scholarly journals Sacubitril/valsartan is well tolerated in patients with longstanding heart failure and history of cancer and improves ventricular function: real-world data

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maria Klara Frey ◽  
Henrike Arfsten ◽  
Noemi Pavo ◽  
Emilie Han ◽  
Stefan Kastl ◽  
...  

Abstract Background Sacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalizations due to heart failure in patients with reduced ejection fraction (HFrEF) when compared to enalapril. Data about sacubitril/valsartan in patients with a history of cancer are scarce, as these patients were excluded from the pivotal trial, PARADIGM-HF. The aim of the current study was to assess tolerability of sacubitril/valsartan in patients with a history of cancer. Methods We identified 225 patients at our heart failure out-patient unit who fulfilled the indication criteria to receive sacubitril/valsartan. Out of these, 9.3% (n = 21) had a history of histologically confirmed cancer. Oncologic surgery was performed in 16 (76.2%) patients, 11 (52.4%) patients received previous antineoplastic therapy and 9 patients (42.9%) radiation. Results Sacubitril/valsartan was withdrawn in 3 of 21 patients (14.3%) because of dizziness (n = 2) or pruritus (n = 1). After a median follow-up of 12 months (range 1–34 months), NYHA functional class improved significantly from NYHA 3 to NYHA 2 (mean -0.6, p = 0.006) and left ventricular ejection fraction as assessed by echocardiography increased significantly from 26.8 ± 5.4% to 39.2 ± 10% (mean + 12%, CI 95% [8.4–16.4], p = 0.0004). NT-proBNP was significantly reduced (baseline median 2774 pg/ml, range 1441 – 12,982 vs follow-up 1266 pg/ml, range 199–6324, p = 0.009). There was no significant change in creatinine levels (1.18 ± 0.4 vs 1.22 ± 0.4 mg/dl; mean + 0.005 mg/dl, CI 95% [-0.21- 0.12], p = 0.566). Conclusions In our pilot study we show that sacubitril/valsartan is generally well tolerated in patients with HFrEF and history of cancer. Importantly, even patients with long-standing cardiotoxicity induced heart failure can be treated and up-titrated with sacubitril/valsartan to usual target dosages, leading to improvement in LV function and biomarkers. Larger studies are needed to confirm these findings in cancer patients with cardiotoxicity.

Author(s):  
Maria Thilén ◽  
Stefan James ◽  
Elisabeth Ståhle ◽  
Lars Lindhagen ◽  
Christina Christersson

Abstract Aims Left ventricular ejection fraction (LVEF) affects the outcome of aortic valve replacement (AVR) in aortic stenosis (AS). The study aim was to investigate the prognostic importance of concomitant cardiovascular disease in relation to pre-operative LVEF. Methods and results All adult patients undergoing AVR due to AS 2008–14 in a national register for heart diseases were included. All-cause mortality and hospitalization for heart failure during follow-up after AVR, stratified by preserved or reduced LVEF (≤50%), were derived from national patient registers and analysed by Cox regression. During the study period, 10 406 patients, median age 73 years, a median follow-up of 35 months were identified. Preserved LVEF was present in 7512 (72.2%). Among them, 647 (8.6%) had a history of heart failure (HF) and 1099 (14.6%) atrial fibrillation (AF) before the intervention. Pre-operative HF was associated with higher mortality irrespective of preserved or reduced LVEF: hazard ratio (HR) 1.64 [95% confidence interval (CI) 1.35–1.99] and 1.58 (95% CI 1.30–1.92). Prior AF was associated with a higher risk of mortality in patients with preserved but not in those with reduced LVEF: HR 1.62 (95% CI 1.36–1.92) and 1.05 (95% CI 0.86–1.28). Irrespective of LVEF, pre-operative HF and AF were associated with an increased risk of post-operative heart failure hospitalization. Conclusion In patients planned for AVR, a history of HF or AF, irrespective of LVEF, worsens the post-operative prognosis. Heart failure and AF can be seen as markers of myocardial fibrosis not necessarily discovered by LVEF and the merely use of it, besides symptoms, for the timing of AVR seems suboptimal.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Rebellius ◽  
R Berzins Schoenenberger ◽  
S Anwer ◽  
S Rogler ◽  
N Kuzo ◽  
...  

