Journal: Circ Cardiovasc Imaging

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Abstract

Cardiac Magnetic Resonance-Derived Extracellular Volume Mapping for the Quantification of Hepatic and Splenic Amyloid.

Chacko L, Boldrini M, Martone R, Law S, ... Hawkins PN, Fontana M
Background
Systemic amyloidosis is characterized by amyloid deposition that can involve virtually any organ. Splenic and hepatic amyloidosis occurs in certain types, in some patients but not others, and may influence prognosis and treatment. SAP (serum amyloid P component) scintigraphy is uniquely able to identify and quantify amyloid in the liver and spleen, thus informing clinical management, but it is only available in 2 centers globally. The aims of this study were to examine the potential for extracellular volume (ECV) mapping performed during routine cardiac magnetic resonance to: (1) detect amyloid in the liver and spleen and (2) estimate amyloid load in these sites using SAP scintigraphy as the reference standard.
Methods
Five hundred thirty-three patients referred to the National Amyloidosis Centre, London, between 2015 and 2017 with suspected systemic amyloidosis who underwent SAP scintigraphy and cardiac magnetic resonance with T1 mapping were studied.
Results
The diagnostic performance of ECV to detect splenic and hepatic amyloidosis was high for both organs (liver: area under the curve, -0.917 [95% CI, 0.880-0.954]; liver ECV cutoff, 0.395; sensitivity, 90.7%; specificity, 77.7%; P<0.001; spleen: area under the curve, -0.944 [95% CI, 0.925-0.964]; spleen ECV cutoff, 0.385; sensitivity, 93.6%; specificity, 87.5%; P<0.001). There was good correlation between liver and spleen ECV and amyloid load assessed by SAP scintigraphy (r=0.504, P<0.001; r=0.693, P<0.001, respectively). There was high interobserver agreement for both the liver and spleen (ECV liver intraclass correlation coefficient, 0.991 [95% CI, 0.984-0.995]; P<0.001; ECV spleen intraclass correlation coefficient, 0.995 [95% CI, 0.991-0.997]; P<0.001) with little bias across a wide range of ECV values.
Conclusions
Our study demonstrates that ECV measurements obtained during routine cardiac magnetic resonance scans in patients with suspected amyloidosis can identify and measure the magnitude of amyloid infiltration in the liver and spleen, providing important clues to amyloid type and offering a noninvasive measure of visceral amyloid burden that can help guide and track treatment.



Circ Cardiovasc Imaging: 19 Apr 2021:CIRCIMAGING121012506; epub ahead of print
Chacko L, Boldrini M, Martone R, Law S, ... Hawkins PN, Fontana M
Circ Cardiovasc Imaging: 19 Apr 2021:CIRCIMAGING121012506; epub ahead of print | PMID: 33876651
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Abstract

Comparison of Admission Lung Ultrasound and Left Ventricular End-Diastolic Pressure in Patients Undergoing Primary Percutaneous Coronary Intervention.

Neves de Araujo G, Beltrame R, Pinheiro Machado G, Luchese Custodio J, ... Vugman Wainstein M, Vugman Wainstein R
Background
Left ventricular end-diastolic pressure (LVEDP) is related to ventricular dysfunction and increased retrograde pulmonary capillary pressure. Lung ultrasound (LUS) is a sensitive and easy-to-use method for assessment of pulmonary congestion. Both methods have shown prognostic value in patients with ST-segment-elevation myocardial infarction. Our aim was to evaluate the correlation between LVEDP and bedside LUS and to compare their prognostic value in patients undergoing primary percutaneous coronary intervention.
Methods
Prospective cohort study of ST-segment-elevation myocardial infarction patients treated in a tertiary care hospital in Brazil. LUS was performed immediately before coronary angiography. LVEDP was recorded before primary percutaneous coronary intervention, blinded to LUS results. Primary outcome was any in-hospital major adverse cardiovascular event, defined as in-hospital mortality, new myocardial infarction, stroke, and new cardiogenic shock.
Results
In total, 218 patients were included; their mean age was 60 (±12) years, and 64% were men. Cardiogenic shock was present in 16.5% of patients on admission. Overall in-hospital mortality was 15%. Median LVEDP was 19 mm Hg (interquartile range, 13-28); median LUS zones positive for pulmonary congestion were 1/patient (interquartile range, 0-5); Spearman correlation between them was 0.33 (P<0.001). LVEDP and LUS C statistic for in-hospital major adverse cardiovascular event was 0.63 ([95% CI, 0.55-0.70] P=0.002) and 0.71 ([95% CI, 0.64-0.77] P<0.001), respectively. In multivariable analysis, LUS remained associated with in-hospital major adverse cardiovascular event (odds ratio, 1.14 [95% CI, 1.06-1.23]; P=0.01) for every positive LUS zone; LVEDP, however, did not (odds ratio, 1.01 [95% CI, 0.99-1.03]; P=0.23).
Conclusions
We found a weak correlation between LVEDP and LUS in our cohort of ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention. Pulmonary congestion in acute heart failure is a complex pathophysiological process and goes beyond fluid overload and hemodynamics. Unlike LVEDP, LUS was significantly associated with in-hospital major adverse cardiovascular event, new cardiogenic shock, and in-hospital mortality in multivariable analysis.



