Insight into the current practice of ototoxicity monitoring during cisplatin therapy.

BACKGROUND: The aim of this study is to evaluate the current state of ototoxicity monitoring for patients receiving cisplatin chemotherapy in an academic medical center with particular attention to how closely monitoring adheres to national ototoxicity guidelines. METHODS: Case series including retrospective medical records review of patients (age > 18) treated with cisplatin at University of California Davis Medical Center between January 2014 and August 2017. Patient and ototoxicity related variables were analyzed. Patients that underwent a transfer of care during treatment and with less than 3 months of follow-up were excluded. RESULTS: Three hundred seventy-nine patients met study criteria, of which 104 (27.4%) had a prior history of hearing loss. Prior to treatment, 196 (51.7%) patients were counseled regarding the ototoxic nature of cisplatin and 92 (24.3%) patients had a pretreatment audiogram. During treatment, 91 (24%) patients had documented otologic complaints. Only 17 patients (4.5%) patients had an audiogram ordered during their cisplatin treatment period. 130 (34.3%) patients had otologic complaints following cisplatin treatment. Audiograms were ordered for 20 (7.8%), 13 (5.1%), and 16 (6.2%) patients at 1-month, 3-month, and 6-month follow-ups, respectively. No patients in the study cohort received baseline, treatment, and post-treatment audiograms as recommended by national ototoxicity monitoring protocols. Patients with Head and Neck Cancer (HNC) represented the largest subgroup that received cisplatin (n = 122, 32.2%) and demonstrated higher rates of ototoxicity counseling (n = 103, 84.4%) and pretreatment audiograms (n = 70, 57.4%) compared to the non HNC group (n = 36, 36.2%, P < 0.0001 and n = 22, 8.5%, P < 0.0001). CONCLUSIONS: There is poor adherence to national ototoxicity monitoring guidelines at a large academic medical center. This is a missed opportunity for intervention and aural rehabilitation. Improved education and collaboration between otolaryngology, audiology, and medical oncology is needed to develop and promote an effective ototoxicity-monitoring program.

Comparative Study of Pediatric Coronary Allograft Vasculopathy Between Single Centers in North America and United Kingdom.

BACKGROUND: Coronary allograft vasculopathy (CAV) is the leading cause of death after pediatric heart transplantation from 1 year postoperation. Anecdotal evidence suggests a difference in the severity of disease between UK and North America. We performed a comparative study using intravascular ultrasound (IVUS). METHODS: Consecutive IVUS procedures from a single year were included from each center. Using standardized techniques, measurement of the vessel area, lumen area, and maximal intimamedial thickening (IMT) were performed with calculation of intimal index (II) for each slice. Mean II, mean IMT, and absolute maximum IMT were calculated along the left coronary artery for each patient. Transplant demographics and treatment details were included in the analysis. RESULTS: One hundred four patients were included between the 2 centers. Interobserver variability for IVUS analysis was excellent. Patients were aged mean 14.2 (SD 3.3) years at the time of the study and 9.2 (SD 6.0) years earlier post-transplant procedure. UK patients were older, at transplant for a shorter time, and demonstrated more severe CAV. Multiple regression analysis demonstrated the detrimental effect of donor age and time from transplant on CAV severity and benefits of sirolimus use. CONCLUSIONS: The data show more severe CAV in the UK cohort despite significantly shorter time post-transplant. Donor age and time post-transplant were associated with more severe CAV and sirolimus use was associated with a reduction in IMT. This study demonstrates a marked difference in the prevalence of CAV in children between UK and North America. The causes are likely to be multifactorial; however, younger donors and recipients have significantly less disease.

Comparison of Segmental Versus Longitudinal Intravascular Ultrasound Analysis for Pediatric Cardiac Allograft Vasculopathy.

