVE: This study aimed to evaluate the efficacy of flecainide vs metoprolol in reducing PVCs in children. METHODS: A randomized open-label crossover trial was conducted of children with a PVC burden of >15% on Holter monitoring successively treated with metoprolol and flecainide, or vice versa, with a drug-free interval of at least 2 weeks. Holter measurements were repeated before and after the start of the antiarrhythmic drug. RESULTS: Sixty patients were screened; 19 patients could be included. Median age was 13.9 years (interquartile range, 5.5 years). Mean baseline PVC burden was 21.7% (n = 18; SD ± 14.0) before the start of flecainide and 21.2% (n = 17; SD ± 11.5) before the start of metoprolol. In a mixed model analysis, the estimated mean reduction in PVC burden was 10.6 percentage points (95% CI, 5.8-15.3) for flecainide and 2.4 percentage points (95% CI,2.7-7.5) for metoprolol, with a significant difference of 8.2 percentage points (95% CI, 0.86-15.46; P = .031). Exploratory analysis revealed that 9 of 18 patients treated with flecainide and 1 of 17 patients treated with metoprolol had a reduction to a PVC burden below 5%. No discriminating factors between flecainide responders and nonresponders were found; the mean plasma level was not significantly different (0.34 mg/L vs 0.52 mg/L; P = .277). CONCLUSION: In children with frequent PVCs, flecainide led to a significantly greater reduction of PVC burden compared with metoprolol. Flecainide was effective in only a subgroup of patients, which appears to be unrelated to the plasma level.

Chronic ventricular pacing in children: toward prevention of pacing-induced heart disease.

In children with congenital or acquired complete atrioventricular (AV) block, ventricular pacing is indicated to increase heart rate. Ventricular pacing is highly beneficial in these patients, but an important side effect is that it induces abnormal electrical activation patterns. Traditionally, ventricular pacemaker leads are positioned at the right ventricle (RV). The dyssynchronous pattern of ventricular activation due to RV pacing is associated with an acute and chronic impairment of left ventricular (LV) function, structural remodeling of the LV, and increased risk of heart failure. Since the degree of pacing-induced dyssynchrony varies between the different pacing sites, 'optimal-site pacing' should aim at the prevention of mechanical dyssynchrony. Especially in children, generally paced from a very early age and having a perspective of life-long pacing, the preservation of cardiac function during chronic ventricular pacing should take high priority. In the perspective of the (patho)physiology of ventricular pacing and the importance of the sequence of activation, this paper provides an overview of the current knowledge regarding possible alternative sites for chronic ventricular pacing. Furthermore, clinical implications and practical concerns of the various pacing sites are discussed. The review concludes with recommendations for optimal-site pacing in children.

Long-term protection and mechanism of pacing-induced postconditioning in the heart.

Brief periods of ventricular pacing during the early reperfusion phase (pacing-induced postconditioning, PPC) have been shown to reduce infarct size as measured after 2 h of reperfusion. In this study, we investigated (1) whether PPC leads to maintained reduction in infarct size, (2) whether abnormal mechanical load due to asynchronous activation is the trigger for PPC and (3) the signaling pathways that are involved in PPC. Rabbit hearts were subjected to 30 min of coronary occlusion in vivo, followed by 6 weeks of reperfusion. PPC consisted of ten 30-s intervals of left ventricular (LV) pacing, starting at reperfusion. PPC reduced infarct size (TTC staining) normalized to area at risk, from 49.0 +/- 3.3% in control to 22.9 +/- 5.7% in PPC rabbits. In isolated ejecting rabbit hearts, replacing LV pacing by biventricular pacing abolished the protective effect of PPC, whereas ten 30-s periods of high preload provided a protective effect similar to PPC. The protective effect of PPC was neither affected by the adenosine receptor blocker 8-SPT nor by the angiotensin II receptor blocker candesartan, but was abrogated by the cytoskeletal microtubule-disrupting agent colchicine. Blockers of the mitochondrial K(ATP) channel (5HD), PKC (chelerythrine) and PI3-kinase (wortmannin) all abrogated the protection provided by PPC. In the in situ pig heart, PPC reduced infarct size from 35 +/- 4 to 16 +/- 12%, a protection which was abolished by the stretch-activated channel blocker gadolinium. No infarct size reduction was achieved if PPC application was delayed by 5 min or if only five pacing cycles were used. The present study indicates that (1) PPC permanently reduces myocardial injury, (2) abnormal mechanical loading is a more likely trigger for PPC than electrical stimulation or G-coupled receptor stimulation and (3) PPC may share downstream pathways with other modes of cardioprotection.

