Extracellular Volume Mapping Research Articles

Study design of the CARDIO-TTRansform cardiac magnetic resonance imaging substudy

Abstract Background Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping can track treatment response in patients with cardiac amyloidosis by assessing changes in cardiac amyloid burden along with associated changes in structure and function. The CARDIO-TTRansform trial is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial designed to assess the efficacy and safety of eplontersen in transthyretin amyloid cardiomyopathy (ATTR-CM). Eplontersen is a ligand-conjugated antisense oligonucleotide designed to reduce hepatic production of transthyretin protein, the amyloid fibril precursor protein in ATTR-CM. Patients with hereditary or wild-type ATTR-CM on available standard of care were randomized 1:1 to receive 45 mg of eplontersen or placebo via subcutaneous injection every 4 weeks. Patients in the main study with no contraindication to CMR were invited to participate in this sub-study. Purpose The primary objective is to measure the change in amyloid burden (defined as % change in ECV from baseline) over time in patients receiving eplontersen versus placebo. Methods Participants will undergo CMR with ECV mapping at baseline, 25, 49, 97 and 140 weeks (Figure 1). Images will be acquired under a standardized protocol comprising cine imaging with steady state free precession sequence, late gadolinium enhancement imaging (LGE) and T1 mapping. T1 mapping will be performed before the administration of contrast and will be repeated 15 minutes post-contrast using the same slice locations, to produce ECV maps. Results In the main study, 1432 patients were randomized from 120 sites across 20 countries. Of these patients, 157 patients were enrolled in the CMR sub-study, from 6 centers across 4 countries. Images will be read centrally at the end of the study. All participants in the study will also receive serial transthoracic echocardiography with strain analysis to correlate findings with conventional imaging techniques, and a subset of patients from the CMR substudy will be co-enrolled in a scintigraphy substudy for further characterization of amyloid deposition in their heart. Conclusion The CARDIO-TTRansform CMR substudy represents the largest CMR study of ATTR-CM. The CMR sub-study has enrolled a broad global population of patients with hereditary and wild-type ATTR-CM and will provide key information on the impact of eplontersen on the cardiac amyloid load and the associated change in structure and function.

Free-breathing 3D cardiac extracellular volume (ECV) mapping using a linear tangent space alignment (LTSA) model.

To develop a new method for free-breathing 3D extracellular volume (ECV) mapping of the whole heart at 3 T. A free-breathing 3D cardiac ECV mapping method was developed at 3 T. T1 mapping was performed before and after contrast agent injection using a free-breathing electrocardiogram-gated inversion recovery sequence with spoiled gradient echo readout. A linear tangent space alignment model-based method was used to reconstruct high-frame-rate dynamic images from (k,t)-space data sparsely sampled along a random stack-of-stars trajectory. Joint T1 and transmit B1 estimation were performed voxel-by-voxel for pre- and post-contrast T1 mapping. To account for the time-varying T1 after contrast agent injection, a linearly time-varying T1 model was introduced for post-contrast T1 mapping. ECV maps were generated by aligning pre- and post-contrast T1 maps through affine transformation. The feasibility of the proposed method was demonstrated using in vivo studies with six healthy volunteers at 3 T. We obtained 3D ECV maps at a spatial resolution of 1.9 × 1.9 × 4.5 mm3 and a FOV of 308 × 308 × 144 mm3, with a scan time of 10.1 ± 1.4 and 10.6 ± 1.6 min before and after contrast agent injection, respectively. The ECV maps and the pre- and post-contrast T1 maps obtained by the proposed method were in good agreement with the 2D MOLLI method both qualitatively and quantitatively. The proposed method allows for free-breathing 3D ECV mapping of the whole heart within a practically feasible imaging time. The estimated ECV values from the proposed method were comparable to those from the existing method.

Evolving capabilities of computed tomography imaging for transcatheter valvular heart interventions - new opportunities for precision medicine.

The last decade has witnessed a substantial growth in percutaneous treatment options for heart valve disease. The development in these innovative therapies has been mirrored by advances in multi-detector computed tomography (MDCT). MDCT plays a central role in obtaining detailed pre-procedural anatomical information, helping to inform clinical decisions surrounding procedural planning, improve clinical outcomes and prevent potential complications. Improvements in MDCT image acquisition and processing techniques have led to increased application of advanced analytics in routine clinical care. Workflow implementation of patient-specific computational modeling, fluid dynamics, 3D printing, extended reality, extracellular volume mapping and artificial intelligence are shaping the landscape for delivering patient-specific care. This review will provide an insight of key innovations in the field of MDCT for planning transcatheter heart valve interventions.

