Elevated T2 Research Articles

Histology-verified myocardial fibrosis and quantification in severe AS patients: correlation with non-invasive LV myocardial tissue assessment

Abstract Background Myocardial fibrosis (MF) is a common finding and a potential adverse prognostic marker in several cardiac diseases, including in severe aortic stenosis (AS). While histological analysis obtained through endomyocardial biopsy remains the gold-standard for MF assessment, non-invasive cardiac imaging may offer surrogate biomarkers for fibrosis. We tried to assess the correlation between MF quantification at histopathology and cardiac magnetic resonance (CMR)-derived tissue characterization data in patients with severe AS. Methodology Single-center prospective cohort enrolling 71 patients with severe symptomatic high-gradient AS undergoing surgical aortic valve replacement (SAVR) (mean age 71±9 years; 49% male, mean valvular transaortic gradient 60±20 mmHg; mean left ventricle [LV] ejection fraction 58±9%). Those with past history of myocardial infarction or cardiomyopathy were excluded. All patients underwent pre-operative CMR study with LV tissue characterization and quantification. Normal T1 mapping value was defined as >1021ms as per center protocol. Myocardial tissue was obtained during SAVR either through myocardial biopsy at basal LV septum or harvested from surgical myectomy specimens. Masson's trichrome stain was used for collagen/fibrosis assessment. Automatic quantification was obtained at QuPathTM digital pathology software after applying a dedicated artificial intelligence algorithm on ultra-high-resolution digital slide scanning images. Results Histology-confirmed MF was observed in all patients (median percentage of fibrotic myocardial tissue 15% [IQR 9–22%]). Median global T1 mapping and extracellular volume (ECV) percentage was 1048ms (IQR 1027–1078) and 24% (IQR 20–30%), respectively. Late gadolinium enhancement (LGE) with a non-ischemic pattern was present in 42 patients (59%) with a median LGE mass of 5.8g [IQR 1.0–10.2]; median percentage of 3.7% [IQR 0.6–10.4]. While neither T1 mapping (global or basal LV septum), ECV nor LGE had any significant correlation with histology-confirmed MF (Figure 1) the vast majority had significantly elevated global and basal LV septum T1 mapping – 81% and 92%, respectively. Conclusion In this single-center prospective study, microscopic MF was present in all patients with severe symptomatic high-gradient AS, was accompanied by elevated T1 mapping values but no correlation was found between myocardial fibrosis at histopathology analysis and CMR-derived LV tissue characterization parameters. This may not only stem from sampling (single point biopsy vs. whole myocardial tissue assessment) but also from distinct evaluation of different types of fibrosis by different methods. Funding Acknowledgement Type of funding sources: None.

Myocardial edema during chemotherapy for gynecologic malignancies: A cardiac magnetic resonance T2 mapping study.

ObjectiveMyocardial edema is an early manifestation of chemotherapy-related myocardial injury. In this study, we used cardiac magnetic resonance (CMR) T2 mapping to assess myocardial edema and its changes during chemotherapy for gynecologic malignancies.MethodsWe enrolled 73 patients receiving chemotherapy for gynecologic malignancies, whose the latest cycle was within one month before the beginning of this study, and 41 healthy volunteers. All participants underwent CMR imaging. Of the 73 patients, 35 completed CMR follow-up after a median interval of 6 (3.3 to 9.6) months. The CMR sequences included cardiac cine, T2 mapping, and late gadolinium enhancement.ResultsMyocardial T2 was elevated in patients who were treated with chemotherapy compared with healthy volunteers [41ms (40ms to 43ms) vs. 41ms (39ms to 41ms), P = 0.030]. During follow-up, myocardial T2 rose further [40ms (39ms to 42ms) vs. 42.70 ± 2.92ms, P < 0.001]. Multivariate analysis showed that the number of chemotherapy cycles was associated with myocardial T2 elevation (β = 0.204, P = 0.029). After adjustment for other confounders, myocardial T2 elevation was independently associated with a decrease in left ventricular mass (β = −0.186; P = 0.024).ConclusionIn patients with gynecologic malignancies, myocardial edema developed with chemotherapy cycles increase, and was associated with left ventricular mass decrease. T2 mapping allows the assessment of myocardial edema and monitoring of its change during chemotherapy.

