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BACKGROUND: Cardiovascular disease (CVD) is excessively prevalent and premature in bipolar disorder (BD), even after controlling for traditional cardiovascular risk factors. The increased risk of CVD in BD may be subserved by microvascular dysfunction. We examined coronary microvascular function in relation to youth BD. METHODS: Participants were 86 youth, ages 13-20 years (n = 39 BD, n = 47 controls). Coronary microvascular reactivity (CMVR) was assessed using quantitative T2 magnetic resonance imaging during a validated breathing-paradigm. Quantitative T2 maps were acquired at baseline, following 60-s of hyperventilation, and every 10-s thereafter during a 40-s breath-hold. Left ventricular structure and function were evaluated based on 12-15 short- and long-axis cardiac-gated cine images. A linear mixed-effects model that controlled for age, sex, and body mass index assessed for between-group differences in CMVR (time-by-group interaction). RESULTS: The breathing-paradigm induced a significant time-related increase in T2 relaxation time for all participants (i.e. CMVR; ß = 0.36, p < 0.001). CMVR was significantly lower in BD v. controls (ß = -0.11, p = 0.002). Post-hoc analyses found lower T2 relaxation time in BD youth after 20-, 30-, and 40 s of breath-holding (d = 0.48, d = 0.72, d = 0.91, respectively; all pFDR < 0.01). Gross left ventricular structure and function (e.g. mass, ejection fraction) were within normal ranges and did not differ between groups. CONCLUSION: Youth with BD showed evidence of subclinically impaired coronary microvascular function, despite normal gross cardiac structure and function. These results converge with prior findings in adults with major depressive disorder and post-traumatic stress disorder. Future studies integrating larger samples, prospective follow-up, and blood-based biomarkers are warranted.
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Transtorno Bipolar , Doenças Cardiovasculares , Transtorno Depressivo Maior , Adulto , Humanos , Adolescente , Transtorno Bipolar/diagnóstico por imagem , Estudos Prospectivos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Novel treatment strategies are needed to improve the structure and function of the myocardium post-infarction. In vitro-matured pluripotent stem cell-derived cardiomyocytes (PSC-CMs) have been shown to be a promising regenerative strategy. We hypothesized that mature PSC-CMs will have anisotropic structure and improved cell alignment when compared to immature PSC-CMs using cardiovascular magnetic resonance (CMR) in a guinea pig model of cardiac injury. METHODS: Guinea pigs (n = 16) were cryoinjured on day -10, followed by transplantation of either 108 polydimethylsiloxane (PDMS)-matured PSC-CMs (n = 6) or 108 immature tissue culture plastic (TCP)-generated PSC-CMs (n = 6) on day 0. Vehicle (sham-treated) subjects were injected with a pro-survival cocktail devoid of cells (n = 4), while healthy controls (n = 4) did not undergo cryoinjury or treatment. Animals were sacrificed on either day +14 or day +28 post-transplantation. Animals were imaged ex vivo on a 7T Bruker MRI. A 3D diffusion tensor imaging (DTI) sequence was used to quantify structure via fractional anisotropy (FA), mean diffusivity (MD), and myocyte alignment measured by the standard deviation of the transverse angle (TA). RESULTS: MD and FA of mature PDMS grafts demonstrated anisotropy was not significantly different than the healthy control hearts (MD = 1.1 ± 0.12 × 10-3 mm2/s vs 0.93 ± 0.01 × 10-3 mm2/s, p = 0.4 and FA = 0.22 ± 0.05 vs 0.26 ± 0.001, p = 0.5). Immature TCP grafts exhibited significantly higher MD than the healthy control (1.3 ± 0.08 × 10-3 mm2/s, p < 0.05) and significantly lower FA than the control (0.12 ± 0.02, p < 0.05) but were not different from mature PDMS grafts in this small cohort. TA of healthy controls showed low variability and was not significantly different than mature PDMS grafts (p = 0.4) while immature TCP grafts were significantly different (p < 0.001). DTI parameters of mature graft tissue trended toward that of the healthy myocardium, indicating the grafted cardiomyocytes may have a similar phenotype to healthy tissue. Contrast-enhanced magnetic resonance images corresponded well to histological staining, demonstrating a non-invasive method of localizing the repopulated cardiomyocytes within the scar. CONCLUSIONS: The DTI measures within graft tissue were indicative of anisotropic structure and showed greater myocyte organization compared to the scarred territory. These findings show that MRI is a valuable tool to assess the structural impacts of regenerative therapies.
