Cardioprotection using strain-guided management of potentially cardiotoxic cancer therapy: 1 year results of the SUCCOUR trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Negishi ◽  
P Thavendiranathan ◽  
M Penicka ◽  
J Lemieux ◽  
S Aakhus ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Global Longitudinal Strain ◽  
Measurement Development ◽  
Lv Function ◽  
Relative Reduction ◽  
Funding Source ◽  
Medical Systems ◽  
Private Company ◽  
Lv Dysfunction

Abstract Background Conventional criteria for diagnosis of chemotherapy-related cardiac dysfunction (CTRCD) are dependent on the recognition of heart failure (HF) symptoms and/or changes in LVEF. However, the low sensitivity of EF for minor changes in LV function may delay initiation of cardio-protective therapy (CPT). Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction (LVD), but existing observational data are insufficient to justify changing the diagnostic criteria for CTRCD. Purpose To identify whether GLS guidance of CPT would improve cardiac function of at risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. Methods In this international multicenter prospective randomized controlled trial, 331 pts from 23 international sites taking anthracyclines with another risk factor for HF were randomly allocated into 166 undergoing GLS-guided (CPT for >12% relative reduction in GLS using Echopac software) and 165 EF-guided (CPT for >10% absolute reduction of EF). Pts were followed over 1 year for the primary end-point (ΔEF) with 3D echo (3DE); 2D echo (2DE) was used when 3D images were unsuitable for measurement. Development of CTRCD (EF reduction of 10% to <55%) was a secondary endpoint. Results Of 331 randomized patients, 24 withdrew before follow-up imaging was performed (2 died, and rest withdrew or were lost to follow-up). Among 307 patients (age 54±12 years, 94% women) with follow-up 1.0±0.2 years, 277 had breast cancer, 30 had lymphoma/leukemia. HF risk factors were prevalent: 89 (29%) had hypertension and 39 (13%) had diabetes mellitus. The most common chemotherapy regimen during this study was the combination of anthracycline and trastuzumab. The baseline 3D LVEF was 61±5%, and GLS was −20.8±3.2%. At 1 year follow-up, 31 (10%) met CTRCD and was reduced in the GLS-guided arm (Table 1), although new LV dysfunction (EF<55%) and change of EF were not different. Conclusion In this international multicentre trial, the incidence of CTRCD was reduced by strain-guided cardioprotection. Although the final EF and the number of pts developing EF <55% was not altered by strain-guided therapy, this reduces meaningful reduction of EF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): General Electric Medical Systems

scholarly journals Left Ventricular Dysfunction in Arrhythmogenic Cardiomyopathy: Association With Exercise Exposure, Genetic Basis, and Prognosis

2021 ◽  
Author(s):  
Øyvind H. Lie ◽  
Monica Chivulescu ◽  
Christine Rootwelt‐Norberg ◽  
Margareth Ribe ◽  
Martin Prøven Bogsrud ◽  
...  
Keyword(s):  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Ventricular Tachyarrhythmia ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Lv Function ◽  
Arrhythmogenic Cardiomyopathy ◽  
Lv Dysfunction ◽  
The Impact

