Early Detection of Anthracycline-Induced Cardiotoxicity in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Low Cumulative Dose.

We investigated the left ventricular (LV) function, using for the first time strain (S) and strain rate (SR) imaging, in long-term survivors affected by acute lymphoblastic leukemia treated with a low cumulative dose of anthracyclines, and in presence of a normal global LV systolic and diastolic function. A total of 21 were enrolled in the study. The mean cumulative dose of anthracylines was 180 mg/m2 (range: 120-210 mg/m2). As control group 21 age-sex matched healthy subjects were included. Radial S (17 ± 3% vs. 55 ± 6%, P < 0.0001) and SR (2.1 ± 0.3 vs. 3.0 ± 0.8 1\s, P < 0.0001), assessed on the midsegment of the posterior wall from the parasternal views were significantly reduced when compared with controls. Conversely, myocardial performance index was not able to discriminate between patients and controls. In this preliminary study, the myocardial deformation indices appear to be a more sensitive noninvasive technique for detecting subclinical LV dysfunction than other echocardiographic measurements.

Preoperative, postoperative and 1-year follow-up N-terminal pro-B-type natriuretic peptide levels in severe chronic aortic regurgitation: correlations with echocardiographic findings.

B-type natriuretic peptide is synthesized in response to increased ventricular wall stress (WS) and hypertrophy. To serially evaluate amino-terminal-pro-BNP (NT-pBNP) serum levels in patients undergoing aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR), blood samples were drawn preoperatively, 15 days postoperatively, at 6- and 12-month follow-up in 25 consecutive patients. Two-dimensional echocardiography was performed concomitantly, assessing left ventricular (LV) dimensional and functional parameters, including WS. Correlations between NT-pBNP, clinical and echocardiographic data were assessed by non-parametric statistics. Median preoperative NT-pro-BNP was 276 pg/ml (IQR=85-1056), being normal or mildly increased in 20 patients, overly increased in five. The most significant correlations of preoperative NT-pBNP were with diastolic (r=0.80, P<0.001) and systolic (r=0.75, P<0.001) meridional WS and inversely with time from symptom onset (r=-0.67, P=0.001). NT-pBNP increased 15 days postoperatively (568 pg/ml, P=0.006 vs. preoperative), then decreased at 6 months (144 pg/ml, P<0.001) to remain stable at 1 year (108 pg/ml, P=0.16). Long-term follow-up NT-pBNP showed direct correlation with diastolic WS (r=0.56, P=0.02). Higher preoperative levels of NT-pBNP predicted greater magnitude of total LV mass regression at follow-up (r=-0.65, P=0.002) independent of preoperative LV mass index, showing that NT-pBNP may have a potential prognostic usefulness in adjunct to echocardiography.

Non-HACEK gram-negative bacillus endocarditis.

BACKGROUND: Infective endocarditis caused by non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species) gram-negative bacilli is rare, is poorly characterized, and is commonly considered to be primarily a disease of injection drug users. OBJECTIVE: To describe the clinical characteristics and outcomes of patients with non-HACEK gram-negative bacillus endocarditis in a large, international, contemporary cohort of patients. DESIGN: Observations from the International Collaboration on Infective Endocarditis Prospective Cohort Study (ICE-PCS) database. SETTING: 61 hospitals in 28 countries. PATIENTS: Hospitalized patients with definite endocarditis. MEASUREMENTS: Characteristics of non-HACEK gram-negative bacillus endocarditis cases were described and compared with those due to other pathogens. RESULTS: Among the 2761 case-patients with definite endocarditis enrolled in ICE-PCS, 49 (1.8%) had endocarditis (20 native valve, 29 prosthetic valve or device) due to non-HACEK, gram-negative bacilli. Escherichia coli (14 patients [29%]) and Pseudomonas aeruginosa (11 patients [22%]) were the most common pathogens. Most patients (57%) with non-HACEK gram-negative bacillus endocarditis had health care-associated infection, whereas injection drug use was rare (4%). Implanted endovascular devices were frequently associated with non-HACEK gram-negative bacillus endocarditis compared with other causes of endocarditis (29% vs. 11%; P < 0.001). The in-hospital mortality rate of patients with endocarditis due to non-HACEK gram-negative bacilli was high (24%) despite high rates of cardiac surgery (51%). LIMITATIONS: Because of the small number of patients with non-HACEK gram-negative bacillus endocarditis in each treatment group and the lack of long-term follow-up, strong treatment recommendations are difficult to make. CONCLUSION: In this large, prospective, multinational cohort, more than one half of all cases of non-HACEK gram-negative bacillus endocarditis were associated with health care contact. Non-HACEK gram-negative bacillus endocarditis is not primarily a disease of injection drug users.

