Monique R.M. Jongbloed

Development of the Right Ventricular Inflow Tract and Moderator Band: A Possible Morphological and Functional Explanation for Mahaim Tachycardia

Atriofascicular accessory bundles with AV-node like conduction properties can sustain atrioventricular (AV) re-entrant tachycardia (Mahaim tachycardia). During early embryogenesis, the AV canal is situated above the primitive left ventricle (LV), and a right AV connection has not been achieved yet. We studied the formation of the right ventricular (RV) inflow tract in relation to the developing cardiac conduction system and hypothesized a morphological explanation for functional atriofascicular bypass tracts. Analysis of lacZ-expression during sequential stages of cardiogenesis was performed in CCS-lacZ transgenic mice (E9.5 to 15.5). Embryos were stained for &bgr;-galactosidase activity and the myocardial marker HHF35. At early stages CCS-lacZ expression was observed in a ring surrounding the AV canal, which connected at the inner curvature to the primary fold. The first sign of formation of the (CCS-lacZ negative) RV inlet component was a groove in the CCS-lacZ positive tissue of the primary fold. Outgrowth of the RV inlet tract resulted in division of the primary fold in a septal part, the trabecula septomarginalis and a lateral part, the moderator band, which extended laterally up to the right AV ring. Electrophysiological measurements in embryonic hearts (E15.5) in which the right atrium (RA) and RV were isolated from the left atrium (LA) and LV supported the functionality of this AV-connection via the moderator band, by demonstrating sequential atrial and ventricular activation in both RA/RV and LA/LV preparations. In conclusion, our observations may provide a possible morphological and functional explanation for atriofascicular accessory pathways via the moderator band, underlying Mahaim tachycardia.

Pulmonary Vein, Dorsal Atrial Wall and Atrial Septum Abnormalities in Podoplanin Knockout Mice With Disturbed Posterior Heart Field Contribution

The developing sinus venosus myocardium, derived from the posterior heart field, contributes to the atrial septum, the posterior atrial wall, the sino-atrial node, and myocardium lining the pulmonary and cardinal veins, all expressing podoplanin, a coelomic and myocardial marker. We compared development and differentiation of the myocardium and vascular wall of the pulmonary veins (PV), left atrial dorsal wall, and atrial septum in wild type with podoplanin knockout mouse embryos (E10.5–E18.5) by 3D reconstruction and immunohistochemistry. Expression of Nkx2.5 in the pulmonary venous myocardium changes from mosaic to positive during development pointing out a high proliferative rate compared with Nkx2.5 negative myocardium of the sino-atrial node and cardinal veins. In mutants, myocardium of the PVs, dorsal atrial wall and atrial septum was hypoplastic. The atrial septum and right-sided wall of the PV almost lacked interposed mesenchyme. Extension of smooth muscle cells into the left atrial body was diminished. We conclude that myocardium of the PVs, dorsal atrial wall, and atrial septum, as well as the smooth muscle cells, are derived from the posterior heart field regulated by podoplanin.

Left-Sided Ablation of Ventricular Tachycardia in Adults with Repaired Tetralogy of Fallot: A Case Series

Background—Radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in repaired Tetralogy of Fallot focuses on isthmuses in the right ventricle but may be hampered by hypertrophied myocardium or prosthetic material. These patients may benefit from ablation at the left side of the ventricular septum. Methods and Results—Records from 28 consecutive repaired Tetralogy of Fallot patients from 2 centers who underwent VT ablation were reviewed. Ablation targeted anatomic isthmuses containing VT re-entry circuits, which were identified by 3-dimensional substrate, pace, and entrainment mapping. A left-sided approach was considered beneficial if (1) right-sided RFCA failed, (2) part of the circuit was mapped to the left side, and (3) left-sided RFCA resulted in isthmus transection and prevention of VT induction. In 4 of 28 patients (52±13 years; 75% men), inducible for 1.5 (quartiles, 1.0 – 2.0) VTs (335±58 ms), left-sided RFCA was performed. In 3 patients, RFCA at aortic sites terminated VT related to a septal isthmus and prevented reinduction. In 1 patient, with prior biventricular implantable cardioverter-defibrillator, diastolic activity was recorded at the left side of the septum in proximity to the His-bundle. RFCA prevented VT reinduction with anticipated complete atrioventricular block. The left-sided approach resulted in complete procedural success (transection of anatomic isthmus and noninducibility) and freedom of VT recurrence during follow-up (20±15 months) in all patients. Right-sided RFCA failure was likely because of septal hypertrophy in 2, overlying pulmonary homograft in 1, and overlying ventricular septal defect patch in 1. Conclusions—Left-sided RFCA for VTs dependent on septal anatomic isthmuses improves ablation outcome in repaired Tetralogy of Fallot.

