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BACKGROUND: Whether aortic valve stenosis (AS) can adversely affect systemic endothelial function independently of standard modifiable cardiovascular risk factors is unknown. METHODS: We therefore investigated endothelial and cardiac function in an experimental model of AS mice devoid of standard modifiable cardiovascular risk factors and human cohorts with AS scheduled for transcatheter aortic valve replacement. Endothelial function was determined by flow-mediated dilation using ultrasound. Extracellular hemoglobin (eHb) concentrations and NO consumption were determined in blood plasma of mice and humans by ELISA and chemiluminescence. This was complemented by measurements of aortic blood flow using 4-dimensional flow acquisition by magnetic resonance imaging and computational fluid dynamics simulations. The effects of plasma and red blood cell (RBC) suspensions on vascular function were determined in transfer experiments in a murine vasorelaxation bioassay system. RESULTS: In mice, the induction of AS caused systemic endothelial dysfunction. In the presence of normal systolic left ventricular function and mild hypertrophy, the increase in the transvalvular gradient was associated with elevated eryptosis, increased eHb and plasma NO consumption; eHb sequestration by haptoglobin restored endothelial function. Because the aortic valve orifice area in patients with AS decreased, postvalvular mechanical stress in the central ascending aorta increased. This was associated with elevated eHb, circulating RBC-derived microvesicles, eryptotic cells, lower haptoglobin levels without clinically relevant anemia, and consecutive endothelial dysfunction. Transfer experiments demonstrated that reduction of eHb by treatment with haptoglobin or elimination of fluid dynamic stress by transcatheter aortic valve replacement restored endothelial function. In patients with AS and subclinical RBC fragmentation, the remaining circulating RBCs before and after transcatheter aortic valve replacement exhibited intact membrane function, deformability, and resistance to osmotic and hypoxic stress. CONCLUSIONS: AS increases postvalvular swirling blood flow in the central ascending aorta, triggering RBC fragmentation with the accumulation of hemoglobin in the plasma. This increases NO consumption in blood, thereby limiting vascular NO bioavailability. Thus, AS itself promotes systemic endothelial dysfunction independent of other established risk factors. Transcatheter aortic valve replacement is capable of limiting NO scavenging and rescuing endothelial function by realigning postvalvular blood flow to near physiological patterns. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05603520. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01805739.
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INTRODUCTION: Since March 2020, the COVID-19 pandemic has tremendously impacted health care all around the globe. We analyzed the impact of the pandemic on donors, recipients, and outcome of heart transplantation (HTx). METHODS: Between 2010 and early 2022, a total of n = 235 patients underwent HTx in our department. Patients were assigned to the study groups regarding the date of the performed HTx. Group 1 (09/2010 to 02/2020): n = 160, Group 2 (03/2020 to 02/2022): n = 75. RESULTS: Since the pandemic, the etiology of heart failure in the recipients has shifted from dilated (Group 1: 53.8%, Group 2: 32.0%) to ischemic cardiomyopathy (Group 1: 39.4%, Group 2: 50.7%, p < .01). The percentage of high urgency status of the recipients dropped from 50.0% to 36.0% (p = .05), and the use of left ventricular assist (LVAD) support from 56.9% to just 37.3% (p < .01). Meanwhile, the waiting time for the recipients also decreased by about 40% (p = .05). Since the pandemic, donors were 2- times more likely to have been previously resuscitated (Group 1: 21.3%, Group 2: 45.3% (p < .01), and drug abuse increased by more than 3-times (p < .01), indicating acceptance of more marginal donors. Surprisingly, the incidence of postoperative severe primary graft dysfunction requiring extracorporeal life support decreased from 33.1% to 19.4% (p = .04) since the pandemic. CONCLUSION: The COVID-19 pandemic affected both donors and recipients of HTX but not the postoperative outcome. Donors nowadays are more likely to suffer from ischemic heart disease and are less likely to be on the high-urgency waitlist and on LVAD support. Simultaneously, an increasing number of marginal donors are accepted, leading to shorter waiting times.