Background Arrhythmogenic cardiomyopathy (AC) is characterized by biventricular dysfunction, exercise intolerance, and high risk of ventricular tachyarrhythmias and sudden death. Predisposing factors for left ventricular (LV) disease manifestation and its prognostic implication in AC are poorly described. We aimed to assess the associations of exercise exposure and genotype with LV dysfunction in AC, and to explore the impact of LV disease progression on adverse arrhythmic outcome. Methods and Results We included 168 patients with AC (50% probands, 45% women, 40±16 years old) with 715 echocardiographic exams (4.1±1.7 exams/patient, follow‐up 7.6 [interquartile range (IQR), 5.4–10.9] years) and complete exercise and genetic data in a longitudinal study. LV function by global longitudinal strain was −18.8% [IQR, −19.2% to −18.3%] at presentation and was worse in patients with greater exercise exposure (global longitudinal strain worsening, 0.09% [IQR, 0.01%–0.17%] per 5 MET‐hours/week, P =0.02). LV function by global longitudinal strain worsened, with 0.08% [IQR, 0.05%–0.12%] per year; ( P <0.001), and progression was most evident in patients with desmoplakin genotype ( P for interaction <0.001). Deterioration of LV function predicted incident ventricular tachyarrhythmia (aborted cardiac arrest, sustained ventricular tachycardia, or implantable cardioverter defibrillator shock) (adjusted odds ratio, 1.1 [IQR, 1.0–1.3] per 1% worsening by global longitudinal strain; P =0.02, adjusted for time and previous arrhythmic events). Conclusions Greater exercise exposure was associated with worse LV function at first visit of patients with AC but did not significantly affect the rate of LV progression during follow‐up. Progression of LV dysfunction was most pronounced in patients with desmoplakin genotypes. Deterioration of LV function during follow‐up predicted subsequent ventricular tachyarrhythmia and should be considered in risk stratification.

scholarly journals Heart failure in survivors of out-of-hospital cardiac arrest – factors associated with reduced systolic ventricular function at follow-up

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H.S.Z Bahrami ◽  
J Kjaergaard ◽  
J.H Thomsen ◽  
F Lippert ◽  
L Koeber ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Arrest ◽  
Hospital Discharge ◽  
Left Ventricular ◽  
Lv Function ◽  
Funding Source ◽  
Factors Associated ◽  
Lv Dysfunction ◽  
Hospital Cardiac Arrest

Abstract Background Survival after out-of-hospital cardiac arrest (OHCA) has increased in recent years but is still only 10%. Little is known about the association between post-resuscitation comorbidity and heart failure after discharge from the initial OHCA-admission. Purpose In OHCA-survivors we aimed to describe predictors of left ventricular (LV) dysfunction, defined as LV ejection fraction (LVEF) &lt;40%, at follow-up. Methods A consecutive cohort of OHCA-patients with cardiac cause from 2007 to 2011 without a pre-OHCA congestive heart failure diagnosis (according to the Danish National Patient Registry, which holds data on all Danish citizens) were retrospectively examined. Logistic regression analyses were used to assess factors associated with LV dysfunction (LVEF &lt;40%) at follow-up after a median of 6 months. Follow-up was not performed systematically in the OHCA-survivors and data from follow-up was assessed by reading of patient charts. Results A total of 365 OHCA-survivors with a mean age of 61 years were discharged alive from hospital. LVEF &lt;40% at hospital discharge was seen in 54% (n=184, 7% missing), and at follow-up after a median of 6 months 19% (n=69) of the total OHCA-cohort of survivors still had LV dysfunction. Factors associated with LV dysfunction at follow-up were chronic ischemic heart disease (IHD) prior to OHCA (odds ratio (OR) = 2.9 (95% CI: 1.2 – 7.1)) and ST-elevation myocardial infarction (STEMI) as cause of OHCA (OR = 2.9 (1.4–6.0)), whereas age, gender, high comorbidity burden prior to OHCA or pre-hospital circumstances (including shockable cardiac arrest rhythm) were not. Conclusion More than half of OHCA-survivors with LVEF &lt;40% at hospital discharge improved LV function and LV dysfunction at follow-up after a median of 6 months after discharge was present in 1 in 5 (19%) of the cohort. Chronic IHD and STEMI were the only factors significantly associated with LV dysfunction at follow-up. A systematic follow-up including echocardiography in the outpatient clinic for OHCA-survivors is recommended especially in patients with reduced LV function at discharge and in STEMI-patients in order to assess the appropriateness of heart failure medication and an implantable cardiac defibrillator. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Foundation Trygfonden

scholarly journals The combined role of NT-proBNP and LV-GLS in the detection of early subtle chemotherapy-induced cardiotoxicity in breast cancer female patients

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Laila Sulaiman ◽  
Dina Hesham ◽  
Magdy Abdel Hamid ◽  
Ghada Youssef
Keyword(s):  
Breast Cancer ◽  
Plasma Level ◽  
Global Longitudinal Strain ◽  
Sandwich Elisa ◽  
Chemotherapeutic Agents ◽  
Left Ventricular ◽  
Lv Function ◽  
Relative Reduction ◽  
Female Patients