P.163 Quantitative MRI in upper limb muscle of patients with dysferlinopathy: preliminary baseline results of the natural history study Jain COS2

Quantitative magnetic resonance imaging (qMRI) has recently shown its benefit in a longitudinal study of lower limb muscles in dysferlinopathy. This study has demonstrated the differential muscle involvement by measuring muscle fat fraction (FF) and significant yearly increases in FF. Additionally, muscle water T2, reflecting the disease activity (i.e. inflammation, edema), was found to be persistently elevated. Other anatomical regions are known to be affected later in the disease progression of dysferlinopathy, so upper limb muscles were investigated in a follow-up natural history study, Jain COS2. Here, we report preliminary baseline results. The qMRI data were acquired on two 3-tesla clinical systems at two centers in Europe between July 2019 and March 2022, in patients (n=27) and controls (n=4). qMRI acquisitions included fat-water imaging and water T2 mapping at the level of the arm (deltoid, triceps, biceps brachialis) and forearm (extensor, flexor). Student's t-tests were performed (P<0.05). Overall, patients (13 female, 14 male, 61% ambulant) were 41±12 years old and had symptoms for 17±9 years. No differences in demographic data for age, sex and years since symptoms existed between sites (P>0.132) although patients were slightly younger in site 1. Whereas in site 2, albeit one patient was assigned to limb-girdle muscular dystrophy type R2 (LGMD R2), site 2 patients were assigned to LGMD R2 or Miyoshi myopathy/other phenotypes in a 50/50 ratio (P=0.004). For all investigated muscles, FF values were significantly higher in patients than in controls (P<0.001). Although FF values were lower in patients at site 1, differences with site 2 were not significant (P<0.125). The lowest FF values were observed in the extensor muscle (site 1: 12.0±6.0%, site 2: 12.1±6.0%, P=0.463) while the highest FF was seen in deltoid muscle (site 1: 27.4±19.0%, site 2: 32.1±21.4%, P=0.278), confirming the predominant proximo-distal muscle involvement in dysferlinopathy. Muscle involvement showed a high inter-individual patient variability, at least for the arm muscles. Water T2 values were increased as compared to controls (90% percentile in controls = 36.5ms) in triceps muscle in both sites (site 1: 39.3±3.0 ms, site 2: 37.2±4.9 ms), which is in line with the finding of elevated water T2 values in lower limb in earlier work. These baseline qMRI results give a quantitative view on the disease progression and activity in the upper limb muscles of dysferlinopathy patients.

COMPARISON OF POST-PROCESSING TECHNIQUES FOR OPTIMIZING THE QUALITY OF CARDIAC MAGNETIC RESONANCE T1 MAPPING IMAGES

COMPARISON OF POST-PROCESSING TECHNIQUES FOR OPTIMIZING THE QUALITY OF CARDIAC MAGNETIC RESONANCE T1 MAPPING IMAGES

OA15 A case of cardiac manifestation of systemic sclerosis

Introduction/BackgroundA 45-year-old lady, originally from Peru, with a background of diffuse cutaneous systemic sclerosis presented with shortness of breath on exertion, frequent palpitations, non-exertional chest tightness, and fatigue.Description/MethodIn 2011, she presented with inflammatory arthritis as well as Raynaud’s phenomenon. Her anti-nuclear antibody screen showed a positive anti-SCL-70 and anti-U3RNP. Over the years she developed pulmonary hypertension, renal involvement (proteinuria), dysphagia, cutaneous involvement (sclerodactyly, digital ulcers, telangiectasia) and interstitial lung disease. She was commenced on methotrexate and prednisolone. Her pulmonary hypertension was controlled on macitentan and sildenafil. Her pulse was 112 beats per minute, regular with a blood pressure of 168/85 mmHg. She had a loud P2 and a parasternal heave. She had sparse basal crepitations. She had mild pitting oedema to her knees. Her JVP was not raised. Her weight was 38kg.Her right heart catheterisation in April 2021 reported a mean pulmonary artery pressure of 24mmHg and pulmonary vascular resistance of 255 ARU. A computerized tomography (CT) scan of her chest showed known interstitial lung disease and no pulmonary embolism. Her lung function tests were stable. A cardiovascular magnetic resonance imaging (CMR) guided cardiac catheter in April 2021 showed scleroderma involvement of the heart, with mild pericardial effusion and elevated native myocardial T1 and T2. Left ventricular ejection fraction was normal. The impression was that of scleroderma with myocardia involvement. Her immunosuppression was escalated to cyclophosphamide. A cardiac MRI in September 2021 showed improvements in T1 and T2 mapping parameters. She completed 4 cycles of cyclophosphamide (15mg/kg). However, due to gastrointestinal side effects (nausea and vomiting) and a diagnosis of latent tuberculosis in February 2022, cyclophosphamide was stopped. In March 2022, her repeat CMR showed that the T1 and T2 mapping had slightly increased and presented again with chest pain and palpitations. Following a multi-disciplinary team discussion, the patient was treated with rituximab 500mg two weeks apart with 100mg of methylprednisolone as premedication prior to the infusions.Discussion/ResultsAlthough subclinical cardiac involvement in scleroderma is common, only 10 to 30% of patients are symptomatic. Our patients complained of non-exertional chest pain. Macrovascular coronary disease had been excluded; the cause of her chest pain was likely secondary to microvascular dysfunction. In patients with cardiac scleroderma, the mechanism of coronary disease is secondary to myocardial inflammation and repeated microvascular ischaemia. This results in reperfusion defects secondary to necrosis, in turn driving myocardial fibrosis. In the late stages, fibrosis results in left ventricular diastolic dysfunction, a complication related to increased mortality.Supraventricular tachycardia is one of the manifestations in conduction abnormalities in cardiac scleroderma: others include conduction defects and bradyarrhythmias. As with our patient, tachyarrhythmias can be associated with symptoms such as generalised fatigue, shortness of breath, and exercise intolerance.Another complication found on imaging was a small pericardial effusion. This is the most common pericardial disease in scleroderma. For most, pericardial effusions are asymptomatic; however, it can be associated with complications such as tamponade.Whilst cyclophosphamide is a common treatment choice for scleroderma with cardiac involvement, evidence for this is limited to case series due to its rarity. Additionally, it carries significant toxicity: Our case developed significant nausea and vomiting following her third and fourth cyclophosphamide infusions and this was discontinued also in light of her diagnosis of latent TB. Rituximab, the agent to which the patient was subsequently switched, similarly has a growing body of evidence in cardiac scleroderma. Since her rituximab infusions, our case has remained stable and she has noticed an improvement of her clinical symptoms.Key learning points/ConclusionCardiac scleroderma is associated with significant reduction in quality of life, morbidity, and mortality. It is often difficult to treat due to sparsity of high-quality evidence (as in other rare conditions) as well as the multiple organ systems and co-morbidities involved. This case illustrates the clinical manifestation of cardiac scleroderma and the difficulty in selecting appropriate immunosuppression medication.

