David R. Koolbergen

Tissue chimerism in human cryopreserved homograft valve explants demonstrated by in situ hybridization

BACKGROUND The presence of viable cells may contribute to increased homograft valve durability. These cells may be of infiltrating recipient or persisting donor origin. In this study, in situ hybridization was used to assess the origin of cells in cryopreserved homograft valve explants. METHODS A total of 10 homografts with a donor-recipient gender mismatch were acquired from patients whose graft had been explanted at reoperation or at autopsy. The period of implantation varied from 14 days to 70 months. Frozen sections were made and alternately examined with hematoxylin and eosin staining and in situ hybridization. Male cells were distinguished from female using a biotinylated Y-chromosome-specific deoxyribonucleic acid probe. RESULTS No endothelial cells were found. Thirty percent of the leaflets showed large acellular zones and 30% were completely acellular. The homograft arterial wall was occupied by a vast majority of penetrating host fibroblasts in 80% of the studied specimens. Donor and recipient cells were coexistent in the wall in 60% of the studied specimens and in 50% of the leaflets. In 30% only host cells could be identified. CONCLUSIONS This finding of tissue chimerism may lead to new insights in homograft pathology. The technique of in situ hybridization may provide an indispensable contribution in further homograft research.

Postoperative arrhythmias in adults with congenital heart disease: Incidence and risk factors

BACKGROUND Little is known about the clinical impact of arrhythmias after surgery for congenital heart disease (CHD) in adults. Therefore, we investigated the prevalence of in-hospital arrhythmias after CHD surgery and their impact on clinical outcome. METHODS This was a multicenter retrospective study and included adults who underwent congenital cardiac surgery between January 2009 and December 2011. Clinical events were defined as all cause mortality, heart failure (HF) requiring medical treatment, thrombo-embolic event, major infections and permanent pacemaker (PM) implantation. RESULTS Overall, 419 patients were included (mean age 38 ± 14 years, 55% male). Arrhythmias occurred in 134 patients (32%) and included supraventricular tachycardia (SVT, n = 100), bradycardias (n = 47) and ventricular tachycardia (VT, n = 19). In multivariate analysis age ≥40 years at surgery (OR 2.48, 95% Cl 1.40-4.60, P = 0.003), NYHA class ≥ II (OR 2.42, 95% Cl 1.18-4.67, P = 0.009), significant subpulmonary AV-valve regurgitation (OR 2.84, 95% Cl 1.19-6.72, P = 0.018), coronary bypass time (OR 1.35/60 minute increase, 95% Cl 1.06-1.82, P = 0.019) and CK-MB (OR 1.05 per 10 U/L increase, 95% Cl 1.01-1.09, P = 0.021) were associated with in-hospital arrhythmias. Overall, 58 clinical events occurred in 55 patients (13%) and included in the majority of the cases permanent PM implantation (5%), HF (4%) and death (2%). In-hospital arrhythmias were independently associated with clinical events (OR 7.80, 95% CI 2.41-25.54, P = 0.001). CONCLUSION Arrhythmias are highly prevalent after congenital heart surgery in adults and are associated with worse clinical outcome. Older and symptomatic patients with significant valvular heart disease at baseline are at risk of in-hospital arrhythmias.

In situ hybridization: A new technique to determine the origin of fibroblasts in cryopreserved aortic homograft valve explants

Tissue degeneration reduces the durability of cryopreserved homografts. Earlier studies indicated that the presence of fibroblasts in homograft leaflets may contribute to increased valve longevity. These fibroblasts may be of recipient origin or represent surviving donor cells. We developed a method, based on in situ hybridization, to determine the origin of fibroblasts in homograft explants. In young pigs we performed aortic valve replacement with a cryopreserved porcine aortic homograft. A male homograft was implanted in a female pig, whereas two male recipients received a female homograft. After 3 to 4 months the homografts were explanted. Frozen sections were made and alternately examined with hematoxylin-eosin staining and in situ hybridization. With a biotinylated porcine Y chromosome-specific deoxyribonucleic acid probe, male fibroblasts could be clearly distinguished from female fibroblasts. In all leaflets we observed both donor and recipient fibroblasts. The distribution of these populations was marked in schematic drawings. Recipient fibroblasts mostly spread onto the leaflet surface but also penetrated the leaflet tissue. Remaining donor fibroblasts did not show morphologic signs of decreased viability on hematoxylin-eosin staining. In situ hybridization may become a useful technique in homograft research. In this porcine model, the fibroblasts in the aortic homograft explants were of both donor and recipient origin.