Circ Cardiovasc Imaging: 18 Apr 2021:CIRCIMAGING120011641; epub ahead of print
Neves de Araujo G, Beltrame R, Pinheiro Machado G, Luchese Custodio J, ... Vugman Wainstein M, Vugman Wainstein R
Circ Cardiovasc Imaging: 18 Apr 2021:CIRCIMAGING120011641; epub ahead of print | PMID: 33866795
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Abstract

Remnant Cholesterol and Common Carotid Artery Intima-Media Thickness in Patients With Ischemic Stroke.

Qian S, You S, Sun Y, Wu Q, ... Cao Y, Zhong C
Background
Remnant cholesterol makes great contribution to residual risk of cardiovascular disease, but population-based evidence on the relationship between remnant cholesterol and atherosclerosis is rare. Common carotid artery intima-media thickness (cIMT) is an imaging marker of subclinical atherosclerosis. We aimed to explore the association between remnant cholesterol levels and cIMT in patients with ischemic stroke.
Methods
One thousand four hundred ninety-six ischemic stroke patients with baseline serum lipids and carotid artery imaging data were included in this analysis. Fasting remnant cholesterol was calculated as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus LDL (low-density lipoprotein) cholesterol. Abnormal cIMT was defined as mean cIMT and maximum cIMT value ≥1 mm. Logistic regression and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and abnormal cIMT.
Results
The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 2.06 (1.46-2.91) for abnormal mean cIMT and 1.70 (1.23-2.35) for abnormal maximum cIMT. There were linear associations between remnant cholesterol levels and both abnormal mean cIMT (P for linearity, <0.001) and abnormal maximum cIMT (P for linearity, 0.003). Moreover, the remnant cholesterol-cIMT association remained significant in the subsample of patients with optimal LDL cholesterol levels (n=179).
Conclusions
Elevated fasting remnant cholesterol levels were positively associated with mean cIMT and maximum cIMT in patients with ischemic stroke, even in patients with optimal LDL cholesterol levels. Future prospective studies are needed to verify our findings and to assess the effect of remnant cholesterol-lowering interventions in patients with ischemic stroke.



Circ Cardiovasc Imaging: 08 Apr 2021:CIRCIMAGING120010953; epub ahead of print
Qian S, You S, Sun Y, Wu Q, ... Cao Y, Zhong C
Circ Cardiovasc Imaging: 08 Apr 2021:CIRCIMAGING120010953; epub ahead of print | PMID: 33832329
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Abstract

Association of Carotid Artery Plaque With Cardiovascular Events and Incident Coronary Artery Calcium in Individuals With Absent Coronary Calcification: The MESA.

Mehta A, Rigdon J, Tattersall MC, German CA, ... Stein JH, Shapiro MD
Background
Absence of coronary artery calcium (CAC) identifies asymptomatic individuals at low cardiovascular disease risk. Carotid artery plaque is a marker of increased risk, but its association with cardiovascular risk and incident CAC in people without CAC is unclear.
Methods
Multi-Ethnic Study of Atherosclerosis participants with CAC score of 0 at enrollment who also underwent carotid plaque measurement using B-mode ultrasonography were prospectively followed for incident coronary heart disease, stroke, and cardiovascular disease events, and CAC (score >0 on up to 3 serial computed tomography scans). The association of carotid plaque presence and plaque score (Ln[score+1]) at baseline with cardiovascular events and incident CAC was evaluated with Cox proportional hazards regression models adjusted for demographics, risk factors, and statin use.
Results
Among these 2673 participants (58 years, 64% women, 34% White, 30% Black, 24% Hispanic, and 12% Chinese), carotid plaque at baseline was observed in 973 (36%) and the median plaque score (range, 1-12) among those with plaque was 1. A total of 79 coronary heart disease, 80 stroke, and 151 cardiovascular disease events were observed during 16.1 years of follow-up. Carotid plaque presence and plaque score were independently associated with coronary heart disease risk (HRs, 1.66 [95% CI, 1.04-2.66]; and 1.48 [95% CI, 1.01-2.17], respectively) but not with stroke and cardiovascular disease risk. A total of 973 (36.4%) participants developed CAC over the evaluation period (median 9.3 years). Carotid plaque presence and plaque score were independently associated with incident CAC (HRs, 1.34 [95% CI, 1.18-1.54]; and 1.37 [95% CI, 1.21-1.54]), respectively.
Conclusions
The presence and extent of carotid plaque are associated with long-term coronary heart disease risk and incident CAC among middle-aged asymptomatic individuals with an initial CAC score of 0.



