Serial Cardiac Magnetic Resonance Imaging Research Articles

Serial Cardiac Magnetic Resonance Imaging in Patients with Mitral Valve Prolapse-A Single-Center Retrospective Registry.

Background: Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac magnetic resonance imaging (CMR) has a key role in risk stratification of VA, including assessment of late gadolinium enhancement (LGE). Methods: Single-center retrospective analysis of patients with MVP or MAD who had >1 CMR and >1 24 h Holter registration available. Data are presented in detail, including evolution of VA and presence of LGE over time. Results: A total of twelve patients had repeated CMR and Holter registrations available, of which in four (33%) patients, it was conducted before and after minimal invasive mitral valve repair (MVR). After a median of 4.7 years, four out of eight (50%) patients without surgical intervention had new areas of LGE. New LGE was observed in the papillary muscles and the mid to basal inferolateral wall. In four patients, presenting with syncope or high-risk non-sustained ventricular tachycardia (VT), programmed ventricular stimulation was performed and in two (50%), sustained monomorphic VT was easily inducible. In two patients who underwent MVR, new LGE was observed in the basal inferolateral wall of which one presented with an increased burden of VA. Conclusions: In patients with MVP and MAD, repeat CMR may show new LGE in a small subset of patients, even shortly after MVR. A subgroup of patients who presented with an increase in VA burden showed new LGE upon repeat CMR. VA in patients with MVP and MAD are part of a heterogeneous spectrum that requires further investigation to establish risk stratification strategies.

Continuous Cardiac Magnetic Resonance Imaging after Coronary Revascularization for Left Ventricular Dysfunction

Objective: To determine the contribution of serial cardiac magnetic resonance imaging (MRI) following coronary revascularization (CR) to the clinical management of patients with left ventricular insufficiency. Methods: The study objects comprised the clinical data of 145 patients with CR undergoing CR surgery for left ventricular insufficiency in our hospital from January 2021 to January 2023. The patients were divided into the case (n = 35, left ventricular ejection fraction (LVEF) <50%) and control (n = 110, LVEF ≥50%) groups based on the LVEF recorded in the medical record system 6 months after surgery. Preoperative LVEF left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), cardiac index (CI), and other cardiac magnetic resonance detection parameters were compared. Logistic regression analysis was performed to analyze the prognostic factors of patients undergoing CR after CR surgery for left ventricular insufficiency. The receiver operating characteristic curve was drawn, the sensitivity, specificity, and area under curve (AUC) were calculated, and the best prediction threshold was determined. The prognostic value of cardiac MRI in CR surgery for left ventricular dysfunction was observed. Results: Cardiac MRI revealed that the case group had higher LVEDV, LVESV, LVEDVI, LVESVI, and CI than the control group. However, the LVEF index was lower than that in the control group (p < 0.05). Logistic regression analysis was conducted for indicators with differences, and the results indicate LVEF as a protective factor for the postoperative efficacy of the patients, with an odds ratio (OR) <1. LVEDV, LVESV, LVEDVI, LVESVI, and CI were all risk factors for the postoperative efficacy of the patients, with an OR >1. The AUC values of LVEF, LVEDV, LVESV, LVEDVI, LVESVI, and CI were 0.698, 0.674, 0.654, 0.700, 0.572, and 0.812, respectively. The optimal threshold values were 53.57%, 112.33 and 68.5 mL, and 205.51, 163.99, and 2.14 L/m2, and their corresponding sensitivities reached 0.618, 0.514, 0.654, 0.800, 0.371, and 0.829 for each index. The specificities were 0.800, 0.836, 0.771, 0.609, 0.836, and 0.645, which indicate that LVEF, LVEDV, LVESV, LVEDVI, LVESVI, and CI had a certain degree of predictive value for postoperative cardiac function recovery. Conclusion: LVEDV, LVESV, LVEDVI, LVESVI, CI, and LVEF are all factors affecting the clinical efficacy in patients undergoing CR after left ventricular insufficiency. In addition, cardiac MRI can effectively detect the above factors and effectively predict the postoperative efficacy among patients.