Intravascular ultrasound (IVUS) has been routinely used in some centers to investigate cardiac allograft vasculopathy in pediatric heart transplant recipients. We present an alternative method using more sophisticated imaging software. This study presents a comparison of this method with an established standard method. All patients who had IVUS performed in 2014 were retrospectively evaluated. The standard technique consisted of analysis of 10 operator-selected segments along the vessel. Each study was re-evaluated using a longitudinal technique, taken at every third cardiac cycle, along the entire vessel. Semiautomatic edge detection software was used to detect vessel imaging planes. Measurements included outer and inner diameter, total and luminal area, maximal intimal thickness (MIT), and intimal index. Each IVUS was graded for severity using the Stanford classification. All results were given as mean ± standard deviation (SD). Groups were compared using Student t test. A P value <.05 was considered significant. There were 59 IVUS studies performed on 58 patients. There was no statistically significant difference between outer diameter, inner diameter, or total area. In the longitudinal group, there was a significantly smaller luminal area, higher MIT, and higher intimal index. Using the longitudinal technique, there was an increase in Stanford classification in 20 patients. The longitudinal technique appeared more sensitive in assessing the degree of cardiac allograft vasculopathy and may play a role in the increase in the degree of thickening seen. It may offer an alternative way of grading severity of cardiac allograft vasculopathy in pediatric heart transplant recipients.

Comparison of swallowing outcomes of laryngotracheal separation versus total laryngectomy in a validated ovine model of profound oropharyngeal dysphagia.

OBJECTIVES: To validate the ovine model of profound oropharyngeal dysphagia and compare swallowing outcomes of laryngotracheal separation with those of total laryngectomy. METHODS: Under real-time fluoroscopy, swallowing trials were conducted using the head and neck of two Dorper cross ewes and one human cadaver, secured in lateral fluoroscopic orientation. Barium trials were administered at baseline, pre- and post-laryngohyoid suspension, following laryngotracheal separation, and following laryngectomy in the ovine model. RESULTS: Mean pre-intervention Penetration Aspiration Scale and National Institutes of Health Swallow Safety Scale scores were 8 ± 0 and 6 ± 0 respectively in sheep and human cadavers, with 100 per cent intra- and inter-species reproducibility. These scores improved to 1 ± 0 and 2 ± 0 post-laryngohyoid suspension (p < 0.01). Aerodigestive tract residue was 18.6 ± 2.4 ml at baseline, 15.4 ± 3.8 ml after laryngotracheal separation and 3.0 ± 0.7 ml after total laryngectomy (p < 0.001). CONCLUSION: The ovine model displayed perfect intra- and inter- species reliability for the Penetration Aspiration Scale and Swallow Safety Scale. Less aerodigestive tract residue after narrow-field laryngectomy suggests that swallowing outcomes after total laryngectomy are superior to those after laryngotracheal separation.

Transforming growth factor beta(2) lowers the incidence of incisional hernias.

BACKGROUND: Approximately 200,000 incisional hernias are repaired annually in the United States. The high incidence (11-20%) and recurrence rate (24-54%) for incisional hernias have not changed appreciably in 75 years. Mechanical advances in suture material, incision orientation, and closure technique have failed to eliminate this common surgical complication. A biological approach to acute wound failure may offer a new strategy. METHODS: A rodent incisional hernia model was used. Seventy rats underwent 5-cm midline celiotomies and were closed with fine, fast-absorbing sutures to induce intentional acute wound failure. Group 1 received no other treatment. The midline fascia in groups 2 and 3 was injected immediately prior to incision with 100 microl of vehicle alone or vehicle containing 1 microg of transforming growth factor beta(2) (TGF-beta(2)). Necropsy was performed on Postoperative Day 28 and the wounds were examined for herniation. RESULTS: Incisional hernias developed in 88% (35/40) and 79% (11/14) of untreated incisions and those treated with vehicle alone. No hernias formed in the TGF-beta(2)-treated incisions (0/16, P < 0.05). Standard histology and immunohistochemistry demonstrated enhanced macrophage, lymphocyte, and fibroblast chemotaxis and increased collagen I and III production in TGF-beta(2) treated incisions. CONCLUSIONS: Treatment of abdominal wall fascial incisions with TGF-beta(2) prevented the development of incisional hernias in this rat model. TGF-beta(2) stimulated fascial macrophage and fibroblast chemotaxis as well as acute wound collagen production. A biological approach such as this may reduce the incidence of incisional hernia formation in humans.

Outcomes of transcatheter balloon angioplasty of obstruction in the neo-aortic arch after the Norwood operation.

