scholarly journals Rationale, Design, and Feasibility of a Prospective Multicenter Registry Study of Anthracycline-Induced Cardiotoxicity (AIC Registry)

2021 ◽  
Vol 10 (7) ◽  
pp. 1370
Author(s):  
Keiko Inoue ◽  
Noriko Iida ◽  
Kazuko Tajiri ◽  
Hiroko Bando ◽  
Shigeru Chiba ◽  
...  

As the number of cancer survivors increases, cardiac management in anthracycline-treated patients has become more important. We planned to conduct a prospective multicenter registry study for comprehensive echocardiographic and biomarker data collection and an evaluation of the current practice in terms of diagnosis and management of anthracycline-induced cardiotoxicity (AIC registry). To examine the feasibility of this registry study, we analyzed the 1-year follow-up data of 97 patients registered during the first year of this registry. The AIC registry was launched in July 2016. Data on echocardiographic parameters (e.g., two-and three-dimensional [(2- and 3-D) left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and biomarkers (e.g., troponin T and brain natriuretic peptide) were collected before anthracycline treatment, every 3 months during the first year after starting anthracycline, and every 6 months during the second year. Eighty-three patients (86%) completed a 1-year follow-up. The measurable rates of 2D LVEF, 3D LVEF, and GLS on each visit were nearly optimal (100%, 86–93%, and 84–94%, respectively). During the 1-year follow-up, 5 patients (6.0%) developed cardiotoxicity (a reduction in LVEF ≥ 10 percentage points from baseline and <55%). The AIC registry study is feasible and will be the first study to collect sizable echocardiographic and biomarker data on cardiotoxicity in Japanese patients treated with anthracycline in a real-world setting.

Author(s):  
Rory Hachamovitch ◽  
Benjamin Nutter ◽  
Manuel D Cerqueira ◽  

Background . The use of implantable cardiac defibrillators has been associated with improved survival in several well-defined patient (pt) subsets. Its utilization for primary prevention in eligible pts, however, is unclear. We sought to examine the frequency of ICD implantation (ICD-IMP) for primary prevention in a cohort prospectively enrolled in a prospective, multicenter registry of ICD candidates. Methods . We identified 961 pts enrolled in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study, a prospective, multicenter study evaluating the prognostic usefulness of 123I-mIBG scintigraphy in a heart failure population. Inclusion criteria limited patients to those meeting guideline criteria for ICD implantation; these criteria included left ventricular ejection fraction ≤35% and New York Heart Association functional class II-III. We excluded pts with an ICD at the time of enrollment, leaving a study cohort of 934 patients. Pts were followed up for 24 months after enrollment. Pts undergoing ICD-IMP after enrollment for secondary prevention were censored at the time of intervention. The association between ICD-IMP utilization and demographic, clinical, laboratory, and imaging data was examined using Cox proportional hazards analysis (CPH). Results . Of 934 pts, 196 (21%) were referred for ICD-IMP over a mean follow-up of 612±242 days. Implantations occurred 167±164 days after enrollment. Patients referred for ICD were younger (61±12 vs. 63±12), but did not differ with respect to proportion female (17% vs. 21%), African-American race (12% vs. 15%), diabetics (37% vs. 36%) (All p=NS). The frequency of ICD-IMP did not differ as a function of age, race, sex, LVEF, or imaging result (All p=NS). CPH revealed that a model including age, race, sex, diabetes, smoking, BMI, NYHA class, hypertension, heart failure etiology, and prior MI identified none of these as predictive of ICD-IMP. Conclusion: This analysis of prospective registry data reveals that in patients who are guideline-defined candidates for ICD-IMP, only about one in five receive an ICD over a two year follow-up interval. Multivariable modeling failed to identify any factor associated with ICD use.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A Banke ◽  
M Schou ◽  
J Dahl ◽  
P Frederiksen ◽  
L Videbaek ◽  
...  

