[Intracavitary and parietal cardiac measurement with nuclear magnetic resonance: comparison with echocardiography in healthy volunteers]. / Misure endocavitarie e parietali cardiache con risonanza magnetica nucleare: confronto con ecocardiografia in volontari sani.

For quantitative evaluation of cardiac dimensions by Nuclear Magnetic Resonance (NMR), we compared the values obtained by ECG gated NMR with those obtained by two-dimensional echocardiography (2D-echo) in 18 adult healthy volunteers aged 20-40 years (mean 31.6 +/- 5.8). NMR was performed using a 2 T super-conducting magnet operating at 0.5 T with a radiofrequency impulse of 21 MHz. Spin-echo pulse sequences with echo-delay times (TEs) of 30-45 msec were used for data acquisition. The interpulse interval was obtained from the R-R interval on the ECG. Slice thickness was set at 1 cm. To obtain planes oriented along the long axis of the left ventricle similar to 2D-echo, paraxial planes were obtained by double angulation. No significant differences of mean values obtained by NMR and 2D-echo were observed. Regression coefficients were not statistically different from 1 for any of the structures measured: left atrium (y = 1.106x), aorta (y = 1.077x), left ventricle (y = 0.66x), interventricular septum (y = x 1.009x), postero-lateral wall of the left ventricle (y = 1.133x), right ventricle (y = 1.093x). However high coefficients of variation were found for measurement of postero lateral wall (79.5) and interventricular septum (41.4) thicknesses; potential causative factors are discussed.

Secondary neoplastic infiltration of the myocardium diagnosed by two-dimensional echocardiography in seven cases with anatomic confirmation.

In seven patients with different types of neoplasm, secondary myocardial infiltration was diagnosed in vivo by two-dimensional echocardiography and confirmed by direct inspection. In all patients, clinical and electrocardiographic findings were suggestive but nonspecific for myocardial involvement. Two patients had cardiac tamponade and three had pericardial effusion. In three patients, the echocardiographic diagnosis made it possible to plan specific therapy. Clinical, electrocardiographic and echocardiographic aspects are discussed. A two-dimensional echocardiographic examination should be performed in all patients when cardiac metastatic involvement is suspected from clinical electrocardiographic findings, because the in vivo diagnosis of such a condition may have important therapeutic implications for such patients.

Cardiac function evaluation in AMSA-treated patients.

Cardiac function was monitored by means of ECG and systolic time intervals in 13 patients submitted to treatment with 4'-(9-acridinylamino) methanesulfon-m-aniside (AMSA) without the classical reconstitution vehicle N1N-dimethylacetamide. ECG changes were represented by flattening of T waves (100%), sporadic atrial extrasystoles (23%), and sporadic or coupled ventricular premature beats (7.6%). These alterations were transient and not dose related. The systolic time interval ratio, recorded at the end of infusion and 2 h after drug administration, did not change significantly from pretreatment values. Systolic time intervals recorded in 6 patients after the mean cumulative dose of 550 mg/m2, and in 3 patients after the mean cumulative dose of 1000 mg/m2, did not change from mean basal values. Present data failed to confirm the occurrence of a significantly cardiotoxic activity of AMSA.

Preliminary evaluation of myocardial toxicity of 4'-deoxydoxorubicin: experimental and clinical results.

4'-deoxydoxorubicin (4'-deoxy-DXR), a new doxorubicin (DXR) analogue with interesting antineoplastic activity, was tested for its cardiotoxicity in guinea pigs and humans. In experiments on isolated guinea pig heart, which is considered a highly predictive model of acute anthracycline cardiotoxicity in humans, 4'-deoxy-DXR was found to be significantly less cardiotoxic than DXR. This effect was correlated with a lower degree of inhibition of the fast-exchanging calcium compartment and of the low affinity sarcolemmal calcium-binding sites. The preliminary study on 4'-deoxy-DXR in humans was conducted on 117 patients affected by advanced malignancies resistant to conventional chemotherapy. The drug was administered by bolus i.v. injection in doses ranging from 10 to 40 mg/m2 in the phase I study and in doses of 35 mg/m2 in the phase II study, which is still ongoing. Cardiologic evaluation consisted of recording of EKG, left ventricular systolic time intervals (STI), echocardiography and radionuclide ejection fraction. Preliminary data indicated a lower percentage of EKG abnormalities in comparison not only with DXR but also with other anthracycline analogues. Analysis of STI recorded 1 h after different doses of 4'-deoxy-DXR failed to show the dose-dependent effect on left ventricular function which has been described for DXR, thus confirming the lower acute cardiotoxic effect. Functional parameters serially measured to evaluate chronic cardiotoxicity in 15 patients who received more than 200 mg/m2 were not significantly different from basal values.

Possible enhancement of the cardiotoxicity of doxorubicin when combined with mitomycin C.

