Dataset Information

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial.

ABSTRACT:

Rationale

Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear.

Objective

The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction.

Methods and results

This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac MRI. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31(+) BMCs (P=0.046) and in those with faster BMC growth rates in colony-forming unit Hill and endothelial-colony forming cell functional assays (P=0.033 and P=0.032, respectively).

Conclusions

This study identified BMC characteristics associated with a better clinical outcome in patients with segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation.

Clinical trial registration information url

http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

SUBMITTER: Schutt RC

PROVIDER: S-EPMC4282599 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Publications

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial.

Schutt Robert C RC Trachtenberg Barry H BH Cooke John P JP Traverse Jay H JH Henry Timothy D TD Pepine Carl J CJ Willerson James T JT Perin Emerson C EC Ellis Stephen G SG Zhao David X M DX Bhatnagar Aruni A Johnstone Brian H BH Lai Dejian D Resende Micheline M Ebert Ray F RF Wu Joseph C JC Sayre Shelly L SL Orozco Aaron A Zierold Claudia C Simari Robert D RD Moyé Lem L Cogle Christopher R CR Taylor Doris A DA

Circulation research 20141118 1

<h4>Rationale</h4>Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear.<h4>Objective</h4>The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction.<h4>Methods and results</h ...[more]

PMID: 25406300

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Project description:BackgroundThe relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients.Methods and resultsIn 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p ≤ 0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p < 0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p ≤ 0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p < 0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p = 0.012). No such observations were encountered for MPO-DNA.ConclusionsHigh day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008)).

Project description:PurposeThe hematopoietically active tissues of skeletal bone marrow are a prime target for computational dosimetry given potential risks of leukemia and, at higher dose levels, acute marrow toxicity. The complex three-dimensional geometry of trabecular spongiosa, however, complicates schema for dose assessment in such a way that only a few reference skeletal models have been developed to date, and which are based upon microimaging of a limited number of cadaveric bone spongiosa cores. The question then arises as to what degree of accuracy is achievable from reference skeletal dose models when applied to individual patients or specific exposed populations?MethodsPatient variability in marrow dosimetry were quantified for three skeletal sites - the ribs, lumbar vertebrae, and cranium - for the beta-emitters 45 Ca, 153 Sm, and 90 Y, and the alpha-particle emitters 223 Ra, 219 Rn, and 215 Po, the latter two being the immediate progeny of the former. For each radionuclide and bone site, three patient parameters were altered from their values in the reference model: (1) bone size as a surrogate for patient stature, (2) marrow cellularity as a surrogate for age- or disease-related changes in marrow adiposity, and (3) the trabecular bone volume fraction as a surrogate for bone mineral density. Marrow dose variability is expressed as percent differences in the radionuclide S value given by the reference model and the patient-parameterized model. The impact of radionuclide biokinetics on marrow dosimetry was not considered.ResultsVariations in overall bone size play a very minor role in active marrow dose variability. Marrow cellularity is a significant factor in dose variability for active marrow self-irradiation, but it plays no role for radionuclides localized to the trabecular bone matrix. Variations in trabecular bone volume fractions impact the active marrow dose variability for short-range particle emitters 45 Ca, 223 Ra, 219 Rn, and 215 Po in the vertebrae and ribs, skeletal sites with small spongiosa proportions of trabecular bone. In the cranium, with its relative high proportion of trabecular bone, significant differences in marrow dosimetry from the reference model were noted for all radionuclides.ConclusionsSkeletal models of active marrow dosimetry should be more fully parameterized to permit closer matching to patient bone density and marrow cellularity, particularly when considering short-range particle emitters localized to either the bone trabeculae or active marrow, respectively.

Dataset Information

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial.

Rationale

Objective

Methods and results

Conclusions

Clinical trial registration information url

Publications

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial.

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