Redefining Cardiac Involvement and Targets of Treatment in Systemic Immunoglobulin AL Amyloidosis

Cardiac amyloid infiltration is the key determinant of survival in systemic light-chain (AL) amyloidosis. Current guidelines recommend early switching therapy in patients with a nonoptimal or suboptimal response regardless of the extent of cardiac amyloid infiltration. To assess the differences between serum biomarkers, echocardiography, and cardiovascular magnetic resonance (CMR) with extracellular volume (ECV) mapping in characterizing cardiac amyloid, the independent prognostic role of these approaches, and the role of ECV mapping to guide treatment strategies. Consecutive patients newly diagnosed with systemic AL amyloidosis (2015-2021) underwent echocardiography, cardiac biomarkers, and CMR with ECV mapping at diagnosis. Data were analyzed from January to June 2024. The primary outcomes of the study were all-cause mortality and hematological response as defined according to validated criteria: no response (NR), partial response (PR), very good partial response (VGPR), and complete response (CR). Secondary outcomes were the depth and speed of hematological response and overall survival according to ECV. Of 560 patients with AL amyloidosis, the median (IQR) age was 68 years (59-74 years); 346 patients were male (61.8%) and 214 female (38.2%). Over a median (IQR) 40.5 months 9-58 months), ECV was independently associated with mortality. In the landmark analysis at 1 month, long-term survival was independent of the achieved hematological response in ECV less than 0.30% and ECV of 0.31% to 0.40%, while it was dependent on the depth of the hematological response in ECV greater than 0.40%. In the landmark analysis at 6 months, survival was independent of the achieved hematological response in ECV less than 0.30% and dependent on achieving at least PR in ECV of 0.31% to 0.40%. Survival was dependent on achieving CR in ECV of 0.41% to 0.50% and ECV greater than 0.50%. Achieving a deep hematological response at 1 month was associated with better survival compared with 6 months in patients with ECV greater than 0.40% but not with ECV less than 0.40%. This study found that ECV mapping, in systemic AL amyloidosis, is an independent predictor of prognosis, can help define the hematological response associated with better long-term outcomes for each patient and potentially inform treatment strategies.

Multiparametric myocardial mapping using cardiac magnetic resonance imaging in healthy dogs: Reproducibility, repeatability, and differences across slices, segments, and sequences.

Myocardial mapping in humans has been widely studied and applied to understand heart disease, facilitate early diagnosis, and determine therapeutic targets; however, the reproducibility, repeatability, and protocol-dependent differences in myocardial mapping in dogs remain unknown, which limits its application in dogs. This study investigated the reproducibility and test-retest repeatability of myocardial mapping in dogs and evaluated the differences according to slice, segment, and sequence. Precontrast T1 (native T1), T2 (T2), and T2* relaxation time (T2*), and extracellular volume (ECV) were measured at the base, midventricle, and apex of the left ventricle in six healthy beagles. To compare the sequences, the saturation recovery-based (SMART1) and inversion recovery-based (MOLLI) sequences were used for native T1 and ECV mapping. The intraclass correlation coefficient was measured to evaluate reproducibility and repeatability using the coefficient of variation and Bland-Altman analysis. All parameters showed good to excellent intra- and interobserver reproducibility and test-retest repeatability. The apex slice showed the lowest repeatability among the slices, whereas ECV had the lowest repeatability among the parameters. Native T1, ECV, and T2* did not differ according to slice, but T2 significantly increased from the base to the apex. Native T1 was significantly higher in SMART1 than in MOLLI, whereas ECV did not differ between the two sequences. Our results suggest that myocardial mapping is applicable in dogs with high reproducibility and repeatability, although slice and sequence differences should be considered. This study can serve as a guide for myocardial mapping studies in dogs with heart disease.

Left ventricular structural integrity on tetralogy of Fallot patients: approach using longitudinal relaxation time mapping.

