Coronary Flow Velocity Reserve Declines After Anthracycline Therapy in Breast Cancer Patients.

Anthracycline therapy (ANT) is associated with cancer therapy-related cardiac dysfunction. Coronary flow velocity reserve (CFVR) has shown prognostic utility in non-cancer cohorts, but no data have been obtained in a cardio-oncology setting. We investigated the acute effect of ANT on CFVR in breast cancer patients. A total of 12 female breast cancer patients undergoing ANT had pre- and post-ANT CFVR assessment. A significant decline in CFVR occurred (baseline: 2.66 ± 0.41 vs post-ANT: 2.47 ± 0.37, P = 0.016). This prospective study is the first to identify ANT-related coronary physiology changes in humans. Further studies are required to determine their clinical significance.

Le traitement par l'anthracycline est associé à une dysfonction cardiaque liée au traitement anticancéreux. La réserve de débit coronaire a démontré son utilité pronostique dans les cohortes sans cancer, mais aucune donnée n'a été obtenue dans un contexte de cardio-oncologie. Nous avons étudié l'effet aigu de l'anthracycline sur la réserve de débit coronaire chez des patientes atteintes d'un cancer du sein. La réserve de débit coronaire a été évaluée avant et après le traitement par l'anthracycline chez un total de 12 femmes atteintes d'un cancer du sein. Un déclin important de la réserve de débit coronaire est survenu (valeur initiale de 2,66 ± 0,41 par rapport à 2,47 ± 0,37 après le traitement par l'anthracycline, p = 0,016). Cette étude prospective est la première à déceler des changements dans la physiologie coronarienne liés à l'anthracycline chez les humains. D'autres études sont nécessaires pour en déterminer la portée clinique.

Rationale and Design of the Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT): A Pilot Study.

BACKGROUND: Cancer therapeutics-related cardiac dysfunction (CTRCD) is a well-recognised complication of cancer treatment. Treatment of CTRCD involves cardioprotective therapy (CPT) which can lead to a recovery of CTRCD with normalisation of the left ventricular ejection fraction (LVEF). As a result, there are potentially millions of cancer survivors with recovered CTRCD on CPT. Cardioprotective therapy can be associated with an undesirable long-term pill burden, financial costs, and side effects. Cancer survivorship is anticipated to increase significantly by the end of this decade. To date, there is no evidence of the safety of stopping CPT in this setting. This study seeks to evaluate the hypothesis that ceasing cardioprotective medication is a feasible and safe option without significant impact on LVEF in low-risk patients who have recovered from CTRCD. METHODS AND ANALYSIS: We will perform a multicentre prospective open-label randomised controlled trial with blinded endpoint (PROBE) of supervised CPT cessation compared to continuing CPT (control). The primary study end point is the change in LVEF by cardiac magnetic resonance imaging at 6 months of enrolment between the two groups. Secondary end points include changes in quality-of-life questionnaires, other cardiac imaging parameters, and recurrence of heart failure. CONCLUSION: Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT) is one of the first studies currently underway to evaluate the safety of ceasing CPT in recovered CTRCD. The results will inform clinical practice in this evidence-free zone.

Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial.

BACKGROUND: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction and guide initiation of cardioprotection (CPT). OBJECTIVES: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years. METHODS: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)-guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (ΔEF) from baseline to 3 years. RESULTS: Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% ± 6%, GLS: 20.7% ± 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P = 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year ΔEF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided (P = 0.99) group; respective 3-year EFs were 58% ± 6% and 59% ± 5% (P = 0.06). At 3 years, 17 patients (5%) had cancer therapeutics-related cardiac dysfunction (11 in the EF-guided group and 6 in the GLS guided group; P = 0.16); 1 patient in each group was admitted for heart failure. CONCLUSIONS: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in ΔEF between GLS- and EF-guided CPT. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

Incremental Value of Myocardial Work over Global Longitudinal Strain in the Surveillance for Cancer-Treatment-Related Cardiac Dysfunction: A Case-Control Study.

