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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Abstract

Risk Factors for Left Ventricular Dysfunction Following Surgical Management of Cardiac Fibroma.

Beroukhim RS, Geva T, Del Nido P, Sleeper LA, ... Walsh EP, Nathan M
Background
Surgical resection of cardiac fibromas in children reduces hemodynamic and arrhythmia burden; however, little is known about postoperative left ventricular (LV) function. We aimed to evaluate factors associated with postoperative LV dysfunction.
Methods
In this retrospective observational cohort study, imaging data were reviewed from 41 patients who had undergone surgical resection of a cardiac fibroma. Tumor volume was indexed to body surface area (tumor volume index). Right ventricular tumors were excluded from analysis of postoperative ventricular function. Postoperative regional wall motion abnormality score was defined as number of wall segments with regional wall motion abnormality, and LV dysfunction was defined as LV ejection fraction <50%. Cardiovascular magnetic resonance-derived strain was low if <5%ile by previously published normative data.
Results
Of 41 patients who underwent resection at a median age of 2.1 years (range, 0.5-19), 37 fibromas were in the LV, (29 free wall and 8 septal), and 4 in the right ventricle. Preoperative median tumor volume index was 66 mL/m2 (range, 11-376). Of 37 patients with LV tumors, younger patients had larger tumor volume index and higher grades of preoperative mitral regurgitation (P<0.001). Larger tumor volume index correlated with higher postoperative regional wall motion abnormality score (P<0.001). By paired pre- and post-operative cardiovascular magnetic resonance (n=14), LV end-diastolic volume increased (mean 76 versus 101 mL/m2, P=0.011), with decreased LV ejection fraction (mean 60% versus 55%, P=0.014), a higher prevalence of low global circumferential strain (36% versus 64%, P=0.045), and decreased cardiac index (mean 4.8 versus 3.9 L/[min·m2], P=0.039). More than mild preoperative mitral regurgitation was the only independent predictor of predischarge LV dysfunction (odds ratio, 22 [95% CI, 2.8-179], P=0.008).
Conclusions
Surgical resection of LV fibroma is associated with regional wall motion abnormality, increased LV volume, and reduced systolic function. Children with significant preoperative mitral regurgitation are at highest risk for LV dysfunction and warrant ongoing close surveillance.



Circ Cardiovasc Imaging: 30 Jan 2021; 14:e011748
Beroukhim RS, Geva T, Del Nido P, Sleeper LA, ... Walsh EP, Nathan M
Circ Cardiovasc Imaging: 30 Jan 2021; 14:e011748 | PMID: 33517672
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Abstract

Impact of New Grading System and New Hemodynamic Classification on Long-Term Outcome in Patients With Severe Tricuspid Regurgitation.

Omori T, Uno G, Shimada S, Rader F, Siegel RJ, Shiota T
Background
A new grading of tricuspid regurgitation (TR) beyond severe has been proposed. However, few studies assessing the validity of such a new grading scheme of TR have been conducted. Therefore, we evaluated associations of TR grades beyond severe with patient outcome and hemodynamics.
Methods
We retrospectively studied patients who underwent 2-dimensional echocardiography and were diagnosed with severe TR between January 2014 and December 2015. According to the vena contracta width of TR (VC), the patients were classified into 2 groups: VC under 14 mm (VC<14 mm) and VC 14 mm or greater (VC≥14 mm). Hemodynamic parameters were estimated by echocardiography and were obtained by right heart catheterization. Cardiovascular events were defined as cardiovascular death or admission for heart failure.
Results
A total of 679 patients (mean 72±17 years, 56% women) were included. During follow-up (median, 158 days; range, 29-891), 210 patients experienced cardiovascular events. By multivariate analysis, VC≥14 mm and left ventricular ejection fraction were independent predictors of cardiovascular events (hazard ratio, 1.57 [1.06-2.33]; hazard ratio, 0.99 [0.98-0.99], respectively). Patients with VC≥14 mm had significantly lower cardiac index (median, 1.8 versus 2.1 L/min per m2, P=0.001) and a higher prevalence of right atrial pressure 15 mm Hg (74% versus 60%, P<0.001) on echocardiography. Also, right heart catheterization confirmed higher right atrial pressure in patients with VC≥14 mm than those with VC<14 mm (16±8 versus 12±6 mm Hg, P=0.004). The new subset classification developed by cardiac index and right atrial pressure both on echocardiography predicted cardiovascular events (Log-rank P<0.001).
Conclusions
The relationship of VC≥14 mm to adverse outcome and poor hemodynamics showed the clinical relevance and need of a new grading system beyond severe. The new hemodynamic subset classification provides additional prognostic value for cardiovascular events in patients with severe TR.