Circ Cardiovasc Imaging: 07 Apr 2021:CIRCIMAGING120011701; epub ahead of print
Mehta A, Rigdon J, Tattersall MC, German CA, ... Stein JH, Shapiro MD
Circ Cardiovasc Imaging: 07 Apr 2021:CIRCIMAGING120011701; epub ahead of print | PMID: 33827231
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Abstract

Implementation of a Myocardial Perfusion Imaging Risk Algorithm to Inform Appropriate Downstream Invasive Testing and Treatment.

Kumar A, Patel DR, Harb SC, Greenberg NL, ... Jaber WA, Cremer PC
Background
To risk stratify patients undergoing single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in accordance with appropriate use criteria for referral to coronary angiography, we developed a risk classification algorithm incorporating appropriate use criteria-defined risk features. We evaluated the association between this algorithm with downstream angiography, revascularization, and all-cause mortality.
Methods
We studied consecutive patients who underwent SPECT-MPI from January 1, 2015, to December 31, 2017, and assigned a scan risk of low, intermediate, high, or indeterminate. With this stratification, we assessed referral for angiography and revascularization within 3 months of SPECT-MPI and intermediate-term mortality.
Results
Among 12 799 patients, the mean age was 66 years, and a majority were men (56.8%). Most patients were low risk (83.6%) followed by intermediate (9.9%) and high risk (5.2%). Compared with low-risk patients, intermediate- and high-risk patients were more frequently referred for angiography (14.8% and 13.6% versus 2.0%; P<0.001) and revascularization (7.7% and 6.8% versus 0.7%; P<0.001). In 1008 propensity-matched patients, scan risk was independently associated with angiography after adjustment for ischemia, scar, or stress ejection fraction. At a mean follow-up of 2.3 years, mortality was higher with increased scan risk (high, 10.4%; intermediate, 7.1%; low, 4.1%; P<0.001). Compared with low scan risk, intermediate (hazard ratio, 1.37 [95% CI, 1.09-1.72]; P=0.008) and high scan risk (hazard ratio, 1.98 [95% CI, 1.53-2.56]; P<0.001) were associated with mortality in multivariable analysis. Similar findings were observed for those undergoing pharmacological and exercise SPECT-MPI with comparatively worse prognosis among pharmacological patients.
Conclusions
This appropriate use criteria-derived risk classification algorithm for SPECT-MPI guided referral for coronary angiography and revascularization and was significantly associated with mortality. This algorithm may serve as an important tool to reaffirm appropriate use criteria and direct management of patients with stable ischemic heart disease undergoing stress testing.



Circ Cardiovasc Imaging: 25 Mar 2021:CIRCIMAGING120011984; epub ahead of print
Kumar A, Patel DR, Harb SC, Greenberg NL, ... Jaber WA, Cremer PC
Circ Cardiovasc Imaging: 25 Mar 2021:CIRCIMAGING120011984; epub ahead of print | PMID: 33765835
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Abstract

Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging Predicts Vein Wall Scarring and Statin Benefit in Murine Venous Thrombosis.

