Multiparametric Cardiovascular Magnetic Resonance Research Articles

Exploring cardiovascular involvement in IgG4-related disease: a case series approach with cardiovascular magnetic resonance

BackgroundIgG4-related disease (IgG4-RD) is a relapsing–remitting, fibroinflammatory, multisystem disorder. Cardiovascular involvement from IgG4-RD has not been systematically characterised. In this study, we sought to evaluate consecutive patients with IgG4-RD using...

A pipeline for developing digital cardiac twins integrating cardiovascular magnetic resonance and electrocardiographic imaging: results from the MyoFit46 study

Abstract Background Personalised cardiovascular medicine uses multimodal screening and diagnostic tools, spanning from organ to tissue to molecular levels, to generate a complex and detailed patient phenotype. Cardiac digital twins are powerful tools capable of merging and explore these multimodal data by developing virtual, mechanistic and predictive versions of the patient's heart. State-of-the-art pipelines are mainly based on artificial intelligence and optimization process to replicate clinical data and not used it as an input. We present a proof-of-principle pipeline for building digital heart twins based on cardiovascular magnetic resonance (CMR) imaging and integrated electrocardiographic imaging (ECGI) for diverse clinical scenarios by integrating them into the model (Fig. 1). Methods CMR at 3T was performed on participants all born in the same week in March 1946, as part of the longest-running continued surveillance birth cohort: the National Survey of Health and Development. Cine steady-state free precession end-diastolic frames provided anatomical information per participant while CMR multiparametric mapping and late gadolinium enhancement (LGE) provided tissue characteristics to the electrical myocardial model used in the finite element solver Alya. Lastly, the ECGI activation map was used as a source to define the intrinsic endocardial activation sequence by applying a case-specific correction based on wall thickness and myofibers orientation. Activation-repolarization intervals map was used to introduce the personalised repolarization heterogeneities. Results In total, 406 prospectively recruited participants (77.8 ± 0.1 years, 44% male) had multiparametric CMR with ECGI for digital twin reconstruction. The pipeline’s performance was evaluated by measuring the root mean square error (RMSE) between the ECGI activation and repolarization maps with the in-silico ones obtained without applying the proposed pipeline (Baseline) and after its application (ecgi2model). Results obtained using ecgi2model pipeline presented a significantly reduced activation and repolarization RMSE (Fig. 2b), even providing accurate results in patients with different LGE patterns (Fig. 2c). Conclusion Personalised virtual heart models can be constructed at scale using real-world myocardial structural, functional, and electrical properties, from advanced CMR and ECGI data. Proposed digital twins provide a framework for personalised arrhythmic risk assessment based on real clinical data and also its applicability for in-silico clinical trials. Fig.1 Digital twins pipeline. Fig.2 a) Flattened epicardial map. b) RMSE of activation (ACT), repolarization (RPL) and activation-repolarization intervals (ARI) for the different methods methods. c) ACT and RPL maps obtained from ECGI, baseline simulation and ecgi2model simulation in a healthy participant with normal myocardial tissue, another with subendocardial LGE, and another with subepicardial LGE.Figure 1Figure 2

Serial quantitative stress perfusion cardiac magnetic resonance in patients undergoing coronary artery bypass grafting; prediction of symptomatic benefit

Abstract Background Serial multiparametric cardiovascular magnetic resonance (CMR) in patients undergoing coronary artery bypass grafting (CABG) may provide mechanistic insight into dynamic and persistent abnormalities of the myocardium in patients with stable coronary artery disease (CAD). Objectives To assess for dynamic CMR markers of myocardial hypoperfusion and cardiac remodelling in patients undergoing CABG. Methods Patients with CAD awaiting elective CABG were recruited into an observational cohort study. Baseline evaluation included bloods, Seattle Angina Questionnaire-7, and adenosine stress perfusion CMR. Automated fully quantitative stress and rest myocardial blood flow was calculated, alongside assessment of the visual ischaemic burden. Native and post-contrast septal T1 indices were also measured. Repeat evaluation at 6-12 months post CABG was performed. Results Of 43 patients who underwent serial evaluation with CMR (mean age 62.1±9.3, median LVEF 68% [IQR: 62-73%]), there was improvement in the median visual ischaemic burden (18% [IQR: 11-21] vs 42% [IQR: 27-51], P<0.001), mean global stress myocardial blood flow (1.5±0.5 ml/min/g vs 1.3±0.5 ml/min/g, P=0.002) and median global myocardial perfusion reserve (2.4 [IQR: 1.7-2.8] vs 1.7 [IQR: 1.4-2.2], P=0.002) following CABG. Greater improvement in the SAQ-7 summary score was associated with a larger visual ischaemic burden at baseline (ρ=0.44, P=0.004) and a greater decrease in the visual ischaemic burden following CABG (ρ=-0.38, P=0.02). Quantitative MBF metrics did not associate with baseline or change in SAQ-7 summary score. Mean LV extracellular matrix volume decreased following CABG (16.6±3.6ml/m2 vs 18.2±4.6ml/m2, P=0.009). Conclusion Multiparametric CMR identifies dynamic changes in markers of myocardial perfusion and interstitial fibrosis in patients following CABG. Visual assessment of inducible myocardial hypoperfusion may identify patients who will derive the most symptomatic benefit from CABG. The results, however, suggest an important degree of residual inducible ischaemia and an unclear clinical role for CMR-derived MBF calculations.Serial CMR perfusion dataAssociation of SAQ with perfusion

Precision prediction of heart failure events in patients with dilated cardiomyopathy and mildly reduced ejection fraction using multi-parametric cardiovascular magnetic resonance.