Impacto de prótesis valvular pulmonar en la función ventricular derecha y eventos cardiacos en pacientes con tetralogía de Fallot: análisis retrospectivo

Introduction and objectivesOur aim was to assess the impact of prosthetic pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) on changes in biventricular volumes and function and on adverse cardiac events. MethodsAdults with rTOF were identified from the SACHER-registry. Data from serial cardiac magnetic resonance imaging, echocardiography, exercise capacity and n-terminal pro b-type natriuretic peptide (NT-proBNP) were collected. The primary endpoint was right ventricular ejection fraction (RVEF) as measured by cardiac magnetic resonance. Secondary endpoints were biventricular volumes, left ventricular ejection fraction, exercise capacity and NT-proBNP levels, and time to adverse cardiac outcomes (atrial and ventricular arrhythmia, endocarditis). Associations between previous PVR and longitudinal changes in functional outcomes and time to adverse cardiac outcomes were analyzed using linear mixed-effects models and Cox proportional hazards models, respectively. ResultsA total of 308 patients (153 with and 155 without PVR) with 887 study visits were analyzed. Previous PVR was not significantly associated with changes in RVEF (CE, -1.33; 95%CI, -5.87 to 3.21; P=.566). Previous PVR was associated with lower right ventricular end-diastolic volume but had no significant effect on left ventricular ejection fraction, exercise capacity, or NT-proBNP-levels. Previous PVR was associated with an increased hazard of atrial arrhythmias (HR, 2.09; 95%CI, 1.17-3.72; P=.012) and infective endocarditis (HR, 12.72; 95%CI, 4.69-34.49; P<.0001) but not with an increased hazard of sustained ventricular arrhythmias (HR, 0.64; 95%CI, 0.18-2.27; P=.490). ConclusionsPrevious PVR was not significantly associated with changes in RVEF but was associated with an increased risk of atrial arrhythmias and infective endocarditis.

Impact of pulmonary valve replacement on ventricular function and cardiac events in patients with tetralogy of Fallot. A retrospective cohort study

Introduction and objectivesOur aim was to assess the impact of prosthetic pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) on changes in biventricular volumes and function and on adverse cardiac events. MethodsAdults with rTOF were identified from the SACHER-registry. Data from serial cardiac magnetic resonance imaging, echocardiography, exercise capacity and n-terminal pro b-type natriuretic peptide (NT-proBNP) were collected. The primary endpoint was right ventricular ejection fraction (RVEF) as measured by cardiac magnetic resonance. Secondary endpoints were biventricular volumes, left ventricular ejection fraction, exercise capacity and NT-proBNP levels, and time to adverse cardiac outcomes (atrial and ventricular arrhythmia, endocarditis). Associations between previous PVR and longitudinal changes in functional outcomes and time to adverse cardiac outcomes were analyzed using linear mixed-effects models and Cox proportional hazards models, respectively. ResultsA total of 308 patients (153 with and 155 without PVR) with 887 study visits were analyzed. Previous PVR was not significantly associated with changes in RVEF (CE, −1.33; 95%CI, −5.87 to 3.21; P=.566). Previous PVR was associated with lower right ventricular end-diastolic volume but had no significant effect on left ventricular ejection fraction, exercise capacity, or NT-proBNP-levels. Previous PVR was associated with an increased hazard of atrial arrhythmias (HR, 2.09; 95%CI, 1.17-3.72; P=.012) and infective endocarditis (HR, 12.72; 95%CI, 4.69-34.49; P<.0001) but not with an increased hazard of sustained ventricular arrhythmias (HR, 0.64; 95%CI, 0.18-2.27; P=.490). ConclusionsPrevious PVR was not significantly associated with changes in RVEF but was associated with an increased risk of atrial arrhythmias and infective endocarditis.

Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. NIH, ASTRO, AHA, Longer Life Foundation.

Association of Coronary Collaterals and Myocardial Salvage Measured by Serial Cardiac Magnetic Resonance Imaging after Acute Myocardial Infarction.

Coronary collateral flow in angiography has been linked with lower mortality rates in patients with coronary artery disease. However, the relevance of the underlying mechanism is sparse. Therefore, we tested the hypothesis that in patients with acute myocardial infarction (AMI), relevant coronary collateral flow is associated with more salvaged myocardium and lower risk of developing heart failure. Patients with first AMI who received a percutaneous coronary intervention within 24 h after symptom onset were classified visually by assigning a Cohen-Rentrop Score (CRS) ranging between 0 (no collaterals) and 3 (complete retrograde filling of the occluded vessel). All 36 patients included in the analysis underwent cardiac magnetic resonance examination within 3 to 5 days after myocardial infarction and after 12 weeks. Patients with relevant collateral flow (CRS 2-3) to the infarct-related artery had significantly smaller final infarct size compared to those without (7 ± 4% vs. 20 ± 12%, p < 0.001). In addition, both groups showed improvement in left ventricular ejection fraction early after AMI, whereas the recovery was greater in CRS 2-3 (+8 ± 5% vs. +3 ± 5%, p = 0.015). In patients with first AMI, relevant collateral flow to the infarct-related artery was associated with more salvaged myocardium at 12 weeks, translating into greater improvement of systolic left ventricular function. The protective effect of coronary collaterals and the variance of infarct location should be further investigated in larger studies.

Abstract 11536: Cardiac Magnetic Resonance Imaging Paralleled Recurrent Pericarditis Clinical Response to Rilonacept Treatment Over 18 Months: A RHAPSODY Subgroup Analysis

Introduction: Rilonacept treatment in RHAPSODY resolved active pericarditis recurrences, and long-term treatment led to sustained risk reduction. Prior analysis linked greater baseline Late Gadolinium Enhancement (LGE), with more rapid recurrence upon rilonacept suspension after 12 weeks of treatment. Serial cardiac magnetic resonance (CMR) imaging (T2-STIR, LGE) enabled longitudinal assessment for tracking clinical improvement, guiding decision-making, and predicting patient outcomes after treatment cessation. Methods: At the long-term extension (LTE) 18-month decision milestone (18MDM), investigators chose, based on clinical status, to continue rilonacept, suspend rilonacept/observe, or discontinue the LTE. An imaging core lab blinded to clinical data measured pericardial thickness and graded pericardial edema (T2-STIR) and LGE at baseline and 18MDM. Pericarditis recurrence was assessed clinically following rilonacept suspension. Results: Baseline and 18MDM CMRs were available for 13 patients. Reductions in pericardial thickness, T2-STIR, and LGE from baseline to 18MDM while on treatment are provided in Figure . CMRs were obtained in 7/8 patients suspending rilonacept at 18MDM: LGE was none/trace, and T2-STIR was negative; yet, 5/7 (71%) had pericarditis recurrence within 1-4 months of rilonacept suspension despite prophylactic colchicine (n=2). Conclusions: Continued clinical improvement during prolonged rilonacept treatment corresponded with improvement on CMR, including reduced pericardial thickness, resolution of pericardial edema on T2-STIR, and resolution of LGE. Negative/trace LGE at 18MDM while on treatment did not predict absence of pericarditis recurrence upon subsequent rilonacept suspension in this size-limited subgroup. Larger prospective studies examining CMR parameters in guiding RP treatment duration decisions and informing associated clinical outcomes are warranted.

Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and two CCTA scans during the two-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026-2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

Adaptation of closed-chest infarction porcine model to adult Pannon minipigs

The aim of the recent study was to collect data on the genotype characteristics of the Hungarian self-bred Pannon minipigs by adapting a standardized infarct model procedure. Closed chest AMI was induced by balloon occlusion for 90 min in the left anterior descendent coronary artery (LAD) in 24 adult intact female minipigs followed by reperfusion. To assess the left ventricular (LV) function, serial cardiac magnetic resonance imaging (cMRI) was performed prior to the experimental procedure, on day 3 post-AMI (72 ± 12 h), and at 1 month follow-up (Day 30 ± 2 days). Compared to baseline cMRI scans the end-diastolic volume (EDV) was increased on days 3 and 30 On day 3 the left ventricular ejection fraction (LVEF) decreased significantly but there was no statistical difference between the baseline and day 30 measurements. Cardiac output, stroke volume, and end-systolic volume significantly were increased compared to baseline on day 30 A high percentage (54%) of malignant arrhythmias occurred during the AMI procedure, with a 25% mortality rate. The compensatory capacity of the Pannon minipig heart is excellent therefore the use of different cardiac parameters and invasive measurements is advisable in chronic pharmacological experiments to complement cMRI data.

Novel Cardiokine GDF3 Predicts Adverse Fibrotic Remodeling After Myocardial Infarction.

Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery by promoting the development of noncontractile fibrotic areas. The mechanisms that lead to cardiac fibrosis are diverse and incompletely characterized. We explored whether the expansion of cardiac fibroblasts after MI can be regulated through a paracrine action of cardiac stromal cells. We performed a bioinformatic secretome analysis of cardiac stromal PW1+ cells isolated from normal and post-MI mouse hearts to identify novel secreted proteins. Functional assays were used to screen secreted proteins that promote fibroblast proliferation. The expressions of candidates were subsequently analyzed in mouse and human hearts and plasmas. The relationship between levels of circulating protein candidates and adverse post-MI cardiac remodeling was examined in a cohort of 80 patients with a first ST-segment-elevation MI and serial cardiac magnetic resonance imaging evaluations. Cardiac stromal PW1+ cells undergo a change in paracrine behavior after MI, and the conditioned media from these cells induced a significant increase in the proliferation of fibroblasts. We identified a total of 12 candidates as secreted proteins overexpressed by cardiac PW1+ cells after MI. Among these factors, GDF3 (growth differentiation factor 3), a member of the TGF-β (transforming growth factor-β) family, was markedly upregulated in the ischemic hearts. Conditioned media specifically enriched with GDF3 induced fibroblast proliferation at a high level by stimulation of activin-receptor-like kinases. In line with the secretory nature of this protein, we next found that GDF3 can be detected in mice and human plasma samples, with a significant increase in the days after MI. In humans, higher GDF3 circulating levels (measured in the plasma at day 4 after MI) were significantly associated with an increased risk of adverse remodeling 6 months after MI (adjusted odds ratio, 1.76 [1.03-3.00]; P=0.037), including lower left ventricular ejection fraction and a higher proportion of akinetic segments. Our findings define a mechanism for the profibrotic action of cardiac stromal cells through secreted cardiokines, such as GDF3, a candidate marker of adverse fibrotic remodeling after MI. URL: https://www. gov; Unique identifier: NCT01113268.

Features of metabolic syndrome and inflammation independently affect left ventricular function early after first myocardial infarction

