First Report of a Successful Pregnancy in an Everolimus-Treated Heart-Transplanted Patient: Neonatal Disappearance of Immunosuppressive Drugs.

The use of everolimus (EVL) as primary immunosuppression is steadily increasing in heart transplantation (HTx) patients. Limited data currently exist in kidney transplantation, but there is no report of EVL use during pregnancy after HTx and its pharmacokinetics in the newborn. We report a case of an unplanned pregnancy discovered at 21 weeks of gestation in a female HTx patient aged 40 years treated with EVL and cyclosporine (CyA). Because pregnancy was advanced, immunosuppression therapy was left unchanged. At 36 weeks, a healthy infant was delivered. At birth, CyA blood levels were lower in the neonate, but EVL concentrations in maternal and neonatal umbilical blood were similar. Amniotic fluid concentrations were undetectable for both drugs. In the newborn, EVL was measurable at 5 days after birth, whereas CyA disappeared within 2 days. Cord blood displayed a normal count of B and T cells and CD4, CD8 and natural killer cell populations. At birth, both mother and newborn displayed the same blood levels of EVL; therefore, a filter effect of the placenta may be hypothesized for CyA but not for EVL. No immediate complications were observed with this pregnancy.

Outcome of patients listed for heart transplantation after a failed surgical ventricular restoration procedure.

Patients with end-stage ischemic cardiomyopathy (IHD) and left ventricular (LV) dilatation are increasingly treated by means of surgical ventricular restoration (SVR). In some patients, SVR can delay heart transplantation (HTX). We retrospectively analyzed our experience, trying to ascertain whether HTX after a failed SVR (fSVR) carried a greater mortality risk. Since 1985, we performed 742 HTX. Since June 1999, 133 IHD patients were listed for HTX. We assigned them to 3 groups: (A) not a redo (n=54); (B) redo after coronary artery bypass grafting (n=54); and (C) redo after fSVR (n=25). Respectively, 37, 33, and 12 patients underwent HTX with in-hospital mortality after HTX of 4/37 (10.8%), 12/33 (36.4%), and 2/12 (16.7%). Mortality on the list was 9/54 (16.7%), 11/54 (20.4%), and 7/25 (28.0%) respectively. Removal from the list occurred in 4, 5, and 2 patients, and 4, 5, and 4 patients are still awaiting HTX, respectively. In group C, the mean time from SVR to HTX list was 45.6+/-43.3 months, and list mortality occurred after 5.83+/-5.81 months. In-hospital mortality in both patients of group C was due to the occurrence of multisystem organ failure; 10/12 were extubated after 19.3+/-9.6 hours and discharged from the intensive care unit after 3.9+/-1.6 days. The recorded complications were: 3 acute renal failure, 1 pericardial effusion, and 2 episodes of acute rejection. Since only 5/25 patients with fSVR had undergone SVR at our institution, we cannot establish which patients were really eligible for HTX at the time of SVR. Our experience showed that patients listed for HTX displayed a high list mortality, but that HTX after a failed SVR did not seem to have a poorer outcome than HTX after previous conventional CABG.

Possible role of everolimus in improving renal function in long-term heart transplantation.

Patient survival after heart transplantation has improved dramatically since the availability of calcineurine inhibitor (CNIs); the number of long-term patients is progressively increasing. However, in these patients, nephrotoxicity of CNIs has been largely responsible for the progressive development of renal dysfunction. Since impaired renal function is an important issue that reduces long-term patient survival, it is important to develop strategies to improve renal function while maintaining immunologic safety to preserve graft function. Everolimus is an mTOR inhibitor sirolimus analogue, that has proved, to be highly efficacious to prevent acute myocardial rejection and reduce the severity of cardiac allograft vasculopathy in de novo HTx patients. There is reasonable evidence that, in long term heart transplanted patients, renal function may improve when everolimus is administered associated with a progressive reduction of CNIs. So far there is no evidence to identify which patient may benefit from this therapeutic approach. Indeed everolimus alone may be equally effective to prevent rejection and improve renal function when CNIs are completely discontinued, but data are still lacking on the risks, dosages and side effects of this type of immunosuppression. Ongoing clinical studies will provide further guidance about the possibility to halt or reduce the progression of renal impairment in long term heart transplant patients.

Atrial natriuretic peptide in diabetic and nondiabetic patients with and without heart transplantation.