Pediatric tracheal reconstruction with pericardial patch and strips of autologous cartilage

OBJECTIVE To analyze the results of pediatric tracheal reconstruction with autologous pericardial patch and strips of cartilage. METHODS From September 2003 to February 2008 14 non-consecutive children were operated using pericardial patch augmentation of the trachea combined with external reinforcement with strips of autologous cartilage. Thin semicircular strips were fashioned from costal arch cartilage. Associated vascular rings, slings and aberrantly coursing arteries were treated first. Cardiopulmonary bypass was used in all. Intraoperative tracheobronchoscopy was done in all. Postoperative bronchoscopies were performed at different time points. A retrospective analysis of patient records, surgical reports, tracheobronchoscopies, echocardiographic studies and CT scans was performed. Pre- and postoperative trachea cross-sectional areas were digitally measured and compared to cricoid cross-sectional areas in six patients. A paired t-test was used to make comparisons. RESULTS Median age at operation was 21.3 (range 2.5-85) months. Ten patients were female. Four had associated surgery for cardiac anomalies. Double aortic arch (8), pulmonary artery sling (2), and aberrant origin of brachiocephalic artery (1) were concomitantly treated. Two patients had pulmonary agenesis. One patient had stenosis due to systemic inflammatory disease. Median follow-up was 27 (1-53) months. Late mortality occurred in one patient with pulmonary agenesis. One patient was reoperated and two bronchoscopies were done to remove granulation tissue. Median postoperative ventilation time was 5.5 (3-12) days with the exception of patients with pulmonary agenesis. Mean preoperative cross-sectional area was 29.4 +/- 22.5% of the lumen at cricoid level. At last bronchoscopy this had increased to 65.0 +/- 12.5% (p = 0.0001). To evaluate the stability of the reconstructed trachea, we compared the mean luminal areas at inspiration and expiration. No difference was observed (p = 0.13). One patient remains with mild stridor at exercise; all others have no respiratory symptoms. CONCLUSION A stable wide trachea can be obtained in the great majority of cases, including whole length tracheal obstructions with complete circular rings. The technique is safe and reproducible with short intensive care stay and good mid-term results. Growth of the reconstructed trachea appears to be unrestricted.

Does the Use of a Decision Aid Improve Decision Making in Prosthetic Heart Valve Selection?: A Multicenter Randomized Trial

Background— A Dutch online patient decision aid to support prosthetic heart valve selection was recently developed. A multicenter randomized controlled trial was conducted to assess whether use of the patient decision aid results in optimization of shared decision making in prosthetic heart valve selection. Methods and Results— In a 5-center randomized controlled trial, patients were allocated to receive either standard preoperative care (control group) or additional access to the patient decision aid (intervention group). Legally capable adult patients accepted for elective isolated or combined aortic and mitral valve replacement were included. Primary outcome was preoperative decisional conflict (Decisional Conflict Scale); secondary outcomes included patient knowledge, involvement in valve selection, anxiety and depression, (valve-specific) quality of life, and regret. Out of 306 eligible patients, 155 were randomized (78 control and 77 intervention). Preoperative decisional conflict did not differ between the groups (34% versus 33%; P=0.834). Intervention patients felt better informed (median Decisional Conflict Scale informed subscore: 8 versus 17; P=0.046) and had a better knowledge of prosthetic valves (85% versus 68%; P=0.004). Intervention patients experienced less anxiety and depression (median Hospital Anxiety and Depression Scale score: 6 versus 9; P=0.015) and better mental well-being (mean Short Form Health Survey score: 54 versus 50; P=0.032). Three months postoperatively, valve-specific quality of life and regret did not differ between the groups. Conclusions— A patient decision aid to support shared decision making in prosthetic heart valve selection does not lower decisional conflict. It does result in more knowledgeable, better informed, and less anxious and depressed patients, with a better mental well-being. Clinical Trial Registration— http://www.trialregister.nl. Unique identifier: NTR4350.