Obstruction of the reconstructed aortic arch, or the neoaortic arch, is now known to be an important factor increasing mortality after the Norwood operation for hypoplastic left heart syndrome. Transcatheter balloon angioplasty has been shown to provide effective relief of both native aortic coarctation and obstructions of the aortic arch occurring subsequent to therapeutic intervention. We sought to determine the outcomes of balloon angioplasty used as an initial treatment for obstruction of the neoaortic arch occurring after the Norwood operation. We gathered the characteristics of 58 patients with such obstruction from 8 institutions, noting procedural factors and outcomes of initial balloon dilation. Obstruction occurred at a median interval of 4 months, with a range from 1.5 months to 6.3 years, after a Norwood operation. Ventricular dysfunction was present before dilation in 13 patients. Mean peak to peak systolic pressure gradients were acutely reduced from 31+/-20 mm Hg to 6+/-9 mmHg (p<0.001), with outcome subjectively judged to be successful in 89%. Three patients with pre-existing ventricular dysfunction died within 48 hours of dilation. There were 10 additional deaths during the period of follow-up, with Kaplan Meier estimates of survival after intervention of 87% at 1 month, 77% at 12 months, and 72% after 15 months. In addition, 9 patients required re-intervention during the period of follow-up, with Kaplan Meier estimates of freedom from re-intervention after dilation of 87% at 6 months, 78% at 12 months and 74% after 18 months. Although transcatheter dilation of neoaortic arch obstructions after Norwood operation is successful, there is a high risk of re-intervention and ongoing mortality in this subgroup of patients. Close follow-up is recommended.

Fascial incisions heal faster than skin: a new model of abdominal wall repair.

BACKGROUND: Optimal healing of the fascial layer is a necessary component of complete abdominal wall repair. The majority of acute wound healing studies have focused on the dermis. We designed a model of abdominal wall repair that, to our knowledge, for the first time simultaneously characterizes differences in the wound healing trajectories of the fascia and skin. METHODS: Full-thickness dermal flaps were raised on the ventral abdominal walls of rats, and midline fascial celiotomies were completed. The dimensions of the flap were developed so as to have no detrimental effect on skin healing. The dermal flaps were replaced so that the fascial incisions would heal separately from the overlying skin incisions. Animals were killed 7, 14, and 21 days after operation and fascial and dermal wounds were harvested and tested for breaking strength. Fascial and dermal wounds were also compared histologically for inflammatory response, fibroplasia, and collagen staining. RESULTS: Fascial wound breaking strength exceeded dermal wound breaking strength at all time points (9.16 +/- 2.17 vs 3.51 +/- 0.49 N at 7 days, P <.05). Fascial wounds also developed greater fibroblast cellularity and greater collagen staining 7 days after the incision. There was no difference in wound inflammatory response. CONCLUSIONS: Fascial incisions regain breaking strength faster than simultaneous dermal incisions. The mechanism for this appears to involve increased fascial fibroplasia and collagen production after acute injury.

Abdominal wall repair is delayed during hepatic regeneration.

BACKGROUND: Abdominal wall wound failure remains a common surgical problem. The signals that activate normal fibroplastic repair versus regeneration pathways are unknown. Transforming growth factor beta levels rise during incisional healing but fall during hepatic regeneration. Changes in the injured host cytokine milieu may therefore differentially effect abdominal wall repair versus hepatic regeneration. MATERIALS AND METHODS: Forty-eight rats were divided into four groups (n = 12). Groups 1-3 underwent sham celiotomy, 70% hepatectomy, or 80% enterectomy with anastamosis. Incisions from Group 4 were treated with either 1 microg of transforming growth factor beta(2) (TGF-beta(2)) or vehicle following hepatectomy. Isolated fascial and dermal incisions were harvested and tested for breaking strength on POD 7. Serum (TGF-beta(2)) and hepatocyte growth factor (HGF) levels were measured by ELISA. RESULTS: Recovery of incisional wound breaking strength was delayed following hepatectomy but not enterectomy (P<0.002). The inhibitory effect was observed in both the fascia and the dermis of the abdominal wall. TGF-beta(2) levels were depressed in hepatectomy animals on POD 7, while at the same time HGF levels were elevated. Exogenous TGF-beta(2) shifted the healing trajectory of deficient wounds back toward a control pattern. CONCLUSION: Abdominal wall fascial and dermal healing is delayed during hepatic regeneration. Elevated HGF and depressed TGF-beta(2) suggest a host mechanism that prioritizes hepatic parenchymal regeneration over fibroplastic repair (scar). Observations such as these are needed as therapeutic wound healing enters the clinical realm.

