Skin cancer in heart transplant recipients: risk factor analysis and relevance of immunosuppressive therapy.

BACKGROUND: The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial. METHODS AND RESULTS: We studied 300 patients (age 49+/-15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P:=0.03, RR=5.3), skin type II (P:=0.05, RR=2.6), rejection score of 19 (P:=0.003, RR=5.7), solar keratosis (P:=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (P:=0.0003, RR=7.6) were risk factors for SCC. CONCLUSIONS: Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.

Sulfinpyrazone reduces cyclosporine levels: a new drug interaction in heart transplant recipients.

BACKGROUND: Management of cyclosporine (CsA)-associated hyperuricemia in heart transplantation (HT) is difficult. Because of the myelotoxicity of combined allopurinol and azathioprine, we tested sulfinpyrazone. METHODS: We studied 120 HT recipients (109 men; mean age at HT, 52+/-10 years). All had received allopurinol for at least 6 months, which was stopped for 1 month before initiation of sulfinpyrazone. Mean follow-up from HT to onset of sulfinpyrazone (200 mg/day) was 59+/-41 months. We stopped the drug after 6+/-2 months. We compared CsA level and daily dose, serum creatinine, blood urea, and uric acid at onset and before interruption of sulfinpyrazone and, as control, in the last 6 months of allopurinol. RESULTS: Mean uricemia decreased with allopurinol (0.58+/-0.12 vs. 0.41+/-0.07 mmol/liter, p = 0.0001) as well as with sulfinpyrazone (0.51+/-0.13 vs. 0.40+/-0.12 mmol/liter, p = 0.0001). Mean creatinine increased (171+/-42 and 164+/-35 micromol/liter, p = 0.01) with allopurinol, whereas it tended to decrease with sulfinpyrazone (160+/-35 and 154+/-48 micromol/liter, p = NS). Mean urea did not change with allopurinol (14+/-5 vs. 15+/-7 mmol/liter, p = NS), but fell with sulfinpyrazone (14.01+/-5 vs. 12.60 +/-5 mmol/liter, p = 0.0004). Mean CsA levels were constant with allopurinol (193+/-73 vs. 188+/-65 ng/ml, p = NS), although CsA dose was slightly reduced (2.7+/-0.8 vs. 2.6+/-0.8 mg/kg/day, p = 0.007). Conversely, CsA levels dropped with sulfinpyrazone (183+/-89 vs. 121 +/-63 ng/ml, p = 0.0001) despite an increase in CsA daily dose (2.6 +/-0.9 vs. 2.8+/-0.9 mg/kg/day, p = 0.0001). Two subjects were treated for acute rejection. We observed no other side effects. In HT recipients sulfinpyrazone, as an alternative to allopurinol, is effective in achieving metabolic control of hyperuricemia. However, this drug reduced CsA levels, thus the risk of rejection is present.

Early and late risk factors in surgical treatment of acute type A aortic dissection.

BACKGROUND: Morbidity and mortality of emergency repair of type A dissecting aneurysms of the aorta are high. This is an attempt to investigate the risk determinants of early and late results. METHODS: A series of preoperative and operative variables were retrospectively collected from the clinical records of 291 patients operated on between January 1, 1979, and December 31, 1995. Risk factors for surgical death were investigated with univariate analysis and stepwise logistic regression. Follow-up was conducted between December 1995 and February 1996. Analysis of late results was conducted by means of actuarial survival curves (life method). After removing the surgical deaths, risk factors for late deaths were analyzed by a Cox model. RESULTS: The in-hospital mortality rate was 36.1%. Significant independent determinants of operative or early death were preoperative shock, preoperative neurologic impairment, operation before 1986, perioperative bleeding, and prolonged clamping time. The 10-year survival rate was 36.9% +/- 4.4%. Twenty-six patients required repeat operation. The long-term prognosis was significantly worse in patients who needed reoperation. CONCLUSIONS: Growing awareness of this disease and quicker diagnosis have increased the number of patients with acute dissection of the ascending aorta who are taken early to operation. This new challenge must be met by better preoperative support and intraoperative monitoring, and by surgical techniques that focus on lowering the rate of late complications, for which lifelong follow-up must be provided.

[Diagnostic usefulness of Holter monitoring in pediatric fainting and syncope]. / Utilità diagnostica del monitoraggio Holter nelle lipotimie e sincopi in età pediatrica.