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BACKGROUND: The prevalence of abnormal cardiac magnetic resonance imaging (MRI) findings indicative of myocardial injury in patients who recovered from coronavirus disease 2019 (COVID-19) is currently unclear, with a high variability in the reported prevalence. PURPOSE: To assess the prevalence of myocardial injury after a COVID-19 infection. STUDY TYPE: Prospective, bicentric study. SUBJECTS: Seventy consecutive patients who recovered from COVID-19 and were previously hospitalized. Mean age was 57 years and 39% of the patients were female. Ten healthy controls and a comparator group of 75 nonischemic cardiomyopathy (NICM) patients were employed. FIELD STRENGTH/SEQUENCE: 1.5-T, steady-state free precession (SSFP) gradient-echo sequence, modified Look-Locker inversion recovery sequence with balanced SSFP readout, T2-prepared spiral readout sequence and a T1-weighted inversion recovery fast gradient-echo sequence was acquired ~4-5 months after recovery from COVID-19. ASSESSMENT: The SSFP sequence was utilized for the calculation of left and right ventricular volumes and ejection fractions (LVEF and RVEF) following manual endocardial contouring. T1 and T2 mapping was performed by pixel-wise exponential fitting, and T1 and T2 values were computed by manual contouring of the left ventricular endocardial and epicardial walls. Late gadolinium enhancement (LGE) images were graded qualitatively as LGE present or absent. STATISTICAL TESTS: T-tests and the χ2 or Fisher's exact tests were used to compare continuous and categorical variables respectively between the COVID-19 and NICM groups. Inter-rater agreement was evaluated by the intraclass correlation coefficient for continuous variables and Cohen's kappa test for LGE. RESULTS: Reduced RVEF occurred in 10%, LGE and elevated native T1 in 9%, reduced LVEF in 4%, and elevated T2 in 3% of COVID-19 patients, respectively. Patients with NICM had lower mean LVEF (41.6% ± 6% vs. 60% ± 7%), RVEF (46% ± 5% vs. 61% ± 9%), and a significantly higher prevalence of LGE (27% vs. 9%) when compared to those post-COVID-19. DATA CONCLUSION: Abnormal cardiac MRI findings may show a low prevalence in patients who recovered from COVID-19 and were previously hospitalized. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
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COVID-19 , Cardiomiopatias , Traumatismos Cardíacos , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Meios de Contraste , Estudos Prospectivos , Prevalência , Gadolínio , Imageamento por Ressonância Magnética , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/epidemiologia , Volume Sistólico , Valor Preditivo dos Testes , Miocárdio , Imagem Cinética por Ressonância MagnéticaRESUMO
Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant ß-values >7). Myocardial oxygen consumption had almost no effect on T2 (ß-values <0.002); since PvO2 is influenced by both oxygen consumption and MBF, PvO2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO2 and MBV confirmed that PvO2 had the strongest influence on T2, but MBV became important at high PvO2 . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue.
