Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk.

BACKGROUND: Effort-induced myocardial ischemia (EMI) has been seldom described. Aims of our study were (A) to evaluate the prevalence of EMI during long-lasting 5-FU infusion; (B) to identify possible risk factors of EMI during 5-FU infusion. PATIENTS AND METHODS: For the purpose (A), we prospectively evaluated a group of patients undergoing in-hospital continuous infusion (c.i.) of 5-FU. Patients with rest ischemia were excluded. Among 358 consecutive patients, 21 (5.9%) had rest ischemia; 109 could not perform a stress test. The remaining 228 patients underwent a treadmill stress test (TST) after >46 h of 5-FU infusion. For the purpose (B), we compared the characteristics of patients with EMI (including 3 previously described in a 2001 paper) with those without EMI. RESULTS: Among 228 patients, 16 (6.9%) had EMI. These 16 had a second TST after stopping 5-FU: in 14, it was negative, 2 patients with coronary artery disease had milder ischemia. The whole group of 231 (including 3 described in a previous paper) patients undergoing TST included 148 males and 83 females, with mean age of 57.5. Cardiovascular risk factors were present in 178 of them. Eight patients had ischemic heart disease. Among 19 patients with EMI, 7 had angina, 12 silent ischemia. ST segment at ECG was elevated in 10 patients, depressed in 9. Comparing the group with toxicity and the one without, the only significant difference was the complaint of atypical symptoms at rest before the TST. No difference was observed as regards: chemotherapy schedule (chronic c.i. in 49, 5 days in 178, FOLFOX type in 12), coronary risk factors or heart disease. CONCLUSIONS: EMI is as frequent as rest ischemia during 5-FU infusion. Patients undergoing 5-FU continuous infusions should be adviced to avoid unusual efforts, to refer any cardiac symptom, and should be investigated for EMI.

Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis.

BACKGROUND: Adjuvant Trastuzumab with chemotherapy is the gold standard for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (HER2+ EBC). Older patients have been largely under-represented in clinical trials, and few data on Trastuzumab cardiotoxicity have been reported in this subgroup. PATIENTS AND METHODS: Four hundred and ninety-nine consecutive HER2+ EBC patients were treated with adjuvant trastuzumab and chemotherapy (aTrastC) at 10 Italian institutions. We evaluated disease prevalence and patient characteristics in the patients older than 60 years of age (over-60), prevalence of aTrastC cardiotoxicity and risk factors. RESULTS: There were 160 'over-60' patients (32%), in whom a higher prevalence of hypertension, diabetes, renal dysfunction, dyslipidemia and treatment with ACEi (40 versus 8%) and beta blockers (20 versus 8%) was found than in the younger patients (339 = 68%). Clinical heart failure occurred in 6% of the 'over-60' and in 2% of the younger patients. A reduction in left ventricular ejection fraction of >10 points was detected in 33% of the 'over-60' and in 23% of the younger patients (all P < 0.05). aTrastC was discontinued in 10% of the 'over-60' and in 4% of the younger patients (P = 0.003), restarted in 44% of the 'over-60' and in 58% of the younger women (P = ns). CONCLUSION: In clinical practice, 32% of HER2+ EBC patients treated with aTrastC are 'over-60'. These patients have an increased cardiovascular risk profile and develop aTrastC cardiotoxicity commonly.

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.

Relation of right ventricular morphology and function in pectus excavatum to the severity of the chest wall deformity.

Although pectus excavatum (PE) is thought to impair right ventricular (RV) performance, the degree of RV dysfunction, if any, produced by this chest wall deformity remains controversial. To address this issue, we performed 2-dimensional echocardiography and chest wall radiography in 28 subjects with mild-to-severe degrees of PE to assess RV morphology and function in relation to the degree of the chest wall deformity. Measurements of RV anatomy and function obtained in these patients were compared to those of 24 normal control subjects of similar age and sex. In subjects with PE, mean RV outflow tract diameter at the aortic root level was narrower (1.4 +/- 0.3 cm/m2) and end-diastolic (10 +/- 2.3 cm2/m2) and end-systolic (5.8 +/- 1.4 cm2/m2) areas were larger than those in normal controls (1.6 +/- 0.3, 8.6 +/- 1.7, and 4.5 +/- 1.2 cm2/m2, respectively; p < 0.013). The magnitude of these abnormalities was related to the degree of the chest wall deformity evaluated on the chest radiogram (r = 0.54, 0.51, and 0.49, respectively). RV planar emptying fraction, an index of RV systolic function, was reduced in subjects with PE (42 +/- 10%) compared to the normal controls (48 +/- 10%; p = 0.047). No relation could be found, however, between this index and the severity of the chest wall deformity.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of transesophageal echocardiography in evaluation of paracardiac neoplastic masses.

