Skin-Related complications of Klippel-Trenaunay Syndrome: a retrospective review of 410 patients.

BACKGROUND: Little is known about skin-related complications in Klippel-Trenaunay syndrome (KTS), a complex vascular anomaly defined by capillary malformation (CM), venous malformation (VM) ± lymphatic malformation (LM) and limb overgrowth. Reported skin-related complications of KTS include ulceration, vascular ectasias (blebs), bleeding and infection. OBJECTIVE: To determine the spectrum, prevalence and predictors of skin-related complications in KTS. METHODS: A retrospective review of 410 patients fulfilling KTS criteria was performed to assess for the presence of skin-related complications. RESULTS: Skin-related complications were present in 45% of patients. Most prevalent were CM-related complications including blebs, bleeding, thickening (25%), cellulitis (22%) and ulceration (21%). Features positively associated with skin-related complications were presence of LM (OR 17.17; P < 0.001), VM on the buttocks/perineum/genitalia (OR 1.92; P = 0.009), CM on the feet (OR 1.77; P = 0.039) and male sex (OR 1.63; P = 0.034). Features negatively associated with skin-related complications were CM on the trunk (OR 0.59; P = 0.029) and tissue hypertrophy of the hands (OR 0.27; P = 0.025). CONCLUSION: Skin-related complications affect nearly half of patients with KTS. Those with lymphatic involvement or malformation presence in the undergarment area or feet are most at risk.

A reduced-energy intake, well-balanced diet improves weight control in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi syndrome (PWS) have a predictable pattern of weight gain, with obesity beginning in early childhood and worsening as they get older and hyperphagia increases. Data on the most effective dietary modifications are scant and primarily anecdotal. As part of a longitudinal study investigating the natural history of PWS, we evaluated the effect of a well-balanced, energy-restricted diet on body composition and weight in young children with PWS. METHODS: Sixty-three children, aged 2-10 years, with genetically proven PWS participated in the present study. These children had measurements of body composition by dual-energy X-ray absorptiometry and resting energy expenditure (REE), as well as a 3-day diet history analysis both before and after intervention. Energy calculations were based on the individual's REE, with the recommendation that the macronutrients of the diet consist of 30% fat, 45% carbohydrates and 25% protein, with at least 20 g of fibre per day. RESULTS: Thirty-three families adhered to our dietary recommendations for both energy intake and macronutrient distribution. Those 33 children had lower body fat (19.8% versus 41.9%; P < 0.001) and weight management (body mass index SD score 0.3 versus 2.23; P < 0.001) than those whose parents followed the energy intake recommendations but did not alter the macronutrient composition of the diet. Those who followed our recommendations also had a lower respiratory quotient (0.84 versus 0.95; P = 0.002). CONCLUSIONS: Our recommendation for an energy-restricted diet with a well-balanced macronutrient composition and fibre intake improves both weight and body composition in children with PWS compared to a simple energy-restricted diet.

The presentation, course and outcome of COVID-19 infection in people with Prader-Willi syndrome: unexpected findings from an international survey.

BACKGROUND: Prader-Willi syndrome (PWS), is a genetically determined neurodevelopmental disorder, associated with intellectual disabilities and a high incidence of obesity, diabetes mellitus, and respiratory disorders. We hypothesised that COVID-19, a viral infection which more severely affects people with these conditions, would, in people with PWS, present atypically and result in severe outcomes. METHOD: A structured on-line questionnaire was piloted with parents and professionals at the International Prader-Willi Syndrome Organization (IPWSO) and promoted internationally through their global network. Family members/other carers were asked to complete if someone they cared for with PWS was strongly suspected or confirmed as having COVID-19. RESULTS: Over 1 year of the pandemic 72 responses were received, 47 adults, 25 children. The following underlying conditions were present: 16 people with PWS were overweight and 18 obese, five had diabetes mellitus and 18 sleep apnoea. Main presenting symptoms were raised temperature, fatigue/daytime sleepiness, dry cough, headache/pain, and feeling unwell, with illnesses generally lasting less than a week. Length of illness was not significantly related to age, BMI, sex, or genetic subtype. No one was ventilated or in an intensive care unit or died, one person was in hospital for four days needing oxygen. CONCLUSIONS: Contrary to our hypothesis, the PWS cohort had asymptomatic infection or mild illness. A possible explanation, supported by anecdotal evidence from parents and professional carers, is that people with PWS have a degree of innate immunity to viral infections. However, likely selection effects and a relatively low number of responses means that further evidence is needed to test this hypothesis.