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Adenosina/farmacologia , Circulação Coronária/fisiologia , Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Animais , Feminino , Hemodinâmica/efeitos dos fármacos , Hiperemia/diagnóstico por imagem , Hiperemia/fisiopatologia , Masculino , Microesferas , Isquemia Miocárdica/diagnóstico por imagem , Oxigênio/sangue , Consumo de Oxigênio , SuínosRESUMO
BACKGROUND: Liver iron concentration (LIC) measured by MRI has become the clinical reference standard for managing iron overload in chronically transfused patients. Transverse relaxivity (R2 or R2* ) measurements are converted to LIC units using empirically derived calibration curves. HYPOTHESIS: That flip angle (FA) error due to B1+ spatial heterogeneity causes significant LIC quantitation error. B1+ scale (b1 , [FAactual /FAspecified ]) variation is a major problem at 3 T which could reduce the accuracy of transverse relaxivity measurements. STUDY TYPE: Prospective. POPULATION: Forty-seven subjects with chronic transfusional iron overload undergoing clinically indicated LIC assessment. FIELD STRENGTH/SEQUENCE: 5 T/3 T dual-repetition time B1+ mapping sequence ASSESSMENT: We quantified the average/standard deviation b1 in the right and left lobes of the liver from B1+ maps acquired at 1.5 T and 3 T. The impact of b1 variation on spin echo LIC estimates was determined using a Monte Carlo model. STATISTICAL TESTS: Mean, median, and standard deviation in whole liver and right and left lobes; two-sided t-test between whole-liver b1 means. RESULTS: Average b1 within the liver was 99.3% ± 12.3% at 1.5 T versus 69.6% ± 14.6% at 3 T and was independent of iron burden (P < 0.05). Monte Carlo simulations demonstrated that b1 systematically increased R2 estimates at lower LIC (<~25 mg/g at 1.5 T, <~15 mg/g at 3 T) but flattened or even inverted the R2 -LIC relationship at higher LIC (≥~25 mg/g to 1.5 T, ≥~15 mg/g to 3 T); changes in the R2 -LIC relationship were symmetric with respect to over and under excitation and were similar at 1.5 T and 3 T (for the same R2 value). The R2* -LIC relationship was independent of b1 . CONCLUSION: Spin echo R2 measurement of LIC at 3 T is error-prone without correction for b1 errors. The impact of b1 error on current 1.5 T spin echo-based techniques for LIC quantification is large enough to introduce measurable intersubject variability but the in vivo effect size needs a dedicated validation study. TECHNICAL EFFICACY STAGE: 2.
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Sobrecarga de Ferro , Ferro , Humanos , Sobrecarga de Ferro/diagnóstico por imagem , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Estudos ProspectivosRESUMO
Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I - HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T2 , T1 ), hemorrhage (T2 *), vasodilator function (T2 BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre- and post-contrast T1 ) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T2 * values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia-alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T2 elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia-alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high-risk patients progressing towards heart failure.
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Hemorragia/diagnóstico por imagem , Hemorragia/fisiopatologia , Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Oxigênio/sangue , Remodelação Ventricular/fisiologia , Animais , Feminino , Testes de Função Cardíaca , Hemorragia/patologia , Microvasos/diagnóstico por imagem , Microvasos/patologia , Infarto do Miocárdio/patologia , SuínosRESUMO
Intramyocardial hemorrhage is an independent predictor of adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Iron deposition resulting from ischemia-reperfusion injury (I/R) is pro-inflammatory and has been associated with adverse remodeling. The role of iron chelation in hemorrhagic acute myocardial infarction (AMI) has never been explored. The purpose of this study was to investigate the cardioprotection offered by the iron-chelating agent deferiprone (DFP) in a porcine AMI model by evaluating hemorrhage neutralization and subsequent cardiac remodeling. Two groups of animals underwent a reperfused AMI procedure: control and DFP treated (N = 7 each). A comprehensive MRI examination was performed in healthy state and up to week 4 post-AMI, followed by histological assessment. Infarct size was not significantly different between the two groups; however, the DFP group demonstrated earlier resolution of hemorrhage (by T2* imaging) and edema (by T2 imaging). Additionally, ventricular enlargement and myocardial hypertrophy (wall thickness and mass) were significantly smaller with DFP, suggesting reduced adverse remodeling, compared to control. The histologic results were consistent with the MRI findings. To date, there is no effective targeted therapy for reperfusion hemorrhage. Our proof-of-concept study is the first to identify hemorrhage-derived iron as a therapeutic target in I/R and exploit the cardioprotective properties of an iron-chelating drug candidate in the setting of AMI. Iron chelation could potentially serve as an adjunctive therapy in hemorrhagic AMI.
