Samir Sarikouch

Use of Fresh Decellularized Allografts for Pulmonary Valve Replacement May Reduce the Reoperation Rate in Children and Young Adults Early Report

Background— Degeneration of xenografts or homografts is a major cause for reoperation in young patients after pulmonary valve replacement. We present the early results of fresh decellularized pulmonary homografts (DPH) implantation compared with glutaraldehyde-fixed bovine jugular vein (BJV) and cryopreserved homografts (CH). Methods and Results— Thirty-eight patients with DPH in pulmonary position were consecutively evaluated during the follow-up (up to 5 years) including medical examination, echocardiography, and MRI. These patients were matched according to age and pathology and compared with BJV (n=38) and CH (n=38) recipients. In contrast to BJV and CH groups, echocardiography revealed no increase of transvalvular gradient, cusp thickening, or aneurysmatic dilatation in DPH patients. Over time, DPH valve annulus diameters converge toward normal z-values. Five-year freedom from explantation was 100% for DPH and 86±8% and 88±7% for BJV and CH conduits, respectively. Additionally, MRI investigations in 17 DPH patients with follow-up time >2 years were compared with MRI data of 20 BJV recipients. Both patient groups (DPH and BJV) were at comparable ages (mean, 12.7±6.1 versus 13.0±3.0 years) and have comparable follow-up time (3.7±1.0 versus 2.7±0.9 years). In DPH patients, the mean transvalvular gradient was significantly (P=0.001) lower (11 mm Hg) compared with the BJV group (23.2 mm Hg). Regurgitation fraction was 14±3% and 4±5% in DPH and BJV groups, respectively. In 3 DPH recipients, moderate regurgitation was documented after surgery and remained unchanged in follow-up. Conclusions— In contrast to conventional homografts and xenografts, decellularized fresh allograft valves showed improved freedom from explantation, provided low gradients in follow-up, and exhibited adaptive growth.

Sex-Specific Pediatric Percentiles for Ventricular Size and Mass as Reference Values for Cardiac MRI Assessment by Steady-State Free-Precession and Phase-Contrast MRI Flow

Background— Cardiac MRI is important in the treatment of children with congenital heart disease, but sufficient normative data are lacking. For ventricular volumes and mass, we sought to deliver reference centiles and to investigate sex effects. Methods and Results— We included 114 healthy children and adolescents, uniformly distributed spanning an age range of 4 to 20 years, as required by the Lambda-Mu-Sigma method to achieve a percentile distribution, thus avoiding arbitrary age categories. Subjects underwent axial volumetry (1.5-T scanner) using standardized 2D steady-state free-precession and flow protocols. Percentiles were computed for age 8 to 20 years (99 subjects) because breath-holds were more consistent in this group. When indexed for body surface area or height, the centile curves of ventricular volumetric parameters showed allometric increase until adolescence, when a plateau was reached, with values comparable to published adult reference data. In contrast, ventricular mass centiles increased without plateau. There was a significant sex difference, with centiles reflecting larger values in boys than in girls ( P <0.05) when ventricular volumes were indexed to body surface area or height but not when indexed to weight (exception: mass). There was excellent agreement of axial and short-axis volumetry and of volumetric and flow-derived stroke volumes. Conclusions— Percentiles for ventricular volumes and mass in healthy children have been established to serve as reference values in pediatric heart disease. Significant sex differences were noted when indexing volumes to body surface area or height. Unisex centiles related to weight may be considered for chamber volumes albeit not for mass. Received February 19, 2009; accepted October 1, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Cardiac MRI is important in the treatment of children with congenital heart disease, but sufficient normative data are lacking. For ventricular volumes and mass, we sought to deliver reference centiles and to investigate sex effects. Methods and Results—We included 114 healthy children and adolescents, uniformly distributed spanning an age range of 4 to 20 years, as required by the Lambda-Mu-Sigma method to achieve a percentile distribution, thus avoiding arbitrary age categories. Subjects underwent axial volumetry (1.5-T scanner) using standardized 2D steady-state free-precession and flow protocols. Percentiles were computed for age 8 to 20 years (99 subjects) because breath-holds were more consistent in this group. When indexed for body surface area or height, the centile curves of ventricular volumetric parameters showed allometric increase until adolescence, when a plateau was reached, with values comparable to published adult reference data. In contrast, ventricular mass centiles increased without plateau. There was a significant sex difference, with centiles reflecting larger values in boys than in girls (P<0.05) when ventricular volumes were indexed to body surface area or height but not when indexed to weight (exception: mass). There was excellent agreement of axial and short-axis volumetry and of volumetric and flow-derived stroke volumes. Conclusions—Percentiles for ventricular volumes and mass in healthy children have been established to serve as reference values in pediatric heart disease. Significant sex differences were noted when indexing volumes to body surface area or height. Unisex centiles related to weight may be considered for chamber volumes albeit not for mass.