Epigenetic regulation of pericentromeric heterochromatin during mammalian meiosis.

Mammalian meiosis is a process that allows diploid progenitor germ cells to produce haploid gametes after proceeding through 2 rounds of cell divisions. The first division (MI) is unique and results in the separation of homologous chromosomes, while the second division (MII) leads to the separation of sister chromatids similar to a somatic cell division. However, the mechanisms by which meiotic cells regulate their 2 very different cell divisions are not well understood. We postulated a role for epigenetic chromatin modifications in regulating these processes. We found prior to the onset of MI that pericentromeric heterochromatic regions, which are enriched with histone H3K9me2 throughout meiosis, become enriched at late pachytene with H3S10ph and at diplotene with H4K5ace and H4K16ace, but remain underacetylated at other sites examined. RNA polymerase II, which is clearly excluded from pericentromeric heterochromatin at pachytene, becomes exclusively associated with these regions from diplotene to MI. By contrast, pericentromeric heterochromatic regions at MII are not engaged by RNA polymerase II nor enriched with H3S10ph. Furthermore, we found DICER to localize exclusively to pericentromeric heterochromatin at MI, but not MII. These results are significant since they suggest: (1) that distinct chromatin modifications differentiate the 2 meiotic divisions; (2) a role for repetitive DNA elements and RNAi in mammalian meiosis; (3) H3K9me2 is not sufficient to block RNA polymerase II elongation through heterochromatin, and (4) H3S10ph provides a 'binary switch' to activate transcription in heterochromatin.

Histone H3 lysine 4 dimethylation is enriched on the inactive sex chromosomes in male meiosis but absent on the inactive X in female somatic cells.

Inactivation of the X chromosome occurs in female somatic cells and in male meiosis. In both cases, the inactive X chromosome undergoes changes in histone modifications including deacetylation of core histone proteins and enrichment with histone H3 lysine 9 (H3-K9) dimethylation. In this study we show that while the inactive X in female somatic cells is largely devoid of H3-K4 dimethylation, the inactive X in male meiosis is enriched with this modification. However, the inactive X chromosome in female somatic cells and the inactive X and Y in male meiosis are devoid of H3-K4 trimethylation. Further, trimethylation of H3-K4 is present at discrete regions along most of the autosomes, while H3-K4 dimethylation shows a more homogenous staining. Also, the Y chromosome is largely devoid of H3-K4 di- and trimethylation in somatic cells of both humans and mice, however, the Y chromosome is enriched with H3-K4 di- but not trimethylation throughout spermatogenesis. Our results provide insights into the differences between female somatic cells and male germ cells in inactivating the X chromosome, and suggest that trimethylation, and not dimethylation, of H3-K4 is a more robust indicator of the active regions of the genome.

Sudden unexpected death in children and adolescents.

To determine the incidence and clinicopathologic spectrum of sudden unexpected death, we reviewed the death certificate of all residents of Olmsted County, Minnesota who were between 1 and 22 years of age when they died during the period from January 1950 to October 1982. Of 515 death certificates reviewed, 12 (2.3%) recorded sudden unexpected death, resulting in an incidence of 1.3 per 100,000 patient-years. The subjects ranged in age from 3 to 20 years (median 13); 8 of the 12 were male. Of the 12 deaths, 4 were definitely cardiac-related and 3 were probably cardiac-related. In the five other cases, the cause of death was unknown. Three of the 12 subjects had a history of syncope; 2 of the 3 had syncope associated with exercise, and both died while exercising. The relative rarity of sudden unexpected death in children and adolescents probably precludes population screening techniques to identify subjects at risk. However, a subset of subjects with 1) exercise-associated syncope, 2) nonvasodepressor syncope, 3) a family history of sudden unexpected death, or 4) a family history of hypertrophic cardiomyopathy deserves extensive and thorough evaluation.