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COVID-19 , Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Isquemia Miocárdica , Humanos , Pandemias , Resultado do Tratamento , COVID-19/epidemiologia , Insuficiência Cardíaca/cirurgia , Doadores de Tecidos , Estudos RetrospectivosRESUMO
BACKGROUND: Macrophages play a pivotal role in vascular inflammation and predict cardiovascular complications. Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorocarbon allows a background-free direct quantification of macrophage abundance in experimental vascular disease models in mice. Recently, perfluorooctyl bromide-nanoemulsion (PFOB-NE) was applied to effectively image macrophage infiltration in a pig model of myocardial infarction using clinical MRI scanners. In the present proof-of-concept approach, we aimed to non-invasively image monocyte/macrophage infiltration in response to carotid artery angioplasty in pigs using 19F MRI to assess early inflammatory response to mechanical injury. METHODS: In eight minipigs, two different types of vascular injury were conducted: a mild injury employing balloon oversize angioplasty only (BA, n = 4) and a severe injury provoked by BA in combination with endothelial denudation (BA + ECDN, n = 4). PFOB-NE was administered intravenously three days after injury followed by 1H and 19F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using X-ray angiography, intravascular ultrasound and immunohistology in at least 10 segments per carotid artery. RESULTS: Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and concomitant infiltration of monocytes/macrophages. No severe adverse reactions were observed following PFOB-NE administration. In vivo 19F signals were only detected in the four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8. Ex vivo analysis revealed a linear correlation of 19F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was estimated at approximately 410 cells/mm2. CONCLUSIONS: In this proof-of-concept study, 19F MRI enabled quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This may provide the opportunity to non-invasively monitor vascular inflammation with MRI in patients after angioplasty or even in atherosclerotic plaques.
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Lesões do Sistema Vascular , Humanos , Animais , Camundongos , Suínos , Porco Miniatura , Valor Preditivo dos Testes , Imageamento por Ressonância Magnética/métodos , Angioplastia , Inflamação/diagnóstico por imagem , Inflamação/etiologiaRESUMO
BACKGROUND: ST-segment elevation myocardial infarction (STEMI) still causes significant mortality and morbidity despite best-practice revascularization and adjunct medical strategies. Within the STEMI population, there is a spectrum of higher and lower risk patients with respect to major adverse cardiovascular and cerebral events (MACCE) or re-hospitalization due to heart failure. Myocardial and systemic metabolic disorders modulate patient risk in STEMI. Systematic cardiocirculatory and metabolic phenotyping to assess the bidirectional interaction of cardiac and systemic metabolism in myocardial ischemia is lacking. METHODS: Systemic organ communication in STEMI (SYSTEMI) is an all-comer open-end prospective study in STEMI patients > 18 years of age to assess the interaction of cardiac and systemic metabolism in STEMI by systematically collecting data on a regional and systemic level. Primary endpoint will be myocardial function, left ventricular remodelling, myocardial texture and coronary patency at 6 month after STEMI. Secondary endpoint will be all-cause death, MACCE, and re-hospitalisation due to heart failure or revascularisation assessed 12 month after STEMI. The objective of SYSTEMI is to identify metabolic systemic and myocardial master switches that determine primary and secondary endpoints. In SYSTEMI 150-200 patients are expected to be recruited per year. Patient data will be collected at the index event, within 24 h, 5 days as well as 6 and 12 months after STEMI. Data acquisition will be performed in multilayer approaches. Myocardial function will be assessed by using serial cardiac imaging with cineventriculography, echocardiography and cardiovascular magnetic resonance. Myocardial metabolism will be analysed by multi-nuclei magnetic resonance spectroscopy. Systemic metabolism will be approached by serial liquid biopsies and analysed with respect to glucose and lipid metabolism as well as oxygen transport. In summary, SYSTEMI enables a comprehensive data analysis on the levels of organ structure and function alongside hemodynamic, genomic and transcriptomic information to assess cardiac and systemic metabolism. DISCUSSION: SYSTEMI aims to identify novel metabolic patterns and master-switches in the interaction of cardiac and systemic metabolism to improve diagnostic and therapeutic algorithms in myocardial ischemia for patient-risk assessment and tailored therapy. TRIAL REGISTRATION: Trial Registration Number: NCT03539133.