Long-term tricuspid valve prosthesis-related complications in patients with congenital heart disease

OBJECTIVESnIn patients with acquired valvar disease, morbidity and mortality rates after tricuspid valve replacement (TVR) are high. However, in adult patients with congenital heart disease, though data concerning outcome after TVR are scarce, even poorer results are suggested in patients with Ebstein anomaly. To investigate the applicability of these results to a broader array of congenital heart disease patients, we report the long-term follow-up of prosthesis-related complications, including re-replacement of patients with a tricuspid valve prosthesis and congenital heart disease.nnnMETHODSnFrom the Dutch Congenital Corvitia (CONCOR) registry, we identified 20 patients with a biological or mechanical tricuspid valve prosthesis implanted between 1977 and 2012 (total of 31 prostheses). We analysed the tricuspid valve-related complications and mortality.nnnRESULTSnTen patients with a median age of 16.2 years at the time of surgery (interquartile range 13.2-28.2 years) received a bioprosthesis while 10 patients with a median age of 36.4 years (interquartile range 14.0-47.0) at the time of surgery received a mechanical prosthesis (P = 0.28). During a mean follow-up of 14 years, 50% needed a re-replacement because of valve-related complications (e.g. valve degeneration or valve thrombosis). The yearly percentage of patients with valve-related complications was 4.2% in patients with a bioprosthesis and 2.7% in those with a mechanical prosthesis. Within 20 years of implantation, the median duration of event-free survival was significantly shorter in 3 patients with a prosthesis-patient mismatch (PPM; 1.0 year; interquartile range 0.01-2.6), compared with 7 without mismatch (8.0 years; interquartile range 5.1-12.3; P = 0.02).nnnCONCLUSIONSnCompared with previous literature on acquired valvar disease, we found a higher incidence of valve-related complications in patients with congenital heart disease that was unrelated to prosthesis material. Our data suggest that PPM may have a negative effect on the event-free interval.

Cardiac adaption during pregnancy in women with congenital heart disease and healthy women

Objective Pregnancy in women with congenital heart disease (CHD) is associated with deterioration in cardiac function. However, longitudinal data are scarce. This study describes serial changes in cardiac dimensions and function during pregnancy in women with CHD and compares these with healthy pregnant women (controls). Methods Eight tertiary centres prospectively enrolled 125 pregnant women with CHD (pregnancy duration <20u2005weeks). Controls (N=49) were recruited from low-risk midwife practices. Standardised echocardiography at 20 and 32u2005weeks gestation and 1u2005year postpartum was performed. Results Age and parity were comparable between both groups (p>0.1). Left ventricular ejection fraction (LVEF) <45% was present in 3.2% of women with CHD and 14.4% had tricuspid annular plane systolic excursion (TAPSE) <16u2005mm. Absolute values of ventricular function parameters and diameters were less favourable in women with CHD. No permanent changes occurred in right and left ventricular function parameters and dimensions in women with CHD. The patterns of change in cardiac function and dimensions were comparable between women with CHD and controls, except for LVEF (p=0.026). In women with right-sided CHD the pattern of TAPSE over time differed from controls (p=0.043) (no decrease in TAPSE postpregnancy in CHD). In women with left-sided CHD left ventricular end-diastolic diameter (LVEDD) tended to increase compared with controls (p=0.045). Conclusions Absolute levels of ventricular function parameters and diameters differ between CHD and controls, but changes during and after pregnancy are generally comparable. However, different patterns over time seen for TAPSE and LVEDD in women with right-sided and left-sided CHD, respectively, compared with controls indicate the importance of echocardiographic follow-up during pregnancy in women with CHD.