Physiology of cardiac pacing in children: the importance of the ventricular pacing site.

Children with congenital or acquired atrioventricular block are provided with ventricular rate support from a pacing lead that traditionally is positioned at the right ventricular (RV) apex. However, RV apical pacing causes dyssynchronous electrical activation and left ventricular (LV) contraction, resulting in decreased LV function. Chronic RV apical pacing leads to deterioration of LV function and morphology, resulting in cardiac failure in approximately 7% of children. This review describes the pathophysiology of pacing-induced dyssynchronous LV activation and contraction, especially as a result of chronic RV apical pacing. Furthermore, this review provides an overview of the possible alternative pacing sites, such as the RV outflow tract, His-bundle, LV apex, and biventricular pacing.

Pacing-induced dys-synchrony preconditions rabbit myocardium against ischemia/reperfusion injury.

BACKGROUND: Because increased mechanical load induces preconditioning (PC) and dys-synchrony increases loading in late-activated regions, we investigated whether dys-synchrony induced by ventricular pacing (VP) at normal heart rate leads to cardioprotection. METHODS AND RESULTS: Isolated working rabbit hearts were subjected to 35 minutes of global ischemia and 2 hours of reperfusion. Seven hearts underwent VP PC (3 periods of 5 minutes VP at the posterior left ventricular [LV] wall), 7 hearts underwent ischemic preconditioning (IPC) (3 periods of 5 minutes of global ischemia), and 9 hearts served as control (C). LV pressure and sonomicrometry were used to assess global hemodynamics and segment work (SW) and end-diastolic segment length (EDSL) in anterior and posterior LV myocardium. Myocardial release of lactate and expression of proBNP mRNA were determined to gain insight in molecular processes involved in VP PC (*P<0.05). Infarct size (triphenyl tetrazolium chloride staining) was 18.3+/-13.0% in group C, and was uniformly reduced in the VP PC and IPC groups (1.8+/-0.8%*, and 3.5+/-3.1%*, respectively; and not significant between VP PC and IPC). LV posterior wall pacing (VP PC group) increased EDSL (by 6.3+/-5.8%*) and SW (to 335+/-207%*) in the LV anterior wall, whereas posterior wall SW decreased to negative values (-23+/-63%*). LV pacing did not significantly change lactate release and coronary flow but significantly increased proBNP mRNA expression in both anterior and posterior myocardium as compared with controls. CONCLUSIONS: Intermittent dys-synchrony is equally cardioprotective as "classical" IPC. Stretch-mediated signaling is a more likely trigger for VP PC than ischemia. VP PC is potentially applicable in cardiac surgery.

Reliability and Validity of a Smartphone-Paired Pulse Oximeter for Screening of Critical Congenital Heart Defects in Newborns.

