Hybrid Cardiac Magnetic Resonance/Fluorodeoxyglucose Positron Emission Tomography to Differentiate Active From Chronic Cardiac Sarcoidosis

ObjectivesThe purpose of this study was to investigate the diagnostic value of simultaneous hybrid cardiac magnetic resonance (CMR) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detection and differentiation of active (aCS) from chronic (cCS) cardiac sarcoidosis.BackgroundLate gadolinium enhancement (LGE) CMR and FDG-PET are both established imaging techniques for the detection of CS. However, there are limited data regarding the value of a comprehensive simultaneous hybrid CMR/FDG-PET imaging approach that includes CMR mapping techniques.MethodsForty-three patients with biopsy-proven extracardiac sarcoidosis (median age: 48 years, interquartile range: 37-57 years, 65% male) were prospectively enrolled for evaluation of suspected CS. After dietary preparation for suppression of myocardial glucose metabolism, patients were evaluated on a 3-T hybrid PET/MR scanner. The CMR protocol included T1 and T2 mapping, myocardial function, and LGE imaging. We assumed aCS if PET and CMR (ie, LGE or T1/T2 mapping) were both positive (PET+/CMR+), cCS if PET was negative but CMR was positive (PET?/CMR+), and no CS if patients were CMR negative regardless of PET findings.ResultsAmong the 43 patients, myocardial glucose uptake was suppressed successfully in 36 (84%). Hybrid CMR/FDG-PET revealed aCS in 13 patients (36%), cCS in 5 (14%), and no CS in 18 (50%). LGE was present in 14 patients (39%); T1 mapping was abnormal in 10 (27%) and T2 mapping abnormal in 2 (6%). CS was diagnosed based on abnormal T1 mapping in 4 out of 18 CS patients (22%) who were LGE negative. PET FDG uptake was present in 17 (47%) patients.ConclusionsComprehensive simultaneous hybrid CMR/FDG-PET imaging is useful for the detection of CS and provides additional value for identifying active disease. Our results may have implications for enhanced diagnosis as well as improved identification of patients with aCS in whom anti-inflammatory therapy may be most beneficial.     

Parametric Imaging of Biologic Activity of Atherosclerosis Using Dynamic Whole-Body Positron Emission Tomography

BackgroundFor molecular imaging of atherosclerotic vessel wall activity, tracer kinetic analysis may yield improved contrast versus blood, more robust quantitative parameters, and more reliable characterization of systems biology.ObjectivesThe authors introduce a novel dynamic whole-body positron emission tomography (PET) protocol that is enabled by rapid continuous camera table motion, followed by reconstruction of parametric data sets using voxel-based Patlak graphical analysis.MethodsTwenty-five subjects were prospectively enrolled and underwent dynamic PET up to 90 minutes after injection of 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG). Two sets of images were generated: 1) the established standard of static standardized uptake value (SUV) images; and 2) parametric images of the metabolic rate of FDG (MR_FDG) using the Patlak plot–derived influx rate. Arterial wall signal was measured and compared using the volume-of-interest technique, and its association with hematopoietic and lymphoid organ signal and atherosclerotic risk factors was explored.ResultsParametric MR_FDG images provided excellent arterial wall visualization, with elimination of blood-pool activity, and enhanced focus detectability and reader confidence. Target-to-background ratio (TBR) from MR_FDG images was significantly higher compared with SUV images (2.6 ± 0.8 vs 1.4 ± 0.2; P < 0.0001), confirming improved arterial wall contrast. On MR_FDG images, arterial wall signal showed improved correlation with hematopoietic and lymphoid organ activity (spleen P = 0.0009; lymph nodes P = 0.0055; and bone marrow P = 0.0202) and increased with the number of atherosclerotic risk factors (r = 0.49; P = 0.0138), where signal from SUV images (SUV_max P = 0.9754; TBR_max P = 0.8760) did not.ConclusionsAbsolute quantification of MR_FDG is feasible for arterial wall using dynamic whole-body PET imaging. Parametric images provide superior arterial wall contrast, and they might be better suited to explore the relationship between arterial wall activity, systemic organ networks, and cardiovascular risk. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of arterial wall disease.     

