Apoptosis and epicardial contributions act as complementary factors in remodeling of the atrioventricular canal myocardium and atrioventricular conduction patterns in the embryonic chick heart.

BACKGROUND: During heart development, it has been hypothesized that apoptosis of atrioventricular canal myocardium and replacement by fibrous tissue derived from the epicardium are imperative to develop a mature atrioventricular conduction. To test this, apoptosis was blocked using an established caspase inhibitor and epicardial growth was delayed using the experimental epicardial inhibition model, both in chick embryonic hearts. RESULTS: Chicken embryonic hearts were either treated with the peptide caspase inhibitor zVAD-fmk by intrapericardial injection in ovo (ED4) or underwent epicardial inhibition (ED2.5). Spontaneously beating embryonic hearts isolated (ED7-ED8) were then stained with voltage-sensitive dye Di-4-ANEPPS and imaged at 0.5-1 kHz. Apoptotic cells were quantified (ED5-ED7) by whole-mount LysoTracker Red and anti-active caspase 3 staining. zVAD-treated hearts showed a significantly increased proportion of immature (base to apex) activation patterns at ED8, including ventricular activation originating from the right atrioventricular junction, a pattern never observed in control hearts. zVAD-treated hearts showed decreased numbers of apoptotic cells in the atrioventricular canal myocardium at ED7. Hearts with delayed epicardial outgrowth showed also increased immature activation patterns at ED7.5 and ED8.5. However, the ventricular activation always originated from the left atrioventricular junction. Histological examination showed no changes in apoptosis rates, but a diminished presence of atrioventricular sulcus tissue compared with controls. CONCLUSIONS: Apoptosis in the atrioventricular canal myocardium and controlled replacement of this myocardium by epicardially derived HCN4-/Trop1- sulcus tissue are essential determinants of mature ventricular activation pattern. Disruption can lead to persistence of accessory atrioventricular connections, forming a morphological substrate for ventricular pre-excitation. Developmental Dynamics 247:1033-1042, 2018. © 2018 Wiley Periodicals, Inc.

Slow Conducting Electroanatomic Isthmuses: An Important Link Between QRS Duration and Ventricular Tachycardia in Tetralogy of Fallot.

OBJECTIVES: This study sought to evaluate the influence of slow conducting anatomic isthmuses (SCAI) as dominant ventricular tachycardia (VT) substrate on QRS duration. BACKGROUND: QRS prolongation has been associated with VT in repaired tetralogy of Fallot. METHODS: Seventy-eight repaired tetralogy of Fallot patients (age 37 ± 15 years, 52 male, QRS duration 153 ± 29 ms, 67 right bundle branch blocks [RBBB]) underwent programmed stimulation and electroanatomic activation mapping during sinus rhythm. Right ventricular (RV) surface, RV activation pattern, RV activation time, conduction velocity at AI, and remote RV sites were determined. RESULTS: Twenty-four patients were inducible for VT (VT+); SCAI was present in 22 of 24 VT+ but only in 2 of 54 patients without inducible VT (VT-). Conduction velocity through AI was slower in VT+ patients (median of 0.3 [0.3 to 0.4] vs. 0.7 [0.6 to 0.9] m/s; p < 0.01) but conduction velocity in the remote RV did not differ between groups. In non-RBBB, QRS duration was similar in VT+ patients (n = 6) and VT- patients (n = 5), but RV activation within SCAI exceeded QRS offset in VT+ patients (37 ± 20 ms vs. -5 ± 9 ms, p < 0.01). In RBBB, both QRS duration and RV activation time were longer in VT+ patients (n = 18, 17 of 18 QRS > 150 ms) compared with VT- patients (n = 49, 27 of 49 QRS > 150 ms) (173 ± 22 ms vs. 156 ± 20 ms; p < 0.01; 141 ± 22 ms vs. 129 ± 21 ms; p = 0.04). In VT+ patients, QRS prolongation >150 ms (n = 17) was due to SCAI or blocked isthmus in 15 patients (88%) and 1 (6%). In contrast, in VT- patients, QRS prolongation >150 ms (n = 27) was due to enlarged RV or blocked isthmus in 10 patients (37%) and 8 (30%), but due to SCAI in only 1 (4%). After exclusion of a severely enlarged RV, a QRS duration >150 ms was highly predictive for SCAI/blocked AI (OR: 17; 95% CI: 3.3 to 84; p < 0.01). CONCLUSIONS: A narrow QRS interval does not exclude VT-related SCAI. In the presence of RBBB, SCAI further prolongs QRS duration. QRS duration >150 ms is highly suspicious for SCAI or isthmus block distinguishable by electroanatomic mapping.

Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after Home Birth and Early Postnatal Discharge.