To assess whether left ventricular (LV) global longitudinal strain (GLS), derived from cardiovascular magnetic resonance (CMR), is associated with (i) progressive heart failure (HF), and (ii) sudden cardiac death (SCD) in patients with dilated cardiomyopathy with mildly reduced ejection fraction (DCMmrEF). We conducted a prospective observational cohort study of patients with DCM and LV ejection fraction (LVEF) ≥40% assessed by CMR, including feature-tracking to assess LV GLS and late gadolinium enhancement (LGE). Long-term adjudicated follow-up included (i) HF hospitalization, LV assist device implantation or HF death, and (ii) SCD or aborted SCD (aSCD). Of 355 patients with DCMmrEF (median age 54 years [interquartile range 43-64], 216 men [60.8%], median LVEF 49% [46-54]) followed up for a median 7.8 years (5.2-9.4), 32 patients (9%) experienced HF events and 19 (5%) died suddenly or experienced aSCD. LV GLS was associated with HF events in a multivariable model when considered as either a continuous (per % hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.00-1.21, p = 0.045) or dichotomized variable (LV GLS > -15.4%: HR 2.70, 95% CI 1.30-5.94, p = 0.008). LGE presence was not associated with HF events (HR 1.49, 95% CI 0.73-3.01, p = 0.270). Conversely, LV GLS was not associated with SCD/aSCD (per % HR 1.07, 95% CI 0.95-1.22, p = 0.257), whereas LGE presence was (HR 3.58, 95% CI 1.39-9.23, p = 0.008). LVEF was neither associated with HF events nor SCD/aSCD. Multi-parametric CMR has utility for precision prognostic stratification of patients with DCMmrEF. LV GLS stratifies risk of progressive HF, while LGE stratifies SCD risk.

Ethnicity differences in geometric remodelling and myocardial composition in hypertension unveiled by cardiovascular magnetic resonance.

Hypertensive patients of African ancestry (Afr-a) have higher incidences of heart failure and worse clinical outcomes than hypertensive patients of European ancestry (Eu-a), yet the underlying mechanisms remain misunderstood. This study investigated right (RV) and left (LV) ventricular remodelling alongside myocardial tissue derangements between Afr-a and Eu-a hypertensives. 63 Afr-a and 47 Eu-a hypertensives underwent multi-parametric cardiovascular magnetic resonance. Biventricular volumes, mass, function, mass/end-diastolic volume (M/V) ratios, T2 and pre-/post-contrast T1 relaxation times, synthetic extracellular volume, and myocardial fibrosis (MF) were measured. 3D shape modelling was implemented to delineate ventricular geometry. LV and RV mass (indexed to body-surface-area) and M/V ratio were significantly greater in Afr-a than Eu-a hypertensives (67.1 ± 21.7 vs. 58.3 ± 16.7 g/m2, 12.6 ± 3.48 vs. 10.7 ± 2.71 g/m2, 0.79 ± 0.21 vs. 0.70 ± 0.14 g/mL, and 0.16 ± 0.04 vs. 0.13 ± 0.03 g/mL, respectively; P < 0.03). Afr-a patients showed greater basal interventricular septum thickness than Eu-a patients, influencing LV hypertrophy and RV cavity changes. This biventricular remodelling was associated with prolonged T2 relaxation time (47.0 ± 2.2 vs. 45.7 ± 2.2 ms, P = 0.005) and higher prevalence (23% vs. 4%, P = 0.001) and extent of MF [2.3 (0.6-14.3) vs. 1.6 (0.9-2.5) % LV mass, P = 0.008] in Afr-a patients. Multivariable linear regression showed that modifiable cardiovascular risk factors and greater end-diastolic volume, but not ethnicity, were independently associated with greater LV mass. Afr-a hypertensives had distinctive biventricular remodelling, including increased RV mass, septal thickening and myocardial tissue abnormalities compared with Eu-a hypertensives. From this study, modifiable cardiovascular risk factors and ventricular geometry, but not ethnicity, were independently associated with greater LV myocardial mass.

Multiparametric Cardiovascular Magnetic Resonance in Nonhospitalized COVID-19 Infection Subjects: An Intraindividual Comparison Study.