BackgroundA high body mass index (BMI) is often associated with metabolic syndrome, which is accompanied by systemic low-grade chronic inflammation. Here, we analyzed whether BMI, other components of metabolic syndrome, and/or inflammatory markers correlate with left ventricular geometry, function, and infarct size as assessed by serial cardiac magnetic resonance imaging (MRI) after a first (clinically evident) ST-elevation MI (STEMI). MethodsWithin the Etiology, Titre-Course, and effect on Survival (ETiCS) study, cardiac MRI conducted 7–9 days and 12 months after MI enabled longitudinal characterization of patients with a first STEMI along with serial routine blood counts and multiplex cytokine measurements. ResultsOf 91 locally included STEMI patients, 47% were overweight (25 kg/m2 < BMI < 30 kg/m2) and 24% were obese (BMI ≥ 30 kg/m2). No patient died during 12 months of follow-up. Left ventricular ejection fraction (LVEF), measured 7–9 days after STEMI, was significantly lower in overweight (49.5 ± 7.1%) and obese (45.8 ± 12.0%) patients than in the normal weight group (56.2 ± 7.7%). Along with BMI (T = -3.8; p < 0.001), hemoglobin A1c (HbA1c; T = -3.1; p = 0.004) and peak C-reactive protein (T = -2.6; p = 0.013) emerged as independent predictors of worse LVEF 7–9 days post MI (R2 = 0.45). Only peak C-reactive protein (T = -4.4; p < 0.001), but not parameters of the metabolic syndrome, predicted worse LVEF 12 months after STEMI (R2 = 0.20). ConclusionBoth BMI and HbA1c correlated negatively with LVEF only early, but not late after STEMI. Peak CRP evolved as strongest predictor of cardiac function at all time points independent of the metabolic syndrome.

Administration of a human recombinant apyrase (AZD3366) limits myocardial tissue injury and improves cardiac function in a pig model of STEMI assessed by serial CMR

Abstract Background Mitigating myocardial tissue injury (MTI) remains an unmet clinical need in the reperfusion era. Stimulating adenosine synthesis through the breakdown of adenosine triphosphate (ATP) by apyrase (CD39), an endothelial ADPase, has emerged as a potential new avenue in the reduction of MTI. Purpose In this study we examined whether the intravenous administration of a recombinant soluble form of human apyrase (AZD3366) prior to reperfusion limits MTI and improves cardiac function in a pig model of STEMI as assessed by serial cardiac magnetic resonance (CMR) imaging. Methods Pigs (n=16) were subjected to STEMI induction (1.5h closed-chest complete LAD coronary balloon occlusion). Immediately prior to reperfusion, pigs were randomized to intravenously receive one single dose of 3 mg/kg AZD3366 (n=8) or vehicle (n=8). Serial-CMR imaging was performed at baseline, 3 days, and 42 days post-MI for the assessment of structural and functional readouts at rest and during dobutamine stress. Light transmittance aggregometry (LTA; challenged by 5, 10 and 20 μM ADP) and ear bleeding time were monitored pre-MI, post-MI and at day 3. Results AZD3366 significantly reduced MTI by limiting (around 60%) oedema formation (21.3±6.7 vs. 12.3±6.7 g LV) and infarct size (14.3±6.1 vs. 8.4±3.4 g LV) and preventing microvascular obstruction (2.3±0.9 vs. 0.5±0.5 g LV) at 3 days post-MI, compared to vehicle-administered STEMI pigs (p&amp;lt;0.05). At a functional level, LVEDV and LVESV showed less deterioration in AZD3366 treated animal as compared to vehicle 3 days post-MI (p&amp;lt;0.05) and less numerical decrease of LVEF. Furthermore, AZD3366-treated animals showed no deterioration in LVEF upon dobutamine stress in contrast to vehicle-infused animals, (p&amp;lt;0.05). AZD3366 treatment nearly abolished LTA at all tested ADP doses early post-STEMI, an effect that remained up to 3 days post-infusion but did not affect ear bleeding time at any of the tested time points. No additional effects were seen at 42 days. Conclusion Infusion of one single dose of the soluble recombinant apyrase AZD3366 prior to reperfusion exerts cardioprotection by reducing oedema formation, microvascular obstruction and necrosis and improving cardiac performance at rest and after dobutamine stress during the acute post-MI period. Administration of AZD3366 as an adjunctive therapy to standard of care for STEMI patients undergoing primary PCI may reduce myocardial tissue injury. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZeneca, Gothenburg, Sweden