BACKGROUND: Natriuretic peptides are useful markers for risk stratification of patients with heart disease. However, conflicting results have been reported about circulating atrial natriuretic peptide (ANP) concentration in heart transplant recipients. METHODS: To ascertain the effects of diabetes and acute insulin administration on plasma ANP concentrations in a model of heart denervation, we studied 12 diabetic (D-OHT) and 6 nondiabetic heart-transplanted (OHT) patients using the euglycemic-hyperinsulinemic clamp and oral glucose tolerance tests. Five patients with type 2 diabetes without heart transplantation (D) and 9 healthy subjects (NOR) matched for anthropometric features served as the controls. RESULTS: Means baseline plasma ANP concentration was higher in D-OHT (82 +/- 15 pg/mL) than in OHT or NOR (27 +/- 4 or 30 +/- 5; P < .01), but was not different than D (69 +/- 12; P = .82). During the clamp plasma ANP showed similar increases in all groups (49 +/- 4, 39 +/- 3, 59 +/- 4, and 49 +/- 3% in D-OHT, OHT, D, and NOR; P < .02 vs basal, P = NS among groups). Plasma osmolarity and catecholamines were also not different among groups and did not increase during the clamp. Fasting plasma ANP concentrations correlated with plasma glucose concentrations measured 120 minutes after oral glucose tolerance testing. CONCLUSIONS: Among heart transplantation recipients fasting plasma ANP concentrations were not different at 5 to 6 years after the surgical procedure than in nondiabetic controls. Increased ANP concentrations were observed among recipients with diabetes and among nontransplanted diabetic patients. Although the insulin-induced increment in ANP concentrations was not different among groups, circulating ANP was strongly associated with glucose tolerance status.

Anti-CD20 antibody (rituximab) administration in patients with late occurring lymphomas after solid organ transplant.

BACKGROUND AND OBJECTIVES: Aggressive diffuse large cell non-Hodgkin's lymphoma (DLCL) occurring late after a solid organ transplant fails to regress after discontinuation of immunosuppression. Moreover, chemotherapy treatment is associated with a high mortality rate due to severe toxicity. Since the majority of post-transplant lymphoproliferative disorders derive from B-lineage lymphocytes, the administration of anti-B monoclonal antibodies represents a rational therapeutic option. DESIGN AND METHODS: Five patients who developed CD20-positive DLCL more than two years after heart or liver transplantation were treated with a weekly chemotherapy program (2 patients), radiotherapy (2 patients) and surgery (1 patient) followed by a minimum of 4 intravenous doses of rituximab (375 mg/m(2)). RESULTS: A favorable clinical outcome was observed in three patients in whom surgery or radiotherapy had produced significant tumor debulking. Only a partial clinical effect was documented in the two patients with advanced clinical stage disease. INTERPRETATION AND CONCLUSIONS: Rituximab can be safely administered to patients with aggressive CD20-positive DLCL occurring late after a solid organ transplant. However, a positive clinical outcome may be expected only in patients in whom surgery or radiotherapy has achieved significant regression of tumor burden.

Continuous retrograde warm blood reperfusion reduces cardiac troponin I release after heart transplantation: a prospective randomized study.

During heart surgery, cardiac troponin I (cTn-I) measurement provides a tool to evaluate different cardioprotective techniques. To investigate myocardial protection during heart transplantation (HTx), cTn-I and creatine kinase (CK)-MB release was measured in 42 patients randomized to receving either continuous retrograde warm blood reperfusion or no reperfusion after cold cardioplegia. A significant linear correlation was found between donor heart ischemic time and peaks and the area under the curve of cTn-I and CK-MB release. In patients with an ischemic time longer than 90 min, cTn-I release was significantly lower in those receiving continuous retrograde warm cardioplegia than in controls. No significant difference was observed for CK-MB, tCK, and myoglobin. Our data suggest that the measurement of postoperative cTn-I release may provide a method to evaluate ischemic cardiac damage after HTx. When the ischemic time is longer than 90 min, warm retrograde blood cardioplegia provides better myocardial protection than no reperfusion.

Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients.

