Induction of anesthesia does not alter tricuspid annular velocities: a tissue Doppler assessment

Purpose

In this prospective observational cohort study, we investigated whether tricuspid annular velocities (TAV) are altered after induction of anesthesia in patients undergoing coronary artery bypass graft (CABG) surgery.

Methods

Twenty-four elective CABG patients were assessed before and after induction of anesthesia, and a convenience sample of nine healthy volunteers was used for comparison of TAV only. Measurements included mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), and cardiac index (CI) as assessed post-induction. Tricuspid annular plane systolic excursion (TAPSE) was measured in anatomical M-mode. The S (systolic) wave velocity and isovolemic acceleration (IVA) were measured from colour tissue Doppler (TD). Paired and unpaired Student’s t tests were used to compare all variables pre-and post-induction.

Results

In response to anesthetic induction, MAP decreased from 105 ± 14 to 79 ± 9 mmHg, but HR was unchanged (67 ± 13 beats · min^?1 pre-induction compared with 67 ± 9 beats · min^?1 post-induction). The mean PAP and CI post-induction were 20 ± 6 mmHg and 2.3 ± 0.4 L · min^?1 · m^?2, respectively. While there was no change post-induction in either S velocity (8.80 ± 1.23 vs 9.0 ± 1.92 cm · sec^?1) or IVA (1.63 ± 0.61 vs 1.84 ± 0.83 m · sec^?2), TAPSE decreased from 23 ± 4 to 21 ± 4 mm (P = 0.039). All pre-induction echocardiographic variables were lower in the CABG group compared with the normal group (IVA: 2.34 ± 0.34 m · sec^?2, S wave: 11.14 ± 2.78 cm · sec^?1, TAPSE 2D: 26 ± 4 mm), respectively.

Conclusions

Induction of anesthesia for CABG surgery does not alter velocity-based parameters of RV function. There was a small decrease in TAPSE. The TD parameters were lower in CABG patients compared with the normal group.     

Treatment of hyperhomocysteinemia in pediatric heart transplant recipients.

BACKGROUND: Graft coronary artery vasculopathy is the main cause of late morbidity and mortality in pediatric cardiac allograft recipients. Growing evidence suggests that elevated plasma homocysteine levels are associated with cardiac allograft vasculopathy following heart transplantation. The purpose of this study was to evaluate the effect of vitamin supplementation as a potential strategy for reducing homocysteine levels in pediatric heart transplant recipients and examine creatinine levels as potential determinants of plasma homocysteine concentration after transplantation. METHODS: We studied 27 pediatric heart transplant patients with homocysteine levels higher than normal. All children received vitamin supplementation (vitamin B(12), vitamin E, vitamin A and folic acid). During treatment, levels of homocysteine, vitamins and creatinine were evaluated after 3, 6, 9 and 12 months. RESULTS: We observed a significant homocysteine concentration decrease after treatment at every determination, whereas no significant change occurred for creatinine. Vitamin B(12) serum level increased markedly, whereas folic acid, vitamin E and vitamin A serum levels showed only minor increases. CONCLUSIONS: We observed a significant increase of mean levels of vitamin B(12) and a moderate increase in the other 3 vitamins. We also observed a significant reduction in homocysteine levels, which returned to normal levels for age. In our patients, there was a correlation, before and after treatment, between homocysteine and creatinine levels, but there was no a direct correlation between creatinine serum levels and homocysteine reduction. We conclude that vitamin supplementation reduces and may normalize homocysteine serum level after pediatric heart transplantation.     

Predictability of tricuspid annular plane systolic excursion for the effectiveness of tolvaptan in patients with heart failure

Background

There is no echocardiographic predictor of the effectiveness of tolvaptan in patients with heart failure (HF). The aim of this study was to investigate the echocardiographic predictor of responders to tolvaptan in patients with HF.

Methods

This observational study consisted of 62 consecutive in-hospital patients with HF who received tolvaptan with volume overload despite standard therapies. The echocardiography data were obtained within 1 week before the administration of tolvaptan. Tolvaptan responders were defined as those having a body weight decrease from baseline >1 kg on the morning of day 8.