18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography in Acute Aortic Syndrome

BackgroundAcute aortic syndrome is associated with aortic medial degeneration. ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) detects microscopic tissue calcification as a marker of disease activity.ObjectivesIn a proof-of-concept study, this investigation aimed to establish whether ¹⁸F-NaF PET combined with computed tomography (CT) angiography could identify aortic medial disease activity in patients with acute aortic syndrome.MethodsPatients with aortic dissection or intramural hematomas and control subjects underwent ¹⁸F-NaF PET/CT angiography of the aorta. Aortic ¹⁸F-NaF uptake was measured at the most diseased segment, and the maximum value was corrected for background blood pool activity (maximum tissue-to-background ratio [TBR_max]). Radiotracer uptake was compared with change in aortic size and major adverse aortic events (aortic rupture, aorta-related death, or aortic repair) over 45 ± 13 months.ResultsAortic ¹⁸F-NaF uptake co-localized with histologically defined regions of microcalcification and elastin disruption. Compared with control subjects, patients with acute aortic syndrome had increased ¹⁸F-NaF uptake (TBR_max: 1.36 ± 0.39 [n = 20] vs 2.02 ± 0.42 [n = 47] respectively; P < 0.001) with enhanced uptake at the site of intimal disruption (+27.5%; P < 0.001). ¹⁸F-NaF uptake in the false lumen was associated with aortic growth (+7.1 mm/year; P = 0.011), and uptake in the outer aortic wall was associated with major adverse aortic events (HR: 8.5 [95% CI: 1.4-50.4]; P = 0.019).ConclusionsIn patients with acute aortic syndrome, ¹⁸F-NaF uptake was enhanced at sites of disease activity and was associated with aortic growth and clinical events. ¹⁸F-NaF PET/CT holds promise as a noninvasive marker of disease severity and future risk in patients with acute aortic syndrome. (¹⁸F Sodium Fluoride PET/CT in Acute Aortic Syndrome [FAASt]; NCT03647566)     

Diagnostic Accuracy of Cardiac Computed Tomography and 18-F Fluorodeoxyglucose Positron Emission Tomography in Cardiac Masses

ObjectivesThis study sought to assess the diagnostic accuracy of cardiac computed tomography (CT) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) with positron emission tomography/computed tomography (PET/CT) in defining the nature of cardiac masses.BackgroundThe diagnostic accuracy of cardiac CT and ¹⁸F-FDG PET/CT in identifying the nature of cardiac masses has been analyzed to date only in small samples.MethodsOf 223 patients with echocardiographically diagnosed cardiac masses, a cohort of 60 cases who underwent cardiac CT and ¹⁸F-FDG PET/CT was selected. All masses had histological confirmation, except for a minority of thrombotic formations. For each mass, 8 morphological CT signs, standardized uptake value (SUV_max, SUV_mean), metabolic tumor volume, and total lesion glycolysis in ¹⁸F-FDG PET were used as diagnostic markers.ResultsIrregular tumor margins, pericardial effusion, invasion, solid nature, mass diameter, CT contrast uptake, and pre-contrast characteristics were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of 3 or 4 CT signs did not accurately discriminate the masses’ nature. The mean SUV_max, SUV_mean, metabolic tumor volume, and total lesion glycolysis values were significantly higher in malignant than in benign masses. The diagnostic accuracy of SUV, metabolic tumor volume, and total lesion glycolysis ¹⁸F-FDG PET/CT parameters was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, the presence of at least 1 abnormal ¹⁸F-FDG PET/CT parameter significantly increased the identification of malignancies.ConclusionsCardiac CT is a powerful tool to diagnose cardiac masses as the number of abnormal signs was found to correlate with the lesions’ nature. Similarly, ¹⁸F-FDG PET/CT accurately identified malignant masses and contributed with additional valuable information in diagnostic uncertainties after cardiac CT. These imaging tools should be performed in specific clinical settings such as involvement of great vessels or for disease-staging purposes.     

18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus

BackgroundBioprosthetic valve thrombosis may have implications for valve function and durability.ObjectivesUsing a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves.MethodsEx vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT.ResultsFlow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake.ConclusionsAdherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875)     

Diagnostic Accuracy of [11C]PIB Positron Emission Tomography for Detection of Cardiac Amyloidosis

ObjectivesThis dual-site study evaluated the diagnostic accuracy of the method.BackgroundPittsburgh compound ([¹¹C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA).MethodsThe study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min^-1) were applied prospectively.ResultsThe diagnostic accuracy of visual inspection of [¹¹C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [¹¹C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [¹¹C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [¹¹C]PIB PET positive.ConclusionsIn a dual-center setting, [¹¹C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were [¹¹C]PIB PET positive, indicating that the method may detect early stages of CA.     

Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis

ObjectivesThe aim of this study was to assess the diagnostic performances of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion.BackgroundPPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of ¹⁸F-FDG PET/CT remains poorly studied in PPVE.MethodsA retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent ¹⁸F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of ¹⁸F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study.ResultsA total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of ¹⁸F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). ¹⁸F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE.ConclusionsUsing ¹⁸F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.     