BACKGROUND: Fungal infections (FI) after solid organ transplantation (Tx) remain a major cause of morbidity and mortality. Aspergillus and Candida account for more than 80% of FI. METHODS: One thousand nine hundred and sixty-three patients undergoing thoracic organ Tx [1,852 heart and 111 lung (35 heart-lung Tx, 30 double-lung Tx, 46 single-lung Tx)] in 12 Italian Centers between November 1985 and January 1997 were included in the study. RESULTS: Fifty-one patients (41 heart Tx - 2.2%; 9 heart-lung Tx - 25.7%; 1 single-lung Tx - 2.2%) developed 53 invasive FI at a median of 58 days (range 6-2479) after Tx. Aspergillosis was the most frequent FI in our series accounting for 64.1% (34/53) of all FI [A fumigatus, n=29 (85.3%); A nidulans, n=2 (5.9%); A niger, n=2 (5.9%); A terreus, n=1 (2.9%)]; 30 (88.2%) patients developed invasive lung aspergillosis, 2 (5.9%) a tracheobronchitis, 1 (2.9%) a skin infection, and 1 (2.9%) a sternal wound infection. Twelve patients (22.6%) developed candidiasis [C albicans, n=8 (66.6%); C krusei, n=1 (8.3%); C glabrata, n=1 (8.3%); C parapsilosis, n=1 (8.3%); C sake, n=1 (8.3%)]. There were seven episodes (58.3%) of candidemia, two (16.7%) esophagitis, two (16.7%) gastritis, and one (8.3%) tracheobronchitis. Mortality was 29.4% for patients developing aspergillosis and 33.3% for those experiencing candidiasis. Furthermore, four patients developed the following: one C neoformans meningitis, one Sporothrix cyanescens pneumonia, one Rhizopus spp. tracheobronchitis, and one Trichosporon beigelii disseminated infection. Three additional patients were diagnosed affected by deep mould infection by histology alone. CONCLUSIONS: Deep-seated FI were relatively rare in our series, although their mortality rate is still very high.

Cyclosporine and graft coronary artery disease after heart transplantation.

Risk factors for graft coronary artery disease after heart transplant are discussed in relationship to cyclosporine dosages. Patients receiving a mean cyclosporine dose higher than 4 mg/kg/day had lower incidence of graft coronary disease than patients receiving lower dosages.

High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders.

Epstein-Barr virus (EBV) DNA was quantitated in peripheral blood mononuclear cells (PBMC) from 25 healthy subjects, 105 asymptomatic solid-organ transplant (SOT) recipients, and 15 SOT recipients with symptomatic EBV infections by using a newly developed quantitative-PCR technique. Patients with symptomatic EBV infections had significantly higher (P < 0.001) median EBV DNA levels than asymptomatic SOT recipients and immunocompetent individuals. In SOT recipients, the positive predictive value of EBV DNA levels of >1, 000 genome equivalents (GE)/0.5 microg of total PBMC DNA was 64.7% for symptomatic EBV infection, while the negative predictive value was 96.1%. In 19 of 32 (59.3%) asymptomatic SOT recipients, EBV DNA levels were consistently below 1,000 GE for as long as 18 months, while 10 of 32 (31.2%) patients had 1,000 to 5,000 EBV GE at least once during follow-up. In a minority of patients (3 of 32; 9.3%), >/=5,000 GE could be detected at least once during follow-up. Reduction of immunosuppressive treatment decreased EBV DNA levels by >/=1 log(10) unit in patients with symptomatic EBV infections. Quantification of EBV DNA is valuable for the diagnosis and monitoring of symptomatic EBV infections in SOT recipients.

Epstein-Barr virus-negative lymphoproliferate disorders in long-term survivors after heart, kidney, and liver transplant.

BACKGROUND: Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. METHODS: We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. RESULTS: All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. CONCLUSIONS: Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.

[Heterotropic heart transplantation in young patients with elevated pulmonary vascular resistance]. / Trapianto cardiaco eterotopico in giovani pazienti con elevate resistenze vascolari polmonari.

UNLABELLED: Right heart failure due to elevated PVR is one of the major causes of mortality and morbidity after orthotopic heart transplantation. In 5 patients (median age 14 years) with dilated or restrictive cardiomyopathy and important elevation of the PVR, a heterotopic heart transplantation was performed using the technique reported by Yacoub (the donor pulmonary artery was implanted on the recipient right atrium). All the patients presented with at least two of the following parameters: PVR/m2 > 6 U, transpulmonary gradient > 15 mmHg, mean pulmonary pressure > 50 mmHg. One patient with restrictive cardiomyopathy died three months after transplantation of severe failure of the native right ventricle. The other four patients, with a mean follow-up of 29 months, are in good clinical and hemodynamic condition and later post-operative catheterizations showed a progressive reduction of the pulmonary pressure. CONCLUSIONS: Our experience suggests that this type of heterotopic heart transplantation can be performed successfully in patients with secondary pulmonary hypertension. Particular attention should be paid to patients with restrictive cardiomyopathy and important right ventricle dysfunction, in which a complete heterotopic heart transplantation could be a better solution.