Results

The mean age of the 62 patients was 75.1 ± 13.9 years, and 45 patients (72.6%) were considered to be responders. Tricuspid annular plane systolic excursion (TAPSE) was significantly higher (17.1 ± 3.8 vs. 13.0 ± 3.9 mm; p = 0.0004) and the tricuspid valve regurgitation pressure gradient (33.3 ± 14.6 vs. 44.9 ± 12.2 mmHg; p = 0.007) and estimated right atrium pressure (7.8 ± 4.2 vs. 10.3 ± 4.5 mmHg; p = 0.043) were significantly lower in the Responder group than in the Non-responder group. In a multivariate logistic regression analysis, TAPSE was found to be an independent predictor of response (odds ratio 1.28; 95% confidence interval 1.03–1.60). According to the receiver operating characteristics analysis, the area under the curve of TAPSE was the largest among the parameters measured by echocardiography. The cut-off value for TAPSE to predict responders was determined to be 17.0 mm (sensitivity = 56.8%, specificity = 94.1%).

Conclusions

TAPSE is a simple predictor of the effectiveness of tolvaptan in patients with HF.

     

Experimental evaluation for tricuspid annular constriction with the model of tricuspid annular dilatation

We have obtained the good result about tricuspid annular constriction (TAC) for secondary tricuspid insufficiency. The purpose of this study is to investigate the effectiveness of TAC for the experimental model of tricuspid annular dilatation. First of all, tricuspid annular dilatation was made surgically in 8 mongrel dogs by placing 8 incisions to tricuspid annulus except septal cusp under the condition of heart-lung preparation. On clinical evaluation, septal annulus was kept to be intact in many cases compared with the two other areas. This experimental model of tricuspid annular dilatation was considered to be substituted to the clinical model of tricuspid annular dilatation. TAC suture was surrounded circumferentially around the dilated tricuspid annulus. And then, TAC suture was pulled out from the right atrial wall, and the circumferential length of tricuspid annulus was completely accommodated by pulling the TAC suture. The hemodynamic status was observed by right atrial pressure (V wave and mean) and right ventricular end-diastolic pressure (RVEDP). After heart resuscitation and gradual increase of preload, right atrial pressure was significantly elevated especially right atrial pressure (V wave) compared with control values. When 2 cm of circumferential length of tricuspid annulus on an average was constricted by shortening of TAC suture, right atrial pressure was significantly decreased, and then RVEDP tended to decrease. It was shown that TAC was an effective operative technique for the secondary tricuspid annular dilatation and tricuspid insufficiency from the standpoint of experimental aspect as well as clinical results.     

Transplant coronary artery disease in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary artery disease (TxCAD) contributes to a large percentage of late morbidity and mortality among adult heart transplant recipients. Intracoronary ultrasound (ICUS) is a sensitive tool in the diagnosis of TxCAD in adult patients and has allowed analysis of factors contributing to disease development. Experience with ICUS in pediatrics, however, has been limited. By using ICUS we sought to determine the overall prevalence of TxCAD in pediatrics and to characterize factors associated with its development in this population. METHODS: Eighty-six studies were performed in 51 pediatric patients a median of 3.4 years after heart transplantation. Evaluation included angiography and ICUS in 83 and angiography alone in 3 studies. Donor and recipient characteristics were obtained. The ICUS images were analyzed for intimal thickening and compared with coronary angiograms. The presence of any intimal thickening on ICUS was considered TxCAD. An intimal index and point of maximal intimal thickening (MIT) were measured. Vessel disease was graded 0 to 4 based on these results. Four patients had evidence of vasculopathy by angiography, whereas 32 patients (63%) had evidence of intimal proliferation by ICUS. Grade 2 or greater disease was present in 19 (37%) patients. A positive correlation was found when comparing time from transplant with intimal index and MIT (p < 0.001). No other factors were found to predict the development of disease. The overall prevalence of disease was 74% in patients studied at least 5 years after transplant.Intracoronary ultrasound can be performed safely in pediatric patients. Transplant coronary artery disease is common in infants and children after heart transplantation, although its prevalence appears to be less than in adult recipients at similar time intervals. We found no factor other than time from transplant was associated with development of disease.     

Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients.