"Z-plasty suture": a new procedure for complex reconstructions of posterior mitral leaflet.

In recent years the conservative techniques to treat degenerative mitral valve insufficiency have developed to such an extent mainly due to a better understanding of the physiology and pathology of the mitral valve and to the possibility to get predictable and satisfactory results. Still a challenge persists for the cardiac surgeon when he has to deal with complex reconstructions. The technique described seems to offer an even better surgical option for patients with complex lesions involving the posterior mitral leaflet, especially as far as the hemodynamic performance is concerned.

Contemporary clinical profile and outcome of prosthetic valve endocarditis.

CONTEXT: Prosthetic valve endocarditis (PVE) is associated with significant mortality and morbidity. The contemporary clinical profile and outcome of PVE are not well defined. OBJECTIVES: To describe the prevalence, clinical characteristics, and outcome of PVE, with attention to health care-associated infection, and to determine prognostic factors associated with in-hospital mortality. DESIGN, SETTING, AND PARTICIPANTS: Prospective, observational cohort study conducted at 61 medical centers in 28 countries, including 556 patients with definite PVE as defined by Duke University diagnostic criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to August 2005. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: Definite PVE was present in 556 (20.1%) of 2670 patients with infective endocarditis. Staphylococcus aureus was the most common causative organism (128 patients [23.0%]), followed by coagulase-negative staphylococci (94 patients [16.9%]). Health care-associated PVE was present in 203 (36.5%) of the overall cohort. Seventy-one percent of health care-associated PVE occurred within the first year of valve implantation, and the majority of cases were diagnosed after the early (60-day) period. Surgery was performed in 272 (48.9%) patients during the index hospitalization. In-hospital death occurred in 127 (22.8%) patients and was predicted by older age, health care-associated infection (62/203 [30.5%]; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.08-2.44; P = .02), S aureus infection (44/128 [34.4%]; adjusted OR, 1.73; 95% CI, 1.01-2.95; P = .05), and complications of PVE, including heart failure (60/183 [32.8%]; adjusted OR, 2.33; 95% CI, 1.62-3.34; P<.001), stroke (34/101 [33.7%]; adjusted OR, 2.25; 95% CI, 1.25-4.03; P = .007), intracardiac abscess (47/144 [32.6%]; adjusted OR, 1.86; 95% CI, 1.10-3.15; P = .02), and persistent bacteremia (27/49 [55.1%]; adjusted OR, 4.29; 95% CI, 1.99-9.22; P<.001). CONCLUSIONS: Prosthetic valve endocarditis accounts for a high percentage of all cases of infective endocarditis in many regions of the world. Staphylococcus aureus is now the leading cause of PVE. Health care-associated infection significantly influences the clinical characteristics and outcome of PVE. Complications of PVE strongly predict in-hospital mortality, which remains high despite prompt diagnosis and the frequent use of surgical intervention.

Risk of embolism and death in infective endocarditis: prognostic value of echocardiography: a prospective multicenter study.