Tetralogy of Fallot (TOF) is a congenital heart disease, and patients undergo surgical repair early in their lives. The evaluation of TOF patients is continuous through their adulthood. The use of cardiac magnetic resonance imaging (CMR) is vital for the evaluation of TOF patients. We aim to correlate advanced MRI sequences [parametric longitudinal relaxation time (T1), extracellular volume (ECV) mapping] with cardiac functionality to provide biomarkers for the evaluation of these patients. A complete CMR examination with the same imaging protocol was conducted in a total of 11 TOF patients and a control group of 25 healthy individuals. A Modified Look-Locker Inversion recovery (MOLLI) sequence was included to acquire the global T1 myocardial relaxation times of the left ventricular (LV) pre and post-contrast administration. Appropriate software (Circle cmr42) was used for the CMR analysis and the calculation of native, post-contrast T1, and ECV maps. A regression analysis was conducted for the correlation between global LV T1 values and right ventricular (RV) functional indices. Statistically significant results were obtained for RV cardiac index [RV_CI= -32.765 + 0.029 × T1 native; ], RV end diastolic volume [RV_EDV/BSA = -1023.872 + 0.902 × T1 native; ], and RV end systolic volume [RV_ESV/BSA = -536.704 + 0.472 × T1 native; ]. We further support the diagnostic importance of T1 mapping as a structural imaging tool in CMR. In addition to the well-known affected RV function in TOF patients, the LV structure is also impaired as there is a strong correlation between LV T1 mapping and RV function, evoking that the heart operates as an entity.

Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy

ObjectivesTo investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features.Materials and methodsOne hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan–Meier method were used to evaluate the predictive performance of the scoring system.ResultsMultivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001).ConclusionECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach.Critical relevance statementThe scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis.Key PointsPredicting the progression of LAPC in patients receiving IORT is important.Our ECV-based scoring system can risk stratifying patients with initial SD.Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.Graphical

Cardiac Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy: What a Cardiologist Should Know

Abstract Hypertrophic cardiomyopathy (HCM) affects 1 in 200–500 of the general population, with about 10%–20% identified clinically. The primary goal of imaging for a cardiologist is to provide an accurate diagnosis and add prognostic value. Multiplanar electrocardiogram-gated cardiac magnetic resonance (CMR) imaging can evaluate all phases of the cardiac cycle. CMR excels in the accurate and reproducible evaluation of cardiac morphology, particularly in determining wall thickness and the distribution of hypertrophy. It can also assess the mitral valvular apparatus. Functional evaluation includes assessing contractility, accurate ejection fraction quantification, and visualizing and quantifying dynamic flow, particularly in the subaortic region. CMR strain imaging with feature tracking software evaluates segmental contractility. Late gadolinium enhancement (delayed enhancement), T1, and extracellular volume mapping add to the prognostic ability of CMR magnetic resonance imaging in predicting outcome by evaluating the myocardial fibrosis. CMR also adds value by evaluating the left atrium and right ventricle. A combination of the above helps accurately differentiate between phenotypes of HCM, suggest genetic forms of HCM, and monitor patients after treatment to track disease progression or changes. This review aims to describe the multiparametric strengths of CMR in the diagnosis and prognosis of HCM.

Subclinical myocardial involvement in a cohort of patients with antisynthetase syndrome.

There is an increasing interest in knowing whether patients with antisynthetase syndrome (ASSD) may have silent myocardial interstitial involvement. Mapping techniques in cardiac magnetic resonance (CMR) can detect subclinical myocardial involvement. The purpose of this study was to identify alterations in multiparametric CMR in ASSD patients without overt cardiac involvement. Patients diagnosed with ASSD underwent a CMR along with the standard clinical workup, investigation of specific and associated myositis antibodies, and high-resolution chest CT. The CMR protocol includes routine morphologic, functional, and late gadolinium enhancement sequences in standard cardiac planes, as well as native T1 and T2 mapping sequences and extracellular volume (ECV) calculation. Twenty-five patients were included in this study (56% women; median age 56.3 years). Three patients were considered in the acute phase at the time of inclusion. Eight patients (32%) showed pathological findings in CMR (6 stable disease, 2 acute phase). Elevated T1, T2 and ECV mapping values were found in 20% (5/25), 17% (4/25) and 24% (6/25) of the group, respectively. Two patients in the acute phase had increased values of both T2 and ECV. Subclinical myocardial involvement in ASSD is not rare (32%) although its clinical significance is uncertain. Myocardial oedema (T2) was the most frequent finding, followed by increased T1 and/or ECV values likely signalling interstitial fibrosis. Of note, patients in the acute phase showed elevated T2 values.

Cardiopulmonary Exercise Testing in Evaluating Transthyretin Amyloidosis.

