Abstract 17313: Multiparametric Cardiac MRI Documents Reduced LV Remodeling and Improved Contractile Function in Regions Adjacent to the Infarct After Pharmacologic Immunomodulation via Adenosine 2a Receptor Stimulation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ya-Jian Cheng ◽  
Elie R Chemaly ◽  
Yikui Tian ◽  
Frederick H Epstein ◽  
Brent A French
Keyword(s):  
Infarct Size ◽  
Contractile Function ◽  
Black Blood ◽  
Inversion Recovery Imaging ◽  
Cardiac Strain ◽  
Lv Mass ◽  
Lv Remodeling ◽  
Acute Mi ◽  
Adenosine 2A Receptor ◽  
A2ar Agonist

Introduction: Agonists of the Adenosine 2a Receptor (A2aR) are used clinically as pharm-stress agents for perfusion imaging, but they are also potent immunomodulators that reduce the size of acute MI when administered at reperfusion in both large and small animal models of MI. Hypothesis: Sustained administration of an A2aR agonist can reduce post-MI LV remodeling and improve cardiac strain even when treatment is withheld until after infarct size has stabilized. Methods: Two groups of mice were studied: C57BL/6 mice treated with Vehicle or a highly selective A2aR agonist (ATL313). All mice received 1h coronary occlusion and 28d of reperfusion. ATL313 was administered for 28 days by subcutaneous micro-osmotic pumps implanted after MI. All mice underwent 7T CMR imaging at baseline and 2, 7 & 28 days post-MI. CMR included short-axis black-blood cines covering the entire heart, with mid-ventricular cine DENSE for circumferential strain (Ecc). Late Gd-enhanced (LGE) inversion recovery imaging was performed on Days 2&7 and molecular imaging with a collagen-targeted Gd contrast agent (EP3533) on Days 14&28. Mice with Day 2 LGE infarct sizes less than 22% or >42% LV mass were excluded from analysis. Results: Examples of LGE and DENSE analysis are shown in Panels A&B. Day 2 infarct size was similar between groups (ATL313 (n=9): 35±2 vs Vehicle (n=8): 34±2, mean±SEM, p=NS). In panel C, ATL313 significantly improved LV end-systolic volume as early as 2 days post-MI (mean±SEM, *p<0.05 vs Vehicle). In panel D, ATL313 improved Day 2 Ecc in adjacent zones vs. Vehicle (-10±2 vs -6±2%, *p<0.05). In panel E, ATL313 reduced LV mass at Day 28 vs Vehicle (121±7 vs 143±7mg, *p<0.05). Conclusions: Pharmacologic immunomodulation with an A2aR agonist inhibits LV remodeling, improves contractile function in infarct-adjacent regions at Day 2 post-MI and reduces LV mass at Day 28. Combined with previous work, these results suggest that A2aR stimulation may prove beneficial in both acute and sub-acute MI.

Abstract 18759: N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein and Infarct Size Measured With Delayed Enhancement Multidetector Computed Tomography

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Doo Sun Sim ◽  
Youngkeun Ahn ◽  
Yun Hyeon Kim ◽  
Hyun Ju Seon ◽  
Keun Ho Park ◽  
...  
Keyword(s):  
Infarct Size ◽  
High Sensitivity ◽  
Lv Function ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Lv Dysfunction ◽  
Lv Remodeling ◽  
Acute Mi ◽  
Lv Ejection Fraction ◽  
Hs Crp

Background: There is a paucity of information on the time-dependent relationship of cardiac biomarkers to infarct size and left ventricular (LV) remodeling after myocardial infarction (MI). We sought to investigate the relationship between levels high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and indices of infarct size and LV volume after acute MI. Methods: A total of 86 patients with ST-elevation MI within 12 hours after the symptom onset underwent delayed enhancement multi-detector computed tomography (DE MDCT) immediately after percutaneous coronary intervention (PCI) to determine infarct size. LV function and remodeling were assessed by echocardiography. Hs-CRP and NT-proBNP were serially measured at admission, 24 hours, and 2 months. DE MDCT and echocardiography were repeated at 2 months after PCI. Results: Levels of both hs-CRP and NT-proBNP at 24 hours showed positive correlation with infarct size at baseline and at 2 months, and negative correlation with LV ejection fraction at baseline and at 2 months. NT-proBNP at 2 months correlated with infarct size (r=0.561, p=0.007), LV ejection fraction (r= - 0.539, p=0.010), and LV end diastolic and systolic volume indices at 2 months (r=0.796, p=0.032 and r=0.831, p=0.021, respectively). NT-proBNP was higher in patients who developed LV remodeling at 2 months: 929 pg/mL vs. 134 pg/mL, p = 0.002. In contrast, hs-CRP at 2 months showed no relationship to infarct size, LV function, or LV volumes at 2 months. Conclusions: Elevated hs-CRP during active myocardial necrosis was associated with infarct size and LV dysfunction, whereas elevated levels of NT-proBNP early and late after the onset of acute MI were both correlated with infarct size, LV dysfunction, and LV remodeling.

