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.

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.

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.

Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous verapamil infusion: clinical experience in the intensive care unit.

OBJECTIVE: Our study aimed at evaluating the pharmacokinetic, cardiovascular, and metabolic effects of high-dose verapamil continuous intravenous infusion in cancer patients. DESIGN: Prospective clinical and pharmacokinetic study. SETTING: Intensive care unit of a Cancer Research Institute. PATIENTS: Nine patients (age range 31 to 57 yrs) with progressive cancer disease and without cardiovascular, renal, or hepatic dysfunctions. INTERVENTIONS: After a loading dose (0.15 mg/kg followed by 12 hrs of continuous intravenous infusion at 0.20 mg/kg/hr), the infusion rate of verapamil was increased every 24 hrs (0.25, 0.30, 0.35, and 0.40 mg/kg/hr). The highest rate was maintained for 48 hrs. Doxorubicin was given from the 60 th to the 108 th hr. Hydrochlorothiazide (25 mg/day) and potassium (36 mmol/day) were given orally. Altogether, 17 courses were completed. MEASUREMENTS AND MAIN RESULTS: Steady state concentration (C(SS) and systemic clearance of verapamil and nor-verapamil (active metabolite) for each infusion rate were calculated. Mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), PR, QT and QTc intervals, and left ventricular ejection fraction (LVEF) were measured, as well as daily body weight, blood glucose and potassium. C(SS) of verapamil and nor-verapamil increased more than proportionally to the infusion rate (p<.001). Systemic clearance of verapamil decreased over the range of the infusion rate (p<.005). MAP and HR decreased at the 12th hr (p<.001) and then plateaued. CVP increased (p<.01). The relationship between MAP, HR, CVP, and verapamil plasma concentrations was significant (r2 = .25, .14, and .35, respectively; p<.0001). LVEF did not change. Six patients (11 courses) developed junctional rhythm. Three patients (six courses) showed a PR interval increase (p<.05). Patients with junctional rhythm had higher Css of verapamil (p<.009). Overall, QT and QTc intervals increased (p<.01). A linear relationship was observed between verapamil plasma concentrations and QT intervals (r2 = .09, p<.01). Cardiovascular side effects did not determine treatment withdrawal in any patient. Body weight, blood glucose, and potassium did not show significant changes. CONCLUSIONS: Our data suggest a capacity-limited clearance of high-dose verapamil. In the absence of heart disease, following a step by step increase of the dosage, the high plasma verapamil concentrations (617 to 2970 ng/mL) produce frequent but well tolerated hemodynamic and electrocardiogram changes.

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)

[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.

Effect of atrial fibrillation on pulmonary venous flow patterns: transoesophageal pulsed Doppler echocardiographic study.

The effect of atrial fibrillation on pulmonary venous flow patterns is still not well known. Twenty-four patients in atrial fibrillation and 21 patients in sinus rhythm were studied by transoesophageal echocardiography. In ninety-five percent (20/21) of sinus rhythm patients, the early systolic wave due to atrial relaxation or reverse wave due to atrial contraction could be distinguished on pulsed Doppler tracings by transoesophageal echocardiography. However, there was no early systolic wave and/or reverse at the end of diastole in any atrial fibrillation patients. In atrial fibrillation patients without mitral regurgitation (n = 14), the onset of systolic flow was delayed (165 +/- 38 vs 50 +/- 46 ms, P < 0.05), and systolic peak velocities, time-velocity integrals and systolic fractions were reduced (31 +/- 13 vs 54 +/- 17 cm.s-1, P < 0.05; 5 +/- 2 vs 13 +/- 6 cm, P < 0.05 and 36 +/- 8 vs 61 +/- 15%, P < 0.05, respectively) as compared to those in sinus rhythm. Significant mitral regurgitation (n = 10) reduced systolic velocity parameters considerably in atrial fibrillation patients but the diastolic flow parameters were not significantly different between sinus rhythm and atrial fibrillation patients. Stepwise multiple regression analysis identified atrial fibrillation as an important independent predictor for changes in systolic flow parameters. The R-R interval is also an important factor for diastolic flow parameters. Thus, the present study demonstrates that atrial fibrillation significantly modifies pulmonary venous flow pattern and is an important factor for systolic flow parameters. Significant mitral regurgitation can further modify systolic flow pattern in atrial fibrillation patients.