Cor triatriatum dexter: two-dimensional echocardiographic diagnosis.

Cor triatriatum dexter is a malformation resulting from lack of normal regression of the embryonic right valve of the sinus venosus. In this situation, the right atrium is divided by a membrane into two chambers. Two-dimensional echocardiography was used in the antemortem diagnosis of this rare cardiac anomaly in a neonate. Associated cardiac lesions were also documented. The patient died, and findings were verified at autopsy.

Spectrum of exercise intolerance in 45 patients with Ebstein's anomaly and observations on exercise tolerance in 11 patients after surgical repair.

To determine the effects of definitive operation for Ebstein's anomaly on rest and exercise cardiorespiratory function, cycle exercise studies were performed on 38 patients with Ebstein's anomaly before definitive operation and on 11 patients after operation. An atrial septal defect was present in 29 of the 38 preoperative patients and in none of the postoperative patients. Seven of the postoperative patients had tricuspid valvuloplasty and four had valve replacement. Exercise tolerance, as defined by maximal oxygen uptake, was significantly greater in patients after operation for Ebstein's anomaly than in the preoperative patients. However, exercise tolerance for preoperative patients without an atrial septal defect was similar to that for postoperative patients. Tricuspid valve repair or replacement appeared to affect favorably cardiac output response to exercise. Rest systemic arterial oxygen saturation increased from 88 to 95% and exercise saturation from 77 to 93% after operation. Rest ventilatory equivalent for oxygen decreased from 48 +/- 13 preoperatively to 37 +/- 6 postoperatively, and exercise ventilatory equivalent for oxygen decreased from 53 +/- 23 preoperatively to 38 +/- 6 postoperatively. Definitive operation (tricuspid valvuloplasty or replacement and atrial septal defect closure) for Ebstein's anomaly results in significant improvement of exercise tolerance, normalization of systemic arterial oxygen saturation and reduction of excess ventilation at rest and during exercise.

Myocardial ischemia in patients with pulmonary atresia and intact ventricular septum.

Children who die after operation for pulmonary atresia and intact ventricular septum may have myocardial ischemia. The relation between histologic evidence of myocardial ischemic injury and the presence of a right ventricle to coronary artery fistula, coronary artery dysplasia and operation in 17 autopsy specimens was assessed. Age at death ranged from 1 day to 16 years (median, 11 days). Of the 17 hearts, 6 (35%) had right ventricle to coronary artery fistulas, 5 of which had coronary artery dysplasia. In three cases, there was segmental or complete absence of a coronary artery. Ischemia was present in four of these six hearts, two of which had right ventricular outflow reconstruction. Six of the 11 hearts without right ventricle to coronary artery fistulas also had myocardial ischemia. Of these six cases, four had right ventricular outflow reconstruction and two had shunt operations. Death occurred from 1 to 8 days (mean 3) after operation. Hearts with pulmonary atresia and intact ventricular septum may have myocardial ischemia with or without either right ventricle to coronary artery fistulas or coronary artery dysplasia. Myocardial ischemia may occur after right ventricular outflow reconstruction or shunt operations. Thus, myocardial ischemia occurs commonly in patients with pulmonary atresia and intact ventricular septum and is not always related to coronary abnormalities or operation.

Syncope in children and adolescents.

