RESUMO
Sudden blockage of arteries supplying the heart muscle contributes to millions of heart attacks (myocardial infarction, MI) around the world. Although re-opening these arteries (reperfusion) saves MI patients from immediate death, approximately 50% of these patients go on to develop chronic heart failure (CHF) and die within a 5-year period; however, why some patients accelerate towards CHF while others do not remains unclear. Here we show, using large animal models of reperfused MI, that intramyocardial hemorrhage - the most damaging form of reperfusion injury (evident in nearly 40% of reperfused ST-elevation MI patients) - drives delayed infarct healing and is centrally responsible for continuous fatty degeneration of the infarcted myocardium contributing to adverse remodeling of the heart. Specifically, we show that the fatty degeneration of the hemorrhagic MI zone stems from iron-induced macrophage activation, lipid peroxidation, foam cell formation, ceroid production, foam cell apoptosis and iron recycling. We also demonstrate that timely reduction of iron within the hemorrhagic MI zone reduces fatty infiltration and directs the heart towards favorable remodeling. Collectively, our findings elucidate why some, but not all, MIs are destined to CHF and help define a potential therapeutic strategy to mitigate post-MI CHF independent of MI size.
Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Animais , Miocárdio , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Hemorragia , Coração , Insuficiência Cardíaca/etiologia , Ferro , Remodelação Ventricular , Modelos Animais de DoençasRESUMO
BACKGROUND: Preclinical studies and pilot patient studies have shown that chronic infarctions can be detected and characterized from cardiac magnetic resonance without gadolinium-based contrast agents using native-T1 maps at 3T. We aimed to investigate the diagnostic capacity of this approach for characterizing chronic myocardial infarctions (MIs) in a multi-center setting. METHODS: Patients with a prior MI (n=105) were recruited at 3 different medical centers and were imaged with native-T1 mapping and late gadolinium enhancement (LGE) at 3T. Infarct location, size, and transmurality were determined from native-T1 maps and LGE. Sensitivity, specificity, receiver-operating characteristic metrics, and inter- and intraobserver variabilities were assessed relative to LGE. RESULTS: Across all subjects, T1 of MI territory was 1621±110 ms, and remote territory was 1225±75 ms. Sensitivity, specificity, and area under curve for detecting MI location based on native-T1 mapping relative to LGE were 88%, 92%, and 0.93, respectively. Native-T1 maps were not different for measuring infarct size (native-T1 maps: 12.1±7.5%; LGE: 11.8±7.2%, P=0.82) and were in agreement with LGE (R2=0.92, bias, 0.09±2.6%). Corresponding inter- and intraobserver assessments were also highly correlated (interobserver: R2=0.90, bias, 0.18±2.4%; and intraobserver: R2=0.91, bias, 0.28±2.1%). Native T1 maps were not different for measuring MI transmurality (native-T1 maps: 49.1±15.8%; LGE: 47.2±19.0%, P=0.56) and showed agreement (R2=0.71; bias, 1.32±10.2%). Corresponding inter- and intraobserver assessments were also in agreement (interobserver: R2=0.81, bias, 0.1±9.4%; and intraobserver: R2=0.91, bias, 0.28±2.1%, respectively). While the overall accuracy for detecting MI with native-T1 maps at 3T was high, logistic regression analysis showed that MI location was a prominent confounder. CONCLUSIONS: Native-T1 mapping can be used to image chronic MI with high degree of accuracy, and as such, it is a viable alternative for scar imaging in patients with chronic MI who are contraindicated for LGE. Technical advancements may be needed to overcome the imaging confounders that currently limit native-T1 mapping from reaching equivalent detection levels as LGE.