Weighing the risks: Thrombotic and bleeding events in adults with atrial arrhythmias and congenital heart disease

INTRODUCTION Atrial arrhythmias are associated to thromboembolism and anticoagulant treatment is installed according to risk profile. This study aimed to assess the rate of thrombotic events and major bleedings in adults with congenital heart disease (CHD) and atrial arrhythmias, as well as to determine the predictive value of specific clinical features and two risk scores for thromboembolism and bleeding. METHODS AND RESULTS In this retrospective study, a total of 229 adult CHD patients with atrial arrhythmias, were included. Incidence and risk factors of thromboembolism were assessed in patients without a mechanical valve (n = 191), whereas bleeding incidence and risk factors were studied in patients receiving vitamin K antagonists (n = 164). In 13 patients without a mechanical valve thrombotic events occurred, the first thrombotic event rate per year being 1.4%. A total of 29 patients on vitamin K antagonists suffered from major bleedings, at an annual first event rate of 4.4%. CHA2DS2-VASc score and HAS-BLED score predicted thromboembolic and bleeding risk best in a dichotomized form. At a cut-off of ≥ 2 for high risk the rate of thrombotic events was 3.0% per year compared to 0.7% for a score of <2 (HR 3.7; 95%-CI 1.2-11.5; p = 0.021). A major bleeding rate of 10.8% per year was found in patients on vitamin K antagonists for HAS-BLED ≥ 2 as opposed to 3.5% with a score of <2 (HR 2.6; 95%-CI: 1.1-6.6; 0.017). CONCLUSION In adult CHD patients, thrombotic events and major bleedings are important complications of atrial arrhythmias and anticoagulant treatment. Assessment of thromboembolic and bleeding risk in this patients group can be performed with dichotomized CHA2DS2-VASc and HAS-BLED scores respectively.

Reoperation for neoaortic root pathology after the arterial switch operation

OBJECTIVES To evaluate incidence and results of surgical intervention for neoaortic root pathology following arterial switch operation (ASO) for transposition of the great arteries (TGA). METHODS Between April 1996 and August 2013, 12 patients underwent reoperation for neoaortic root dilatation (ARD) and/or neoaortic valve regurgitation (AR). Maximal aortic sinus and annulus diameter Z-scores were recorded. Original diagnoses were TGA/IVS (6), TGA/ventricular septal defect (VSD) (4) and Taussig-Bing anomaly (2) with ASO at a median age of 0.1 (range: 0-10.6) years. Age at ASO, VSD and complex TGA were reviewed as possible risk factors for reoperation. RESULTS Twelve patients with tricuspid neoaortic valves underwent 15 root operations; indications were root dilatation (4) and root dilatation with AR (8). Median age was 18.0 (3.0-29.0) years at first reoperation. Median aortic root Z-score at reoperation was 6.33 (range: 3.84-12.15). Procedures were: Bentall procedure (6), aortic valve replacement (2), neoaortic valve plasty (1), supracoronary tube (1) and switch-back operation (2). Mean follow-up was 7.0 ± 5.7 years and complete. No mortality occurred. One patient had two reoperations for late endocarditis. Technical difficulties were encountered related to specific anatomy post-ASO concerning coronary anatomy, poor exposure and thin-walled aorta at the site of pulmonary artery bifurcation after Lecompte manoeuvre. Valve sparing surgery seemed not feasible due to specific anatomy of the neoaortic root and valve. No risk factors for reoperation could be identified. CONCLUSIONS After ASO, surgery for neoaortic root pathology may become necessary when follow-up is long enough and regardless of primary diagnosis or other risk factors. Redo neoaortic surgery can be performed with low risk taking into account the specific technical difficulties.

Follow-up after tricuspid valve surgery in adult patients with systemic right ventricles