Circ Cardiovasc Imaging: 30 Jan 2021; 14:e011805
Omori T, Uno G, Shimada S, Rader F, Siegel RJ, Shiota T
Circ Cardiovasc Imaging: 30 Jan 2021; 14:e011805 | PMID: 33517670
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Abstract

Image-Based Computational Model Predicts Dobutamine-Induced Hemodynamic Changes in Patients With Aortic Coarctation.

Runte K, Brosien K, Schubert C, Nordmeyer J, ... Kelm M, Goubergrits L
Background
Pharmacological stress testing can help to uncover pathological hemodynamic conditions and is, therefore, used in the clinical routine to assess patients with structural heart diseases such as aortic coarctation with borderline indication for treatment. The aim of this study was to develop and test a reduced-order model predicting dobutamine stress induced pressure gradients across the coarctation.
Methods
The reduced-order model was developed based on n=21 imaging data sets of patients with aortic coarctation and a meta-analysis of subjects undergoing dobutamine stress testing. Within an independent test cohort of n=21 patients with aortic coarctation, the results of the model were compared with dobutamine stress testing during catheterization.
Results
In n=19 patients responding to dobutamine stress testing, pressure gradients across the coarctation during dobutamine stress increased from 15.7±5.1 to 33.6±10.3 mm Hg (paired t test, P<0.001). The model-predicted pressure gradients agreed with catheter measurements with a mean difference of -2.2 mm Hg and a limit of agreement of ±11.16 mm Hg according to Bland-Altman analysis. Significant equivalence between catheter-measured and simulated pressure gradients during stress was found within the study cohort (two 1-sided tests of equivalence with a noninferiority margin of 5.0 mm Hg, 33.6±10.33 versus 31.5±11.15 mm Hg, P=0.021).
Conclusions
The developed reduced-order model can instantly predict dobutamine-induced hemodynamic changes with accuracy equivalent to heart catheterization in patients with aortic coarctation. The method is easy to use, available as a web-based calculator, and provides a promising alternative to conventional stress testing in the clinical routine. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02591940.



Circ Cardiovasc Imaging: 30 Jan 2021; 14:e011523
Runte K, Brosien K, Schubert C, Nordmeyer J, ... Kelm M, Goubergrits L
Circ Cardiovasc Imaging: 30 Jan 2021; 14:e011523 | PMID: 33591212
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Abstract

Epicardial Surface Area of Infarction: A Stable Surrogate of Microvascular Obstruction in Acute Myocardial Infarction.