Monitoring kidney size to interpret MRI-based assessment of renal oxygenation in acute pathophysiological scenarios.

Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers T2 and T2 * enables insights into renal pathophysiology. This assessment can be confounded by changes in the blood and tubular volume fractions, occurring upon pathological insults. These changes are mirrored by changes in kidney size (KS). Here, we used dynamic MRI to monitor KS for physiological interpretation of T2 * and T2 changes in acute pathophysiological scenarios. KS was determined from T2 *, T2 mapping in rats. Six interventions that acutely alter renal tissue oxygenation were performed directly within the scanner, including interventions that change the blood and/or tubular volume. A biophysical model was used to estimate changes in O2 saturation of hemoglobin from changes in T2 * and KS. Upon aortic occlusion KS decreased; this correlated with a decrease in T2 *, T2 . Upon renal vein occlusion KS increased; this negatively correlated with a decrease in T2 *, T2 . Upon simultaneous occlusion of both vessels KS remained unchanged; there was no correlation with decreased T2 *, T2 . Hypoxemia induced mild reductions in KS and T2 *, T2 . Administration of an X-ray contrast medium induced sustained KS increase, with an initial increase in T2 *, T2 followed by a decrease. Furosemide caused T2 *, T2 elevation and a minor increase in KS. Model calculations yielded physiologically plausible calibration ratios for T2 *. Monitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T2 *, T2 . KS monitoring should accompany MRI-oximetry, for new insights into renal pathophysiology and swift translation into human studies.

Cardiac Assessment in Children with MIS-C: Late Magnetic Resonance Imaging Features.

Multisystem Inflammatory Syndrome (MIS-C) is a new entity that emerges 2–4 weeks after the SARS-CoV-2 infection in children. MIS-C can affect all systems, the most severe of which is cardiac involvement. The duration of the cardiac symptoms is still uncertain and may be persistent or prolonged. The American College of Rheumatology Clinical Guidelines recommends cardiac magnetic resonance imaging (MRI) 2–6 months after the diagnosis of MIS-C in patients presenting with significant transient left ventricular (LV) dysfunction in the acute phase of illness (LV ejection fraction 50%) or persistent LV dysfunction. There are a few studies investigating cardiac MRI findings in MIS-C patients. In this study, we aimed to evaluate cardiac MRI findings, at the earliest 3 months after diagnosis, and compare these findings with the echocardiograms in children with MIS-C. A retrospective study including 34 MIS-C patients was conducted at a tertiary-level University Hospital between June 2020 and July 2021. Centers for Disease Control and Prevention criteria were used in the diagnosis of MIS-C. Cardiac MRI was performed at least 3 months after MIS-C diagnosis. The study included 17 (50%) boys and 17 (50%) girls with a mean age of 9.31 ± 4.72 years. Initial echocardiographic evaluation revealed cardiac abnormality in 13 (38.2) patients; 4 (11.8%) pericardial effusion, 4 (11.8%) left ventricular ejection fraction (LVEF) < 55%, and 5 (14.7%) coronary artery dilatation. Echocardiography showed normal LV systolic function in all patients during follow-up; coronary dilatation persisted in 2 of 5 (40%) patients at the 6th-month visit. Cardiac MRI was performed in 31 (91.2%) patients, and myocardial hyperemia was not detected in any patients (T1 relaxation time was < 1044 ms in all children). However, 9 (29%) patients’ MRI showed isolated elevated T2 levels, and 19 (61.3%) revealed at least one of the following findings: pericardial effusion, right ventricular dysfunction, or LVEF abnormality. In patients with MIS-C, a high rate of cardiac involvement, particularly pericardial effusion was determined by cardiac MRI performed at the earliest 2–6 months after diagnosis. Even if echocardiography does not reveal any abnormality in the initial phase, cardiac MRI should be suggested in MIS-C patients in the late period. This is the first study reporting cardiac MRI findings in the late period of MIS-C patients.