Diagnosis of heart tumours by transoesophageal echocardiography: a multicentre study in 154 patients. European Cooperative Study Group.

In a retrospective multicentre study, the diagnostic potential of transoesophageal 2D-echocardiography (TEE) as compared to precordial 2D-echocardiography (TTE) was determined in 154 patients with primary or secondary tumours of the heart. Additionally, the value of standard diagnostic parameters, such as symptoms, X-ray of the chest and electrocardiogram were evaluated. In 84 patients (24 male, 60 female; age 20-85, mean 56.6 years) intracardial tumours were present, and 70 patients (37 male, 33 female; age 18-79, mean 44.3 years) presented with peri- or paracardial tumours. The main symptoms of patients with intracardial tumours were dyspnoea (60.7%), vena cava syndrome (22.2%) and chest pain (20.2%). Embolization was found in 11.9%. Left or right atrial enlargement was observed on chest X-ray in 23 patients, and echocardiographic abnormalities in 17 cases. The patients with peri- or paracardial tumours presented with dyspnoea in 51.4% of cases, loss in body weight in 20.0% and with vena cava syndrome and chest pain in 17.1%. The chest X-ray was abnormal in 56 patients. Unspecific ST segment changes in the electrocardiogram were observed in five, and arrhythmias in seven cases. Diagnosis of atrial myxomas was achieved by TTE in 95.2%, by TEE in 100%, by angiography in 78.4%, by computed tomography (CT) or magnetic resonance tomography (NMR) in 70%. Identification of the attachment point was made by angiography in 8.1%, by TTE in 64.5% and by TEE in 95.2%. In 22 patients with intracardial tumours (myxomas excepted) diagnosis was achieved by TTE in 90.9%, by TEE in 100%, by CT or NMR in 88.9% and by angiography in 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic prediction of the final event in patients dying of acute myocardial infarction.

From an autopsy series of 346 patients who died of acute myocardial infarction, we selected 36 cases for whom echocardiographic data preceding death were available: 17 cases died from a rupture of the left ventricular free wall (group A) and 19 from pump failure (group B). Our aim was to investigate whether any echocardiographic parameter could predict the final event. The total wall motion score, regional wall motion score index and percent of abnormally contracting myocardium were calculated. Diastolic and systolic volumes, ejection fraction and the eccentricity index, as a rough indicator of the left ventricular shape, were also estimated. Interventricular septum and posterior wall thicknesses were also measured. All measured parameters were similar in both groups except posterior wall thickness. Even though an unavoidable selection bias is present in our series, we failed to identify any echocardiographic predictor of the final event in this patient group.

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.

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.

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.

Quantification of mitral regurgitation: comparison between transthoracic and transesophageal color Doppler flow mapping.

We reviewed transthoracic (TTE) and transesophageal (TEE) echocardiograms of 100 consecutive patients: 63 male, 37 female, mean age 50 years (range 16-83 years), 32 with neoplastic disease, 18 aortic disease, 28 mitral valve disease, and 22 with other diseases. Absence or presence of mitral regurgitation (defined as mild, moderate, or severe) was assessed. TEE showed mild mitral regurgitation in 26 patients where TTE was negative. The overall estimate of regurgitant lesion severity was concordant at TEE and TTE in 64% of cases. The overall estimate of regurgitant lesion severity was also greater by one grade in 1% of cases at TTE, and in 35% of cases at TEE. Maximal digitized jet areas were 3.60 +/- 6.35 cm 2 at TTE and 3.04 +/- 3.79 cm 2 at TEE (P = NS). Correlation was r = 0.69 (TEE = 0.41 TTE + 1.55; P less than 0.001). TEE yielded a higher prevalence of mitral regurgitation than TTE with a trend toward greater overall estimate of mitral regurgitation at the semi-quantitative analysis. TTE and TEE showed similar mean results at the quantitative assessment of maximal jet areas. However, a highly significant random variability was observed in quantifying mitral regurgitation at TEE.

[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.