The load dependence of global longitudinal strain (GLS) means that changes in systolic blood pressure (BP) between visits may confound the diagnosis of cancer-treatment-related cardiac dysfunction (CTRCD). We sought to determine whether the estimation of myocardial work, which incorporates SBP, could overcome this limitation. In this case-control study, 44 asymptomatic patients at risk of CTRCD underwent echocardiography at baseline and after oncologic treatment. CTRCD was defined on the basis of the change in the ejection fraction. Those with CTRCD were divided into subsets with and without a follow-up SBP increment >20 mmHg (CTRCD+BP+ and CTRCD+BP-), and matched with patients without CTRCD (CTRCD-BP+ and CTRCD-BP-). The work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were assessed in addition to the GLS. The largest increases in the GWI and GCW at follow-up were found in CTRCD-BP+ patients. The CTRCD+BP- patients demonstrated significantly larger decreases in GWI and GCW than their CTRCD+BP+ and CTRCD-BP- peers. ROC analysis for the discrimination of LV functional changes in response to increased afterload in the absence of cardiotoxicity revealed higher AUCs for GCW (AUC = 0.97) and GWI (AUC = 0.93) than GLS (AUC = 0.73), GWW (AUC = 0.51), or GWE (AUC = 0.63, all p-values < 0.001). GCW (OR: 1.021; 95% CI: 1.001-1.042; p < 0.04) was the only feature independently associated with CTRCD-BP+. Myocardial work is superior to GLS in the serial assessments in patients receiving cardiotoxic chemotherapy. The impairment of GLS in the presence of an increase in GWI and GCW indicates the impact of elevated afterload on LV performance in the absence of actual myocardial impairment.

Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy.

BACKGROUND: In patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardioprotective therapy (CPT) is constrained by the low sensitivity of ejection fraction (EF) for minor changes in left ventricular (LV) function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT. OBJECTIVES: This study sought to identify whether GLS-guided CPT prevents reduction in LVEF and development of CTRCD in high-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. METHODS: In this international, multicenter, prospective, randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either ≥12% relative reduction in GLS (n = 166) or >10% absolute reduction of LVEF (n = 165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction of >5% or >10% asymptomatic to <55%) over 1 year. RESULTS: Of 331 randomized patients, 2 died, and 22 withdrew consent or were lost to follow-up. Among 307 patients (age: 54 ± 12 years; 94% women; baseline LVEF: 59 ± 6%; GLS: -20.6 ± 2.4%) with a median (interquartile range) follow-up of 1.02 years (0.98 to 1.07 years), most (n = 278) had breast cancer. Heart failure risk factors were prevalent: 29% had hypertension, and 13% had diabetes mellitus. At the 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the 2 arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs. 13.7%; p = 0.02), and the 1-year EF was 57 ± 6% versus 55 ± 7% (p = 0.05). Patients who received CPT in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1 ± 10.9% vs. 2.9 ± 7.4%; p = 0.03). CONCLUSIONS: Although the change in LVEF was not different between the 2 arms as a whole, when patients who received CPT were compared, those in the GLS-guided arm had a significantly lower reduction in LVEF at 1 year follow-up. Furthermore, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

Association of Asymptomatic Diastolic Dysfunction Assessed by Left Atrial Strain With Incident Heart Failure.