scholarly journals P1572 The role of 3D echocardiography in the evaluation of left ventricular remodeling

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
O Guseva ◽  
O Guseva ◽  
O Mamaeva ◽  
N Pavlova ◽  
D Pavlov ◽  
...  
Keyword(s):  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Black Blood ◽  
Lv Mass ◽  
Lv Remodeling ◽  
3D Echo ◽  
Group A ◽  
High Dynamic ◽  
Group B

Abstract Purpose to assess the left ventricular (LV) remodeling with using transthoracic 3D Echo and MRI in young athletes. Materials for the period from October 2015 to April 2018, 88 athletes (61 men and 27 women) were examined. Mean age was 20.8 ± 3.9 years. Group A (professionals) – 65 athletes (4 or more training days a week, experience in sports for at least 7 years, the presence of at least the 1st sports category). Group B (Amateurs) – 23 athletes (3 or less training days a week). By types of loads were identified 4 groups: 1st - high-static, low-dynamic (climbing); 2nd - medium-static, medium-dynamic (volleyball, Rugby, sports dancing); 3rd - medium-static, high-dynamic (badminton, orienteering, hockey); 4th - high-static, high-dynamic (triathlon, water polo, rowing). Methods 2D-, 3D-Echo was performed on Vivid E9 XDclear 4D (GE, USA). With the help of software package for processing 3D arrays (4D auto LVQ and 4D Strain and LV-mass) in automatic and semi-automatic mode was obtained end diastolic and end systolic volumes (EDV, ESV), ejection fraction (EF) and LV mass. The device was used for MRI - Avanto (Siemens) - 1.5 T, using: sensors for breathing and synchronization with ECG, standard surface coil Body Matrix. Visualization of the mobile myocardium was carried out by SSFP protocols in standard two-and four-chamber view, as well as on the short axis. In addition, the black-blood Protocol was performed in axial projection for visualization of mediastinal organs and chest. Evaluation of the results was performed on a workstation Syngo Via VB10B (Siemens) using a worker thread MR Cardiac analisis. Results There were significant differences in the types of loads (p &lt; 0.001): 22% of men in Group B had 1st type, 2nd type - 78% of men and 93% of women in group B, 3rd type - 45% of men and 36% of women in group A, 4th type - 39% of men and 21% of women in group A. In the evaluation of LV remodeling and its relationship with the type of loads revealed significant differences (p &lt; 0.01): 87.5% had LV remodeling (95.4% - aggregate type load 1, 2, 3), 6.8% - concentric remodeling (21.7% of all type 4), and 4.5% eccentric hypertrophy (8.7% of all type 4), 1.1 per cent of concentric hypertrophy (4.4% of all type 4). Consequently, most athletes with loads of type 4 had different types of LV remodeling. Comparing 3D Echo and MRI, high-grade positive correlations were obtained in indicators: EDV (R 0.82, p &lt; 0.0001), ESV (R 0.80, p &lt; 0.0001), LV mass (R 0.85, p &lt; 0.0001), as well as moderate positive the index of EDV (R 0.54, p &lt; 0.037) and unreliable for the EF. Conclusions three-dimensional visualization allows to carry out a reliable assessment of the volumetric parameters of the heart chambers, comparable with MRI data and to identify the signs and type of LV remodeling. Requires further study of the performance of 3D Echo in athletes, given the lack of normative data on the modern stage.

scholarly journals Preclinical trial of a MAP4K4 inhibitor to reduce infarct size in the pig: does cardioprotection in human stem cell-derived myocytes predict success in large mammals?