Cardiac function by MRI in congenital heart disease: Impact of consensus training on interinstitutional variance

To investigate the impact of interinstitutional variance (=interobserver variance between institutions) for volumetric and flow cardiac MR (CMR) data and if training on image reading could improve bias.

Functional analysis of the components of the right ventricle in the setting of tetralogy of Fallot.

Background—Anatomic and functional observations suggest that the right ventricle (RV) can be analyzed in terms of its inlet, apical trabecular, and outlet components. Our study was designed to evaluate the regional adaptation of these components to different conditions of loading, with additional analysis of the surgical techniques used for primary repair. Methods and Results—We studied prospectively 45 patients with tetralogy of Fallot (age, 20.5±8.1 years) and 24 control subjects (age, 20.1±5.8 years). All subjects were studied by using cardiac MRI. End-diastolic (EDV), end-systolic (ESV), stroke volumes (SV), and ejection fraction (EF) were determined for the overall RV and separately for its inlet, apical trabecular, and outlet components. The patients had pulmonary regurgitant fractions of 33.2±11.1%, and RV peak-systolic pressures of 40.7±16.1 mm Hg. In controls, the apical trabecular component EDV was 51.5±11.1 mL/m2 (54.3±6.8% of the total RV EDV), ESV was 19.2±6.3 mL/m2 (47.6±10.5% of RV ESV), and SV was 32.3±6.9 mL/m2 (58.9±6.6% of RV SV), resulting in an EF of 63.1±7.7%. When considering all patients, the apical trabecular component took up the greatest part of the overload, having an EDV of 76.5±18.1 mL/m2, and an ESV of 31.6±12.8 mL/m2, reflecting an increase of 49 and 67% over controls, respectively (P<0.001). EF was 59.7±10.7%, and was maintained at control levels (P=0.132). In controls, the outlet had considerable ejecting force, with an EF of 54.8±9.1%, whereas it was decreased in the patients with tetralogy (EF=28.5±11.9%). There was significant increase of ESV (P<0.001), but not of EDV, with EF decreased by 45% (P<0.001). The inlet was not significantly affected by overload. The surgical technique did not significantly affect any measured parameter for any component. Conclusions—In patients with tetralogy of Fallot, subsequent to surgical correction, the individual components of the RV respond in characteristic fashion to RV overload.

Long-term results after aortic valve-sparing operation (David I)

OBJECTIVE Aortic valve-sparing David procedure has gained broad acceptance. However, few long-term results have been published. We present our results. METHODS More than 450 David procedures have been performed in our institution so far. Of these, 126 patients were operated between July 1993 and December 2000. Median age was 57 (8-83) years and 46 (36.5%) were female. As many as 26 (20.6%) had Marfan syndrome, 21 (16.7%) had acute aortic dissection type A (AADA) and 67 (53.2%) had additional procedures. RESULTS There were six (4.8%) deaths in 30 post-operative period (POD), four of whom had AADA. In the follow-up, there were 32 (25.4%) late deaths, 11 (34.4%) of these were caused by cardiac or underlying disease or op-related. As many as 15 (11.9%) patients were re-operated; six (40%) were Marfan patients and two (13.3%) had early endocarditis. Follow-up echocardiography of 76 (60.3%) event-free patients showed valve insufficiency (AI)≤AI I° in 68 (89.5%) and grade II in 7 (9.2%) patients. Leaflet degeneration due to proposed leaflet contact with the straight Dacron graft was not observed. A total of 36 (47.4%) patients were in New York Heart Association (NYHA) class I, 33 (43.4%) in NYHA II, and five (6.6%) were in class III. During the entire follow-up of 790 patient-years, there was no stroke or major bleeding. Survival at 1, 5 and 10 years was 93%, 85% and 70%, respectively. Freedom from valve replacement at 1, 5 and 10 years was 96%, 91% and 87%, respectively. CONCLUSIONS Regardless of the underlying pathology, valve-sparing David I procedure has acceptable long-term results. Valve-related complications such as stroke or major bleeding is exceedingly low.