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Cardiotônicos/farmacologia , Deferiprona/uso terapêutico , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Quelantes de Ferro/uso terapêutico , Infarto do Miocárdio/complicações , Miocárdio/patologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Cardiotônicos/farmacocinética , Cardiotônicos/uso terapêutico , Deferiprona/farmacocinética , Deferiprona/farmacologia , Modelos Animais de Doenças , Feminino , Hemorragia/patologia , Quelantes de Ferro/farmacocinética , Quelantes de Ferro/farmacologia , Infarto do Miocárdio/patologia , SuínosRESUMO
AIMS: Bipolar electrogram (BiEGM)-based substrate maps are heavily influenced by direction of a wavefront to the mapping bipole. In this study, we evaluate high-resolution, orientation-independent peak-to-peak voltage (Vpp) maps obtained with an equi-spaced electrode array and omnipolar EGMs (OTEGMs), measure its beat-to-beat consistency, and assess its ability to delineate diseased areas within the myocardium compared against traditional BiEGMs on two orientations: along (AL) and across (AC) array splines. METHODS AND RESULTS: The endocardium of the left ventricle of 10 pigs (three healthy and seven infarcted) were each mapped using an Advisor™ HD grid with a research EnSite Precision™ system. Cardiac magnetic resonance images with late gadolinium enhancement were registered with electroanatomical maps and were used for gross scar delineation. Over healthy areas, OTEGM Vpp values are larger than AL bipoles by 27% and AC bipoles by 26%, and over infarcted areas OTEGM Vpp values are 23% larger than AL bipoles and 27% larger than AC bipoles (P < 0.05). Omnipolar EGM voltage maps were 37% denser than BiEGM maps. In addition, OTEGM Vpp values are more consistent than bipolar Vpps showing less beat-by-beat variation than BiEGM by 39% and 47% over both infarcted and healthy areas, respectively (P < 0.01). Omnipolar EGM better delineate infarcted areas than traditional BiEGMs from both orientations. CONCLUSION: An equi-spaced electrode grid when combined with omnipolar methodology yielded the largest detectable bipolar-like voltage and is void of directional influences, providing reliable voltage assessment within infarcted and non-infarcted regions of the heart.
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Cicatriz , Técnicas Eletrofisiológicas Cardíacas , Coração/fisiopatologia , Infarto do Miocárdio , Miocárdio/patologia , Taquicardia Ventricular , Animais , Cicatriz/complicações , Cicatriz/patologia , Cicatriz/fisiopatologia , Eletrocardiografia/métodos , Técnicas Eletrofisiológicas Cardíacas/instrumentação , Técnicas Eletrofisiológicas Cardíacas/métodos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Prognóstico , Suínos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologiaRESUMO
BACKGROUND: Following acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilator dysfunction. It has been observed that both infarcted and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR is a novel non-contrast technique that can quantitatively measure MBF. This study investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in swine. METHODS: Thirty-one swine were included in this study. Resting ASL-CMR was performed on 24 healthy swine (baseline group). A subset of 13 swine from the baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen swine were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1-2 days (N = 9, of which 6 were from the baseline group), 1-2 weeks (N = 8, of which 4 were from the day 1-2 group), and 4 weeks (N = 4, of which 2 were from the week 1-2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were performed post-AMI for reference. RESULTS: At rest, regional MBF and physiological noise measured from ASL-CMR were 1.08 ± 0.62 and 0.15 ± 0.10 ml/g/min, respectively. Regional MBF increased to 1.47 ± 0.62 ml/g/min with dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in the infarcted region 1-2 days, 1-2 weeks, and 4 weeks post-AMI compared to baseline (P < 0.03). This was consistent with perfusion deficit seen on first-pass CMR and with MVO seen on LGE. There were no significant differences between measured MBF in the remote regions pre and post-AMI (P > 0.60). CONCLUSIONS: ASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.