OBJECTIVE: To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) in a setting with home births and early discharge after hospital deliveries, by using an adapted protocol fitting the work patterns of community midwives. STUDY DESIGN: Pre- and postductal oxygen saturations (SpO2) were measured ≥1 hour after birth and on day 2 or 3. Screenings were positive if the SpO2 measurement was <90% or if 2 independent measures of pre- and postductal SpO2 were <95% and/or the pre-/postductal difference was >3%. Positive screenings were referred for pediatric assessment. Primary outcomes were sensitivity, specificity, and false-positive rate of pulse oximetry screening for CCHD. Secondary outcome was detection of noncardiac illnesses. RESULTS: The prenatal detection rate of CCHDs was 73%. After we excluded these cases and symptomatic CCHDs presenting immediately after birth, 23 959 newborns were screened. Pulse oximetry screening sensitivity in the remaining cohort was 50.0% (95% CI 23.7-76.3) and specificity was 99.1% (95% CI 99.0-99.2). Pulse oximetry screening was false positive for CCHDs in 221 infants, of whom 61% (134) had noncardiac illnesses, including infections (31) and respiratory pathology (88). Pulse oximetry screening did not detect left-heart obstructive CCHDs. Including cases with prenatally detected CCHDs increased the sensitivity to 70.2% (95% CI 56.0-81.4). CONCLUSION: Pulse oximetry screening adapted for perinatal care in home births and early postdelivery hospital discharge assisted the diagnosis of CCHDs before signs of cardiovascular collapse. High prenatal detection led to a moderate sensitivity of pulse oximetry screening. The screening also detected noncardiac illnesses in 0.6% of all infants, including infections and respiratory morbidity, which led to early recognition and referral for treatment.

Arrhythmias in congenital heart disease: a position paper of the European Heart Rhythm Association (EHRA), Association for European Paediatric and Congenital Cardiology (AEPC), and the European Society of Cardiology (ESC) Working Group on Grown-up Congenital heart disease, endorsed by HRS, PACES, APHRS, and SOLAECE.

The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults. Within the past 20 years, management of patients with arrhythmias has gained remarkable progress including pharmacological treatment, catheter ablation, and device therapy. Catheter ablation in patients with CHD has paralleled the advances of this technology in pediatric and adult patients with structurally normal hearts. Growing experience and introduction of new techniques like the 3D mapping systems into clinical practice have been particularly beneficial for this growing population of patients with abnormal cardiac anatomy and physiology. Finally, device therapies allowing maintanence of chronotropic competence and AV conduction, improving haemodynamics by cardiac resynchronization, and preventing sudden death are increasingly used. For pharmacological therapy, ablation procedures, and device therapy decision making requires a deep understanding of the individual pathological anatomy and physiology as well as detailed knowledge on natural history and long-term prognosis of our patients. Composing expert opinions from cardiology and paediatric cardiology as well as from non-invasive and invasive electrophysiology this position paper was designed to state the art in management of young individuals with congenital heart defects and arrhythmias.

Pulse Oximetry Screening for Critical Congenital Heart Disease after Home Birth and Early Discharge.

OBJECTIVES: To assess the feasibility of pulse oximetry (PO) screening in settings with home births and very early discharge. We assessed this with an adapted protocol in The Netherlands. STUDY DESIGN: PO screening was performed in the Leiden region in hospitals and by community midwives. Measurements were taken ≥ 1 hour after birth and on day 2 or 3 during the midwife visit. Primary outcome was the percentage of screened infants with parental consent. The time point of screening, oxygen saturation, false positive (FP) screenings, critical congenital heart defects (CCHDs), and other detected pathology were registered. RESULTS: In a 1-year period, 3625 eligible infants were born. Parents of 491 infants were not approached for consent, and 44 refused the screening. PO screening was performed in 3059/3090 (99%) infants with obtained consent. Median (IQR) time points of the first and second screening were 1.8 (1.3-2.8) and 37 (27-47) hours after birth. In 394 infants with screening within 1 hour after birth, the median pre- and postductal oxygen saturations were 99% (98%-100%) and 99% (97%-100%). No CCHD was detected. The FP prevalence was 1.0% overall (0.6% in the first hours after birth). After referral, important noncritical cardiac and other noncardiac pathology was found in 62% of the FP screenings. CONCLUSIONS: PO screening for CCHD is feasible after home births and very early discharge from hospital. Important neonatal pathology was detected at an early stage, potentially increasing the safety of home births and early discharge policy.

Long-term outcome of ablative therapy of postoperative supraventricular tachycardias in patients with univentricular heart: a European multicenter study.

BACKGROUND: Catheter ablation has evolved as a possible curative treatment modality for supraventricular tachycardias (SVT) in patients with univentricular heart. However, the long-term outcome of ablation procedures is unknown. We evaluated the procedural and long-term outcome of ablative therapy of late postoperative SVT in patients with univentricular heart. METHODS AND RESULTS: Patients with univentricular heart (n=19, 11 male; age, 29+/-9 years) referred for ablation of SVT were studied. Ablation was guided by 3D electroanatomic mapping in all but 2 procedures. A total of 41 SVT were diagnosed as intra-atrial reentrant tachycardia (n=30; cycle length, 310+/-68 ms), typical atrial flutter (n=4; cycle length, 288+/-42 ms), focal atrial tachycardia (n=6; cycle length, 400+/-60 ms), and atrial fibrillation (n=1). Ablation was successful in 73% of intra-atrial reentrant tachycardia, 75% of atrial flutter, and all focal atrial tachycardia and focal atrial fibrillation. During the follow-up period of 53+/-34 months, 2 patients were lost to follow-up, 3 died of heart failure, 2 underwent heart transplantation, and 1 underwent conduit replacement. Of the remaining group, 8 had sinus rhythm and 3 had SVT. CONCLUSIONS: Focal and reentrant mechanisms underlie postoperative SVT in patients with univentricular heart. Successive SVT developing over time may be caused by different mechanisms. Ablative therapy is potentially curative, with a procedural success rate of 78%. In patients who had multiple ablation procedures, the SVT originated from different atrial sites, suggesting that these new SVT were caused by progressive atrial disease. Despite recurrent SVT, sinus rhythm at the end of the follow-up period was achieved in 72%.