Cardiopulmonary exercise testing (CPET) has an established role in the assessment of patients with heart failure. However, data are lacking in patients with transthyretin (ATTR) amyloidosis. To use CPET to characterize the spectrum of functional phenotypes in patients with ATTR amyloidosis and assess their association with the cardiac amyloid burden as well as the association between CPET parameters and prognosis. This single-center study evaluated patients diagnosed with ATTR amyloidosis from May 2019 to September 2022 who underwent CPET at the National Amyloidosis Centre. Of 1045 patients approached, 506 were included and completed the study. Patients were excluded if they had an absolute contraindication to CPET or declined participation. The mean (SD) follow-up period was 22.4 (11.6) months. Comparison of CPET parameters across disease phenotypes (ATTR with cardiomyopathy [ATTR-CM], polyneuropathy, or both [ATTR-mixed]), differences in CPET parameters based on degree of amyloid infiltration (as measured by cardiovascular magnetic resonance [CMR] with extracellular volume mapping), and association between CPET parameters and prognosis. Among the 506 patients with ATTR amyloidosis included in this study, the mean (SD) age was 73.5 (10.2) years, and 457 participants (90.3%) were male. Impairment in functional capacity was highly prevalent. Functional impairment in ATTR-CM and ATTR-mixed phenotypes (peak mean [SD] oxygen consumption [VO2], 14.5 [4.3] mL/kg/min and 15.7 [6.2] mL/kg/min, respectively) was observed alongside impairment in the oxygen pulse, with ventilatory efficiency highest in ATTR-CM (mean [SD] ventilatory efficiency/volume of carbon dioxide expired slope, 38.1 [8.6]). Chronotropic incompetence and exercise oscillatory ventilation (EOV) were highly prevalent across all phenotypes, with both the prevalence and severity being higher than in heart failure from different etiologies. Worsening of amyloid burden on CMR was associated with decline in multiple CPET parameters, although chronotropic response and EOV remained abnormal irrespective of amyloid burden. On multivariable Cox regression analysis, peak VO2 and peak systolic blood pressure (SBP) were independently associated with prognosis (peak VO2: hazard ratio, 0.89 [95% CI, 0.81-0.99; P = .03]; peak SBP: hazard ratio, 0.98 [95% CI, 0.97-0.99; P < .001]). In this study, ATTR amyloidosis was characterized by distinct patterns of functional impairment between all disease phenotypes. A high prevalence of chronotropic incompetence, EOV, and ventilatory inefficiency were characteristic of this population. CPET parameters were associated with amyloid burden by CMR and with peak VO2, and SBP, which have been shown to be independent predictors of mortality. These findings suggest that CPET may be useful in characterizing distinct patterns of functional impairment across the spectrum of amyloid infiltration and predicting outcomes, and potentially offers a more comprehensive method of evaluating functional capacity for future prospective studies.

Cardiometabolic biomarker patterns associated with cardiac MRI defined fibrosis and microvascular dysfunction in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex disease process influenced by metabolic disorders, systemic inflammation, myocardial fibrosis, and microvascular dysfunction. The goal of our study is to identify potential relationships between plasma biomarkers and cardiac magnetic resonance (CMR) imaging markers in patients with HFpEF. Nineteen subjects with HFpEF and 15 age-matched healthy controls were enrolled and underwent multiparametric CMR and plasma biomarker analysis using the Olink® Cardiometabolic Panel (Olink Proteomics, Uppsala, Sweden). Partial least squares discriminant analysis (PLS-DA) was used to characterize CMR and biomarker variables that differentiate the subject groups into two principal components. Orthogonal projection to latent structures by partial least squares (OPLS) analysis was used to identify biomarker patterns that correlate with myocardial perfusion reserve (MPR) and extracellular volume (ECV) mapping. A PLS-DA could differentiate between HFpEF and normal controls with two significant components explaining 79% (Q2 = 0.47) of the differences. For OPLS, there were 7 biomarkers that significantly correlated with ECV (R2 = 0.85, Q = 0.53) and 6 biomarkers that significantly correlated with MPR (R2 = 0.92, Q2 = 0.32). Only 1 biomarker significantly correlated with both ECV and MPR. Patients with HFpEF have unique imaging and biomarker patterns that suggest mechanisms associated with metabolic disease, inflammation, fibrosis and microvascular dysfunction.