Vascular Positron Emission Tomography and Restenosis in Symptomatic Peripheral Arterial Disease: A Prospective Clinical Study

ObjectivesThis study determined whether in vivo positron emission tomography (PET) of arterial inflammation (¹⁸F-fluorodeoxyglucose [¹⁸F-FDG]) or microcalcification (¹⁸F-sodium fluoride [¹⁸F-NaF]) could predict restenosis following PTA.BackgroundRestenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty.MethodsIn this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent ¹⁸F-FDG and ¹⁸F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months.ResultsForty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (¹⁸F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p < 0.001) and microcalcification (¹⁸F-NaF TBR 2.61 [IQR: 2.50 to 2.77] vs. 1.69 [IQR: 1.54 to 1.77]; p < 0.001) were higher in patients who developed restenosis. The predictive value of both ¹⁸F-FDG (cut-off TBR_max value of 1.98) and ¹⁸F-NaF (cut-off TBR_max value of 2.11) uptake demonstrated excellent discrimination in predicting 1-year restenosis (Kaplan Meier estimator, log-rank p < 0.001).ConclusionsBaseline and persistent femoral arterial inflammation and micro-calcification are associated with restenosis following lower limb PTA. For the first time, we describe a method of identifying complex metabolically active plaques and patients at risk of restenosis that has the potential to select patients for intervention and to serve as a biomarker to test novel interventions to prevent restenosis.     

Prognostic Value of Quantitative Metrics From Positron Emission Tomography in Ischemic Heart Failure

ObjectivesThe aim of this study was to investigate the prognostic and clinical value of quantitative positron emission tomographic (PET) metrics in patients with ischemic heart failure.BackgroundAlthough myocardial flow reserve (MFR) is a strong predictor of cardiac risk in patients without heart failure, it is unknown whether quantitative PET metrics improve risk stratification in patients with ischemic heart failure.MethodsThe study included 254 patients referred for stress and rest myocardial perfusion imaging and viability testing using PET. Major adverse cardiac event(s) (MACE) consisted of death, resuscitated sudden cardiac death, heart transplantation, acute coronary syndrome, hospitalization for heart failure, and late revascularization.ResultsMACE occurred in 170 patients (67%) during a median follow-up of 3.3 years. In a multivariate Cox proportional hazards model including multiple quantitative PET metrics, only MFR predicted MACE significantly (p = 0.013). Beyond age, symptom severity, diabetes mellitus, previous myocardial infarction or revascularization, 3-vessel disease, renal insufficiency, ejection fraction, as well as presence and burden of ischemia, scar, and hibernating myocardium, MFR was strongly associated with MACE (adjusted hazard ratio per increase in MFR by 1: 0.63; 95% confidence interval: 0.45 to 0.91). Incorporation of MFR into a risk assessment model incrementally improved the prediction of MACE (likelihood ratio chi-square test [16] = 48.61 vs. chi-square test [15] = 39.20; p = 0.002).ConclusionsIn this retrospective analysis of a single-center cohort, quantitative PET metrics of myocardial blood flow all improved risk stratification in patients with ischemic heart failure. However, in a hypothesis-generating analysis, MFR appears modestly superior to the other metrics as a prognostic index.     

Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance

ObjectivesThis study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans.BackgroundExperimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake.MethodsThe study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo.ResultsMedian plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m² vs. 82 ± 15 ml/m²; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP.ConclusionsOnly primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).     

Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping

ObjectivesThe authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD).BackgroundVA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD.MethodsOne hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps.ResultsIn patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%).ConclusionsVA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.     

Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging

ObjectivesThis study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).BackgroundMyocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19.MethodsTwenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Edema ratio and LGE were assessed in post–COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.ResultsFifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs. 38.1 ms ± 2.4 vs. 39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs. 24.8% [23.1% to 25.4%] vs. 23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).ConclusionsCardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.     