Intracardiac anatomical relationships and potential for streaming in double inlet left ventricles

The aim of this study was to gain better understanding of the variable anatomical features of double inlet left ventricle hearts without cavopulmonary connection that would potentially facilitate favorable streaming. Thirty-nine post-mortem specimens of double inlet left ventricle without cavopulmonary connection were investigated. The focus was on anatomical characteristics that could influence the flow and separation of deoxygenated and oxygenated blood in the ventricles. Elements of interest were the ventriculoarterial connection, the spatial relationship of the ventricles, the position and size of the great arteries, the ventricular septal defect, the presence of relative outflow tract stenosis and the relationship of the inflow and outflow tracts. The most common anatomy was a discordant ventriculoarterial connection with an anatomically left-sided morphologically right ventricle (n = 12, 31%). When looking at the pulmonary trunk/aorta ratio, 21 (72%) hearts showed no pulmonary stenosis relative to the aorta. The ventricular septal defect created a relative subpulmonary or subaortic stenosis in 13 (41%) cases. Sixteen (41%) hearts had a parallel relationship of the inflow and outflow tracts, facilitating separation of deoxygenated and oxygenated blood streams. On the other end of the spectrum were 10 (25%) hearts with a perpendicular relationship, which might lead to maximum mixing of the blood streams. The relationship of the inflow and outflow tracts as well as the presence of (sub-) pulmonary stenosis might play a crucial role in the distribution of blood in double inlet left ventricle hearts. Additional in vivo studies will be necessary to confirm this postulation.

NT-proBNP and exercise capacity in adult patients with congenital heart disease and a prosthetic valve: a multicentre PROSTAVA study

ObjectivesN-terminal B‑type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and axa0prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with axa0prosthetic valve and investigate its relationship with cardiac function and exercise capacity.MethodsIn this multi-centre cross-sectional observational study, data regarding medical history, echocardiography, exercise testing (VO2peak) and laboratory blood evaluation (including NT-proBNP) were collected in ACHD patients with axa0single prosthetic valve (either homografts, heterografts or mechanical valves).ResultsAxa0total of 306xa0ACHD patients with pulmonary valve replacement (PVR, nxa0= 139), aortic valve replacement (nxa0= 141), mitral valve replacement (nxa0= 21) or tricuspid valve replacement (nxa0= 5) were investigated. The majority of patients (77u2009%) were in NYHA classxa0I orxa0II. Elevated NT-proBNP levels (cut-off ≥125xa0pg/ml) were found in 50u2009% of the patients, with the highest levels in patients with mitral valve replacements. In this study population, NT-proBNP levels were associated with gender (pxa0= 0.029) and VO2max (pxa0< 0.001). In PVR patients, NT-proBNP levels were associated with lower VO2peak, also after adjustment for age, gender and age at valve replacement in axa0multivariate model (pxa0= 0.015).ConclusionsIn patients with ACHD and axa0prosthetic valve, elevated NT-proBNP levels are frequently observed despite preserved NYHA class. In PVR patients, axa0higher NT-proBNP level was associated with axa0lower VO2peak. These results may be of importance in the ongoing discussion about the timing of valve replacement in patients with CHD.

Noninvasive Identification of Ventricular Tachycardia–Related Anatomical Isthmuses in Repaired Tetralogy of Fallot: What Is the Role of the 12-Lead Ventricular Tachycardia Electrocardiogram