Cardiovascular Magnetic Resonance in Early Detection of Radiation Associated Cardiotoxicity With Chest Radiation.

BackgroundChest radiation therapy (RT) is known to be associated with cardiotoxicity. However, the changes in myocardial tissue characterization with radiation-induced cardiotoxicity are not well-understood.ObjectivesThis study sought to assess the changes in left ventricular function and tissue characterization using cardiovascular magnetic resonance (CMR) in patients receiving RT.Materials and MethodsBetween June 2015 and July 2018, we enrolled patients with breast, lung cancer, or lymphoma with plan to receive chest radiation after chemotherapy. CMR was performed using a 1.5T scanner at baseline and 6 months after RT. Myocardial volume, function, strain analysis using feature tracking, and tissue characterization including late gadolinium enhancement (LGE), T1, T2, T1ρ (rho), and extracellular volume fraction (ECV) were measured and compared using non-parametric methods.ResultsThe final cohort consisted of 16 patients, 11 of whom completed both baseline and follow-up CMRs. Patients were matched to 10 healthy controls. At baseline prior to RT, compared to controls, patients had lower global circumferential strain (GCS) (15.3 ± 2.2% vs.18.4 ± 2.1%, p = 0.004), and elevated T2 (47.9 ± 4.8 ms vs. 45.0 ± 1.5 ms, p = 0.04) and T1ρ values (78.4 ± 5.9 vs. 66.9 ± 4.6 ms, p < 0.001). Two patients had LGE. There was no significant difference in the average T1 values or ECV. There was a trend toward lower LV ejection fraction and global longitudinal strain (GLS). At 6-month follow-up after RT, there were no significant changes in all the CMR parameters.ConclusionAt 6-month following chest radiation therapy, there was no change in LV and RV EF, LV and RV GLS, LV GCS, and myocardial tissue characterization using LGE, T1, ECV, T2, and T1ρ in a small cohort of patients. However, the baseline T2 and T1ρ were elevated and LV GCS was reduced compared to controls indicating ongoing myocardial edema and subclinical dysfunction post-chemotherapy.

Cardiac MRI Findings in COVID-19 Vaccine-Related Myocarditis: A Pooled Analysis of 468 Patients.

Understanding the pattern and severity of myocarditis caused by the coronavirus disease 2019 (COVID‐19) vaccine is imperative for improving the care of the patients, and cardiac evaluation by MRI plays a key role in this regard. Our systematic review and meta‐analysis aimed to summarize cardiac MRI findings in COVID‐19 vaccine‐related myocarditis. We performed a comprehensive systematic review of literature in PubMed, Scopus, and Google Scholar databases using key terms covering COVID‐19 vaccine, myocarditis, and cardiac MRI. Individual‐level patient data (IPD) and aggregated‐level data (AD) studies were pooled through a two‐stage analysis method. For this purpose, all IPD were first gathered into a single data set and reduced to AD, and then this AD (from IPD studies) was pooled with existing AD (from the AD studies) using fixed/random effect models. I 2 was used to assess the degree of heterogeneity, and the prespecified level of statistical significance (P value for heterogeneity) was <0.1. Based on meta‐analysis of 102 studies (n = 468 patients), 79% (95% confidence interval [CI]: 54%–97%) of patients fulfilled Lake Louise criteria (LLC) for diagnosis of myocarditis. Cardiac MRI abnormalities included elevated T2 in 72% (95% CI: 50%–90%), myocardial late gadolinium enhancement (LGE) in 93% (95% CI: 83%–99%; nearly all with a subepicardial and/or midwall pattern), impaired left ventricular ejection fraction (LVEF) (<50%) in 4% (95% CI: 1.0%–9.0%). Moreover, elevated T1 and extracellular volume fraction (ECV) (>30), reported only by some IPD studies, were detected in 74.5% (76/102) and 32% (16/50) of patients, respectively. In conclusion, our findings may suggest that over two‐thirds of patients with clinically suspected myocarditis following COVID‐19 vaccination meet the LLC. COVID‐19 vaccine‐associated myocarditis may show a similar pattern compared to other acute myocarditis entities. Notably, preserved LVEF is probably a common finding in these patients.Evidence Level4Technical EfficacyStage 3

Comparing imaging biomarkers of cerebral edema after TBI in young adult male and female rats

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Cerebral edema following TBI is known to play a critical role in injury severity and prognosis. In the current study we used multimodal magnetic resonance imaging (MRI) to assess cerebral edema 24 h after unilateral contusive TBI in male and female rats. We then directly quantified brain water content in the same subjectsex vivo.We found that both males and females had similarly elevated T2 values after TBI compared with sham controls. Apparent diffusion coefficient (ADC) was more variable than T2 and did not show significant injury effects in males or females. Brain water was elevated in male TBI rats compared with sham controls, but there was no difference between female TBI and sham groups. Notably, MRI biomarkers of edema were more closely correlated with brain water in male rats; female rats did not show any relationship between brain water and T2 or ADC. These observations raise questions about the interpretation of radiological findings traditionally interpreted as edema in female TBI patients. A better understanding of sex differences and similarities in the pathophysiology of post-traumatic edema is needed to help improve patient management and the development of effective treatment strategies for men and women.