Myocardial Contractile Mechanics in Ischemic Mitral Regurgitation: Multicenter Data Using Stress Perfusion Cardiovascular Magnetic Resonance

BackgroundLeft ventricular (LV) ischemia has been variably associated with functional mitral regurgitation (FMR). Determinants of FMR in patients with ischemia are poorly understood.ObjectivesThis study sought to test whether contractile mechanics in ischemic myocardium underlying the mitral valve have an impact on likelihood of FMR.MethodsVasodilator stress perfusion cardiac magnetic resonance was performed in patients with coronary artery disease (CAD) at multiple centers. FMR severity was confirmed quantitatively via core lab analysis. To test relationship of contractile mechanics with ischemic FMR, regional wall motion and strain were assessed in patients with inducible ischemia and minimal (≤5% LV myocardium, nontransmural) infarction.ResultsA total of 2,647 patients with CAD were studied; 34% had FMR (7% moderate or greater). FMR severity increased with presence (P < 0.001) and extent (P = 0.01) of subpapillary ischemia: patients with moderate or greater FMR had more subpapillary ischemia (odds ratio [OR]: 1.13 per 10% LV; 95% CI: 1.05-1.21; P = 0.001) independent of ischemia in remote regions (P = NS); moderate or greater FMR prevalence increased stepwise with extent of ischemia and infarction in subpapillary myocardium (P < 0.001); stronger associations between FMR and infarction paralleled greater wall motion scores in infarct-affected territories. Among patients with inducible ischemia and minimal infarction (n = 532), wall motion and radial strain analysis showed impaired subpapillary contractile mechanics to associate with moderate or greater FMR (P < 0.05) independent of remote regions (P = NS). Conversely, subpapillary ischemia without contractile dysfunction did not augment FMR likelihood. Mitral and interpapillary dimensions increased with subpapillary radial strain impairment; each remodeling parameter associated with impaired subpapillary strain (P < 0.05) independent of remote strain (P = NS). Subpapillary radial strain (OR: 1.13 per 5% [95% CI: 1.02-1.25]; P = 0.02) and mitral tenting area (OR: 1.05 per 10 mm² [95% CI: 1.00-1.10]; P = 0.04) were associated with moderate or greater FMR controlling for global remodeling represented by LV end-systolic volume (P = NS): when substituting sphericity for LV volume, moderate or greater FMR remained independently associated with subpapillary radial strain impairment (OR: 1.22 per 5% [95% CI: 1.02-1.47]; P = 0.03).ConclusionsAmong patients with CAD and ischemia, FMR severity and adverse mitral apparatus remodeling increase in proportion to contractile dysfunction underlying the mitral valve.     

T1 Mapping by Cardiac Magnetic Resonance and Multidimensional Speckle-Tracking Strain by Echocardiography for the Detection of Acute Cellular Rejection in Cardiac Allograft Recipients

ObjectivesThe aim of this study was to test the hypothesis that echocardiographic strain imaging, by tracking subtle alterations in myocardial function, and cardiac magnetic resonance T1 mapping, by quantifying tissue properties, are useful and complement each other to detect acute cellular rejection in heart transplant recipients.BackgroundNoninvasive alternatives to endomyocardial biopsy are highly desirable to monitor acute cellular rejection.MethodsSurveillance endomyocardial biopsies, catheterizations, and echocardiograms performed serially according to institutional protocol since transplantation were retrospectively reviewed. Sixteen-segment global longitudinal strain (GLS) and circumferential strain were measured before, during, and after the first rejection and at 2 time points for patients without rejection using Velocity Vector Imaging for the first part of the study. The second part, with cardiac magnetic resonance added to the protocol, served to validate previously derived strain cutoffs, examine the progression of strain over time, and to determine the accuracy of strain and T1 measurements to define acute cellular rejection. All tests were performed within 48 h.ResultsMedian time to first rejection (16 grade 1 rejection, 15 grade ≥2 rejection) was 3 months (interquartile range: 3 to 36 months) in 49 patients. GLS and global circumferential strain worsened significantly during grade 1 rejection and ≥2 rejection and were independent predictors of any rejection. In the second part of the study, T1 time ≥1,090 ms, extracellular volume ≥32%, GLS >−14%, and global circumferential strain ≥−24% had 100% sensitivity and 100% negative predictive value to define grade ≥2 rejection with 70%, 63%, 55%, and 35% positive predictive values, respectively. The combination of GLS >−16% and T1 time ≥1,060 ms defined grade 1 rejection with 91% sensitivity and 92% negative predictive value. After successful treatment, T1 times decreased significantly.ConclusionsT1 mapping and echocardiographic GLS can serve to guide endomyocardial biopsy selectively.     