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Maaike te Lintel Hekkert ◽  
Gary Newton ◽  
Kathryn Chapman ◽  
Rehan Aqil ◽  
Robert Downham ◽  
...  
Keyword(s):  
Stem Cell ◽  
Infarct Size ◽  
Clinical Success ◽  
Heart Tissue ◽  
Balloon Occlusion ◽  
Large Mammals ◽  
Preclinical Trial ◽  
Large Mammal ◽  
Lv Mass ◽  
Technical Issues

AbstractReducing infarct size (IS) by interfering with mechanisms for cardiomyocyte death remains an elusive goal. DMX-5804, a selective inhibitor of the stress-activated kinase MAP4K4, suppresses cell death in mouse myocardial infarction (MI), human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), and 3D human engineered heart tissue, whose fidelity to human biology is hoped to strengthen the route to clinical success. Here, DMX-10001, a soluble, rapidly cleaved pro-drug of DMX-5804, was developed for i.v. testing in large-mammal MI. Following pharmacodynamic studies, a randomized, blinded efficacy study was performed in swine subjected to LAD balloon occlusion (60 min) and reperfusion (24 h). Thirty-six animals were enrolled; 12 were excluded by pre-defined criteria, death before infusion, or technical issues. DMX-10001 was begun 20 min before reperfusion (30 min, 60 mg/kg/h; 23.5 h, 17 mg/kg/h). At all times tested, beginning 30 min after the start of infusion, DMX-5804 concentrations exceeded > fivefold the levels that rescued hPSC-CMs and reduced IS in mice after oral dosing with DMX-5804 itself. No significant reduction occurred in IS or no-reflow corrected for the area at ischemic risk, even though DMX-10001 reduced IS, expressed in grams or % of LV mass, by 27%. In summary, a rapidly cleaved pro-drug of DMX-5804 failed to reduce IS in large-mammal MI, despite exceeding the concentrations for proven success in both mice and hPSC-CMs.

scholarly journals Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy

2018 ◽  
Vol 64 (9) ◽  
pp. 1370-1379 ◽  
Author(s):  
Peder L Myhre ◽  
Torbjørn Omland ◽  
Sebastian I Sarvari ◽  
Heikki Ukkonen ◽  
Frank Rademakers ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Wall Motion ◽  
Troponin T ◽  
Left Ventricular ◽  
Reference Limit ◽  
Lv Mass ◽  
Lv Remodeling ◽  
Perfusion Defects ◽  
Stable Cad ◽  
Upper Reference Limit

Abstract BACKGROUND Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8–11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (&gt;14 ng/L). Patients with hs-cTnT &gt;14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P &lt; 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P &lt; 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

Abstract 13610: Native T1-based Cardiovascular Magnetic Resonance Imaging for Characterizing Chronic Myocardial Infarctions in Patients

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Avinash Kali ◽  
Eui Y Choi ◽  
Behzad Sharif ◽  
Young J Kim ◽  
Xiaoming Bi ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Infarct Size ◽  
Sensitivity And Specificity ◽  
Remote Myocardium ◽  
Myocardial Infarctions ◽  
Native T1 ◽  
Threshold Criterion ◽  
Acute Mi ◽  
End Stage

Introduction: Late Gadolinium Enhancement (LGE) Cardiovascular Magnetic Resonance (CMR) is the gold standard for characterizing chronic myocardial infarctions (MIs), but it is contraindicated in patients with end-stage chronic kidney disease. Hypothesis: We investigated whether native T1 mapping at 3T can reliably characterize chronic MIs in two pilot patient populations with prior STEMI and NSTEMI. Methods: Patients with prior STEMI (n=15) and NSTEMI (n=17) underwent CMR at a median of 13.6 years after acute MI and native T1 maps and LGE images were acquired. Infarct location, size and transmurality were measured from LGE and T1 maps using standard threshold criterion and compared against one another. Visual conspicuity for detecting chronic MI territories on LGE images and T1 maps were assessed by independent reviewers. Results: LGE images and native T1 maps were not different for measuring infarct size (STEMI: p=0.87; NSTEMI: p=0.93) and transmurality (STEMI: p=0.19; NSTEMI: p=0.24). Statistical analyses showed good agreement between LGE images and T1 maps for measuring infarct size (STEMI: bias = -0.4±2.1%; R2=0.97; NSTEMI: bias = -1.1±3.9%; R2=0.87) and transmurality (STEMI: bias = 1.5±2.9%; R2=0.99; NSTEMI: bias = -2.2±7.4%; R2=0.71). Sensitivity and specificity of native T1 maps for detecting chronic MIs based on threshold criterion were 93% and 97% respectively (STEMI); and 93% and 92% respectively (NSTEMI). Mean visual conspicuity score for detecting chronic MI on LGE images was greater than that of native T1 maps (p<0.001). Sensitivity and specificity of native T1 maps using visual detection were: 61% and 85% (STEMI); and 67% and 90% (NSTEMI). Conclusions: Chronic MIs in STEMI and NSTEMI patients can be reliably characterized using threshold-based detection with native T1 maps when the location of remote myocardium is known. The current visual detectability of remote myocardium on native T1 maps has a certainty of 85% in STEMI and 90% in NSTEMI patients.