Cytokine manipulation of explanted Dupuytren's affected human palmar fascia.

INTRODUCTION: Dupuytren's disease plagues human hands and digits producing fibrotic nodules and fascial cords with resultant debilitating flexion contracture deformities. Interest in this condition is great but because the disease is specific to humans and study has been hampered by the lack of an in vivo model. By utilizing an in vivo "nude" rat model it is possible to maintain and study explanted Dupuytren's contracted palmar fascia for prolonged periods of time. MATERIALS AND METHODS: Human specimens were divided into four, one for in vitro analysis, and three for model explantation. The explanted tissue was perfused with either transforming growth factor beta-2 (TGFbeta2), its antibody, or a control vehicle. Explant biopsies were obtained at 30 and 60 days and compared to tissue prior to explantation. Immunohistochemistry of collagen I and III, DNA synthesis, protein production, and fibroblast kinetics were serially determined. RESULTS: Perfusion of explanted Dupuytren's tissue by TGFbeta2 upregulated collagen I and III from biopsies obtained from the explants at 30 days when compared to vehicle control (P < 0.001). Perfusion with antibody prevented this upregulation when compared to vehicle control (P < 0.001). Cell cultures derived from fibroblasts obtained from biopsies of the explants perfused with TGFbeta2 increased DNA synthesis, protein production and fibroblast kinetics. CONCLUSION: These findings paralleled those from other fibroproliferative disorders suggesting a role for TGFbeta2 in the pathogenesis of Dupuytren's contracture as well as possible novel treatment approaches.

Silicone sheeting decreases fibroblast activity and downregulates TGFbeta2 in hypertrophic scar model.

BACKGROUND: Fibroproliferative disorders, which include hypertrophic scars and keloids, represent deviations from the normal process of wound healing. The fibrogenic cytokines have been associated with excessive scarring. It has been proposed that placing silicone in contact with hypertrophic scars may prove to be an effective form of treatment. This may be a result of downregulating fibroblasts and/or decreasing the fibrogenic cytokines. An in vitro model to study wound contraction is a fibroblast populated collagen lattice (FPCL). This study used FPCL as a method to study the effect of silicone sheeting on hypertrophic scar fibroblasts. METHODS: Fibroblast cultures were obtained and collagen lattices were prepared. Silicone sheeting was placed over the collagen matrix versus Saran wrap used as a treatment control. The amount of gel contraction was measured every 24 hours for five days. The supernatant obtained from the culture medium following completion of the FPCL portion of the experiment was then used in an immunoassay for TGFbeta2. RESULTS: A statistically significant decrease in amount of FPCL contraction occurred between three of the four brands of silicone sheets used compared to untreated control or Saran wrap treated FPCL. The immunoassay for TGFbeta2 showed a statistically significant decrease with all four types of silicone sheeting. CONCLUSION: FPCLs populated with burn hypertrophic scar fibroblasts exposed to silicone sheeting have decreased contraction compared to an unexposed control and Saran wrap treated control. In addition, TGFbeta2 is downregulated in the silicone exposed group. It appears that silicone sheeting may act by downregulating fibroblasts and decreasing fibrogenic cytokines.

The role of sentinel lymph node biopsy in women undergoing prophylactic mastectomy.