To investigate intraindividual cardiac structural and functional changes before and after COVID-19 infection in a previously healthy population with a 3T cardiac magnetic resonance (CMR). A total of 39 unhospitalized patients with COVID-19 were recruited. They participated in our previous study as non-COVID-19 healthy volunteers undergoing baseline CMR examination and were recruited to perform a repeated CMR examination after confirmed COVID-19 infection in December 2022. The CMR parameters were measured and compared between before and after COVID-19 infection with paired t tests. The laboratory measures including myocardial enzymes and inflammatory indicators were also collected when performing repeated CMR. The median duration was 393 days from the first to second CMR and 26 days from clinical symptoms onset to the second CMR. Four patients (10.3%, 4/39) had the same late gadolinium enhancement pattern at baseline and repeated CMR and 5 female patients (12.8%, 5/39) had myocardial T2 ratio >2 (2.07 to 2.27) but with normal T2 value in post-COVID-19 CMR. All other CMR parameters were in normal ranges before and after COVID-19 infection. Between before and after the COVID-19 infection, there were no significant differences in cardiac structure, function, and tissue characterization, no matter with or without symptoms (fatigue, chest discomfort, palpitations, shortness of breath, and insomnia/sleep disorders) (all P >0.05). The laboratory measures at repeated CMR were in normal ranges in all participants. These intraindividual CMR studies showed unhospitalized patients with COVID-19 with normal myocardial enzymes had no measurable CMR abnormalities, which can help alleviate wide social concerns about COVID-19-related myocarditis.

The epicardial adipose tissue confined in the atrioventricular groove can be used to assess atrial adipose tissue and atrial dysfunction in cardiac magnetic resonance imaging.

The growing interest in epicardial adipose tissue (EAT) as a biomarker of atrial fibrillation is limited by the difficulties in isolating EAT from other paracardial adipose tissues. We tested the feasibility and value of measuring the pure EAT contained in the atrioventricular groove (GEAT) using cardiovascular magnetic resonance (CMR) imaging in patients with distinct metabolic disorders. CMR was performed on 100 patients from the MetaCardis cohort: obese (n = 18), metabolic syndrome (MSD) (n = 25), type-2 diabetes (T2D) (n = 42), and age- and gender-matched healthy controls (n = 15). GEAT volume measured from long-axis views was obtained in all patients with a strong correlation between GEAT and atrial EAT (r = 0.95; P < 0.0001). GEAT volume was higher in the three groups of patients with metabolic disorders and highest in the MSD group compared with controls. GEAT volume, as well as body mass and body fat, allowed obese, T2D, and MSD patients to be distinguished from controls. GEAT T1 relaxation and peak longitudinal left atrial (LA) strain in CMR were decreased in T2D patients. Logistic regression and random forest machine learning methods were used to create an algorithm combining GEAT volume, GEAT T1, and peak LA strain to identify T2D patients from other groups with an area under curve (AUC) of 0.81 (Se: 77%, Spe: 80%; 95% confidence interval 0.72-0.91, P < 0.0001). Atrioventricular groove adipose tissue characteristics measured during routine CMR can be used as a proxy of atrial EAT and integrated in a multi-parametric CMR biomarker for early identification of atrial cardiomyopathy.

Cardiac MR Fingerprinting: Overview, Technical Developments, and Applications.

Cardiovascular magnetic resonance (CMR) is an established imaging modality with proven utility in assessing cardiovascular diseases. The ability of CMR to characterize myocardial tissue using T1- and T2-weighted imaging, parametric mapping, and late gadolinium enhancement has allowed for the non-invasive identification of specific pathologies not previously possible with modalities like echocardiography. However, CMR examinations are lengthy and technically complex, requiring multiple pulse sequences and different anatomical planes to comprehensively assess myocardial structure, function, and tissue composition. To increase the overall impact of this modality, there is a need to simplify and shorten CMR exams to improve access and efficiency, while also providing reproducible quantitative measurements. Multiparametric MRI techniques that measure multiple tissue properties offer one potential solution to this problem. This review provides an in-depth look at one such multiparametric approach, cardiac magnetic resonance fingerprinting (MRF). The article is structured as follows. First, a brief review of single-parametric and (non-Fingerprinting) multiparametric CMR mapping techniques is presented. Second, a general overview of cardiac MRF is provided covering pulse sequence implementation, dictionary generation, fast k-space sampling methods, and pattern recognition. Third, recent technical advances in cardiac MRF are covered spanning a variety of topics, including simultaneous multislice and 3D sampling, motion correction algorithms, cine MRF, synthetic multicontrast imaging, extensions to measure additional clinically important tissue properties (proton density fat fraction, T2*, and T1ρ), and deep learning methods for image reconstruction and parameter estimation. The last section will discuss potential clinical applications, concluding with a perspective on how multiparametric techniques like MRF may enable streamlined CMR protocols. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1.