Assuntos
Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/patologia , Idoso , China , Doença Crônica , Meios de Contraste/administração & dosagem , Feminino , Humanos , Los Angeles , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Variações Dependentes do Observador , Compostos Organometálicos/administração & dosagem , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Seul , Fatores de TempoRESUMO
OBJECTIVES: This study sought to determine whether T2 cardiac magnetic resonance (CMR) can stage both hemorrhagic and nonhemorrhagic myocardial infarctions (MIs). BACKGROUND: CMR-based staging of MI with or without contrast agents relies on the resolution of T2 elevations in the chronic phase, but whether this approach can be used to stage both hemorrhagic and nonhemorrhagic MIs is unclear. METHODS: Hemorrhagic (n = 15) and nonhemorrhagic (n = 9) MIs were created in dogs. Multiparametric noncontrast mapping (T1, T2, and T2*) and late gadolinium enhancement (LGE) were performed at 1.5- and 3.0-T at 5 days (acute) and 8 weeks (chronic) post-MI. CMR relaxation values and LGE intensities of hemorrhagic, peri-hemorrhagic, nonhemorrhagic, and remote territories were measured. Histopathology was performed to elucidate CMR findings. RESULTS: T2 of nonhemorrhagic MIs was significantly elevated in the acute phase relative to remote territories (1.5-T: 39.8 ± 12.8%; 3.0-T: 27.9 ± 16.5%; p < 0.0001 for both) but resolved to remote values by week 8 (1.5-T: -0.0 ± 3.2%; p = 0.678; 3.0-T: -0.5 ± 5.9%; p = 0.601). In hemorrhagic MI, T2 of hemorrhage core was significantly elevated in the acute phase (1.5-T: 17.7 ± 10.0%; 3.0-T: 8.6 ± 8.2%; p < 0.0001 for both) but decreased below remote values by week 8 (1.5-T: -8.2 ± 3.9%; 3.0-T: -5.6 ± 6.0%; p < 0.0001 for both). In contrast, T2 of the periphery of hemorrhage within the MI zone was significantly elevated in the acute phase relative to remote territories (1.5-T: 35.0 ± 16.1%; 3.0-T: 24.2 ± 10.4%; p < 0.0001 for both) and remained elevated at 8 weeks post-MI (1.5-T: 8.6 ± 5.1%; 3.0-T: 6.0 ± 3.3%; p < 0.0001 for both). The observed elevation of T2 in the peri-hemorrhagic zone of MIs and the absence of T2 elevation in nonhemorrhagic MIs were consistent with ongoing or absence of histological evidence of inflammation, respectively. CONCLUSIONS: Hemorrhagic MIs are associated with persisting myocardial inflammation and edema, which can confound staging of hemorrhagic MIs when T2 elevations alone are used to discriminate between acute and chronic MI. Moreover, given the poor prognosis in patients with hemorrhagic MI, CMR evidence for myocardial hemorrhage with persistent edema may evolve as a risk marker in patients after acute MI.
Assuntos
Hemorragia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Animais , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Cães , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Valor Preditivo dos TestesRESUMO
Myocardial blood flow (MBF) is the critical determinant of cardiac function. However, its response to increases in partial pressure of arterial CO2 (PaCO2), particularly with respect to adenosine, is not well characterized because of challenges in blood gas control and limited availability of validated approaches to ascertain MBF in vivo. Methods: By prospectively and independently controlling PaCO2 and combining it with 13N-ammonia PET measurements, we investigated whether a physiologically tolerable hypercapnic stimulus (â¼25 mm Hg increase in PaCO2) can increase MBF to that observed with adenosine in 3 groups of canines: without coronary stenosis, subjected to non-flow-limiting coronary stenosis, and after preadministration of caffeine. The extent of effect on MBF due to hypercapnia was compared with adenosine. Results: In the absence of stenosis, mean MBF under hypercapnia was 2.1 ± 0.9 mL/min/g and adenosine was 2.2 ± 1.1 mL/min/g; these were significantly higher than at rest (0.9 ± 0.5 mL/min/g, P < 0.05) and were not different from each other (P = 0.30). Under left-anterior descending coronary stenosis, MBF increased in response to hypercapnia and adenosine (P < 0.05, all territories), but the effect was significantly lower than in the left-anterior descending coronary territory (with hypercapnia and adenosine; both P < 0.05). Mean perfusion defect volumes measured with adenosine and hypercapnia were significantly correlated (R = 0.85) and were not different (P = 0.12). After preadministration of caffeine, a known inhibitor of adenosine, resting MBF decreased; and hypercapnia increased MBF but not adenosine (P < 0.05). Conclusion: Arterial blood CO2 tension when increased by 25 mm Hg can induce MBF to the same level as a standard dose of adenosine. Prospectively targeted arterial CO2 has the capability to evolve as an alternative to current pharmacologic vasodilators used for cardiac stress testing.
