Cancer therapy related cardiac dysfunction as a result of Panitumumab.

Panitumumab is a human immunoglobulin monoclonal antibody designed to target the epidermal growth factor receptor (EGFR) which is used in the treatment of metastatic colorectal cancer alone or in combination with chemotherapy. In this report, we present a case of new onset heart failure with reduced ejection fraction in a patient following panitumumab therapy. A 73-year-old gentleman with metastatic rectal adenocarcinoma presented to his local hospital with increased shortness of breath, two months after his first and only dose of panitumumab. A transthoracic echocardiogram demonstrated dilated left ventricle with global hypokinesis and an estimated left ventricular ejection fraction of 25%. Our patient underwent a comprehensive diagnostic assessment at his presentation, including ECG, transthoracic echocardiogram, cardiac magnetic resonance, computed tomography coronary angiography (CTCA), invasive coronary angiogram and 18F-FDG PET-CT. These investigations revealed no evidence of ischemic events or inflammatory processes that could account for the severe left ventricular dysfunction. To our knowledge, this is the first reported case of heart failure with reduced ejection fraction linked to panitumumab with subsequent deep phenotyping. The current guidelines do not recommend specific cardiovascular monitoring protocols for patients receiving anti-EGFR monoclonal antibodies. Until more data are available, it would be prudent to implement the same cardiovascular surveillance measures outlined for individuals receiving osimertinib, which is an EGFR tyrosine kinase inhibitor.

Late cardiotoxicity related to HER2-targeted cancer therapy.

Long-term anti-HER2 therapy in metastatic HER2 + cancers is increasing, but data about the incidence and risk factors for developing late Cancer therapy-related cardiac dysfunction (CTRCD) are missing. We conducted a single-centre, retrospective analysis of a cohort of late anti-HER2 related cardiac dysfunction referred to our Cardio-Oncology service. We include seventeen patients with metastatic disease who developed CTRCD after at least five years of continuous anti-HER2 therapy. Events occurred after a median time of 6.5 years (IQR 5.3-9.0) on anti-HER2 therapy. The lowest (median) LVEF and GLS were 49% (IQR 45-55) and - 15.4% (IQR - 14.9 - -16.3) respectively. All our patients continued or restarted, after a brief interruption, their anti-HER2 therapy. Most (16/17) were started on heart failure medical therapy and normalized their left ventricular ejection fraction at a follow-up. Our study has demonstrated that CTRCD can occur after many years of stability on anti-HER2 therapy and reinforces the importance of continuing cardiovascular surveillance in this population.

Echocardiography versus Cardiac MRI for Measurement of Left Ventricular Ejection Fraction in Individuals with Cancer and Suspected Cardiotoxicity.

Purpose To compare left ventricular ejection fraction (LVEF) measured with echocardiography and cardiac MRI in individuals with cancer and suspected cardiotoxicity and assess the potential effect on downstream clinical decision-making. Materials and Methods In this prospective, single-center observational cohort study, participants underwent same-day two-dimensional (2D) echocardiography and cardiac MRI between 2011 and 2021. Participants with suboptimal image quality were excluded. A subset of 74 participants also underwent three-dimensional (3D) echocardiography. The agreement of LVEF derived from each modality was assessed using Bland-Altman analysis and at relevant thresholds for cardiotoxicity. Results A total of 745 participants (mean age, 60 years ± 5 [SD]; 460 [61.7%] female participants) underwent same-day echocardiography and cardiac MRI. According to Bland-Altman analysis, the mean bias was -3.7% ± 7.6 (95% limits of agreement [LOA]: -18.5% to 11.1%) for 2D echocardiography versus cardiac MRI. In 74 participants who underwent cardiac MRI, 3D echocardiography, and 2D echocardiography, the mean LVEFs were 60.0% ± 10.4, 58.4% ± 9.4, and 57.2% ± 8.9, respectively (P < .001). At the 50% LVEF threshold for detection of cardiotoxicity, there was disagreement for 9.3% of participants with 2D echocardiography and cardiac MRI. Agreement was better with 3D echocardiography and cardiac MRI (mean bias, -1.6% ± 6.3 [95% LOA: -13.9% to 10.7%]) compared with 2D echocardiography and cardiac MRI (mean bias, -2.8% ± 6.3 [95% LOA: -15.2% to 9.6%]; P = .016). Conclusion Two-dimensional echocardiography had variations of ±15% for LVEF measurement compared with cardiac MRI in participants with cancer and led to misclassification of approximately 10% of participants for cardiotoxicity detection. Three-dimensional echocardiography had better agreement with cardiac MRI and should be used as first-line imaging. Keywords: Echocardiography, MR Functional Imaging, Cardiac Supplemental material is available for this article. © RSNA, 2024.