Ablation of focal atrial arrhythmia in patients with congenital heart defects after surgery: role of circumscribed areas with heterogeneous conduction.

BACKGROUND: In patients late after surgical repair of congenital heart disease (CHD), areas with abnormal electrophysiologic properties may serve as slow conducting pathways within a macroreentrant circuit or may be the source of focal atrial tachycardia. OBJECTIVES: The purpose of this study was to evaluate the role of abnormal areas during focal atrial tachycardia prior to ablation. METHODS: Electroanatomic activation mapping of 62 atrial tachycardias was performed in 43 consecutive patients (37 +/- 12 years) after surgical repair of CHD. The mechanism of atrial tachycardia was scar related intra-atrial reentry (n = 27), cavotricuspid-related atrial flutter (n = 21), atrial fibrillation (n = 2), or focal atrial tachycardia (n = 10). During intra-atrial reentry, channels of slow conduction could be identified in all patients. Subsequent ablation was directed toward connecting two nonconductive borders. The site of origin during focal atrial tachycardia showed fractionated potentials and/or continuous electrical activity. RESULTS: Ablation directed at isolating the source area resulted in termination of focal atrial tachycardia in all cases. In two patients, ablation of an area showing continuous electrical activity giving rise to fibrillatory conduction resulted in termination of atrial fibrillation. Ablation of intra-atrial reentry was successful in 70%. Atrial flutter and focal atrial tachycardia were successfully ablated in all patients. No complications were observed. CONCLUSION: In patients with surgically corrected CHD, atrial tachycardia most often is caused by a macroreentrant mechanism but in some is the result of a focal mechanism. Areas of abnormal conduction may serve not only as a zone of slow conduction within a macroreentrant circuit but also as the site of origin of a focal atrial arrhythmia. Catheter ablation directed at "source isolation" is effective in eliminating focal atrial tachycardia in patients with CHD.

Transvenous biventricular pacing in a child after congenital heart surgery as an alternative therapy for congestive heart failure.

Transvenous Biventricular Pacing in Children. Cardiac resynchronization therapy improves short-term and long-term hemodynamics in adult patients with congestive heart failure and left bundle branch block. We describe the feasibility of transvenous biventricular pacemaker implantation in a 6-year-old child with heart failure and wide QRS complex after congenital heart surgery. Myocardial tissue Doppler imaging was used to demonstrate intraventricular dyssynchrony and resynchronization after cardiac resynchronization therapy. During 1-year follow-up, symptomatology and hemodynamic parameters improved.

Voltage and activation mapping: how the recording technique affects the outcome of catheter ablation procedures in patients with congenital heart disease.

BACKGROUND: Endocardial mapping is mandatory before radiofrequency catheter ablation (RFCA). Mapping can be performed with either unipolar or bipolar recordings. Impact of the recording technique used was studied in patients with and without structural heart disease using the 3D electroanatomic CARTO mapping system. METHODS AND RESULTS: Patients (n=44; 16 males; age 43+/-16 years) referred for RFCA of atrial flutter (AFL, n=18), focal atrial tachycardia (FAT, n=4), AV nodal reentrant tachycardia (AVNRT, n=5), or scar-related atrial reentrant tachycardia (IART, n=17) were studied. Voltage and activation maps were constructed. Unipolar and bipolar voltage distribution in the different groups was studied to establish a cutoff voltage value to facilitate delineation of scar tissue. Electrograms were recorded during tachycardia (FAT: n=246, cycle length [CL]=449+/-35 ms; AVNRT: n=182, CL=359+/-47 ms; AFL: n=1164, CL=255+/-56 ms; IART: n=2431, CL=280+/-74 ms). Unipolar voltages were greater than bipolar voltages (P<0.001). Unipolar voltages < or =1.0 mV were equally distributed in both AFL and IART patients. Bipolar voltages < or =0.1 mV were only found in patients with IART, and subsequently 0.1 mV was used as the cutoff value to delineate scar tissue. No unipolar cutoff value could be established. Timing of unipolar and bipolar local activation was correlated in all patient groups. CONCLUSIONS: The recording technique used has considerable impact on reconstruction of reentrant pathways and on the outcome of RFCA. In general, unipolar and bipolar recordings provide complementary information; however, only bipolar recordings allow voltage-based scar tissue delineation in patients with congenital heart disease.