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Mechanisms for overestimating acute myocardial infarct size with gadolinium-enhanced cardiovascular magnetic resonance imaging in humans: a quantitative and kinetic study.

ABSTRACT: It remains controversial whether cardiovascular magnetic resonance imaging with gadolinium only enhances acutely infarcted or also salvaged myocardium. We hypothesized that enhancement of salvaged myocardium may be due to altered extracellular volume (ECV) and contrast kinetics compared with normal and infarcted myocardium. If so, these mechanisms could contribute to overestimation of acute myocardial infarction (AMI) size.Imaging was performed at 1.5T ? 7 days after AMI with serial T1 mapping and volumetric early (5 min post-contrast) and late (20 min post-contrast) gadolinium enhancement imaging. Infarcts were classified as transmural (>75% transmural extent) or non-transmural. Patients with non-transmural infarctions (n = 15) had shorter duration of symptoms before reperfusion (P = 0.02), lower peak troponin (P = 0.008), and less microvascular obstruction (P < 0.001) than patients with transmural infarcts (n = 22). The size of enhancement at 5 min was greater than at 20 min (18.7 ± 12.7 vs. 12.1 ± 7.0%, P = 0.003) in non-transmural infarctions, but similar in transmural infarctions (23.0 ± 10.0 vs. 21.9 ± 9.9%, P = 0.21). ECV of salvaged myocardium was greater than normal (39.5 ± 5.8 vs. 24.1 ± 3.1%) but less than infarcted myocardium (50.5 ± 6.0%, both P < 0.001). In kinetic studies of non-transmural infarctions, salvaged and infarcted myocardium had similar T1 at 4 min but different T1 at 8-20 min post-contrast.The extent of gadolinium enhancement in AMI is modulated by ECV and contrast kinetics. Image acquisition too early after contrast administration resulted in overestimation of infarct size in non-transmural infarctions due to enhancement of salvaged myocardium.

SUBMITTER: Hammer-Hansen S

PROVIDER: S-EPMC4684160 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Mechanisms for overestimating acute myocardial infarct size with gadolinium-enhanced cardiovascular magnetic resonance imaging in humans: a quantitative and kinetic study.

Hammer-Hansen Sophia S Bandettini W Patricia WP Hsu Li-Yueh LY Leung Steve W SW Shanbhag Sujata S Mancini Christine C Greve Anders M AM Køber Lars L Thune Jens Jakob JJ Kellman Peter P Arai Andrew E AE

European heart journal. Cardiovascular Imaging 20150516 1

<h4>Aims</h4>It remains controversial whether cardiovascular magnetic resonance imaging with gadolinium only enhances acutely infarcted or also salvaged myocardium. We hypothesized that enhancement of salvaged myocardium may be due to altered extracellular volume (ECV) and contrast kinetics compared with normal and infarcted myocardium. If so, these mechanisms could contribute to overestimation of acute myocardial infarction (AMI) size.<h4>Methods and results</h4>Imaging was performed at 1.5T ≤ ...[more]

PMID: 25983233

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Project description:AimsThe heart rejuvenating effects of circulating growth differentiation factor 11 (GDF11), a transforming growth factor-β superfamily member that shares 90% homology with myostatin (MSTN), remains controversial. Here, we aimed to probe the role of GDF11 in acute myocardial infarction (MI), a frequent cause of heart failure and premature death during ageing.Methods and resultsIn contrast to endogenous Mstn, myocardial Gdf11 declined during the course of ageing and was particularly reduced following ischaemia/reperfusion (I/R) injury, suggesting a therapeutic potential of GDF11 signalling in MI. Unexpectedly, boosting systemic Gdf11 by recombinant GDF11 delivery (0.1 mg/kg body weight over 30 days) prior to myocardial I/R augmented myocardial infarct size in C57BL/6 mice irrespective of their age, predominantly by accelerating pro-apoptotic signalling. While intrinsic cardioprotective signalling pathways remained unaffected by high circulating GDF11, targeted transcriptomics and immunomapping studies focusing on GDF11-associated downstream targets revealed attenuated Nkx2-5 expression confined to CD105-expressing cells, with pro-apoptotic activity, as assessed by caspase-3 levels, being particularly pronounced in adjacent cells, suggesting an indirect effect. By harnessing a highly specific and validated liquid chromatography-tandem mass spectrometry-based assay, we show that in prospectively recruited patients with MI circulating GDF11 but not MSTN levels incline with age. Moreover, GDF11 levels were particularly elevated in those at high risk for adverse outcomes following the acute event, with circulating GDF11 emerging as an independent predictor of myocardial infarct size, as estimated by standardized peak creatine kinase-MB levels.ConclusionOur data challenge the initially reported heart rejuvenating effects of circulating GDF11 and suggest that high levels of systemic GDF11 exacerbate myocardial injury in mice and humans alike. Persistently high GDF11 levels during ageing may contribute to the age-dependent loss of cardioprotective mechanisms and thus poor outcomes of elderly patients following acute MI.