Abstract Funding Acknowledgements The Danish Heart Foundation, Copenhagen (grant number: 14-R97-A5188-22839 and 15-R99-A5940). The Research Fond of the Region of Southern Denmark. Background Global longitudinal strain (GLS) is recommended to detect subclinical changes preceding reduced left ventricular ejection fraction (LVEF) in trastuzumab related cardiotoxicity. The possibility to detect signs of acute myocardial deterioration at treatment initiation is not thoroughly investigated. Accordingly, the aim of this study was to assess changes in GLS and biomarkers within the first two weeks of trastuzumab treatment. Methods In a prospective cohort study 45 patients with non-metastatic breast cancer (age 54, LVEF 62.8% (SD ± 3.6), GLS -19.9% (SD ± 2.1), 40% hypertension) were included. Examinations including echocardiography and measurement of troponin T and NT-proBrain Natriuretic Peptide were conducted before initiation of trastuzumab, at day 3, 7 and 14 and after 3, 6 and 9 months. Results A significant deterioration in LVEF, GLS, s’, e’ septal and s’RV occurred during the 9 months study period and was proceed by significant changes in all these parameters within the first 14 days. After 14 days 12 patients (27%) had an increase in GLS ≥10 %, which was associated with significantly lower LVEF at nine month at 55.2% (SD ± 4.1) vs. 59.5% (SD ± 3.5) (p = 0.001) compared to patients with &lt;10 % early increase in GLS (Figure 1). No difference in plasma concentrations of cardiac biomarkers was observed between the two groups. Conclusion In this cohort study deteriorations in key echocardiographic parameters were detected within the first two weeks of trastuzumab treatment, and an early 10 % increase in GLS was associated with a lower LVEF at nine months. Abstract P1533 Figure 1


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Steen ◽  
M Montenbruck ◽  
P Wuelfing ◽  
S Esch ◽  
A K Schwarz ◽  
...  

Abstract Background The incidence of cardiotoxicity during cancer therapy is underestimated due to limitations of current diagnostic tests. Current biomarkers (BNP, NT-pro-BNP, hs-Troponin, etc.) and imaging calculations (e.g. echocardiography) such as left ventricular ejection fraction (LVEF) are currently included in the guidelines to designate cardiotoxicity during cancer therapy. Unfortunately, these diagnostics identify systemic damage in symptomatic patients after the heart is unable to compensate for regional dysfunction. Fast-SENC segmental intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) test that regionally detects subclinical intramyocardial dysfunction in 1 heartbeat. Methods This single center, prospective Prefect Study was used to evaluate cardiotoxicity and the impact of cardioprotective therapy in Breast Cancer and Lymphoma patients (NCT03543228). fSENC was acquired with a 1.5T MRI and processed with the software to quantify intramyocardial strain. Segmental strain was measured in three short axis scans (basal, midventricular, apical) with 16 LV/6 RV longitudinal segments & three long axis scans (2-, 3-, 4-chamber) with 21 LV/5 RV circumferential segments. fSENC CMR was performed before chemotherapy, during and after anthracycline/taxane therapy, at 1 year follow-up, and as needed in between designated follow-up periods. Cardioprotective therapy was offered to patients meeting the definition of cardiotoxicity by the ESC Guidelines on Cardiotoxicity and/or ESMO Clinical Practice Guidelines or those observing a substantial decline in cardiac function. Results Two hundred eight (208) CMRs were performed in fifty-two (52) patients (44 female). Patients had an average (± stdev) age of 53 (15) yrs, BMI of 26 (5) kg/m2; 77% had breast cancer, 23% had Lymphoma. fSENC CMRs required 11 (2) min total exam time. The % of normal fSENC (segmental stain <−17%) with a threshold of 65% showed a sensitivity of 87% and specificity of 89% in detecting cardiotoxicity while echocardiography GLS with a threshold of −17% observed a sensitivity of 20% and specificity of 88%. Figure 1 shows receiver operating characteristic curves for fSENC based on the percent of normal myocardium, and echocardiography global longitudinal strain (GLS) respectively. Global fSENC had substantially lower sensitivity than segmental fSENC despite having higher accuracy than the other global metrics. Figure 1 Conclusion Segmental fSENC intramyocardial strain detects subclinical dysfunction due to cardiotoxic response of chemotherapy before other biomarkers and imaging modalities. The ability to detect the subclinical cardiotoxicity of chemotherapy agents, or other pharmacological agents that cause or worsen heart failure, enables proactive prescription of cardioprotective medications to avoid tissue remodeling that precedes systemic cardiac dysfunction and worsening of global measures such as LVEF and current biomarkers.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
I H Jung ◽  
Y S Byun ◽  
J H Park