Parametric mapping CMR for the measurement of inflammatory reactions of the pericardium

ObjectivesAlthough cardiovascular magnetic resonance (CMR) is increasingly used to diagnose pericardial inflammation, imaging can still be challenging using conventional CMR techniques. Parametric mapping (T1/T2 mapping) techniques have emerged as novel...

Too Much Too Soon? The Catch-22 of Catching COVID-19

IntroductionMyocarditis has become a well-recognised cardiac complication of SARS-CoV-2 infection. Now, there are growing reports of rare incidences of myocarditis following receipt of mRNA COVID-19 vaccines.Case ReportA previously healthy 35-year-old male tested positive for COVID-19 on 8/12/21. He never required hospitalisation and was thought to have cleared the infection by 9/5/21. Three weeks later he received the first dose of Pfizer-BioNTech BNTT162b2/Comirnaty mRNA COVID-19 vaccine. Five days later he presented to emergency with chest pain alongside myalgia, headache and cough. His troponin-T was below reference range (RR), electrocardiogram showed sinus rhythm with mild, diffuse T-wave flattening, and no evidence of pericardial effusion was seen on bedside transthoracic echocardiogram (TTE) so was discharged. Two days later he represented to hospital with fevers, vomiting, diarrhea and a maculopapular rash. His subsequent admission was complicated by rapid deterioration and his management reflected a diagnostic dilemma with wide differentials. On day 2 of admission he became haemodynamically unstable requiring vasopressor therapy with a high sensitivity (hs) troponin-I of 103ng/L (RR <26ng/L). On day 4 he developed atrial fibrillation, worsening respiratory distress, peak hs troponin-I of 1474ng/L and required intubation, direct-current cardioversion and venoarterial extracorporeal membrane oxygenation (ECMO) for intractable heart failure. TTE here showed severe global systolic impairment with a left ventricular ejection fraction of 15% and small pericardial effusion. His subsequent treatment targeted possible multiorgan sepsis with antibiotics, vaccine-induced myocarditis with immunosuppressive therapy including anakinra and parental corticosteroids, or delayed COVID-19 myocarditis with supportive care. He was later extubated and successfully decannulated from 5 days on ECMO on day 11. Cardiac magnetic resonance imaging on day 12 showed elevated T1 and T2 values consistent with ongoing myocardial edema, but normal ventricular volume, thickness and function.SummaryThis is a case of fulminant myocarditis whereby the aetiology is unclear considering recent COVID-19 infection and mRNA vaccination. This raises questions as to the ideal timing of vaccine, type of vaccine and requirement for cardiac screening prior to vaccination in patients who have recovered from COVID-19.

T1 Mapping and Extracellular Volume in Cardiomyopathy Showing Left Ventricular Hypertrophy: Differentiation Between Hypertrophic Cardiomyopathy and Hypertensive Heart Disease.

BackgroundThe aim of this study was to evaluate the capability of different magnetic resonance imaging (MRI) parameters for distinguishing between hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD).MethodsThirty-eight patients with HCM, 35 patients with HHD, and 29 healthy controls subjects were enrolled in this study. All subjects underwent cardiac MRI to measure T1 values and extracellular volume (ECV), as well as the extent and patterns of late gadolinium enhancement (LGE). Myocardial segments were categorized as non-hypertrophic, mild-hypertrophic, moderate-hypertrophic, and severe-hypertrophic based on end-diastolic wall thickness (EDWT). The differences in native T1 values between all four groups were evaluated.ResultsNative T1 values were significantly higher in patients with HCM than in patients with HHD and in healthy controls (both P < 0.001). Moreover, significantly increased ECV was shown in patients with HCM than in patients with HHD and in healthy controls (both P = 0.001). Native T1 values in the basal slice and apex slice were significantly higher in patients with HCM than in patients with HHD (P < 0.01). In patients with HCM, the non-hypertrophic myocardial segments demonstrated significantly elevated T1 values compared with patients with HHD (both P < 0.001). Using a cut-off value of 28.8% for ECV, it could differentiate between HCM and HHD with 85% sensitivity, 62.07% specificity, and an area under the curve of 0.772.ConclusionIn patients with HCM, T1 tissue remodeling occurs in the normal-appearing myocardial segments, but not in patients with HHD. Both native T1 values and ECV can support clinically relevant discrimination between HCM and HHD, although ECV had better diagnostic efficacy.

Left ventricular thrombus after acute ST-segment elevation myocardial infarction: multi-parametric cardiac magnetic resonance imaging with long-term outcomes.