Assuntos
Adenosina/administração & dosagem , Dióxido de Carbono/sangue , Estenose Coronária/sangue , Estenose Coronária/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Animais , Cães , Teste de Esforço/métodos , Imagem Multimodal/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , VasodilatadoresRESUMO
BACKGROUND: Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resolves into chronic iron crystals within MI territories, which in turn are proinflammatory and favor adverse remodeling post-MI. METHODS AND RESULTS: Canines (n=40) were studied with cardiac magnetic resonance imaging to characterize the spatiotemporal relationships among PMO, iron deposition, infarct resorption, and left ventricular remodeling between day 7 (acute) and week 8 (chronic) post-MI. Histology was used to assess iron deposition and to examine relationships between iron content with macrophage infiltration, proinflammatory cytokine synthesis, and matrix metalloproteinase activation. Atomic resolution transmission electron microscopy was used to determine iron crystallinity, and energy-dispersive X-ray spectroscopy was used to identify the chemical composition of the iron composite. PMO with or without reperfusion hemorrhage led to chronic iron deposition, and the extent of this deposition was strongly related to PMO volume (r>0.8). Iron deposits were found within macrophages as aggregates of nanocrystals (≈2.5 nm diameter) in the ferric state. Extent of iron deposits was strongly correlated with proinflammatory burden, collagen-degrading enzyme activity, infarct resorption, and adverse structural remodeling (r>0.5). CONCLUSIONS: Crystallized iron deposition from PMO is directly related to proinflammatory burden, infarct resorption, and adverse left ventricular remodeling in the chronic phase of MI in canines. Therapeutic strategies to combat adverse remodeling could potentially benefit from taking into account the chronic iron-driven inflammatory process.
Assuntos
Circulação Coronária , Compostos Férricos/metabolismo , Mediadores da Inflamação/metabolismo , Microcirculação , Infarto do Miocárdio/complicações , Traumatismo por Reperfusão Miocárdica/etiologia , Miocárdio/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Cristalização , Modelos Animais de Doenças , Cães , Macrófagos/metabolismo , Macrófagos/patologia , Imageamento por Ressonância Magnética , Microscopia Eletrônica de Transmissão , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Espectrometria por Raios X , Fatores de TempoRESUMO
PURPOSE: To develop and test a time-efficient, free-breathing, whole heart T2 mapping technique at 3.0T. METHODS: ECG-triggered three-dimensional (3D) images were acquired with different T2 preparations at 3.0T during free breathing. Respiratory motion was corrected with a navigator-guided motion correction framework at near perfect efficiency. Image intensities were fit to a monoexponential function to derive myocardial T2 maps. The proposed 3D, free breathing, motion-corrected (3D-FB-MoCo) approach was studied in ex vivo canine hearts and kidneys, healthy volunteers, and canine subjects with acute myocardial infarction (AMI). RESULTS: Ex vivo T2 values from proposed 3D T2 -prep gradient echo were not different from two-dimensional (2D) spin echo (P = 0.7) and T2 -prep balanced steady-state free precession (bSSFP) (P = 0.7). In healthy volunteers, compared with 3D-FB-MoCo and breath-held 2D T2 -prep bSSFP (2D-BH), non-motion-corrected (3D-FB-Non-MoCo) myocardial T2 was longer, had a larger coefficient of variation (COV), and had a lower image quality (IQ) score (T2 = 40.3 ms, COV = 38%, and IQ = 2.3; all P < 0.05). Conversely, the mean and COV and IQ of 3D-FB-MoCo (T2 = 37.7 ms, COV = 17%, and IQ = 3.5) and 2D-BH (T2 = 38.0 ms, COV = 15%, and IQ = 3.8) were not different (P = 0.99, P = 0.74, and P = 0.14, respectively). In AMI, T2 values and edema volumes from 3D-FB-MoCo and 2D-BH were closely correlated (R(2) = 0.88 and 0.96, respectively). CONCLUSION: The proposed whole heart T2 mapping approach can be performed within 5 min with similar accuracy to that of the 2D-BH T2 mapping approach.