Abstract Funding Acknowledgements no Background Left ventricular global longitudinal strain (LV GLS) offers sensitive and reproducible measurement of myocardial dysfunction. The authors sought to evaluate whether LV GLS at the time of diagnosis may predict LV reverse remodeling (LVRR) in DCM patients with sinus rhythm and also investigate the relationship between baseline LV GLS and follow-up LVEF. Methods We enrolled patients with DCM who had been initially diagnosed, evaluated, and followed at our institute. Results During the mean follow-up duration of 37.3 ± 21.7 months, LVRR occurred in 28% of patients (n = 45) within 14.7 ± 10.0 months of medical therapy. The initial LV ejection fraction (LVEF) of patients who recovered LV function was 26.1 ± 7.9% and was not different from the value of 27.1 ± 7.4% (p = 0.49) of those who did not recover. There was a moderate and highly significant correlation between baseline LV GLS and follow-up LVEF (r = 0.717; p &lt;0.001). Conclusion There was a significant correlation between baseline LV GLS and follow-up LVEF in this population. Baseline Follow-up Difference (95% CI) p-value All patients (n = 160) LVEDDI, mm/m2 35.6 ± 6.6 35.6 ± 6.6 -2.7 (-3.4 to -2.0) &lt;0.001 LVESDI, mm/m2 30.3 ± 6.1 26.6 ± 6.6 -3.7 (-4.6 to -2.8) &lt;0.001 LVEDVI, mL/m2 95.0 ± 30.7 74.3 ± 30.2 -20.7 (-25.6 to -15.8) &lt;0.001 LVESVI, mL/m2 70.0 ± 24.8 50.2 ± 26.8 -19.8 (-24.2 to -15.4) &lt;0.001 LVEF, % 26.8 ± 7.5 33.9 ± 12.6 7.2 (5.2 to 9.2) &lt;0.001 LV GLS (-%) 9.2 ± 3.1 11.0 ± 4.8 1.8 (1.3 to 2.2) &lt;0.001 Patients without LVRR (n = 115) LVEDDI, mm/m2 34.9 ± 6.8 34.1 ± 6.8 -0.8 (-1.3 to -0.3) 0.002 LVESDI, mm/m2 29.5 ± 6.1 28.4 ± 6.4 -1.4 (-1.8 to -0.4) 0.002 LVEDVI, mL/m2 92.0 ± 30.5 83.4 ± 29.8 -8.6 (-12.4 to -4.8) &lt;0.001 LVESVI, mL/m2 67.1 ± 24.4 59.5 ± 25.3 -7.6 (-10.9 to -4.3) &lt;0.001 LVEF, % 27.1 ± 7.4 27.8 ± 7.4 0.7 (-0.2 to 1.6) 0.126 LV GLS (-%) 8.2 ± 2.9 8.7 ± 3.2 0.5 (0.7 to 3.6) &lt;0.001 Patients with LVRR (n = 45) LVEDDI, mm/m2 37.4 ± 5.5 29.8 ± 5.2 -7.5 (-9.1 to -6.0) &lt;0.001 LVESDI, mm/m2 32.2 ± 5.7 21.9 ± 4.4 -10.3 (-11.9 to -8.6) &lt;0.001 LVEDVI, mL/m2 102.7 ± 30.2 51.1 ± 15.0 -51.7 (-61.6 to -41.7) &lt;0.001 LVESVI, mL/m2 77.3 ± 24.5 26.4 ± 11.3 -50.9 (-58.8 to -43.1) &lt;0.001 LVEF, % 26.1 ± 7.9 49.4 ± 9.5 23.9 (20.4 to 27.5) &lt;0.001 LV GLS (-%) 11.9 ± 1.6 16.9 ± 2.7 5.1 (4.2 to 5.9) &lt;0.001 Baseline and Follow-up LV Functional Echocardiographic Data Abstract P818 Figure.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Klimczak-Tomaniak ◽  
V Van Den Berg ◽  
M Strachinaru ◽  
K M Akkerhuis ◽  
S Baart ◽  
...  