OBJECTIVES: The first tissue engineered decellularized porcine heart valve, Synergraft (Cryolife Inc., USA) was introduced in Europe as an alternative to conventional biological valves. This is the first report of the rapid failure of these new grafts in a small series. MATERIALS AND METHODS: In 2001, 2 model 500 and 2 model 700 Synergraft valves were implanted in four male children (age 2.5-11 years) in the right ventricular outflow tract as a root. Two patients had a Ross operation and two had a homograft replacement. RESULTS: The cryopreserved Synergraft valves appeared macroscopically unremarkable at implantation. Recovery from surgery was uneventful and good valve function was demonstrated postoperatively. Three children died, two suddenly with severely degenerated Synergraft valves 6 weeks and 1 year after implantation. The third child died on the 7th day due to Synergraft rupture. Subsequently the fourth graft was explanted prophylactically 2 days after implantation. Macroscopically all four grafts showed severe inflammation starting on the outside (day 2 explant) leading to structural failure (day 7 explant) and severe degeneration of the leaflets and wall (6 weeks and 1 year explant). Histology demonstrated severe foreign body type reaction dominated by neutrophil granulocytes and macrophages in the early explants and a lymphocytic reaction at 1 year. In addition significant calcific deposits were demonstrated at all stages. Surprisingly pre-implant samples of the Synergraft revealed incomplete decellularization and calcific deposits. No cell repopulation of the porcine matrix occurred. CONCLUSION: The xenogenic collagen matrix of the Synergraft valve elicits a strong inflammatory response in humans which is non-specific early on and is followed by a lymphocyte response. Structural failure or rapid degeneration of the graft occurred within 1 year. Calcific deposits before implantation and incomplete decellularization may indicate manufacturing problems. The porcine Synergraft treated heart valves should not be implanted at this stage and has been stopped.     

Dobutamine stress echocardiography: experience in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary arteriopathy causes late death and is difficult to detect noninvasively. Dobutamine stress echocardiography is being used for risk stratification in adult recipients at some transplant centers, thus we investigated its role in a pediatric population. METHODS: We performed 46 stress echo studies (mean age = 11.8 years; mean years post transplantation = 4.3). An atropine/dobutamine protocol (5-40 mcg/kg/min) was used to attain a predicted target heart rate. Serial echocardiographic images were acquired at baseline and at each increment of dobutamine and recovery, and were digitized online. Data were correlated with endomyocardial biopsy (n = 23), coronary angiography (n = 26) or autopsy (n = 6). All studies were well tolerated. RESULTS: Target heart rate was achieved in 41/46 (89%) studies. The mean heart rate significantly increased from 95 to 169 beats/min and mean systolic blood pressure from 123 to 153 mm Hg (p<.05). The mean peak pressure-rate product was 23,041 beats-mm Hg/min. Coronary arteriopathy was confirmed in 5 patients by angiography (n = 3) explanted heart (n = 1) or autopsy (n = 4). In this group, abnormalities included a new reversible wall motion abnormality (n = 2), left ventricular cavity dilation with stress (n = 3), ischemia (n = 2), increased mitral insufficiency (n = 1) and marked diastolic dysfunction (n = 1). A positive study predicted death or graft failure (p< .0005). CONCLUSIONS: Echocardiographic abnormalities during stress correlated with coronary arteriopathy in this small cohort of patients; however, larger multi-center studies are warranted to assess the utility of dobutamine stress echocardiography for risk stratification for coronary disease in pediatric transplant recipients.     

Serum lipid abnormalities in pediatric liver transplant patients.