Kiosk 6R-FC-02 - Machine Learning Diagnosis of Hypertrophic Disease States FBom Native T1 and Extracellular Volume Mapping Using a Fully Automated Radiomics Pipeline

Kiosk 6R-FC-02 - Machine Learning Diagnosis of Hypertrophic Disease States FBom Native T1 and Extracellular Volume Mapping Using a Fully Automated Radiomics Pipeline

Prognostic value of left ventricular hypertrophy in patients with myocardial fibrosis by ECV mapping on cardiac MRI

Abstract Background Cardiovascular magnetic resonance (CMR) can noninvasively identify myocardial fibrosis using extracellular volume (ECV) mapping. In patients with elevated ECV, and without hypertrophic cardiomyopathy (HCM) or cardiac amyloidosis, the prognostic significant of mild-to-moderate left ventricular hypertrophy (LVH) has not been well established. Purpose To determine if the presence of mild to moderate LVH has an impact on major adverse cardiovascular outcomes (MACE) in patients with elevated ECV without HCM or cardiac amyloidosis. Methods This was a retrospective cohort study assessing a group of patients referred for CMR between July 2019 and January 2023 to Mount Sinai Morningside. Patients with ECV&amp;gt;30% and left ventricular wall thickness &amp;lt;1.6 cm (to exclude patients with the possible diagnosis of HCM or cardiac amyloidosis) were considered for inclusion. Those with an established diagnosis of HCM or cardiac amyloidosis were also excluded. The LVH group comprised of patients with mild-to-moderate LVH, defined as a maximum wall thickness of 1.2-1.5 cm. The control group included patients without LVH (wall thickness &amp;lt;1.2 cm). Patients were further stratified by ECV, using the median value for our sample, as "high ECV" (≥35%) or "low ECV" (&amp;lt;35%). The outcome of interest was time-to-first MACE (all-cause death, or incident acute coronary syndrome, acute heart failure, or arrhythmia). Time-to-first MACE within 1 year was compared among groups using unadjusted Kaplan-Meier curves. Additional Cox regression analyses were performed to adjust for significant univariate analysis, including hypertension, hyperlipidemia, diabetes mellitus, use of beta-blocker, use of diuretic, and category of glomerular filtration rate. The results are presented as hazard ratios and 95% confidence intervals. All analyses were performed in SAS Enterprise using α&amp;lt;0.05. Results Out of the cohort, we identified 186 patients that met our selection criteria. The mean age was 61.1 ± 15.5 years, and 58.1% of patients were female. The median follow-up was 175 days in the control group and 115 days in the LVH group. There were 61 MACE (32.8%) in our sample. After adjusting for covariates, mild-to-moderate LVH was associated with 2.2 times the risk of MACE (95%CI 1.3 to 3.8; p=0.0047) at 1 year, compared to patients without LVH. A higher ECV (≥35%) was not significantly associated with worse outcomes within each study arm (p=0.3450). Kaplan Meier survival curves for patients with and without LVH are shown in Figure 1 (p=0.0002). Conclusions In patients with evidence of elevated ECV without underlying cardiac amyloidosis or hypertrophic cardiomyopathy, mild-to-moderate LVH is associated with 2.2 times the risk of MACE compared to normal left ventricular wall thickness.Figure 1

Anthracycline therapy induces an early decline of cardiac contractility with transient edema in low risk patients with breast cancer

Abstract Background Cancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy in the treatment of breast cancer. CTRCD most frequently appears in patients with cardiovascular risk factors or known cardiovascular disease. There is limited evidence of incidence and prospective course of anthracycline-induced CTRCD in young patients without common risk factors for CTRCD. Purpose To longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease. Methods 59 women with first-diagnosed breast cancer and planned anthracycline regime-based therapy were enrolled. Exclusion criteria were cardiovascular risk factors or known cardiovascular disease. We conducted a longitudinal assessment before, immediately after- and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping. Results Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3 % immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation (Figure 1). LVEF reduction was accompanied by a decrease in stroke volume and cardiac power index while enddiastolic volume index remained stable. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired. Conclusion Among breast cancer patients without pre-existing risk factors for CTRCD anthracyclines induce a decline of myocardial contractility in every single patient, which may lead to an increased risk of future cardiovascular diseases in these patients. Figure 1: Patients with diagnosed CTRCD directly after CT and after 12 months follow up stratified by underlying CTRCD criteria. Boldness of arrows proportionally represents the number of patients changing between the criteria. Some patients fulfilled more than one criterium for CTRCD.Graphical Abstract Figure 1

Absence of long-term structural and functional cardiac abnormalities on multimodality imaging in a multi-ethnic group of COVID-19 survivors from the early stage of the pandemic.