Derivation and validation of diagnostic models for myocardial fibrosis in duchenne muscular dystrophy: assessed by multi-parameter cardiovascular magnetic resonance

BackgroundGadolinium-enhanced cardiovascular magnetic resonance (CMR) is the most widely used approach for diagnosing myocardial fibrosis with late gadolinium enhancement (LGE) in cardiomyopathy associated with Duchenne muscular dystrophy. Given the limitations and safety of gadolinium use, we wanted to develop and evaluate multi-parametric pre-contrast CMR models for the diagnosis of LGE and investigate whether they could be utilised as surrogates for LGE in DMD patients.MethodsA total of 136 DMD patients were prospectively recruited and separated into LGE − and LGE + groups. In the first subset of patients (derivation cohort), regression models for the diagnosis of LGE were built by logistic regression using pre-contrast sequence parameters. In a validation cohort of other patients, the models’ performances were evaluated.ResultsEF, native T1 and longitudinal strain alone, as well as their combinations form seven models. The model that included EF, native T1 and longitudinal strain had the best diagnostic value, but there was no significant difference in diagnostic accuracy among the other models except EF. In the validation cohort, the diagnosis outcomes of models were moderate consistent with the existence of LGE. The longitudinal strain outperformed the other models in terms of diagnostic value (sensitivity: 83.33%, specificity: 54.55%).ConclusionsPre-contrast sequences have a moderate predictive value for LGE. Thus, pre-contrast parameters may be considered only in a specific subset of DMD patients who cannot cooperate for long-time examinations and have contradiction of contrast agent to help predict the presence of LGE.Trial registration number (TRN)ChiCTR1800018340Date of registration20180107

Multi-Parametric Cardiac Magnetic Resonance for Prediction of Heart Failure Death in Thalassemia Major.

We assessed the prognostic value of multiparametric cardiovascular magnetic resonance (CMR) in predicting death from heart failure (HF) in thalassemia major (TM). We considered 1398 white TM patients (30.8 ± 8.9 years, 725 women) without a history of HF at baseline CMR, which was performed within the Myocardial Iron Overload in Thalassemia (MIOT) network. Iron overload was quantified by using the T2* technique, and biventricular function was determined with cine images. Late gadolinium enhancement (LGE) images were acquired to detect replacement myocardial fibrosis. During a mean follow-up of 4.83 ± 2.05 years, 49.1% of the patients changed the chelation regimen at least once; these patients were more likely to have significant myocardial iron overload (MIO) than patients who maintained the same regimen. Twelve (1.0%) patients died from HF. Significant MIO, ventricular dysfunction, ventricular dilation, and replacement myocardial fibrosis were identified as significant univariate prognosticators. Based on the presence of the four CMR predictors of HF death, patients were divided into three subgroups. Patients having all four markers had a significantly higher risk of dying for HF than patients without markers (hazard ratio (HR) = 89.93; 95%CI = 5.62-1439.46; p = 0.001) or with one to three CMR markers (HR = 12.69; 95%CI = 1.60-100.36; p = 0.016). Our findings promote the exploitation of the multiparametric potential of CMR, including LGE, for better risk stratification for TM patients.

Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans.

South Asians (SA) constitute a quarter of the global population and are disproportionally affected by both type 2 diabetes (T2D) and heart failure. There remains limited data of the acceptability and efficacy of low-energy meal replacement plans to induce remission of T2D in SA. The objective of this exploratory secondary analysis of the DIASTOLIC study was to determine if there was a differential uptake, glycometabolic and cardiovascular response to a low-energy meal replacement plan (MRP) between SA and White European (WE) people with T2D. Obese adults with T2D without symptomatic cardiovascular disease were allocated a low-energy (~810 kcal/day) MRP as part of the DIASTOLIC study (NCT02590822). Comprehensive multiparametric cardiovascular magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing and metabolic profiling were undertaken at baseline and 12 weeks. A comparison of change at 12 weeks between groups with baseline adjustment was undertaken. Fifteen WE and 12 SAs were allocated the MRP. All WE participants completed the MRP versus 8/12 (66%) SAs. The degree of concentric left ventricular remodelling was similar between ethnicities. Despite similar weight loss and reduction in liver fat percentage, SA had a lower reduction in Homeostatic Model Assessment for Insulin Resistance [-5.7 (95% CI: -7.3, -4.2) versus -8.6 (-9.7, -7.6), p = 0.005] and visceral adiposity compared to WE [-0.43% (-0.61, -0.25) versus -0.80% (-0.91, -0.68), p = 0.002]. Exercise capacity increased in WE with no change observed in SA. There was a trend towards more reverse remodelling in WE compared to SAs. Compliance to the MRP was lower in SA versus WE. Overall, those completing the MRP saw improvements in weight, body composition and indices of glycaemic control irrespective of ethnicity. Whilst improvements in VAT and insulin resistance appear to be dampened in SA versus WE, given the small sample, larger studies are required to confirm or challenge this potential ethnic disparity. NCT02590822.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in asymptomatic heart-transplanted patients.

