Dietmar Boethig

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.

Long-term results of simultaneous carotid endarterectomy and myocardial revascularization with cardiopulmonary bypass used for both procedures.

OBJECTIVE Controversy continues about the treatment of patients with a concomitant occlusive disease of the coronary and carotid arteries. Our operative strategy in these patients is to do simultaneous carotid endarterectomy and myocardial revascularization in conjunction with cardiopulmonary bypass with mild hypothermia. We report our experience with this kind of one-stage procedure and its retrospective long-term results. METHODS From February 1985 to September 1998, 340 patients underwent simultaneous carotid endarterectomy and myocardial revascularization. The average age of the patients was 65.3 years; 45.6% were neurologically symptomatic, and 44.4% had bilateral carotid stenosis. The indication for carotid endarterectomy was lumen diameter reduction of more than 75%, angiographic signs of thrombogenic endovascular morphology, or both. Carotid endarterectomy was performed in conjunction with cardiopulmonary bypass with mild hypothermia, hemodilution, systemic heparinization, and controlled hemodynamics under pulsatile perfusion for additional cerebral protection. RESULTS There were 16 perioperative neurologic complications (4.7%), 11 permanent deficits (3.2%), and 9 cardiac complications (2.6%). Early mortality was 2.6% (SE 0.8%): 2 patients had a stroke and 2 had a myocardial infarction. The 5-year survival was 78.9% (SE 2.6%), and freedom from ipsilateral stroke and cardiac event were 93.2% (SE 1.5%) and 87.5% (SE 2.1%), respectively. The predictor for early death was age over 70 years, and predictors for late death were age over 70 years, previous myocardial infarction, previous stroke, and bilateral carotid stenosis of greater than 90%. CONCLUSION On the basis of our long-term results, we believe that simultaneous carotid endarterectomy and myocardial revascularization in conjunction with cardiopulmonary bypass is a method safe enough to prefer its routine use with acceptable low operative risk and satisfactory long-term morbidity.

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.

Whole blood coagulation measured by modified thrombelastography (ROTEM) is impaired in infants with congenital heart diseases

Patients with congenital heart disease (CHD) often do have a variety of coagulation abnormalities that results in bleeding diathesis. Our study aimed to determine the impact of cyanosis and CHD on modified thrombelastography parameters, compared with children without CHD. Preoperative blood samples were taken for TEM analyses from a total of 51 infants scheduled for surgery. The following groups were examined: normal patients without CHD, acyanotic patients with acyanotic CHD, and cyanotic patients with CHD and with preoperative hemoglobin values higher than 15 g dl−1. Mean values of all patient groups as well as all individual values of normal patients were within their normal ranges. Within these limits, however, clots were significantly inferior in cyanotic patients (worse mean values of eight out of 10 measured TEM parameters representing the intrinsic, extrinsic, and plasmatic pathways of coagulation) and in acyanotic patients (two out of 10 TEM parameters). Individually, pathological TEM parameters were found in seven (41%) cyanotic patients (P = 0.003; vs. normal patients) and in three (17%) acyanotic patients (P = 0.01). More than one abnormal TEM coagulation parameter was found in four patients, all of them cyanotic patients. Hyperfibrinolysis was detected in one patient, a cyanotic patient. The present investigation confirms previous findings that in patients with CHD the heart defect itself compromises coagulation monitored with TEM, but in addition, we demonstrate that cyanosis and/or polycythemia exert the essential negative impact on hemostasis. Preoperative hyperfibrinolysis detected with TEM seems to play no important role.

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.

Reference values for atrial size and function in children and young adults by cardiac MR: a study of the German competence network congenital heart defects.

To provide reference data for atrial size and function during childhood and adolescence by cardiac MR (CMR).

Long-term morbidity and quality of life after surgical repair of transposition of the great arteries: atrial versus arterial switch operation

Since a growing number of patients after surgical repair of transposition of the great arteries (TGA) survive until adulthood the focus of attention has shifted to the management of associated long-term morbidity and quality of life (QoL). Therefore, we reviewed all patients that underwent surgical repair of TGA at our institution and compared long-term results after atrial and arterial switch operation. Between 1973 and 2000, a total of 302 patients underwent either atrial switch operation (n=222) or arterial switch operation (n=80). Mean follow-up was 14.5±10.1 years. The arterial switch repair was associated with a higher early mortality whereas long-term survival was comparable between both groups. Postoperative arrhythmias including loss of sinus rhythm and pacemaker implantation occurred significantly more often after atrial switch repair. There was a trend towards a more favourable outcome of the arterial switch group concerning freedom from re-interventions, severe systemic ventricular dysfunction and need for heart failure medication. However, also the arterial switch operation was associated with an increased incidence of loss of sinus rhythm and neo-aortic valve regurgitation during late follow-up. Health related QoL according to the SF-36 questionnaire was not significantly different between both groups and comparable to a healthy population.

Preemptive treatment with therapeutic plasma exchange and rituximab for early donor-specific antibodies after lung transplantation.

OBJECTIVE De novo donor-specific anti-human leukocyte antigen antibodies develop in a high proportion of lung transplant recipients early after lung transplantation. We recently showed that de novo donor-specific antibodies (DSA) occurrence is associated with significantly increased mortality. Here, we studied the efficacy of a preemptive treatment protocol. METHODS A retrospective observational study was conducted on all lung transplantations at Hanover Medical School between January 2009 and May 2013. RESULTS Among the 500 transplant recipients, early DSA developed in 86 (17%). Of these, 56 patients (65%; Group A) received therapeutic plasma exchange, and 30 patients (35%; Group B) did not. Among Group A patients, 51 also received rituximab. Between groups, there was no statistically significant difference in mortality, incidence of pulsed steroid therapies, rejections diagnosed by biopsy specimen, incidence of bronchitis obliterans syndrome (BOS), or infections requiring hospitalization at 1 year and 3 years. Also, there were no statistically significant differences after matching 21 Group A with 21 Group B patients through propensity score analysis. Significantly more Group A patients (65%) than Group B patients (34%) cleared DSA at hospital discharge (p = 0.01). At the last control after transplantation (median, 14 months; interquartile range, 5-24 months), 11 Group A (22%) and 9 Group B patients (33%) still showed DSA (p = 0.28). CONCLUSIONS Preemptive treatment with therapeutic plasma exchange and rituximab led to improved elimination of DSA early after lung transplantation (p = 0.01). However, spontaneous elimination in untreated Group B patients also occurred frequently. This treatment protocol was not associated with significantly improved outcome.

Optimized preoperative fasting times decrease ketone body concentration and stabilize mean arterial blood pressure during induction of anesthesia in children younger than 36 months: a prospective observational cohort study

In pediatric anesthesia, preoperative fasting guidelines are still often exceeded.