OBJECTIVES: The objectives of this study were to 1) define the incidence of syncope coming to medical attention among children and adolescents, 2) determine the outcome of syncope in these patients, and 3) determine changes over time in the evaluation and charges for evaluating this problem. BACKGROUND: Syncope occurs commonly in children and adolescents. However, the mid- and long-term outcome of children and adolescents who experience syncope is unknown. METHODS: Utilizing the Rochester Epidemiology Project, we determined the incidence, outcome and charges for medical evaluation for patients seeking medical attention for syncope during an early 5-year period (1950 to 1954) and a more recent 5-year period (1987 to 1991). RESULTS: The incidence of syncope coming to medical attention was 71.9 and 125.8/100,000 population for the early and more recent cohort, respectively. The incidence was higher for female than for male patients. The incidence peaked in 15- to 19-year old patients. Acute illness and noxious stimuli were associated with 24% and 23% of the episodes, respectively. Although long-term survival was not different from that of the general population, one child died suddenly, and another had hereditary prolonged QT interval syndrome. These were two of only six patients who had exertional syncope. Total charges for evaluation of syncope were similar in the two time periods. However, charges for testing procedures were greater for the more recent cohort. CONCLUSIONS: In general, syncope in children and adolescents is a benign event. Syncope occurring during exercise may identify patients with a potentially fatal condition. Detailed evaluation should be considered for patients who have syncope during exercise or who have a family history of syncope, sudden death, myocardial disease or arrhythmias. It may be prudent to obtain an electrocardiogram for all patients who seek medical attention for syncope.

Pulmonary atresia with ventricular septal defect: preoperative and postoperative responses to exercise.

Between April 1982 and June 1984, maximal exercise testing was performed 35 times in 34 consecutive patients with pulmonary atresia and ventricular septal defect (14 studies in patients without repair, 11 studies in patients with partial repair [insertion of a right ventricle to pulmonary artery conduit without ventricular septal defect closure] and 10 studies in patients with complete repair [insertion of a conduit with septal defect closure]). Total work performed, maximal power achieved, exercise time and maximal oxygen uptake were significantly greater in patients after partial or complete repair than in patients without repair. Systemic arterial blood oxygen saturations at rest and during exercise were directly related to the degree of repair. Although heart rate at rest in the three study groups was similar to that in a separate group of normal control subjects, patients in all three study groups had a blunted heart rate response to exercise. The ventilatory equivalent for oxygen was increased both at rest and during exercise for patients without conduit repair and those with a right ventricle to pulmonary artery conduit without ventricular septal defect closure but was similar to that of control subjects in the group with conduit insertion and septal defect closure. This study indicates that patients with pulmonary atresia and ventricular septal defect have decreased exercise tolerance both before and after corrective surgery. Exercise tolerance improves significantly after placement of a conduit from the right ventricle to the pulmonary artery with or without ventricular septal defect closure. Although no further improvement in exercise tolerance occurs with closure of the septal defect, ventilatory function and systemic arterial blood oxygen saturation are improved.

Fixed subaortic stenosis in atrioventricular canal defect: a Doppler echocardiographic study.

OBJECTIVES: The objectives of this retrospective study were to describe the Doppler and echocardiographic features of fixed subaortic stenosis in the setting of atrioventricular (AV) canal defect and to document the de novo occurrence of subaortic stenosis and progression of this lesion over time on the basis of sequential echocardiographic studies. BACKGROUND: The coexistence of fixed subaortic and AV canal defect has been sporadically noted, but no single or multicenter experience with this constellation of abnormalities has been previously described. METHODS: All patients with a diagnosis of subaortic stenosis and complete or partial AV canal defect who had one or more Doppler echocardiographic examinations were identified from a computer data bank. Retrospective analysis was performed, including review of patients' charts, operative notes, recorded videotapes and hard copy recordings when available. RESULTS: Twenty-one patients with both subaortic stenosis and AV canal defect were identified over a 13-year period. Fifteen were female and the mean age at diagnosis of subaortic stenosis was 16 years. Fifteen patients had partial AV canal defect with prior repair in 10; 6 patients had complete AV canal defect with prior repair in 4. The mean interval from prior repair to recognition of subaortic stenosis was 6.8 years. In six patients, serial examinations demonstrated the de novo occurrence of subaortic obstruction over a period of 10 to 87 months. In five patients, progression of known subaortic stenosis was documented over a 10- to 59-month period. Surgical resection of subaortic stenosis was performed in 16 patients; the echocardiographic diagnosis was confirmed in 15 of the 16. CONCLUSIONS: In the largest reported echocardiographic series of this lesion complex, it is concluded that subaortic stenosis can occur de novo, is often recognized only after repair of the canal defect and is progressive. Doppler echocardiography is the method of choice for diagnosis and serial follow-up of these patients.