To describe the dynamic changes in cardiac deformation and tissue characteristics using cardiac magnetic resonance (CMR) in asymptomatic patients during 12 months after heart transplantation (HT). From April 2020 to January 2021, 21 consecutive HT patients without clinical symptoms were included in this prospective study. Multiparametric CMR was performed at 3, 6, and 12 months after HT. Twenty-five healthy volunteers served as controls. During follow-up, a decline in left ventricular (LV) global radial strain (GRS) (p = 0.020) and right ventricular (RV) global longitudinal strain (GLS) (p < 0.001) and an increase in post-contrast T1 (p = 0.024) and T2 (p < 0.001) in asymptomatic HT patients occurred at 3 months, which normalized at 6 months postoperatively, compared with those in healthy controls. A decline in LVGLS (p < 0.001) and LV global circumferential strain (GCS) (p < 0.001) and an increase in native T1 (p < 0.001), T2 (p < 0.001), and extracellular volume (ECV) (p < 0.001) occurred at 3 months. Although most parameters improved gradually, LVGLS, native T1, and ECV remained abnormal compared with those in healthy controls at 12 months; only T2 and LVGCS were normalized at 6 months and 12 months, respectively. ECV was significantly correlated with LVGLS, LVGCS, and LVGRS. Cardiac deformation and tissue characteristics were abnormal early after HT, although the patients were clinically asymptomatic. The dynamic changes in CMR characteristics demonstrate a gradual recovery of myocardial injury associated with transplantation during the first 12 months after HT. • Multiparametric CMR can detect the dynamic changes of transplantation-associated myocardial injury. • Post-contrast T1, T2, LVGRS, and RVGLS values are normalized at 6 months after HT. • Native T1, ECV, and LVGLS values remain abnormal compared with those in healthy controls at 12 months after HT.

A compartment-based myocardial density approach helps to solve the native T1 vs. ECV paradox in cardiac amyloidosis

Cardiovascular magnetic resonance (CMR) plays an important clinical role for diagnosis and therapy monitoring of cardiac amyloidosis (CA). Previous data suggested a lower native T1 value in spite of a higher LV mass and higher extracellular volume fraction (ECV) value in wild-type transthyretin amyloidosis (ATTRwt) compared to light-chain amyloidosis (AL)—resulting in the still unsolved “native T1 vs. ECV paradox” in CA. The purpose of this study was to address this paradox. The present study comprised N = 90 patients with ATTRwt and N = 30 patients with AL who underwent multi-parametric CMR studies prior to any specific treatment. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as T2-mapping and pre-/post-contrast T1-mapping allowing to measure myocardial ECV. Left ventricular ejection fraction (LV-EF), left ventricular mass index (LVMi) and left ventricular wall thickness (LVWT) were significantly higher in ATTRwt in comparison to AL. Indexed ECV (ECVi) was also higher in ATTRwt (p = 0.041 for global and p = 0.001 for basal septal). In contrast, native T1- [1094 ms (1069–1127 ms) in ATTRwt vs. 1,122 ms (1076–1160 ms) in AL group, p = 0.040] and T2-values [57 ms (55–60 ms) vs. 60 ms (57–64 ms); p = 0.001] were higher in AL. Considering particularities in myocardial density, “total extracellular mass” (TECM) was substantially higher in ATTRwt whereas “total intracellular mass” (TICM) was rather similar between ATTRwt and AL. Consequently, the “ratio TICM/TECM” was lower in ATTRwt compared to AL (0.58 vs. 0.83; p = 0.007). Our data confirm the presence of a “native T1 vs. ECV paradox” with lower native T1 values in spite of higher myocardial mass and ECV in ATTRwt compared to AL. Importantly, this observation can be explained by particularities regarding myocardial density that result in a lower TICM/TECM “ratio” in case of ATTRwt compared to AL—since native T1 is determined by this ratio.

Prospective multiparametric CMR characterization and MicroRNA profiling of anthracycline cardiotoxicity: A pilot translational study.

Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required. The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery. Twenty-four patients (age 56 range 18-75years; 42% female) with haematological malignancy scheduled to receive anthracycline chemotherapy (median dose 272mg/m2 doxorubicin equivalent) were recruited and evaluated at three timepoints (baseline, completion of chemotherapy, and 6months after completion of chemotherapy) with multiparametric 1.5T CMR, echocardiography and circulating miRNAs sequencing. Seventeen complete datasets were obtained. CMR left ventricular ejection fraction (LVEF) fell significantly between baseline and completion of chemotherapy (61±3 vs 53±3%, p<0.001), before recovering significantly at 6-month follow-up (55±3%, p=0.018). Similar results were observed for 3D echocardiography-derived LVEF and CMR-derived longitudinal, circumferential and radial feature-tracking strain. Patients were divided into tertiles according to LVEF recovery (poor recovery, partial recovery, good recovery). CMR-derived mitral annular plane systolic excursion (MAPSE) was significantly different at baseline in patients exhibiting poor LVEF recovery (11.7±1.5mm) in comparison to partial recovery (13.7±2.7mm), and good recovery (15.7±3.1mm; p=0.028). Furthermore, baseline miRNA-181-5p and miRNA-221-3p expression were significantly higher in this group. T2 mapping increased significantly on completion of chemotherapy compared to baseline (54.0±4.6 to 57.8±4.9ms, p=0.001), but was not predictive of LVEF recovery. No changes to LV mass, extracellular volume fraction, T1 mapping or late gadolinium enhancement were observed. Baseline CMR-derived MAPSE, circulating miRNA-181-5p, and miRNA-221-3p were associated with poor recovery of LVEF 6months after completion of anthracycline chemotherapy, suggesting their potential predictive role in this context. T2 mapping increased significantly on completion of chemotherapy but was not predictive of LVEF recovery.