OBJECTIVES: This study is to establish the association of left atrial reservoir strain (LARS) with incident heart failure (HF), and the impact of substituting LARS for left atrial (LA) volume index (LAVI) in diastolic assessment. BACKGROUND: LARS measures passive LA stretch and is a sensitive marker of left ventricular diastolic dysfunction (DD). The potential contribution of LARS to diastolic assessment is unclear. METHODS: Baseline clinical and echocardiographic assessments were obtained in 758 asymptomatic, community-dwelling elderly subjects (age 70 [interquartile range: 67 to 74] years, 53% women) with nonischemic HF risk factors. LARS-defined DD (LARS-DD) was assessed by speckle-tracking echocardiography, and grades were assigned as normal (>35%), grade 1 (25% to 35%) and grade 2 (≤24%). DD grade using current recommendations was compared with grading using LARS <24% in place of LAVI >34 ml/m2. Patients were followed for up to 2 years for incident HF. RESULTS: LA strain analysis was feasible in 738 (97%) patients; average LARS was 39% (range 34% to 43%). Incident HF was associated with LARS-DD grade; 8 (36%) of those had grade 2+, 14 (10%) had grade 1, and 39 (9%) had normal function (p < 0.001). LARS-DD grade 2+ predicted incident HF after adjustment for clinical and echocardiographic markers (adjusted hazard ratio: 2.5; 95% confidence interval: 1.02 to 6.3; p = 0.049); there was no significant HF risk associated with LARS-DD grade 1. Dichotomized abnormal LARS <24% had an adjusted hazard ratio of 2.9 (95% confidence interval: 1.25 to 6.79; p = 0.013). Substituting LARS for LAVI provided a 75% reduction in indeterminate diastolic function; all were recategorized as normal. There was no increased risk associated normal diastolic function by this grading compared to conventional grading (C-statistic = 0.76 for both models). CONCLUSIONS: LARS-DD grade 2+ is associated with incident HF in the elderly, independent of LAVI. The substitution of LARS for LAVI reduces the number of indeterminate cases without impacting prognosis in normal diastolic function and grade 1 DD.

Echocardiographic Risk Assessment to Guide Screening for Atrial Fibrillation.

BACKGROUND: Although atrial fibrillation (AF) is a significant population health burden, and an avoidable cause of stroke, AF screening remains controversial. The aim of this study was to investigate whether coincidental echocardiography could provide information about patients at risk for AF. METHODS: Asymptomatic participants ≥65 years of age with more than one AF risk factor (N = 445) undergoing echocardiography for risk evaluation were followed over a median of 15 months for incident AF. Left atrial volume index (LAVi), left ventricular (LV) global longitudinal strain (GLS; absolute value), left atrial (LA) strain, and LV mass were measured. During the follow-up period, AF was diagnosed clinically by primary care physicians or by using a single-lead portable electrocardiographic monitoring device (five 60-sec recordings performed by participants over 1 week). RESULTS: AF was diagnosed in 45 patients (10%; mean age, 70.5 ± 4.2 years; 55% women). AF detection was higher in those with LV hypertrophy, GLS < 16%, LAVi > 34 mL/m2, and LA reservoir strain < 34%. GLS, LAVi, and LA reservoir strain were independently associated with AF (P < .05). Those with AF had reduced GLS, higher LAVi, and higher LV mass (P < .05), but LA strain was similar in both groups (P > .05). GLS and LAVi were the strongest predictors, and cut points of 14.3% for GLS and 39 mL/m2 were associated with increased risk for developing AF. Those with all four risk parameters (LV hypertrophy, GLS < 16%, LA reservoir strain < 34%, and LAVi > 34 mL/m2) had a 60% AF detection rate, compared with 7% without these features (P = .004). CONCLUSION: Echocardiography is widely used in patients at risk for AF, and simple LV and LA measurements may be used to enrich the process of AF screening.

Echocardiography and Cardio-Oncology.

Owing to the ongoing increase in cancer survivors because of the remarkable and continuous progress in cancer management, a paradigm shift is occurring from cancer as a 'terminal illness' to a 'chronic condition' with cardiovascular risks. This also affects cardiology practice with increased cardiovascular morbidity and mortality rates among patients with cancer due to direct and/or indirect side effects of anticancer treatment. Thus, cardio-oncology has emerged as a new cardiology subspecialty, which focusses on risk stratification, prevention, diagnosis, treatment, and follow-up of cardiovascular disease related to cancer treatment. This review summarises echocardiographic evaluation of cardiac dysfunction and heart failure as they are the most concerning cardiovascular complications of cancer therapy and worsen its morbidity and mortality. This review covers cardiac function assessment and proposed cut-off values before/during/after cancer chemotherapy. The goal of this review is to aid clinicians to manage the patients with cancer sufficiently by connecting the existing knowledge in clinical cardiology with novel information from current advances in cardio-oncology.