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Doença da Artéria Coronariana , Insuficiência Cardíaca , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Estudos de Coortes , Estudos Prospectivos , Intervenção Coronária Percutânea/efeitos adversos , Doença da Artéria Coronariana/complicações , Insuficiência Cardíaca/etiologia , Resultado do TratamentoRESUMO
Aortic valve stenosis (AS) is the most frequent valve disease with relevant prognostic impact. Experimental model systems for AS are scarce and comprehensive imaging techniques to simultaneously quantify function and morphology in disease progression are lacking. Therefore, we refined an acute murine AS model to closely mimic human disease characteristics and developed a high-resolution magnetic resonance imaging (MRI) approach for simultaneous in-depth analysis of valvular, myocardial as well as aortic morphology/pathophysiology to identify early changes in tissue texture and critical transition points in the adaptive process to AS. AS was induced by wire injury of the aortic valve. Four weeks after surgery, cine loops, velocity, and relaxometry maps were acquired at 9.4 T to monitor structural/functional alterations in valve, aorta, and left ventricle (LV). In vivo MRI data were subsequently validated by histology and compared to echocardiography. AS mice exhibited impaired valve opening accompanied by significant valve thickening due to fibrotic remodelling. While control mice showed bell-shaped flow profiles, AS resulted not only in higher peak flow velocities, but also in fragmented turbulent flow patterns associated with enhanced circumferential strain and an increase in wall thickness of the aortic root. AS mice presented with a mild hypertrophy but unaffected global LV function. Cardiac MR relaxometry revealed reduced values for both T1 and T2 in AS reflecting subtle myocardial tissue remodelling with early alterations in mitochondrial function in response to the enhanced afterload. Concomitantly, incipient impairments of coronary flow reserve and myocardial tissue integrity get apparent accompanied by early troponin release. With this, we identified a premature transition point with still compensated cardiac function but beginning textural changes. This will allow interventional studies to explore early disease pathophysiology and novel therapeutic targets.
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Estenose da Valva Aórtica , Imageamento por Ressonância Magnética Multiparamétrica , Animais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Camundongos , Função Ventricular EsquerdaRESUMO
Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.
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Meios de Contraste , Infarto do Miocárdio , Animais , Gadolínio , Hemorragia/patologia , Inflamação , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Infarto do Miocárdio/patologia , SuínosRESUMO
OBJECTIVES: Distinguishing hypertrophic cardiomyopathy (HCM) from left ventricular hypertrophy (LVH) due to systematic training (athlete's heart, AH) from morphologic assessment remains challenging. The purpose of this study was to examine the role of T2 mapping and deformation imaging obtained by cardiovascular magnetic resonance (CMR) to discriminate AH from HCM with (HOCM) or without outflow tract obstruction (HNCM). METHODS: Thirty-three patients with HOCM, 9 with HNCM, 13 strength-trained athletes as well as individual age- and gender-matched controls received CMR. For T2 mapping, GRASE-derived multi-echo images were obtained and analyzed using dedicated software. Besides T2 mapping analyses, left ventricular (LV) dimensional and functional parameters were obtained including LV mass per body surface area (LVMi), interventricular septum thickness (IVS), and global longitudinal strain (GLS). RESULTS: While LVMi was not significantly different, IVS was thickened in HOCM patients compared to athlete's. Absolute values of GLS were significantly increased in patients with HOCM/HNCM compared to AH. Median T2 values were elevated compared to controls except in athlete's heart. ROC analysis revealed T2 values (AUC 0.78) and GLS (AUC 0.91) as good parameters to discriminate AH from overall HNCM/HOCM. CONCLUSION: Discrimination of pathologic from non-pathologic LVH has implications for risk assessment of competitive sports in athletes. Multiparametric CMR with parametric T2 mapping and deformation imaging may add information to distinguish AH from LVH due to HCM. KEY POINTS: ⢠Structural analyses using T2 mapping cardiovascular magnetic resonance imaging (CMR) may help to further distinguish myocardial diseases. ⢠To differentiate pathologic from non-pathologic left ventricular hypertrophy, CMR including T2 mapping was obtained in patients with hypertrophic obstructive/non-obstructive cardiomyopathy (HOCM/HNCM) as well as in strength-trained athletes. ⢠Elevated median T2 values in HOCM/HNCM compared with athlete's may add information to distinguish athlete's heart from pathologic left ventricular hypertrophy.
