1 ASSESSMENT OF LEFT VENTRICULAR SYSTOLIC DYSFUNCTION BY TISSUE DOPPLER IMAGING SHOWS EVIDENCE OF SUBCLINICAL CARDIOMYOPATHY EARLY AFTER ATHRACYCLINE THERAPY M. LOTRIONTE1, R. NATALI1, G. PALAZZONI1, G. BIONDI-ZOCCAI2, G. COMERCI1, M. SAVINO1, F. LOPERFIDO1 (1)Catholic University, Rome, Italy (2)University of Turin, Turin, Italy

2 BACKGROUND Anthracycline (ANT) chemotherapy for breast cancer, while associated with high response rates, is fraught by risks of irreversible cardiotoxicity Unfortunately, means to detect such cardiotoxicity early on and at a sublinical stage are lacking

3 OBJECTIVES We aimed to evaluate early and late effects of ANT-chemotherapy in patients with breast cancer using standard and systolic tissue Doppler imaging (TDI) echocardiography We appraised changes from baseline to follow- up of TDI-derived LV systolic parameters, and explored whether these TDI-parameters could be used to detect myocardial dysfunction before conventional echocardiographic indexes

4 METHODS Consecutive patients undergoing ANT-chemotherapy for breast cancer at our Institution, who were routinely referred for standard echocardiography at baseline and after chemotherapy (usually 6 to 12 months after beginning antineoplastic treatment) were enrolled between May 2004 and September 2006 Comprehensive transthoracic echocardiography was performed using a commercially available ultrasound system with TDI capabilities (Sonos 5500, Philips Medical System, Italy) with a 3.5 MHz phased-array ultrasound probe, by operators unaware of individual chemotherapy schemes

5 METHODS TDI measurements were acquired using a 5-10 mm sample volume placed at the lateral and septal mitral annular margins, and at the lateral annulus of the tricuspid valve in the 4-chamber view We measured the TDI peak systolic (Sm), early and late diastolic velocities in the LV lateral and septum wall, as well as in the lateral wall of the right ventricle (RV) All images were stored onto magneto-optical disc and were measured offline after the completion of the echocardiogram by a single experienced investigator unaware of individual chemotherapy schemes, and with measurements averaged over 3 cycles

6 METHODS LVEF was considered abnormal if <50% We a priori decided to stratify patients according to the pattern of systolic TDI remodelling from baseline to follow- up as follows: –group 1 (no LV TDI systolic worsening) including patients without any evidence of significant LV systolic dysfunction at follow-up; –group 2 (minor LV TDI systolic worsening) including subjects with evidence of significant LV systolic remodelling at follow-up in only one of the LV regions (ie either in the basal lateral wall or in the basal septum, but not in both); –group 3 (major LV TDI systolic worsening) including those with evidence of significant LV systolic remodelling at follow-up in both the LV lateral wall and the septum

7 RESULTS We enrolled a total of 56 patients (55 females), and followed them all for 8.8±5.7 months (range 6-24) All patients but one with atrial fibrillation had normal sinus rhythm (80±18) at the time of the ultrasound examination Notably, no patient had abnormal LVEF or evidence of significant LV TDI systolic dysfunction at baseline Stratification according to pattern of LV TDI systolic remodelling allocated 29 (51.8%) patients to group 1, 17 (30.4%) to group 2, and 10 (17.9%) to group 3

8 RESULTS No significant increase in major or minor bleedings (respectively p=0.55 and p=0.98) was found in patients treated with a high clopidogrel dose Sensitivity analysis restricted to randomized trials confirmed the superiority of a high loading dose regimen on risk of death or infarction (p=0.001) Meta-regression disclosed a significant interaction between event rate and benefits of high loading dose (p=0.005), suggesting that the higher the underlying risk, the greater the favorable impact of high loading

9 PATIENT CHARACTERISTICS

10 CHANGES IN ECHOGRAPHIC DATA AT FOLLOW-UP

11 CHANGES IN TDI DATA AT FOLLOW-UP

12 CHANGES IN END-DIASTOLIC DIAMETER AT FOLLOW-UP

13 CHANGES IN END-SYSTOLIC DIAMETER AT FOLLOW-UP

14 CHANGES IN TELEDIASTOLIC DIAMETER AT FOLLOW-UP

15 CONCLUSIONS Subclinical systolic dysfunction occurs in almost 50% of patients early after chemotherapy for breast cancer A more adverse by LV-TDI remodelling implies a more pronounced deterioration of standard echocardiographic parameters TDI monitoring could thus be envisaged to identify at an earlier stage post-chemotherapy cardiomyopathy, in order to tailor management strategies

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