BACKGROUND: The incidence of embolic events (EE) and death is still high in patients with infective endocarditis (IE), and data about predictors of these 2 major complications are conflicting. Moreover, the exact role of echocardiography in risk stratification is not well defined. METHODS AND RESULTS: In a multicenter prospective European study, including 384 consecutive patients (aged 57+/-17 years) with definite IE according to Duke University criteria, we tested clinical, microbiological, and echocardiographic data as potential predictors of EE and 1-year mortality. Transesophageal echocardiography was performed in all patients. Embolism occurred before or after IE diagnosis (total-EE) in 131 patients (34.1%) and after initiation of antibiotic therapy (new-EE) in 28 patients (7.3%). Staphylococcus aureus and Streptococcus bovis were independently associated with total-EE, whereas vegetation length >10 mm and severe vegetation mobility were predictors of new-EE, even after adjustment for S aureus and S bovis. One-year mortality was 20.6%. In multivariable analysis, independently of the other predictors of death (age, female sex, creatinine serum >2 mg/L, moderate or severe congestive heart failure, and S aureus) and comorbidity, vegetation length >15 mm was a predictor of 1-year mortality (adjusted relative risk=1.8; 95% CI, 1.10 to 2.82; P=0.02). CONCLUSIONS: In IE, vegetation length is a strong predictor of new-EE and mortality. In combination with clinical and microbiological findings, echocardiography may identify high-risk patients who will need a more aggressive therapeutic strategy.

Evaluation of left ventricular function in long-term survivors of childhood Hodgkin disease.

BACKGROUND: Data on the presence of myocardial abnormalities in long-term Hodgkin disease survivors are contradictory. The purpose of this study was to determine if myocardial performance index (MPI) was capable of discovering cardiac abnormalities. PROCEDURE: Echocardiographic evaluation was performed in 31 survivors of Hodgkin disease (mean age 17.0 years), who received doxorubicin as part of chemotherapeutic treatment (median dose 164.8 +/- 42.5 mg/m(2)). Control group comprised 22 healthy subjects (mean age 16.7 years). RESULTS: Peak A velocity was increased (P = 0.004) and peak E/A velocity ratio was lower (P = 0.002) in patients compared to controls. Mean isovolumetric contraction time was longer in patients than in controls (P = 0.0001). Ejection time was significantly shorter in patients than in the controls (P = 0.001). Consequently, the MPI was significantly greater in the patients than in the controls (P = 0.0001). Abnormal MPI was found in 25/31 patients (83%). CONCLUSIONS: The Doppler-derived index of combined systolic and diastolic myocardial performance demonstrates the presence of subtle cardiac abnormalities in the majority of Hodgkin disease survivors.

Anthracycline-induced cardiotoxicity in children with cancer: strategies for prevention and management.

The fact that anthracyclines are cardiotoxic seriously narrows their therapeutic index in cancer therapy. The cardiotoxic risk increases with the cumulative dose and may lead to congestive heart failure (CHF) and dilated cardiomyopathy in adults and in children. The prevention of anthracycline-induced cardiotoxicity is particularly important in children who can be expected to survive for decades after being cured of their malignancy. Attempts to reduce anthracycline cardiotoxicity have been directed towards: (i) decreasing myocardial concentrations of anthracyclines and their metabolites by dose limitation and schedule modification; (ii) developing less cardio-toxic analogs; and (iii) concurrently administering cardioprotective agents to attenuate the effects of anthracyclines on the heart. As regards schedule modification, avoidance of anthracycline peak levels may reduce the pathologic and clinical cardiotoxicity, although this has not always been observed. The analogs of doxorubicin, such as idarubicin and epirubicin, have similar cardiotoxicity to that of doxorubicin when given in amounts of equivalent myelotoxicity. Liposomal anthracyclines are a new class of agents that may permit more specific organ targeting, thereby producing less systemic and cardiac toxicity, but more studies are required to assess the advantages, if any, of these preparations over classical anthracyclines. The cardioprotective agent, dexrazoxane, an iron chelator, is highly effective and provides short-term cardioprotection to most patients receiving even the most intensive doxorubicin-containing regimens. Its long-term benefits remain to be determined. In addition, data remain insufficient to make specific recommendations regarding current use of dexrazoxane in children. It is thought that subtle abnormalities, related to anthracycline treatment in childhood, can develop into more permanent myocardial disease resulting in cardiomyopathy, which may progress to CHF. As regards the therapy of patients with anthracycline cardiotoxicity, two different situations have, therefore, to be considered: (i) if the patient presents with cardiac abnormalities, such as a reduction in fractional shortening at echocardiogram, without cardiac symptoms; and (ii) if the patient has CHF. In the presence of CHF, recovery with digitalis-diuretic therapy alone seldom occurs, and in patients who have refractory hemodynamic decompensation, heart transplantation is indicated. In patients with CHF, therapy with ACE inhibitors induces improvement in left ventricular structure and function, but this improvement is transient. Randomized clinical trials are, therefore, necessary to determine the effects of ACE inhibitors in mild-to-moderate left ventricular dysfunction. The beneficial effects of beta-adrenoceptor antagonists (beta-blockers) on cardiac function in heart failure due to anthracyclines seem comparable with those observed in other forms of heart failure with systolic dysfunction. Many drugs are available to treat children with CHF due to anthracycline treatment, but they are only palliative.

