Tacrolimus-Eluting Suture Inhibits Neointimal Hyperplasia: An Experimental In Vivo Study in Rats.

OBJECTIVE/BACKGROUND: Neointimal hyperplasia (NIH) remains one of the leading causes of graft failure after vascular anastomoses. Cytotoxic drugs, such as rapamycin and tacrolimus, have been shown to inhibit the development of NIH. In this study, the aim was to test the impact of a sustained releasing tacrolimus-chitosan-eluting suture on the development of NIH in a rat model. METHODS: After tacrolimus-chitosan coating of a 7/0 polyvinylidene difluoride (PVDF) Trofilen® suture, the tacrolimus concentration on the coated suture and in vitro release trials were performed spectrophotometrically. Twelve Wistar rats were included. After midline laparotomy, a 7-8 mm longitudinal aortotomy in the infrarenal aorta was made and then closed by a bare 7/0 PVDF (group C, n = 6) and a 7/0 tacrolimus-chitosan coated PVDF suture (0.65 µg/cm tacrolimus [0.9 wt%] + 1.82 µg/cm chitosan [2.28 wt%]) (group T, n = 6). After 1 month, rats were sacrificed and aortotomy sites were examined histologically by ratio of intimal area (including neointima) and immunohistochemically by α-smooth muscle actin (ASMA) and proliferating cell nuclear antigen (PCNA) immunostaining. The PCNA positive cells were indexed to total cell number and expressed as percentage. RESULTS: In vitro tacrolimus release tests for a 7/0 tacrolimus-chitosan coated PVDF suture were confirmed for 1 month without an initial burst release. Endothelialisation over the aortotomy line occurred in both groups. The area of neointima was significantly reduced in group T compared with group C (ratio 0.22 ± 0.12 vs. 0.42 ± 0.11; p = .017) 1 month post-operatively. Likewise, the percentage of PCNA immunostaining significantly decreased in group C compared with group T (3.83 ± 2.85% vs. 11.17 ± 7.78%; p = .026). The cells constituting NIH were positive for ASMA immunostaining. CONCLUSIONS: Tacrolimus-chitosan-eluting suture is shown to be an effective way to reduce NIH without interfering with normal endothelialisation.

Results of pericardiectomy for constrictive pericarditis : Single-center experience.

BACKGROUND: We evaluated our early and late outcomes after pericardiectomy in patients with constrictive pericarditis (CP). PATIENTS AND METHODS: We retrospectively reviewed 31 patients who underwent pericardiectomy for CP from 1997 to 2015. Their mean age was 49.2 ± 18.5 years and 74.2 % of them were male. The vast majority had severe functional impairment (NYHA class III-IV) with a mean duration of symptoms of 14.2 ± 10.1 months. RESULTS: Early mortality was 9.7 %: n = 3; multiorgan failure (MOF) in 1, respiratory failure in 1, and left heart failure in 1. Preoperative systolic pulmonary artery pressure over 60 mmHg (p = 0.038, odds ratio [OR] = 0.12) and postoperative low cardiac output syndrome (p = 0.005, OR = 13.5) were significant predictors of early mortality in univariate analysis. Mean follow-up time was 57.8 ± 61.9 months (4-216 months). Late mortality was 6.8 % (2/28 patients) and the cause was MOF secondary to end-stage right heart failure. In Kaplan-Meier analyses, actuarial (including early mortality) and event-free survival rates were 83.9 and 51.1 % at 216 months, respectively. At the end of follow-up, the majority of patients (23/26, 92.9 %) were in good functional status (NYHA class I-II). There were fewer patients under diuretic therapy in the postoperative than in the preoperative period; however, the difference was not statistically significant (12/31 vs. 4/26, p = 0.76). There was no significant difference between the preoperative and follow-up tricuspid annular plane systolic excursion values (15.5 ± 2.2 and 16.6 ± 2.2 mm, respectively, p = 0.088). Left ventricular systolic function was preserved in all patients postoperatively. CONCLUSION: Although early mortality after pericardiectomy remains high, the procedure provides significant improvement in functional status in the long term.

