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.

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.

Reliability of updated left ventricular diastolic function recommendations in predicting elevated left ventricular filling pressure and prognosis.

An updated 2016 echocardiographic algorithm for diagnosing left ventricular (LV) diastolic dysfunction (DD) was recently proposed. We aimed to assess the reliability of the 2016 echocardiographic LVDD grading algorithm in predicting elevated LV filling pressure and clinical outcomes compared to the 2009 version. METHODS: We retrospectively identified 460 consecutive patients without atrial fibrillation or significant mitral valve disease who underwent transthoracic echocardiography within 24 hours of elective heart catheterization. LV end-diastolic pressure (LVEDP) and the time constant of isovolumic pressure decay (Tau) were determined. The association between DD grading by 2009 LVDD Recommendations and 2016 Recommendations with hemodynamic parameters and all-cause mortality were compared. RESULTS: The 2009 LVDD Recommendations classified 55 patients (12%) as having normal, 132 (29%) as grade 1, 156 (34%) as grade 2, and 117 (25%) as grade 3 DD. Based on 2016 Recommendations, 177 patients (38%) were normal, 50 (11%) were indeterminate, 124 (27%) patients were grade 1, 75 (16%) were grade 2, 26 (6%) were grade 3 DD, and 8 (2%) were cannot determine. The 2016 Recommendations had superior discriminatory accuracy in predicting LVEDP (P<.001) but were not superior in predicting Tau. During median follow-up of 416 days (interquartile range: 5 to 2004 days), 54 patients (12%) died. Significant DD by 2016 Recommendations was associated with higher risk of mortality (P=.039, subdistribution HR1.85 [95% CI, 1.03-3.33]) in multivariable competing risk regression. CONCLUSIONS: The grading algorithm proposed by the 2016 LV diastolic dysfunction Recommendations detects elevated LVEDP and poor prognosis better than the 2009 Recommendations.

Grading diastolic function by echocardiography: hemodynamic validation of existing guidelines.

BACKGROUND: While echocardiographic grading of left ventricular (LV) diastolic dysfunction (DD) is used every day, the relationship between echocardiographic DD grade and hemodynamic abnormalities is uncertain. METHODS: We identified 460 consecutive patients who underwent transthoracic echocardiography within 24 h of elective left heart catheterization and had: normal sinus rhythm, no confounding structural heart disease, no change in medications between catheterization and echo, and complete echocardiographic data. Patients were grouped based on echocardiographic DD grade. Hemodynamic tracings were used to determine time constant of isovolumic pressure decay (Tau), LV end-diastolic pressure (LVEDP) and end-diastolic volume index at a pressure of 20 mmHg (EDVi20). RESULTS: Normal diastolic function was found in 55 (12.0%) patients, while 132 (28.7%) patients had grade 1, 156 (33.9%) grade 2 and 117 (25.4%) grade 3 DD. The median value for Tau was 46.9 ms for the overall population (interquartile range 38.6-58.1 ms), with a prevalence of a prolonged Tau (>48 ms) of 47.5%. While there was an association between DD grade and Tau (p = 0.003), LV dysfunction (ejection fraction <50%) was more strongly associated with increased Tau (p < 0.001) than was DD grade (p = 0.19). There was also an association between DD grade and LVEDP (p < 0.001), with both LV dysfunction (p = 0.029) and DD grade (p < 0.001) independently associated with LVEDP. Calculated EDVi20 was related to DD grade, but this relationship was driven by findings of paradoxically increased compliance in patients with severe DD. CONCLUSIONS: Although echocardiographic grading of DD was related to invasive hemodynamics in this population, the relationship was modest.

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.

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).

Role of temporal resolution in selection of the appropriate strain technique for evaluation of subclinical myocardial dysfunction.

OBJECTIVE: To assess the effects of frame and volume rate on the concordance between two-dimensional speckle tracking strain (2DS) and three-dimensional speckle tracking strain (3DS), and between 2DS and triplane imaging of speckle tracking (Tri-P). METHODS: Global longitudinal strains (GLSs) derived from 2DS, 3DS, and Tri-P were compared among 142 prospectively recruited patients who underwent evaluation of subclinical left ventricle (LV) function. RESULTS: Feasibility to obtain GLS of 3DS was significantly higher than that of Tri-P (76% vs. 47%, P < 0.001). The correlation between 2DS and 3DS was only modest (r = 0.47) whereas that of 2DS and Tri-P was better (r = 0.67). The difference in frame/volume rate between two methods also affected their correlation. A volume rate between 34 and 50 volumes/sec had the highest correlation between 2DS and 3DS (r = 0.72). The correlation between 2DS and Tri-P was better with a difference in frame-rate ≤20 per second than with a difference >20 per second. Likewise, there was a better correlation between 2DS and 3DS when the difference between 2D frame rate and 3D volume rate was ≤40 per second, compared to when it was >40 per second. These associations differed from segment to segment and the apical segments had the highest correlation and the basal the lowest. CONCLUSIONS: The feasibility of each means of strain calculation showed important differences, with 2DS being the most attainable. Strain values were not interchangeable among 2DS, Tri-P, and 3DS. Importantly, poor correlations seemed to be driven by differences in acquisition rate. Currently, 2DS offers the most robust measurement of subclinical myocardial dysfunction.

How to standardize measurement of global longitudinal strain.