Viability and Outcomes With Revascularization or Medical Therapy in Ischemic Ventricular Dysfunction: A Prespecified Secondary Analysis of the REVIVED-BCIS2 Trial.

Importance: In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear. Objective: To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function. Design, Setting, and Participants: Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years (IQR, 2.3-5.0 years). A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023. Intervention: Percutaneous coronary intervention in addition to optimal medical therapy. Main Outcomes and Measures: Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months. Results: The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome (hazard ratio per 10% increase, 0.98; 95% CI, 0.93-1.04) or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome (hazard ratio, 1.07; 95% CI, 1.00-1.15), all-cause death, cardiovascular death, and improvement in left ventricular function. Conclusions and Relevance: This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function. Trial Registration: ClinicalTrials.gov Identifier: NCT01920048.

Clinical Utility and Prognostic Value of Coronary Computed Tomography Angiography in Patients With Cancer.

There is growing interest in the role of coronary computed tomography angiography (CTA) in cardio-oncology. However, there is a paucity of real-world experience and outcome data for patients with cancer. This study sought to determine the clinical utility and prognostic value of coronary CTA in patients with cancer. In this prospective, single-center study, we recruited patients with cancer who underwent coronary CTA. Coronary artery disease (CAD) extent was classified as normal, nonobstructive (1% to 49% stenosis), and potentially obstructive (≥50% stenosis). Patients were followed up for a median of 9 months (interquartile range 3 to 30 months) for cancer-related deaths and major adverse cardiovascular events (MACEs) defined as nonfatal myocardial infarction, urgent unplanned revascularization, or cardiovascular death. The mean age of patients (n = 113) was 61 ± 12 years, and 68 were female (60%). The most common underlying cancers were breast (29%) and lymphoma (13%). A total of 25 patients had potentially obstructive CAD, most commonly of the left anterior descending artery. After coronary CTA, 88% statin-naive patients with potentially obstructive CAD were initiated on statin therapy. A total of 28/32 patients who were taking fluoropyrimidine chemotherapy (5-fluorouracil or capecitabine) continued therapy, of whom none had MACEs. Overall, there were no episodes of MACEs in this cohort and 11% had cancer-related deaths. Coronary CTA has an important role in the clinical decision-making in patients with cancer to detect CAD, initiate primary preventative therapy, and guide coronary revascularization. No MACEs occurred. Using this coronary CTA-guided approach, preventative therapy was initiated, and most patients continued prognostically important cancer therapy.

Intracardiac shunt assessment using CT coronary angiography.

BACKGROUND: Detection of intracardiac shunts using CT Coronary Angiography (CTCA) is currently based on anatomical demonstration of defects. We assessed a novel technique using a standard CTCA test bolus in detecting shunts independent of anatomical assessment and to provide an estimate of Qp/Qs. METHODS: We retrospectively reviewed 51 CTCAs: twenty-one from patients with known simple left to right intracardiac shunts with contemporaneous functional assessment (using CMR) within 6 months, 20 controls with structurally normal hearts, and 10 patients with shunt repairs. From the dynamic acquisition of a test bolus, we measured mean Hounsfield Units (HU) in various anatomical structures. We created time/density curves from the test bolus data, and calculated disappearance time (DT) from the ascending aorta (deriving a Qp/Qs), peak ascending aortic HU, and mean coefficient of variation of the arterial curves, and compared these with the Qp/Qs from the respective CMR. RESULTS: Patients with intracardiac shunts had significantly higher test bolus derived Qp/Qs compared with both the controls, and the repaired shunt comparator group. There was a very strong agreement between the test bolus derived Qp/Qs, and Qp/Qs as measured by CMR (Intraclass correlation 0.89). Mean bias was 0.032 â€‹± â€‹0.341 (95% limits of agreement -0.64 to 0.70). Interobserver, and intraobserver agreement of the disappearance time was excellent (0.99, 0.99 (reader 1) and 1.00 (reader 2) respectively). CONCLUSION: In this proof-of-concept study, we demonstrate a novel technique to detect, and to estimate severity of left to right intracardiac shunts on routine Cardiac CT.