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Cardiomegalia Induzida por Exercícios , Cardiomiopatia Hipertrófica , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Espectroscopia de Ressonância MagnéticaRESUMO
Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.
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Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/fisiopatologia , Animais , Estenose da Valva Aórtica/patologia , Comunicação Celular , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Humanos , Inflamação/fisiopatologia , Lipoproteínas/metabolismo , Miofibroblastos/fisiologia , Osteoblastos/fisiologia , Osteoclastos/fisiologia , RNA não Traduzido/metabolismo , Calcificação Vascular/fisiopatologiaRESUMO
OBJECTIVES: Fluorine-19 (19F) MRI with intravenously applied perfluorocarbons allows the in vivo monitoring of infiltrating immune cells as demonstrated in small animal models at high field. Here, we aimed to transfer this approach to a clinical scanner for detection of inflammatory processes in the heart after acute myocardial infarction (AMI) in a large animal model. MATERIALS AND METHODS: Optimization of coil and sequence performance was carried out on phantoms and in vivo at a 3 T Philips Achieva. AMI was induced in Munich mini pigs by 90-min occlusion of the left anterior descending artery. At day 3 after AMI, pigs received a body weight-adjusted intravenous dose of a perfluorooctyl bromide nanoemulsion followed by 1H/19F MRI at day 6 after AMI. RESULTS: A balanced steady-state free precession turbo gradient echo sequence using an ellipsoidal 19F/1H surface coil provided the best signal-to-noise ratio and a superior localization of 19F patterns in vivo. This approach allowed the reliable detection of 19F signals in the injured myocardium within less than 20 min. The 19F signal magnitude correlated significantly with the functional impairment after AMI. CONCLUSION: This study demonstrates the feasibility of in vivo 19F MR inflammation imaging after AMI at 3 T within a clinically acceptable acquisition time.
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Imagem por Ressonância Magnética de Flúor-19 , Flúor/química , Infarto do Miocárdio/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Emulsões , Desenho de Equipamento , Fluorocarbonos/administração & dosagem , Coração/diagnóstico por imagem , Hidrocarbonetos Bromados , Sistema Imunitário , Inflamação , Infarto do Miocárdio/imunologia , Nanotecnologia , Imagens de Fantasmas , Razão Sinal-Ruído , Suínos , Porco MiniaturaRESUMO
Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorooctyl bromide-nanoemulsions (PFOB-NE) has proven its feasibility to visualize inflammatory processes in experimental disease models. This approach is based on the properties of monocytes/macrophages to ingest PFOB-NE particles enabling specific cell tracking in vivo. However, information on safety (cellular function and viability), mechanism of ingestion and impact of specific disease environment on PFOB-NE uptake is lacking. This information is, however, crucial for the interpretation of 19F MRI signals and a possible translation to clinical application. To address these issues, whole blood samples were collected from patients with acute ST-elevation myocardial infarction (STEMI), stable coronary artery disease (SCAD) and healthy volunteers. Samples were exposed to fluorescently-labeled PFOB-NE and particle uptake, cell viability and migration activity was evaluated by flow cytometry and MRI. We were able to show that PFOB-NE is ingested by human monocytes in a time- and subset-dependent manner via active phagocytosis. Monocyte function (migration, phagocytosis) and viability was maintained after PFOB-NE uptake. Monocytes of STEMI and SCAD patients did not differ in their maximal PFOB-NE uptake compared to healthy controls. In sum, our study provides further evidence for a safe translation of PFOB-NE for imaging purposes in humans.