Global longitudinal strain (GLS) is a robust and sensitive marker of left-ventricular systolic function, reflecting longitudinal shortening of the ventricle. A growing body of evidence indicates its superiority in identifying subclinical, early alterations in cardiac function compared to traditional markers, such as ejection fraction. Therefore, there is a growing demand to assess GLS in clinical settings, but limited availability on how to obtain GLS accurately and appropriately in the current literature. This review summarizes key aspects of GLS measurement, including image acquisition, post-processing, and training/experience needed to facilitate the clinical implication with standardization.

The importance of calibration method in determining the association between central blood pressure with left ventricular and left atrial strain.

Afterload is an important determinant of left ventricular (LV) and atrial (LA) function, including myocardial strain. Central blood pressure (CBP) is the major component of cardiac afterload and independently associated with cardiovascular risk. However, the optimal means of calibrating CBP is unclear-standard CBP assessment uses systolic (SBP) and diastolic blood pressure (DBP) from brachial waveforms, but calibration with mean pressure (MAP) and DBP purports to be more accurate. Therefore, we sought to determine which CBP is best associated with LA and LV strain. CBP was measured using both standard and MAP based calibration methods in 546 participants (age 70.7 ± 4.7 years, 45% male) with risk factors for heart failure. Echocardiography was performed in all patients and strain analysis conducted to assess LA/LV function. The associations of CBP with LA and LV strain were assessed using linear regression. MAP-derived CSBP (150 ± 20 mmHg) was higher than standard CSBP (128 ± 15 mmHg) and brachial SBP (140 ± 17 mmHg, p < 0.001), whereas DBPs were similar (84 ± 10, 83 ± 10, and 82 ± 10 mmHg). MAP-derived CSBP was not independently associated with LV strain (p > 0.05), however was independently associated with LA reservoir strain (p < 0.05). Brachial and central DBP were more strongly associated with LA reservoir/conduit and LV strain than brachial and central SBP. LA pump strain was not independently associated with any SBP or DBP parameter (p > 0.05). MAP-derived CBP was more accurate in identifying patients with abnormal LA and LV strain than brachial SBP and standard CBP calibration. In conclusion, CBP calibrated using MAP and DBP may be more accurate in identifying patients with abnormal LA and LV function than standard brachial calibration methods.

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.

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.

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).

Association of the Active and Passive Components of Left Atrial Deformation with Left Ventricular Function.

BACKGROUND: Left atrial (LA) strain imaging enables the quantitative assessment of LA function. The clinical relevance of these measurements is dependent on the provision of information incremental to the left ventricular (LV) evaluation. The aim of this study was to test the hypothesis that LA pump function but not reservoir function is independent of measurement of LV mechanics. METHODS: Echocardiography was undertaken in a community-based study of 576 participants ≥65 years of age with one or more risk factors (e.g., hypertension, diabetes mellitus, obesity). Strain analysis was conducted using a dedicated software package, using R-R gating. LV function was classified as normal in the presence of global longitudinal strain (GLS) (≤-18%) or global circumferential strain (GCS) (≤-22%). The associations between GLS or GCS and LA reservoir, conduit, and pump strain were assessed using univariate and multivariate linear regression. RESULTS: Patients (mean age 71 ± 5 years, 54% women) with reduced GLS had higher blood pressure and rates of diabetes and obesity (P < .05). LA reservoir strain and conduit strain were lower in the group with impaired GLS (38.2 ± 7.3% vs 39.9 ± 6.4% [P = .004] and 18.7 ± 5.7% vs 20.5 ± 5.1% [P < .001], respectively), but there was no difference in LA pump strain (19.5 ± 5.5% vs 19.3 ± 4.6%, P = .72). GLS was independently associated with LA reservoir and conduit strain (P < .05) but not independently associated with LA pump strain (P = .91). Reduced GCS was associated with a larger body mass index, male sex, and diabetes (P < .05). There were no differences in LA reservoir, conduit, and pump strain in patients with normal and abnormal GCS (P > .05). CONCLUSIONS: The application of LA strain is specific to the component measured. LA pump strain is independent of LV mechanics.

Effect of Experience and Training on the Concordance and Precision of Strain Measurements.

OBJECTIVES: This study sought to show the degree to which experience and training affect the precision and validity of global longitudinal strain (GLS) measurement and to evaluate the variability of strain measurement after feedback. BACKGROUND: The application of GLS for the detection of subclinical dysfunction has been recommended in an expert consensus document and is being used with increasing frequency. The role of experience in the precision and validity of GLS measurement is unknown, as is the efficacy of training. METHODS: Fifty-eight readers, divided into 4 groups on the basis of their experience with GLS, calculated GLS from speckle strain analysis of 9 cases with various degrees of image quality. Intraclass correlation coefficients (ICCs), mean difference, SD, and coefficient of variation (CV) were compared against the measurements of a reference group that had experience with >1,000 cases of strain measurement. Individualized feedback was distributed, and repeat measurements were performed by 40 readers. Comparisons with the baseline variation provided information about whether feedback was effective. RESULTS: The ICC for GLS was significantly greater than that for ejection fraction regardless of image quality. Experience with strain measurement affected the concordance in strain values among the readers; the group with the highest level of experience showed significantly better ICC than those with no experience, although the ICC of the inexperienced readers was still very good (0.996 vs. 0.975; p = 0.0002). As experience increased, the mean difference, SD, and CV became significantly smaller. The CV of segmental strain analysis showed significant improvement after training, regardless of experience. CONCLUSIONS: The favorable interobserver agreement of GLS makes it more attractive than ejection fraction for follow-up of left ventricular function by multiple observers. Although experience is important, the precision of GLS was high for all groups. Training appears to be of most value for the assessment of segmental strain.