BACKGROUND: Indications for prophylactic mastectomy (PM) range from LCIS to BRCA 1-2 positive, cosmesis, and cancer phobia. Occult cancers have been found in up to 5% of PM cases. Consequently, consideration must be given to the role of sentinel lymph node (SLN) biopsy as a diagnostic procedure in these patients as PM excludes the subsequent option of SLN biopsy. METHODS: From April 1994 to November 1999, all patients undergoing PM had SLN biopsy after four quadrant periareolar injections of radiocolloid (450 mci) and blue dye (5 cc). All patients were prospectively accrued to the computerized database of breast patients. The SLN were all evaluated with hematoxylin and eosin (H&E) as well as CAM5.2 cytokeratin immunohistochemical (CK-IHC) stains. RESULTS: Over a 67-month period, 1,356 patients were mapped; 57 patients underwent PM in which 148 nodes (2.6 nodes per patient) were evaluated. Nodes were examined by routine H&E and CK-IHC staining. Two patients, neither of whom was found to have a cancer in the prophylactic mastectomy breast, were found to have a positive SLN by CK-IHC staining. Infiltrating carcinoma was discovered within the PM breasts of 2 additional patients. Sentinel lymph node biopsy was negative for malignancy by H&E as well as CK-IHC stains. No lymphedema has been detected in PM patients. CONCLUSIONS: Sentinel node biopsy has been shown to be an accurate and minimally invasive method of evaluating the lymphatic basin. This study shows that the absence of known disease within the breast does not preclude the presence of occult cancer or metastatic nodal disease. Four patients (7%) had a significant change in their surgical management as a direct result of sentinel lymph node biopsy. Two patients were spared the complications of a complete axillary node dissection. This minimally invasive procedure accurately evaluated the known disease status and provided new diagnostic information. Most important, once a mastectomy is performed, the opportunity for SLN biopsy is lost should a cancer be found within the breast specimen.

Overexpression of transforming growth factor beta-2 and its receptor in rhinophyma: an alternative mechanism of pathobiology.

Proliferative scarring is one of the clinical features of rhinophyma. The following study was undertaken to test the authors' hypothesis that fibrosis might also play an important role in the pathobiology of rhinophyma. The rhinophyma specimens were obtained from 5 white men (mean age, 67.8 years). Normal skin biopsies near benign facial lesions from 5 additional white men of similar age were obtained to serve as controls. Peroxidase-labeled immunohistochemical staining was performed in the rhinophyma and normal skin specimens for the presence of transforming growth factor (TGF) beta-2 and/or TGF-beta II receptor. Histological slides were then measured for the intensity of staining for TGF-beta2 and TGF-beta II receptor using a computer-aided imaging system. The dermis of the rhinophyma tissue displayed stronger immunoreactivity of TGF-beta2 (p = 0.014) and TGF-beta II receptor (p = 0.006) compared with the normal skin. The results of this study demonstrate the overexpression of the fibrogenic protein TGF-beta 2 and TGF-beta II receptor in rhinophyma tissues. These findings support the authors' hypothesis that fibrosis may also play an important role in the pathobiology of rhinophyma.

Outcome of infants with hypoplastic left heart syndrome who undergo atrial septostomy before heart transplantation.

This study evaluated the procedural and long-term outcome of infants who underwent atrial septostomy while awaiting transplant. The results suggest that septostomy improved outcome in these patients although infants needing a transseptal perforation were at higher risk.

In vitro fibroblast populated collagen lattices are not good models of in vivo clinical wound healing.

In chronic wounds, the healing process is prolonged and incomplete, proceeding in an uncoordinated manner, and resulting in poor anatomical and functional outcome. There have been numerous attempts to discover models that mimic human wound healing processes. The fibroblast populated collagen lattice is one such model that has been proposed. This study evaluated whether the fibroblast populated collagen lattice can be a model of chronic wound healing using the pressure ulcer as a paradigm. Fibroblast cultures of wound biopsies and wound volume measurements were obtained serially during a four arm blinded, placebo-controlled sequential cytokine clinical trial of pressure ulcers. Fibroblasts obtained from study patients were added to collagen lattices and contraction was determined daily for 10 days. Collagen gel-area measurements were converted to reflect percentage of gel contraction. These data of both edge and base wound biopsies on days 0, 10, and 36 were categorized into treatment groups and one-way analysis of variance showed no significant differences in contraction among these groups. When considering all fibroblast populated collagen lattices, there was significantly greater contraction at days 10 and 36 for cells from both edge and base biopsies compared to day 0 (p < 0.05). The Spearman Rank Correlation test comparing all patients with fibroblast populated collagen lattice results from fibroblasts obtained at the edge or base of the wound at days 0, 10, and 36 and clinical pressure ulcer healing on day 36 showed no correlation. This lack of correlation not only persisted for each of the four treatment arms but also for responder status based on decrease in wound volume over the 35 day trial period. In conclusion, chronic wound healing is a complex process that is not modeled by in vitro fibroblast populated collagen lattices.