HLA-DR mismatching correlates with early cardiac allograft rejection, incidence, and graft survival when high-confidence-level serological DR typing is used.

To determine if cardiac allograft outcome is improved among patients with fewer HLA-DR mismatches with their donors, we studied 132 recipients of a primary cardiac allograft who were transplanted between December 1985 and December 1991. These recipients and their donors all had high-confidence-level serological HLA-DR typing, previously shown to correlate highly with DNA DR typing. Patients were divided in two groups based on the HLA-DR mismatch with their donors. Group I consisted of 78 patients with 1 or zero DR mismatch and group II of 54 patients with 2 DR mismatches. Allograft outcome measurements included incidence of moderate rejection, incidence of allograft vasculopathy at 12 months, cardiac function measured as left ventricular ejection fraction (LVEF) and cardiac index (CI), and actuarial graft survival up to 7 years. Groups I and group II were not different with regard to recipient age, donor age, ischemia time, pulmonary vascular resistance, sex, or PRA greater than 0%. Group II had a higher incidence of moderate rejection on the first-week biopsy (47% vs. 25%, P = 0.019), and during the first month (84% vs. 58%, P = 0.006), but no difference was found in frequency of rejection from months 2 to 12. LVEF was not different in the groups at any point. CI was better in group I at 12 months (2.76 vs. 2.5, P = 0.03). No statistically significant difference was found in incidence of allograft vasculopathy (17% vs. 26%, P = 0.204). Actual graft survival at 1 year was better for group I (91% vs. 74%, P = 0.008), and actuarial graft survival at 6 years also favored group I (76% vs. 56%, P = 0.04). Using high-confidence-level serological HLA-DR typing assignments we demonstrated that HLA-DR mismatching correlates highly with cardiac allograft outcome. Implications are that heart transplant survival could be improved if prospective matching were feasible and prioritized or if immunosuppression were tailored to the HLA-DR match.

Predicting hospital charge and length of stay for congenital heart disease surgery.

Three hundred twenty-two consecutive operations between December 1985 and December 1989 for 10 types of low-risk congenital cardiac malformations were reviewed to determine the hospital charge and postoperative length of stay. Multiple regression analysis of variance was used to predict the influence of the primary diagnosis and various preoperative parameters. The average hospital charge was $27,262 +/- $20,644 and the postoperative length of stay was 9.3 +/- 8.3 days. Age at operation alone did not influence the dependent variables. The diagnosis of atrial septal defect (p = 0.002) or coarctation of the aorta (p = 0.002) decreased the mean charge, whereas the 8 other primary diagnoses did not significantly influence the mean charge. Other preoperative factors found to be predictive of increased hospital charge were: the date of operation (p < 0.001), cyanosis (p = 0.008), previous thoracic surgery (p = 0.02), failure to thrive (p < 0.001), associated major extra cardiac anomalies (p < 0.001), oxygen requirement (p = 0.02), and distance > 100 miles from home to hospital (p = 0.05). A primary diagnosis of atrial septal defect decreased the mean postoperative length of stay by 3.1 days (p < 0.001). Other preoperative conditions increased the mean postoperative length of stay: major extracardiac malformation (p < 0.001), failure to thrive (p < 0.001), and oxygen requirement (p = 0.003). Charge and length of stay equations were generated which may assist in the prediction of resource utilization in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative transesophageal echocardiography using high-resolution biplane 7.5 MHz probes with continuous-wave Doppler capability in infants and children with tetralogy of Fallot.

This study reports the role of biplane transesophageal echocardiography in monitoring surgical repairs of tetralogy of Fallot. In our patients, 3 repairs were revised based on transesophageal echocardiography and continuous-wave Doppler results, and intraoperative management was altered in 2 others.

Usefulness of transesophageal imaging of flow convergence region in the operating room for evaluating isolated patent ductus arteriosus.