[Heart failure in a subject treated with anthracyclines in childhood: myocardial dysfunction is not always the only reason of it]. / Scompenso cardiaco biventricolare in soggetto trattato nell'infanzia con antracicline: non sempre la disfunzione miocardica ne è la causa.

Anthracyclines, found to be efficacious in the treatment of a broad spectrum of pediatric malignancies, are cardiotoxic and may lead to heart failure even a long time after successful treatment of cancer. It is thought that subtle abnormalities can progress to the more permanent myocardial disease, resulting in cardiomyopathy which may progress to congestive heart failure. There are some precipitating factors leading to the sudden onset of cardiac symptoms such as increase in afterload or preload. We describe a young patient with congestive heart failure treated with doxorubicin (cumulative mean dose 420 mg/m2) in infancy because of pelvic sarcoma in whom the appearance of symptoms was related to pulmonary embolism. Four years before hospital admission, the patient presented echocardiographic abnormalities such as left ventricular fractional shortening and thickness reduction and he was treated with ACE-inhibitors. The myocardial ischemia, which is present in pulmonary embolism, probably worsened the left ventricular systolic function and caused congestive heart failure.

Cardiac involvement in beta-thalassemia major and beta-thalassemia intermedia.

The forms and severity of cardiac complications were investigated in patients with asymptomatic thalassemia intermedia and thalassemia major by M-mode, bi-dimensional echocardiography (ECHO) and echo-Doppler. Twenty-eight patients of both sexes with beta-thalassemia intermedia (beta-TI), mean age 23.2 +/- 6.3 years, untransfused or minimally transfused, were compared to 42 age- and sex-matched subjects with thalassemia major, who were regularly treated with hemotransfusive therapy [pre-transfusion hemoglobin (Hb) values 9.5 +/- 0.9 g/dL] and iron chelation. All patients were splenectomized. Age and sex matched healthy control subjects were randomly selected. beta-Thalassemia major (beta-TM) patients showed a marked reduction in contractile state and a milder left ventricular (LV) enlargement than beta-TI patients. Cardiac output (CO) and cardiac index (CI) were increased in both groups of patients but appeared significantly higher in beta-TI patients with consequent altered LV diastolic function indices. In addition, beta-TI patients had reduced indices of pulmonary artery flow related to long-term chronic anemia rather than iron overload. The progressive rise in CO and CI casts doubts on the current management of beta-TI syndromes.

[Biventricular heart failure in patient treated with anthracycline in childhood: myocardial dysfunction is not always the cause]. / Scompenso cardiaco biventricolare in soggetto trattato nell'infanzia con antracicline: non sempre la disfunzione miocardica ne è la causa.