Cardiac Magnetic Resonance Predicts Heart Failure Mortality in Patients with Thalassemia Major

Iron-induced Heart Failure (HF) still remains the main cause of mortality in patients with thalassemia major (TM), although the introduction of the T2* Cardiovascular Magnetic Resonance (CMR) for the non-invasive assessment of Myocardial Iron Overload (MIO) led to a significant increase in survival rate. However, the pathophysiology of heart failure in TM can be multifactorial. Thanks to its multiparametric potential, CMR represents a unique tool for characterization of myocardial involvement. It is the gold standard for the quantification of biventricular size and function by cine images and for the detection of replacement fibrosis by late gadolinium enhancement (LGE) technique. The aim of this multicenter study was to evaluate the prognostic value of multiparametric CMR in predicting death for HF. We considered 1398 white TM patients who performed a baseline CMR exam within the Myocardial Iron Overload in Thalassemia (MIOT) network. As per inclusion criteria, no patient had a history of HF. Mean age was 30.8±8.9 years and 725 (51.9%) patients were females. During a mean follow-up of 4.83±2.05 years, 49.1% of the patients changed at least once the chelation regimen (i.e.: either switched to a different type of chelator or underwent dose/frequency modification); these patients were more likely to have a global heart T2* value<20ms than patients who maintained the same regimen (33.2% vs 19.7%; P<0.0001) Twelve (1.0%) patients died from heart failure. Table 1 shows the results, presented as hazard ratio (HR) with 95% confidence intervals (CI), of the univariate Cox Regression analysis, performed to test the association between the considered prognostic variables and the outcome. No association was detected between age or gender and HF mortality. Significant MIO (global heart T2*<20 ms), ventricular dysfunction, ventricular dilation, and replacement myocardial fibrosis were identified as significant univariate prognosticators. Due to the low number of deaths for HF, it was not possible to perform a multivariate model. However, based on the presence of the four CMR predictors of HF death, patients were divided into three subgroups: four markers (7 patients; one HF death-14.3%), one to four markers (617 patients, 9 HF deaths-1.5%), and none of the four markers (488 patients; one HF death-0.2%). Patients having all four markers had a significantly higher risk of dying for HF than patients without markers (HR=89.93; 95%CI=5.62-1439.46; P=0.001) or with one to three CMR markers (HR=12.69; 95%CI=1.60-100.36; P=0.016). In our homogeneous white and well-treated Italian/Mediterranean population, we detected a low incidence of deaths for HF, since the T2* report guided the patient-specific adjustment of the chelation regimen. As expected, MIO was a significant predictor of HF death but also other CMR parameters, namely ventricular dilatation, ventricular dysfunction, and replacement myocardial fibrosis emerged as unfavorable prognosis determinant. Importantly, when the four CMR indices were evaluated in combination, they fine-tuned the prognostic stratification of TM patients. Hence, the findings of the present study promote the exploitation of the full potential of CMR, including LGE, for a better risk stratification of TM patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cardiovascular magnetic resonance phenotyping of heart failure with mildly reduced ejection fraction.

The 2016 European Society of Cardiology Heart Failure Guidelines defined a new category: heart failure with mid-range ejection fraction (HFmrEF) of 40-49%. This new category was highlighted as having limited evidence and research was advocated into underlying characteristics, pathophysiology, and diagnosis. We used multi-parametric cardiovascular magnetic resonance (CMR) to define the cardiac phenotype of presumed non-ischaemic HFmrEF. Patients (N = 300, 62.7 ± 13 years, 63% males) with a clinical diagnosis of heart failure with no angina symptoms, history of myocardial infarction, or coronary intervention were prospectively recruited. Patients underwent clinical assessment and CMR including T1 mapping, extracellular volume (ECV) mapping, late gadolinium enhancement, and measurement of myocardial blood flow at rest and maximal hyperaemia. Of 273 patients in the final analysis, 93 (34%) patients were categorized as HFmrEF, 46 (17%) as heart failure with preserved ejection fraction (HFpEF), and 134 (49%) as heart failure with reduced ejection fraction (HFrEF). Nineteen (20%) patients with HFmrEF had evidence of occult ischaemic heart disease. Diffuse fibrosis and hyperaemic myocardial blood flow were similar in HFmrEF and HFpEF, but HFmrEF showed significantly lower native T1 (1311 ± 32 vs. 1340 ± 45 ms, P < 0.001), ECV (24.6 ± 3.2 vs. 26.3 ± 3.1%, P < 0.001), and higher myocardial perfusion reserve (2.75 ± 0.84 vs. 2.28 ± 0.84, P < 0.001) compared with HFrEF. Patients with HFmrEF share most phenotypic characteristics with HFpEF, including the degree of microvascular impairment and fibrosis, but have a high prevalence of occult ischaemic heart disease similar to HFrEF. Further work is needed to confirm how the phenotype of HFmrEF responds to medical therapy.