Transesophageal echocardiography (TEE) was performed in 21 patients with isolated patent ductus arteriosus (PDA) with a color Doppler flow convergence method during surgical closure of the ductus. Evaluation of PDA by TEE with the flow convergence method may provide valuable information during surgery and/or thorascopic ductus clipping.

Micromultiplane transesophageal echocardiographic probe for intraoperative study of congenital heart disease repair in neonates, infants, children, and adults.

This study reports the development of a micromultiplane 8.2-mm transesophageal echocardiographic probe. The probe is applicable to newborn infants and can deliver diagnostic images in adults.

Late results of ascending aorta-descending aorta bypass grafts for recurrent coarctation of aorta.

Ten patients between the ages of 10 and 17 years underwent ascending aorta-descending aorta bypass grafts for recurrent coarctation at the Oregon Health Sciences University from 1975 to 1984. The combined approach through a left thoracotomy and median sternotomy was used in all the patients. This operation was used when the segment of recoarctation was long, dense adhesions were present, collaterals were inadequate, or when a cardiac operation was necessary for an associated lesion. All the patients survived the operation, and the long-term results to date have been satisfactory.

What dictates the position of the diaphragm--the heart or the liver? A review of sixty-five cases.

Case histories of 65 patients with cardiac malposition were reviewed to assess abdominal taxis and hemidiaphragm posture. We present their roentgenographic findings to support the hypothesis that the cardiac mass determines the caudad displacement and lower position of the related hemidiaphragm. The popular hypothesis that the liver lifts the corresponding hemidiaphragm is questioned. Incidentally, a review of their echocardiographic findings demonstrate the presence of complex congenital heart defects in a majority of these patients.

Purine efflux from transplanted human cardiac allografts. Correlation with graft function.

Purine efflux from transplanted human cardiac allografts was investigated as a potential biochemical correlate to graft preservation and eventual function. Coronary sinus effluent from 14 allografts was sampled at 1, 5, 10, 15, 20, and 25 minutes after reperfusion. The plasma fraction from each sample was analyzed for hypoxanthine, xanthine, urate, inosine, and adenosine by high-performance liquid chromatography. Total organ preservation time, aortic crossclamp and bypass times, and initial cardiac index off bypass were recorded. An inotropic score was calculated from the dosages of inotropic agents each recipient required immediately after transplantation. Inosine and adenosine were not detectable in the coronary sinus effluent at any time during reperfusion. Hypoxanthine concentration rose sevenfold (p < 0.001) 1 minute after reperfusion. Xanthine concentration peaked later at 5 minutes after reperfusion, a twofold increase (p < 0.02). As reperfusion continued, hypoxanthine and xanthine concentrations returned toward baseline levels. The rise in coronary sinus xanthine concentration provides evidence for hypoxanthine degradation by xanthine oxidase during the immediate reperfusion period. The extent of hypoxanthine efflux correlated with total graft ischemic time (p < 0.05), inotropic score (p < 0.005), and the time from crossclamp release to cessation of bypass (p < 0.01). Hypoxanthine efflux can be used as a sensitive and objective biochemical indicator of graft preservation and immediate function.

Combined intracardiac and extracardiac repair of scimitar syndrome with anomalous pulmonary veins to both cavae.

Anomalous pulmonary venous drainage from the right lung to the inferior vena cava (scimitar syndrome) is a rare finding. This paper briefly discusses this syndrome and presents a case of anomalous pulmonary venous return to both the superior and the inferior cavae, which was corrected with a combined extracardiac and intracardiac approach. Polytetrafluoroethylene was utilized for reconstruction of pathways to the left atrium. To our knowledge, this is the first time this technique has been used to correct this anomaly.

Coarctation of the aorta in patients younger than three months. A critique of the subclavian flap operation.