Rationale and Design of the Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes: The SUCCOUR Trial.

OBJECTIVES: This study sought to evaluate the hypothesis that global longitudinal strain (GLS) guidance of cardioprotective therapy would improve cardiac function of at-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. BACKGROUND: The conventional criteria for diagnosis of chemotherapy-related cardiac dysfunction (CTRCD) are dependent on the recognition of heart failure symptoms and/or changes in left ventricular ejection fraction. However, the measurement variability of left ventricular ejection fraction necessitates broad diagnostic ranges, with the consequence of low sensitivity for CTRCD. Observational data have shown GLS to be a robust and sensitive marker to predict CTRCD and thereby guide the initiation of cardioprotective therapy, but these data are insufficient to justify changing the diagnostic criteria for CTRCD. METHODS: The SUCCOUR (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes) trial is an international multicenter prospective randomized controlled trial. Patients who are taking cardiotoxic chemotherapy (n = 320) with at least 1 risk factor will be randomly allocated into GLS- and ejection fraction-guided strategies. All participants will be followed over 3 years for the primary endpoint (change in 3-dimensional ejection fraction) and other secondary endpoints. RESULTS: Among the first 185 patients (age 54 ± 13 years; 93% women) from 23 international sites, 88% had breast cancer, 9% had lymphoma, and 3% had other cancers. Heart failure risk factors were prevalent: 34% had hypertension and 10% had diabetes mellitus. The most common chemotherapy regimen during this study was the combination of anthracycline and trastuzumab. The baseline 3-dimensional left ventricular ejection fraction was 61 ± 4%, and GLS was 20.3 ± 2.5%. Of 93 patients followed up in the first year of the study, 10 had to withdraw for noncardiac reasons. Of 40 patients randomized to the GLS-guided arm, 15 have been started on cardioprotective therapy, whereas 4 of 46 patients in the ejection fraction-guided arm have been started on therapy. CONCLUSIONS: The SUCCOUR trial will be the first randomized controlled trial of GLS and will provide evidence to inform guidelines regarding the place of GLS for surveillance for CTRCD. (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes [SUCCOUR]; ANZ Clinical Trials ACTRN12614000341628).

Single Versus Standard Multiview Assessment of Global Longitudinal Strain for the Diagnosis of Cardiotoxicity During Cancer Therapy.

OBJECTIVES: The goal of this study was to compare echocardiographic measurements of global longitudinal strain (GLS) (using 3 apical views) with single-view longitudinal strain (LS, 4- or 2-chamber [4CV_LS and 2CV_LS, respectively]) for detection of cancer-therapy related cardiotoxicity. BACKGROUND: GLS is useful for the detection of cardiotoxicity, but the need for repeated measurements poses a significant burden on busy echocardiography laboratories. A single-view LS measurement, possibly at point of care, could improve efficiency. METHODS: Seventeen international centers prospectively recruited 108 patients (mean age 54 ± 13 years) at high risk for cardiotoxicity as part of the ongoing SUCCOUR (Strain Surveillance for Improving Cardiovascular Outcomes During Chemotherapy) randomized controlled trial. Echocardiography performed at baseline and follow-up were analyzed in a core laboratory setting blinded to clinical information. Peak systolic GLS and LS were measured from raw data. Cardiotoxicity was defined by reduction in left ventricular ejection fraction >0.10 to <0.55 or a relative drop in GLS by ≥12%. RESULTS: Cardiotoxicity developed in 46 patients by either criteria. Baseline and follow-up 2-dimensional left ventricular ejection fraction were 61 ± 4% and 58 ± 5%, respectively (p < 0.001). The baseline GLS (-20.9 ± 2.4%) was not different from 4CV_LS (-20.7 ± 2.5%; p = 0.09) or 2CV_LS (-21.1 ± 3.1%; p = 0.25). The follow-up GLS (-19.5 ± 2.4%) was also similar to 4CV_LS (-19.5 ± 2.6%; p = 0.80) and 2CV_LS (-19.7 ± 3.1%; p = 0.19). There was good correlation between GLS and 4CV_LS at baseline (r = 0.86; p < 0.001) and follow-up (r = 0.89; p < 0.001) and with 2CV_LS at baseline (r = 0.87; p < 0.001) and follow-up (r = 0.88; p < 0.001). However, there was 15% to 22% disagreement between GLS and 4CV_LS or 2CV_LS for the detection of cardiotoxicity. The interobserver and intraobserver reproducibility was higher for GLS (intraclass correlation: 0.93 to 0.95; coefficient of variance: 2.9% to 3.7%) compared with either single-chamber-based LS measurement (intraclass correlation: 0.85 to 0.91; coefficient of variance: 4.1% to 4.8%). CONCLUSIONS: Although there was good correlation between GLS and single-view LS measurements, single-view LS measurement led to disagreement in the diagnosis of cardiotoxicity in up to 22% of patients. GLS measurements were more reproducible than single-view LS. GLS based on 3 apical views should remain the preferred technique for detection of cardiotoxicity. (Strain Surveillance for Improving Cardiovascular Outcomes During Chemotherapy [SUCCOUR]; ACTRN12614000341628).