BACKGROUND: Barriers to widespread implementation of pulse oximetry screening of critical congenital heart defects (CCHD) in newborns include increasing trends of out-of-hospital births and cost of equipment. In recent years, smartphone-compatible pulse oximeters have appeared on the market, but the validity of such devices in the setting of CCHD screening has not been evaluated. OBJECTIVES: To compare the performance in CCHD screening of a smartphone-paired pulse oximeter (Masimo iSpO2-Rx™) and a hospital-grade pulse oximeter (Masimo Radical-7™). METHODS: Preductal (right hand) and postductal (either foot) saturations were determined in a population of 201 term newborns by 2 independent teams, one using the Radical-7 and the other using the iSpO2-Rx. Bland-Altman analysis was applied to calculate mean bias and 95% limits of agreement between the 2 pulse oximeters. RESULTS: For the preductal oxygen saturation, the mean bias (Radical-7 minus iSpO2-Rx) was -0.08 (SD 1.76) and the lower and upper limits of agreement were -3.52 and 3.36, respectively. For the postductal oxygen saturation, the mean bias was -0.11 (SD 1.68) and the lower and upper limits of agreement were -3.49 and 3.18, respectively. In addition, the iSpO2-Rx provided reliable measurements of saturations below 95% in a group of 12 infants admitted to the neonatal intensive care unit. CONCLUSIONS: Our data suggest that CCHD screening with the Masimo iSpO2-Rx is feasible and accurate. The use of reliable smartphone-paired pulse oximeters may contribute to the extension of CCHD screening to home births and low resource settings.

Does heart-type fatty acid-binding protein predict clinical outcomes after pediatric cardiac surgery?

INTRODUCTION: The early identification of vulnerable pediatric cardiac surgery patients can help clinicians provide them with timely support. Heart-type fatty acid-binding protein. (H-FABP) is an early biomarker of myocardial injury in acute myocardial infarction in adults. In this study, we evaluated the correlations between postoperative H-FABP, creatine kinase-myocardial band (CK-MB), troponin-I, total bypass time, and clinical outcomes. METHODS: In 32 pediatric patients that underwent ventricular septal defect. closure we measured H-FABP, troponin-I and CK-MB preoperatively and 1, 3, and 6 h after aortic declamping. Spearman's Rho correlations were calculated between laboratory and clinical parameters including inotropic support duration, aortic cross-clamp time, total bypass time, ventilation-weaning-time, and total Intensive Care Unit stay. RESULTS: H-FABP, CK-MB, troponin-I, and total bypass time have a similarly weak to moderate correlation with clinical outcome measures. CONCLUSIONS: The predictive value of H-FABP for clinical outcome is not stronger than that of CK-MB, Troponin-I, or bypass times.

Preoperative Sildenafil administration in children undergoing cardiac surgery: a randomized controlled preconditioning study.

OBJECTIVES: Sildenafil has strong cardiac preconditioning properties in animal studies and has a safe side-effect profile in children. Therefore, we evaluated the application of Sildenafil preconditioning to reduce myocardial ischaemia/reperfusion injury in children undergoing surgical ventricular septal defect (VSD) closure. METHODS: This is a randomized, double-blind study. Children (1-17 years) undergoing VSD closure were randomized into three groups: placebo (Control group), preconditioning with 0.06 mg/kg (Sild-L group) and 0.6 mg/kg Sildenafil (Sild-H group). PRIMARY ENDPOINT: troponin release. CK-MB, Troponin I, inflammatory response (IL-6 and TNF-α), bypass and ventilation weaning times, inotropy score and echocardiographic function were assessed. Data expressed as median (range), and a value of P < 0.05 was considered significant. RESULTS: Thirty-nine patients were studied (13/group). Aortic cross-clamp time was similar [27 (18-85) and 27 (12-39) min] in the Control and Sild-L groups, respectively, but significantly longer [39 (20-96) min] in the Sild-H group when compared with the Control group. Area under the curve of CK-MB release was 1105 (620-1855) h ng/ml in the Control group, 1672 (564-2767) h ng/ml in the Sild-L group and was significantly higher in the Sild-H group [1695 (1252-3377) h ng/ml] when compared with the Control group. There were no significant differences in inflammatory response markers, cardiopulmonary bypass and ventilation weaning times, inotropy scores and echocardiographic function between the groups. CONCLUSIONS: In this small study, Sildenafil failed to reduce myocardial injury in children undergoing cardiac surgery, nor does it alter cardiac function, inotropic needs or postoperative course. A subclinical increase in cardiac enzyme release after Sildenafil preconditioning cannot be excluded. CLINICAL TRIALS REGISTRY: CTRI/2014/03/004468.