Mediastinal paracardiac tumors may cause both cardiovascular complications and problems in differential diagnosis of cardiac diseases. Transesophageal echocardiography (TEE) may give an additional new window to mediastinal neoplasms, but only a few studies have been reported. TEE was performed in 70 patients with paracardiac neoplastic masses. The procedure was indicated to solve particular clinical problems in 20 patients, and as a prospective study on 50 unselected patients with mediastinal neoplasms. Twenty-three patients underwent follow-up studies; a total of 101 echocardiograms were recorded. The procedure was tolerated well or very well by most patients, and provided additional anatomic or hemodynamic data in every patient in group a and in 45 of 50 in group b. The additional data were relevant for clinical management in 14 of 20 patients in group a, and in 3 of 45 in group b. Based on the results of this study, TEE is useful in association with other radiologic techniques in patients with paracardiac neoplasms. As an imaging technique, it may represent a reliable alternative to computed tomography whenever the latter is not feasible.

Role of transesophageal echocardiography in evaluation of pulmonary venous obstruction by paracardiac neoplastic masses.

From 71 consecutive patients with paracardiac neoplastic masses who underwent transesophageal echocardiography (TEE), obstruction of individual right upper pulmonary venous flow by compression by contiguous mass was detected by TEE in 4 patients before and disappeared after anti-neoplastic treatments. Pulmonary vein, contiguous neoplastic mass and their relation could be clearly visualized and assessed by TEE. Pulmonary venous obstruction was assessed as moderate degree by combination of Doppler flow characteristics and diameter of pulmonary vein. Before therapy, peak velocities and time-velocity integrals in obstructed right upper pulmonary venous flow were increased, whereas deceleration times of systolic flow were prolonged. After therapy, peak velocities and time-velocity integrals were reduced and deceleration times of systolic flow were shortened, with normalization of the diameter of the right upper pulmonary veins. Thus, TEE may be used to detect and evaluate pulmonary venous obstruction by neoplastic masses and its changes after antineoplastic treatments.

Sensitivity and specificity of electrocardiographic ST-T changes as markers of neoplastic myocardial infiltration. Echocardiographic correlation.

We evaluated the correlations between electrocardiographic ST-T changes (negative T waves, ST segment elevation) and echocardiographic diagnosis of neoplastic infiltration of the myocardium in 95 patients with neoplastic masses in contact with the heart. We compared echocardiographic results to computed tomography, nuclear magnetic resonance, surgery or autopsy data in 49 patients: the concordance was 86 percent. Significant ST-T changes were present in 77.7 percent of the patients with myocardial infiltration at echocardiography. The "false negatives" (normal ECG, nonspecific changes) were mainly related to infiltration limited to the right side of the heart; in some of these cases, the appearance of right bundle branch block was observed. The "false positives" (ST-T changes without echocardiographic signs of infiltration) were observed in the older patients and in those with pericardial effusion or other heart diseases. The ST segment elevation was a more specific sign of myocardial infiltration as compared to negative T waves (86 vs 47 percent). A progression or the disappearance of electrocardiographic and echocardiographic abnormalities was observed during follow-up in 24 cases. Serial electrocardiograms are useful for screening in clinical settings in neoplastic patients; the appearance of ST-T changes or of conduction disturbances should suggest the need for two-dimensional echocardiography in order to define the diagnosis.

Pharmacokinetics of VM 26 given intrapericardially or intravenously in patients with malignant pericardial effusion.