TIMI flow and myocardial blushing after rescue PCI and cardiac magnetic resonance: Results from the Myocardial Salvage After Rescue Angioplasty: Evaluation by Magnetic Resonance (SAVE-ME) study

IntroductionThrombolysis is currently reserved for ST-elevation myocardial infarction (STEMI) patients who cannot access timely percutaneous coronary intervention (PCI). In case of failed thrombolysis, rescue PCI is a viable option. Substantial data concerning the outcomes in terms of infarct size and myocardial function after rescue PCI are lacking. MethodsForty patients treated with rescue PCI underwent serial contrast-enhanced cardiac magnetic resonance imaging (CMR) at 1 week, 3 months and 6 months from the index STEMI. Angiographic images were reviewed to assess Thrombolysis in Myocardial Infarction (TIMI) blood flow and TIMI Myocardial Blush Grade (TMBG) in the infarct related artery after PCI. ResultsPatients with lower TMBG at the end of procedure, but not patients with worse TIMI flow, had lower left ventricular ejection fraction (LVEF) and higher volume of late gadolinium enhancement (LGE) on baseline CMR (44 ± 13% vs 52 ± 9%, p = 0.026, and 41 ± 21 ml vs 26 ± 12, p = 0.030, respectively). Patients with lower TMBG remained with significantly lower LVEF at 6 months follow up (48 ± 16% vs 59 ± 14, p = 0.049). ConclusionTMBG after rescue PCI is associated with reduced LVEF and increased LGE burden. As TMBG is a known marker of microvascular damage after STEMI, novel strategies aimed at improving microvascular function in the setting of rescue PCI are needed to improve the outcomes in this patient population.

Right Ventricular Involvement of an Aggressive Malignant Peripheral Nerve Sheath Tumor

We present a case of a 58-year-old woman who had a painful right thigh mass for a few months. A transthoracic echocardiogram revealed no evidence of an intracardiac mass. She had a whole-body positron emission tomography/computed tomography scan two months later that revealed masses in her right lower extremity and a mass in her right ventricle that had not been initially reported. She had been initially diagnosed with an undifferentiated pleomorphic sarcoma, but this diagnosis was changed to a malignant peripheral nerve sheath tumor with repeat pathology. She was subsequently hospitalized. An echocardiogram showed a mass covering 80% of her right ventricle (RV). Serial cardiac magnetic resonance imaging revealed a 9.4 × 5.6 cm RV mass with vascular and avascular portions and inflow and outflow tract obstruction. Computed tomography showed no other metastases. Due to a delay in diagnosis and a decline in left ventricular ejection fraction, the patient could not undergo palliative chemotherapy or radiotherapy.

Monitoring the evolution of myocarditis following COVID-19 mRNA vaccination with serial cardiac magnetic resonance imaging.

Monitoring the evolution of myocarditis following COVID-19 mRNA vaccination with serial cardiac magnetic resonance imaging.

High Variability of Right Ventricular Volumes and Function in Adults with Severe Pulmonary Regurgitation Late After Tetralogy of Fallot Repair