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Circulação Coronária , Vasos Coronários/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Microcirculação , Microvasos/diagnóstico por imagem , Infarto do Miocárdio/diagnóstico por imagem , Marcadores de Spin , Vasodilatação , Animais , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Dipiridamol/administração & dosagem , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Microcirculação/efeitos dos fármacos , Microvasos/efeitos dos fármacos , Microvasos/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Sus scrofa , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagemRESUMO
BACKGROUND: Myocardial hemorrhage is a frequent complication following reperfusion in acute myocardial infarction and is predictive of adverse outcomes. However, it remains unsettled whether hemorrhage is simply a marker of a severe initial ischemic insult or directly contributes to downstream myocardial damage. Our objective was to evaluate the contribution of hemorrhage towards inflammation, microvascular obstruction and infarct size in a novel porcine model of hemorrhagic myocardial infarction using cardiovascular magnetic resonance (CMR). METHODS: Myocardial hemorrhage was induced via direct intracoronary injection of collagenase in a novel porcine model of ischemic injury. Animals (N = 27) were subjected to coronary balloon occlusion followed by reperfusion and divided into three groups (N = 9/group): 8 min ischemia with collagenase (+HEM); 45 min infarction with saline (I-HEM); and 45 min infarction with collagenase (I+HEM). Comprehensive CMR was performed on a 3 T scanner at baseline and 24 h post-intervention. Cardiac function was quantified by cine imaging, edema/inflammation by T2 mapping, hemorrhage by T2* mapping and infarct/microvascular obstruction size by gadolinium enhancement. Animals were subsequently sacrificed and explanted hearts underwent histopathological assessment for ischemic damage and inflammation. RESULTS: At 24 h, the +HEM group induced only hemorrhage, the I-HEM group resulted in a non-hemorrhagic infarction, and the I+HEM group resulted in infarction and hemorrhage. Notably, the I+HEM group demonstrated greater hemorrhage and edema, larger infarct size and higher incidence of microvascular obstruction. Interestingly, hemorrhage alone (+HEM) also resulted in an observable inflammatory response, similar to that arising from a mild ischemic insult (I-HEM). CMR findings were in good agreement with histological staining patterns. CONCLUSIONS: Hemorrhage is not simply a bystander, but an active modulator of tissue response, including inflammation and microvascular and myocardial damage beyond the initial ischemic insult. A mechanistic understanding of the pathophysiology of reperfusion hemorrhage will potentially aid better management of high-risk patients who are prone to adverse long-term outcomes.
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Hemorragia/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Miocardite/diagnóstico por imagem , Miocárdio/patologia , Animais , Meios de Contraste/administração & dosagem , Circulação Coronária , Modelos Animais de Doenças , Edema Cardíaco/diagnóstico por imagem , Edema Cardíaco/patologia , Edema Cardíaco/fisiopatologia , Feminino , Gadolínio DTPA/administração & dosagem , Hemorragia/patologia , Hemorragia/fisiopatologia , Microcirculação , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocardite/patologia , Miocardite/fisiopatologia , Valor Preditivo dos Testes , Sus scrofa , Fatores de TempoRESUMO
BACKGROUND: Diabetes mellitus (DM) is estimated to become the 7th leading cause of death by 2030. Right ventricular dysfunction (RVD) complicating ST elevation myocardial infarction (STEMI) is independently associated with a higher mortality; however the relationship between DM and RVD is currently unknown. The purpose of this study was to determine whether DM is an independent predictor for the presence of right ventricular dysfunction (RVD) post STEMI. METHODS: 106 patients post primary PCI for STEMI were enrolled in the study. Cardiac MRI was performed within 48-72 h after admission in order to assess ventricular function. Statistical analysis consisted initially of descriptive statistics including Chi square, Fisher's exact, or the Wilcoxon rank sum as appropriate. Subsequently, logistic regression analysis was performed to determine independent predictors of RVD. RESULTS: The median age in the study was 58 years (IQR 53, 67). 30 % of the patients had diabetes. Of 99 patients for which RV data was available, 40 had RVD and 59 did not. Patients with DM were significantly more likely to have RVD when compared to those without diabetes (45 vs 22 %, p = 0.03). There was no significant difference in age, hypertension, smoking status, dyslipidemia, serum creatinine or peak CK levels between the two groups. After adjusting for other factors, presence of DM remained an independent predictor for the presence of RV dysfunction (OR 2.78, 95 % CI 1.12, 6.87, p = 0.03). Amongst diabetic patients, those with HbA1C ≥ 7 % had greater odds of having RVD vs those with HbA1C < 7 % (OR 5.58 (1.20, 25.78), p = 0.02). CONCLUSIONS: The presence of DM conferred an approximately threefold greater odds of being associated with RVD post STEMI. No other major cardiovascular risk factors were independently associated with the presence of RVD.