Many patients with coronavirus disease-2019 (COVID-19), particularly from the pandemic's early phase, have been reported to have evidence of cardiac injury such as cardiac symptoms, troponinaemia, or imaging or ECG abnormalities during their acute course. Cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) have been widely used to assess cardiac function and structure and characterize myocardial tissue during COVID-19 with report of numerous abnormalities. Overall, findings have varied, and long-term impact of COVID-19 on the heart needs further elucidation. We performed TTE and 3 T CMR in survivors of the initial stage of the pandemic without pre-existing cardiac disease and matched controls at long-term follow-up a median of 308 days after initial infection. Study population consisted of 40 COVID-19 survivors (50% female, 28% Black, and 48% Hispanic) and 12 controls of similar age, sex, and race-ethnicity distribution; 35% had been hospitalized with 28% intubated. We found no difference in echocardiographic characteristics including measures of left and right ventricular structure and systolic function, valvular abnormalities, or diastolic function. Using CMR, we also found no differences in measures of left and right ventricular structure and function and additionally found no significant differences in parameters of tissue structure including T1, T2, extracellular volume mapping, and late gadolinium enhancement. With analysis stratified by patient hospitalization status as an indicator of COVID-19 severity, no differences were uncovered. Multimodal imaging of a diverse cohort of COVID-19 survivors indicated no long-lasting damage or inflammation of the myocardium.

Radiotherapy-induced diffuse myocardial fibrosis in early-stage breast cancer patients – multimodality imaging study with six-year follow-up

BackgroundBreast radiotherapy (RT) induces diffuse myocardial changes, which may increase the incidence of heart failure with preserved ejection fraction. This study aimed to evaluate the early signs of diffuse fibrosis after RT and their evolution during a six-year follow-up.MethodsThirty patients with early-stage left-sided breast cancer were studied with echocardiography and electrocardiography (ECG) at baseline, after RT, and at three-year and six-year follow-up visits. Echocardiography analysis included an off-line analysis of integrated backscatter (IBS). ECG was analysed for fragmented QRS (fQRS). In addition, cardiac magnetic resonance (CMR) imaging was performed at the six-year control. The left ventricle 16-segment model was used in cardiac imaging, and respective local radiation doses were analysed.ResultsRegional myocardial reflectivity in inferoseptal segments increased by 2.02 (4.53) dB (p = 0.026) and the percentage of leads with fQRS increased from 9.2 to 16.4% (p = 0.002) during the follow-up. In CMR imaging, abnormal extracellular volume (ECV) and T1 mapping values were found with anteroseptal and apical localization in a median of 3.5 (1.00–5.75) and 3 (1.25–4.00) segments, respectively. A higher left ventricle radiation dose was associated with an increased likelihood of having changes simultaneously in CMR and echocardiography (OR 1.26, 95% Cl. 1.00–1.59, p = 0.047).ConclusionsAfter radiotherapy, progressive changes in markers of diffuse myocardial fibrosis were observed in a multimodal manner in ECG and echocardiography. Changes in echocardiography and abnormal values in CMR were localized in the septal and apical regions, and multiple changes were associated with higher radiation doses.

Tracking multi-organ treatment response in systemic AL amyloidosis with cardiac magnetic resonance derived extracellular volume mapping

