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.

Endomyocardial biopsy in right ventricular cardiomyopathy.

Right ventricular cardiomyopathy is characterized by a progressive myocyte loss and fibro-fatty substitution of the right ventricle. The aim of our study was to assess the diagnostic accuracy of right ventricular endomyocardial biopsy. Using an imaging analyser system, histomorphometric parameters of myocytes, interstitium, fibrous tissue and fatty tissue were evaluated on endomyocardial biopsy from 30 patients with arrhythmogenic right ventricular cardiomyopathy, 29 patients with dilated cardiomyopathy and 30 control patients. The percent area of myocytes decreased from 78.10 +/- 7.34 in control to 63.39 +/- 9.22 in dilated cardiomyopathy (P < 0.05) and to 47.28 +/- 15.01 in arrhythmogenic right ventricular cardiomyopathy (P < 0.01). Fibrous tissue increased from 8.10 +/- 3.89 in control to 21.80 +/- 9.29 in dilated cardiomyopathy (P < 0.05) and to 24.60 +/- 11.37 in arrhythmogenic right ventricular cardiomyopathy (P < 0.05). Fatty tissue varied from 0.33 +/- 1.44 in control and 0.07 +/- 0.31 in dilated cardiomyopathy to 13.30 +/- 17.30 in arrhythmogenic right ventricular cardiomyopathy (P < 0.05). Fatty tissue was a feature of arrhythmogenic right ventricular cardiomyopathy (67% of patients vs. 6% of control and dilated cardiomyopathy patients). Diagnostic values typifying arrhythmogenic right ventricular cardiomyopathy, obtained by excluding any overlapping between confidence intervals in the three groups, were: myocytes < 44.95%; fibrous tissue > 40.38%, and fatty tissue > 3.21%, with 67% sensitivity and 91.53% specificity for at least one parameter. In conclusion, a significant difference between arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and control exists in terms of amount of myocytes, fibrous tissue and fatty tissue. Presence of fatty tissue and fibrous tissue exceeding 3.21% and 40.38%, respectively should be considered highly suspect for arrhythmogenic right ventricular cardiomyopathy in right ventricular endomyocardial biopsy.

Hypertrophic cardiomyopathy: two-dimensional echocardiographic score versus clinical and electrocardiographic findings.

The severity and site of hypertrophy is important in determining the clinical picture and the natural history of hypertrophic cardiomyopathy (HCM). We evaluated left ventricular hypertrophy by means of two-dimensional echocardiographic score and score index, and correlated these findings with symptoms, electrovector-cardiographic data, and ventricular arrhythmias. A total of 42 patients with HCM were studied by clinical examination, ECG, VCG, M-mode and 2D echocardiography, and 24-h Holter monitoring. The extent and severity of the hypertrophic process were calculated by a score system. The left ventricle was divided into 11 segments and a hypertrophic score (HS) was given to each segment. A hypertrophy score index (HSI) was also calculated by dividing the number of hypertrophied segments by 13. No correlation was found between symptoms and HS and HSI, nor ECG-VCG abnormalities and HS and HSI. A statistically significant relationship between the severity of ventricular arrhythmias and HS and HSI was found (p less than 0.01). The mechanism responsible for ventricular tachyarrhythmias in severe and diffuse hypertrophy might reside in the high intraventricular pressures which produce or worsen areas of myocardial ischemia.

[Complete transposition of the great arteries: hypertensiol pulmonary vascular disease in the first six months of life (author's transl)]. / Trasposizione completa delle grandi arterie: vasculopatia polmonare ipertensiva nei primi sei mesi di vita

Lung specimens of 27 patients under six months of age with complete transposition of the great arteries (TGA), obtained at autopsy, were studied histologically. No evidence of hypertensive pulmonary vascular disease was found in patients under four months of age (23 patients), while obstructive intimal proliferations were seen in 2 patients, aged four and five months, with TGA and VSD. Since pulmonary vascular lesions in transposition with VSD appear early in infancy, timely palliative procedures, such as banding of the pulmonary artery, are strongly indicated when the radical corrective operation is to be postponed.

[Model of the normal left ventricle]. / Simulazione del ventricolo sinistro normale.

The aim of the present study is to simulate left ventricular function using parametres directly measurable "in vivo". Taking the definition of contractility as sigma EDV/ESV (sigma = end systolic stress; EDV = end diastolic volume; ESV = end systolic volume), a slight modification of Suga's index, and an equation taken from Sunagawa, relating arterial pressure to resistance, compliance and stroke volume, a basic programme able to predict stroke volume and systolic pressure starting from EDV, left ventricular mass, contractility, peripheral resistance and compliance was developed. Various curves describing left ventricular function were simulated: Starling's curve, pump curve (mean left ventricular pressure against mean left ventricular flow), Ford's curve (mass to volume ratio against systemic pressure), and pressure-volume loops. A close affinity with literature data was always found. Left ventricular performances were predicted in 23 normal subjects, using the same input parameters. The correlation with real values was always linear, and particularly striking for cardiac index and source resistance. Thus this model seems to explain low-frequency hemodynamic events adequately, and is therefore suitable of clinical use in order to clarify pathophysiological mechanisms.