Impact of Gender and Age on Cardiovascular Function Late After Repair of Tetralogy of Fallot Percentiles Based on Cardiac Magnetic Resonance

Background— The impact of gender and age on cardiac function by cardiac magnetic resonance (CMR) in repaired tetralogy of Fallot (TOF) is unknown, which limits the value of currently discussed volumetric thresholds and the accuracy of individual follow-up. Methods and Results— In a nationwide, prospective, 14-center study, 407 consecutive patients with repaired TOF (age, 17.9±8.3 years; range, 8–59 years; 226 male patients) underwent standardized CMR ventricular volumetry and flow quantification (pulmonary artery/ascending aorta). There were no sex differences for age at TOF repair, type of repair, number of prior repair palliations or reinterventions after repair, pulmonary regurgitation fraction, and maximal gradient across the right ventricular outflow tract. Biventricular volumes and mass (indexed to body surface area), available in 380 of 407 patients, respectively, were higher in male patients (P<0.003), but biventricular ejection fraction was higher in female patients (P<0.012). As opposed to reported data of healthy populations, sex-specific reference percentiles computed for an age range of 8 to 40 years (lambda-mu-sigma method) demonstrated (1) an increase of end-diastolic and end-systolic left ventricular volumes, particularly in female patients; (2) an increase of end-systolic right ventricular volumes in both sexes; and (3) a decrease of biventricular ejection fraction in male patients, whereas in female patients, only right ventricular ejection fraction decreased. Conclusions— Significant gender differences of biventricular volumes, function, and mass by CMR exist late after repair of TOF, suggesting that age and gender cannot be ignored when discussing thresholds. Gender-specific percentiles may present a more relevant framework of reference for an individual patient at a given age and suggest a gradual decline of biventricular systolic function over time. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00266188.

Myocardial deformation parameters predict outcome in patients with repaired tetralogy of Fallot

Background Parameters of myocardial deformation have been suggested to be superior to conventional measures of ventricular function and to predict outcome in repaired tetralogy of Fallot (ToF). We aimed to test the hypothesis that parameters of myocardial deformation on cardiac MRI (CMR) relate to symptoms and provide prognostic information in patients with repaired ToF. Methods and results We included 372 patients with ToF (median age 16 years; 55% male), recruited within a nationwide, prospective study. Longitudinal (LS), circumferential (CS) and radial global strain (RS) were analysed by CMR-based feature tracking (FT). A combined endpoint of death, successful resuscitation or documented ventricular tachycardia was employed. Parameters of global strain were associated with New York Heart Association (NYHA) class and symptomatic deterioration. During a median follow-up of 7.4 years, 20 events occurred. Left ventricular (LV) CS and right ventricular (RV) LS emerged as predictors of outcome, independent of QRS duration, LV/RV ejection fraction and volumes, NYHA class and peak oxygen uptake. In combination, these parameters also identified a subgroup of patients at significantly increased risk of adverse of outcomes (HR 3.3, p=0.002). Furthermore, LV LS, RS, CS and RV LS were related to the risk of death and nearly missed death (p<0.05 for all). Conclusions FT-CMR provides myocardial deformation parameters, easily derived from standard CMR studies. They relate to symptoms and clinical deterioration in patients with ToF. More importantly, they predict adverse outcome independent of established risk markers, and should be considered as a useful adjunct to established outcome predictors, especially in younger patients with ToF. Clinical trial registration number http://www.clinicaltrials.gov: NCT00266188; Results.

Integrated analysis of atrioventricular interactions in tetralogy of Fallot

The atria play an important role in cardiac performance. We evaluated their function and the atrioventricular interaction in operated patients with tetralogy of Fallot (TOF). Twenty patients who had undergone surgical repair of TOF and seven controls were investigated. Patients had residual pulmonary but no major tricuspid valve insufficiency. Atrial and ventricular strain rates were obtained by echocardiographic speckle tracking. Cine MRI-derived volumetric analysis provided atrial and ventricular time volume and time volume change curves yielding emptying and filling parameters. In addition, at the atrial level, reservoir, conduit and pump function, and cyclic volume change were calculated. At the atrioventricular valve level, tricuspid and mitral annular plane systolic excursion (TAPSE and MAPSE, respectively) were measured by two-dimensional echocardiography. In the patients compared with controls, right ventricular end-diastolic volumes were increased and biventricular ejection fraction was decreased (all P < 0.05). Biventricular measures of early diastolic ventricular filling were at control levels, but in late diastole, right ventricular filling parameters and strain rates were decreased (P < 0.001). The maximal right atrial size was slightly but not significantly diminished, but cyclic volume change was significantly reduced (P < 0.0001). Pump and reservoir function were decreased (P < 0.05), and conduit function was elevated (P < 0.001). The left atrium showed reduced reservoir function and cyclic volume change (P < 0.05). TAPSE and MAPSE were also decreased (P < 0.05). There were statistically significant interdependencies between RV ejection fraction, TAPSE, and right atrial filling and emptying parameters (all P < 0.05). In TOF patients, moderate systolic and diastolic right ventricular dysfunction is associated with clearly impaired right atrial function. The left atrium is affected to a lesser extent.

Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience

OBJECTIVES Decellularized homografts have shown auspicious early results when used for pulmonary valve replacement (PVR) in congenital heart disease. The first clinical application in children was performed in 2002, initially using pre-seeding with endogenous progenitor cells. Since 2005, only non-seeded, fresh decellularized allografts have been implanted after spontaneous recellularization was observed by several groups. METHODS A matched comparison of decellularized fresh pulmonary homografts (DPHs) implanted for PVR with cryopreserved pulmonary homografts (CHs) and bovine jugular vein conduits (BJVs) was conducted. Patients’ age at implantation, the type of congenital malformation, number of previous cardiac operations and number of previous PVRs were considered for matching purposes, using an updated contemporary registry of right ventricular outflow tract conduits (2300 included conduits, >12 000 patient-years). RESULTS A total of 131 DPHs were implanted for PVR in the period from January 2005 to September 2015. Of the 131, 38 were implanted within prospective trials on DPH from October 2014 onwards and were therefore not analysed within this study. A total of 93 DPH patients (58 males, 35 females) formed the study cohort and were matched to 93 CH and 93 BJV patients. The mean age at DPH implantation was 15.8 ± 10.21 years (CH 15.9 ± 10.4, BJV 15.6 ± 9.9) and the mean DPH diameter was 23.9 mm (CH 23.3 ± 3.6, BJV 19.9 ± 2.9). There was 100% follow-up for DPH, including 905 examinations with a mean follow-up of 4.59 ± 2.76 years (CH 7.4 ± 5.8, BJV 6.4 ± 3.8), amounting to 427.27 patient-years in total (CH 678.3, BJV 553.0). Tetralogy-of-Fallot was the most frequent malformation (DPH 50.5%, CH 54.8%, BJV 68.8%). At 10 years, the rate of freedom of explantation was 100% for DPH, 84.2% for CH (P = 0.01) and 84.3% for BJV (P= 0.01); the rate of freedom from explantation and peak trans-conduit gradient ≥50 mmHg was 86% for DPH, 64% for CH (n.s.) and 49% for BJV (P < 0.001); the rate of freedom from infective endocarditis (IE) was 100% for DPH, 97.3 ± 1.9% within the matched CH patients (P = 0.2) and 94.3 ± 2.8% for BJV patients (P = 0.06). DPH valve annulus diameters converged towards normal Z-values throughout the observation period, in contrast to other valve prostheses (BJV). CONCLUSIONS Mid-term results of DPH for PVR confirm earlier results of reduced re-operation rates compared with CH and BJV.

Assessment of interventricular and right- intraventricular dyssynchrony in patients with surgically repaired tetralogy of Fallot by two-dimensional speckle tracking

AIMS We aimed to assess interventricular and right-intraventricular dyssynchrony in patients after tetralogy of Fallot (TOF) repair by two-dimensional (2D) speckle tracking and to identify factors associated with dyssynchrony. METHODS AND RESULTS Forty-two patients after TOF repair with a mean age of 19.8 years and 42 age-matched healthy controls were studied. Longitudinal myocardial deformation (strain) and time-to-peak intervals were assessed by 2D speckle tracking and tissue Doppler imaging (TDI) in an apical four-chamber view. Dyssynchrony was defined as delay above 3 standard deviations of mean values in the control group. Magnetic resonance imaging (MRI) was performed for evaluation of ventricular function. Using 2D speckle tracking, 22 patients (52%) showed interventricular dyssynchrony and 16 (38%) had right-intraventricular dyssynchrony. The interventricular delay correlated significantly with right ventricular (RV) strain (r = 0.687, P < 0.001), RV systolic pressure (r = 0.535, P = 0.001), QRS duration (r = 0.466, P = 0.002), RV end-diastolic (r = 0.377, P = 0.018), and RV end-systolic volumes (r = 0.452, P = 0.004) as well as RV ejection fraction (r = -0.378, P = 0.018). Similarly, the right-intraventricular delay correlated significantly with RV strain (r = 0.534, P < 0.001), QRS duration (r = 0.428, P = 0.005), RV end-systolic volume (r = 0.34, P = 0.038), and RV systolic pressure (r = 0.413, P = 0.015). In multivariate regression analysis, reduced RV strain and prolonged QRS duration remained the main determinant factors predicting dyssynchrony. Moreover, 2D speckle tracking and TDI showed a significant correlation in the assessment of the interventricular (r = 0.738, P < 0.001) and right-intraventricular delay (r = 0.747, P < 0.001). CONCLUSION Interventricular and right-intraventricular dyssynchrony are detectable in patients after TOF repair by 2D speckle tracking. Reduced RV myocardial deformation and QRS prolongation are the main factors associated with the observed dyssynchrony.