Biphasic temporal pattern in exercise capacity after myocardial infarction in the rat: relationship to left ventricular remodeling

2005 ◽  
Vol 288 (1) ◽  
pp. H244-H249 ◽  
Author(s):  
Nathan A. Trueblood ◽  
Patrick R. Inscore ◽  
Daniel Brenner ◽  
Daniel Lugassy ◽  
Carl S. Apstein ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Exercise Capacity ◽  
Time Course ◽  
Ventricular Remodeling ◽  
Contractile Function ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Early Recovery ◽  
Functional Changes ◽  
Lv Remodeling

After myocardial infarction (MI), there is progressive left ventricular (LV) remodeling and impaired exercise capacity. We tested the hypothesis that LV remodeling results in structural and functional changes that determine exercise impairment post-MI. Rats underwent coronary artery ligation ( n = 12) or sham ( n = 11) surgery followed by serial exercise tests and echocardiography for 16 wk post-MI. LV pressure-volume relationships were determined using a blood-perfused Langendorff preparation. Exercise capacity was 60% of shams immediately post-MI ( P < 0.05) followed by a recovery to near normal during weeks 5– 8. Thereafter, there was a progressive decline in exercise capacity to ±40% of shams ( P < 0.01). At both 8 and 16 wk post-MI, fractional shortening (FS) was reduced and end-diastolic diameter (EDD) was increased ( P < 0.01). However, neither FS nor EDD correlated with exercise at 8 or 16 wk ( r2 < 0.12, P > 0.30). LV septal wall thickness was increased at both 8 ( P = 0.17 vs. shams) and 16 wk ( P = 0.035 vs. shams) post-MI and correlated with exercise at both times ( r2 ≥ 0.50 and P ≤ 0.02 at 8 and 16 wk). Neither end-diastolic volume nor maximum LV developed pressure at 16 wk correlated with exercise capacity. Exercise capacity follows a biphasic time course post-MI. An immediate decrease is followed by an early recovery phase that is associated with compensatory LV hypertrophy. Subsequently, there is a progressive decrease in exercise capacity that is independent of further changes in LV volume or contractile function.

scholarly journals Sex-differences in left ventricular remodeling and mechanics after aortic valve surgery in patients with severe aortic valve disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G K Singh ◽  
E M Vollema ◽  
E A Prihadi ◽  
M V Regeer ◽  
S H Ewe ◽  
...  
Keyword(s):  
Sex Differences ◽  
Aortic Valve ◽  
Ejection Fraction ◽  
Aortic Valve Disease ◽  
Valve Disease ◽  
Men And Women ◽  
Lv Mass ◽  
Lv Remodeling ◽  
Lv Ejection Fraction