Abstract Introduction Left ventricular non-compaction (LVNC) is a rare cardiomyopathy with a progressive clinical course, resulting in symptoms such as heart failure, cardiac arrhythmias, or thrombo-embolic events. Little is known about the natural course of disease, in particular in individuals with normal LV ejection fraction (EF) at diagnosis. In this study, we aim to evaluate the outcome of this group of patients. Methods 48 LVNC patients with normal LV EF at diagnosis (defined as ≥50% by Simpson) were retrospectively analysed followed-up for median duration of 3656 days (2017–4965). All outcome data and conventional echocardiographic parameters were obtained; and in 27 patients, LV and right ventricular (RV) global longitudinal strain (GLS) were also determined using TomTec Image Arena (v.4.6). Results Mean age was 25.5 years. Median LVEF was 58.5% [IQR: 52.75 - 65.25]). The localization of non-compacted segments displayed a typical distribution with apical and inferolateral midventricular segments most frequently involved. Although LVEF was normal at baseline, median LV GLS was 16.8% (IQR: 20.0 - 14.2) and RV GLS was 18.7% (23.3–15.6). Furthermore, only 30 patients (73.2%) had a normal diastolic function, while others showed impaired relaxation (19.5%; n=8) or restrictive filling pattern (7.3%; n=3). During follow-up, LVEF decreased slightly from the initial visit (59%, [53.3–65.0]) to last follow-up (56%, [53.0–61.8], p=0.0009), and LV end-systolic and end-diastolic volumes increased (p=0.009 and 0.001, respectively). The other echocardiographic parameters did not show any significant changes. During follow-up, 3 patients (7.7%) died, 5 (12.8%) were hospitalized for heart failure, 3 (7.7%) had a thromboembolic event, 5 (12.8%) a syncope, 3 (8.1%) a non-sustained ventricular tachycardia, 9 (22.5%) a supraventricular tachycardia, and 14 (35.9%) suffered other complications during follow-up. The change in LVEF and LV volumes during follow-up was not significantly associated with outcome. Conclusion Patients presenting with a LVNC phenotype and normal LVEF did not display a completely normal LV function as revealed by LV strain and LV diastolic function. LVEF decreased slightly during follow-up, but was surprisingly stable in most patients. Nevertheless, a significant number of individuals experienced a clinically relevant event. Hence, a LVNC phenotype is important even in individuals with normal LVEF and such patients should be followed-up regularly.


2021 ◽  
Vol 10 (23) ◽  
pp. 5513
Author(s):  
Fatema Said ◽  
Jozine M. ter Maaten ◽  
Pieter Martens ◽  
Kevin Vernooy ◽  
Mathias Meine ◽  
...  

Introduction: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF). Women appear to respond differently to CRT, yet it remains unclear whether this is inherent to the female sex itself, or due to other patient characteristics. In this study, we aimed to investigate sex differences in response to CRT. Methods: This is a post-hoc analysis of a prospective, multicenter study (MARC) in the Netherlands, studying HFrEF patients with an indication for CRT according to the guidelines (n = 240). Primary outcome measures are left ventricular ejection fraction (LVEF) and left ventricular end systolic volume (LVESV) at 6 months follow-up. Results were validated in an independent retrospective Belgian cohort (n = 818). Results: In the MARC cohort 39% were women, and in the Belgian cohort 32% were women. In the MARC cohort, 70% of the women were responders (defined as >15% decrease in LVESV) at 6 months, compared to 55% of men (p = 0.040) (79% vs. 67% in the Belgian cohort, p = 0.002). Women showed a greater decrease in LVESV %, LVESV indexed to body surface area (BSA) %, and increase in LVEF (all p < 0.05). In regression analysis, after adjustment for BSA and etiology, female sex was no longer associated with change in LVESV % and LVESV indexed to BSA % and LVEF % (p > 0.05 for all). Results were comparable in the Belgian cohort. Conclusions: Women showed a greater echocardiographic response to CRT at 6 months follow-up. However, after adjustment for BSA and ischemic etiology, no differences were found in LV-function measures or survival, suggesting that non-ischemic etiology is responsible for greater response rates in women treated with CRT.