Smulders MW, Van Assche LMR, Bekkers SCAM, Nijveldt R, ... Judd RM, Kim RJ
Background
Microvascular obstruction (MO) is a pathophysiologic complication of acute myocardial infarction that portends poor prognosis; however, it is transient and disappears with infarct healing. Much remains unknown regarding its pathophysiology and whether there are predictors of MO that could function as stable surrogates. We tested for clinical and cardiovascular magnetic resonance predictors of MO to gain insight into its pathophysiology and to find a stable surrogate.
Methods
Three hundred two consecutive patients from 2 centers underwent cardiovascular magnetic resonance within 2 weeks of first acute myocardial infarction. Three measures of infarct morphology: infarct size, transmurality, and a new index-the epicardial surface area (EpiSA) of full-thickness infarction-were quantified on delayed-enhancement cardiovascular magnetic resonance.
Results
Considering all clinical characteristics, only measures of infarct morphology were independent predictors of MO. EpiSA was the strongest predictor of MO and provided incremental predictive value beyond that of infarct size and transmurality (P<0.0001). In patients with 3-month follow-up cardiovascular magnetic resonance (n=81), EpiSA extent remained stable while MO disappeared, and EpiSA was a predictor of adverse ventricular remodeling. After 20 months of follow-up, 11 died and 1 had heart transplantation. Patients with an EpiSA larger than the median value (≥6%) had worse outcome than those with less than the median value (adverse events: 6.4% versus 1.9%, P=0.045).
Conclusions
The EpiSA of infarction is a novel index of infarct morphology which accurately predicts MO during the first 2 weeks of MI, but unlike MO, does not disappear with infarct healing. This index has potential as a stable surrogate of the presence of acute MO and may be useful as a predictor of adverse remodeling and outcome which is less dependent on the time window of patient assessment.



Circ Cardiovasc Imaging: 30 Jan 2021; 14:e010918
Smulders MW, Van Assche LMR, Bekkers SCAM, Nijveldt R, ... Judd RM, Kim RJ
Circ Cardiovasc Imaging: 30 Jan 2021; 14:e010918 | PMID: 33586449
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Abstract

Hemodynamics and Clinical Implications of Occult Left Ventricular Dysfunction in Adults Undergoing Ebstein Anomaly Repair.

Egbe AC, Miranda WR, Dearani JA, Connolly HM
Background
Left ventricular global longitudinal strain (LVGLS) can detect early phases of LV systolic dysfunction, but its application has not been studied in Ebstein anomaly. We hypothesized that LVGLS can detect early phases of LV systolic dysfunction and that patients with occult LV systolic dysfunction will have worse hemodynamics, end-organ dysfunction, and suboptimal postoperative LV reverse remodeling after tricuspid valve surgery in comparison to patients with normal LV systolic function.
Methods
In this retrospective cohort study, 371 Ebstein patients that underwent tricuspid valve surgery were divided into 3 groups: normal LV systolic function (normal LVGLS and LV ejection fraction; n=244, 77%), occult LV systolic dysfunction (abnormal LVGLS with normal LV ejection fraction; n=44, 14%), and overt LV systolic dysfunction (abnormal LVGLS and LV ejection fraction; n=27, 9%).
Results
Compared with the normal LV function group, the occult group had smaller LV volume and cardiac output (2.1±0.4 versus 2.9±0.6 L/min per m2, P<0.001), worse end-organ dysfunction (glomerular filtration rate, 78±14 versus 91±18 mL/min per 1.73 m2, P=0.01), and suboptimal postoperative LV reverse remodeling. Although both the occult and overt groups had a similar degree of end-organ dysfunction (glomerular filtration rate, 78±14 versus 82±16 mL/min per 1.73 m2, P=0.3), the occult group was less likely to be on heart failure therapy (48% versus 96%, P<0.001).
Conclusions
Abnormal LVGLS was associated with suboptimal postoperative LV reverse remodeling. These data suggest that LVGLS can potentially be used for risk stratification and provides a foundation for further studies to determine whether optimal heart failure therapy or tricuspid valve intervention can improve outcomes for LV systolic dysfunction in patients with Ebstein anomaly.



Circ Cardiovasc Imaging: 30 Jan 2021; 14:e011739
Egbe AC, Miranda WR, Dearani JA, Connolly HM
Circ Cardiovasc Imaging: 30 Jan 2021; 14:e011739 | PMID: 33583197
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Abstract

Prognostic Value of Pulmonary Transit Time by Cardiac Magnetic Resonance on Mortality and Heart Failure Hospitalization in Patients With Advanced Heart Failure and Reduced Ejection Fraction.