Abstract Introduction Linking temporal biomarker evolutions to changes within myocardial structure and function could provide additional insights into the mechanisms that underlie associations between blood biomarkers and clinical outcome, which have been reported in previous studies. Purpose We aimed to investigate whether serum biomarkers reflect the functional state of the heart in a longitudinal setting. We examined the relationship between serial simultaneous measurements of echocardiographic parameters and serum biomarkers C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin t (hs-TnT) in chronic heart failure (CHF) patients. Materials and methods In total, 117 CHF patients enrolled in a prospective observational study underwent serial measurement of hs-TnT, NT-proBNP and CRP, accompanied by echocardiographic evaluation at six-month intervals until the end of 30-month follow-up or until an adverse clinical event (HF hospitalization, left ventricular assist device implantation, cardiac transplantation, cardiac death) occurred. Linear mixed effects (LME) models were used for data-analysis. Results Mean age was 58±11 years, 80% were male, 76% in NYHA class I or II and all had reduced left ventricular ejection fraction (LVEF). Median follow-up was 2.2 years [IQR: 1.5–2.6]. We performed up to 6 follow-up evaluations with 55% of patients having at least 3 evaluations performed. A model containing all three biomarkers revealed a significant, independent association between NT-proBNP and all the echocardiographic parameters, including LVEF (Beta coefficient per doubling of NT-proBNP [95% CI]: −0.12 [−0.16; −0.07] log2 (%EF), p<0.0001); mitral E/e' (0.17 [0.09; 0.24] log2 (change in ratio), p<0.0001); mitral E/A (0.22 [0.13; 0.30] log2 (change in ratio), p<0.0001); TAPSE (−0.06 [−0.11; −0.02] log2(mm), p=0.008), tricuspid regurgitation gradient (0.13 [0.07; 0.20] log2(mmHg), p=0.0001) as well as left ventricular and left atrial dimensions (p<0.001). Hs-TnT and CRP showed significant associations with some echocardiographic parameters after adjustment for clinical covariates, but associations lost significance after correction for the other biomarkers. Figure 1. Associations between repeatedly measured NT-proBNP and repeatedly measured echocardiographic parameters (Panel A). Temporal evolution of echocardiographic parameters (B) and biomarker levels (C). Conclusion Serum NT-proBNP independently reflects temporal changes in echocardiographic parameters of systolic and diastolic function, left ventricular filling pressure, estimated pulmonary pressure and chamber diameters. Our results support further studies on NT-proBNP as a surrogate marker for hemodynamic congestion and herewith support its potential value for therapy guidance. Acknowledgement/Funding The Bio-SHiFT study was supported by the Jaap Schouten Foundation (Rotterdam, the Netherlands) and the Noordwest Academie (Alkmaar, the Netherlands).