Our aim was to assess changes of right ventricular end-diastolic volumes (RVEDVi) and right ventricular ejection fraction (RVEF) in asymptomatic adults with repaired tetralogy of Fallot, with native right ventricular outflow tract and severe pulmonary regurgitation by serial cardiac magnetic resonance imaging (CMR). The study included 23 asymptomatic adults who underwent ≥3 CMR studies (total of 88 CMR studies). We compared changes in RVEDVi and RVEF between first and last study (median follow-up: 8.8years, interquartile range: 6.3 to 13.1 years) and between all study pairs. Variability of measurements between study pairs (65 consecutive and 139 nonconsecutive CMR study pairs) were assessed using Bland-Altman analysis and intraclass correlation coefficients. On average, there were no significant changes of RVEDVi or RVEF over the study period (change in RVEDVi: +0.4 ± 17.8ml/m2, change in RVEF: -1.0 ± 5.5%). Assessment of variability of measurements between study pairs demonstrated no systematic change in RVEDVi and RVEF between study pairs with limits of agreement within the range of previously published studies (RVEDVi -29.1 to +27.2ml/m2; RVEF -11.5% to 10.2%). High intraclass correlation coefficients for RVEDVi (0.943, 95% CI 0.906 to 0.965, p <0.001) and RVEF (0.815, 95% CI 0.697 to 0.887, p <0.0001) indicate high reliability of reported measurements. In conclusion, in asymptomatic adults with repaired tetralogy of Fallot with native right ventricular outflow tracts and severe pulmonary regurgitation, CMR measurements of RV volumes and RVEF remain stable during follow-up with variability between CMR studies in individual patients, as expected for interobserver and interstudy variability. Measurements derived from a single CMR study or changes occurring between 2 CMR studies should be used with caution for clinical decision-making.

Abstract 13056: The Novel Cardiokine GDF3 Predicts Fibrotic Remodeling Post-Myocardial Infarction

Introduction: Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery. Hypothesis: To explore the regulation of fibroblasts proliferation through a paracrine action of cardiac stromal cells post-MI Methods: We carried out a bioinformatic secretome analysis of cardiac stromal PW1 + cells isolated from normal and post-MI mouse hearts to identify novel secreted proteins. Functional assays were used to screen secreted proteins that promote fibroblast proliferation. The expressions of secreted proteins candidates were subsequently analyzed in mouse and human hearts and plasmas. The relation between levels of circulating protein candidates and adverse post-MI cardiac remodeling was examined in a cohort of 80 patients with a first ST-elevation MI and serial cardiac magnetic resonance imaging (MRI) evaluations. Results: Cardiac stromal PW1 + cells undergo a change in paracrine behavior post-MI and secrete factors that promote fibroblast proliferation. Among these factors, growth differentiation factor 3 (GDF3), a member of the transforming growth factor-β family, was markedly upregulated in the ischemic hearts and induced fibroblast proliferation at high level. In humans, GDF3 was detected in the plasma at day 4 post-MI and GDF3 circulating levels were significantly associated with an increased risk of adverse remodeling 6-month post-MI (adjusted Odds Ratio (OR) = 1.76 [1.03 - 3.00], p = 0.037). Conclusions: Our findings define a mechanism for the pro-fibrotic action of cardiac stromal cells through secreted cardiokines, such as GDF3, a candidate marker of adverse fibrotic remodeling following MI.

Tafamidis treatment delays structural and functional changes of the left ventricle in patients with transthyretin amyloid cardiomyopathy.