Houard L, Amzulescu MS, Colin G, Langet H, ... Pouleur AC, Gerber BL
Background
Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause.
Methods
We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease. Results PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively, P<0.001), and correlated not only with New York Heart Association class, cMR-LV and cMR-right ventricular (RV) volumes, cMR-RV and cMR-LV ejection fraction, and feature tracking global longitudinal strain, but also with cardiac output. Over 6-year median follow-up, 182 patients died and 200 reached the secondary endpoint. By multivariate Cox analysis, PTT was an independent and significant predictor of both endpoints after adjustment for Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Importantly in multivariable analysis, PTT in beats had significantly higher additional prognostic value to predict not only overall mortality (χ2 to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16-1.58]; P<0.001) but also the secondary composite endpoints (χ2 to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21-1.60]; P<0.001) than cMR-LV ejection fraction, cMR-RV ejection fraction, LV-feature tracking global longitudinal strain, or RV-feature tracking global longitudinal strain. Importantly, PTT was independent and complementary to both pulmonary artery pressure and reduced RV ejection fraction<42% to predict overall mortality and secondary combined endpoints.
Conclusions
Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03969394.



Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011680
Houard L, Amzulescu MS, Colin G, Langet H, ... Pouleur AC, Gerber BL
Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011680 | PMID: 33438438
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Abstract

Prognostic Impact of Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance in Myocarditis: A Systematic Review and Meta-Analysis.

Georgiopoulos G, Figliozzi S, Sanguineti F, Aquaro GD, ... Masci PG, Ismail TF
Background
Patients with acute myocarditis (AM) are at increased risk of adverse cardiac events after the index episode. Late gadolinium enhancement (LGE) detected by cardiovascular magnetic resonance in patients with AM plays an important diagnostic role, but its prognostic significance remains unresolved. This systematic review and meta-analysis sought to assess the prognostic implications of cardiovascular magnetic resonance-derived LGE in patients with AM.
Methods
Data search was conducted from inception through February 28, 2020, using the following Medical Subject Heading terms: Myocarditis, CMR, Magnetic Resonance Imaging, Magnetic Resonance. From 2422 articles retrieved, we selected 11 studies reporting baseline cardiovascular magnetic resonance assessment and long-term clinical follow-up in patients with AM. Hazard ratios and CIs for a combined clinical end point were recorded for LGE presence, extent (>2 segments or >10% of left ventricular [LV] mass or >17g) and location (anteroseptal versus non-anteroseptal). A combined end point comprised all-cause mortality, cardiac mortality, and major adverse cardiovascular events. Hartung and Knapp correction improved robustness of the results. Prespecified sensitivity analyses explored potential sources of heterogeneity. The meta-analysis was conducted according to the Meta-analysis of Observational Studies in Epidemiology guidelines.
Results
LGE presence (pooled hazard ratios, 3.28 [95% CIs, 1.69-6.39], P<0.001 [95% CIs, 1.33-8.11] after Hartung and Knapp correction) and anteroseptal LGE (pooled-hazard ratios, 2.58 [95% CIs, 1.87-3.55], P<0.001 [95% CIs, 1.64-4.06] after Hartung and Knapp correction) were associated with an increased risk of the combined end point. Extensive LGE was associated with worse outcomes (pooled-hazard ratios, 1.96 [95% CIs, 1.08-3.56], P=0.027), but this association was not confirmed after Hartung and Knapp correction (95% CIs, 0.843-4.57).
Conclusions
LGE presence and anteroseptal location at baseline cardiovascular magnetic resonance are important independent prognostic markers that herald an increased risk of adverse cardiac outcomes in patients with AM. Registration: https://www.crd.york.ac.uk/PROSPERO/ Unique identifier: CRD42019146619.



Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011492
Georgiopoulos G, Figliozzi S, Sanguineti F, Aquaro GD, ... Masci PG, Ismail TF
Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011492 | PMID: 33441003
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Abstract

Left Atrial Volumetric/Mechanical Coupling Index: A Novel Predictor of Outcome in Heart Failure With Reduced Ejection Fraction.

Benfari G, Essayagh B, Nistri S, Maalouf J, ... Michelena HI, Enriquez-Sarano M
Background
Left atrial assessment is complex, particularly in heart failure with reduced ejection fraction due to interactions with functional mitral regurgitation (FMR). Pilot data suggest that left atrial volumetric/mechanical coupling index (LACI) may be useful, but large outcome data are lacking.
Methods
We enrolled a comprehensively characterized cohort of patients in sinus rhythm with heart failure with reduced ejection fraction diagnosis at Mayo Clinic from 2007 to 2011. Routinely measured left atrial volume index and tissue-doppler-imaging a\' allowed LACI calculation as (left atrial volume index)/(tissue-doppler-imaging a\'). Survival was the outcome measured.
Results
The cohort\'s 4196 patients (69 [58-77] years, ejection fraction 40 [31-45]%) had mild FMR in 1505 and moderate-severe FMR in 1068. LACI was overall 5.06 (3.50-8.10) and increased with each FMR grade (3.86 [2.94-5.29] without FMR, 5.38 [3.80-8.02] with mild, 5.45 [1.49-8.07] with moderate/severe FMR; P<0.0001). At diagnosis, higher LACI was independently determined by more severe FMR and by higher left ventricular mass index, lower ejection fraction, higher E/e\', and lower glomerular filtration rate (all P<0.0001). During follow-up 1588 (38%) patients died. In spline modeling, excess mortality appeared around LACI=6 and steeply increased thereafter (5-year survival 72±1% with LACI<6 and 49±2% with LACI ≥6, P<0.0001). Multivariable comprehensive adjustment showed LACI strong association with excess mortality (adjusted hazard ratio, 1.41 [1.23-1.61], P<0.0001 for LACI ≥6). Independent link to mortality persistent across FMR grades (adjusted hazard ratio, 1.45 [1.13-1.86], P=0.004 without FMR, 1.42 [1.16-1.77], P=0.0008 with mild FMR, and 1.38 [1.01-1.66], P=0.04 with moderate/severe FMR) without interaction (P=0.3). LACI independent impact on outcome was incremental to that of left atrial volume index, tissue-doppler-imaging a\', or any other characteristic including the Meta-Analysis Global Group in Chronic-score (least significant P=0.02).
Conclusions
In this large cohort, left atrial volumetric/mechanical coupling measured by LACI in routine practice integrates the influence of several morphological/hemodynamic determinants but displays progressive deterioration with increasing FMR severity in heart failure with reduced ejection fraction. About outcome, higher LACI is strongly, independently, and incrementally associated with excess mortality, irrespective of FMR grade and in all subsets. Hence, LACI is a novel and critical measure in heart failure with reduced ejection fraction, quantifiable in routine practice, which should be integrated in prognostication and decision-making.



Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011608
Benfari G, Essayagh B, Nistri S, Maalouf J, ... Michelena HI, Enriquez-Sarano M
Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011608 | PMID: 33463368
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Abstract

Myocardial Inflammation and Dysfunction in COVID-19-Associated Myocardial Injury.