Left ventricular thrombus (LVT) after acute ST-segment elevation myocardial infarction (STEMI) are generally associated with poorer outcomes for patients at long-term follow-up. We hypothesis that tissue characteristics and strain parameters by cardiac magnetic resonance (CMR) imaging may indicate the interactions of LVT with ventricular myocardium remodeling at both acute stage and chronic stages in STEMI patients. This retrospective study included 111 consecutive STEMI patients (38 with LVT and 73 without LVT). All patients underwent CMR during acute stage (within 7days) and chronic stage (after at least 2months) periods after percutaneous coronary intervention (PCI). Left ventricular native T1, extracellular volume (ECV), radial, circumferential, and longitudinal strain were analyzed in both phases. Major adverse cardiac events (MACE, including cardiovascular death, myocardial reinfarction, and hospitalization for heart failure), thromboembolic and bleeding events, were the clinical endpoints of the study. During the acute stage, left ventricular ejection fraction (LVEF) (OR 0.77, P value = 0.01) and longitudinal strain (OR 1.90, P value < 0.001) were correlated with LVT formation. Strain parameters were reduced, while the native T1 and ECV values of both the infarcted area and remote myocardium were elevated in LVT patients. During the chronic stage, LVT resolved in 29 of 38 patients (76%). LVT remaining patients had lower LVEF, a larger LV, and higher ECV in the acute stage than those of the LVT-resolved patients. In the long-term follow up of 678days, LVT (HR 2.45, P value = 0.02), aneurysm (HR 1.81, P value = 0.04), and native T1 (HR 2.44, P value = 0.01) were identified as three independent predictors of MACE, the incidence of thromboembolic events and bleeding events by a multivariable stepwise Cox proportional hazards regression. STEMI patients developing LVT had worse LV function, myocardial infarction extent, strain, and higher T1 and ECV values than STEMI patients without LVT. The LVT-remaining patients in the chronic stage had poorer functional and mapping parameters beginning in the first week. During the acute stage, LVEF and global longitudinal strain were independent correlated with LVT formation. During the long-term follow up, LVT, aneurysm and elevated myocardial T1 were associated with adverse outcomes in acute STEMI patients.

Cardiac magnetic resonance imaging in preeclampsia complicated by pulmonary edema shows myocardial edema with normal left ventricular systolic function

Preeclampsia complicates approximately 5% of all pregnancies. When pulmonary edema occurs, it accounts for 50% of preeclampsia-related mortality. Currently, there is no consensus on the degree to which left ventricular systolic dysfunction contributes to the development of pulmonary edema. This study aimed to use cardiac magnetic resonance imaging to detect subtle changes in left ventricular systolic function and evidence of acute left ventricular dysfunction (through tissue characterization) in women with preeclampsia complicated by pulmonary edema compared with both preeclamptic and normotensive controls. Cases were postpartum women aged ≥18 years presenting with preeclampsia complicated by pulmonary edema. Of note, 2 control groups were recruited: women with preeclampsia without pulmonary edema and women with normotensive pregnancies. All women underwent echocardiography and 1.5T cardiac magnetic resonance imaging with native T1 and T2 mapping. Gadolinium contrast was administered to cases only. Because of small sample sizes, a nonparametric test (Kruskal-Wallis) with pairwise posthoc analysis using Bonferroni correction was used to compare the differences between the groups. Cardiac magnetic resonance images were interpreted by 2 independent reporters. The intraclass correlation coefficient was calculated to assess interobserver reliability. Here, 20 women with preeclampsia complicated by pulmonary edema, 13 women with preeclampsia (5 with severe features and 8 without severe features), and 6 normotensive controls were recruited. There was no difference in the baseline characteristics between groups apart from the expected differences in blood pressure. Left atrial sizes were similar across all groups. Women with preeclampsia complicated by pulmonary edema had increased left ventricular mass (P=.01) but had normal systolic function compared with the normotensive controls. Furthermore, they had elevated native T1 values (P=.025) and a trend toward elevated T2 values (P=.07) in the absence of late gadolinium enhancement consistent with myocardial edema. Moreover, myocardial edema was present in all women with eclampsia or hemolysis, elevated liver enzymes, and low platelet count. Women with preeclampsia without severe features had similar findings to the normotensive controls. All cardiac magnetic resonance imaging measurements showed a very high level of interobserver correlation. This study focused on cardiac magnetic resonance imaging in women with preeclampsia complicated by pulmonary edema, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count. We have demonstrated normal systolic function with myocardial edema in women with preeclampsia with these severe features. These findings implicate an acute myocardial process as part of this clinical syndrome. The pathogenesis of myocardial edema and its relationship to pulmonary edema require further elucidation. With normal left atrial sizes, any hemodynamic component must be acute.