Kessinger CW, Qi G, Hassan MZO, Henke PK, Tawakol A, Jaffer FA
Background
The postthrombotic syndrome is a common, often morbid sequela of venous thrombosis (VT) that arises from thrombus persistence and inflammatory scarring of juxtaposed vein walls and valves. Noninvasive 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can measure neutrophil inflammation in VT. Here, we hypothesized (1) early fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) VT inflammation can predict subsequent vein wall scarring (VWS) and (2) statin therapy can reduce FDG-PET VT inflammation and subsequent VWS.
Methods
C57BL/6J mice (n=75) underwent induction of stasis-induced VT of the inferior vena cava or jugular vein. Inferior vena cava VT mice (n=44) were randomized to daily oral rosuvastatin 5 mg/kg or saline starting at day -1. Subgroups of mice then underwent FDG-PET/CT 2 days after VT induction. On day 14, a subset of mice was euthanized, and VWS was assessed via histology. In vitro studies were further performed on bone marrow-derived neutrophils.
Results
Statin therapy reduced early day 2 FDG-PET VT inflammation, thrombus neutrophil influx, and plasma IL (interleukin)-6 levels. At day 14, statin therapy reduced VWS but did not affect day 2 thrombus mass, cholesterol, or white blood counts, nor reduce day 2 glucose transporter 1 or myeloperoxidase expression in thrombus or in isolated neutrophils. In survival studies, the day 2 FDG-PET VT inflammation signal as measured by mean and maximum standardized uptake values predicted the extent of day 14 VWS (area under the receiver operating characteristic curve =0.82) with a strong correlation coefficient (r) of r=0.73 and r=0.74, respectively. Mediation analyses revealed that 40% of the statin-induced VWS reduction was mediated by reductions in VT inflammation as quantified by FDG-PET.
Conclusions
Early noninvasive FDG-PET/CT imaging of VT inflammation predicts the magnitude of subsequent VWS and may provide a new translatable approach to identify individuals at risk for postthrombotic syndrome and to assess anti-inflammatory postthrombotic syndrome therapies, such as statins.



Circ Cardiovasc Imaging: 15 Mar 2021:CIRCIMAGING120011898; epub ahead of print
Kessinger CW, Qi G, Hassan MZO, Henke PK, Tawakol A, Jaffer FA
Circ Cardiovasc Imaging: 15 Mar 2021:CIRCIMAGING120011898; epub ahead of print | PMID: 33724049
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Abstract

Myocardial Fibrosis in Pediatric Patients With Ebstein\'s Anomaly.

Aly S, Seed M, Yoo SJ, Lam C, Grosse-Wortmann L
Background
Left ventricular dysfunction in Ebstein\'s anomaly (EA) is associated with higher mortality. The health of the left ventricular myocardium in children and adolescents with EA has not been investigated in detail.
Methods
Patients with unrepaired EA who had undergone cardiac magnetic resonance imaging including T1 mapping were retrospectively reviewed. Patients were compared with age- and sex-matched controls. EA severity index was calculated using volumetric measurements at end diastole ([right atrial+atrialized right ventricular volumes]/[functional right ventricular+left atrial+left ventricular volumes]). Global circumferential and radial strain and as well as strain rate were examined using cardiac magnetic resonance feature tracking.
Results
Twelve EA patients and an equal number of controls were included. Functional and atrialized right ventricular end-diastolic volumes were 84±15 and 21±13 mL/m2, respectively. Late gadolinium enhancement, confined to the right ventricle, was found in 2 patients (16%). Left ventricular native T1 values and extracellular volume fractions were higher in patients compared with controls (1026±47 versus 956±40 ms, P=0.0004 and 28.5±3.4% versus 22.5±2.6%, P<0.001, respectively). Native T1 times correlated inversely with patients\' age, body surface area, and O2 saturations (r=-0.63, -0.62, and -0.91, respectively; P=0.02, P=0.02, and P<0.0001, respectively). EA severity index ranged between 0.15 and 0.94 and correlated with T1 values (r=0.76, P=0.003). Native T1 correlated with global circumferential strain (r=0.58, P=0.04) but not ejection fraction (EF). EA patients had reduced maximum oxygen uptake (Vo2max). Vo2max correlated inversely with T1 values (r=-0.79, P=0.01).
Conclusions
Children and adolescents with EA experience an abnormal degree of diffuse myocardial fibrosis. Its association with O2 saturation points toward a role of hypoxemia in the pathogenesis of fibrosis. Larger and prospective studies are needed to evaluate the value of T1 mapping for risk stratification and monitoring in EA.



Circ Cardiovasc Imaging: 15 Mar 2021:CIRCIMAGING120011136; epub ahead of print
Aly S, Seed M, Yoo SJ, Lam C, Grosse-Wortmann L
Circ Cardiovasc Imaging: 15 Mar 2021:CIRCIMAGING120011136; epub ahead of print | PMID: 33722068
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Abstract

Right Ventricular Ejection Fraction for the Prediction of Major Adverse Cardiovascular and Heart Failure-Related Events: A Cardiac MRI Based Study of 7131 Patients With Known or Suspected Cardiovascular Disease.