Absence of reverse electrical remodeling during regression of volume overload hypertrophy in canine ventricles.

OBJECTIVE: Ventricular hypertrophy predisposes for cardiac arrhythmias, presumably due to prolongation of repolarization (electrical remodeling). The temporal relation between the development of hypertrophy and electrical remodeling, as well as their reversibility upon restoration of normal load, however, are poorly understood. This was investigated in the present study using volume overload hypertrophy induced by atrio-ventricular (AV) block and normalization of load by pacing. METHODS: Dogs were subjected to either 16 weeks of AV-block (CAVB group, n=9) or 8 weeks of AV-block followed by 8 weeks of right ventricular (RV) pacing at physiological heart rate (CAVB+PACE group, n=9). RESULTS: Left ventricular (LV) mass (2D-echocardiography) increased after 8 weeks of AV-block to approximately 30% above baseline and returned to 10+/-14% after 8 weeks of pacing. QT-time (surface ECG) also increased after AV-block. However, 8 weeks of pacing did not decrease QT and QTc-time (c=corrected for heart rate), neither during physiological pacing nor during temporary pacing at 100 beats/min. Lack of reverse electrical remodeling was confirmed by the absence of changes in LV and RV action potential duration (monophasic action potentials) at week 8 and 16. CONCLUSIONS: In volume overload hypertrophy due to AV-block, structural and electrical remodeling develop in parallel but restoration of physiological heart rate causes dissociation between reverse structural remodeling and reverse electrical remodeling.

Infective endocarditis of a transcatheter pulmonary valve in comparison with surgical implants.

BACKGROUND: Melody valved stents (Medtronic Inc, Minneapolis, Minnesota, USA) have become a very competitive therapeutic option for pulmonary valve replacement in patients with congenital heart disease. After adequate prestenting of the right ventricular outflow tract (RVOT) Melody valved stents have a good medium term functional result but are exposed to infective endocarditis (IE). PATIENTS AND METHODS: Retrospective study of tertiary centre Congenital Heart Disease database; to compare incidence of IE in three different types of valved conduits in RVOT: Melody valved stent, cryopreserved homograft (European Homograft Bank) and Contegra graft (Medtronic Inc). RESULTS: Between 1989 and 2013, 738 conduits were implanted in 677 patients. 107 Melody valved stents were implanted in 107 patients; IE occurred in 8 (7.5%) patients during a follow-up of 2.0 years (IQR 2.4 years, range 0.3-7.8 years). 577 Homografts were implanted in 517 patients; IE occurred in 14 patients (2.4%) during a median follow-up of 6.5 years (IQR 9.2 years; range 0.1-23.7 years). Finally, 54 Contegra grafts were implanted in 53 patients; 11 patients (20.4%) had IE during a follow-up of 8.8 years (IQR 7.7 years; range 0.2-3.5 years). Survival free of IE by Kaplan-Meier for homografts was 98.7% at 5 years and 97.3% at 10 years; for Contegra 87.8% at 5 years and 77.3% at 10 years and for Melody 84.9% at 5 years (log-rank test; p<0.001). CONCLUSIONS: The Contegra conduit and Melody valved stents have a significantly higher incidence of IE than homografts. IE is a significant threat for long-term conduit function.

Proteins involved in salvage of the myocardium.