Cardiac Magnetic Resonance Findings after Multisystem Inflammatory Syndrome in Children

To describe the cardiac magnetic resonance (MR) findings of children recovered from multisystem inflammatory syndrome in children (MIS-C) longer than 3months after acute illness. We performed a retrospective cohort study of children hospitalized with MIS-C at a single institution receiving cardiac MR imaging between July 2020 and May 2021. Patient demographics, echocardiogram data from diagnosis through follow-up, and cardiac MR data obtained at approximately 3months after hospitalization were recorded. In total, 51 children with a median age of 11.3years were included; 80% of patients had left ventricular ejection fraction <55%, 65% of patients developed valvular regurgitation, and 20% of patients developed coronary artery dilation during acute illness. Cardiac MR was performed at a median time of 105days after diagnosis; 8% of patients had left ventricular ejection fraction <55%; 1 patient had residual valvular regurgitation; and 2 patients had residual coronary artery dilation. Two of 51 patients were found to have late gadolinium enhancement, T1 mapping abnormalities, and abnormal or borderline extracellular volume calculations suggesting myocardial fibrosis. No patient had T2 mapping abnormalities corresponding with edema, and no patient met the modified Lake Louise criteria for acute myocarditis; 10 of 51 patients had isolated elevated T1 values. At 3-5months following diagnosis, cardiac MR reveals no evidence of acute myocarditis as described by the modified Lake Louise criteria in patients with MIS-C. Two patients were observed to have myocardial fibrosis without regional wall motion abnormalities, and 10 had isolated imaging changes (elevated T1 values) in the absence of macroscopic fibrosis.

Cardiac Fibroblast Activation in Patients Early After Acute Myocardial Infarction: Integration with MR Tissue Characterization and Subsequent Functional Outcome.

After acute myocardial infarction (AMI), fibroblast activation protein (FAP) upregulation exceeds the infarct region. We sought further insights into the physiologic relevance by correlating FAP-targeted PET with tissue characteristics from cardiac MRI (CMR) and functional outcome. Methods: Thirty-five patients underwent CMR, perfusion SPECT, and 68Ga-FAP inhibitor (FAPI)-46 PET/CT within 11 d after AMI. Infarct size was determined from SPECT by comparison to a reference database. For PET, regional SUVs and isocontour volumes of interest determined the extent of cardiac FAP upregulation (FAP volume). CMR yielded functional parameters, area of injury (late gadolinium enhancement [LGE]) and T1/T2 mapping. Follow-up was available from echocardiography or CMR after 139.5 d (interquartile range, 80.5-188.25 d) (n = 14). Results: The area of FAP upregulation was significantly larger than the SPECT perfusion defect size (58% ± 15% vs. 23% ± 17%, P < 0.001) and infarct area by LGE (28% ± 11%, P < 0.001). FAP volume significantly correlated with CMR parameters at baseline (all P < 0.001): infarct area (r = 0.58), left ventricle (LV) mass (r = 0.69), end-systolic volume (r = 0.62), and end-diastolic volume (r = 0.57). Segmental analysis revealed FAP upregulation in 308 of 496 myocardial segments (62%). Significant LGE was found in only 56% of FAP-positive segments, elevated T1 in 74%, and elevated T2 in 68%. Fourteen percent (44/308) of FAP-positive segments exhibited neither prolonged T1 or T2 nor significant LGE. Of note, FAP volume correlated only weakly with simultaneously measured LV ejection fraction at baseline (r = -0.32, P = 0.07), whereas there was a significant inverse correlation with LV ejection fraction obtained at later follow-up (r = -0.58, P = 0.007). Conclusion: Early after AMI and reperfusion therapy, activation of fibroblasts markedly exceeds the hypoperfused infarct region and involves noninfarcted myocardium. The 68Ga-FAPI PET signal does not match regional myocardial tissue characteristics as defined by CMR but is predictive of the evolution of ventricular dysfunction. FAP-targeted imaging may provide a novel biomarker of LV remodeling that is complementary to existing techniques.

Characterization of cardiac amyloidosis using cardiac magnetic resonance fingerprinting

BackgroundCardiac amyloidosis (CA) is an infiltrative cardiomyopathy with poor prognosis absent appropriate treatment. Elevated native myocardial T1 and T2 have been reported for CA, and tissue characterization by cardiac MRI may expedite diagnosis and treatment. Cardiac Magnetic Resonance Fingerprinting (cMRF) has the potential to enable tissue characterization for CA through rapid, simultaneous T1 and T2 mapping. Furthermore, cMRF signal timecourses may provide additional information beyond myocardial T1 and T2. MethodsNine CA patients and five controls were scanned at 3 T using a prospectively gated cMRF acquisition. Two cMRF-based analysis approaches were examined: (1) relaxometric-based linear discriminant analysis (LDA) using native T1 and T2, and (2) signal timecourse-based LDA. The Fisher coefficient was used to compare the separability of patient and control groups from both approaches. Leave-two-out cross-validation was employed to evaluate the classification error rates of both approaches. ResultsElevated myocardial T1 and T2 was observed in patients vs controls (T1: 1395 ± 121 vs 1240 ± 36.4 ms, p < 0.05; T2: 36.8 ± 3.3 vs 31.8 ± 2.6 ms, p < 0.05). LDA scores were elevated in patients for relaxometric-based LDA (0.56 ± 0.28 vs 0.18 ± 0.13, p < 0.05) and timecourse-based LDA (0.97 ± 0.02 vs 0.02 ± 0.02, p < 0.05). The Fisher coefficient was greater for timecourse-based LDA (60.8) vs relaxometric-based LDA (1.6). Classification error rates were lower for timecourse-based LDA vs relaxometric-based LDA (12.6 ± 24.3 vs 22.5 ± 30.1%, p < 0.05). ConclusionsThese findings suggest that cMRF may be a valuable technique for the detection and characterization of CA. Analysis of cMRF signal timecourse data may improve tissue characterization as compared to analysis of native T1 and T2 alone.