2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
E Marcusohn ◽  
O Kobo ◽  
M Postnikov ◽  
D Epstein ◽  
Y Agmon ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background  The diagnosis of atrial fibrillation (AF) induced cardiomyopathy can be challenging. It relies on ruling out other causes of dilated cardiomyopathy, upon recovery of left ventricular ejection fraction (LVEF) following return to sinus rhythm (SR). Aim  The aim of this study was to identify clinical and echocardiographic predictors for developing new dilated cardiomyopathy in patients with AF or atrial flutter (AFL). Methods  This is a retrospective study conducted in a large tertiary care center. Patients that suffered deterioration of LVEF under 50% during AF demonstrated by pre-cardioversion trans-esophageal echocardiography (TEE) were compared to those with preserved LV function during AF. All patients had documented preserved LVEF at baseline (EF &gt;50%) while in SR. Patients with a previous history of reduced LVEF during SR were excluded. Results From a total of 482 patients included in the final analysis, 80 (17%) patients had reduced LV function and 402 (83%) had preserved LV function during the pre-cardioversion TEE. Patients with reduced LVEF were more likely to be male and with a more rapid ventricular response during AF/AFL. A history of prosthetic valves was also identified as a risk factor for reduced LVEF. Patients with reduced LVEF also had higher incidence of TR and RV dysfunction. Conclusion In "real world" experience, male patients with rapid ventricular response during AF or AFL are more prone to LVEF reduction. Patients with prosthetic valves are also at risk for LVEF reduction during AF/AFL. Lastly, TR and RV dysfunction may indicate relatively long-standing AF with an associated reduction in LVEF.


2021 ◽  
Vol 10 (21) ◽  
pp. 4989
Author(s):  
Mohammad Abumayyaleh ◽  
Christina Pilsinger ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Jürgen Kuschyk ◽  
...  

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.


Author(s):  
Parisa Gholami ◽  
Shoutzu Lin ◽  
Paul Heidenreich

Background: BNP testing is now common though it is not clear if the test results are used to improve patient care. A high BNP may be an indicator that the left ventricular ejection fraction (LVEF) is low (<40%) such that the patient will benefit from life-prolonging therapy. Objective: To determine how often clinicians obtained a measure of LVEF (echocardiography, nuclear) following a high BNP value when the left ventricular ejection fraction (LVEF) was not known to be low (<40%). Methods and Results: We reviewed the medical records of 296 consecutive patients (inpatient or outpatient) with a BNP values of at least 200 pg/ml at a single medical center (tertiary hospital with 8 community clinics). A prior diagnosis of heart failure was made in 65%, while 42% had diabetes, 79% had hypertension, 59% had ischemic heart disease and 31% had chronic lung disease. The mean age was 73 ± 12 years, 75% were white, 10% black, 15% other and the mean BNP was 810 ± 814 pg/ml. The LVEF was known to be < 40% in 84 patients (28%, mean BNP value of 1094 ± 969 pg/ml). Of the remaining 212 patients without a known low LVEF, 161 (76%) had a prior LVEF >=40% ( mean BNP value of 673 ± 635 pg/ml), and 51 (24%) had no prior LVEF documented (mean BNP 775 ± 926 pg/ml). Following the high BNP, a measure of LVEF was obtained (including outside studies documented by the primary care provider) within 6 months in only 53% (113 of 212) of those with an LVEF not known to be low. Of those with a follow-up echocardiogram, the LVEF was <40% in 18/113 (16%) and >=40% in 95/113 (84%). There was no significant difference in mean initial BNP values between those with a follow-up LVEF <40% (872 ± 940pg/ml), >=40% (704 ± 737 pg/ml), or not done (661 ± 649 pg/ml, p=0.5). Conclusions: Follow-up measures of LVEF did not occur in almost 50% of patients with a high BNP where the information may have led to institution of life-prolonging therapy. Of those that did have a follow-up study a new diagnosis of depressesd LVEF was noted in 16%. Screening of existing BNP and LVEF data and may be an efficient strategy to identify patients that may benefit from life-prolonging therapy for heart failure.


Cardiology ◽  
2020 ◽  
Vol 145 (5) ◽  
pp. 275-282 ◽  
Author(s):  
Pablo Díez-Villanueva ◽  
Lourdes Vicent ◽  
Francisco de la Cuerda ◽  
Alberto Esteban-Fernández ◽  
Manuel Gómez-Bueno ◽  
...  