Anthracyclines, found to be efficacious in the treatment of a broad spectrum of pediatric malignancies, are cardiotoxic and may lead to heart failure even a long time after successful treatment of cancer. It is thought that subtle abnormalities can progress to the more permanent myocardial disease, resulting in cardiomyopathy which may progress to congestive heart failure. There are some precipitating factors leading to the sudden onset of cardiac symptoms such as increase in afterload or preload. We describe a young patient with congestive heart failure treated with doxorubicin (cumulative mean dose 420 mg/m2) in infancy because of pelvic sarcoma in whom the appearance of symptoms was related to pulmonary embolism. Four years before hospital admission, the patient presented echocardiographic abnormalities such as left ventricular fractional shortening and thickness reduction and he was treated with ACE-inhibitors. The myocardial ischemia, which is present in pulmonary embolism, probably worsened the left ventricular systolic function and caused congestive heart failure.

Endocarditis in the elderly: clinical, echocardiographic, and prognostic features.

AIMS: Infective endocarditis (IE) is more and more frequent in elderly persons and it has been associated with various clinical, bacteriological, and prognostic features. The aim of the study was to define the clinical, echographic, and prognostic characteristics of IE in a large population of elderly patients from four European centres (three French, one Italian). METHODS AND RESULTS: Three hundred and fifteen consecutive patients with definite IE underwent clinical evaluation, echocardiography, blood cultures, and follow-up. Patients were separated into three groups: group A: 117 patients aged <50 years, group B: 111 patients aged >50 and <70 years, group C: 87 patients aged >70 years. Elderly patients (group C) presented more frequently than other groups with digestive or urinary portal of entry, pacemaker endocarditis, and anaemia. S bovis endocarditis was less frequent and S aureus endocarditis more frequent in younger (group A) patients than in other groups. No difference was observed among groups concerning echocardiographic data as well as the incidence and localization of embolic events. Elderly patients were operated on as frequently as younger patients and their operative risk was similar than in other groups (11%, 3%, and 5% in groups C, B, and A, respectively, P=ns). Overall mortality in elderly patients was low (17%) but significantly higher than in younger patients (10% in group A, 7% in group B, P=0.02). By multivariate analysis, the only risk factors for in-hospital mortality were age (P=0.003), prosthetic valve (P=0.002), and cerebral embolism (P=0.006). Conversely, surgical management was associated with a lower in-hospital mortality (P=0.03). CONCLUSIONS: In this largest series of elderly patients with IE, IE in elderly carries specific features when compared with younger patients, although the echographic characteristics and embolic risk are similar. The overall mortality rate in elderly patients is higher than in younger, but the mortality in operated patients is low and similar than that of younger patients.

Endocarditis abscess of the aortic annulus involving the left ventricular inferior wall and causing a moderate aortic systolic obstruction: diagnosis by transthoracic and transesophageal echocardiography.

Abscesses are an important and potentially devastating complication of aortic valve endocarditis. The extension of the infectious process from the aortic valve to surrounding tissue can occur in different directions. This case report describes a 28-year-old man in whom the abscess of the aortic annulus was very large, causing a moderate aortic systolic obstruction, and also involved the left ventricular inferior wall. The diagnosis was provided by a combination of TTE and TEE examination and was confirmed by cardiac surgery.

Comparison of left ventricular function by echocardiogram in patients with Wilms' tumor treated with anthracyclines versus those not so treated.

The aim of this report was to evaluate late left ventricular function in survivors of Wilms' tumor and to compare patients treated with anthracyclines with those treated without anthracycline and with normal subjects. Wilms' tumor survivors treated without anthracycline had no myocardial abnormalities. A large percentage of patients treated with anthracycline presented with increased end-systolic wall stress. Results indicate that there is a high incidence of subclinical cardiovascular abnormalities in such patients.

Pulsed Doppler tissue imaging and myocardial function in thalassemia major.

Few studies are available on left ventricular diastolic function in beta-thalassemia major, and these have conflicting results. Our aim in this study was to analyze myocardial systolic and diastolic functions in patients with beta-thalassemia major using, for the first time, pulsed Doppler tissue imaging (DTI), and compare data with standard Doppler echocardiography. We studied 30 young patients with beta-thalassemia major (age

The heart in neurofibromatosis type 1: an echocardiographic study.