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Imagem por Ressonância Magnética de Flúor-19 , Fluorocarbonos , Imagem Molecular , Monócitos/fisiologia , Nanopartículas , Fagocitose/fisiologia , Adulto , Biomarcadores , Sobrevivência Celular , Doença da Artéria Coronariana/diagnóstico , Emulsões , Imunofluorescência , Imagem por Ressonância Magnética de Flúor-19/métodos , Fluorocarbonos/química , Humanos , Hidrocarbonetos Bromados , Macrófagos , Imagem Molecular/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Fatores de TempoRESUMO
BACKGROUND: T cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The proinflammatory danger signal ATP, released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. METHODS: Myocardial ischemia (50 minutes followed by reperfusion) was induced in global CD73-/- and CD4-CD73-/- mice. Tissue injury, T-cell purinergic signaling, cytokines, and cardiac function (magnetic resonance tomography at 9.4 T over 4 weeks) were analyzed. RESULTS: Changes in functional parameters of CD4-CD73-/- mice were identical to those in global CD73 knockouts (KOs). T cells infiltrating the injured heart significantly upregulated at the gene (quantitative polymerase chain reaction) and protein (enzymatic activity) levels critical transporters and enzymes (connexin43, connexin37, pannexin-1, equilibrative nucleoside transporter 1, CD39, CD73, ecto-nucleotide pyrophosphatase/phosphodiesterases 1 and 3, CD157, CD38) for the accelerated release and hydrolysis of ATP, cAMP, AMP, and NAD to adenosine. It is surprising that a lack of CD39 on T cells (from CD39-/- mice) did not alter ATP hydrolysis and very likely involves pyrophosphatases (ecto-nucleotide pyrophosphatase/phosphodiesterases 1 and 3). Circulating T cells predominantly expressed A2a receptor (A2aR) transcripts. After myocardial infarction, A2b receptor (A2bR) transcription was induced in both T cells and myeloid cells in the heart. Thus, A2aR and A2bR signaling may contribute to myocardial responses after myocardial infarction. In the case of T cells, this was associated with an accelerated secretion of proinflammatory and profibrotic cytokines (interleukin-2, interferon-γ, and interleukin-17) when CD73 was lacking. Cytokine production by T cells from peripheral lymph nodes was inhibited by A2aR activation (CGS-21680). The A2bR agonist BAY 60-6583 showed off-target effects. The adenosine receptor agonist NECA inhibited interferon-γ and stimulated interleukin-6 production, each of which was antagonized by a specific A2bR antagonist (PSB-603). CONCLUSIONS: This work demonstrates that CD73 on T cells plays a crucial role in the cardiac wound healing process after myocardial infarction. The underlying mechanism involves a profound increase in the hydrolysis of ATP/NAD and AMP, resulting primarily from the upregulation of pyrophosphatases and CD73. We also define A2bR/A2aR-mediated autacoid feedback inhibition of proinflammatory/profibrotic cytokines by T cell-derived CD73.