Assuntos
Artefatos , Técnicas de Imagem de Sincronização Cardíaca/métodos , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Algoritmos , Animais , Cães , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Movimento (Física) , Infarto do Miocárdio/patologia , Mecânica RespiratóriaRESUMO
OBJECTIVES: The purpose of this study was to investigate whether native T1 maps at 3-T can reliably characterize chronic myocardial infarctions (MIs) in patients with prior ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: Late gadolinium enhancement (LGE) cardiac magnetic resonance is the gold standard for characterizing chronic MIs, but it is contraindicated in patients with end-stage chronic kidney disease. METHODS: Native T1 and LGE images were acquired at 3-T in patients with prior STEMI (n = 13) and NSTEMI (n = 12) at a median of 13.6 years post-MI. Infarct location, size, and transmurality were measured using mean ± 5 SDs thresholding criterion from LGE images and T1 maps and compared against one another. Independent reviewers assessed visual conspicuity of MIs on LGE images and T1 maps. RESULTS: Native T1 maps and LGE images were not different for measuring infarct size (STEMI: p = 0.46; NSTEMI: p = 0.27) and transmurality (STEMI: p = 0.13; NSTEMI: p = 0.21) using thresholding criterion. Using thresholding criterion, good agreement was observed between LGE images and T1 maps for measuring infarct size (STEMI: bias = 0.6 ± 3.1%; R(2) = 0.93; NSTEMI: bias = -0.4 ± 4.4%; R(2) = 0.85) and transmurality (STEMI: bias = 2.0 ± 4.2%; R(2) = 0.89; NSTEMI: bias = -2.7 ± 7.9%; R(2) = 0.68). Sensitivity and specificity of T1 maps for detecting chronic MIs based on thresholding criterion were 89% and 98%, respectively (STEMI), and 87% and 95%, respectively (NSTEMI). Relative to LGE images, the mean visual conspicuity score for detecting chronic MIs was significantly lower for T1 maps (p < 0.001 for both cases). Median infarct-to-remote myocardium contrast-to-noise ratio was 2.5-fold higher for LGE images relative to T1 maps (p < 0.001). Sensitivity and specificity of T1 maps for visual detection were 60% and 86%, respectively (STEMI), and 64% and 91% (NSTEMI), respectively. CONCLUSIONS: Chronic MIs in STEMI and NSTEMI patients can be reliably characterized using threshold-based detection on native T1 maps at 3-T. Visual detection of chronic MIs on native T1 maps in both patient populations has high specificity, but modest sensitivity.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico , Miocárdio/patologia , Idoso , Doença Crônica , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Variações Dependentes do Observador , Compostos Organometálicos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
BACKGROUND: Recent canines studies have shown that iron deposition within chronic myocardial infarction (CMI) influences the electric behavior of the heart. To date, the link between the iron deposition and malignant ventricular arrhythmias in humans with CMI is unknown. METHODS AND RESULTS: Patients with CMI (n=94) who underwent late-gadolinium-enhanced cardiac magnetic resonance imaging before implantable cardioverter-defibrillator implantation for primary and secondary preventions were retrospectively analyzed. The predictive values of hypointense cores (HIC) in balanced steady-state free precession images and conventional cardiac magnetic resonance imaging and ECG malignant ventricular arrhythmia parameters for the prediction of primary combined outcome (appropriate implantable cardioverter-defibrillator therapy, survived cardiac arrest, or sudden cardiac death) were studied. The use of HIC within CMI on balanced steady-state free precession as a marker of iron deposition was validated in a canine MI model (n=18). Nineteen patients met the study criteria with events occurring at a median of 249 (interquartile range of 540) days after implantable cardioverter-defibrillator placement. Of the 19 patients meeting the primary end point, 18 were classified as HIC+, whereas only 1 was HIC-. Among the cohort in whom the primary end point was not met, there were 28 HIC+ and 47 HIC- patients. Receiver operating characteristic curve analysis demonstrated an additive predictive value of HIC for malignant ventricular arrhythmias with an increased area under the curve of 0.87 when added to left ventricular ejection fraction (left ventricular ejection fraction alone, 0.68). Both cardiac magnetic resonance imaging and histological validation studies performed in canines demonstrated that HIC regions in balanced steady-state free precession images within CMI likely result from iron depositions. CONCLUSIONS: Hypointense cores within CMI on balanced steady-state free precession cardiac magnetic resonance imaging can be used as a marker of iron deposition and yields incremental information toward improved prediction of malignant ventricular arrhythmias.
Assuntos
Ferro/metabolismo , Imageamento por Ressonância Magnética , Infarto do Miocárdio/complicações , Miocárdio/metabolismo , Taquicardia Ventricular/etiologia , Fibrilação Ventricular/etiologia , Idoso , Animais , Área Sob a Curva , Meios de Contraste , Desfibriladores Implantáveis , Cães , Cardioversão Elétrica/instrumentação , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Compostos Organometálicos , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/prevenção & controle , Fatores de Tempo , Resultado do Tratamento , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/prevenção & controle , Função Ventricular EsquerdaRESUMO
BACKGROUND: Endocardial mapping for scars and abnormal electrograms forms the most essential component of ventricular tachycardia ablation. The utility of ultra-high resolution mapping of ventricular scar was assessed using a multielectrode contact mapping system in a chronic canine infarct model. METHODS: Chronic infarcts were created in five anesthetized dogs by ligating the left anterior descending coronary artery. Late gadolinium-enhanced magnetic resonance imaging (LGE MRI) was obtained 4.9 ± 0.9 months after infarction, with three-dimensional (3D) gadolinium enhancement signal intensity maps at 1-mm and 5-mm depths from the endocardium. Ultra-high resolution electroanatomical maps were created using a novel mapping system (Rhythmia Mapping System, Rhythmia Medical/Boston Scientific, Marlborough, MA, USA) Rhythmia Medical, Boston Scientific, Marlborough, MA, USA with an 8.5F catheter with mini-basket electrode array (64 tiny electrodes, 2.5-mm spacing, center-to-center). RESULTS: The maps contained 7,754 ± 1,960 electrograms per animal with a mean resolution of 2.8 ± 0.6 mm. Low bipolar voltage (<2 mV) correlated closely with scar on the LGE MRI and the 3D signal intensity map (1-mm depth). The scar areas between the MRI signal intensity map and electroanatomic map matched at 87.7% of sites. Bipolar and unipolar voltages, compared in 592 electrograms from four MRI-defined scar types (endocardial scar, epicardial scar, mottled transmural scar, and dense transmural scar) as well as normal tissue, were significantly different. A unipolar voltage of <13 mV correlated with transmural extension of scar in MRI. Electrograms exhibiting isolated late potentials (ILPs) were manually annotated and ILP maps were created showing ILP location and timing. ILPs were identified in 203 ± 159 electrograms per dog (within low-voltage areas) and ILP maps showed gradation in timing of ILPs at different locations in the scar. CONCLUSIONS: Ultra-high resolution contact electroanatomical mapping accurately localizes ventricular scar and abnormal myocardial tissue in this chronic canine infarct model. The high fidelity electrograms provided clear identification of the very low amplitude ILPs within the scar tissue and has the potential to quickly identify targets for ablation.
Assuntos
Técnicas de Imagem de Sincronização Cardíaca/métodos , Cicatriz/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Animais , Meios de Contraste , Modelos Animais de Doenças , Cães , Eletrocardiografia , Gadolínio DTPA , Processamento de Imagem Assistida por ComputadorRESUMO
PURPOSE: To examine whether controlled and tolerable levels of hypercapnia may be an alternative to adenosine, a routinely used coronary vasodilator, in healthy human subjects and animals. MATERIALS AND METHODS: Human studies were approved by the institutional review board and were HIPAA compliant. Eighteen subjects had end-tidal partial pressure of carbon dioxide (PetCO2) increased by 10 mm Hg, and myocardial perfusion was monitored with myocardial blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. Animal studies were approved by the institutional animal care and use committee. Anesthetized canines with (n = 7) and without (n = 7) induced stenosis of the left anterior descending artery (LAD) underwent vasodilator challenges with hypercapnia and adenosine. LAD coronary blood flow velocity and free-breathing myocardial BOLD MR responses were measured at each intervention. Appropriate statistical tests were performed to evaluate measured quantitative changes in all parameters of interest in response to changes in partial pressure of carbon dioxide. RESULTS: Changes in myocardial BOLD MR signal were equivalent to reported changes with adenosine (11.2% ± 10.6 [hypercapnia, 10 mm Hg] vs 12% ± 12.3 [adenosine]; P = .75). In intact canines, there was a sigmoidal relationship between BOLD MR response and PetCO2 with most of the response occurring over a 10 mm Hg span. BOLD MR (17% ± 14 [hypercapnia] vs 14% ± 24 [adenosine]; P = .80) and coronary blood flow velocity (21% ± 16 [hypercapnia] vs 26% ± 27 [adenosine]; P > .99) responses were similar to that of adenosine infusion. BOLD MR signal changes in canines with LAD stenosis during hypercapnia and adenosine infusion were not different (1% ± 4 [hypercapnia] vs 6% ± 4 [adenosine]; P = .12). CONCLUSION: Free-breathing T2-prepared myocardial BOLD MR imaging showed that hypercapnia of 10 mm Hg may provide a cardiac hyperemic stimulus similar to adenosine.