OBJECTIVES In patients with congenitally corrected transposition of the great arteries (ccTGA) or after atrial (Mustard or Senning) correction for transposition of the great arteries (acTGA), the right ventricle (RV) supports the systemic circulation. The tricuspid valve (TV) (systemic atrioventricular valve) is prone to regurgitation in these patients and this is associated with impending RV failure and decreased survival. This study evaluates mid-term functional improvements, echocardiographic findings and survival after TV surgery in this patient group. METHODS From July 1999 to November 2014, 26 patients (mean age 37.1 ± 12.3 years, 14 females) with ccTGA (n = 15) or acTGA (n = 11) had TV surgery. All patients had RV dysfunction and more-than-moderate TV regurgitation (TR); 14 underwent TV replacement (TVR) and 12 had valvuloplasty (TVP). Main outcomes were New York Heart Association (NYHA) functional class, TR and RV dysfunction at 1 year postoperatively and at latest follow-up. Complications and freedom from the composite end-point of death or recurrent TR were analysed. RESULTS The median follow-up time was 5.9 years (range, 0-16.1 years). Mean NYHA functional class significantly improved to 1.7 [95% confidence interval (CI): 1.3-2.1] at 1 year (P= 0.004) and was 2.1 (95% CI: 1.7-2.6) at latest follow-up (P= 0.14). TV competence significantly improved to a mean TR grade of 1.1 (95% CI: 0.5-1.7) at latest follow-up (P< 0.001). The mean grade for RV function at latest follow-up was 2.7 (95% CI: 2.3-3.0). Most encountered postoperative complications were arrhythmias and temporary haemodynamic instability due to low cardiac output. Early mortality was 11.5% (n = 3); late mortality was 15.4% (n = 4). Estimated freedom from the composite end-point of death or recurrent TR was 76.9% (95% CI: 55.7-88.9%) at 1 year and 64.8% (95% CI: 43.2-79.9%) at 5 years. In TVP patients, TV function at 1 year and at latest follow-up was significantly worse than in TVR patients (P< 0.001 and P= 0.003, respectively). Also, TVP patients had a significantly lower composite end-point survival curve compared with TVR patients (P= 0.018). CONCLUSIONS In this patient group, TV surgery showed stabilization of RV function and improvement of NYHA functional class for at least several years. In this series, TVR appears superior to TVP with respect to occurrence of recurrent TR. Early and late mortality after TV surgery is substantial, and we believe that patients with significant TR should be referred earlier for surgery for better outcome.

Valve-sparing aortic root replacement †

OBJECTIVES To evaluate our results of valve-sparing aortic root replacement and associated (multiple) valve repair. METHODS From September 2003 to September 2013, 97 patients had valve-sparing aortic root replacement procedures. Patient records and preoperative, postoperative and recent echocardiograms were reviewed. Median age was 40.3 (range: 13.4-68.6) years and 67 (69.1%) were male. Seven (7.2%) patients were younger than 18 years, the youngest being 13.4 years. Fifty-four (55.7%) had Marfan syndrome, 2 (2.1%) other fibrous tissue diseases, 15 (15.5%) bicuspid aortic valve and 3 (3.1%) had earlier Fallot repair. The reimplantation technique was used in all, with a straight vascular prosthesis in 11 (26-34 mm) and the Valsalva prosthesis in 86 (26-32 mm). Concomitant aortic valve repair was performed in 43 (44.3%), mitral valve repair in 10 (10.3%), tricuspid valve repair in 5 (5.2%) and aortic arch replacement in 3 (3.1%). RESULTS Mean follow-up was 4.2 ± 2.4 years. Follow-up was complete in all. One 14-year old patient died 1.3 years post-surgery presumably of ventricular arrhythmia. One patient underwent reoperation for aneurysm of the proximal right coronary artery after 4.9 years and 4 patients required aortic valve replacement, 3 of which because of endocarditis after 0.1, 0.8 and 1.3 years and 1 because of cusp prolapse after 3.8 years. No thrombo-embolic complications occurred. Mortality, root reoperation and aortic regurgitation were absent in 88.0 ± 0.5% at 5-year follow-up. CONCLUSIONS Results of valve-sparing root replacement are good, even in association with a high incidence of concomitant valve repair. Valve-sparing aortic root replacement can be performed at a very young age as long as an adult size prosthesis can be implanted.

Ruptured aneurysm of the right coronary sinus of Valsalva in a child with Down syndrome.

Aneurysms of one of the aortic sinuses of Valsalva are rare congenital or acquired lesions. Here we present the case of an adolescent with Down syndrome with ruptured aneurysm of the right coronary sinus into the right atrium. All sinuses of Valsalva were normal during cardiological screening owing to Down syndrome at the age of 2 weeks. Paediatricians should have a low threshold for referring patients with Down syndrome for cardiac re-evaluation because of the new onset of cardiac symptoms or cardiac physical findings, even in the situation in which there are normal echocardiographic findings in the past.