Nathan Mewton

Publications (34) View all

• Article: Postconditioning the Heart of ST-Elevation Myocardial Infarction Patients.

  Nathan Mewton, Thomas Bochaton, Michel Ovize
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  ABSTRACT: Over the past decade, the therapeutic strategies for acute myocardial infarction have changed considerably. Progress in experimental models, as well as noninvasive myocardial imaging techniques, has identified myocardial reperfusion injury as a significant contributor to the final infarct size in human patients. Following 3 decades devoted to the improvement of reperfusion therapy, recent major advances in myocardial protection after reperfusion slowly move the attention from the vessel to the muscle. In the past 20 years, several pharmacologic treatments or techniques applied at early reperfusion have been tested in experimental models and in the clinical setting. Numerous promising therapies in experimental models have failed to show significant benefit in the clinical realm. But to date, ischemic postconditioning applied at the onset of reperfusion is among the most promising therapies to treat reperfusion injury in myocardial infarction patients, with a 35% significant reduction of final infarct size in small groups of patients and different settings. However, clinical evidence in large population studies is still lacking for their widespread usage in the catheter laboratory at the time of reperfusion. After a brief review of the underlying molecular mechanisms of ischemic postconditioning, this review will focus on the clinical studies assessing the postconditioning effect in STEMI patients and review the findings and explore the future of this technique.
  Circulation Journal 04/2013; · 3.77 Impact Factor
• Article: Left Ventricular Global Function Index by Magnetic Resonance Imaging--A Novel Marker for Assessment of Cardiac Performance for the Prediction of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.

  Nathan Mewton, Anders Opdahl, Eui-Young Choi, Andre L C Almeida, Nadine Kawel, Colin O Wu, Gregory L Burke, Songtao Liu, Kiang Liu, David A Bluemke, Joao A C Lima
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  ABSTRACT: Left ventricular (LV) function is generally assessed independent of structural remodeling and vice versa. The purpose of this study was to evaluate a novel LV global function index (LVGFI) that integrates LV structure with global function and to assess its predictive value for cardiovascular (CV) events throughout adult life in a multiethnic population of men and women without history of CV diseases at baseline. A total of 5004 participants in the Multi-Ethnic Study of Atherosclerosis underwent a cardiac magnetic resonance study and were followed up for a median of 7.2 years. The LVGFI by cardiac magnetic resonance was defined by the ratio of stroke volume divided by LV total volume defined as the sum of mean LV cavity and myocardial volumes. Cox proportional hazard models were constructed to predict the end points of heart failure, hard CV events, and a combined end point of all CV events after adjustment for established risk factors, calcium score, and biomarkers. A total of 579 (11.6%) CV events were observed during the follow-up period. In adjusted models, the end points of heart failure, hard CV events, and all events were all significantly associated with LVGFI (heart failure, hazard ratio=0.64, P<0.0001; hard CV events, hazard ratio=0.79, P=0.007; all events, hazard ratio=0.79, P<0.0001). LVGFI had a significant independent predictive value in the multivariable models for all CV event categories. The LVGFI was a powerful predictor of incident HF, hard CV events, and a composite end point, including all events in this multiethnic cohort.
  Hypertension 02/2013; · 6.21 Impact Factor
• Article: Administration of Cardiac Stem Cells in Patients With Ischemic Cardiomyopathy: The SCIPIO Trial: Surgical Aspects and Interim Analysis of Myocardial Function and Viability by Magnetic Resonance.

  Atul R Chugh, Garth M Beache, John H Loughran, Nathan Mewton, Julius B Elmore, Jan Kajstura, Patroklos Pappas, Antone Tatooles, Marcus F Stoddard, Joao A C Lima, Mark S Slaughter, Piero Anversa, Roberto Bolli
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  ABSTRACT: SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results. A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5±1.6% to 35.1±2.4% [P=0.004, n=8] and 41.2±4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9±1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8±3.5 g [-30.2%] at 12 months [P=0.039, n=6]). LV nonviable mass decreased even more (-11.9±2.5 g [-49.7%] at 4 months [P=0.001] and -14.7±3.9 g [-58.6%] at 12 months [P=0.013]), whereas LV viable mass increased (+11.6±5.1 g at 4 months after CSC infusion [P=0.055] and +31.5±11.0 g at 12 months [P=0.035]). Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration. This study is registered with clinicaltrials.gov, trial number NCT00474461.
  Circulation 09/2012; 126(11 Suppl 1):S54-64. · 14.74 Impact Factor
• Article: Scaring myocardial scars: new targets for the electrical fairy?

  Nathan Mewton, Philippe Chevalier
  Journal of the American College of Cardiology 07/2012; 60(5):421-2. · 14.16 Impact Factor
• Source

  Available from: Michel Ovize

  Article: Cardioprotection by clopidogrel in acute ST-elevated myocardial infarction patients: a retrospective analysis.

  François Roubille, Olivier Lairez, Nathan Mewton, Gilles Rioufol, Sylvain Ranc, Ingrid Sanchez, Thien Tri Cung, Meyer Elbaz, Christophe Piot, Michel Ovize
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  ABSTRACT: Antiplatelet agents have been extensively used in acute coronary syndromes and improve clinical outcome in STEMI patients. Previous experimental studies of the impact of antiplatelet agents on infarct size have been equivoqual. We questioned whether clopidogrel might reduce infarct size in STEMI patients, independently of any antithrombotic effect, by activating a post-conditioning-like myocardial protection. We retrospectively analyzed three recent controlled, randomized, proof of concept clinical trials aimed at determining whether PCI post-conditioning might attenuated infarct size in STEMI. We addressed whether clopidogrel (300-600 mg before angioplasty) might have influenced infarct size using a multivariable linear regression analysis with infarct size as the continuous outcome variable and age, clopidogrel and GP IIb/IIIa inhibitors, post-conditioning, area at risk, ischemia time, coronary thrombectomy and final TIMI flow, as covariates. In this population of 88 STEMI patients, ischemic post-conditioning and clopidogrel administration were the only two therapeutic independent predictors of the final infarct size as determined by cardiac enzymes release (p = 0.005 and p < 0.0001, respectively) This retrospective analysis supports the proposal that clopidogrel attenuates lethal reperfusion injury.
  Archiv für Kreislaufforschung 07/2012; 107(4):275. · 7.35 Impact Factor