[99mTc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression.

BACKGROUND: Myocardial programmed death-ligand 1 (PD-L1) expression is implicated in immune checkpoint inhibitor (ICI)-associated myocarditis. Measurement of myocardial PD-L1 expression may have potential use as a mechanistic and predictive biomarker. The aim of this study was to determine non-invasive assessment of myocardial PD-L1 expression using [99mTc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT. METHODS: Thoracic [99mTc]NM-01 SPECT/CT was performed in lung cancer patients (n = 10) at baseline and 9-weeks following anti-programmed cell death protein 1 (PD-1) therapy. Baseline and 9-week left ventricular and right ventricular to blood pool ratios (LVmax:BP) and (RVmax:BP) were measured. LVmax was compared to background skeletal muscle (musclemax). Intra-rater reliability was determined by intraclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Mean LVmax:BP values were 2.76 ± 0.67 at baseline vs 2.55 ± 0.77 at 9 weeks (p = 0.42). Mean RVmax:BP was 1.82 ± 0.32 at baseline vs 1.76 ± 0.45 at 9 weeks (p = 0.67). Myocardial PD-L1 expression was at least threefold greater than skeletal muscle at baseline for the LV (LVmax to musclemax 3.71 ± 0.77 vs 0.98 ± 0.20 (p < 0.001)) and at least twofold for the RV (LVmax to musclemax 2.49 ± 0.63 vs 0.98 ± 0.20 (p < 0.001)). There was excellent intra-rater reliability for LVmax:BP with ICC 0.99 (95% confidence interval 0.94-0.99, p < 0.001), mean bias -0.05 ± 0.14 (95% limits of agreement -0.32 to 0.21). There were no major adverse cardiovascular events or myocarditis during follow-up. CONCLUSION: This study is the first to report PD-L1 expression of the heart that can be quantified non-invasively without invasive myocardial biopsy, with high reliability and specificity. This technique can be applied to investigate myocardial PD-L1 expression in ICI-associated myocarditis and cardiomyopathies. Clinical trial registration PD-L1 Expression in Cancer (PECan) study (NCT04436406). https://clinicaltrials.gov/ct2/show/NCT04436406 June 18th, 2020.

Automated segmentation of long and short axis DENSE cardiovascular magnetic resonance for myocardial strain analysis using spatio-temporal convolutional neural networks.

BACKGROUND: Cine Displacement Encoding with Stimulated Echoes (DENSE) facilitates the quantification of myocardial deformation, by encoding tissue displacements in the cardiovascular magnetic resonance (CMR) image phase, from which myocardial strain can be estimated with high accuracy and reproducibility. Current methods for analyzing DENSE images still heavily rely on user input, making this process time-consuming and subject to inter-observer variability. The present study sought to develop a spatio-temporal deep learning model for segmentation of the left-ventricular (LV) myocardium, as spatial networks often fail due to contrast-related properties of DENSE images. METHODS: 2D + time nnU-Net-based models have been trained to segment the LV myocardium from DENSE magnitude data in short- and long-axis images. A dataset of 360 short-axis and 124 long-axis slices was used to train the networks, from a combination of healthy subjects and patients with various conditions (hypertrophic and dilated cardiomyopathy, myocardial infarction, myocarditis). Segmentation performance was evaluated using ground-truth manual labels, and a strain analysis using conventional methods was performed to assess strain agreement with manual segmentation. Additional validation was performed using an externally acquired dataset to compare the inter- and intra-scanner reproducibility with respect to conventional methods. RESULTS: Spatio-temporal models gave consistent segmentation performance throughout the cine sequence, while 2D architectures often failed to segment end-diastolic frames due to the limited blood-to-myocardium contrast. Our models achieved a DICE score of 0.83 ± 0.05 and a Hausdorff distance of 4.0 ± 1.1 mm for short-axis segmentation, and 0.82 ± 0.03 and 7.9 ± 3.9 mm respectively for long-axis segmentations. Strain measurements obtained from automatically estimated myocardial contours showed good to excellent agreement with manual pipelines, and remained within the limits of inter-user variability estimated in previous studies. CONCLUSION: Spatio-temporal deep learning shows increased robustness for the segmentation of cine DENSE images. It provides excellent agreement with manual segmentation for strain extraction. Deep learning will facilitate the analysis of DENSE data, bringing it one step closer to clinical routine.