OBJECTIVESnThis study sought to evaluate the relation between 12-lead ventricular tachycardia (VT) electrocardiography (ECG) and VT-related anatomical isthmuses (AIs) in repaired tetralogy of Fallot (rTOF).nnnBACKGROUNDnSlow-conducting AIs are the dominant VT substrate in rTOF. Whether an AI is considered critical relies on pace mapping (PM) guided by the VT ECG.nnnMETHODSnVT ECGs, electroanatomical mapping data and PM results were analyzed in 25 rTOF patients (group 1) (agexa057xa0±xa013 years). Selection of PM and ablation sites was guided by VT ECG. In 7 patients (group 2) (age 33 ± 14 years), PM was systematically performed within all AIs, irrespective of the VT ECG.nnnRESULTSnIn group 1, all 35 induced VTs (median VT cycle length 270 [interquartile range: 240 to 310] ms) were AI related. All 11 right bundle branch block (RBBB) VTs were related to AI3 (right ventricular septum if positive concordant [7xa0of 7]), coronary cusp if V2 transition break [3 of 4]). Left bundle branch block (LBBB) VTs with transitionxa0<V5 were mapped to AI3 (8 of 10) or AI2 (2 of 10) and LBBB VTs with transitionxa0≥V5 to AI1 (8 of 14), AI3 (5 of 14), and AI4 (1 of 14). In group 2, all 8 induced VTs (median VT cycle length 240 [interquartile range: 230 to 268] ms) were AI related. All RBBB VTs were related to AI3 (right ventricular septum). For LBBB VTs, paced matches were obtained in AI3 and AI1. Activation mapping and/or ablation success confirmed AI3 to be critical for all 8 VTs.nnnCONCLUSIONSnIn rTOF with only AI1 and AI3, RBBB VTs are due to clockwise and LBBB VTs to counterclockwise activation of AI3. Involvement of both AIs in the VT circuit limits the role of the 12-lead VT ECG and PM. AI3 can always be targeted irrespective of the 12-lead VT ECG.

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

OBJECTIVESnThis study sought to evaluate the influence of slow conducting anatomic isthmuses (SCAI) as dominant ventricular tachycardia (VT) substrate on QRS duration.nnnBACKGROUNDnQRS prolongation has been associated with VT in repaired tetralogy of Fallot.nnnMETHODSnSeventy-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.nnnRESULTSnTwenty-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 (nxa0= 6) and VT- patients (nxa0= 5), but RV activation within SCAI exceeded QRS offset in VT+ patients (37 ± 20 ms vs. -5 ± 9 ms, pxa0< 0.01). In RBBB, both QRS duration and RV activation time were longer in VT+ patients (nxa0= 18, 17 of 18 QRS > 150 ms) compared with VT- patients (nxa0= 49, 27 of 49 QRS > 150 ms) (173xa0± 22 ms vs. 156 ± 20 ms; pxa0< 0.01; 141 ± 22 ms vs. 129xa0± 21 ms; pxa0= 0.04). In VT+ patients, QRS prolongation >150xa0ms (nxa0= 17) was due to SCAI or blocked isthmus in 15 patients (88%) and 1 (6%). In contrast, in VT- patients, QRS prolongation >150 ms (nxa0= 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; pxa0< 0.01).nnnCONCLUSIONSnA narrow QRS interval does not exclude VT-related SCAI. In the presence of RBBB, SCAI further prolongsxa0QRS duration. QRS duration >150 ms is highly suspicious for SCAI or isthmus block distinguishable by electroanatomic mapping.

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

OBJECTIVESnThis study sought to evaluate the influence of slow conducting anatomic isthmuses (SCAI) as dominant ventricular tachycardia (VT) substrate on QRS duration.nnnBACKGROUNDnQRS prolongation has been associated with VT in repaired tetralogy of Fallot.nnnMETHODSnSeventy-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.nnnRESULTSnTwenty-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 (nxa0= 6) and VT- patients (nxa0= 5), but RV activation within SCAI exceeded QRS offset in VT+ patients (37 ± 20 ms vs. -5 ± 9 ms, pxa0< 0.01). In RBBB, both QRS duration and RV activation time were longer in VT+ patients (nxa0= 18, 17 of 18 QRS > 150 ms) compared with VT- patients (nxa0= 49, 27 of 49 QRS > 150 ms) (173xa0± 22 ms vs. 156 ± 20 ms; pxa0< 0.01; 141 ± 22 ms vs. 129xa0± 21 ms; pxa0= 0.04). In VT+ patients, QRS prolongation >150xa0ms (nxa0= 17) was due to SCAI or blocked isthmus in 15 patients (88%) and 1 (6%). In contrast, in VT- patients, QRS prolongation >150 ms (nxa0= 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; pxa0< 0.01).nnnCONCLUSIONSnA narrow QRS interval does not exclude VT-related SCAI. In the presence of RBBB, SCAI further prolongsxa0QRS duration. QRS duration >150 ms is highly suspicious for SCAI or isthmus block distinguishable by electroanatomic mapping.