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5'-Nucleotidase/metabolismo , Infarto do Miocárdio/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptor A2B de Adenosina/metabolismo , Linfócitos T/metabolismo , Cicatrização/fisiologia , 5'-Nucleotidase/imunologia , Animais , Movimento Celular/fisiologia , Reprogramação Celular/fisiologia , Feminino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Infarto do Miocárdio/imunologia , Receptor A2A de Adenosina/imunologia , Receptor A2B de Adenosina/imunologia , Linfócitos T/imunologiaAssuntos
Diabetes Mellitus Tipo 2 , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Valor Preditivo dos Testes , Função Ventricular EsquerdaRESUMO
BACKGROUND: While most patients recover from suspected acute myocarditis (sAMC) some develop progressive disease with 5-year mortality up to 20%. Recently, parametric Cardiovascular Magnetic Resonance (CMR) approaches, quantifying native T1 and T2 relaxation time, have demonstrated the ability to increase diagnostic accuracy. However, prognostic implications of T2 values in this cohort are unknown. The purpose of the study was to investigate the prognostic relevance of elevated CMR T2 values in patients with sAMC. METHODS AND RESULTS: We carried out a prospective study in 46 patients with sAMC defined by current ESC recommendations. A combined endpoint was defined by the occurrence of at least one major adverse cardiac event (MACE) and hospitalisation for heart failure. Event rate was 24% (n = 11) for 1-year-MACE and hospitalisation. A follow-up after 11 ± 7 months was performed in 98% of the patients. Global T2 values were significantly increased at acute stage of disease compared to controls and decreased over time. During acute disease, elevated global T2 time (odds ratio 6.3, p < 0.02) as well as myocardial fraction with T2 time >80 ms (odds ratio 4.9, p < 0.04) predicted occurrence of the combined endpoint. Patients with clinical recovery revealed significantly decreased T2 relaxation times at follow-up examinations; however, T2 values were still elevated compared to healthy controls. CONCLUSION: Assessment of myocardial T2 relaxation times at initial presentation facilitates CMR-based risk stratification in patients with acute myocarditis. T2 Mapping may emerge as a new tool to monitor inflammatory myocardial injuries during the course of disease.
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Imageamento por Ressonância Magnética , Miocardite/diagnóstico por imagem , Doença Aguda , Adulto , Estudos de Casos e Controles , Progressão da Doença , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Miocardite/complicações , Miocardite/mortalidade , Miocardite/terapia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Endocarditis parietalis fibroplastica Löfflein (EPF) is a rare form of primary restrictive cardiomyopathy with poor prognosis. It is generally caused by hypereosinophilic syndrome with eosinophilic penetration of the heart. This leads to congestive heart failure in three different stages. As a frequent manifestation of neoplastic diseases, cardiac involvement means poor prognosis. CASE PRESENTATION: The present report deals with a case of EPF caused by non-specified T-cell lymphoma (T-NOS). Besides an elevated Troponin-T enzyme, the electrocardiogram and the transthoracic echocardiography did not show any characteristic results. Due to risk/benefit assessment and low thrombocyte amounts, endomyocardial biopsy and catheterization were discarded. Using cardiovascular magnetic resonance (CMR) with steady-state free precession sequences, T2-mappping, strain analysis and late gadolinium enhancement, we were able to clearly highlight cardiac involvement at different stages. These findings characterized T-NOS as a palliative situation. CONCLUSION: Multiparametric CMR can not only identify EPF but also characterize the patchy disease state. This provides an individual prognosis assessment. Aside from prognosis estimation, it can also be used for therapy monitoring.