Applying quantitative CMR parameters for detecting myocardial lesion in immune checkpoint inhibitors-associated myocarditis

PurposeSparse researches evaluated the quantitative cardiovascular magnetic resonance (CMR) parameters for immune checkpoint inhibitors (ICI)-associated myocarditis. We aimed to apply quantitative CMR mappings and late gadolinium enhancement (LGE) extent for detecting ICI-associated myocarditis. MethodThe retrospective study included patients with ICI-associated myocarditis and CMR examination from August 2018 to August 2021 in our hospital. ICI-associated myocarditis was clinically diagnosed based on the clinical criteria by European Society of Cardiology guidelines. The multiparametric CMR images including T2 mapping and black blood T2-weighted images were used to evaluate myocardial edema. The myocardial edema ratio (ER) ≥ 2.0 was applied for determining myocardial edema on T2-weighted images. Results56 patients with ICI-associated myocarditis were included. The global T2 value and native T1 value of patients with ICI-associated myocarditis were significantly higher than the reference ranges in our hospital (p < 0.05). The rate of elevated global T2 value (92%) was significantly higher than those of abnormal native T1 value (73%), ER (52%) and LGE presence (68%) in patients with ICI-associated myocarditis (p < 0.05). The LGE extent and left ventricular ejection fraction of patients with ICI-associated myocarditis were 10.38 ± 9.64% and 56.42 ± 8.54%, respectively. LGE extent inversely correlated with left ventricular ejection fraction (r = -0.38, p = 0.004) but positively correlated with native T1 value (r = 0.28, p < 0.04) and extracellular volume (r = 0.50, p = 0.001). ConclusionsT2 mapping could detect higher rate of patients with ICI-associated myocarditis than native T1 mapping, ER and LGE presence. LGE extent inversely correlated with left ventricular ejection fraction but positively correlated with native T1 value and extracellular volume in patients with ICI-associated myocarditis.

Ethnicity-specific myocardial remodelling in hypertensive heart disease by multi-parametric cardiovascular magnetic resonance

Abstract Background Patients with systemic hypertension (HTN) of African ancestry (Afr-a) are at greater risk of incident heart failure (HF), hospitalisation and death than those of European ancestry (Eu-a). This has been related to higher prevalence of HTN-related target organ damage, including high level of circulating cardiac troponins, which is not fully explained by blood pressure level. Thus, one may speculate that Afr-a hypertensives have a higher tendency to develop myocardial damage in response to arterial afterload. However, myocardial composition differences between Afr-a and Eu-a hypertensives remain speculative. Purpose To investigate ethnic-specific differences in myocardial tissue composition in Eu-a and Afr-a hypertensives by multi-parametric cardiovascular magnetic resonance (CMR). Methods This cross-sectional study included 63 Afr-a and 47 Eu-a hypertensive patients. All patients underwent multi-parametric CMR (1.5-Tesla Aera, Siemens-Healthcare, Erlangen-Germany). Left (LV) and right ventricular (RV) volumes, mass and function, atrial dimensions, and myocardial tissue characterisation (including T1- and T2-mapping) were measured using a standardised imaging protocol, and post-processing recommendations from international scientific societies. Analysis was completed using a commercially available cardiac-software (CVI-42, Calgary-Canada). Central pulse-wave-velocity (PWV) between the ascending and proximal descending thoracic aorta was measured by high-temporal, resolution 2D phase-contrast velocity-encoded parasagittal cine images, using in-house MATLAB software. Results Although Afr-a were 5 years older than Eu-a hypertensives, cardiovascular risk factors, anthropometric, body composition and haemodynamic measures were similar between the two groups (Figure 1). Segmental PWV was greater in Afr-a than Eu-a patients (8.16±2.71 vs 6.97±2.82 m/s, P=0.044), underlying higher aortic stiffness in Afr-a hypertensives. Afr-a hypertensives also had greater LV mass and LV-mass/end-diastolic volume ratio than Eu-a (Figure 2), whilst no difference was observed in LV systolic/diastolic function. Native T1 relaxation time and synthetic extracellular volume were also similar between the two ethnicities, though T2 relaxation time was significantly higher in Afr-a hypertensives. Late gadolinium enhancement (LGE), a well-established metric of replacement fibrosis (scarring), was more prevalent in Afr-a than Eu-a hypertensives (14% vs 4%, P=0.001). In patients with LGE, the extent of LGE was higher in Afr-a than Eu-a hypertensives (Figure 2). Conclusion Afr-a hypertensives have higher arterial afterload, LV mass and remodelling than Eu-a, despite comparable mean blood pressure, body-mass-index, and body composition. These changes in LV structure and geometry were associated with higher T2 relaxation time, likely reflecting low-grade inflammation, as well as higher prevalence and extent of replacement myocardial fibrosis. Funding Acknowledgement Type of funding sources: None.