Abstract Funding Acknowledgements Type of funding sources: None. Background Systemic light-chain (AL) amyloidosis commonly involves the liver, spleen and heart. Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping has demonstrated accuracy in measuring cardiac, hepatic and splenic amyloid infiltration. Purpose We sought to: (1) assess the association between baseline multi-organ ECVs and prognosis (2) assess the multi-organ response to treatment using ECV mapping, and (3) assess the association between multi-organ treatment response and prognosis. Methods We identified 351 patients with a confirmed diagnosis of systemic AL amyloidosis who underwent baseline serum amyloid P component (SAP) scintigraphy and CMR at diagnosis, of which 171 had follow-up imaging. We also recruited 20 healthy volunteers who underwent CMR with ECV mapping, without corresponding SAP scintigraphy, to allow calculation of the ECV normal ranges. Results At diagnosis, ECV mapping demonstrated that 304(86.7%) had cardiac involvement, 114(32.5%) significant hepatic involvement and 147(41.9%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial: HR=1.05,95CI%[1.03–1.07],P&amp;lt;0.001; liver: HR=1.03,95%CI[1.01–1.05],P&amp;lt;0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R=0.751,P&amp;lt;0.001; R=0.765,P&amp;lt;0.001, respectively). Serial multi-organ ECV measurements accurately tracked treatment response as validated against serial SAP scintigraphy (the current reference standard). Multi-organ ECV regression was observed as early as 6-months in patients with a good haematological response (liver=15%, spleen=15%, heart=5%). The remaining patients with a good haematological response had stable liver and spleen ECVs, but 20% had cardiac progression. By 12-months more patients with a good haematological response demonstrated cardiac regression (liver=30%, spleen=36%, heart=32%), and this trend was maintained at 24-months. Multi-variable analysis adjusting for haematological response, change in myocardial, liver and spleen ECV demonstrated that haematological response, change in myocardial ECV (HR=1.11, 95%CI[1.02–1.19], P=0.011) and liver ECV (HR=1.06, 95%CI[1.01–1.11], P=0.015) remained independent predictors of prognosis at 6-months. Conclusions Multi-organ ECV quantification accurately tracks treatment response, and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. A good haematological response alone is likely to induce visceral organ stabilisation/regression, but may not be sufficient to induce myocardial stabilisation/regression. Liver and myocardial ECV at diagnosis and changes in ECV at 6-months independently predict mortality. ECV mapping offers a comprehensive multi-organ assessment of treatment response and accurate prognostication.

Tracking treatment response in cardiac AL amyloidosis with native-T1 mapping

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac magnetic resonance (CMR) derived extracellular volume (ECV) mapping has demonstrated utility in determining the cardiac response to chemotherapy in systemic AL amyloidosis, but concomitant renal dysfunction is a common contraindication for the required gadolinium contrast. Objectives To assess the ability of native-T1 mapping to measure the cardiac response to treatment, and assess the association between changes in native-T1 and prognosis. Methods We studied 221 patients who underwent cardiac magnetic resonance (CMR) scans at diagnosis and a repeat scan following chemotherapy. Results At 6-months a reduced native-T1 of ≥50ms occurred in 8(4%) patients, all of whom had a good haematological response; by contrast an increased native-T1 of ≥50ms occurred in 42(23%) patients, most of whom had a poor haematological response (n=27,68%). At 12-months, a reduced native-T1 occurred in 24(15%) patients, all of whom had a good haematological response, and was associated with a reduction in median N-terminal pro-brain natriuretic peptide (NT-proBNP) (2638ng/L vs 432ng/L,P&amp;lt;0.001) and E/e’ (14.9±6.8 vs 12.0±5.2, P=0.007), improved longitudinal strain (−14.8±4.0 vs −16.7±4.0, P=0.004) and reduction in both T2 (52.3±2.9 vs 49.4±2.0, P&amp;lt;0.001) and ECV (0.47±0.07 vs 0.42±0.08, P&amp;lt;0.001); increased native-T1 occurred in 24(15%) patients, most of whom had a poor haematological response (n=17,71%) and was associated with an increased median NT-proBNP (1622ng/L vs 3150ng/L, P=0.007), reduced ejection fraction (65.8±11.4% vs 61.5±12.4%, P=0.009) and both increased T2 (52.5±2.7 vs 55.3±4.2, P&amp;lt;0.001) and ECV (0.48±0.09 vs 0.56±0.09, P&amp;lt;0.001). Change in native-T1 at 6-months predicted mortality even after adjusting for haematological response and NT-proBNP response (HR=2.41,95%CI[1.36–4.27],P=0.003). Conclusion Changes in myocardial native-T1 in response to treatment, are reflected in changes in the traditional markers of the cardiac response provide a powerful independent predictor of mortality. Change in native-T1 represents an important addition to the standard armamentarium of amyloid assessment, and provides an alternative measure of the cardiac treatment response, that not only limits exposure of patients to contrast but could also have implications on clinical workflow by reducing scan time.