[Study of the descending phase of the aortic pressure curve. Possible applications to the monitoring of peripheral resistance and arterial compliance (author's transl)]. / Studio della fase discendente della curva di pressione aortica. Sue possibili applicazioni alla misura della resistenza periferica e della compliance arteriosa

In 21 patients aortic pressure was recorded just above the diaphragm. The curve after the dicrotic notch is an exponential function of the time, and it is possible to characterize it by a unique time-constant. This constnat is shown to depend on aortic compliance and peripheral resistance: as aortic compliance does not vary abruptly in physiological conditions, this allows monitoring of peripheral resistance by monitoring time constant. Mathematical bases of time constant and of the peripheral resistance are briefly discussed.

[Hematic and plasmatic viscosity in cyanotic congenital heart diseases (author's transl)]. / La viscosita' ematica e plasmatica nelle cardiopatie congenite cianotiche

57 patients with cyanotic congenital heart diseases were studied. 39 patients presented t. of Fallot, 18 patients had patent ductus arterious with pulmonary hypertension and right to left shunt. The average whole blood viscosity in patients with t. of Fallot was 6.86+/-0.32 cps. This parameter was correlated with hematocrit, fibrinogen, euglobulin lysis time, pulmonary output, systemic output, and O2 saturation. The value of "r" resulted as statistically significant only for the correlation between viscosity and hematocrit and between viscosity and fibrinogen (t=13.22, p less than 0.0005; t=3.35, p less than 0.001 respectively). The average value of plasma viscosity in patients with t. of Fallot was 1.61+/-0.024 cps. The correlations of this parameter with fibrinogen, euglobulin lysis time, pulmonary output and systemic output did not result as statistically significant. The average fibrinogen value was 256.10+/-20.63 mg%, whereas that of euglobulin lysis time was 12,67+/-1.50 hours. In patients with patent ductus arteriosus the average blood viscosity was 6.65+/-0.56 cps. Such parameter was correlated with hematocrit, fibrinogen, euglobulin lysis time, pulmonary output, systemic output and O2 saturation. The value of "r" resulted as statistically significant only between blood viscosity and hematocrit and between blood viscosity and O2 saturation (t=9.30, p less than 0.0005; t=5.800, p less than 0.001 respectively). The average value of plasma viscosity was 1.61+/-0.04 cps. This parameter was correlated with fibrinogen, euglobulin lysis time, pulmonary output and systemic output. The correlation index "r" never resulted as statistically significant. The average fibrinogen value was 299.20+/-20.30 mg. The average euglobulin lysis time was 16.02+/-2.73 hours.

Programmed chest-wall stimulation to evaluate the progress of A-V block after pacemaker insertion in patients with trifascicular disease.

Twenty six patients (aged 46-80, mean age 64) with bifascicular block in the presence of prolonged H-V interval (trifascicular block), were followed for an average of 31 months after inserting an R-wave inhibited pacemaker (PM) because of syncope and/or dizzy attacks. The underlying rhythm was evaluated at 4-6-month intervals by three different techniques: 1) 12-lead ECG when intrinsic patient rate was faster than PM rate; 2) abrupt PM inhibition (APMI) by the rapid chest-wall stimulation technique, and 3) progressive PM inhibition (PPMI) using a programmed chest-wall stimulation technique capable of decreasing the PM rate gradually to 30 beats/min before complete PM inhibition. In addition, the PPMI allowed the underlying rhythm to be induced and sustained and properly evaluated without any discomfort to the patient. Following PM insertion, 4 patients (15%) developed complete heart block after a mean follow-up of 43 months, and one patient (4%) developed 2nd degree 2:1 A-V block (VX) after 83 months. The P-R interval increased in 5 patients (19%) and decreased in 2 (8%). No change of A-V conduction was found in 9 patients (34%). Three patients developed low atrial rhythm, atrial flutter and atrial fibrillation, respectively (12%). After PM insertion 2 patients still complained of dizziness. None reported syncope. Two patients died during follow-up, both of congestive heart failure (8%). By detection of intrinsic rhythm it was recognized that a long symptomatic paroxysmal phase may precede the development of chronic complete A-V block. Therefore, the insertion of a permanent PM is recommended in patients with unexplained neurologic symptoms and trifascicular disease, without waiting for documented episodes of complete A-V block.