Purmah Y, Lei LY, Dykstra S, Mikami Y, ... Gaztanaga J, White JA
Background
There is increasing evidence that right ventricular ejection fraction (RVEF) may provide incremental value to left ventricular (LV) ejection fraction for the prediction of major adverse cardiovascular events. To date, generalizable utility for RVEF quantification in patients with cardiovascular disease has not been established. Using a large prospective clinical outcomes registry, we investigated the prognostic value of RVEF for the prediction of major adverse cardiovascular events- and heart failure-related outcomes.
Methods
Seven thousand one hundred thirty-one consecutive patients with known or suspected cardiovascular disease undergoing cardiovascular magnetic resonance imaging were prospectively enrolled. Multichamber volumetric quantification was performed by standardized operational procedures. Patients were followed for the primary composite outcome of all-cause death, survived cardiac arrest, admission for heart failure, need for transplantation or LV assist device, acute coronary syndrome, need for revascularization, stroke, or transient ischemic attack. A secondary, heart failure focused outcome of heart failure admission, need for transplantation/LV assist device or death was also studied.
Results
Mean age was 54±15 years. The mean LV ejection fraction was 55±14% (range 6%-90%) with a mean RVEF of 54±10% (range 9%-87%). At a median follow-up of 908 days, 870 (12%) patients experienced the primary composite outcome and 524 (7%) the secondary outcome. Each 10% drop in RVEF was associated with a 1.3-fold increased risk of the primary outcome (P<0.001) and 1.5-fold increased risk of the secondary outcome (P<0.001). RVEF was an independent predictor following comprehensive covariate adjustment, inclusive of LV ejection fraction. Patients with an RVEF<40% experienced a 3.1-fold risk of the primary outcome (P<0.001) with a 1-year cumulative event rate of 22% versus 7% above this cutoff.
Conclusions
RVEF is a powerful and independent predictor of major adverse cardiac events with broad generalizability across patients with known or suspected cardiovascular disease. These findings support migration towards biventricular phenotyping for the classification of risk in clinical practice.
Registration
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04367220.



Circ Cardiovasc Imaging: 15 Mar 2021:CIRCIMAGING120011337; epub ahead of print
Purmah Y, Lei LY, Dykstra S, Mikami Y, ... Gaztanaga J, White JA
Circ Cardiovasc Imaging: 15 Mar 2021:CIRCIMAGING120011337; epub ahead of print | PMID: 33722059
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Abstract

Radiomics: The Next Frontier of Cardiac Computed Tomography.

Xu P, Xue Y, Schoepf UJ, Varga-Szemes A, ... Xing W, Zhang L
Radiomics uses advanced image analysis to extract massive amounts of quantitative information from digital images, which is not otherwise distinguishable to the human eye. The mined data can be used to explore and establish new and undiscovered correlations between these imaging features and clinical end points. Cardiac computed tomography (CT) is a first-line imaging modality for evaluating coronary artery disease and has a primary role in the assessment of cardiac structures. Conventional interpretation of cardiac CT images relies mostly on subjective and qualitative analysis, as well as basic geometric quantification. To date, some proof-of-concept studies have demonstrated the feasibility and diagnostic performance of cardiac CT radiomics analysis. This review describes the current literature on radiomics in cardiac CT and discusses its advantages, challenges, and future directions. Although much evidences are needed in this field, cardiac CT radiomics has a lot to offer to patients and physicians with potential to define cardiac disease phenotypes on imaging with higher precision.



Circ Cardiovasc Imaging: 15 Mar 2021:CIRCIMAGING120011747; epub ahead of print
Xu P, Xue Y, Schoepf UJ, Varga-Szemes A, ... Xing W, Zhang L
Circ Cardiovasc Imaging: 15 Mar 2021:CIRCIMAGING120011747; epub ahead of print | PMID: 33722057
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Abstract

Global Left Ventricular Myocardial Work Efficiency and Long-Term Prognosis in Patients After ST-Segment-Elevation Myocardial Infarction.