Unexpected and disappointing late results with the subclavian flap operation prompted this analysis of repair of coarctation in infants under 3 months of age. A total of 134 such patients underwent surgical repair since 1960 with 55 end-to-end anastomoses performed earlier in our experience (mean follow-up 5.0 years) and 67 subclavian flap angioplasty operations performed more recently (mean follow-up 2.0 years). The operative mortality was not significantly different (p = 0.3) between end-to-end anastomosis (29%) and subclavian flap angioplasty (19%), but it was significantly higher (p less than 0.01) in the first week of life (56%). Recurrent coarctation occurred in 16 cases, necessitating reoperation. The reoperation-free rates (with standard error) at 5 years for end-to-end anastomosis and subclavian flap angioplasty were 92% +/- 5% and 75% +/- 7%, respectively (p = 0.01). Eight of 10 patients who had reoperation after angioplasty had early recurrence with continued involution of the periductal tissues and growth of the posterior aortic ridge. Six patients who had recurrence after anastomosis demonstrated late anastomotic growth failure. The most common reoperation technique was patch aortoplasty (10 patients). The high incidence of early recurrence with subclavian flap angioplasty in infants under 3 months of age suggests end-to-end anastomosis as the procedure of choice when applicable.

Influence of age at operation on late results with subclavian flap aortoplasty.

Despite the popularity of subclavian flap aortoplasty for repair of aortic coarctation, reported experience and follow-up in neonates is surprisingly limited. This paucity of reports prompted this review of age-related late recurrence rates. Of 83 patients having subclavian flap aortoplasty from 1976 to 1983, 60 were less than 8 weeks of age at operation (mean 2.6 weeks). Operative and late mortality were 18% and 14%, respectively. After a mean follow-up of 26 months, 10 patients have experienced recurrent coarctation (a mean of 10 months elapsed between operations). For 23 patients older than 8 weeks of age at operation (mean 20 months), operative and late mortality were 13% and 10%, mean follow-up is 16 months, and no patient has yet experienced recurrence. Thus, 75% of infants less than 8 weeks of age at operation are free of recoarctation at 2 years, and 100% of older children are free of recoarctation at 2 years (p = 0.06). Review of the literature corroborates our findings. The difference in recurrence rates may be due to age-dependent involution of residual coarctation tissue unavoidably left in place during subclavian flap aortoplasty. We conclude that subclavian flap aortoplasty is effective for correction of coarctation in infants, but patients less than 8 weeks old have a significant risk of early recurrence. Based on this review and our recently reviewed experience with end-to-end anastomosis, our preference is to use the latter in this age group when technically feasible.

Valvotomy for pulmonary atresia with intact ventricular septum. A disciplined approach to achieve a functioning right ventricle.

During the past 20 years, a consistent policy in applying early valvotomy has resulted in a unique opportunity to appraise the long-term results of this approach in pulmonary atresia with intact ventricular septum. Since 1964, 27 of 35 patients with pulmonary atresia with intact ventricular septum had type 1 or 2 right ventricle, 25 of these had early valvotomy, seven with and 18 without concomitant shunt. The remaining two patients with type 2 right ventricle and the eight patients with type 3 right ventricle received a shunt alone. Overall operative mortality was 34%; for those patients weighing more than 3 kg and those operated upon since 1977, it was 18% and 16%, respectively. There were 17 survivors of early valvotomy: 11 had valvotomy alone and six had valvotomy with shunt; 12 had type 1 right ventricle and five had type 2 right ventricle. Survival rates (+/- standard error) for these 17 patients were 85% +/- 10% and 68% +/- 17% at 5 and 10 years, respectively. The probability of reoperation was 100% by 6 years of age; outflow patch reconstruction was employed in all patients in whom reoperation has been performed. Aggressive follow-up and early recatheterization were essential features of management. Delayed reconstruction after shunt alone was unsuccessful in three patients. Primary valvotomy without shunt is the operation of choice for patients with pulmonary atresia with intact ventricular septum and type 1 right ventricle. Concomitant shunt may be required for some patients with type 1 and most with type 2 right ventricle, selected preoperatively by angiography or after valvotomy by clinical necessity. Delayed right ventricular reconstruction after shunt alone is not an acceptable approach when an outflow tract is present.