Tracking Multiorgan Treatment Response in Systemic AL-Amyloidosis With Cardiac Magnetic Resonance Derived Extracellular Volume Mapping

BackgroundSystemic light chain amyloidosis is a multisystem disorder that commonly involves the heart, liver, and spleen. Cardiac magnetic resonance with extracellular volume (ECV) mapping provides a surrogate measure of the myocardial, liver, and spleen amyloid burden. ObjectivesThe purpose of this study was to assess multiorgan response to treatment using ECV mapping, and assess the association between multiorgan treatment response and prognosis. MethodsThe authors identified 351 patients who underwent baseline serum amyloid-P-component (SAP) scintigraphy and cardiac magnetic resonance at diagnosis, of which 171 had follow-up imaging. ResultsAt diagnosis, ECV mapping demonstrated that 304 (87%) had cardiac involvement, 114 (33%) significant hepatic involvement, and 147 (42%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial HR: 1.03 [95% CI: 1.01-1.06]; P = 0.009; liver HR: 1.03; [95% CI: 1.01-1.05]; P = 0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R = 0.751; P < 0.001; R = 0.765; P < 0.001, respectively). Serial measurements demonstrated ECV correctly identified changes in liver and spleen amyloid load derived from SAP scintigraphy in 85% and 82% of cases, respectively. At 6 months, more patients with a good hematologic response had liver (30%) and spleen (36%) ECV regression than myocardial regression (5%). By 12 months, more patients with a good response demonstrated myocardial regression (heart 32%, liver 30%, spleen 36%). Myocardial regression was associated with reduced median N-terminal pro-brain natriuretic peptide (P < 0.001), and liver regression with reduced median alkaline phosphatase (P = 0.001). Changes in myocardial and liver ECV, 6 months after initiating chemotherapy, independently predict mortality (myocardial HR: 1.11 [95% CI: 1.02-1.20]; P = 0.011; liver HR: 1.07 [95% CI: 1.01-1.13]; P = 0.014). ConclusionsMultiorgan ECV quantification accurately tracks treatment response and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. Baseline myocardial and liver ECV and changes at 6 months independently predict mortality, even after adjusting for traditional predictors of prognosis.

Cardioprotective effects of shock wave therapy: A cardiac magnetic resonance imaging study on acute ischemia-reperfusion injury.

Cardioprotection strategies remain a new frontier in treating acute myocardial infarction (AMI), aiming at further protect the myocardium from the ischemia-reperfusion damage. Therefore, we aimed at investigating the mechano-transduction effects induced by shock waves (SW) therapy at time of the ischemia reperfusion as a non-invasive cardioprotective innovative approach to trigger healing molecular mechanisms. We evaluated the SW therapy effects in an open-chest pig ischemia-reperfusion (IR) model, with quantitative cardiac Magnetic Resonance (MR) imaging performed along the experiments at multiple time points (baseline (B), during ischemia (I), at early reperfusion (ER) (∼15 min), and late reperfusion (LR) (3 h)). AMI was obtained by a left anterior artery temporary occlusion (50 min) in 18 pigs (32 ± 1.9 kg) randomized into SW therapy and control groups. In the SW therapy group, treatment was started at the end of the ischemia period and extended during early reperfusion (600 + 1,200 shots @0.09 J/mm2, f = 5 Hz). The MR protocol included at all time points LV global function assessment, regional strain quantification, native T1 and T2 parametric mapping. Then, after contrast injection (gadolinium), we obtained late gadolinium imaging and extra-cellular volume (ECV) mapping. Before animal sacrifice, Evans blue dye was administrated after re-occlusion for area-at-risk sizing. During ischemia, LVEF decreased in both groups (25 ± 4.8% in controls (p = 0.031), 31.6 ± 3.2% in SW (p = 0.02). After reperfusion, left ventricular ejection fraction (LVEF) remained significantly decreased in controls (39.9 ± 4% at LR vs. 60 ± 5% at baseline (p = 0.02). In the SW group, LVEF increased quickly ER (43.7 ± 11.4% vs. 52.4 ± 8.2%), and further improved at LR (49.4 ± 10.1) (ER vs. LR p = 0.05), close to baseline reference (LR vs. B p = 0.92). Furthermore, there was no significant difference in myocardial relaxation time (i.e. edema) after reperfusion in the intervention group compared to the control group: ΔT1 (MI vs. remote) was increased by 23.2±% for SW vs. +25.2% for the controls, while ΔT2 (MI vs. remote) increased by +24.9% for SW vs. +21.7% for the control group. In conclusion, we showed in an ischemia-reperfusion open-chest swine model that SW therapy, when applied near the relief of 50' LAD occlusion, led to a nearly immediate cardioprotective effect translating to a reduction in the acute ischemia-reperfusion lesion size and to a significant LV function improvement. These new and promising results related to the multi-targeted effects of SW therapy in IR injury need to be confirmed by further in-vivo studies in close chest models with longitudinal follow-up.