Primary effusion lymphoma after heart transplantation: a new entity associated with human herpesvirus-8.

Deep immunosuppression and Epstein-Barr virus (EBV) infection promote the emergence of lymphoproliferative disorders in patients undergoing solid organ transplantation. In the last few years a new herpesvirus, named human herpesvirus-8 (HHV-8), has been identified in Kaposi's sarcoma and primary effusion lymphoma (PEL) developing in AIDS patients. Subsequently, the same viral DNA sequences have been identified in almost all cases of Kaposi's sarcoma emerged outside HIV infection, thus suggesting their possible pathogenetic role in this tumor. Similarly, the association between HHV-8 and PEL also emerged in cases without HIV infection, even though the total number of these patients is still limited. Here, we focus on the emergence of this unusual lymphoma in patients undergoing solid organ transplant and underline once again its association with the HHV-8. Moreover, despite the characteristic local growth of this peculiar type of lymphoma, we demonstrate at the molecular level, an early neoplastic spread to the bone marrow suggesting the need to investigate in more detail the origin of the disease, as well as the molecular mechanisms controlling its systemic dissemination.

Troponin I as a specific marker for heart damage after heart transplantation in a patient with becker type muscular dystrophy.

In a patient with Becker type muscular dystrophy, the development of cardiomyopathy may require heart transplantation, and during both the perioperative period and later it is useful to determine whether myocardial cell damage is occurring; however, the measurement of serum levels of creatine kinase (CK), MB isoenzyme, is not useful because that isoenzyme is released by the dystrophic skeletal muscle, as well as damaged myocardium. Because cardiac troponin I (cTn I) seems to be quite specific for myocardial cells, we reasoned that measurement of serum levels of this protein could distinguish between myocardial damage and skeletal muscle disease in this patient during and after transplantation. During the immediate postoperative period, the time course of the release of total CK (tCK), CK MB mass, myoglobin, and cTn I were different, yielding a peak within 4 hours for CK MB, 24 hours for myoglobin and 36 hours for tCK and cTn I. During the first postoperative year, the patient displayed a release of tCK, CK MB, and myoglobin; cTn I was constantly lower than the reference value for cardiac myocyte necrosis, suggesting the presence of a continuous muscular damage without any myocardial involvement and an accurate specificity of cTn I to differentiate between myocardial and muscular cell damage in patients with neuromuscular disorders.

The risk of coronary artery disease after heart transplantation is increased in patients receiving low-dose cyclosporine, regardless of blood cyclosporine levels.

BACKGROUND: Coronary artery disease (CAD) of allografted hearts is the main cause of late mortality after cardiac transplant, but its etiology is still undetermined. HYPOTHESIS: This study was undertaken to evaluate the relevance of several risk factors, including cyclosporine (CsA) dose and blood CsA levels, to the incidence of CAD. METHODS: In 163 heart transplants performed between November 1985 and August 1994 at our Institution, CAD was diagnosed by coronary angiography or at postmortem examination. Patients in whom postmortem examination or coronary angiography was not performed, as well as those < 15 years of age and those who died within 1 month of surgery, were excluded from the study. The following risk factors were analyzed: recipient age, gender, pretransplant diagnosis, donor age, number of human leukocyte antigen (HLA)-AB mismatches, cytomegalovirus serology, mear serum cholesterol and triglyceride levels, the number of treated acute rejections, mean weighted CsA dose (CsA dosew and weighted blood CsA levels (blood CsA levelw). RESULTS: Coronary artery disease was diagnosed in 32 patients (19.6%). A low mean CsA dosew was the only significant predictor for CAD at multivariate analysis (p < 0.01): there was no correlation with blood CsA levelw. In the patients receiving a CsA dosew > 4 mg/kg/day, the 8.9 year probability of their remaining CAD free was 69% [confidence interval (CI) 50-87%] in comparison with 31% (CI 0-65%) in patients receiving a CsA dosew < 4 mg/kg/day. CONCLUSION: In our experience, a low CsA maintenance dose is the main risk factor for CAD, irrespective of blood CsA levels.

Medical treatment of end-stage heart failure.

Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.

Heart rate variability in the human transplanted heart: nonlinear dynamics and QT vs RR-QT alterations during exercise suggest a return of neurocardiac regulation in long-term recovery.