Assuntos
Circulação Coronária/fisiologia , Hipercapnia/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Adenosina/farmacologia , Animais , Cães , Eletrocardiografia , Humanos , Aumento da Imagem/métodos , Oximetria , Reprodutibilidade dos Testes , Vasodilatadores/farmacologiaRESUMO
BACKGROUND: Late-gadolinium-enhanced (LGE) cardiac MRI (CMR) is a powerful method for characterizing myocardial infarction (MI), but the requisite gadolinium infusion is estimated to be contraindicated in ≈20% of patients with MI because of end-stage chronic kidney disease. The purpose of this study is to investigate whether T1 CMR obtained without contrast agents at 3 T could be an alternative to LGE CMR for characterizing chronic MIs using a canine model of MI. METHODS AND RESULTS: Canines (n=29) underwent CMR at 7 days (acute MI [AMI]) and 4 months (chronic MI [CMI]) after MI. Infarct location, size, and transmurality measured by using native T1 maps and LGE images at 1.5 T and 3 T were compared. Resolution of edema between AMI and CMI was examined with T2 maps. T1 maps overestimated infarct size and transmurality relative to LGE images in AMI (P=0.016 and P=0.007, respectively), which was not observed in CMI (P=0.49 and P=0.81, respectively) at 3 T. T1 maps underestimated infarct size and transmurality relative to LGE images in AMI and CMI (P<0.001) at 1.5 T. Relative to the remote territories, T1 of the infarcted myocardium was increased in CMI and AMI (P<0.05), and T2 of the infarcted myocardium was increased in AMI (P<0.001) but not in CMI (P>0.20) at both field strengths. Histology showed extensive replacement fibrosis within the CMI territories. CMI detection sensitivity and specificity of T1 CMR at 3 T were 95% and 97%, respectively. CONCLUSIONS: Native T1 maps at 3 T can determine the location, size, and transmurality of CMI with high diagnostic accuracy. Patient studies are necessary for clinical translation.
Assuntos
Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico , Animais , Doença Crônica , Modelos Animais de Doenças , Cães , Seguimentos , Gadolínio DTPA , Processamento de Imagem Assistida por Computador/métodos , Magnetismo , Infarto do Miocárdio/patologia , Miocárdio , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
PURPOSE: Iron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. METHODS: Two groups of dogs (ex-vivo (n = 12) and in-vivo (n = 10)) were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity ([Formula: see text]) and conductivity ([Formula: see text]). Mass spectrometry was used to classify and characterize tissue sections with (IRON+) and without (IRON-) iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR) for estimation of scar volume (late-gadolinium enhancement, LGE) and iron deposition (T2*) relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR), QT interval (QT), QT corrected for HR (QTc) and QTc dispersion (QTcd). In a fraction of these animals (n = 5), ultra-high resolution electroanatomical mapping (EAM) was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs). RESULTS: Compared to IRON- sections, IRON+ sections had higher[Formula: see text], but no difference in[Formula: see text]. A linear relationship was found between iron content and [Formula: see text] (p<0.001), but not [Formula: see text] (p = 0.34). Among two groups of animals (Iron (<1.5%) and Iron (>1.5%)) with similar scar volumes (7.28% ± 1.02% (Iron (<1.5%)) vs 8.35% ± 2.98% (Iron (>1.5%)), p = 0.51) but markedly different iron volumes (1.12% ± 0.64% (Iron (<1.5%)) vs 2.47% ± 0.64% (Iron (>1.5%)), p = 0.02), QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05). EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron. CONCLUSION: The electrical behavior of infarcted hearts with iron appears to be different from those without iron. Iron within infarcted zones may evolve as an arrhythmogenic substrate in the post MI period.