Forty-six patients with recurrent metastatic breast cancer were treated with a combination chemotherapy including doxorubicin and mitomycin C. Myocardial contractility was monitored by means of echocardiography. During therapy there was a progressive deterioration of myocardial function, and this phenomenon was found to be linearly correlated to the cumulative dose of doxorubicin. Six patients (13.8%) developed congestive heart failure during therapy; it occurred after the median cumulative dose of 322 mg/m2 (range 135-472). Possible risk factors of cardiomyopathy could be identified in only two patients. These results suggest that mitomycin C could enhance the cardiotoxicity of doxorubicin.

Relationship between pulmonary function tests and morphologic changes in the lung in bleomycin-treated patients.

The transfer factor of the lung for carbon monoxide (TLCO) and the respiratory response to moderate exercise were determined in 16 patients with pulmonary metastasis pretreated with bleomycin who underwent pulmonary partial resection. The results of pulmonary function tests were related to histologic findings. No significant correlation was found between pulmonary morphologic changes and the TLCO: this questions the usefulness of TLCO as a predictive method for detecting subclinical bleomycin pulmonary toxicity. No significant correlation was found between morphologic findings and cumulative dose of bleomycin: this confirms the limit of a dose limitation strategy. In contrast, evaluation of pulmonary response to exercise seemed to improve the sensitivity of monitoring such patients for clinical evidence of latent pulmonary toxicity; however, it seems that critical morphologic changes must occur before pulmonary performance begins to deteriorate.

Preliminary echocardiographic and polygraphic evaluation of cardiac toxicity of 4'-epi-doxorubicin.

Data recorded by ECG, poly ECG, and echocardiography in 101 cancer patients treated with 4'-epi-doxorubicin are reported and compared with those previously obtained in a comparable group of 78 patients treated with doxorubicin. 4'-Epi-doxorubicin was administered by i.v. route in doses ranging from 50 to 90 mg/m2 in a three-weekly regimen; the maximum cumulative dose was 630 mg/m2. The results obtained demonstrate that this new antitumor anthracycline develops a lower acute cardiotoxic effect and suggest that 4'-epi-doxorubicin is endowed with a reduced chronic cardiotoxicity as compared to doxorubicin.

Evaluation of doxorubicin cardiotoxicity in patients treated intermittently with beta-methyldigoxin.

Twenty-one patients with various advanced neoplasms were treated with 60 to 75 mg/m2 of doxorubicin every 3 to 4 weeks and monitored by ECG and systolic time intervals (PEP/LVET) with the aim to establish whether a pretreatment with beta-methyldigoxin, administered intermittently, could prevent doxorubicin-induced cardiotoxicity. It was found that until patients received digitalis pretreatment the PEP/LVET ratio did not change significantly from mean basal values even after the highest cumulative dosages of doxorubicin. However, after interruption of the therapy with both drugs, PEP/LVET increased reaching a value not significantly different from that observed in a comparable group of patients treated only with doxorubicin. Moreover, of 9 patients who reached the cumulative limiting dose, 2 developed congestive heart failure. These results question the possibility that digitalis administered according to an intermittent treatment scheme may prevent doxorubicin cardiomyopathy.

5-Fuorouracil cardiotoxicity.

Two cases of 5-fluorouracil cardiotoxicity, resulting in one patient in myocardial infarction, are described. A review of the literature confirms that cardiotoxicity is a rare but genuine complication of 5-fluorouracil treatment; the cardiotoxic effect seems to range from mild angina without persistent electrocardiographic changes to severe myocardial infarction. No factors predictive of this complication were identified. The authors therefore feel it is advisable to stop 5-fluorouracil treatment when precordial pain occurs, even if the ECG (after angina) is normal, since angina can in some cases result in myocardial infarction.

Evaluation of early doxorubicin-induced cardiotoxicity by means of systolic time intervals.

Systolic time intervals (PEP/LVET ratio) were used for detection of acute variations in myocardial contractility after a single dose of 30, 60, or 75 mg of doxorubicin/m2. This drug induces an acute impairment of left ventricular function (increase in the PEP/LVET ratio) detectable 1 h after doxorubicin injection. The phenomenon appears to be dose-related, with a threshold dose of 30-40 mg/m2. The decrease in myocardial contractility is fully reversible within 24 h, at least after the first dose. This kind of evaluation appears applicable to phase I studies of new anthracycline derivatives.

Differential effects of fasting and nicotinic acid on various enzymatic activities of the 9,000 g fraction of the perfused rat liver.

Perfused livers obtained from rats fasted for 24 or 48h show a marked impairment of the N-demethylation (substrate aminopyrine) without major changes of the O-demethylation (p-nitro anisol) and hydroxylation (aniline). The infusion with nicotinic acid restored N-demethylation but it inhibited O-demethylation and hydroxylation.