RATIONALE: Functional reinnervation of the transplanted human heart by the autonomic nervous system has not been demonstrated. A lack of autonomic control of the transplanted allograft is reflected by an increased resting heart rate, a sluggish heart rate response to dynamical exercise and a reduced heart rate variability. Recent evidence suggests that a measure of deterministic chaos in the heartbeat interval series (point correlation dimension, PD2i) is superior to the conventional power spectrum or other stochastic measures in detecting changes in the mechanism underlying heartbeat generation. METHODS: The PD2i is based on the presumption that the variability is determined and patterned, whereas the stochastic measures all assume that the variability is around a stationary mean and is noise. The PD2i reconstructs the degrees of freedom (number of independent variables) in the system that generates the time series examined, and does this irrespective of whether the system is stochastic or deterministic and is stationary in time. RESULTS: PD2i was determined for heartbeat intervals (RR, ECG digitized at 1200 Hz; supine posture) of 23 heart transplant recipients (HTR: 9 adults, 14 children; 0.04-7.7 years after transplantation) and 21 healthy control subjects (CTL; 13 adults, 8 children). The PD2i (+/-SD) averaged 5.4 +/- 0.7 for the CTL adults and 5.4 +/- 0.6 for the CTL children. Mean PD2i was reduced after transplantation to 1.1 +/- 0.1 in 6 HTRs recorded within 1 year after surgery; in one HTR recorded 2 weeks after surgery the mean PD2i was 3.7. Between 1 to 2 years PD2i was found increased in 2 of 3 subjects and between 2 to 8 years it was increased in 13 of 13, but not to control levels. In normal hearts the QT subinterval of each heartbeat cycle is associated with inotropy and the RR-QT remainder with chronotropy (i.e., the dyastolic interval during which RR is primarily regulated). To examine more closely the residual and returning heartbeat dynamics of the HTR subjects, these subinterval series were examined during mild exercise (40 to 90 Watts) and its recovery. In recent HTRs, resting QT and RR-QT were moderately reduced and modulated by exercise and recovery, but with an approximate 100 beat latency. In long-term (7-8 years) HTR subjects there was a rapid and larger response to exercise/recovery, but compared to normal the range was smaller and the complexity of the subinterval trajectories in time was simpler. CONCLUSIONS: Recurrence of low-dimensional deterministic dynamics after transplantation suggests recovery of neurocardiac control attributable to 1) reorganization of the viable intrinsic cardiac nervous system, 2) reinnervation by the extrinsic autonomic nervous system, or 3) both.

Possible pathogenic role for Sporothrix cyanescens isolated from a lung lesion in a heart transplant patient.

Sporothrix cyanescens is a fungus rarely isolated from human specimens. Its pathogenic role has never been demonstrated but has been postulated on the basis of its occurrence in normally sterile body sites, its isolation from debilitated individuals and its thermotolerance. A first case of nodular pulmonary lesions developing in an immunosuppressed, heart transplant patient is reported. Sporothrix cyanescens was isolated from a fine needle lung biopsy. The patient failed to respond to itraconazole therapy, whereas he was successfully treated with amphotericin B.

Balloon aortic valvuloplasty in the first year of life.

Between February 1988 and September 1993 balloon aortic valvuloplasty was attempted in 33 consecutive patients in the first year of life: 20 patients (61%) were younger than 1 month. Major associated anomalies such as mitral stenosis, coarctation, and hypoplastic left ventricle were found in 11 cases (33%). The balloon dilation of the aortic valve was accomplished through the right carotid cut-down approach in neonates and patients with body weight < 5 kg, through a percutaneous femoral approach in the others; the procedure was completed in all. The peak systolic gradient across the aortic valve measured at catheterization fell from 80 +/- 33 mmHg (range 25-165) before the dilation to 27 +/- 17 mmHg (range 0-65), afterwards (p < 0.0001). The left ventricular ejection fraction increased from 44% +/- 26% to 61% +/- 17%, 24-48 hours after the procedure (p < 0.0001). Aortic insufficiency developed in 17 cases, being moderate in 2, mild in 6, and trivial in 9. Seven patients (21%), all in the first month of life, died within 30 days from the valvuloplasty; major associated anomalies were present in six; the death was due to a procedure related complication in one. No mortality was observed among the patients undergoing valvuloplasty beyond the first month of life. On follow-up (6 months to 6 years) aortic restenosis occurred in 3 cases; 1 was treated by surgical valvotomy, 2 by repeat balloon valvatomy; in another 2 cases, a subvalvular aortic obstruction developed and was relieved by surgical resection. There was no late mortality. Thus, balloon valvuloplasty appears to be an effective palliation for critical aortic stenosis in infancy. Early mortality is mainly related to associated anomalies.