In the Western world, cardiac ischemic disease is still the most common cause of death despite significant improvements of therapeutic drugs and interventions. The fact that the heart possesses an intrinsic protection mechanism has been systematically overlooked before the 1980s. It has been clearly shown that the activation of this mechanism can reduce the infarct size after an ischemic insult. Prerequisite is the induction of the synthesis of such cardio-protective proteins as heat shock proteins (HSPs) and anti-oxidative enzymes. HSPs are involved in the maintenance of cell homeostasis by guiding the synthesis, folding and degradation of proteins. Besides, the various family members cover a broad spectrum of anti-oxidative, anti-apoptotic and anti-inflammatory activities. Although the major inducible HSP72 has received most attention, other HSPs are able to confer cardioprotection as well. In addition, it seems that there is a concerted action between the various cardio-protective proteins. One drawback is that the beneficial effects of HSPs seem to be less effective in the compromised than in the normal heart. Although clinical studies have shown that there is a therapeutic potential for HSPs in the compromised heart, major efforts are needed to fully understand the role of HSPs in these hearts and to find a safe and convenient way to activate these protective proteins.

Use of covered Cheatham-Platinum stents in congenital heart disease.

BACKGROUND: Controversy remains regarding the use of covered stents in congenital heart disease (CHD). We evaluate the possibilities and safety of covered Cheatham-Platinum (CCP) stents in CHD. METHODS: Single-center retrospective CHD-database study of all CCP stents, 2003-2012. Three study groups: aortic coarctation (CoA), right ventricular outflow tract pre-stenting for percutaneous revalvulation (RVOT), and miscellaneous. Continuous data expressed as median (range). RESULTS: 114 CCP stents in 105 patients, age 16.8 years (4.2-71.2). CoA group: 54 CCP stents in 51 patients: 3/54 for aneurysm exclusion, in 51/54 covering used "prophylactically" because of increased risk for vessel tear. Overall, CCP stenting increased the coarctation diameter from 6mm (0-15) to 15 mm (10-20) (p<0.001). RVOT group: 39 CCP stents in 37 patients (34 with RVOT graft, 3 with transannular patch): the graft lumen had shrunken from nominal 21 mm (10-26) to 13 mm (5-22); with the CCP stent the RVOT was redilated to 22 mm (16-26, p<0.001 vs stenosis). Miscellaneous group: 21 CCP stents in 17 patients: closure of Fontan-circuit fenestration (n=5), restoration of superior caval vein (n=2) or pulmonary artery (n=3) patency, relief of supra-pulmonary stenosis (n=2), exclusion of aberrant pulmonary arteries (n=1), cavopulmonary conduit expansion (n=2), Blalock-Taussig shunt flow reduction (n=1), and defibrillator lead protection from sharp stents (n=1). Hybrid procedures performed in 3/17 patients. CCP stent was used as rescue treatment in 2/patients to seal iatrogenic bleeding. CONCLUSION: CCP stents can safely be applied in CHD patients. The covering allows adequate sealing of existing or expected tears, thereby increasing the safety margin with more complete dilation.

Late recovery of atrioventricular conduction after postsurgical chronic atrioventricular block is not exceptional.

OBJECTIVE: Postsurgical atrioventricular block may complicate surgery for congenital heart defects and is generally considered permanent when persisting longer than 14 days after surgery. In this study, we evaluate the occurrence of spontaneous late recovery of atrioventricular conduction in postsurgical chronic atrioventricular block and discuss its clinical implications. METHODS: We retrospectively reviewed all cardiac surgical procedures on cardiopulmonary bypass between January 1993 and November 2010 in subjects younger than 18 years. Patients with postsurgical advanced second- or third-degree atrioventricular block persisting longer than 14 days after surgery were included. RESULTS: Of a total of 2850 cardiac surgical procedures on cardiopulmonary bypass, 59 (2.1%) were immediately complicated by chronic postsurgical atrioventricular block of advanced second (n = 4) or third degree (n = 55). In another 6 patients (0.2%), late occurrence of chronic advanced second- (n = 3) or third-degree (n = 3) atrioventricular block, without signs of any etiology other than previous surgery, was seen 0.4 to 10 years after surgery (median, 5.7 years). Late (>2 weeks) regression to either completely normal atrioventricular conduction or asymptomatic first-degree atrioventricular block occurred 3 weeks to 7 years (median, 3.1 years) after surgery in 7 (12%) patients with immediate postsurgical chronic atrioventricular block. CONCLUSIONS: Complete recovery of atrioventricular conduction or regression to asymptomatic first-degree atrioventricular block occurred in 12% of patients with postsurgical chronic second- or third-degree atrioventricular block. To prevent unnecessary adverse side effects of chronic ventricular pacing and to prolong battery longevity, ventricular pacing should be minimized in patients with recovered normal atrioventricular conduction.