The medium-term findings in coronary arteries by intravascular ultrasound in infants and children after heart transplantation.

OBJECTIVES: The study purposes were to determine 1) whether intravascular ultrasound (IVUS) was more sensitive than angiography for the detection of post-transplant coronary artery disease (PTCAD) in pediatric patients; and 2) whether those transplanted as neonates reacted differently than older patients. BACKGROUND: Experience with IVUS for the diagnosis of PTCAD in children is limited. METHODS: Patients were divided into two groups: those transplanted as neonates (early group) and those transplanted in infancy or childhood (late group). Morphometric analysis was performed, including maximal intimal thickness (MIT) and intimal index (II). Stanford classification was used to grade lesion severity. Acute rejection and cytomegalovirus (CMV) status were correlated with MIT and II. RESULTS: Thirty children were studied (early group, n = 13; late group, n = 17). All segments studied were angiographically normal. Mean MIT and mean II were significantly greater in the late group (0.26 +/- 0.14 vs. 0.13 +/- 0.04 mm, p < 0.001 and 0.11 +/- 0.07 vs. 0.07 +/- 0.03 mm, p = 0.04, respectively). There was a significant correlation between MIT and II in those who had acute rejection in the late group. Patients in the late group who were CMV-positive had a significantly higher MIT compared with those in the late group with negative serology (p = 0.04). CONCLUSIONS: Intravascular ultrasound was more sensitive than angiography in detecting PTCAD after pediatric heart transplantation. There is a possible role for acute rejection and CMV in the development of PTCAD.

Initiating the inflammatory phase of incisional healing prior to tissue injury.

BACKGROUND: The time required for incisional healing accounts for the majority of postoperative pain and convalescence. Impaired healing prolongs the process further. If a method for accelerating acute incisional wound healing could be developed, patients would benefit from decreased wound failure and an earlier return to their premorbid condition. MATERIALS AND METHODS: In a rat dermal model, cytokine or vehicle infiltration prior to incision was performed using a single dose or four daily doses preincision. Planned incision sites were primed with the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) or platelet-derived growth factor BB (PDGF-BB) in an effort to activate the inflammatory phase of healing prior to wounding. At the time of incision closure, one half of the incisions were treated with transforming growth factor beta(2) (TGF-beta(2)). Incisional sites were biopsied and stained with hematoxylin and eosin and immunohistochemistry for inflammatory cells and fibroblast populations and breaking strength was measured. RESULTS: Priming skin with GM-CSF or PDGF-BB mimicked the early inflammatory phase of wound healing. Macrophage staining (EB1) and fibroblast staining (vimentin) were significantly increased prior to incision. Inflammatory priming as well as priming coupled with TGF-beta(2) at the time of the incision closure synergistically improved breaking strength. CONCLUSION: This study demonstrates that sequential therapy consisting of priming of tissue with an inflammatory cytokine followed by application of a proliferative cytokine at the time of incision closure nearly doubles the breaking strength of an acute wound. By manipulating the inflammatory and early proliferative phases of wound healing with tissue growth factors, it may be possible to accelerate acute wound repair and shift the wound healing trajectory to the left.

Use of the wound healing trajectory as an outcome determinant for acute wound healing.

Accurate and clinically practical methods for measuring the progress of acute wound healing is necessary before interventions designed to optimize and even accelerate acute wound healing can be applied. Complete wound closure rates and operative wound closure severity are irrelevant to most acute wounds since most are closed at the time of primary tissue repair and remain closed throughout healing. Analogous to chronic wound closure, the rate of increase of incision tensile strength progressively decreases as time passes and 100% unwounded tissue strength is never achieved making the endpoint definition of "healed" vague. Conceptualizing acute wound healing in terms of its design elements with reintegration into a final outcome lends itself to the description of acute wound healing as a mathematical trajectory. Frequently such an equation is a rate expressing the change in an acute healing parameter, most often tensile strength, over time. Such an approach also normalizes misinterpretations in analysis or errors in theory developed by measuring healing parameters at fixed points in time. Distributions of fractional strength gain times (e.g., 85% normal strength) can be determined using statistical methodology similar that used for failure time of survival analysis. Preclinical studies show that acute wound healing trajectories can be shifted to the left from a "normal" or "impaired" curve to an accelerated or more "ideal" curve. A useful method for measuring acute wound healing outcomes is therefore required before the basic science of acute wound healing is inevitably applied to the problem of acute surgical wounds.