Lustosa RP, Butcher SC, van der Bijl P, El Mahdiui M, ... Bax JJ, Delgado V
Background
Left ventricular (LV) global longitudinal strain has demonstrated incremental prognostic value over LV ejection fraction in patients with ST-segment-elevation myocardial infarction. However, LV global longitudinal strain does not take into consideration the effect of afterload. Novel speckle-tracking echocardiographic indices of myocardial work integrate blood pressure measurements (afterload) with LV global longitudinal strain. The present study aimed to investigate the prognostic value of global LV myocardial work efficiency (GLVMWE; reflecting LV performance) obtained from pressure-strain loops with echocardiography in patients with ST-segment-elevation myocardial infarction.
Methods
A total of 507 ST-segment-elevation myocardial infarction patients (mean age, 61±11 years; 76% men) were retrospectively analyzed. LV ejection fraction and GLVMWE were measured by transthoracic echocardiography within 48 hours of admission. GLVMWE was defined as the ratio of constructive work divided by the sum of constructive and wasted work in all LV segments and expressed as a percentage. Spline curve analysis was used to define the association between reduced GLVMWE and all-cause death.
Results
After a median follow-up of 80 months (interquartile range, 67-97 months), 40 (8%) patients died. Patients with reduced GLVMWE (<86%) showed higher cumulative rates of all-cause mortality (17.5% versus 4.7%; log-rank P<0.001) in comparison with patients with preserved GLVMWE (≥86%). Reduced GLVMWE (<86%) showed an independent association with all-cause mortality (hazard ratio, 3.167 [95% CI, 1.679-5.972]; P<0.001).
Conclusions
Reduced GLVMWE (<86%) measured by transthoracic echocardiography within 48 hours of admission in ST-segment-elevation myocardial infarction patients is associated with worse long-term survival.



Circ Cardiovasc Imaging: 27 Feb 2021; 14:e012072
Lustosa RP, Butcher SC, van der Bijl P, El Mahdiui M, ... Bax JJ, Delgado V
Circ Cardiovasc Imaging: 27 Feb 2021; 14:e012072 | PMID: 33653082
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Abstract

Molecular Mechanisms of Adenosine Stress T1 Mapping.

Shah SA, Reagan CE, French BA, Epstein FH
Background
Adenosine stress T1 mapping is an emerging magnetic resonance imaging method to investigate coronary vascular function and myocardial ischemia without application of a contrast agent. Using gene-modified mice and 2 vasodilators, we elucidated and compared the mechanisms of adenosine myocardial perfusion imaging and adenosine T1 mapping.
Methods
Wild-type (WT), A2AAR-/- (adenosine A2A receptor knockout), A2BAR-/- (adenosine A2B receptor knockout), A3AR-/- (adenosine A3 receptor knockout), and eNOS-/- (endothelial nitric oxide synthase knockout) mice underwent rest and stress perfusion magnetic resonance imaging (n=8) and T1 mapping (n=10) using either adenosine, regadenoson (a selective A2AAR agonist), or saline. Myocardial blood flow and T1 were computed from perfusion imaging and T1 mapping, respectively, at rest and stress to assess myocardial perfusion reserve and T1 reactivity (ΔT1). Changes in heart rate for each stress agent were also calculated. Two-way ANOVA was used to detect differences in each parameter between the different groups of mice.
Results
Myocardial perfusion reserve was significantly reduced only in A2AAR-/- compared to WT mice using adenosine (1.06±0.16 versus 2.03±0.52, P<0.05) and regadenoson (0.98±026 versus 2.13±0.75, P<0.05). In contrast, adenosine ΔT1 was reduced compared with WT mice (3.88±1.58) in both A2AAR-/- (1.63±1.32, P<0.05) and A2BAR-/- (1.55±1.35, P<0.05). Furthermore, adenosine ΔT1 was halved in eNOS-/- (1.76±1.46, P<0.05) versus WT mice. Regadenoson ΔT1 was approximately half of adenosine ΔT1 in WT mice (1.97±1.50, P<0.05), and additionally, it was significantly reduced in eNOS-/- mice (-0.22±1.46, P<0.05). Lastly, changes in heart rate was 2× greater using regadenoson versus adenosine in all groups except A2AAR-/-, where heart rate remained constant.
Conclusions
The major findings are that (1) although adenosine myocardial perfusion reserve is mediated through the A2A receptor, adenosine ΔT1 is mediated through the A2A and A2B receptors, (2) adenosine myocardial perfusion reserve is endothelial independent while adenosine ΔT1 is partially endothelial dependent, and (3) ΔT1 mediated through the A2A receptor is endothelial dependent while ΔT1 mediated through the A2B receptor is endothelial independent.



Circ Cardiovasc Imaging: 27 Feb 2021; 14:e011774
Shah SA, Reagan CE, French BA, Epstein FH
Circ Cardiovasc Imaging: 27 Feb 2021; 14:e011774 | PMID: 33706537
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This program is still in alpha version.