Little is known about serum lipid abnormalities in pediatric liver transplant recipients. We performed a longitudinal cohort review of 102 outpatient pediatric liver recipients surviving greater than 6 months and immunosuppressed with cyclosporine and prednisone (+/- azathioprine). The median age was 6 years, median months posttransplant 25, and male-to-female ratio 1:1.5. The average cholesterol (mean of individual means) was 177 +/- 45 mg/dl and average triglyceride level 158 +/- 71 mg/dl. The mean percent of cholesterol levels greater than 170 mg/dl and triglyceride levels greater than 140 mg/dl was 47% and 50%, respectively. Age, obesity, sex, and family history of risk factors had no significant effect on cholesterol or triglyceride levels. Bivariate regression analysis showed no meaningful association between cholesterol or triglyceride levels and cyclosporine levels, cyclosporine dose, prednisone dose, or diastolic blood pressure. Triglyceride and cholesterol neither increased nor decreased with time posttransplant. The rate of change of triglyceride or cholesterol could not be predicted by the rate of change of cyclosporine levels (or dose), or prednisone dose. We found no evidence that rises or falls in cholesterol or triglyceride levels coincided with rises or falls in either cyclosporine level or prednisone dose. Cholestasis was significantly associated with increased cholesterol and triglyceride levels (P = 0.05). A multivariate analysis was unable to predict cholesterol or triglyceride levels from three predictors: cyclosporine level, prednisone dose, and liver function. The mean dietary intake of fat and cholesterol was above RDA and exercise patterns were suboptimal in school-aged children. Conclusions: 50% of children had a mean cholesterol greater than 75th percentile (170 mg/dl); 20% were above the 95th percentile; 56% had a mean triglyceride level greater than 140 mg/dl. By these criteria the majority of pediatric liver transplant patients have lipid abnormalities that may predispose them to atherosclerosis in later life.     

Cardiac allograft vasculopathy in pediatric heart transplant recipients

Metabolic parameters for coronary allograft vasculopathy (CAV) have not been well defined in children. CAV (by angiography or autopsy) was studied in 337 heart recipients on a cyclosporine-based steroid-sparing regimen. Freedom from CAV for all was 79% at 10 years. Fifty-nine patients (18%) developed CAV at a mean of 6.5 +/- 3 years post-transplant. First year rejections were significantly higher in CAV, mean 2.3 vs. 1.4, P = 0.003, odds ratio (OR) 1.8. Rejection with hemodynamic compromise beyond 1 year post-transplant was associated with CAV, P < 0.001, OR 8.4. There was no significant correlation among human leukocyte antigen DR (HLA DR) mismatch, pacemaker use or homocysteine levels and the development of CAV. Maximum cholesterol and low density lipoprotein (LDL) levels were not significantly different. Neither diabetes nor hypertension was significant predictors of CAV on multivariate logistic regression analysis. In conclusion, frequent and severe rejection episodes may predict pediatric CAV. Neither glucose intolerance nor lipid abnormalities appeared to alter risk for CAV in this population.     

Spectrum of left ventricular dysfunction in potential pediatric heart transplant donors.

BACKGROUND: Although myocardial dysfunction severe enough to preclude harvest for transplantation has been reported in approximately 20% of potential adult organ donors, the incidence of myocardial dysfunction in the pediatric population has not been studied systematically. Therefore, the purpose of this study was to determine the spectrum of myocardial dysfunction in potential pediatric heart transplant donors. METHODS: We reviewed the pediatric cardiology database at Primary Children's Medical Center to identify all children who had screening echocardiograms for potential organ donation. We reviewed charts for patient age and size, cause of brain death, and type of pharmacologic support. Echocardiograms were reviewed retrospectively for left ventricular systolic function (shortening or ejection fraction), wall motion abnormalities, diastolic function (mitral E/A ratio), Tei index, and mitral regurgitation. RESULTS: We identified 23 potential donors (age, 6.7 +/- 4.4 years; range, 5 days to 15 years). All patients were receiving pharmacologic support. We found systolic left ventricular dysfunction, defined as an ejection fraction <50% or a shortening fraction <28%, in 57% (13/23) of the patients. We found mitral regurgitation in 85% (11/13) of the patients with systolic dysfunction and in zero of 10 with normal ejection phase indices. Diastolic dysfunction (mitral E/A reversal) was found in 45% (6/13) of those with systolic dysfunction and in 60% (6/10) of patients with normal systolic ejection phase indices. The Tei index was abnormal in 8 of 13 patients with left ventricular systolic dysfunction (range, 0.5-1.4), and was normal in the 6 patients with isolated diastolic dysfunction. One patient, who was electrocuted, had regional wall motion abnormalities. Of the 23 potential donors, 19 (87%) had evidence of systolic or diastolic dysfunction. A total of 13 hearts (3 with normal systolic function, 4 with systolic dysfunction, and 6 with isolated diastolic dysfunction) were harvested for transplantation. CONCLUSIONS: Left ventricular systolic and diastolic dysfunctions are common findings in potential pediatric organ donors. Despite this, previous studies have shown that some of these hearts can be transplanted successfully. We speculate that some of the abnormalities occur as a physiologic consequence of brain death and, thus, may be reversible after transplantation. To avoid wasting a valuable, limited resource, further study is needed to identify the donors suitable for pediatric heart transplantation.     