Echocardiographic evaluation of cardiac function after cancer chemotherapy.

Progress in cancer therapy has led to improved prognosis of patients with cancer and thus to a continuous rise of cancer survivors. However, it has simultaneously increased cardiovascular morbidity and mortality rates due to direct and/or indirect side effects of anticancer treatment. Similar to the rapid rise of patients with adult congenital disease, the number of patients suffering or at risk of cardiotoxicity has been steeply increasing and getting an emerging issue. Among the many facets of chemotherapy-induced cardiovascular toxicity, this review attempts to summarize echocardiographic evaluation of cardiac function after cancer chemotherapy by reviewing the definition, risk factors, brief history, limitation of left ventricular ejection fraction and myocardial strain imaging, as well as the limitations of this technique.

Pericardiectomy is Associated with Improvement in Longitudinal Displacement of Left Ventricular Free Wall Due to Increased Counterclockwise Septal-to-Lateral Rotational Displacement.

BACKGROUND: Pericardiectomy is an effective intervention for constrictive pericarditis. Speckle-tracking echocardiography can provide quantitative information not only about longitudinal strain (LS) but about longitudinal displacement (LD) and septal-to-lateral rotational displacement (SLRD). The aim of this study was to investigate whether pericardiectomy improves myocardial mechanics using speckle-tracking analysis. METHODS: Eighty-three patients with constrictive pericarditis who underwent echocardiography were retrospectively assessed (mean age, 58 ± 12 years; 72 men; 50 idiopathic, 20 postoperative, four viral, three radiation, and six others) and compared with 20 healthy volunteers. LD and SLRD were measured from the apical four-chamber view and global LS from three apical views. RESULTS: LD was less in the constrictive pericarditis group compared with control subjects (P < .001). Only lateral LS was significantly less than that of control subjects (P < .001), but septal LS was similar (P = .48). In pre- and post-pericardial surgery comparisons (n = 27), values of septal and lateral LD were almost identical (mean, 13.6 ± 4.7 vs 13.3 ± 5.4 mm; P = .70) before pericardiectomy, but septal LD decreased (mean, 9.3 ± 3.5 mm; P < .001) and lateral LD increased (mean, 16.8 ± 4.7 mm; P = .0106) after the surgery, even though the difference in LS between the septal and lateral walls decreased (from 5.6 ± 5.3% to 2.5 ± 4.2%, P = .008). Systolic whole-heart swinging motion significantly increased to a counterclockwise direction after surgery (mean SLRD, -0.8 ± 3.3° vs 2.1 ± 3.0°; P = .001). Although the change in SLRD after pericardiectomy was not different between patients with decreases and increases in New York Heart Association class, SLRD change was significantly greater in patients who received fewer diuretics after surgery (mean, 4.00 ± 0.91 vs 0.27 ± 1.47; P = .027). CONCLUSIONS: After surgical removal of the pericardium, LD of the septal and lateral walls became significantly different, and counterclockwise SLRD increased, reflecting loss of pericardial support.