BACKGROUND: Comprehensive data are unavailable for cardiac abnormalities in patients with neurofibromatosis type 1 (NF1). The goal of this study was to evaluate the prevalence of cardiovascular abnormalities with echocardiography with color Doppler scan (ECHO) in a large, consecutive series of patients with NF1. METHODS: We studied 48 patients with NF1 (mean age, 10 years). Thirty healthy subjects comparable for age and sex served as the control group. All ECHO studies were performed by the same cardiologist and reviewed by a second cardiologist blinded to the physical findings of the subjects. RESULTS: Cardiac abnormalities were found in 13 of the 48 young patients (27%). A secundum atrial septal defect with a left to right shunt was found in 2 children. ECHO evidence of mild left pulmonary artery stenosis was found in 1 participant. A moderate coarctation of the thoracic aorta was found in 1 patient. ECHO criteria for mitral valve prolapse and evidence of trivial mitral regurgitation with myxomatous mitral valve was present in 1 case. Mild mitral regurgitation was found in 2 patients. A regurgitant mild flow signal was detected from the aortic valve in 2 subjects. Atrial septal aneurysm was found in 2 patients without patent foramen ovale. Two patients had septal to posterior left ventricular free wall ratio greater than 1.5, suggesting hypertrophic cardiomyopathy. CONCLUSION: This is the first attempt to evaluate the prevalence of cardiovascular abnormalities in patients with NF1 with ECHO. The study's most striking finding is the high prevalence of cardiovascular abnormalities. Congenital lesions have potential long-term hemodynamic consequences that justify an early diagnosis. Thus, a cardiologic assessment at regular intervals, including ECHO study, is mandatory for patients with NF1.

The prognostic role of the ECG in primary pulmonary hypertension.

BACKGROUND/RATIONALE: Doppler echocardiography and invasive hemodynamic parameters reflective of right ventricular failure are associated with a poor prognosis in patients with primary pulmonary hypertension (PPH). The aims of the present study were to examine whether ECG features in patients with PPH are associated with a decrease in survival, and to determine the value of the ECG in risk stratification. METHODS/RESULTS: We analyzed the ECG, New York Heart Association (NYHA) class, and hemodynamic parameters in 51 untreated patients with PPH (88% women; mean age, 41.7 years; 79% NYHA classes III and IV) evaluated between 1992 and 1998. Subsequent treatment included epoprostenol in 37 patients, calcium channel blockers in 10 patients, epoprostenol and atrial septostomy in 2 patients, and lung transplant in 3 patients. As of 1999, 16 patients had died. Based on Kaplan-Meier estimates, median survival was > 6.5 years and estimated survival at 1 year, 3 years, and 5 years was 86%, 71%, and 57%, respectively. Significant predictors of decreased survival by Cox regression analysis include pulmonary vascular resistance (PVR; hazard ratio [HR], 1.11 per Wood unit), cardiac index (HR, 0.22 per L/min/m(2)), p wave amplitude in lead II (HR, 3.06 per mm), p > or = 0.25 mV in lead II (HR, 2.77), qR in V(1) (HR, 3.55), and World Health Organization criteria for right ventricular hypertrophy (HR, 4.26). After controlling for PVR, the HRs attributable to the ECG criteria were only slightly diminished. NYHA class and pulmonary artery pressures did not correlate with a decrease in survival. CONCLUSIONS: ECG parameters reflective of physiologic and anatomic abnormalities in the right ventricle are associated with decreased survival in patients with PPH, and may be useful for deciding therapeutic choices including the timing for lung transplantation listing.

Unusual cases of infective endocarditis.

We report 2 patients with unusual cases of infective endocarditis. The first patient had a large, mural vegetation on left ventricle that was diagnosed with transthoracic echocardiography; and the second patient had a large, mobile vegetation in the descending prosthetic aorta with an abscess cavity around the vessel, diagnosed by transesophageal echocardiography. This report confirms the usefulness of transthoracic and transesophageal echocardiography in the diagnosis and management of uncommon cases of endocarditis.