Tafamidis improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, it is not yet known whether tafamidis affects cardiac amyloid deposition and structural changes in the myocardium. We aimed to determine disease-modifying effects on myocardial amyloid progression and to identify imaging parameters that could be applied for specific therapy monitoring. ATTR-CM patients underwent serial cardiac magnetic resonance (CMR) imaging using T1 mapping techniques to derive extracellular volume (ECV). Patients receiving tafamidis 61 mg (n = 35) or 20 mg (n = 15) once daily showed stable measurements at follow-up (FU) {61 mg: 9.0 [interquartile range (IQR) 7.0-11.0] months, 20 mg: 11.0 (IQR 8.0-18.0) months} in left ventricular (LV) ejection fraction (LVEF; 61 mg: 47.6% vs. 47.5%, P = 0.935; 20 mg: 52.4% vs. 52.1%, P = 0.930), LV mass index (LVMI; 61 mg: 110.2 vs. 106.2 g/m2, P = 0.304; 20 mg: 114.5 vs. 115.4 g/m2, P = 0.900), and ECV (61 mg: 47.5% vs. 47.7%, P = 0.861; 20 mg: 56.7% vs. 57.5%, P = 0.759), whereas treatment-naïve ATTR-CM patients (n = 19) had clear signs of disease progression at the end of the observation period [12.0 (IQR 10.0-21.0) months; LVEF: 53.3% vs. 45.7%, P = 0.031; LVMI: 98.9 vs. 106.9 g/m2, P = 0.027; ECV: 49.3% vs. 54.6%, P = 0.023]. Between-group comparison at FU revealed positive effects in tafamidis 61 mg-treated compared to treatment-naïve patients (LVEF: P = 0.035, LVMI: P = 0.036, ECV: P = 0.030), while those treated with 20 mg showed no difference in the above LV measurements when compared with treatment-naïve (P = 0.120, P = 0.287, P = 0.158). However, both treatment groups showed clinically beneficial effects compared to the natural course [61 mg, 6-min walk distance (6-MWD): P = 0.005, N-terminal prohormone of brain natriuretic peptide (NT-proBNP): P = 0.002; 20 mg, 6-MWD: P = 0.023, NT-proBNP: P = 0.003]. Tafamidis delays myocardial amyloid progression in ATTR-CM patients, resulting in structural, functional, and clinical benefits compared to the natural course. Serial CMR including measurement of ECV may be appropriate for disease-specific therapy monitoring.

Myocardial injury detected by T1 and T2 mapping on CMR predicts subsequent cancer therapy\u2013related cardiac dysfunction in patients with breast cancer treated by epirubicin-based chemotherapy or left-sided RT

ObjectivesCancer therapy-related cardiac dysfunction (CTRCD) is a relevant clinical problem and needs early prediction. This study aimed to analyze myocardial injury using serial laboratory and cardiac magnetic resonance imaging (CMR) parameters after epirubicin-based chemotherapy compared with left-sided radiotherapy and to study their value for early prediction of CTRCD.MethodsSixty-six consecutive women (53 ± 13 years) including n = 39 with epirubicin-based chemotherapy and n = 27 with left-sided radiotherapy were prospectively studied by 3 T CMR including left ventricular (LV) mass and volumes for ejection fraction (LVEF), as well as feature-tracking with global longitudinal strain (GLS) and T1/T2 mapping. CMR was performed at baseline, at therapy completion (follow-up 1, FU1), and after 13 ± 2 months (FU2). CTRCD was defined as LVEF decline of at least 10% to < 55% or a > 15% GLS change at FU2.ResultsT1 and T2 increased at FU1 after epirubicin-based chemotherapy, but not after left-sided radiotherapy. CTRCD occurred in 20% of patients after epirubicin-based chemotherapy and in 4% after left-sided radiotherapy. T1 at FU1 was the best single parameter to predict CTRCD with an area under the curve (AUC) of 0.712 (CI 0.587–0.816, p = 0.005) with excellent sensitivity (100%, 66–100%), but low specificity (44%, 31–58%). Combined use of increased T1 and LVEF ≤ 60% at FU1 improved AUC to 0.810 (0.695–0.896) resulting in good sensitivity (78%, 44–95%) and specificity (84%, 72–92%).ConclusionOnly epirubicin-based chemotherapy, but not left-sided radiotherapy, resulted in increased T1/T2 myocardial relaxation times as a marker of myocardial injury. Combined use of CMR parameters may allow an early prediction of subsequent CTCRD.Key Points• Myocardial T1 and T2 relaxation times increased at FU1 after epirubicin-based chemotherapy, but not after left-sided radiotherapy.• Cancer therapy–related cardiac dysfunction (CTRCD) occurred in 20% of patients after epirubicin-based chemotherapy and in 4% after left-sided radiotherapy.• Combined use of increased T1 and reduced LVEF had an AUC of 0.810 (0.695–0.896) to predict CTRCD with good sensitivity (78%, 44–95%) and specificity (84%, 72–92%).

Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5–6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate. The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2, and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5–6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.