2020 ◽  
Author(s):  
Joseph Odunga Abuodha ◽  
Asim Jamal Shaikh ◽  
Jasmit Shah ◽  
Mohamed Jeilan ◽  
Anders Barasa

Abstract Background Anthracyclines are associated with irreversible cardiotoxicity, with changes in echocardiographic parameters preceding clinically manifest cardiac dysfunction. We sought to evaluate the incidence of early cardiac dysfunction post anthracyclines, and associated clinical, echocardiographic and treatment parameters in a sub-Saharan African population. Methods Cancer patients aged ≥18years at anthracycline initiation with archived baseline echocardiograms, underwent repeat echocardiographic assessment. Cases (with cardiac dysfunction) had (1) >15% relative decline from baseline in global longitudinal strain (GLS), or (2) a decline in left ventricular ejection fraction (LVEF) from baseline to <53% with either (i) symptoms (assessed by the Duke Activity Status Index at follow-up echocardiogram) and LVEF decline by >5 to ≤10%, or (ii) LVEF decline >10% regardless of symptoms. Comparisons in clinical, echocardiographic and treatment parameters were made with controls (no cardiac dysfunction). Results Among 141 patients (mean age, 47.7years ± 11.2, Africans 95%, females 85.1%, breast cancer 82%), 39 (27.7%) had cardiac dysfunciton at a mean inter-echocardiogram interval of 14.9months ± 14.3, mean cumulative anthracycline dose of 244.7mg/m 2 ± 72.2, and mean DASI score was 50.0 ± 13.3. Mean cardiotoxic doxorubicin equivalence dose was 236.7mg/m 2 ± 57.4 for cases and 217.3 ± 61.9 for controls [p = 0.033, OR = 1.00 (95% CI: 0.99 - 1.01)]. The assessed clinical, echocardiographic and treatment parameters were not associated with cardiac dysfunction. Conclusion Incidence of early cardiac dysfunction after standard dose anthracyclines in an adult Sub-Saharan population is 27.7% at a mean follow-up of 14.9 months post anthracycline. Routine pre- and post-exposure cardiac assessment should be considered.


Heart ◽  
2021 ◽  
pp. heartjnl-2021-319504
Author(s):  
Marco Merlo ◽  
Marco Masè ◽  
Andrew Perry ◽  
Eluisa La Franca ◽  
Elena Deych ◽  
...  

ObjectivePatients with non-ischaemic dilated cardiomyopathy (NICM) may experience a normalisation in left ventricular ejection fraction (LVEF). Although this correlates with improved prognosis, it does not correspond to a normalisation in the risk of death during follow-up. Currently, there are no tools to risk stratify this population. We tested the hypothesis that absolute global longitudinal strain (aGLS) is associated with mortality in patients with NICM and recovered ejection fraction (LVEF).MethodsWe designed a retrospective, international, longitudinal cohort study enrolling patients with NICM with LVEF <40% improved to the normal range (>50%). We studied the relationship between aGLS measured at the time of the first recording of a normalised LVEF and all-cause mortality during follow-up. We considered aGLS >18% as normal and aGLS ≥16% as of potential prognostic value.Results206 patients met inclusion criteria. Median age was 53.5 years (IQR 44.3–62.8) and 56.6% were males. LVEF at diagnosis was 32.0% (IQR 24.0–38.8). LVEF at the time of recovery was 55.0% (IQR 51.7–60.0). aGLS at the time of LVEF recovery was 13.6%±3.9%. 166 (80%) and 141 (68%) patients had aGLS ≤18% and <16%, respectively. During a follow-up of 5.5±2.8 years, 35 patients (17%) died. aGLS at the time of first recording of a recovered LVEF correlated with mortality during follow-up (HR 0.90, 95% CI 0.91 to 0.99, p=0.048 in adjusted Cox model). No deaths were observed in patients with normal aGLS (>18%). In unadjusted Kaplan-Meier survival analysis, aGLS <16% was associated with higher mortality during follow-up (31 deaths (22%) in patients with GLS <16% vs 4 deaths (6.2%) in patients with GLS ≥16%, HR 3.2, 95% CI 1.1 to 9, p=0.03).ConclusionsIn patients with NICM and normalised LVEF, an impaired aGLS at the time of LVEF recovery is frequent and associated with worse outcomes.