Safety and utility of endomyocardial biopsy in infants, children and adolescents: a review of 66 procedures in 53 patients.

The benefits and risks of endomyocardial biopsy in infants, children and adolescents were determined by reviewing the indications for and complications and results of 66 procedures in 53 patients aged 2 months to 20 years. One patient had a pneumothorax, and three had a right ventricular perforation. Ventricular tachycardia developed in four patients; it was treated with lidocaine in three and was self-limited in one. The procedure was unsuccessful in two patients. Among 25 patients with a prebiopsy diagnosis of idiopathic dilated cardiomyopathy, microscopic features were consistent with cardiomyopathy in 24 (96%) and were normal in 1. Of nine patients with clinically suspected myocarditis, only two (22%) had microscopic evidence of inflammation, and seven had chronic nonspecific features suggestive of dilated cardiomyopathy. Of eight patients with unexplained arrhythmias, six (75%) had microscopic findings compatible with dilated cardiomyopathy and two had myocarditis. Biopsy tissue samples from seven patients with nondilated forms of cardiomyopathy (four hypertrophic, three restrictive) were consistent with the clinical diagnosis in six and were inadequate in one. Cardiac biopsies were also performed in four patients with other disorders. Among the 51 patients with adequate biopsy specimens, microscopic features were considered diagnostic in 5, confirmatory in 44 and not helpful in 2 with normal tissue. The results indicate that endomyocardial biopsy is safe in infants, children and adolescents. It is useful for the evaluation of cardiomyopathy and specific secondary forms of myocardial disease. There seems to be little correlation, however, between clinical and tissue diagnoses of myocarditis.

Cardiorespiratory response to exercise after the Fontan operation: a serial study.

OBJECTIVES: The purpose of this study was to assess whether there is deterioration of aerobic capacity over time after the Fontan operation in individual patients. BACKGROUND: We previously observed that maximal aerobic capacity after the Fontan operation was lower in older patients than in younger patients. It was unclear whether this represented a decrease in aerobic capacity with time after operation or was a function of studying patients of different ages at different times postoperatively. METHODS: All patients who had more than one postoperative exercise study were included. There were 25 patients (19 male, 6 female), aged 3.8 to 39 years at the time of the operation. The first exercise test was performed, on average, 2.2 years after the Fontan operation, and the last exercise test was performed, on average, 5.9 years (range 1.8 to 13) after the operation. In 11 patients, coronary sinus drainage was left on the pulmonary venous side. Five patients had had a previous Glenn operation. Exercise was performed to exhaustion with use of a 3-min incremental cycle protocol. RESULTS: Exercise duration, oxygen uptake, blood pressure, respiratory rate, minute ventilation, pulmonary blood flow index, exercise factor, ST-T wave changes and the prevalence of arrhythmias were similar during the first and last tests. Exercise systemic arterial blood oxygen saturation decreased from the first to the last postoperative test (p < 0.006) regardless of age. The percent of predicted heart rate, at rest and during maximal exercise, decreased more in older patients from the first to the last test (p < 0.05 for rest and exercise). CONCLUSIONS: In this select group of patients, exercise tolerance remained relatively unchanged over the range of 13 years after the Fontan operation. Heart rate at rest and during maximal exercise decreased more than predicted for age in older patients. A small but significant progressive decrease in systemic arterial blood oxygen saturation was found. The former might represent abnormal sinus node function in patients with functional single ventricle, and the latter might represent a tendency toward development of abnormal ventilation/perfusion patterns resulting from the development of small pulmonary arteriovenous fistulas or an effect of position of the coronary sinus postoperatively.

Exercise tolerance and cardiorespiratory response to exercise after the Fontan operation for tricuspid atresia or functional single ventricle.