Racial differences of right ventricular remodelling in systemic hypertension unveiled by multiparametric cardiovascular magnetic resonance

Abstract Background Patients with systemic hypertension (HTN) of African ancestry (Afr-a) are at greater risk of heart failure (HF), hospitalisation and death than those of European ancestry (Eu-a). Compelling evidence suggests that left ventricular (LV) remodelling and hypertrophy are more prevalent in Afr-a than Eu-a hypertensives due to either a high clustering of cardiovascular risk-factors and/or a difference in genetic background. Prior studies in Eu-a subjects have shown that uncomplicated HTN is associated with right ventricular (RV) hypertrophy and remodelling which may contribute to development of HF. However, the impact of ethnicity on RV remodelling in HTN remains speculative. Purpose To investigate the influence of ethnicity on RV remodelling/hypertrophy in patients with HTN using cardiovascular magnetic resonance (CMR). Methods In this cross-sectional study we included 16 Afr-a and 32 Eu-a age- and sex-matched healthy-volunteers, and 63 Afr-a and 47 Eu-a hypertensives. All participants underwent a CMR exam (1.5-Tesla, Aera, Siemens-Healthcare, Erlangen-Germany). LV and RV volumes, masses and function were measured according to the current recommendations. Blood pressure was recorded during the CMR. Results Age- and sex-matched Afr-a and Eur-a healthy-volunteers (37±10 vs 37±12 years, P=0.975; male 53% vs 44%; P=0.539) exhibited closely comparable LV and RV volumes, masses, and end-diastolic volume/mass ratios. In the HTN group, despite Afr-a hypertensives being roughly 5 years older than Eu-a, baseline characteristics including cardiovascular risk factors, mean blood pressure, body-mass-index, and body composition metrics were similar between the two groups (Figure 1). Afr-a hypertensives also had greater LV and RV masses and mass/end-diastolic volume ratios than Eur-a hypertensives (Figure 2). RV mass correlated with LV mass in both ethnic groups (r=0.593 in Eu-a and r=0.569 in Afr-a; both P&amp;lt;0.001). Multivariable linear regression analysis showed that RV mass was independently associated with African descendance after correction for major confounders including LV mass, biventricular volumes, and body composition. Conclusion Our findings support the notion that Afr-a and Eur-a healthy-volunteers have comparable left and right ventricular geometry and masses, arguing against genetic-determinate ventricular geometry and myocardial mass in this population. However, Afr-a individuals exhibit higher sensitivity to myocardial hypertrophy in response to HTN which translates into greater biventricular masses and remodelling, compared to Eu-a hypertensives. Funding Acknowledgement Type of funding sources: None.

Therapeutic value of tafamidis in patients with wild-type transthyretin amyloidosis (ATTRwt) with cardiomyopathy based on cardiovascular magnetic resonance (CMR) imaging

Abstract Background Tafamidis was approved in Europe for the treatment of cardiomyopathy (CM) in patients with transthyretin amyloidosis (ATTR) in April 2020. So far, real-world data addressing the therapeutic value of tafamidis for the treatment of ATTR-CM are scarce. The purpose of this study was to carefully analyse the therapeutic benefit of tafamidis in patients with wild-type ATTR (ATTRwt) and CM (ATTRwt-CM) after one year of therapy based on serial multi-parametric cardiovascular magnetic resonance (CMR) imaging. Purpose The purpose of this study was to carefully analyse the therapeutic benefit of tafamidis in patients with wild-type transthyretin amyloidosis (ATTRwt) and cardiomyopathy (ATTRwt-CM) after one year of therapy based on serial multi-parametric cardiovascular magnetic resonance (CMR) imaging. Methods The present study comprised N=40 patients with ATTRwt-CM who underwent two serial multi-parametric CMR studies within a follow-up period of 12±3 months. Baseline (BL) clinical parameters, serum biomarkers and CMR findings were compared to follow-up (FU) values in patients with treated “with” tafamidis 61mg daily (n=20, group A) and those “without” tafamidis therapy (n=16, group B). CMR studies were performed on a 1.5-T system and comprised (amongst others) cine-imaging for assessment of cardiac anatomy and function including 3D longitudinal strain assessment. In addition, a modified Look-Locker inversion recovery (MOLLI) T1-mapping sequence was performed for measurement of pre- and post-contrast myocardial T1-values with additional calculation of extracellular volume fraction (ECV)-values. Results While left ventricular ejection fraction (LV-EF), left ventricular mass index (LVMi), left ventricular wall thickness (LVWT), native T1- and ECV-values remained unchanged in the tafamidis group A, a slight reduction in LV-EF (p=0.003) as well as a subtle increase in LVMi (p=0.034), in LVWT (p=0.001), in native T1- (p=0.038) and ECV-values (p=0.017) were observed in the untreated group B. Serum NT-proBNP levels showed an overall increase in both groups, however, with the untreated group B showing a relatively higher increase compared to the treated group A. Assessment of NYHA class did not result in significant intra-group differences when BL were compared with FU, but a trend to improvement in the treated group A compared to a worsening trend in the untreated group B (Δp=0.005). Conclusion Tafamidis does not improve cardiac phenotype in patients with ATTRwt-CM after one year of therapy. However, tafamidis seems to slow down cardiac disease progression in patients with ATTRwt-CM compared to those without tafamidis therapy based on multi-parametric CMR data already after one year of therapy. Funding Acknowledgement Type of funding sources: None.