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Complicações do Diabetes/etiologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Disfunção Ventricular Direita/etiologia , Função Ventricular Direita , Idoso , Distribuição de Qui-Quadrado , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Razão de Chances , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/fisiopatologiaRESUMO
BACKGROUND: Infarct heterogeneity, as assessed by determination of the peri-infarct zone (PIZ) by cardiac magnetic resonance imaging, has been shown to be an independent predictor for the development of cardiac arrhythmias and mortality post myocardial infarction (MI). The temporal evolution of the PIZ post MI is currently unknown. Thus, the main objective of our study was to describe the temporal evolution of the PIZ over a 6 month time period in contemporarily managed ST elevation myocardial infarction (STEMI) patients. Further, given the poor prognosis associated with microvascular obstruction (MVO) post STEMI, we sought to compare the temporal evolution of the PIZ in patients with and without MVO. We hypothesized that patients with MVO would show a relative persistence of PIZ over time when compared to those without MVO. METHODS: Twenty-one patients post primary percutaneous coronary intervention were enrolled and treated with evidence based therapy. Each patient had three cardiac MRI scans at 48 h, 3 weeks and 6 months post infarction. Repeated Measures Analysis of Variance (ANOVA) was used to assess the evolution of core infarct size and peri-infarct zone size across the three time frames. RESULTS: The patients in this study were predominantly male, with ~40 % LAD territory infarction and a mean LVEF of 46 ± 7 %. Core infarct size and PIZ size both decreased significantly across the three time frames. The presence of microvascular obstruction (MVO), a known adverse prognostic factor, influenced PIZ size. Both patients with and without MVO had a significant reduction in core infarct size over time. Patients with MVO did not have a significant change in PIZ size over time (11.9 ± 6.8 %, 12.2 ± 7.5 %, 10.7 ± 6.6 % p = 0.77). In contrast, non-MVO patients did have a significant decrease in PIZ size over time (7.0 ± 5.5 %, 7.1 ± 6.5 %, 2.7 ± 2.6 %, p = 0.01). CONCLUSIONS: Peri-infarct zone size, like core infarct size, varies depending upon the timing of measurement. Patients with MVO displayed a persistence of the PIZ over time.
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Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Vasos Coronários/fisiopatologia , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Índice de Gravidade de Doença , Fatores de TempoRESUMO
PURPOSE: R2* (1/T2*) and single echo R2 (1/T2) have been calibrated to liver iron concentration (LIC) in patients with thalassemia and transfusion-dependent sickle cell disease at 1.5T. The R2*-LIC relationship is linear, whereas that of R2 is curvilinear. However, the increasing popularity of high-field scanners requires generalizing these relationships to higher field strengths. In this study, we tested the hypothesis that numerical simulation can accurately determine the field dependence of iron-mediated transverse relaxation rates. METHODS: We previously replicated the calibration curves between R2 and R2* and iron at 1.5T using Monte Carlo models incorporating realistic liver structure, iron deposit susceptibility, and proton mobility. In this paper, we extend our model to predict relaxivity-iron calibrations at higher field strengths. Predictions were validated by measuring R2 and R2* at 1.5T and 3T in six ß-thalassemia major patients. RESULTS: Predicted R2* increased twofold at 3T from 1.5T, whereas R2 increased by a factor of 1.47. Patient data exhibited a coefficient of variation of 3.6% and 7.2%, respectively, to the best-fit simulated data. Simulations over the range 0.25T-7T showed R2* increasing linearly with field strength, whereas R2 exhibited a concave-downward relationship. CONCLUSION: A model-based approach predicts alterations in relaxivity-iron calibrations with field strength without repeating imaging studies. The model may generalize to alternative pulse sequences and tissue iron distribution.
Assuntos
Sobrecarga de Ferro/fisiopatologia , Ferro/análise , Fígado/química , Imageamento por Ressonância Magnética/métodos , Modelos Biológicos , Calibragem , Humanos , Fígado/fisiologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Método de Monte CarloRESUMO
BACKGROUND: Distal coronary embolization (DCE) of thrombotic material occurs frequently during percutaneous interventions for acute myocardial infarction and can alter coronary flow grades. The significance of DCE on infarct size and myocardial function remains unsettled. The aims of this study were to evaluate the effects of DCE sufficient to cause no-reflow on infarct size, cardiac function and ventricular remodeling in a porcine acute myocardial infarction model. METHODS AND RESULTS: Female Yorkshire pigs underwent 60 min balloon occlusion of the left anterior descending coronary artery followed by reperfusion and injection of either microthrombi (prepared from autologous porcine blood) sufficient to cause no-reflow (DCE), or saline (control). Animals were sacrificed at 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI. Cardiovascular magnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) and survival kinase (Akt) activities were assessed. At 3d, DCE increased infarct size (CMR: 18.8% vs. 14.5%, p = 0.04; serum troponin-I: 13.3 vs. 6.9 ng/uL, p < 0.05) and MMP-2 activity levels (0.81 vs. 0.49, p = 0.002), with reduced activation of Akt (0.06 versus 0.26, p = 0.02). At 6 weeks, there were no differences in infarct size, ventricular volume or ejection fraction between the two groups, although infarct transmurality (70% vs. 57%, p< 0.04) and ventricular thinning (percent change in mid anteroseptal wall thickness:-25.6% vs. 0.7%, p = 0.03) were significantly increased in the DCE group. CONCLUSIONS: DCE increased early infarct size, but without affecting later infarct size, cardiac function or ventricular volumes. The significance of the later remodelling changes (ventricular thinning and transmurality) following DCE, possibly due to changes in MMP-2 activity and Akt activation, merits further study.