Incremental value of three-dimensional echocardiography in the evaluation of left ventricular size in mitral regurgitation: a follow-up study after mitral valve surgery.

BACKGROUND: Increased left ventricular (LV) dimensions are an indication for surgery in patients with asymptomatic mitral regurgitation, but M-mode or two-dimensional measurements have known limitations. The aim of this study was to determine the value of three-dimensional echocardiography in predicting postoperative outcomes after mitral surgery. METHODS: Sixty-seven patients with severe asymptomatic or minimally symptomatic mitral regurgitation (69% men; mean age, 62 ± 13 years) who underwent mitral valve surgery from January 2010 to December 2011 were studied. In addition to standard echocardiography, baseline three-dimensional echocardiography was performed for accurate quantification of LV size. Patients were followed over a median time of 1 month (interquartile range, 0-8 months) for postoperative development of atrial fibrillation or LV dysfunction. A multivariate regression analysis was performed to identify associations with events. RESULTS: Postoperative LV dysfunction developed in 15 patients (22%), and 21 patients (31%) had postoperative atrial fibrillation. There was no association between two-dimensional end-systolic volume index and outcomes (hazard ratio, 1.02; P = .18). Postoperative atrial fibrillation or LV dysfunction was associated with baseline three-dimensional LV end-systolic volume index (hazard ratio, 1.06; 95% confidence interval, 1.04-1.16), independent of age and presence of coronary artery disease. LVESVi ≥ 40 mL/m(2) was the best cutoff value to predict postoperative events (sensitivity, 80%; specificity, 85%). After adding LVESVi to a model containing clinical and echocardiographic parameters, net reclassification improvement was 0.27 (95% confidence interval, 0.25-0.29; P = .024). CONCLUSIONS: LVESVi from three-dimensional echocardiography is an independent predictor of postoperative outcomes in patients with severe mitral regurgitation that is incremental to other clinical and echocardiographic variables.

Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection.

AIMS: The variability of ejection fraction (EF) poses a problem in the assessment of left ventricular (LV) function in patients receiving potentially cardiotoxic chemotherapy. We sought to use global longitudinal strain (GLS) to compare LV responses to various cardiotoxic chemotherapy regimens and to examine the response to cardioprotection with beta-blockers (BB) in patients showing subclinical myocardial damage. METHODS AND RESULTS: We studied 159 patients (49 ± 14 year, 127 women) receiving anthracycline (group A, n = 53, 46 ± 17 year), trastuzumab (group T, n = 61, 53 ± 12 year), or trastuzumab after anthracyclines (group AT, n = 45, 46 ± 9 year). LV indices [ejection fraction (EF), mitral annular systolic velocity, and GLS] were measured at baseline and follow-up (7 ± 7 months). Patients who decreased GLS by ≥11% were followed for another 6 months; initiation of BB was at the discretion of the clinician. Anthracycline dose was similar between group A and group AT (213 ± 118 vs. 216 ± 47 mg/m(2), P = 0.85). Although ΔEF was similar among the groups, attenuation of GLS was the greatest in group AT (group A, 0.7 ± 2.8% shortening; T, 1.1 ± 2.7%; and AT, 2.0 ± 2.3%; P = 0.003, after adjustment). Of 52 patients who decreased GLS by ≥-11%, 24 were treated with BB and 28 were not. GLS improved in BB groups (from -17.6 ± 2.3 to -19.8 ± 2.6%, P < 0.001) but not in non-BB groups (from -18.0 ± 2.0 to -19.0 ± 3.0%, P = 0.08). Effects of BB were similar with all regimens. CONCLUSIONS: GLS is an effective parameter for identifying systolic dysfunction (which appears worst with combined anthracycline and trastuzumab therapy) and responds to cardioprotection in patients administered beta-blockers.

Independent and incremental value of deformation indices for prediction of trastuzumab-induced cardiotoxicity.