The aim of the study was to assess the diagnostic efficacy of ambulatory electrocardiographic monitoring in children with a previous history of fainting and/or syncope. Sixty-one children, from 2 months to 17 years of age, all at the time undergoing different physical examinations because of previous syncopal episodes were examined. All the children had a normal electrocardiogram at rest and all underwent 24 hour electrocardiographic monitoring (Holter). The ECG was normal in 48 patients. Eight children had several dysrhythmias, classified as "borderline" and five children showed a clearly pathological trend. These results are even more significant considering that standard electrocardiogram results are negative. These data underline the diagnostic importance of the dynamic electrocardiogram particularly in cases of very frequently repeated symptoms.

Abnormal hypertensive response during exercise test in normotensive transplanted children and adolescents.

We investigated the cardiovascular and respiratory conditions, at rest and in response to stress testing, in 10 children and adolescents with successful renal transplantation, to release certifications for participation in sports. Our patients were aged more than 6 years, transplanted 6 months or more before the study, with creatinine clearance > 40 ml/min/1.73 m2, without hypertension at rest. All but 1 were on cyclosporine A, prednisone and azathioprine. Two control study groups with the same chronological age and body surface area were paired with our patients. They underwent a graded exercise tread-mill test, during which maximal blood pressure and heart rate were recorded. Resting electrocardiogram, dynamic 24-hour electrocardiogram Holter monitoring and mono- and bidimensional echocardiograms were obtained before the test. Spirometry was performed to study lung flow and volume. A questionnaire collected information about physical activity patterns. Four categories, according to practice, frequency and duration of exercise, were identified: nonactive, starters, experienced and very experienced. Most children and adolescents were sedentary or mildly interested in sports and during treadmill test we observed reduced exercise capacity and systolic hypertensive response to increasing exercise testing.

[Transesophageal atrial stimulation in the oral treatment of supraventricular reciprocal paroxysmal tachycardia in infants]. / La stimolazione atriale transesofagea nel trattamento orale della tachicardia parossistica reciprocante sopraventricolare del lattante.

INTRODUCTION: The aim of the study was the evaluation of the usefulness of transesophageal atrial pacing in predicting chronic oral treatment efficacy of symptomatic reciprocating supraventricular tachycardia in infants and in avoiding the risk of very dangerous recurrences at home. METHODS: We studied 13 infants (11 males, 2 females, mean age 43 +/- 31 days) with symptomatic reciprocating supraventricular tachycardia and no structural heart disease. All patients had chronic oral therapy, using the drug effective in acute i.v. somministration. Each patient was discharged when supraventricular tachycardia was not inducible with transesophageal atrial pacing after 5 half-lives of the drug used in chronic oral treatment. All patients, every 6 months, were retested with transesophageal atrial pacing alternatively during chronic oral therapy and after complete wash out. Oral therapy was stopped in each patient when supraventricular tachycardia was not inducible after the wash out. RESULTS: The number of oral treatments tested for each patient were 2 +/- 1 (range 1-5). The number of transesophageal studies performed for each patient were 4 +/- 2 (range 3-7). No patient had symptomatic episodes of supraventricular tachycardia or needed to change therapy during the follow-up. The oral treatment was stopped after the twelfth month of life in 8 patients and after the twenty-fourth in 2 others without recurrences. CONCLUSION: Transesophageal atrial pacing seems to be useful in predicting accurately and rapidly the oral treatment efficacy of supraventricular tachycardia in infants. Our protocol seems to be effective to avoid dangerous recurrences of tachycardia and to decide when we can stop therapy without risk.

Reciprocating supraventricular tachycardia in children: low rate at rest as a major factor related to propensity to syncope during exercise.