Three patients with lung cancer (1 SCLC, 2 NSCLC) and pericardial malignant effusion received 100 mg/m2 Teniposide (VM 26) i.v. and, 1 week later, 50 mg/m2 intrapericardially. Plasma, pericardial, and urine levels of the drug were measured in all patients after the two treatments by a HPLC assay. After intrapericardial administration, a high VM 26 concentration was found in the pericardial cavity and slow systemic drug absorption was observed. Since the drug AUC after intrapericardial administration was approximately 15-21 times that after i.v. administration, it could be that this treatment is more effective against neoplastic deposits localized in the pericardium. Even though this small series does not permit conclusions to be drawn on the efficacy of VM 26 given intrapericardially, the lack of local toxicity, minimal systemic toxicity, and the response observed in two out of three patients given intrapericardial VM 26 suggest that further investigation should be carried out on this method of VM 26 administration.

Familial dilated cardiomyopathy: a transverse and longitudinal clinical and echocardiographic study.

The familial occurrence of hypertrophic cardiomyopathy is well known; familial dilated cardiomyopathy has so far received less attention. Ten families with two or more members affected by dilated cardiomyopathy were studied by echocardiography. In 3 out of 10 families, a transverse study extended to even apparently healthy subjects was carried out, which included a total of 45 subjects. In 19 out of the 45, dilated cardiomyopathy (either symptomatic or asymptomatic) was diagnosed at echocardiography. Three more relatives, already dead of the disease, were identified through hospital records. A clinical and echocardiographic longitudinal study, lasting up to 11 years, was carried out in 5 of the 10 families. During the follow-up, 8 out of 19 patients who, at first examination were affected by dilated cardiomyopathy, died, one improved, 3 remained in stable condition and 7 were lost at follow-up. One of two patients who presented echocardiographic findings suggestive of border-line dilated cardiomyopathy returned to normality and the other developed dilated cardiomyopathy. The clinical and echocardiographic findings in our patients, and in their relatives, suggest the possibility that idiopathic dilated cardiomyopathy may be a multifactorial disease in which genetic factors might play a variable role.

Echocardiographic findings of left ventricular hypertrophy and normalization of parameters of left ventricular function in patients with previous evidence of dilated and poorly contracting left ventricle and coexisting systemic hypertension.

We report 6 cases of dilated left ventricle with poor left ventricular function and coexisting systemic hypertension in whom left ventricular hypertrophy and normalization of left ventricular function and dimensions have been subsequently documented by M-mode and two-dimensional echocardiographic follow-up studies. Four patients were in New York Heart Association functional Class IV, one in Class III, and one in Class II when first seen. Normalization of left ventricular function and dimensions and features of left ventricular hypertrophy (fractional shortening from 15.0 +/- 5.2 to 39.7 +/- 5.4, left ventricular end-diastolic diameter from 6.6 +/- 0.6 to 4.6 +/- 0.6 cm, left ventricular end-systolic diameter from 5.6 +/- 0.8 to 2.8 +/- 0.6 cm, left ventricular end-diastolic radius/posterior wall thickness from 3.1 +/- 0.5 to 2.0 +/- 0.4, interventricular septum thickness from 1.2 +/- 0.3 to 1.5 +/- 0.3 cm, left atrium from 4.6 +/- 0.6 to 3.5 +/- 0.9 cm) were achieved after adequate medical treatment at the end of the follow-up (11-39 months). It appears from this study that normalization of left ventricular dimensions and function with features of left ventricular hypertrophy can occur after adequate treatment in patients with echocardiographic findings of dilated and poorly contracting left ventricle and coexisting systemic hypertension. It is conceivable, in such cases, to classify the dilatation of the left ventricle as secondary and to suggest the hypothesis of a cause-effect relationship between therapy and normalization of left ventricular parameters with findings of left ventricular hypertrophy. Further studies are needed to clarify this phenomenon.

Innovative schedule of oral idarubicin in elderly patients with metastatic breast cancer: comprehensive results of a phase II multi-institutional study with pharmacokinetic drug monitoring.