Simultaneous multi-slice steady-state free precession myocardial perfusion with iterative reconstruction and integrated motion compensation.

PURPOSE: Simultaneous multi-slice (SMS) balanced steady-state free precession (bSSFP) acquisition and iterative reconstruction can provide high spatial resolution and coverage for cardiac magnetic resonance (CMR) perfusion. However, respiratory motion remains a challenge for iterative reconstruction techniques employing temporal regularisation. The aim of this study is to evaluate an iterative reconstruction with integrated motion compensation for SMS-bSSFP first-pass myocardial stress perfusion in the presence of respiratory motion. METHODS: Thirty-one patients with suspected coronary artery disease were prospectively recruited and imaged at 1.5 T. A SMS-bSSFP prototype myocardial perfusion sequence was acquired at stress in all patients. All datasets were reconstructed using an iterative reconstruction with temporal regularisation, once with and once without motion compensation (MC and NMC, respectively). Three readers scored each dataset in terms of: image quality (1:poor; 4:excellent), motion/blurring (1:severe motion/blurring; 3:no motion/blurring), and diagnostic confidence (1:poor confidence; 3:high confidence). Quantitative assessment of sharpness was performed. The number of uncorrupted first-pass dynamics was measured on the NMC datasets to classify patients into 'suboptimal breath-hold (BH)' and 'good BH' groups. RESULTS: Compared across all cases, MC performed better than NMC in terms of image quality (3.5 ± 0.5 vs. 3.0 ± 0.8, P = 0.002), motion/blurring (2.9 ± 0.1 vs. 2.2 ± 0.8, P < 0.001), diagnostic confidence (2.9 ± 0.1 vs. 2.3 ± 0.7, P < 0.001) and sharpness index (0.34 ± 0.05 vs. 0.31 ± 0.06, P < 0.001). Fourteen patients with a suboptimal BH were identified. For the suboptimal BH group, MC performed better than NMC in terms of image quality (3.8 ± 0.4 vs. 2.6 ± 0.8, P < 0.001), motion/blurring (3.0 ± 0.1 vs. 1.6 ± 0.7, P < 0.001), diagnostic confidence (3.0 ± 0.1 vs. 1.9 ± 0.7, P < 0.001) and sharpness index (0.34 ± 0.05 vs. 0.30 ± 0.06, P = 0.004). For the good BH group, sharpness index was higher for MC than NMC (0.34 ± 0.06 vs 0.31 ± 0.07, P = 0.03), while there were no significant differences observed for the other three metrics assessed (P > 0.11). There were no significant differences between suboptimal BH MC and good BH MC for any of the reported metrics (P > 0.06). CONCLUSIONS: Integrated motion compensation significantly reduces motion/blurring and improves image quality, diagnostic confidence and sharpness index of SMS-bSSFP perfusion with iterative reconstruction in the presence of motion.

High-resolution non-contrast free-breathing coronary cardiovascular magnetic resonance angiography for detection of coronary artery disease: validation against invasive coronary angiography.

BACKGROUND: Coronary artery disease (CAD) is the single most common cause of death worldwide. Recent technological developments with coronary cardiovascular magnetic resonance angiography (CCMRA) allow high-resolution free-breathing imaging of the coronary arteries at submillimeter resolution without contrast in a predictable scan time of ~ 10 min. The objective of this study was to determine the diagnostic accuracy of high-resolution CCMRA for CAD detection against the gold standard of invasive coronary angiography (ICA). METHODS: Forty-five patients (15 female, 62 ± 10 years) with suspected CAD underwent sub-millimeter-resolution (0.6 mm3) non-contrast CCMRA at 1.5T in this prospective clinical study from 2019-2020. Prior to CCMR, patients were given an intravenous beta blockers to optimize heart rate control and sublingual glyceryl trinitrate to promote coronary vasodilation. Obstructive CAD was defined by lesions with ≥ 50% stenosis by quantitative coronary angiography on ICA. RESULTS: The mean duration of image acquisition was 10.4 ± 2.1 min. On a per patient analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 95% (75-100), 54% (36-71), 60% (42-75) and 93% (70-100), respectively. On a per vessel analysis the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 80% (63-91), 83% (77-88), 49% (36-63) and 95% (90-98), respectively. CONCLUSION: As an important step towards clinical translation, we demonstrated a good diagnostic accuracy for CAD detection using high-resolution CCMRA, with high sensitivity and negative predictive value. The positive predictive value is moderate, and combination with CMR stress perfusion may improve the diagnostic accuracy. Future multicenter evaluation is now required.