Background: A significant number of heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) experience ventricular function recovery during follow-up. We studied the variables associated with LVEF recovery in patients treated with sacubitril/valsartan (SV) in clinical practice. Methods: We analyzed data from a prospective and multicenter registry including 249 HF outpatients with reduced LVEF who started SV between October 2016 and March 2017. The patients were classified into 2 groups according to LVEF at the end of follow-up (>35%: group R, or ≤35%: group NR). Results: After a mean follow-up of 7 ± 0.1 months, 62 patients (24.8%) had LVEF >35%. They were older (71.3 ± 10.8 vs. 67.5 ± 12.1 years, p = 0.025), and suffered more often from hypertension (83.9 vs. 73.8%, p = 0.096) and higher blood pressure before and after SV (both, p < 0.01). They took more often high doses of beta-blockers (30.6 vs. 27.8%, p = 0.002), with a smaller proportion undergoing cardiac resynchronization therapy (14.8 vs. 29.0%, p = 0.028) and fewer implanted cardioverter defibrillators (ICD; 32.8 vs. 67.9%, p < 0.001), this being the only predictive variable of NR in the multivariate analysis (OR 0.26, 95% CI 0.13–0.47, p < 0.0001). At the end of follow-up, the mean LVEF in group R was 41.9 ± 8.1% (vs. 26.3 ± 4.7% in group NR, p < 0.001), with an improvement compared with the initial LVEF of 14.6 ± 10.8% (vs. 0.8 ± 4.5% in group NR, p < 0.0001). Functional class improved in both groups, mainly in group R (p = 0.035), with fewer visits to the emergency department (11.5 vs. 21.6%, p = 0.07). Conclusions: In patients with LVEF ≤35% treated with SV, not carrying an ICD was independently associated with LVEF recovery, which was related to greater improvement in functional class.


2020 ◽  
Vol 9 (9) ◽  
pp. 2932
Author(s):  
Mauro Feola ◽  
Arianna Rossi ◽  
Marzia Testa ◽  
Cinzia Ferreri ◽  
Alberto Palazzuoli ◽  
...  

Background. The diuretic response has been shown to be a robust independent marker of cardiovascular outcomes in acute heart failure patients. The objectives of this clinical research are to analyze two different formulas (diuretic response (DR) or response to diuretic (R-to-D)) in predicting 6-month clinical outcomes. Methods: Consecutive patients discharged alive after an acute decompensated heart failure (ADHF) were enrolled. All patients underwent N-terminal-pro hormone BNP (NT-proBNP) and an echocardiogram together with DR and R-to-D calculation during diuretic administration. Death by any cause, cardiac transplantation and worsening heart failure (HF) requiring readmission to hospital were considered cardiovascular events. Results: 263 patients (62% male, age 78 years) were analyzed at 6-month follow-up. During the follow-up 58 (22.05%) events were scheduled. Patients who experienced CV-event had a worse renal function (p = 0.001), a higher NT-proBNP (p = 0.001), a lower left ventricular ejection fraction (p = 0.01), DR (p = 0.02) and R-to-D (p = 0.03). Spearman rho’s correlation coefficient showed a strong direct correlation between DR and R to D in all patients (r = 0.93; p < 0.001) and both in heart failure with reduced ejection fraction (HFrEF) (r = 0.94; p < 0.001) and HF preserved ejection fraction (HFpEF) (r = 0.91; p < 0.001). At multivariate analysis, a value of R-to-D <1.69 kg/40 mg, but only <0.67 kg/40 mg for DR were significantly related to poor 6-month outcome (p = 0.04 and p = 0.05, respectively). Receiver operating characteristic (ROC) curve analyses demonstrated that DR and R-to-D are equivalent in predicting prognosis (area under curve (AUC): 0.39 and 0.40, respectively). Only R-to-D was inversely related to in-hospital stay (r = −0.23; p = 0.01). Conclusion: Adding diuresis to DR seemed to provide a better risk assessment in alive HF patients discharged after an acute decompensation.


2020 ◽  
Vol 9 (6) ◽  
pp. 1897 ◽  
Author(s):  
Francesco Giallauria ◽  
Giuseppe Vitale ◽  
Mario Pacileo ◽  
Anna Di Lorenzo ◽  
Alessandro Oliviero ◽  
...  

Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients’ services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = −0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = −0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = −0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = −2.065, SE = 0.354, p < 0.001). Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.


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.


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