Assuntos
Trombose Coronária/patologia , Embolia/patologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Fenômeno de não Refluxo/patologia , Remodelação Ventricular , Angioplastia Coronária com Balão , Animais , Biomarcadores/sangue , Biópsia , Angiografia Coronária , Trombose Coronária/sangue , Trombose Coronária/fisiopatologia , Modelos Animais de Doenças , Embolia/sangue , Embolia/fisiopatologia , Feminino , Imagem Cinética por Ressonância Magnética , Metaloproteinase 2 da Matriz/metabolismo , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Fenômeno de não Refluxo/sangue , Fenômeno de não Refluxo/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Suínos , Fatores de Tempo , Troponina I/sangueRESUMO
PURPOSE: To characterize the evolution of right ventricular (RV) function post-myocardial infarction (MI), to describe the culprit vessel involved with RV injury and to assess the concordance between RV injury on magnetic resonance imaging (MRI) and RV infarct on electrocardiogram (EKG). MATERIALS AND METHODS: Thirty-one patients underwent cardiovascular magnetic resonance (CMR) examinations at three time frames post-ST elevation MI (STEMI). RESULTS: Of those with an initial normal scan, RV function did not significantly change over time (60.6 ± 6.3, 57.8 ± 6.0, 55.4 ± 5.7, P > 0.05). However, in those whose RVEF (RV ejection fraction) was initially low, it significantly increased from the first scan to the third scan (46.2 ± 3.6, 50 ± 6.6, 51.3 ± 5.2, P < 0.01). Post-hoc testing revealed a significant difference between the 48-hour and the 6-month scan, and between the 48-hour and the 3-week scan; however, there was no significant difference between the 3-week and 6-month scans. Interestingly, 23% of patients with low RVEF at baseline had the left anterior descending (LAD) as the culprit vessel. Only 15% of the low RVEF at baseline group were classified as having an RVMI by EKG criteria. CONCLUSIONS: The optimal timepoint to assess for RV injury via CMR may be 3 weeks post-acute MI. Standard EKG criteria may underestimate RV injury when compared to CMR.
Assuntos
Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Disfunção Ventricular Direita/fisiopatologia , Meios de Contraste , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Intervenção Coronária Percutânea/métodos , Prognóstico , Estudos ProspectivosRESUMO
INTRODUCTION: Cardiac magnetic resonance imaging (MRI), including late gadolinium enhancement (LGE), plays an important role in the diagnosis and prognostication of ischemic and non-ischemic myocardial injury. Conventional LGE sequences require patients to perform multiple breath-holds and require long acquisition times. In this study, we compare image quality and assessment of myocardial LGE using an accelerated free-breathing sequence to the conventional standard-of-care sequence. METHODS: In this prospective cohort study, a total of 41 patients post Coronavirus 2019 (COVID-19) infection were included. Studies were performed on a 1.5 Tesla scanner with LGE imaging acquired using a conventional inversion recovery rapid gradient echo (conventional LGE) sequence followed by the novel accelerated free-breathing (FB-LGE) sequence. Image quality was visually scored (ordinal scale from 1 to 5) and compared between conventional and free-breathing sequences using the Wilcoxon rank sum test. Presence of per-segment LGE was identified according to the American Heart Association 16-segment myocardial model and compared across both conventional LGE and FB-LGE sequences using a two-sided chi-square test. The perpatient LGE extent was also evaluated using both sequences and compared using the Wilcoxon rank sum test. Interobserver variability in detection of per-segment LGE and per-patient LGE extent was evaluated using Cohen's kappa statistic and interclass correlation (ICC), respectively. RESULTS: The mean acquisition time for the FB-LGE sequence was 17 s compared to 413 s for the conventional LGE sequence (P < 0.001). Assessment of image quality was similar between both sequences (P = 0.19). There were no statistically significant differences in LGE assessed using the FB-LGE versus conventional LGE on a per-segment (P = 0.42) and per-patient (P = 0.06) basis. Interobserver variability in LGE assessment for FB-LGE was good for per-segment (= 0.71) and per-patient extent (ICC = 0.92) analyses. CONCLUSIONS: The accelerated FB-LGE sequence performed comparably to the conventional standard-of-care LGE sequence in a cohort of patients post COVID-19 infection in a fraction of the time and without the need for breath-holding. Such a sequence could impact clinical practice by increasing cardiac MRI throughput and accessibility for frail or acutely ill patients unable to perform breath-holding.