Weckbach LT, Curta A, Bieber S, Kraechan A, ... Hausleiter J, Grabmaier U
Background
Myocardial injury, defined by elevated troponin levels, is associated with adverse outcome in patients with coronavirus disease 2019 (COVID-19). The frequency of cardiac injury remains highly uncertain and confounded in current publications; myocarditis is one of several mechanisms that have been proposed.
Methods
We prospectively assessed patients with myocardial injury hospitalized for COVID-19 using transthoracic echocardiography, cardiac magnetic resonance imaging, and endomyocardial biopsy.
Results
Eighteen patients with COVID-19 and myocardial injury were included in this study. Echocardiography revealed normal to mildly reduced left ventricular ejection fraction of 52.5% (46.5%-60.5%) but moderately to severely reduced left ventricular global longitudinal strain of -11.2% (-7.6% to -15.1%). Cardiac magnetic resonance showed any myocardial tissue injury defined by elevated T1, extracellular volume, or late gadolinium enhancement with a nonischemic pattern in 16 patients (83.3%). Seven patients (38.9%) demonstrated myocardial edema in addition to tissue injury fulfilling the Lake-Louise criteria for myocarditis. Combining cardiac magnetic resonance with speckle tracking echocardiography demonstrated functional or morphological cardiac changes in 100% of investigated patients. Endomyocardial biopsy was conducted in 5 patients and revealed enhanced macrophage numbers in all 5 patients in addition to lymphocytic myocarditis in 1 patient. SARS-CoV-2 RNA was not detected in any biopsy by quantitative real-time polymerase chain reaction. Finally, follow-up measurements of left ventricular global longitudinal strain revealed significant improvement after a median of 52.0 days (-11.2% [-9.2% to -14.7%] versus -15.6% [-12.5% to -19.6%] at follow-up; P=0.041).
Conclusions
In this small cohort of COVID-19 patients with elevated troponin levels, myocardial injury was evidenced by reduced echocardiographic left ventricular strain, myocarditis patterns on cardiac magnetic resonance, and enhanced macrophage numbers but not predominantly lymphocytic myocarditis in endomyocardial biopsies.



Circ Cardiovasc Imaging: 30 Dec 2020; 14:e012220
Weckbach LT, Curta A, Bieber S, Kraechan A, ... Hausleiter J, Grabmaier U
Circ Cardiovasc Imaging: 30 Dec 2020; 14:e012220 | PMID: 33463366
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Abstract

Spatially Weighted Coronary Artery Calcium Score and Coronary Heart Disease Events in the Multi-Ethnic Study of Atherosclerosis.

Shea S, Navas-Acien A, Shimbo D, Brown ER, ... Barr RG, Kronmal R
Background
A limitation of the Agatston coronary artery calcium (CAC) score is that it does not use all of the calcium density information in the computed tomography scan such that many individuals have a score of zero. We examined the predictive validity for incident coronary heart disease (CHD) events of the spatially weighted coronary calcium score (SWCS), an alternative scoring method for CAC that assigns scores to individuals with Agatston CAC=0.
Methods
The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study that conducted a baseline exam from 2000 to 2002 in 6814 participants including computed tomography scanning for CAC. Subsequent exams and systematic follow-up of the cohort for outcomes were performed. Statistical models were adjusted using the MESA risk score based on age, sex, race/ethnicity, systolic blood pressure, use of hypertension medications, diabetes, total and HDL (high-density lipoprotein) cholesterol, use of lipid-lowering medications, smoking status, and family history of heart attack.
Results
In the 3286 participants with Agatston CAC=0 at baseline and for whom SWCS was computed, 98 incident CHD events defined as definite or probably myocardial infarction or definite CHD death occurred during a median follow-up of 15.1 years. In this group, SWCS predicted incident CHD events after multivariable adjustment (hazard ratio=1.30 per SD of natural logarithm [SWCS] [95% CI, 1.04-1.60]; P=0.005); and progression from Agatston CAC=0 at baseline to CAC>0 at subsequent exams (multivariable-adjusted incidence rate difference per SD of natural logarithm [SWCS] per 100 person-years 1.68 [95% CI, 1.03-2.33]; P<0.0001).
Conclusions
SWCS predicts incident CHD events in individuals with Agatston CAC score=0 as well as conversion to Agatston CAC>0 at repeat computed tomography scanning at later exams. SWCS has predictive validity as a subclinical phenotype and marker of CHD risk in individuals with Agatston CAC=0.



Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011981
Shea S, Navas-Acien A, Shimbo D, Brown ER, ... Barr RG, Kronmal R
Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011981 | PMID: 33461306
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Abstract

Higher Acceleration/Ejection Time Ratio Predicts Impaired Outcome in Aortic Valve Stenosis.

Einarsen E, Cramariuc D, Bahlmann E, Midtbo H, Chambers JB, Gerdts E
Background
Acceleration time (AT)/ejection time (ET) ratio is a marker of aortic valve stenosis (AS) severity and predicts outcome in moderate-severe AS.
Methods
We explored the association of increased AT/ET ratio on prognosis in 1530 asymptomatic patients with presumably mild-moderate AS, normal ejection fraction, and without known diabetes or cardiovascular disease. Patients were part of the SEAS study (Simvastatin Ezetimibe Aortic Stenosis). Patients were grouped according to the optimal AT/ET ratio threshold to predict cardiovascular death and heart failure hospitalization. Low-gradient severe AS was identified as combined valve area ≤1.0 cm2 and mean gradient <40 mm Hg. Outcome was assessed in Cox regression analyses, and results are reported as hazard ratio and 95% CI.
Results
Higher AT/ET ratio was significantly associated with lower systolic blood pressure, lower left ventricular ejection fraction, lower stress-corrected midwall shortening, low flow, and with higher left ventricular mass and higher peak aortic jet velocity. AT/ET ratio ≥0.32 provided the optimal cutoff for predicting incident cardiovascular death and heart failure hospitalization in the total study sample. In patients with low-gradient severe AS, this threshold was >0.32. AT/ET ratio ≥0.32 had a 79% higher risk of cardiovascular death and heart failure hospitalization (hazard ratio, 1.79 [95% CI, 1.20-2.68]). In patients with low-gradient severe AS, AT/ET ratio >0.32 was associated with a 2-fold higher risk of cardiovascular death and heart failure hospitalization (hazard ratio, 2.15 [95% CI, 1.22-3.77]).
Conclusions
In asymptomatic nonsevere AS and low-gradient severe AS, higher AT/ET ratio was associated with increased cardiovascular morbidity and mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00092677.



Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011467
Einarsen E, Cramariuc D, Bahlmann E, Midtbo H, Chambers JB, Gerdts E
Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011467 | PMID: 33461302
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Abstract

Myocardial Ischemia in the Management of Chronic Coronary Artery Disease: Past and Present.

Gibbons RJ
For many years, stress-induced myocardial ischemia has been considered important in the management of chronic coronary artery disease. Early evidence focused on the exercise ECG and the Duke treadmill score. In the 1970s, randomized clinical trials, which compared coronary artery bypass surgery to medical therapy, enrolled patients who were very different from contemporary practice and had inconsistent results. Surgery appeared to be of greatest benefit in high-risk patients defined by anatomy (such as left main disease) or stress-induced ischemia. However, randomized clinical trials of revascularization versus contemporary medical therapy over the past 20 years have been surprisingly negative. Nuclear cardiology substudies from these trials reported inconsistent results. Two observational studies from a single-center provided the best evidence for the use of stress-induced ischemia to identify patients who were most likely to benefit from revascularization. The recently completed ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) was designed to test the hypothesis that revascularization would improve outcomes in patients with moderate-severe ischemia on stress testing. Unfortunately, 14.2% of the randomized patients had either mild or no ischemia on core lab review. Nearly one-quarter of the patients were randomized on the basis of an exercise ECG without imaging. The negative results of the trial reflect the long-term population decline in coronary artery disease and abnormal stress tests, as well as improvements in patient outcome due to optimal medical therapy. Topics requiring further research are presented. The implications of the trial for the use of both stress imaging and coronary computed tomography angiography in clinical practice are examined.



Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011615
Gibbons RJ
Circ Cardiovasc Imaging: 30 Dec 2020; 14:e011615 | PMID: 33455408
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This program is still in alpha version.