Combined simultaneous FDG-PET/MRI with T1 and T2 mapping as an imaging biomarker for the diagnosis and prognosis of suspected cardiac sarcoidosis

PurposeTo evaluate the diagnostic and prognostic significance of combined cardiac 18F-fluorodeoxyglucose (FDG) PET/MRI with T1/T2 mapping in the evaluation of suspected cardiac sarcoidosis.MethodsPatients with suspected cardiac sarcoidosis were prospectively enrolled for cardiac 18F-FDG PET/MRI, including late gadolinium enhancement (LGE) and T1/T2 mapping with calculation of extracellular volume (ECV). The final diagnosis of cardiac sarcoidosis was established using modified JMHW guidelines. Major adverse cardiac events (MACE) were assessed as a composite of cardiovascular death, ventricular tachyarrhythmia, bradyarrhythmia, cardiac transplantation or heart failure. Statistical analysis included Cox proportional hazard models.ResultsForty-two patients (53 ± 13 years, 67% male) were evaluated, 13 (31%) with a final diagnosis of cardiac sarcoidosis. Among patients with cardiac sarcoidosis, 100% of patients had at least one abnormality on PET/MRI: FDG uptake in 69%, LGE in 100%, elevated T1 and ECV in 100%, and elevated T2 in 46%. FDG uptake co-localized with LGE in 69% of patients with cardiac sarcoidosis compared to 24% of those without, p = 0.014. Diagnostic specificity for cardiac sarcoidosis was highest for FDG uptake (69%), elevated T2 (79%), and FDG uptake co-localizing with LGE (76%). Diagnostic sensitivity was highest for LGE, elevated T1 and ECV (100%). After median follow-up duration of 634 days, 13 patients experienced MACE. All patients who experienced MACE had LGE, elevated T1 and elevated ECV. FDG uptake (HR 14.7, p = 0.002), elevated T2 (HR 9.0, p = 0.002) and native T1 (HR 1.1 per 10 ms increase, p = 0.044) were significant predictors of MACE even after adjusting for left ventricular ejection fraction and immune suppression treatment. The presence of FDG uptake co-localizing with LGE had the highest diagnostic performance overall (AUC 0.73) and was the best predictor of MACE based on model goodness of fit (HR 14.9, p = 0.001).ConclusionsCombined cardiac FDG-PET/MRI with T1/T2 mapping provides complementary diagnostic information and predicts MACE in patients with suspected cardiac sarcoidosis.

A pragmatic guide to choosing biologic therapies in severe asthma.

There are now several monoclonal antibody (mAb) therapies (“biologics”) available to treat severe asthma. Omalizumab is an anti-IgE mAb and is licensed in severe allergic asthma. Current evidence suggests it may decrease exacerbations by augmenting deficient antiviral immune responses in asthma. Like all other biologics, clinical efficacy is greatest in those with elevated T2 biomarkers. Three biologics target the interleukin (IL)-5–eosinophil pathway, including mepolizumab and reslizumab that target IL-5 itself, and benralizumab that targets the IL-5 receptor (IL-5R-α). These drugs all reduce the exacerbation rate in those with raised blood eosinophil counts. Mepolizumab and benralizumab have also demonstrated steroid-sparing efficacy. Reslizumab is the only biologic that is given intravenously rather than by the subcutaneous route. Dupilumab targets the IL-4 receptor and like mepolizumab and benralizumab is effective at reducing exacerbation rate as well as oral corticosteroid requirements. It is also effective for the treatment of nasal polyposis and atopic dermatitis. Tezepelumab is an anti-TSLP (thymic stromal lymphopoietin) mAb that has recently completed phase 3 trials demonstrating significant reductions in exacerbation rate even at lower T2 biomarker thresholds.Many patients with severe asthma qualify for more than one biologic. To date, there are no head-to-head trials to aid physicians in this choice. However, post-hoc analyses have identified certain clinical characteristics that are associated with superior responses to some therapies. The presence of allergic and/or eosinophilic comorbidities, such as atopic dermatitis, nasal polyposis or eosinophilic granulomatosis with polyangiitis, that may additionally benefit by the choice of biologic should also be taken into consideration, as should patient preferences which may include dosing frequency. To date, all biologics have been shown to have excellent safety profiles.