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Neoplasias Cardíacas/diagnóstico por imagem , Síndrome Hipereosinofílica/diagnóstico por imagem , Linfoma de Células T/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Adulto , Meios de Contraste/administração & dosagem , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/terapia , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/etiologia , Imunossupressores/uso terapêutico , Linfoma de Células T/complicações , Linfoma de Células T/terapia , Masculino , Valor Preditivo dos Testes , Resultado do TratamentoAssuntos
Diabetes Mellitus/epidemiologia , Intervenção Coronária Percutânea/estatística & dados numéricos , Hemorragia Pós-Operatória/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/cirurgia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/cirurgia , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/cirurgia , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Hemorragia Pós-Operatória/etiologia , Fatores de RiscoRESUMO
RATIONALE: Ecto-5'-nucleotidase (CD73) on immune cells is emerging as a critical pathway and therapeutic target in cardiovascular and autoimmune disorders. OBJECTIVE: Here, we investigated the role of CD73 in postinfarction inflammation, cardiac repair, and remodeling in mice after reperfused myocardial infarction (50-minute ischemia). METHODS AND RESULTS: We found that compared with control mice (1) cardiac function in CD73(-/-) mice more severely declined after infarction (systolic failure with enhanced myocardial edema formation) as determined by MRI and was associated with the persistence of cardiac immune cell subsets, (2) cardiac adenosine release was augmented 7 days after ischemia/reperfusion in control mice but reduced by 90% in CD73 mutants, (3) impaired healing involves M1-driven immune response with increased tumor necrosis factor-α and interleukin-17, as well as decreased transforming growth factor-ß and interleukin-10, and (4) CD73(-/-) mice displayed infarct expansion accompanied by an immature replacement scar and diffuse ventricular fibrosis. Studies on mice after bone marrow transplantation revealed that CD73 present on immune cells is a major determinant promoting cardiac healing. CONCLUSIONS: These results, together with the upregulation of CD73 on immune cells after ischemia/reperfusion, demonstrate the crucial role of purinergic signaling during cardiac healing and provide groundwork for novel anti-inflammatory strategies in treating adverse cardiac remodeling.
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5'-Nucleotidase/biossíntese , Imunidade Celular/fisiologia , Remodelação Ventricular/fisiologia , 5'-Nucleotidase/genética , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologiaRESUMO
BACKGROUND: T2 mapping indicates to be a sensitive method for detection of tissue oedema hidden beyond the detection limits of T2-weighted Cardiovascular Magnetic Resonance (CMR). However, due to variability of baseline T2 values in volunteers, reference values need to be defined. Therefore, the aim of the study was to investigate the effects of age and sex on quantitative T2 mapping with a turbo gradient-spin-echo (GRASE) sequence at 1.5 T. For that reason, we studied sensitivity issues as well as technical and biological effects on GRASE-derived myocardial T2 maps. Furthermore, intra- and interobserver variability were calculated using data from a large volunteer group. METHODS: GRASE-derived multiecho images were analysed using dedicated software. After sequence optimization, validation and sensitivity measurements were performed in muscle phantoms ex vivo and in vivo. The optimized parameters were used to analyse CMR images of 74 volunteers of mixed sex and a wide range of age with typical prevalence of hypertension and diabetes. Myocardial T2 values were analysed globally and according to the 17 segment model. Strain-encoded (SENC) imaging was additionally performed to investigate possible effects of myocardial strain on global or segmental T2 values. RESULTS: Ex vivo studies in muscle phantoms showed, that GRASE-derived T2 values were comparable to those acquired by a standard multiecho spinecho sequence but faster by a factor of 6. Besides that, T2 values reflected tissue water content. The in vivo measurements in volunteers revealed intra- and interobserver correlations with R2=0.91 and R2=0.94 as well as a coefficients of variation of 2.4% and 2.2%, respectively. While global T2 time significantly decreased towards the heart basis, female volunteers had significant higher T2 time irrespective of myocardial region. We found no correlation of segmental T2 values with maximal systolic, diastolic strain or heart rate. Interestingly, volunteers´ age was significantly correlated to T2 time while that was not the case for other coincident cardiovascular risk factors. CONCLUSION: GRASE-derived T2 maps are highly reproducible. However, female sex and aging with typical prevalence of hypertension and diabetes were accompanied by increased myocardial T2 values. Thus, sex and age must be considered as influence factors when using GRASE in a diagnostic manner.