Cost-effectiveness in diagnosis of stable angina patients: a decision-analytical modelling approach.

OBJECTIVE: Given recent data on published diagnostic accuracies, this study sought to determine the most cost-effective diagnostic strategy for detection of significant coronary artery disease (CAD) in stable angina patients using invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the reference standard. METHODS: A probabilistic decision-analytical model was developed which modelled a cohort of patients with stable angina. We investigated 17 diagnostic strategies between standalone and combination of different imaging tests to establish a correct diagnosis of CAD, using no testing as the baseline reference. These tests included CT coronary angiography (CTCA), stress echocardiography, CT-based FFR, single-photon emission computed tomography (SPECT), cardiovascular magnetic resonance (CMR), positron emission tomography, ICA, and ICA with FFR. Incremental cost-effectiveness ratios were calculated as the additional cost per correct diagnosis. RESULTS: SPECT followed by CTCA and ICA-FFR is the most cost-effective strategy between a cost-effectiveness threshold (CET) value of £1000-£3000 per correct diagnosis. CMR followed by CTCA and ICA-FFR is cost-effective within a CET range of £3000-£17 000 per correct diagnosis. CMR and ICA-FFR is cost-effective within a CET range of £17 000-£24 000. ICA-FFR as first line is the most-cost effective if the CET value exceeds the £24 000 per correct diagnosis. Sensitivity analysis showed that direct ICA-FFR may be cost-effective in patients with a high pre-test probability of CAD. CONCLUSION: First-line testing with functional imaging is cost-effective at low to intermediate value of correct diagnosis in patients with low to intermediate risk of CAD. ICA is not cost effective although ICA-FFR may be at higher CET.

Simultaneous multislice steady-state free precession myocardial perfusion with full left ventricular coverage and high resolution at 1.5 T.

PURPOSE: To implement and evaluate a simultaneous multi-slice balanced SSFP (SMS-bSSFP) perfusion sequence and compressed sensing reconstruction for cardiac MR perfusion imaging with full left ventricular (LV) coverage (nine slices/heartbeat) and high spatial resolution (1.4 × 1.4 mm2 ) at 1.5T. METHODS: A preliminary study was performed to evaluate the performance of blipped controlled aliasing in parallel imaging (CAIPI) and RF-CAIPI with gradient-controlled local Larmor adjustment (GC-LOLA) in the presence of fat. A nine-slice SMS-bSSFP sequence using RF-CAIPI with GC-LOLA with high spatial resolution (1.4 × 1.4 mm2 ) and a conventional three-slice sequence with conventional spatial resolution (1.9 × 1.9 mm2 ) were then acquired in 10 patients under rest conditions. Qualitative assessment was performed to assess image quality and perceived signal-to-noise ratio (SNR) on a 4-point scale (0: poor image quality/low SNR; 3: excellent image quality/high SNR), and the number of myocardial segments with diagnostic image quality was recorded. Quantitative measurements of myocardial sharpness and upslope index were performed. RESULTS: Fat signal leakage was significantly higher for blipped CAIPI than for RF-CAIPI with GC-LOLA (7.9% vs. 1.2%, p = 0.010). All 10 SMS-bSSFP perfusion datasets resulted in 16/16 diagnostic myocardial segments. There were no significant differences between the SMS and conventional acquisitions in terms of image quality (2.6 ± 0.6 vs. 2.7 ± 0.2, p = 0.8) or perceived SNR (2.8 ± 0.3 vs. 2.7 ± 0.3, p = 0.3). Inter-reader variability was good for both image quality (ICC = 0.84) and perceived SNR (ICC = 0.70). Myocardial sharpness was improved using the SMS sequence compared to the conventional sequence (0.37 ± 0.08 vs 0.32 ± 0.05, p < 0.001). There was no significant difference between measurements of upslope index for the SMS and conventional sequences (0.11 ± 0.04 vs. 0.11 ± 0.03, p = 0.84). CONCLUSION: SMS-bSSFP with multiband factor 3 and compressed sensing reconstruction enables cardiac MR perfusion imaging with three-fold increased spatial coverage and improved myocardial sharpness compared to a conventional sequence, without compromising perceived SNR, image quality, upslope index or number of diagnostic segments.