Project description:Infarct size is a major prognostic factor in ST-segment elevation myocardial infarction (STEMI). It is often assessed using repeated blood sampling and the estimation of biomarker area under the concentration versus time curve (AUC) in translational research. We aimed at developing limited sampling strategies (LSS) to accurately estimate biomarker AUC using only a limited number of blood samples in STEMI patients. This retrospective study was carried out on pooled data from five clinical trials of STEMI patients (TIMI blood flow 0/1) studies where repeated blood samples were collected within 72 h after admission to assess creatine kinase (CK), cardiac troponin I (cTnI) and muscle-brain CK (CK-MB). Biomarker kinetics was assessed using previously described biomarker kinetic models. A number of LSS models including combinations of 1 to 3 samples were developed to identify sampling times leading to the best estimation of AUC. Patients were randomly assigned to either learning (2/3) or validation (1/3) subsets. Descriptive and predictive performances of LSS models were compared using learning and validation subsets, respectively. An external validation cohort was used to validate the model and its applicability to different cTnI assays, including high-sensitive (hs) cTnI. 132 patients had full CK and cTnI dataset, 49 patients had CK-MB. For each biomarker, 180 LSS models were tested. Best LSS models were obtained for the following sampling times: T4-16 for CK, T8-T20 for cTnI and T8-T16 for CK-MB for 2-sample LSS; and T4-T16-T24 for CK, T4-T12-T20 for cTnI and T8-T16-T20 for CK-MB for 3-sample LSS. External validation was achieved on 103 anterior STEMI patients (TIMI flow 0/1), and the cTnI model applicability to recommended hs cTnI confirmed. Biomarker kinetics can be assessed with a limited number of samples using kinetic modelling. This opens the way for substantial simplification of future cardioprotection studies, more acceptable for the patients.

Project description:BACKGROUND:Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). METHODS:STEMI patients underwent 3?T cardiovascular magnetic resonance (CMR), within 3?h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3?h was compared with changes at 24-h to predict final infarct size. RESULTS:Forty patients were included in this study. Patients with average T1 values of AAR ?1400?ms within 3?h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P?=?0.003) and at 6-months (27% ±9 vs. 12% ±9; P?<?0.001), higher incidence and larger extent of MVO (85% vs. 40%, P?=?0.016) & [4.0 (0.5-9.5)% vs. 0 (0-3.0)%, P?=?0.025]. The average T1 value was an independent predictor of acute LGE (? 0.61, 95%CI 0.13 to 1.09; P?=?0.015), extent of MVO (? 0.22, 95%CI 0.03 to 0.41, P?=?0.028) and final infarct size (? 0.63, 95%CI 0.21 to 1.05; P?=?0.005). Receiver-operating-characteristic analysis showed that T1 value of AAR obtained within 3-h, but not at 24-h, predicted large infarct size (LGE >?9.5%) with 100% positive predictive value at the optimal cut-off of 1400?ms (area-under-the-curve, AUC 0.88, P?=?0.006). CONCLUSION:Hyper-acute T1 values of the AAR (within 3?h post PPCI, but not 24?h) predict a larger extent of MVO and infarct size at both 24?h and 6?months follow-up. Delayed CMR scanning for 24?h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics.

Project description:Background Despite optimized medical management and techniques of primary percutaneous coronary intervention, a substantial proportion of patients with ST-segment-elevation myocardial infarction (STEMI) display significant microvascular damage. Thrombotic microvascular obstruction (MVO) has been implicated in the pathogenesis of microvascular and subsequent myocardial damage attributed to distal embolization and microvascular platelet plugging. However, there are only scarce data regarding the effect of platelet reactivity on MVO. Methods and Results We prospectively evaluated 105 patients in 2 distinct periods (2012-2013 and 2016-2018) who presented with first ST-segment-elevation myocardial infarction and underwent primary percutaneous coronary intervention. All patients were treated with dual antiplatelet therapy (DAPT). Blood samples were analyzed for platelet reactivity, and cardiac magnetic resonance imaging scans were evaluated for late gadolinium enhancement and MVO. DAPT suboptimal response was defined as hyporesponsiveness to either aspirin or P2Y12 receptor inhibitor agents and demonstrated in 31 patients (29.5%) of the current cohort. Suboptimal platelet response to DAPT was associated with a significantly greater extent of MVO when expressed as a percentage of the left ventricular mass, left ventricular scar, and the number of myocardial left ventricular segments showing MVO (P<0.01 for each). Adjusted multivariable logistic regression model revealed that suboptimal response to DAPT is significantly associated with both greater late gadolinium enhancement (P<0.01) and MVO extent (odds ratio, 3.7 [95% CI, 1.3-10.5]; P=0.01). Patients with a greater extent of MVO were more likely to sustain major adverse cardiovascular events at a 1-year follow-up (37% versus 11%; P<0.01). Conclusions In patients undergoing primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, platelet reactivity in response to DAPT is a key predictor of the extent of both myocardial and microvascular damage.

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Mechanisms for overestimating acute myocardial infarct size with gadolinium-enhanced cardiovascular magnetic resonance imaging in humans: a quantitative and kinetic study.

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Mechanisms for overestimating acute myocardial infarct size with gadolinium-enhanced cardiovascular magnetic resonance imaging in humans: a quantitative and kinetic study.

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