Right coronary artery occlusion as a complication of accessory pathway ablation in a 12-year-old treated with stenting.

We describe a complication of radiofrequency ablation of a posteroseptal pathway that resulted in acute occlusion of a distal right coronary artery in a pediatric patient. The complication was treated with coronary stenting after unsuccessful angioplasty.

Posttransplant recoarctation of the aorta: a twelve year experience.

OBJECTIVES: This study was undertaken to investigate the incidence of posttransplant recoarctation of the aorta, delineate the mode of presentation, identify risk factors that predict recoarctation and examine the results of intervention for posttransplant recoarctation. BACKGROUND: Patients with aortic arch hypoplasia require extended arch reconstruction at transplant, with an inherent possibility of subsequent recoarctation of the aorta. METHODS: This was a retrospective review of all children (age <18 years) who underwent cardiac transplantation over a 10-year period. Collected data included pretransplant diagnosis, details of the transplant procedure and posttransplant data including development of recoarctation of the aorta, interventions for recoarctation and the most recent follow-up assessment of the aortic arch. RESULTS: Two hundred eighty-eight transplants were performed on 279 children (follow-up = 1,075 patient-years; range 0 to 133 months, median 43.7). Thirty-two of 152 patients (21%) who underwent extended aortic arch reconstruction subsequently developed recoarctation. All but one patient developed recoarctation within 2 years after transplant; 87% were hypertensive at presentation. Of 30 patients who underwent intervention for recoarctation (balloon angioplasty [n = 26] and surgical repair of recoarctation [n = 4]), 26 (87%) have remained recurrence-free (follow-up = 133 patient-years; range 8 to 106 months, median 47). CONCLUSIONS: The high frequency of recoarctation after cardiac transplantation with extended aortic arch reconstruction mandates serial echocardiographic evaluation of the aortic arch. Patients typically present with systemic hypertension within the first two years after transplantation. Balloon angioplasty is a safe, effective and durable method of treatment.

Dobutamine stress echocardiography for assessing coronary artery disease after transplantation in children.

OBJECTIVES: The purpose of this study was to determine the feasibility, safety and diagnostic accuracy of dobutamine stress echocardiography (DSE) for evaluating posttransplant coronary artery disease (TxCAD) in children, and to determine the frequency of selected cardiac events after normal or abnormal DSE. BACKGROUND: Posttransplant coronary artery disease is the most common cause of graft loss (late death or retransplantation) after cardiac transplantation (CTx) in children. Coronary angiography, routinely performed to screen for TxCAD, is an invasive procedure with limited sensitivity. The efficacy of DSE for detecting atherosclerotic coronary artery disease is established, but is unknown in children after CTx. METHODS: Of the 78 children (median age 5.7 years, range 3 to 18) entered into the study, 72 (92%) underwent diagnostic DSE by means of a standard protocol, 4.6 +/- 1.9 years after CTx. The results of coronary angiography performed in 70 patients were compared with DSE findings. After DSE, subjects were monitored for TxCAD-related cardiac events, including death, retransplantation and new angiographic diagnosis of TxCAD. RESULTS: No major complications occurred. Minor complications, most often hypertension, occurred in 11% of the 72 subjects. The sensitivity and specificity of DSE were 72% and 80%, respectively, when compared with coronary angiography. At follow-up (21 +/- 8 months), TxCAD-related cardiac events occurred in 2 of 50 children (4%) with negative DSE, versus 6 of 22 children (27%) with positive DSE (p < 0.01). CONCLUSIONS: DSE is a feasible, safe and accurate screening method for TxCAD in children. Positive DSE identifies patients at increased risk of TxCAD-related cardiac events. Negative DSE predicts short-term freedom from such events.