To determine the impact of the Fontan operation on exercise tolerance and on the cardiorespiratory response to exercise, we compared the results of graded exercise to maximal effort of 81 patients with tricuspid atresia or single functional ventricle studied preoperatively with those of 29 patients studied postoperatively. Postoperatively, the values for total work performed, duration of exercise and maximal oxygen uptake increased significantly. Regardless of operative status, the maximal heart rate during exercise was reduced. The cardiac output and stroke volume response to exercise were subnormal after operation. Systemic arterial blood oxygen saturation was reduced markedly preoperatively both at rest and during exercise; postoperatively, it was significantly greater than the preoperative value but it remained slightly abnormal. The ventilatory response to exercise (respiratory rate, minute ventilation and ventilatory equivalent for oxygen) decreased toward normal after operation. Exercise tolerance and the cardiorespiratory responses to exercise improve after the Fontan operation. Formal exercise testing is essential to quantitate the degree of improvement.

Exercise tolerance in patients with Ebstein's anomaly.

OBJECTIVES: The purpose of this study was to identify the determinants of exercise tolerance in patients with Ebstein's anomaly. BACKGROUND: Patients with Ebstein's anomaly of the tricuspid valve may have exercise limitation that improves after surgical repair. METHODS: One hundred seventeen patients performed cycle ergometry for a total of 124 tests (preoperative test in 76 patients, postoperative test in 23, test but no operation in 18, preoperative and postoperative test in 7). Multiple linear regression analysis was used to identify predictors of maximal oxygen uptake, oxygen saturation and heart rate at peak exercise. RESULTS: Age at the time of exercise ranged from 6 to 60 years (median 15). An atrial septal defect was present in 67 patients (88%) preoperatively. Compared with the preoperative group, the postoperative group had significantly higher maximal oxygen uptake (mean [+/- SD] 20.5 +/- 7.4 vs. 25.3 +/- 7.0 ml/kg body weight per min, p = 0.006). Postoperative rest and exercise blood oxygen saturation was higher than that measured preoperatively (p = 0.0001). Six of seven patients tested before and after the operation showed improved exercise tolerance. Preoperatively, major predictors of maximal oxygen uptake were oxygen saturation at rest (p = 0.01) and age (p = 0.0001). Preoperatively, the major predictor of oxygen saturation at peak exercise was rest oxygen saturation (p = 0.0001), and major predictors of peak exercise heart rate were rest heart rate (p = 0.01) and rest oxygen saturation (p = 0.01). In the postoperative group, predictors of maximal oxygen uptake included age at exercise testing, male gender and heart size. CONCLUSIONS: Definitive operation for Ebstein's anomaly results in improved exercise tolerance. Before the operation, rest oxygen saturation is the major predictor of exercise tolerance, oxygen saturation at peak exercise and peak heart rate. Postoperatively, age, gender and heart size influenced maximal oxygen uptake.

Correlation of two-dimensional echocardiographic and autopsy findings in complete transposition of the great arteries.

Autopsy and antemortem two-dimensional echocardiographic findings were compared in 30 cases to assess the predictive accuracy of two-dimensional echocardiography in complete transposition of the great arteries, and thus its potential for replacing or altering an invasive examination. These cases represent consecutive autopsy cases of transposition between January 1978 and December 1982. Ages at echocardiographic study ranged from 1 day to 15.5 years (median 8.5 months). Transposition of the great arteries had been diagnosed correctly in every case, and all associated anomalies identified by two-dimensional echocardiography were confirmed at autopsy. Several additional anomalies not found by two-dimensional echocardiography were apparent at autopsy; however, most were minor and insignificant. The only potentially significant false negative findings were one ventricular septal defect, two small atrial septal defects, one mitral valve anomaly, one tricuspid valve anomaly, three instances of patent ductus arteriosus and four instances of persistent left superior vena cava. Although significant pulmonary stenosis was predicted correctly, the site of stenosis was not accurately defined in four cases. Two-dimensional echocardiography is a reliable means of diagnosing transposition of the great arteries. It can limit the need for angiocardiography in the neonate; and in older infants and children, it should be used to complement cardiac catheterization and angiocardiography. The latter may be indicated, especially before surgical repair, to better define small ventricular septal defects, site of pulmonary stenosis, atrioventricular valve insufficiency and patent ductus arteriosus.