Long-term follow-up after total lymphoid irradiation in pediatric heart transplant recipients.

BACKGROUND: Total lymphoid irradiation (TLI) is used to treat recurrent allograft rejection. Short-term success and complication rates have been reported in pediatric and adult cardiac transplant populations. We report the long-term efficacy and safety of TLI in treating intractable rejection in pediatric patients. METHODS: Eight pediatric patients were treated with TLI (7 for recurrent rejection, 1 for risk of medication non-compliance). Therapy consisted of a mid-plane dose of 8 Gy administered with a 6-MeV linear accelerator using an anterior-posterior opposed technique. We reviewed outcomes for a total of 40 patient-years of follow-up. RESULTS: We encountered rejection (>Grade 2 by International Society for Heart and Lung Transplantation criteria) in 56.7% +/- 34.7% of biopsies performed within 90 days before TLI. Rejection rates dropped to 3.1% +/- 8.8% within the first 90 days (p < 0.005) after therapy and remained low at 5.6% +/- 1.3% (p < 0.05) during the first year after completion of TLI. Median time from TLI to the first subsequent rejection episode was 305 days (range, 77-1,920 days). Long-term follow-up (>3 years) of 5 patients demonstrated a continuing low incidence of rejection. Non-Hodgkin's lymphoma was diagnosed in 1 of 8 patients, graft coronary artery disease in 4 of 8 patients, and restrictive cardiomyopathy in 1 of 8 patients after TLI. CONCLUSIONS: Total lymphoid irradiation is an effective treatment for recurrent rejection and has short- and long-term efficacy. Morbid events may include cancer, graft coronary artery disease, and restrictive cardiomyopathy.     

Sirolimus immunosuppression in pediatric heart transplant recipients: a single-center experience.

BACKGROUND: Sirolimus has been used in heart transplant recipients for treatment of rejection, alternative immunosuppression (IS) and promotion of regression and prevention of graft vasculopathy (coronary artery disease [CAD]). This study reports on our center's experience with 16 children who underwent heart transplantation. METHODS: Data were obtained by retrospective review. RESULTS: Median age at time of review was 12.3 years (n = 16, 5.1 to 18.0 years; 9 boys, 7 girls), and at time of transplant 7.5 years (6 months to 18.0 years). Median time of sirolimus introduction was 2.7 years (1 month to 8.2 years) post-transplant. Fifteen patients were on steroids, 10 on tacrolimus (FK) and mycophenolate mofetil (MMF), 5 on FK and 1 on MMF with no calcineurin inhibitors (CNIs). The average dose of sirolimus was 0.25 mg/kg or 7.0 mg/m(2) to maintain a target level of 5 to 15 mug/liter. Sirolimus was started for CAD in 6 patients (38%), rejection in 5 (31%), and in 5 with combinations of CNI intolerance, CAD, renal dysfunction and rejection. All 6 who received sirolimus for rejection (International Society for Heart and Lung Transplantation [ISHLT] Grade 3A) showed improvement on follow-up biopsies. Two of 3 who received sirolimus for renal dysfunction showed improvement (glomerular filtration rate [GFR] 43 to 67 and 32 to 106 ml/min per 1.73 m(2), respectively). Side effects included hyperlipidemia (38%), abdominal pain (31%), mouth ulcers (26%), anemia or neutropenia (12.5%), persistent pericardial effusion (6%) and interstitial lung disease (6%). Sirolimus therapy was discontinued in 3 patients due to side effects. CONCLUSIONS: In this study sirolimus was found to be a valuable IS agent for the management of rejection, significant renal dysfunction and CNI side effects. These results support the need for prospective studies of the role of sirolimus in primary rejection prophylaxis, primary CAD prophylaxis and CAD regression. There also exists a need to establish an adverse event profile for this drug.