Impact of Temporal Resolution and Methods for Correction on Cardiac Magnetic Resonance Perfusion Quantification.

BACKGROUND: Acquisition of magnetic resonance first-pass perfusion images is synchronized to the patient's heart rate (HR) and governs the temporal resolution. This is inherently linked to the process of myocardial blood flow (MBF) quantification and impacts MBF accuracy but to an unclear extent. PURPOSE: To assess the impact of temporal resolution on quantitative perfusion and compare approaches for accounting for its variability. STUDY TYPE: Prospective phantom and retrospective clinical study. POPULATION AND PHANTOM: Simulations, a cardiac perfusion phantom, and 30 patients with (16, 53%) or without (14, 47%) coronary artery disease. FIELD STRENGTH/SEQUENCE: 3.0 T/2D saturation recovery spoiled gradient echo sequence. ASSESSMENT: Dynamic perfusion data were simulated for a range of reference MBF (1 mL/g/min-5 mL/g/min) and HR (30 bpm-150 bpm). Perfusion imaging was performed in patients and a phantom for different temporal resolutions. MBF and myocardial perfusion reserve (MPR) were quantified without correction for temporal resolution or following correction by either MBF scaling based on the sampling interval or data interpolation prior to quantification. Simulated data were quantified using Fermi deconvolution, truncated singular value decomposition, and one-compartment modeling, whereas phantom and clinical data were quantified using Fermi deconvolution alone. STATISTICAL TESTS: Shapiro-Wilk tests for normality, percentage error (PE) for measuring MBF accuracy in simulations, and one-way repeated measures analysis of variance with Bonferroni correction to compare clinical MBF and MPR. Statistical significance set at P < 0.05. RESULTS: For Fermi deconvolution and an example simulated 1 mL/g/min, the MBF PE without correction for temporal resolution was between 55.4% and -62.7% across 30-150 bpm. PE was between -22.2% and -6.8% following MBF scaling and between -14.2% and -14.2% following data interpolation across the same HR. An interpolated HR of 240 bpm reduced PE to ≤10%. Clinical rest and stress MBF and MPR were significantly different between analyses. DATA CONCLUSION: Accurate perfusion quantification needs to account for the variability of temporal resolution, with data interpolation prior to quantification reducing MBF variability across different resolutions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Dark-blood late gadolinium enhancement CMR improves detection of papillary muscle fibrosis in patients with mitral valve prolapse.

PURPOSE: Papillary muscle fibrosis may act as an arrhythmogenic substrate in patients with mitral valve prolapse (MVP). Previous studies used conventional bright-blood late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) imaging to assess papillary muscle fibrosis, although this technique suffers from poor scar-to-blood contrast which may limit its sensitivity, in contrast to dark-blood LGE. This study sought to compare bright-blood and dark-blood LGE for the detection of papillary muscle fibrosis in patients with MVP. METHOD: 60 patients with known isolated MVP referred for CMR were prospectively recruited. A routine CMR protocol was used to obtain cine imaging, dark-blood LGE and bright-blood LGE in three long-axis views and a stack of short-axis views. Flow mapping of the proximal aorta was performed to calculate mitral regurgitant volume. Images were analysed for cardiac volumes, ejection fraction, mitral regurgitation severity, MVP characteristics (mitral annular disjunction, prolapse volume) and presence of LGE at the papillary muscles and myocardium. RESULTS: Dark-blood LGE detected significantly more subjects with LGE at the papillary muscles than bright-blood LGE (35% vs 15%, p = 0.002). There was no difference between LGE techniques regarding myocardial (non-papillary muscle) fibrosis (present in 25% each). No statistical differences were observed between patients with or without LGE at the papillary muscles regarding demographics, clinical data (including ventricular arrhythmia) and MVP characteristics. Furthermore, no association was found between LGE at the papillary muscles and at the myocardium. CONCLUSIONS: Compared to bright-blood LGE, dark-blood LGE CMR improves the detection of LGE at the papillary muscles in patients with MVP.