Abstract Background Sex-differences in left ventricular (LV) remodeling in patients with aortic valve disease have been reported. However, sex-differences in LV remodeling and mechanics in response to aortic valve replacement (AVR) remained largely unexplored. Purpose The present study aimed to evaluate the sex-differences during the time course of LV remodeling and LV mechanics (by LV global longitudinal strain (GLS)) after aortic valve replacement. Methods Patients with severe aortic valve disease (aortic stenosis (AS) or aortic regurgitation (AR)) undergoing AVR with echocardiographic follow-up at 1,2, and/or 5 years were evaluated. LV mass index, LV ejection fraction, LV GLS and stroke volume (SV) were measured. Linear mixed models analyses were used to assess changes in LV mass index, LVEF, LV GLS and SV between time points. The models were corrected for age, LV end-diastolic diameter at baseline and time between echocardiograms. Results A total of 211 patients (61±14 years, 61% male) with severe aortic valve disease (AS 63% or AR 39%) were included. Before AVR, men had larger LV mass index and higher SV compared to women. Both men and women had a preserved LV ejection fraction (54±12 and 56±9, P=0.102, respectively), but moderately impaired LV GLS (14.6±4.1 and 16.1±4.1, P=0.009, respectively). After AVR, both groups showed LV mass regression, improvement in LV ejection fraction and LV GLS. LV mass index and SV remained higher in men. During follow-up women showed significantly better LV GLS compared to men (P=0.030, figure 1). Conclusion In men and women with severe aortic valve disease undergoing AVR, the time course of changes in LV mass regression, LV ejection fraction, LV GLS and SV are similar. During follow-up LV mass index remained larger in men and women showed significantly better LV GLS. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The department of Cardiology received unrestricted research grants from Abbott Vascular, Bayer, Bioventrix, Biotronik, Boston Scientific, Edwards Lifesciences, GE Healthcare and Medtronic. Victoria Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, MSD and Medtronic. Nina Ajmone Marsan received speakers fees from Abbott Vascular and GE healthcare. Jeroen J Bax received speaker fees from Abbott Vascular. The remaining authors have nothing to disclose.

Contractile Function of Papillary Muscle From Rats With Different Infarct Size Afterβ-Adrenergic Blockade and ACE-inhibition

1997 ◽  
Vol 29 (11) ◽  
pp. 2941-2951 ◽  
Author(s):  
K.D. Wagner ◽  
H. Theres ◽  
A. Born ◽  
S. Strube ◽  
N. Wunderlich ◽  
...  
Keyword(s):  
Infarct Size ◽  
Papillary Muscle ◽  
Contractile Function ◽  
Ace Inhibition ◽  
Adrenergic Blockade

scholarly journals Dissociation between cardiomyocyte function and remodeling with β-adrenergic receptor blockade in isolated canine mitral regurgitation

2008 ◽  
Vol 295 (6) ◽  
pp. H2321-H2327 ◽  
Author(s):  
Betty Pat ◽  
Cheryl Killingsworth ◽  
Thomas Denney ◽  
Junying Zheng ◽  
Pamela Powell ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Adrenergic Receptor ◽  
Volume Overload ◽  
Left Ventricular ◽  
Ultrastructural Changes ◽  
Receptor Blockade ◽  
Lv Mass ◽  
Lv Remodeling ◽  
Fractional Shortening ◽  
Adrenergic Receptor Blockade

The low-pressure volume overload of isolated mitral regurgitation (MR) is associated with increased adrenergic drive, left ventricular (LV) dilatation, and loss of interstitial collagen. We tested the hypothesis that β1-adrenergic receptor blockade (β1-RB) would attenuate LV remodeling after 4 mo of MR in the dog. β1-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using MRI and three-dimensional (3-D) analysis, there was a 70% increase in the LV end-diastolic (LVED) volume-to-LV mass ratio, a 23% decrease in LVED midwall circumferential curvature, and a >50% increase in LVED 3-D radius/wall thickness in MR dogs that was not attenuated by β1-RB. However, β1-RB caused a significant increase in LVED length from the base to apex compared with untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171 ± 5 μm, P < 0.05) compared with normal (156 ± 3 μm) and MR (165 ± 4 μm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared with normal dogs (3.73 ± 0.31 vs. 5.02 ± 0.26%, P < 0.05) and normalized with β1-RB (4.73 ± 0.48%). In addition, stimulation with the β-adrenergic receptor agonist isoproterenol (25 nM) increased cardiomyocyte fractional shortening by 215% ( P < 0.05) in β1-RB dogs compared with normal (56%) and MR (50%) dogs. In summary, β1-RB improved LV cardiomyocyte function and β-adrenergic receptor responsiveness despite further cell elongation. The failure to attenuate LV remodeling associated with MR could be due to a failure to improve ultrastructural changes in extracellular matrix organization.

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