Assuntos
Ferro/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Animais , Cães , Capacitância Elétrica , Eletrocardiografia , Sistema de Condução Cardíaco , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: To evaluate T2 and T2* changes in acute reperfused hemorrhagic and nonhemorrhagic myocardial infarctions and to determine which technique is more suitable in the detection of intramyocardial hemorrhage at 1.5 T. MATERIALS AND METHODS: Patient studies were approved by the institutional review board and were HIPAA compliant. Patients (n = 14, three women) with first ST-elevation myocardial infarction underwent cardiac magnetic resonance (MR) imaging 3 days after angioplasty. T2* maps, T2 short inversion time inversion-recovery (STIR) images, and late gadolinium enhancement (LGE) images were acquired. Animal studies were approved by the institutional animal care and use committee. Canines (n = 20) were subjected to ischemia-reperfusion injury, and cardiac MR imaging was performed 5 days after reperfusion. T2* and T2 maps and T2 STIR and LGE images were acquired. Repeated-measures analysis of variance or the Friedman test was used to compare T2 and T2* changes in patients with hemorrhagic infarctions and those with nonhemorrhagic infarctions. RESULTS: Relative to remote myocardium, mean T2* of hemorrhagic infarctions was 54% ± 13 (standard deviation) lower in patients (15.9 msec ± 4.5 vs 35.2 msec ± 2.1, P < .001) and 40% ± 10 lower in canines (23.0 msec ± 4.0 vs 39.3 msec ± 2.5, P < .001). Mean T2* of nonhemorrhagic infarctions was marginally elevated by 6% ± 2.5 (37.8 msec ± 2.5, P = .021) in patients and by 8% ± 5 (44.6 msec ± 4.8, P = .012) in canines. In contrast, mean T2 STIR signal intensity (SI) of both hemorrhagic infarctions and nonhemorrhagic infarctions was higher than that in remote myocardium both in patients (hemorrhagic: 37% ± 19, P < .001; nonhemorrhagic: 78% ± 27, P < .001) and in canines (hemorrhagic: 42% ± 22, P < .001; nonhemorrhagic: 65% ± 22, P < .001). Consistent with STIR SI findings, mean T2 of both hemorrhagic (62.0 msec ± 4.9) and nonhemorrhagic (71.7 msec ± 7.3) infarctions in canines was elevated relative to mean T2 of remote myocardium (52.1 msec ± 4.8) by 18% ± 9 and 38% ± 13, respectively (P < .001 for both). CONCLUSION: T2* cardiac MR imaging is more suitable than T2 cardiac MR imaging in the detection and characterization of acute reperfusion myocardial hemorrhage. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122397/-/DC1.
Assuntos
Hemorragia/diagnóstico , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico , Traumatismo por Reperfusão/diagnóstico , Doença Aguda , Idoso , Angioplastia Coronária com Balão , Animais , Meios de Contraste , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapiaRESUMO
BACKGROUND: Intramyocardial hemorrhage frequently accompanies large reperfused myocardial infarctions. However, its influence on the makeup and the ensuing effect on the infarcted tissue during the chronic phase remain unexplored. METHODS AND RESULTS: Patients (n=15; 3 women), recruited after successful percutaneous coronary intervention for first segment-elevation myocardial infarction, underwent cardiovascular magnetic resonance imaging on day 3 and month 6 after percutaneous coronary intervention. Patients with hemorrhagic (Hemo+) infarctions, as determined by T2* cardiovascular magnetic resonance on day 3 (n=11), showed persistent T2* losses colocalized with scar tissue on the follow-up scans, suggesting chronic iron deposition. T2* values of Hemo+ territories were significantly higher than nonhemorrhagic (Hemo-) and remote territories (P<0.001); however, T2* values of nonhemorrhagic (Hemo-) and remote territories were not different (P=0.51). Canines (n=20) subjected to ischemia-reperfusion injury (n=14) underwent cardiovascular magnetic resonance on days 3 and 56 after ischemia-reperfusion injury. Similarly, sham-operated animals (Shams; n=3) were imaged using cardiovascular magnetic resonance at similar time points. Subsequently, hearts were explanted and imaged ex vivo, and samples of Hemo+, Hemo-, remote, and Sham myocardium were isolated and stained. The extent of iron deposition ([Fe]) within each sample was measured using mass spectrometry. Hemo+ infarcts showed significant T2* losses compared with the other (control) groups (P<0.001), and Perls stain confirmed localized iron deposition. Mean [Fe] of Hemo+ was nearly an order of magnitude greater than that of the control groups (P<0.001), but no significant differences were observed among the control groups. A strong linear relationship was observed between log(T2*) and -log([Fe]); R(2)=0.7 and P<0.001. The monoclonal antibody Mac387 stains, along with Perls stains, showed preferential localization of newly recruited macrophages at the site of chronic iron deposition. CONCLUSIONS: Hemorrhagic myocardial infarction can lead to iron depositions within the infarct zones, which can be a source of prolonged inflammatory burden in the chronic phase of myocardial infarction.