Abstract Background Chemotherapeutic agents have many side effects; among them is cardiotoxicity. Ejection fraction fails to detect the subtle alterations of left ventricular (LV) function; that is why there is a need for a more sensitive tool. The aim is to detect subclinical LV systolic dysfunction after chemotherapeutic treatment, using NT-BNP plasma level as well as speckle tracking echo-global longitudinal strain (STE-GLS). Seventy-four asymptomatic, non-metastasizing breast cancer female patients without risk factors were included. They were assessed before and 6 weeks after taking their first chemotherapeutic session. Assessment included clinical characteristics, conventional two-dimensional (2D) and three-dimensional (3D) echocardiography, and 2D STE-GLS. Blood samples for NT-BNP plasma level were collected on both visits and were later analyzed using a Sandwich ELISA technique. Results The median NT-proBNP almost doubled after 6 weeks of chemotherapy (73.50 vs 34.4 pg/L, p value <0.001). Only two patients showed significant reduction of LVEF >10% to less <55%. One patient died before her scheduled follow-up visit, and the cause of death is unknown. Fifty patients showed elevated follow-up levels of the NT-BNP. As compared to the baseline visit, 12 patients had a high relative reduction of the LV-GLS (>15%) and all of them had a relatively higher NT-proBNP. A 2.2 relative elevation of the NT-proBNP was able to define a relative reduction of LV-GLS >15% by a 100% sensitivity and 81.8% specificity. Conclusion The relative reduction of LV-GLS and the relative elevation of NT-proBNP were successful in defining subclinical, subtle chemotherapy-induced cardiotoxicity after 6 weeks of the first chemotherapeutic agent administration.

scholarly journals Silent cerebral embolisation during TAVI: evolution, predictors and neurocognitive effects

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M De Carlo ◽  
R Liga ◽  
G.M Migaleddu ◽  
M Scatturin ◽  
C Spaccarotella ◽  
...  
Keyword(s):  
White Matter ◽  
Median Number ◽  
Funding Source ◽  
Private Company ◽  
Diffuse White Matter ◽  
Transcatheter Aortic Valve ◽  
Age Related ◽  
Cerebral Mri ◽  
Neurocognitive Evaluation

Abstract Background Most patients undergoing transcatheter aortic valve implantation (TAVI) develop silent cerebral ischemic lesions (SCIL) detectable at magnetic resonance imaging (MRI). The natural history and clinical relevance of SCIL are not well established. We aimed to assess the characteristics, predictors, evolution, and neurocognitive effects of SCIL. Methods Cerebral MRI was performed within 7 days before TAVI to assess baseline status and age-related white matter changes (ARWMC) score. MRI was repeated postoperatively to assess the occurrence, location, number and dimensions of SCIL. Patients developing SCIL underwent a third MRI at 3–5 months follow-up. A neurocognitive evaluation was performed before TAVI, at discharge and at 3-month follow-up. Results Of the 117 patients enrolled, 96 underwent a postprocedural MRI; SCIL were observed in 76% of patients, distributed in all vascular territories, with a median number of 2 lesions, median diameter 4.5 mm, and median total volume 140 mm3. Independent predictors of SCIL occurrence were a higher baseline ARWMC score and the use of self-expanding or mechanically-expanded bioprostheses. Among 47 patients who underwent follow-up MRI, only 26.7% of postprocedural SCIL evolved into a gliotic scar. SCIL occurrence was associated with a more pronounced transient neurocognitive decline early after TAVI and with a lower recovery at follow-up. Conclusions SCIL occur in the vast majority of patients undergoing TAVR and are predicted by a more diffuse white matter damage at baseline and by the use of non-balloon-expandable prostheses. Although most SCIL disappear within months, their occurrence has a limited but significant impact on neurocognitive function. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): unrestricted grants from Edwards Lifesciences SA, Nyon, Switzerland, and from Medtronic Italia SpA, Milan, Italy

Benefits of tafamidis in patients with advanced transthyretin amyloid cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Rapezzi ◽  
A.V Kristen ◽  
B Gundapaneni ◽  
M.B Sultan ◽  
M Hanna
Keyword(s):  
Disease Severity ◽  
Nyha Class ◽  
Funding Source ◽  
Class Iii ◽  
Private Company ◽  
Risk Of Death ◽  
6Mwt Distance ◽  
All Cause Mortality ◽  
Amyloid Cardiomyopathy

Abstract Background In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis was shown to be an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Further assessment of the efficacy of tafamidis in patients with more advanced ATTR-CM would aid treatment decisions. Purpose To characterize the benefits of tafamidis in patients with advanced ATTR-CM. Methods In ATTR-ACT, ATTR-CM patients were randomized to tafamidis (n=264) or placebo (n=177) for 30 months. Efficacy outcomes included all-cause mortality and frequency of cardiovascular (CV)-related hospitalisations. Key secondary endpoints were change from baseline to Month 30 in 6MWT distance and KCCQ-OS score. Efficacy assessments in NYHA Class III patients at baseline (n=141) were a pre-specified analysis. In a post-hoc analysis, mortality and CV-related hospitalizations were assessed in all patients grouped into quartiles of increasing disease severity based on 6MWT distance at baseline. Longer-term all-cause mortality (as of 1 Aug 2019) was assessed in NYHA Class III patients utilizing data from ATTR-ACT patients who enrolled in a long-term, extension study (LTE) and continued treatment with higher dose tafamidis (n=55; median treatment duration 51.6 months); or, if previously treated with placebo, started tafamidis treatment (placebo/tafamidis; n=63 [50.1 months]). Results In advanced ATTR-CM patients (NYHA Class III), tafamidis reduced the risk of death (HR [95% CI] 0.837, [0.541, 1.295], P=0.4253), and the decline in 6MWT distance (LS mean [SE], 31.6 (22.1) m; P=0.1526) and KCCQ-OS score (LS mean [SE], 13.1 (5.0); P=0.0090), vs placebo. Paradoxically, there was a higher frequency of CV-related hospitalizations with tafamidis (RR [95% CI] vs placebo, 1.411 [1.048, 1.900]). In all patients by 6MWT quartile, CV-related hospitalizations/year with tafamidis and placebo increased with disease severity, with the exception that placebo-treated patients in the highest severity quartile had fewer CV-related hospitalisations (0.73) than those in the third quartile (0.92). Mortality with tafamidis and placebo increased, and was greater with placebo, in every quartile (Figure). Survival (NYHA Class III patients in ATTR-ACT and LTE) was improved with high dose tafamidis with longer term follow-up (HR vs placebo/tafamidis [95% CI], 0.6569 [0.4175, 1.0336]; P=0.0692). Conclusions These analyses, including longer-term follow-up, demonstrate that patients with advanced ATTR-CM benefit from tafamidis. The decrease in CV-related hospitalisations in more severe patients treated with placebo suggests that the comparatively greater hospitalisation frequency in NYHA Class III patients treated with tafamidis is a consequence of their lower mortality rate. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer

scholarly journals Time saving, simple and reproducible method to quantify left ventricular function in patients with atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.V Bunting ◽  
S Gill ◽  
A Sitch ◽  
S Mehta ◽  
K O'Connor ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Controlled Trial ◽  
Global Longitudinal Strain ◽  
Intraclass Correlation ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction

Abstract Introduction Echocardiography is essential for the management of patients with atrial fibrillation (AF), but current methods are time consuming and lack any evidence of reproducibility. Purpose To compare conventional averaging of consecutive beats with an index beat approach, where systolic and diastolic measurements are taken once after two prior beats with a similar RR interval (not more than 60 ms difference). Methods Transthoracic echocardiography was performed using a standardized and blinded protocol in patients enrolled into the RAte control Therapy Evaluation in permanent AF randomised controlled trial (RATE-AF; NCT02391337). AF was confirmed in all patients with a preceding 12-lead ECG. A minimum of 30-beat loops were recorded. Left ventricular function was determined using the recommended averaging of 5 and 10 beats and using the index beat method, with observers blinded to clinical details. Complete loops were used to calculate the within-beat coefficient of variation (CV) and intraclass correlation coefficient (ICC) for Simpson's biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and filling pressure (E/e'). Results 160 patients (median age 75 years (IQR 69–82); 46% female) were included, with median heart rate 100 beats/min (IQR 86–112). For LVEF, the index beat had the lowest CV of 32% compared to 51% for 5 consecutive beats and 53% for 10 consecutive beats (p&lt;0.001). The index beat also had the lowest CV for GLS (26% versus 43% and 42%; p&lt;0.001) and E/e' (25% versus 41% and 41%; p&lt;0.001; see Figure for ICC comparison). Intra-operator reproducibility, assessed by the same operator from two different recordings in 50 patients, was superior for the index beat with GLS bias −0.5 and narrow limits of agreement (−3.6 to 2.6), compared to −1.0 for 10 consecutive beats (−4.0 to 2.0). For inter-operator variability, assessed in 18 random patients, the index beat also showed the smallest bias with narrow confidence intervals (CI). Using a single index beat did not impact on the validity of LVEF, GLS or E/e' measurement when correlated with natriuretic peptides. Index beat analysis substantially shortened analysis time; 35 seconds (95% CI 35 to 39 seconds) for measuring E/e' with the index beat versus 98 seconds (95% CI 92 to 104 seconds) for 10 consecutive beats (see Figure). Conclusion Index beat determination of left ventricular function improves reproducibility, saves time and does not compromise validity compared to conventional quantification in patients with heart failure and AF. After independent validation, the index beat method should be adopted into routine clinical practice. Comparison for measurement of E/e' Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research UK

scholarly journals Angiographic control versus ischaemia-driven management of patients undergoing percutaneous revascularisation of the unprotected left main coronary artery with second-generation drug-eluting stents: rationale and design of the PULSE trial

Open Heart ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. e001253
Author(s):  
Ovidio De Filippo ◽  
Matteo Bianco ◽  
Matteo Tebaldi ◽  
Mario Iannaccone ◽  
Luca Gaido ◽  
...  
Keyword(s):  
Second Generation ◽  
Controlled Trial ◽  
Drug Eluting Stents ◽  
Major Adverse Cardiovascular Events ◽  
Relative Reduction ◽  
Left Main ◽  
Bleeding Events ◽  
Open Label ◽  
Drug Eluting

BackgroundThe role of planned angiographic control (PAC) over a conservative management driven by symptoms and ischaemia following percutaneous coronary intervention (PCI) of the unprotected left main (ULM) with second-generation drug-eluting stents remains controversial. PAC may timely detect intrastent restenosis, but it is still unclear if this translated into improved prognosis.Methods and analysisPULSE is a prospective, multicentre, open-label, randomised controlled trial. Consecutive patients treated with PCI on ULM will be included, and after the index revascularisation patients will be randomised to PAC strategy performed with CT coronary after 6 months versus a conservative symptoms and ischaemia-driven follow-up management. Follow-up will be for at least 18 months from randomisation. Major adverse cardiovascular events at 18 months (a composite endpoint including death, cardiovascular death, myocardial infarction (MI) (excluding periprocedural MI), unstable angina, stent thrombosis) will be the primary efficacy outcome. Secondary outcomes will include any unplanned target lesion revascularisation (TLR) and TLR driven by PAC. Safety endpoints embrace worsening of renal failure and bleeding events. A sample size of 550 patients (275 per group) is required to have a 80% chance of detecting, as significant at the 5% level, a 7.5% relative reduction in the primary outcome.Trial registration numberNCT04144881

scholarly journals RNAi inhibition of angiopoietin-like protein 3 (ANGPTL3) with ARO-ANG3 mimics the lipid and lipoprotein profile of familial combined hypolipidemia