Cardiac Magnetic Resonance Feature Tracking Global Longitudinal Strain and Prognosis After Heart Transplantation

ObjectivesThis study determined the long-term prognostic significance of GLS assessed using CMR-FT in a large cohort of heart transplant recipients.BackgroundIn heart transplant recipients, global longitudinal strain (GLS) assessed using echocardiography has shown promise in the prediction of clinical outcomes. We hypothesized that CMR feature tracking (CMR-FT) GLS is independently associated with long-term outcomes in heart transplant recipients.MethodsIn a cohort of consecutive heart transplant recipients who underwent routine CMR for clinical surveillance, CMR-FT GLS was calculated from 3 long-axis cine CMR images. Associations between GLS and a composite endpoint of death or major adverse cardiac events (MACE), including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization, were investigated.ResultsA total of 152 heart transplant recipients (age 54 ± 15 years; 29% women; 5.0 ± 5.4 years after heart transplantation) were included. The median GLS was −11.6% (interquartile range: −13.6% to −9.2%). Over a median follow-up of 2.6 years, 59 recipients reached the composite endpoint. On Kaplan-Meier analyses, recipients with GLS worse than the median had a higher estimated cumulative incidence of the composite endpoint compared with recipients with GLS better than the median (log rank p = 0.004). On multivariate Cox proportional hazards regression, GLS was independently associated with the composite endpoint after adjustment for cardiac allograft vasculopathy, history of rejection, left ventricular ejection fraction (LVEF), right ventricular EF, and presence of myocardial fibrosis, with a hazard ratio of 1.15 for every 1% worsening in GLS (95% confidence interval: 1.06 to 1.24; p < 0.001). Similar results were seen in subgroups of recipients with LVEF >50% and with no myocardial fibrosis. GLS provided incremental prognostic value over other variables in the multivariate model as determined by the log-likelihood chi-squared test.ConclusionsIn a large cohort of heart transplant recipients, CMR-FT GLS was independently associated with the long-term risk of death or MACE.     

Long-Term Prognosis of Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance

ObjectivesThis study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD).BackgroundPatients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI <1.4. The prognosis of CMD as determined by MPRI is unknown.MethodsChest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke.ResultsA total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI >1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p < 0.001).ConclusionsStress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.     

Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis

BackgroundIt remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis.ObjectivesThe purpose of this study was to demonstrate that ¹¹C-Pittsburgh B compound positron emission tomography (¹¹C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition.MethodsThis study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial ¹¹C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure.ResultsThe degree of myocardial ¹¹C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R² = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial ¹¹C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005).ConclusionsThese proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by ¹¹C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.     

Prognostic Value of Magnetic Resonance Phenotype in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

BackgroundCardiac magnetic resonance (CMR) is widely used to assess tissue and functional abnormalities in arrhythmogenic right ventricular cardiomyopathy (ARVC). Recently, a ARVC risk score was proposed to predict the 5-year risk of malignant ventricular arrhythmias in patients with ARVC. However, CMR features such as fibrosis, fat infiltration, and left ventricular (LV) involvement were not considered.ObjectivesThe authors sought to evaluate the prognostic role of CMR phenotype in patients with definite ARVC and to evaluate the effectiveness of the novel 5-year ARVC risk score to predict cardiac events in different CMR presentations.MethodsA total of 140 patients with definite ARVC were enrolled (mean age 42 ± 17 years, 97 males) in this multicenter prospective registry. As per study design, CMR was performed in all the patients at enrollment. The novel 5-year ARVC risk score was retrospectively calculated using the patient’s characteristics at the time of enrollment. During a median follow-up of 5 years (2 to 8 years), the combined endpoint of sudden cardiac death, appropriate implantable cardioverter-defibrillator intervention, and aborted cardiac arrest was considered.ResultsCMR was completely negative in 14 patients (10%), isolated right ventricular (RV) involvement was found in 58 (41%), biventricular in 52 (37%), and LV dominant in 16 (12%). During the follow-up, 48 patients (34%) had major events, but none occurred in patients with negative CMR. At Kaplan-Meier analysis, patients with LV involvement (LV dominant and biventricular) had a worse prognosis than those with lone RV (p < 0.0001). At multivariate analysis, the LV involvement, a LV-dominant phenotype, and the 5-year ARVC risk score were independent predictors of major events. The estimated 5-year risk was able to predict the observed risk in patients with lone RV but underestimated the risk in those with LV involvement.ConclusionsDifferent CMR presentations of ARVC are associated with different prognoses. The 5-year ARVC risk score is valid for the estimation of risk in patients with lone-RV presentation but underestimated the risk when LV is involved.     

Subclinical Leaflet Thrombosis in Transcatheter and Surgical Bioprosthetic Valves: PARTNER 3 Cardiac Computed Tomography Substudy

BackgroundSubclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction.ObjectivesThe U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes.MethodsThe PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low–surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory.ResultsThe incidence of HALT increased from 10% at 30 days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04).ConclusionsSubclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment.