Circulating biomarkers and cardiac function over 3 years after chemotherapy with anthracyclines: the ICOS-ONE trial.

AIMS: A multicentre trial, ICOS-ONE, showed increases above the upper limit of normality of cardiac troponin (cTn) in 27% of patients within 12 months after the end of cancer chemotherapy (CT) with anthracyclines, whether cardiac protection with enalapril was started at study entry in all (prevention arm) or only upon first occurrence on supra-normal cTn (troponin-triggered arm). The aims of the present post hoc analysis were (i) to assess whether anthracycline-based treatment could induce cardiotoxicity over 36 month follow-up and (ii) to describe the time course of three cardiovascular biomarkers (i.e. troponin I cTnI-Ultra, B-type natriuretic peptide BNP, and pentraxin 3 PTX3) and of left ventricular (LV) function up to 36 months. METHODS AND RESULTS: Eligible patients were those prescribed first-in-life CT, without evidence of cardiovascular disease, normal cTn, LV ejection fraction (EF) >50%, not on renin-angiotensin aldosterone system antagonists. Patients underwent echocardiography and blood sampling at 24 and 36 months. No differences were observed in biomarker concentration between the two study arms, 'prevention' vs. 'troponin-triggered'. During additional follow-up 13 more deaths occurred, leading to a total of 23 (9.5%), all due to a non-cardiovascular cause. No new occurrences of LV-dysfunction were reported. Two additional patients were admitted to the hospital for cardiovascular causes, both for acute pulmonary embolism. No first onset of raised cTnI-Ultra was reported in the extended follow-up. BNP remained within normal range: at 36 months was 23.4 ng/L, higher (N.S.) than at baseline, 17.6 ng/L. PTX3 peaked at 5.2 ng/mL 1 month after CT and returned to baseline values thereafter. cTnI-Ultra peaked at 26 ng/L 1 month after CT and returned to 3 ng/L until the last measurement at 36 months. All echocardiographic variables remained stable during follow-up with a median LVEF of 63% and left atrial volume index about 24 mL/m2 . CONCLUSIONS: First-in-life CT with median cumulative dose of anthracyclines of 180 mg/m2 does not seem to cause clinically significant cardiac injury, as assessed by circulating biomarkers and echocardiography, in patients aged 51 years (median), without pre-existing cardiac disease. This may suggest either a 100% efficacy of enalapril (given as preventive or troponin-triggered) or a reassuringly low absolute cardiovascular risk in this cohort of patients, which may not require intensive cardiologic follow-up.

Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial.

BACKGROUND: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit. METHODS: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; 'prevention' arm), and enalapril started only in patients with an increase in troponin during or after CT ('troponin-triggered' arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold. FINDINGS: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270-360] and 240 [240-240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%. INTERPRETATION: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.

Mitral effective regurgitant orifice area versus left ventricular ejection fraction as prognostic indicators in patients with dilated cardiomyopathy and heart failure.

BACKGROUND: This study aimed at investigating the relative powers of the quantitative evaluation of functional mitral regurgitation (FMR) and ejection fraction (EF) in predicting the clinical changes and prognosis of dilated cardiomyopathy (DCM) with severe systolic dysfunction. METHODS: A total of 81 patients with DCM, EF < 0.40 and at least mild FMR were prospectively evaluated during a mean follow-up of 24 +/- 7 months. Twenty cardiac deaths were recorded. At the time of enrolment all patients underwent echocardiographic evaluation of the effective regurgitant orifice area (ERO), EF, left atrial area, and tenting area. In 42/81 patients, the data obtained at enrolment were compared to those measured at a mean follow-up of 10 +/- 2 months. A multivariate analysis was performed to determine the best predictor of NYHA class and mortality. RESULTS: There was a correlation between the NYHA class and the ERO (chi2 = 26.1, p = 0.0001) but not with EF (chi2 = 4.3, p = 0.22) and at multivariate analysis, the ERO was found to be the main determinant of the NYHA class (r = 0.64, standard error 0.6, p = 0.0001). The NYHA class remained unchanged or improved in 28/42 (67%) and deteriorated in 14/42 (33%) patients. In the first group, the ERO increased from 22.3 +/- 10 to 30.2 +/- 16.4 mm2 (p = 0.05) and the tenting area from 5.8 +/- 1.8 to 6.8 +/- 1.8 cm2 (p = 0.001); in the second group, the ERO increased from 25.1 +/- 5.6 to 39.0 +/- 14.5 mm2 (p = 0.04) and the tenting area from 5.9 +/- 2.1 to 7.6 +/- 1.8 cm2 (p = 0.0001), in both groups without significant changes in EF. The mortality was 8.1% in patients with an ERO < 21 mm2, 30.3% in patients with an ERO of 21-30 mm2, and 50% in those with an ERO > 30 mm2. The EF was similar in the three subgroups. At Cox multivariate analysis the best predictors of mortality were the ERO (chi2 = 13.83, p = 0.0001), EF (chi2 = 5.48, p = 0.019), and left atrial area (chi2 = 4.52, p = 0.04). CONCLUSIONS: FMR in DCM well correlated with the clinical status of the patients and its worsening was suggestive of progression of the disease. The ERO was found to be the best predictor of the NYHA class and mortality.

[Quantitative evaluation of functional mitral insufficiency in dilated cardiomyopathy: morphological and functional correlations]. / Valutazione quantitativa dell'insufficienza mitralica funzionale nella cardiomiopatia dilatativa: correlazioni morfologiche e funzionali.

BACKGROUND: Angiography and echo-color Doppler imaging are routinely used for the semiquantitative grading of functional mitral regurgitation (MR) in dilated cardiomyopathy. However, in case of severe regurgitation the results obtained using these two methods are discrepant. We propose quantitative echocardiographic evaluation and the related morphological parameters of remodeling of the ventricular and mitral apparatuses for the estimate of severe regurgitation. METHODS: Fifty-two patients with dilated cardiomyopathy and functional MR (28 males, 24 females, ejection fraction < or = 40%) were evaluated by means of echocardiography for a total of 73 echocardiograms (basal and 21 at the sixth month). The echo measurements included the left ventricular end-diastolic and end-systolic volumes, ejection fraction, area jet/left atrial area, diastolic and systolic mitral annulus areas and fractional contraction (MAC, %), systolic tenting area (TA, cm2, area enclosed between the annular plane and mitral leaflets), systolic tethering length (TL, cm, papillary tips and intervalvular fibrosa distance); quantitative Doppler (using the mitral and aortic stroke volumes) and PISA methods were averaged to calculate the regurgitant volume (RV, ml/beat), regurgitant fraction (RF, %), and effective regurgitant orifice (ERO, mm2). RESULTS: The strongest correlation with ERO, RV and RF was obtained with systolic TA (beta = 0.40, 0.67 and 0.60; SE 1.68, 1.56 and 1.38; p = 0.01, p = 0.0001 and p = 0.0001, respectively) and MAC (beta = -0.33, -0.61 and -0.61; SE 0.31, 0.31 and 1.49; p = 0.03, p = 0.0001 and p = 0.0001, respectively). We did not find any correlation with ejection fraction (p = NS). The following values were found to be indicative of severe functional MR: ERO > or = 40 mm2, RV > or = 49 ml/beat, RF > or = 57%, MAC < or = 12.5%, TA > or = 7.7 cm2, and TL > or = 4.7 cm. CONCLUSIONS: We did not find any significant correlation between the quantitative functional MR echo parameters and systolic dysfunction. The major determinants of ERO, RV and RF were the loss of MAC and larger systolic TAs. These parameters are significantly proportional to the severity of functional MR as assessed by the semiquantitative criteria commonly adopted in the clinical practice. We propose the values of ERO, RV, RF, TA, MAC and TL as indicative of severe functional MR.

Prevalence and clinical characteristics of adult patients with congenital heart disease in Tuscany.

AIMS: The clinical features of the adult population with congenital heart disease (CHD) are still not well characterized, particularly in the subset with more severe lesions. We report the data collected in the National Association of Hospital Cardiologists Toscana grown-up CHD (GUCH) registry over its first 8-month enrolment period. METHODS: The Registry included consecutive patients aged more than 16 years with a documented diagnosis of CHD, enrolled in seven different Tuscan hospitals using a web-based electronic form. Severe CHD was defined as cyanotic CHD, or acyanotic lesion with significant haemodynamic impact requiring surgical and/or percutaneous correction. RESULTS: Between November 2009 and June 2010 a total of 1641 patients (mean age 41.8 ±â€Š19.3 years, 52.2% women) were enrolled. Atrial septal defect was the most common lesion, accounting for more than one-third of cases. Atrial and ventricular septal defects together accounted for about half of all CHDs. Nearly one-third of patients had New York Heart Association (NYHA) class 2 or more. A history of recurrent arrhythmias was reported in 15% of cases, and 12% of patients were on oral anticoagulants at the time of enrolment. The prevalence of pulmonary hypertension was 6%, and the prevalence of Eisenmenger syndrome was 1.2%. Severe CHD was present in 42% of patients. Younger age, higher NYHA class, male sex, and the need for oral anticoagulants were the only independent predictors of severe CHD. CONCLUSION: Information about the clinical characteristics and the CHD type distribution of a sample of Tuscan GUCH population was provided. Severe CHD accounts for about 40% of all CHDs in this population. CHD severity is associated with younger age, male gender, worse NYHA class, and need for oral anticoagulation.