Surgical repair of univentricular heart (double inlet left ventricle) with obstructed anterior subaortic outlet chamber.

The results of operation in all patients with univentricular heart and an obstructed anterior subaortic outlet chamber who were operated on utilizing extracorporeal circulation at the Mayo Clinic from 1973 through 1983 were reviewed. Ten of the 18 patients died during the immediate postoperative period and there was one late death. Factors significantly related to operative and immediate postoperative mortality were age at operation, cardiothoracic ratio on X-ray examination, degree of ST depression on electrocardiogram and pressure gradient across the outlet foramen at catheterization. Autopsy in eight cases revealed significant hypertrophy of ventricular myocardium and a small outlet foramen that was considered stenotic relative to either body surface area or aortic root area. The ventricular myocardium showed histologic changes of chronic ischemia that predated the surgical procedure.

The modified Fontan operation for children less than 4 years old.

Of 500 patients who had a modified Fontan operation at this institution between 1973 and 1987, 54 (33 boys and 21 girls) were less than 4 years old. This retrospective study related preoperative clinical and hemodynamic data to subsequent survival. Twenty patients less than 4 years old had tricuspid atresia, 13 had double inlet ventricle and 21 had other complex heart defects. There were 14 early deaths (less than 30 days after operation) and 6 late deaths. Multivariate analysis of survival for the entire group of 500 patients revealed the following factors to be significantly associated with poorer survival: absence of tricuspid atresia (p = 0.011), asplenia (p less than 0.001), age less than 4 years at operation (p = 0.042), atrioventricular valve dysfunction (p = 0.017), early calendar year of operation (p less than 0.001) and the presence of either one or more of the following: left ventricular ejection fraction less than 60%, mean pulmonary artery pressure greater than 15 mm Hg and pulmonary arteriolar resistance greater than 4 U.m2 (p less than 0.001). On the basis of this study of 500 patients, age less than 4 years at operation appears to be an independent risk factor for poorer survival after the modified Fontan operation.

Cardiorespiratory response to exercise after modified Fontan operation: determinants of performance.

OBJECTIVES: This study sought to measure the cardiorespiratory responses to exercise and to identify the perioperative determinants of exercise performance in children, adolescents and young adults who underwent the modified Fontan operation. BACKGROUND: Several studies of the cardiorespiratory responses to exercise after the Fontan operation have demonstrated subnormal maximal oxygen uptake and exercise heart rate, but the perioperative variables that ultimately affect exercise responses have not been assessed systematically. METHODS: The study included 59 of the 548 patients who underwent a modified Fontan operation between January 1, 1984 and December 31, 1993 at the Mayo Clinic. Spirometry was performed at rest in all patients before exercise testing. The patients then exercised using a previously calibrated cycle ergometer and a 3-min incremental cycle exercise protocol. Multiple linear regression analysis was used to determine a subset of variables associated with oxygen uptake at peak exercise (VO2max), blood oxygen saturation (O2sat) and heart rate at peak exercise (HRmax). RESULTS: VO2max ranged from 29% to 95% of normal value; O2sat at peak exercise ranged from 77% to 96%; and HRmax ranged from 39.7% to 97.4% of normal value. Multivariate analysis showed that log VO2max/kg2/3 was associated with age at exercise, male gender, body surface area, preoperative confluent pulmonary arteries and rest VO2max/kg2/3. Preoperative left pulmonary artery stenosis, the presence of a classic Glenn anastomosis at exercise and rest O2sat were associated with O2sat at peak exercise. Age, body surface area at exercise, heart rate at rest and diastolic blood pressure were associated with HRmax at exercise. CONCLUSIONS: Subnormal VO2max and HRmax values were demonstrated at peak exercise. Several perioperative variables were associated with VO2max and O2sat at peak exercise. The presence of a classic Glenn anastomosis was associated with decreased O2sat at peak exercise, suggesting intrapulmonary shunting with the classic Glenn anastomosis.