Pericardial baffle complications following the Mustard operation. Age-related incidence and ease of management.

Pericardial baffle complications with the standard Mustard operation led first to the use of alternative materials of various shapes and finally to the recent popularity of the Senning procedure. At The Oregon Health Sciences University, we have persisted since the mid-1960s in the use of a modified Mustard operation in which a rectangular pericardial baffle is employed. Among 75 patients, there were baffle complications necessitating reoperation in 13. The reoperation-free rates (+/- standard error) at 9 years for patients less than or equal to 6 months, 7 to 12 months, and greater than 12 months of age were 59% +/- 15%, 60% +/- 17%, and 95% +/- 5%, respectively. All 10 patients reoperated upon during the past decade survived with complete relief of symptoms. A double patch to widen both the superior portion of the baffle and the superior vena cava was used most commonly and is our current procedure-of-choice. Baffle complications after the use of pericardium can be managed easily and reoperation on these patients carries a low risk. However, even with experience, the incidence of reoperation remains high in patients under 1 year of age and prompts a critical age-related comparison of these late results with the Senning procedure.

Late surgical results for ischemic mitral regurgitation. Role of wall motion score and severity of regurgitation.

The indication for concomitant valve operations for ischemic mitral regurgitation is examined in 120 consecutive patients with regurgitation who had coronary bypass. Ischemic mitral regurgitation was mild in 56%, moderate in 18%, and severe in 27%. Compared with patients without mitral regurgitation who underwent coronary bypass, significantly more patients with regurgitation had cardiomegaly (31% versus 5%), left heart failure (42% versus 6%), and abnormal wall motion scores (71% versus 42%). Eighty-three patients (69%) with ischemic mitral regurgitation had coronary bypass alone and 37 (31%) also had a valve operation. All patients with mild ischemic mitral regurgitation were treated by coronary bypass alone, as compared to 67% with moderate and 6% with severe regurgitation. Operative mortalities for mild, moderate, and severe ischemic mitral regurgitation were 4%, 10%, and 38%, respectively; 5 year survival rates were 82%, 60%, and 48%, respectively. Other significant determinants of survival were wall motion score, shock, cardiomegaly, left heart failure, and acute and multiple myocardial infarctions. Patients with mild ischemic mitral regurgitation and a low wall motion score (n = 40) had a 5 year survival rate of 94%. For patients with either moderate/severe regurgitation (n = 27) or a high wall motion score (n = 25), but not both, the 5 year survival rate was 70%. In 20 patients with both a high wall motion score and moderate/severe regurgitation, it was 33%. An additive detrimental effect is apparent. The change from mild to moderate/severe ischemic mitral regurgitation was equivalent to an increase of about 8 wall motion score units in terms of effect on survival. Ischemic mitral regurgitation is a powerful additive risk factor to wall motion score in coronary bypass. Mild regurgitation is best managed by coronary bypass alone. If regurgitation is moderate, it may still be possible to avoid a valve operation and have acceptable results. Severe ischemic mitral regurgitation usually necessitates coronary bypass and a mitral valve operation.

Heart transplantation in patients with previous cardiac operations. Excellent clinical results.