2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Hubert ◽  
A Galard ◽  
V Le Rolle ◽  
E Galli ◽  
A Hernandez ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Hospital university of Rennes INSERM - LTSI Background Non-invasive estimation of myocardial work by trans-thoracic echocardiography is a novel tool to analyze myocardial contraction efficiency during systole. Two methods are described, on using Left ventricular (LV) strain and a LV pressure estimation, and another with only LV strain integrals. The present study analyzes their utility in prediction of CRT-response. Methods and results: 243 patients implanted by a CRT according to current recommendations were retrospectively included in hospital university of Rennes. All patients had a complete trans-thoracic echocardiography at implantation and at 6-moths follow-up. Responders were defined as having a 15% decrease in indexed LV end-systolic volume at follow-up compared to baseline. Baseline characteristics are described in table 1. 25.1% were non-responders. In this group, there were more men, more ischemic cardiomyopathies with more dilated LV. Strain signals ware analyzed only in the most informative loop, the apical 4 cavities. Myocardial work estimation with LV pressure estimation was previously described. The 3 different integral of strain signal were represented in figure 1. According to ROC curves, myocardial work (particularly wasted work in septal wall with AUC = 0.718 ± 0.04) estimated with LV pressure estimation is better than strain integrals to predict LV positive remodeling (best AUC 0.631 ± 0.040) after CRT-implantation. Conclusion Left ventricular pressure estimation give useful information on top of strain curves for prediction for CRT-response. Table 1 Responders n = 182 Non-responders n = 61 Men (%) 109 (59.9%) 52 (85%) Ischemic cardiomyopathy (%) 42 (23.1%) 34 (55.7%) LVEF (%) 28 ± 6 28 ± 7 GLS (%) -9 ± 3 -7 ± 3 LVEDD (mm) 62 ± 8 67 ± 7 LVEDVi (ml/m2) 85 ± 34 88 ± 30 LVEF Left ventricular ejection fraction; GLS: global longitudinal strain; LVEDD: left ventricular end-diastolic diameter; LVEDVi: left ventricular end diastolic volume index Abstract Figure 1


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Meimoun ◽  
S Abdani ◽  
M Gannem ◽  
V Stracchi ◽  
F Elmkies ◽  
...  

Abstract Background Predicting left ventricular (LV) recovery after acute ST-elevation myocardial infarction (STEMI) is challenging and of prognostic importance. Objective To evaluate the usefulness of non-invasive myocardial work (MW), a new index of global and regional myocardial performance, to predict LV recovery and in-hospital complications after STEMI. Methods Ninety-three consecutive patients with anterior STEMI (mean age, 59±12 years) treated by primary angioplasty underwent transthoracic echocardiography (TTE) within 24–48 hours after angioplasty and a median of 92 days at follow-up. MW is derived from the non-invasive strain-pressure loop obtained from the 2D strain data, integrating in its calculation the non-invasive brachial arterial pressure. Segmental LV recovery was defined as a normalization of segmental wall motion abnormalities of the affected segments and global recovery as an absolute improvement of left ventricular ejection fraction (LVEF) greater than 5% in patients with baseline LVEF &lt;50%. In-hospital complications were defined as a composite of death, reinfarction, heart failure, and LV apical thrombus. Results 1642 segments were studied and MW was impaired in infarct segments, more severely in no recovery versus recovery segments (MW index, constructive MW, MW efficiency, all, p&lt;0.01). Furthermore, global MW was significantly correlated to acute and follow-up LVEF and global longitudinal strain (GLS) (all, p&lt;0.01). Constructive MW was the best indice to predict segmental (p&lt;0.01 versus MW index, MW efficiency, and wasted work), and global recovery (p&lt;0.05 versus GLS) with an independent association (all, p&lt;0.01). Moreover, global constructive MW was independently associated to in-hospital complications which occurred in 18 patients (p&lt;0.01). Conclusion In patients with anterior STEMI treated by primary angioplasty, acute constructive MW is an independent predictor of segmental and global LV recovery, as well as in-hospital complications. Funding Acknowledgement Type of funding source: None


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