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G.F Watts ◽  
C Schwabe ◽  
R Scott ◽  
P Gladding ◽  
D Sullivan ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Response ◽  
Minimal Change ◽  
Funding Source ◽  
Private Company ◽  
Good Tolerability ◽  
Duration Of Action ◽  
Mixed Dyslipidemia ◽  
Genetic Deficiency

Abstract Background Elevated LDL-C and triglyceride rich lipoproteins (TRLs) are independent risk factors for cardiovascular disease (CVD). Genetic deficiency of angiopoietin-like protein 3 (ANGPTL3) is associated with reduced circulating levels of LDL-C, triglycerides (TGs), VLDL-C, HDL-C and reduced CVD risk, with no described adverse phenotype. ARO-ANG3 is a RNA interference drug designed to silence expression of ANGPTL3. Single doses of ARO-ANG3 have been shown to reduce ANGPTL3, TGs, VLDL-C and LDL-C in healthy volunteers (HVs, AHA 2019). We report the effects of multiple doses of ARO-ANG3 in HVs with a focus on the duration of action. Methods ARO-ANG3 was administered subcutaneously to HVs on days 1 and 29 at doses of 100, 200 or 300 mg (n=4 per group). Measured parameters included ANGPTL3, LDL-C, TGs, VLDL-C and HDL-C. Follow up is ongoing. Results All HVs have received both doses and follow-up is currently through week 16 (12 weeks after second dose). Mean nadir for ANGPTL3 levels occurred 2 weeks after the second dose (−83–93%) with minimal change for 200 and 300 mg but 16% recovery for 100 mg at week 16. Mean TGs and VLDL-C reached nadir earlier (3 wks, −61–65%) without apparent dose response and minimal change for any dose at wk 16. LDL-C nadir occurred 4–6 wks after the second dose (−45–54%), again with minimal evidence for dose response or change through wk 16. HDL-C was reduced 14–37% at wk 16. ARO-ANG3 was well tolerated without serious or severe adverse events or dropouts related to drug. The most common adverse events have been headache and upper respiratory infections. Conclusions Genetic deficiency of ANGPTL3 is a cause of familial combined hypolipemia and is associated with a decreased risk of CVD. Using RNAi to selectively suppress ANGPTL3 production reproduces these genetic effects with a duration of at least 12 weeks following a second dose and with good tolerability over 16 wks. ANGPTL3 inhibition results in lowering of LDL-C and TRLs which may confer protection against CVD in patients with atherogenic mixed dyslipidemia. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Arrowhead Pharmaceuticals

scholarly journals Evolution of left ventricular function after Wharton's jelly mesenchymal stem cells transcoronary administration: 5-year follow up in a pilot cohort of CIRCULATE-AMI Randomized Trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Kwiecien ◽  
L Drabik ◽  
A Mazurek ◽  
M Sikorska ◽  
L Czyz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Infarct Size ◽  
Troponin T ◽  
Left Ventricular ◽  
Lv Function ◽  
Funding Source ◽  
Double Blind ◽  
Wharton's Jelly