Assuntos
COVID-19 , Meios de Contraste , Humanos , Gadolínio , Estudos Prospectivos , Respiração , Imageamento por Ressonância Magnética/métodos , Miocárdio/patologia , COVID-19/diagnóstico por imagemRESUMO
Background: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) show tremendous promise for cardiac regeneration following myocardial infarction (MI), but their transplantation gives rise to transient ventricular tachycardia (VT) in large-animal MI models, representing a major hurdle to translation. Our group previously reported that these arrhythmias arise from a focal mechanism whereby graft tissue functions as an ectopic pacemaker; therefore, we hypothesized that hPSC-CMs engineered with a dominant negative form of the pacemaker ion channel HCN4 (dnHCN4) would exhibit reduced automaticity and arrhythmogenic risk following transplantation. Methods: We used CRISPR/Cas9-mediated gene-editing to create transgenic dnHCN4 hPSC-CMs, and their electrophysiological behavior was evaluated in vitro by patch-clamp recordings and optical mapping. Next, we transplanted WT and homozygous dnHCN4 hPSC-CMs in a pig MI model and compared post-transplantation outcomes including the incidence of spontaneous arrhythmias and graft structure by immunohistochemistry. Results: In vitro dnHCN4 hPSC-CMs exhibited significantly reduced automaticity and pacemaker funny current (I f ) density relative to wildtype (WT) cardiomyocytes. Following transplantation with either dnHCN4 or WT hPSC-CMs, all recipient hearts showed transmural infarct scar that was partially remuscularized by scattered islands of human myocardium. However, in contrast to our hypothesis, both dnHCN4 and WT hPSC-CM recipients exhibited frequent episodes of ventricular tachycardia (VT). Conclusions: While genetic silencing of the pacemaker ion channel HCN4 suppresses the automaticity of hPSC-CMs in vitro, this intervention is insufficient to reduce VT risk post-transplantation in the pig MI model, implying more complex mechanism(s) are operational in vivo.
RESUMO
The type and extent of myocardial infarction encountered clinically is primarily determined by the severity of the initial ischemic insult. The purpose of the study was to differentiate longitudinal fluctuations in remodeling mechanisms in porcine myocardium following different ischemic insult durations. Animals (N = 8) were subjected to coronary balloon occlusion for either 90 or 45 min, followed by reperfusion. Imaging was performed on a 3 T MRI scanner between day-2 and week-6 postinfarction with edema quantified by T2, hemorrhage by T2*, vasodilatory function by blood-oxygenation-level-dependent T2 alterations and infarction/microvascular obstruction by contrast-enhanced imaging. The 90-min model produced large transmural infarcts with hemorrhage and microvascular obstruction, while the 45 min produced small nontransmural and nonhemorrhagic infarction. In the 90-min group, elevation of end-diastolic-volume, reduced cardiac function, persistence of edema, and prolonged vasodilatory dysfunction were all indicative of adverse remodeling; in contrast, the 45-min group showed no signs of adverse remodeling. The 45- and 90-min porcine models seem to be ideal for representing the low- and high-risk patient groups, respectively, commonly encountered in the clinic. Such in vivo characterization will be a key in predicting functional recovery and may potentially allow evaluation of novel therapies targeted to alleviate ischemic injury and prevent microvascular obstruction/hemorrhage.