Reciprocating supraventricular tachycardia may have several clinical presentations, with symptoms often more severe during exercise or emotional stress. This study shows by using transesophageal atrial pacing, the factors related to syncope during exercise. Between May 1989 and June 1994, transesophageal atrial pacing was performed at rest and during exercise in 75 children aged > 6 years with suspected or documented episodes of paroxysmal supraventricular tachycardia. Reciprocating supraventricular tachycardia could be induced both at rest and during exercise in 22 patients (8 girls, 14 boys; mean age 10.6 +/- 2.7 years, range 7 to 15 years) with ventriculoatrial interval < 70 msec in 11 patients and > 70 msec in 11. At rest, all patients had palpitations caused by the induction of tachycardia. After conversion to sinus rhythm, when tachycardia was induced during exercise, symptoms did not change in 14 patients (group A), whereas symptoms worsened (presyncope) in eight (group B). The statistical analysis showed a significant difference of mean reciprocating supraventricular tachycardia rate at rest between the two groups (group A, 211 +/- 23 beats/min; group B, 173 +/- 33 beats/min; p = 0.0057) and reciprocating supraventricular tachycardia rate variation from rest to exercise (group A, 62 +/- 18 beats/min; group B, 105 +/- 24 beats/min; p = 0.0001). These data suggest that children with low tachycardia rate during normal activities may have syncope more frequently, independently of the tachycardia rate during exercise or emotional stress.

Radiographic findings in Wiedemann-Rautenstrauch syndrome.

We describe a girl who presents the features of Wiedemann-Rautenstrauch syndrome. This autosomal recessive condition has characteristic radiographic findings which can be considered manifestations of the syndrome.

[The heart of anorexic adolescents]. / Il cuore nelle adolescenti anoressiche.

BACKGROUND: Anorexia nervosa (AN) is often associated with cardiac changes, such as thinning of the left ventricle (LV), reduction of LV mass, abnormalities of mitral valve function and systolic dysfunction. Some authors have reported QT interval prolongation and sudden death in these patients. METHODS: We studied 23 adolescent females, aged 14.7 +/- 2 years (mean +/- SD), with AN. Serum electrolytes, proteins and albumin were measured in all patients. Electrocardiogram, Doppler-echocardiogram and chest X-rays were also performed on the same day. Eighteen patients were also examined via indirect calorimetry (difference from basal metabolic rate) and 21 underwent dosage of thyroid hormones. RESULTS: The patients, who were of normal height (159 +/- 7.4 cm), were underweight (36 +/- 4.8 kg) and had a body mass index (BMI) of less than 19 (14.2 +/- 1.3). Serum electrolytes, proteins, albumin and chest X-rays were substantially normal in all patients; 74% of them showed reduction of FT3. The calorimetry was reduced (-27.1 +/- 10.6%) with the exception of one patient. Resting heart rate was 58 +/- 12 bpm. We found normal values for PR, QRS, QT (0.41 +/- 0.03 s1/2) and QTc intervals (0.40 +/- 0.03 s1/2) and QT dispersion (40.9 +/- 14.1 ms). Echocardiography showed a reduction in the dimensions of the interventricular septum (52% of patients), LV free wall (61%), left atrium (31%) and LV mass (61%). Fractional shortening was normal in all but one patient. In 61% of cases, there was mild or moderate pericardial effusion that was clinically silent and inversely related to BMI (r = -0.38, p 0.08, ns), to calorimetry (r = -0.56, p < 0.0055), to FT3 (r = -0.53, p < 0.05) and to sodium concentration (r = -0.43, p 0.04). CONCLUSIONS: Teen-agers with AN often show a reduction in LV thickness and mass, as well as clinically silent pericardial effusion that is inversely related to BMI, calorimetry, FT3 and sodium serum concentrations. We did not find any prolongation of QTc interval or of QT dispersion.

Cardiovascular hemodynamics: relationships with insulin resistance in obese children.

We investigated blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR) and their relationships with insulin and glucose blood levels in a group of 24 obese children (mean age, 11.9 +/- 2.1 years; 19 males). The data were compared to those obtained from a group of 19 healthy controls of the same age (12.4 +/- 2.1 years; p = NS; 13 males). BP at rest was measured and all subjects underwent an exercise testing on the treadmill (Bruce Prot.), time of exercise, maximal heart rate, maximum systolic blood pressure, CO, and SVR at rest and at peak exercise were considered. Only in the OC group were an oral glucose tolerance test were performed to calculate insulin sensitivity index (ISI) and echocardiography performed to determine the left ventricular mass (LVM). The relationships between cardiovascular and metabolic parameters were investigated. Student's t-test and linear regression analysis were used when appropriate. OC had a significant reduction in TE and higher BP, and linear regression analysis showed significant correlations between BP, ISI, and LVM. We speculate that OC need a regular cardiovascular and metabolic screening to prevent the development of early cardiovascular damage.