BACKGROUND: Assessment of left ventricular systolic function is necessary during trastuzumab-based chemotherapy because of potential cardiotoxicity. Deformation indices have been proposed as an adjunct to clinical risk factors and ejection fraction (EF), but the optimal parameter and optimal cutoffs are undefined. The aim of this study was to determine the best means of early detection of subsequent reduction of EF in patients with breast cancer treated with trastuzumab. METHODS: Eighty-one consecutive women (mean age, 50 ± 11 years) receiving trastuzumab were prospectively studied, 37 of whom received concurrent anthracyclines. Conventional echocardiographic indices (mitral annular systolic [s'] and diastolic [e'] velocities) and myocardial deformation indices (global longitudinal peak systolic strain [GLS], global longitudinal peak systolic strain rate [GLSR-S], and global longitudinal early diastolic strain rate [GLSR-E]) were measured at baseline and at 6 and 12 months. Cardiotoxicity was defined as a >10% decline as a percentage of baseline EF in 12 months. RESULTS: In the 24 patients (30%) who later developed cardiotoxicity, myocardial deformation indices decreased at 6 months (GLS, P < .001; GLSR-S, P = .009; GLSR-E, P = .002 vs baseline), but e' was unchanged. The strongest predictor of cardiotoxicity was ΔGLS (area under the curve, 0.84); an 11% reduction (95% confidence interval, 8.3%-14.6%) was the optimal cutoff, with sensitivity of 65% and specificity of 94%. In sequential models, the clinical model (χ(2) = 10.2) was improved by GLSR-S (χ(2) = 14.7, P = .03) and even more so by GLSR-E (χ(2) = 18.0, P = .005) or GLS (χ(2) = 21.3, P = .0008). Discrimination improvement by adding GLS was confirmed by an integrated discrimination improvement of 18.6% (95% confidence interval, 8.6%-28.6%; P = .0003). A net 29% of the patients without events were reclassified into lower risk categories, and a net 48% of the patients with events were reclassified into higher risk categories, resulting in a total continuous net reclassification improvement (>0) of 0.77 (95% confidence interval, 0.33-1.22; P = .036). CONCLUSIONS: GLS is an independent early predictor of later reductions in EF, incremental to usual predictors in patients at risk for trastuzumab-induced cardiotoxicity.

Reproducibility of echocardiographic techniques for sequential assessment of left ventricular ejection fraction and volumes: application to patients undergoing cancer chemotherapy.

OBJECTIVES: The aim of this study was to identify the best echocardiographic method for sequential quantification of left ventricular (LV) ejection fraction (EF) and volumes in patients undergoing cancer chemotherapy. BACKGROUND: Decisions regarding cancer therapy are based on temporal changes of EF. However the method for EF measurement with the lowest temporal variability is unknown. METHODS: We selected patients in whom stable function in the face of chemotherapy for breast cancer was defined by stability of global longitudinal strain (GLS) at up to 5 time points (baseline, 3, 6, 9, and 12 months). In this way, changes in EF were considered to reflect temporal variability of measurements rather than cardiotoxicity. A comprehensive echocardiogram consisting of 2-dimensional (2D) and 3-dimensional (3D) acquisitions with and without contrast administration was performed at each time point. Stable LV function was defined as normal GLS (≤-16.0%) at each examination. The EF and volumes were measured with 2D-biplane Simpson's method, 2D-triplane, and 3-dimensional echocardiography (3DE) by 2 investigators blinded to any clinical data. Inter-, intra-, and test-retest variability were assessed in a subgroup. Variability was assessed by analysis of variance and compared with Levene's or t test. RESULTS: Among 56 patients (all female, 54 ± 13 years of age), noncontrast 3D EF, end-diastolic volume, and end-systolic volume had significantly lower temporal variability than all other methods. Contrast only decreased the temporal variability of LV end-diastolic volume measurements by the 2D biplane method. Our data suggest that a temporal variability in EF of 0.06 might occur with noncontrast 3DE due to physiological differences and measurement variability, whereas this might be >0.10 with 2D methods. Overall, 3DE also had the best intra- and inter-observer as well as test-retest variability. CONCLUSIONS: Noncontrast 3DE was the most reproducible technique for LVEF and LV volume measurements over 1 year of follow-up.