Assuntos
Aumento da Imagem/métodos , Imagem Cinética por Ressonância Magnética/métodos , Contração Miocárdica , Miocárdio/patologia , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Fatores SexuaisRESUMO
Healing of the myocardium after infarction comprises a variety of local adaptive processes which contribute to the functional outcome after the insult. Therefore, we aimed to establish a setting for concomitant assessment of regional alterations in contractile function, morphology, and immunological state to gain prognostic information on cardiac recovery after infarction. For this, mice were subjected to myocardial ischemia/reperfusion (I/R) and monitored for 28 days by cine MRI, T2 mapping, late gadolinium enhancement (LGE), and (19)F MRI. T2 values were calculated from gated multi-echo sequences. (19)F-loaded nanoparticles were injected intravenously for labelling circulating monocytes and making them detectable by (19)F MRI. In-house developed software was used for regional analysis of cine loops, T2 maps, LGE, and (19)F images to correlate local wall movement, tissue damage as well as monocyte recruitment over up to 200 sectors covering the left ventricle. This enabled us to evaluate simultaneously zonal cardiac necrosis, oedema, and inflammation patterns together with sectional fractional shortening (FS) and global myocardial function. Oedema, indicated by a rise in T2, showed a slightly better correlation with FS than LGE. Regional T2 values increased from 19 ms to above 30 ms after I/R. In the course of the healing process oedema resolved within 28 days, while myocardial function recovered. Infiltrating monocytes could be quantitatively tracked by (19)F MRI, as validated by flow cytometry. Furthermore, (19)F MRI proved to yield valuable insight on the outcome of myocardial infarction in a transgenic mouse model. In conclusion, our approach permits a comprehensive surveillance of key processes involved in myocardial healing providing independent and complementary information for individual prognosis.
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Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/patologia , Cicatrização/fisiologia , Animais , Modelos Animais de Doenças , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
OBJECTIVE: This paper introduces a new approach permitting for the first time a specific, non-invasive diagnosis of myocarditis by visualizing the infiltration of immune cells into the myocardium. MATERIALS AND METHODS: The feasibility of this approach is shown in a murine model of viral myocarditis. Our study uses biochemically inert perfluorocarbons (PFCs) known to be taken up by circulating monocytes/macrophages after intravenous injection. RESULTS: In vivo (19)F MRI at 9.4 T demonstrated that PFC-loaded immune cells infiltrate into inflamed myocardial areas. Because of the lack of any fluorine background in the body, detected (19)F signals of PFCs are highly specific as confirmed ex vivo by flow cytometry and histology. CONCLUSION: Since PFCs are a family of compounds previously used clinically as blood substitutes, the technique described in our paper holds the potential as a new imaging modality for the diagnosis of myocarditis in man.
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Imageamento por Ressonância Magnética/métodos , Miocardite/virologia , Animais , Citometria de Fluxo/métodos , Flúor/química , Fluorocarbonos/química , Injeções Intravenosas , Macrófagos/citologia , Masculino , Camundongos , Monócitos/citologia , Miocárdio/imunologia , Miocárdio/patologiaRESUMO
OBJECTIVES: Dynamic Coronary Roadmap (DCR) is a software tool that creates a real-time dynamic coronary artery overlay on fluoroscopic images. The efficacy of DCR in significantly reducing contrast medium use during percutaneous coronary interventions (PCI) has previously been shown. In this study, we aimed to determine if DCR is equally effective irrespective of the performing investigator's experience level. METHODS: In this sub-analysis of a monocentric, open-label, randomized trial, 130 patients with hemodynamic relevant coronary type A and B lesions were randomized and contrast medium use was conducted with (+) or without (-) DCR software. PCI was randomly allocated and performed by an investigator with high (A) or medium (B) experience level. RESULTS: Overall, contrast medium use was significantly reduced by both investigators in the +DCR group, and Investigator B used significantly less contrast medium with the software than Investigator A. The DCR software was not accompanied by increased radiation exposure for the patients or the teams. On the contrary, dose area product was reduced by both investigators, but was significantly reduced by the highly experienced investigator when using DCR. Fluoroscopy time was not different between investigators. Procedural success was 100%. Serious in-hospital adverse events were not observed. One of Investigator A's patients suffered from post-procedural acute kidney injury in the -DCR group. CONCLUSIONS: DCR significantly reduces contrast medium use during PCI irrespective of investigator's experience level.