A significant proportion of potential transplant recipients have undergone previous cardiac procedures and may be subject to an increased risk because of technical and other factors inherent in a reoperation. Between December 1985 and June 1991, 155 orthotopic heart transplantations were carried out in 146 patients. Eighty-five transplantations (54.8%) were carried out as the initial cardiac operation (group I); 61 operations (45.2%) were performed in patients who had previous nontransplant cardiac operations (group II). Preoperative variables including hemodynamic indexes, renal function, and status on the waiting list were similar between these groups; however, group II patients tended to be older than group I patients (51.9 +/- 10.7 versus 47.7 +/- 11.6 years, respectively; p < 0.05) and were more likely to have ischemic heart disease (80.3% versus 34.1%) than were those in group I. Significantly longer cardiopulmonary bypass time (127.6 +/- 44.7 minutes versus 108.2 +/- 18.8 minutes, p < 0.01) and duration of operation (448.1 +/- 120.9 minutes versus 353.2 +/- 85.1 minutes, p < 0.01) was found in group II. Operative mortality in group I was 4.7% and in group II was 6.6% (p > 0.9). Group I actuarial survival at 1 year and 5 years was 87.1% +/- 3.6% and 72.9% +/- 6.2%, respectively. Group II actuarial survival was 85.3% +/- 4.5% and 76.0% +/- 6.6%, respectively, for the same time periods. In spite of the greater technical challenge implied by previous cardiac operations, no significant survival differences occurred between these groups (p > 0.9). However, patients undergoing a second cardiac transplantation (n = 9) were identified as a high-risk subset with operative mortality of 22.8% and 1-year survival of only 33.3% +/- 15.7% (p < 0.0003). Cardiac transplantation in patients who have undergone previous nontransplant cardiac operations can be carried out without compromising immediate or long-term outcome.

ABO-incompatible heart transplantation: a special case for the A2 donor.

Limited clinical experience concerning heart transplantation across ABO blood group barriers suggests a high incidence of hyperacute rejection and poor patient outcome. Reported is a case of the short-term survival of an ABO-mismatched cardiac graft without evident adverse immunologic effects. A 41-year-old man with blood type O underwent heart transplantation receiving a blood type A2 donor organ. Cyclosporine-based immunosuppression was augmented with daily plasmapheresis and OKT3 therapy. Circulating anti-A antibodies were reduced quickly and held to a very low level with this regimen. The patient remained hemodynamically stable until retransplantation 4 days later. The explanted heart showed no evidence of cellular infiltrate or antibody deposition. Long-term success with the use of type A2 organs in type O recipients has been shown in select series with other types of solid organ transplants. Although this patient underwent retransplantation early, the lack of rejection phenomena gives evidence that the relatively low antigenicity of the A2 subtype may allow planned heart transplantation across this blood group barrier, either as a bridge or on a permanent basis.

Squamous and basal cell carcinoma in heart transplant recipients.

BACKGROUND: Cutaneous malignancies are frequent in organ transplant recipients. We retrospectively reviewed a large series of heart transplant recipients and report on the prevalence and risk factors for development of cutaneous squamous and basal cell carcinoma. METHODS: Between Dec. 4, 1985, and Dec. 27, 1996, 299 heart transplantations were performed at the Oregon Health Sciences University. Heart transplant recipients with more than 6 months survival or follow-up were investigated for squamous and basal cell carcinoma (n = 248). RESULTS: Forty-one patients (17%) were found to have 192 squamous or basal cell carcinomas. Squamous cell carcinoma was the predominate skin malignancy, constituting 172 (90%) of the lesions. The mean number of skin malignancies per patient was 4.7 +/- 0.81 (range 125). Patients with development of a skin malignancy were 8 years older on average, with a male-to-female ratio of 19.5:1. The predominant skin type and eye color were fair (59%) and blue (59%), respectively. Cumulative risk, based on actuarial survival analysis for development of a squamous or basal cell carcinoma at 1 year, was 3% and increased to 21% and 35% at 5 and 10 years, respectively. In addition, cumulative risk increased in patients who received treatment with OKT3. CONCLUSION: Cumulative risk of development of a skin malignancy increased with time and use of OKT3. Additional patient risk factors included older age, male sex, fair skin, and blue eyes.

The lack of predictive value of preoperative psychologic distress for postoperative medical outcome in heart transplant recipients.

This follow-up study of 58 heart recipients an average of 2 years after transplantation did not show that the Symptom Checklist 90R, a self-report measure of psychologic distress, predicted medical outcome. Mortality and medical morbidity (graft rejection and infection rate) were the outcome variables used. The findings tend to argue against the validity of some aspects of the psychiatric screening of transplant candidates if prediction of patients' ultimate risk of mortality or medical morbidity is the validation standard.