Abstract Introduction CIRCULATE-Acute Myocardial Infarction is a double-blind controlled trial randomizing (RCT) in 105 consecutive patients with their first, large AMI (cMRI-LVEF ≤45% and/or cMRI-infarct size ≥10% of LV) with successful infarct-related artery (IRA) primary percutaneous coronary intervention (pPCI) to transcoronary administration of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) vs. placebo (2:1). The pilot study cohort (PSC) preceded the RCT. Aim To evaluate WJMSCs long-term safety, and evolution of left-ventricular (LV) function in CIRCULATE-AMI PSC. Material and methods 30 000 000 WJMSCs (50% labelled with 99mTc-exametazime) were administered via IRA in a ten-patient PCS (age 32–65 years, peak hs-Troponin T 17.3±9.1ng/mL and peak CK-MB 533±89U/L, cMRI-LVEF 40.3±2.7% and infarct size 20.1±2.8%) at ≈5–7 days after AMI using a cell delivery-dedicated, coronary-non-occlusive method. Other treatments were per guidelines. WJMSCs showed an unprecedented high myocardial uptake (30.2±5.3%; 95% CI 26.9–33.5%), corresponding to ≈9×10 000 000 cells retention in the infarct zone – in absence of epicardial flow or myocardial perfusion impairment (TIMI-3 in all; cTFC 45±8 vs. 44±9, p=0.51) or any hs-Troponin T elevation. Five-year follow up included cardiac Magnetic Resonance Imaging (cMRI) (at baseline, 1 year and 3 years) and detailed echocardiography (echo) at baseline, 1 year, 3 years and 5 years. Results By 5 years, one patient died from a new, non-index territory AMI. There were no other cardiovascular events and MACCE that might be related to WJMSCs transplantation. On echo (Fig), there was an increase in left ventricular ejection fraction (LVEF) between WJMSCs administration point and 1 year (37.7±2.9% vs. 48.3±2.5%, p=0.002) that was sustained at 3 years (47.2±2.6%, p=0.005 vs. baseline) and at 5 years: (44.7±3.2%, p=0.039 vs. baseline). LVEF reached a peak at 1 year after the AMI and WJMSCs transfer (Fig). cMRI data (obtained up to 3 years; 1 year 41.9±2.6% vs. 51.0±3.3%, p&lt;0.01; 3 years 52.2±4.0%, p&lt;0.01 vs. baseline) were consistent with the echo LVEF assessment. Conclusions 5-year follow up in CIRCULATE-AMI PSC indicates that WJMSC transcoronary application is safe and may be associated with an LVEF improvement. The magnitude of LV increase appears to peak at 1 year, suggesting a potential role for repeated WJMSCs administration(s). Currently running double-blind RCT will provide placebo-controlled insights into the WJMSCs effect(s) on changes in LV function, remodelling, scar reduction and clinical outcomes. Echo-LVEF evolution Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): STRATEGMED 265761 “CIRCULATE” National Centre for Research and Development/Poland/ZDS/00564 Jagiellonian University Medical College

Baseline characteristics and follow-up outcomes in routine clinical practice patients categorised by renal function in the ETNA-AF-Europe registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R De Caterina ◽  
M Gwechenberger ◽  
A Bakhai ◽  
P Monteiro ◽  
P Kelly ◽  
...  
Keyword(s):  
Renal Function ◽  
Total Mortality ◽  
Haemorrhagic Stroke ◽  
Risk Scores ◽  
Funding Source ◽  
Private Company ◽  
Group I ◽  
Baseline Characteristics ◽  
Event Rates

Abstract Background Edoxaban is an oral factor Xa inhibitor anticoagulant with 50% renal clearance, and proven efficacy and safety in patients (pts) with atrial fibrillation (AF). The post-authorisation, observational, ETNA-AF-Europe registry (NCT02944019) assessed the risks and benefits of edoxaban in pts with AF from 10 European countries. Purpose Evaluate baseline characteristics and event rates in pts categorised by creatinine clearance (CrCl) at 1-year follow-up of the ETNA-AF-Europe registry. Methods In this analysis, pts were divided into three groups according to CrCl: ≤50 ml/min (I), 50–80 mL/min (II) and ≥80 mL/min (III) (calculated using Cockcroft-Gault). Outcomes were descriptively analysed. Results Pts with the lowest CrCl (Group I) were mostly females, and had a higher mean age, lower body weight, higher stroke and bleeding risk scores and were considered more frail than those with higher CrCl (Groups II and III) (Table). Group I experienced higher rates of stroke or SEE, major or CRNM bleeding, cardiovascular death, and had a higher total mortality (Figure). Rates of intracranial haemorrhage (ICH) and haemorrhagic stroke (intracerebral and subarachnoid haemorrhage) were low and similar in pts across the range of CrCl. Conclusions Those with lower CrCl had more comorbidities and higher event rates than those with higher CrCl, with the exception of ICH and haemorrhagic stroke. A steep rise in the proportion of pts perceived as frail and in overall mortality in the lowest renal function tertile, raises the question whether low renal function is a determinant or a correlate of mortality. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH, Munich, Germany

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