BACKGROUND: To determine if protracted low-dose oral idarubicin (IDA), feasible in a previous dose-finding study, would result in similar activity and a better toxicity profile in patients with metastatic breast cancer. PATIENTS AND METHODS: Elderly women (> or=65 years) with metastatic breast carcinoma were treated with 7.5 mg/day for 21 consecutive days, every 4 weeks. After the first fourteen patients, due to excessive toxicity, the protocol was amended to 5 mg/day. IDA and Idarubicinol (IDOL) plasma concentrations (C(trough)) were investigated in all patients. RESULTS: Between April 1999 and June 2004, 47 elderly patients were accrued in this two-part study (14 and 33 patients respectively). The median age was 74 and 75 years respectively. Visceral involvement was present in most patients. A partial response was noted in 7/31 patients (22%; 95% CI, 9.6-41.1%). Eleven patients had stable disease (33%). At the dose of 5 mg/day the treatment was well tolerated. Neutropenia grade 4 was present in only 6% of patients; alopecia > grade 1 and cardiotoxicity did not occur. The median time to progression was 3 months and the median overall survival was 17 months. IDA C(trough) and IDOL C(trough) levels were significantly associated with haematologic toxicity. CONCLUSION: This study shows that idarubicin at the dose of 5 mg/day for 21 consecutive days is feasible and effective in elderly breast cancer patients but do not demonstrate an improvement in efficacy. A determination of the IDA and IDOL plasma levels (C(trough)) is predictive for toxicity.

[Normalization of left ventricular function and subsequent recurrence of dilatation and pump failure in a patient with hypertensive heart disease in dilated phase after treatment with anthracycline]. / Normalizzazione della funzione ventricolare sinistra e successiva recidiva di dilatazione e deficit di pompa in paziente con cardiopatia ipertensiva in fase dilatativa dopo trattamento con antracicline.

A 71 years old man, ex-smoker, moderate drinker, with a history of diabetes mellitus (type II), moderate arterial hypertension, mild aortic stenosis and moderate uniform left ventricular hypertrophy echographically documented, developed a non Hodgkin low malignancy cavum lymphoma. He has underwent chemotherapy for two years (adriamycin and other chemotherapy drugs) at moderate dosages. A complete remission of the lymphoma followed the treatment, but an initial deterioration of left ventricular function, with heart dilatation and congestive heart failure, was found. The patient improved by medical treatment, returning to the previously stable clinical condition. However a ventricular dilatation reoccurred and a paroxysmal complete atrio-ventricular block developed, necessitating the implantation of a pace maker. The patient died suddenly, during sleep, at home. This is a unique case, because of the numerous cardiac factors associated (chemotherapy and clinical findings). More probably the combination of these multiple factors and their interrelationship could explain the unique non-linear evolution of the left ventricular hypertrophy. In conclusion in these patients a very strict clinical and pharmacological follow up with serial echocardiographical examinations is fundamental and highly recommended.

Left atrial invasion by lung carcinoma through a pulmonary vein.

We describe a rare case of small-cell lung carcinoma invading the left atrium through a pulmonary vein. Echocardiography was particularly useful in this case in assessing the intracavitary extension of the tumor and the outcome of therapy. Echocardiography is a low-cost, easy imaging tool, complementary to radiological techniques and useful in evaluating thoracic tumors involving the cardiovascular structures.

[Evolving electrocardiographic changes in massive neoplastic infiltration of the right ventricle. Description of a case and review of the literature]. / Alterazioni elettrocardiografiche evolutive nell'infiltrazione neoplastica massiva del ventricolo destro. Descrizione di un caso e revisione della letteratura.

We report a case of metastasis of lung carcinoma infiltrating the inferior left ventricular wall, the interventricular septum and the right ventricle. The metastatic invasion of the heart caused the appearance of pseudoischemic electrocardiographic changes, arrhythmias and eventually a conduction disturbances. The relevance of electrocardiographic changes as an indicator of cardiac metastasis in neoplastic patients is discussed.

[2-dimensional echocardiography in the evaluation of pericardial pathology: new prospects for its differential diagnosis]. / L'ecocardiografia bidimensionale nella valutazione della patologia del pericardio: nuove prospettive di diagnosi differenziale.

We examined retrospectively the M-mode and two-dimensional echocardiograms performed in our laboratory on 227 patients with pericardial diseases, in order to assess the capabilities and limits of echocardiography in this field. We observed 4 patients with congenital absence of the pericardium, 10 with of constrictive or infiltrative-adhesive pericarditis, 213 pericardial effusions, associated with left pleural effusion in 36 cases and with different kinds of intrapericardial masses in 33 cases. Through qualitative analysis of the echogenicity of such masses some aspects were singled out which may prove useful in identifying intrapericardial fat, as well as tumors. We also suggest new ways of using specific echocardiographic sections to differentiate left pleural effusions from pericardial effusions, and to identify very small pericardial effusions.