Extreme windkessel effect can cause right heart failure early after truncus repair.

An infant developed severe right heart failure early after truncal repair with a pulmonary homograft. A mechanical obstruction by narrowing could not be identified at the homograft or pulmonary arteries. However, functional obstruction was caused by an extreme windkessel effect in a massively dilated homograft that absorbed rather than transmitted the pulse wave. Effective treatment consisted of replacing the dilated homograft by a rigid aortic homograft of equal size as the initial homograft. When confronted with circulatory failure after allograft placement, the clinician should not only look for obstruction by narrowing, but also consider the windkessel phenomenon.

Pacing postconditioning: impact of pacing algorithm, gender, and diabetes on its myocardial protective effects.

Pacing postconditioning (PPC) induces cardioprotection. The aim of this study was to determine the optimal pacing algorithm and possible influence of gender and diabetes on PPC. Unprotected regional ischemia for 30 min served as negative control and classical PPC (ten cycles of 30 s left ventricular pacing alternated with 30 s right atrial pacing) as positive control. Area at risk and infarct size were determined by blue dye and triphenyltetrazolium chloride staining. For achieving protection, the minimal number of PPC cycles was seven and the minimal duration of a PPC protocol was 200 s. The protective effect of PPC was comparable in male and female hearts, but no protection could be induced by PPC in diabetic hearts. PPC can provide myocardial protection when using at least seven cycles of ventricular pacing. PPC protection is independent of gender, but sensitive to experimental diabetes.

Impact of the permanent ventricular pacing site on left ventricular function in children: a retrospective multicentre survey.

BACKGROUND: Chronic right ventricular (RV) pacing is associated with deleterious effects on cardiac function. OBJECTIVE: In an observational multicentre study in children with isolated atrioventricular (AV) block receiving chronic ventricular pacing, the importance of the ventricular pacing site on left ventricular (LV) function was investigated. METHODS: Demographics, maternal autoantibody status and echocardiographic measurements on LV end-diastolic and end-systolic dimensions and volumes at age <18 years were retrospectively collected from patients undergoing chronic ventricular pacing (>1 year) for isolated AV block. LV fractional shortening (LVFS) and, if possible LV ejection fraction (LVEF) were calculated. Linear regression analyses were adjusted for patient characteristics. RESULTS: From 27 centres, 297 children were included, in whom pacing was applied at the RV epicardium (RVepi, n = 147), RV endocardium (RVendo, n = 113) or LV epicardium (LVepi, n = 37). LVFS was significantly affected by pacing site (p = 0.001), and not by maternal autoantibody status (p = 0.266). LVFS in LVepi (39 ± 5%) was significantly higher than in RVendo (33 ± 7%, p < 0.001) and RVepi (35 ± 8%, p = 0.001; no significant difference between RV-paced groups, p = 0.275). Subnormal LVFS (LVFS < 28%) was seen in 16/113 (14%) RVendo-paced and 21/147 (14%) RVepi-paced children, while LVFS was normal (LVFS ≥ 28%) in all LVepi-paced children (p = 0.049). These results are supported by the findings for LVEF (n = 122): LVEF was <50% in 17/69 (25%) RVendo- and in 10/35 (29%) RVepi-paced patients, while LVEF was ≥ 50% in 17/18 (94%) LVepi-paced patients. CONCLUSION: In children with isolated AV block, permanent ventricular pacing site is an important determinant of LV function, with LVFS being significantly higher with LV pacing than with RV pacing.