Quantification of balanced SSFP myocardial perfusion imaging at 1.5 T: Impact of the reference image.

PURPOSE: To investigate the use of a high flip-angle (HFA) balanced SSFP (bSSFP) reference image (in comparison to conventional proton density [PD]-weighted reference images) for conversion of bSSFP myocardial perfusion images into dynamic T1 maps for improved myocardial blood flow (MBF) quantification at 1.5 T. METHODS: The HFA-bSSFP (flip angle [FA] = 50°), PD gradient-echo (PD-GRE; FA = 5°), and PD-bSSFP (FA = 8°) reference images were acquired before a dual-sequence bSSFP perfusion acquisition. Simulations were used to study accuracy and precision of T1 and MBF quantification using the three techniques. The accuracy and precision of T1 , and the precision and intersegment variability of MBF were compared among the three techniques in 8 patients under rest conditions. RESULTS: In simulations, HFA-bSSFP demonstrated improved T1 /MBF precision (higher T1 /MBF SD of 30%-80%/50%-100% and 30%-90%/60%-115% for PD-GRE and PD-bSSFP, respectively). Proton density-GRE and PD-bSSFP were more sensitive to effective FA than HFA-bSSFP (maximum T1 /MBF errors of 13%/43%, 20%/43%, and 1%/3%, respectively). Sensitivity of all techniques (defined as T1 /MBF errors) to native T1 , native T2 , and effective saturation efficiency were negligible (<1%/<1%), moderate (<14%/<19%), and high (<63%/<94%), respectively. In vivo, no difference in T1 accuracy was observed among HFA-bSSFP, PD-GRE, and PD-bSSFP (-9 ± 44 ms vs -28 ± 55 ms vs -22 ± 71 ms, respectively; p > .08). The HFA-bSSFP led to improved T1 /MBF precision (T1 /MBF SD: 41 ± 19 ms/0.24 ± 0.08 mL/g/min vs PD-GRE: 48 ± 20 ms/0.29 ± 0.09 mL/g/min and PD-bSSFP: 59 ± 23 ms/0.33 ± 0.11 mL/g/min; p ≤ .02) and lower MBF intersegment variability (0.14 ± 0.09 mL/g/min vs PD-GRE: 0.21 ± 0.09 mL/g/min and PD-bSSFP: 0.20 ± 0.10 mL/g/min; p ≤ .046). CONCLUSION: We have demonstrated the feasibility of using a HFA-bSSFP reference image for MBF quantification of bSSFP perfusion imaging at 1.5 T. Results from simulations demonstrate that the HFA-bSSFP reference image results in improved precision and reduced sensitivity to effective FA compared with conventional techniques using a PD reference image. Preliminary in vivo data acquired at rest also demonstrate improved precision and intersegment variability using the HFA-bSSFP technique compared with PD techniques; however, a clinical study in patients with coronary artery disease under stress conditions is required to determine the clinical significance of this finding.

2D high resolution vs. 3D whole heart myocardial perfusion cardiovascular magnetic resonance.

AIMS: Developments in myocardial perfusion cardiovascular magnetic resonance (CMR) allow improvements in spatial resolution and/or myocardial coverage. Whole heart coverage may provide the most accurate assessment of myocardial ischaemic burden, while high spatial resolution is expected to improve detection of subendocardial ischaemia. The objective of this study was to compare myocardial ischaemic burden as depicted by 2D high resolution and 3D whole heart stress myocardial perfusion in patients with coronary artery disease. METHODS AND RESULTS: Thirty-eight patients [age 61 ± 8 (21% female)] underwent 2D high resolution (spatial resolution 1.2 mm2) and 3D whole heart (in-plane spatial resolution 2.3 mm2) stress CMR at 3-T in randomized order. Myocardial ischaemic burden (%) was visually quantified as perfusion defect at peak stress perfusion subtracted from subendocardial myocardial scar and expressed as a percentage of the myocardium. Median myocardial ischaemic burden was significantly higher with 2D high resolution compared with 3D whole heart [16.1 (2.0-30.6) vs. 13.4 (5.2-23.2), P = 0.004]. There was excellent agreement between myocardial ischaemic burden (intraclass correlation coefficient 0.81; P < 0.0001), with mean ratio difference between 2D high resolution vs. 3D whole heart 1.28 ± 0.67 (95% limits of agreement -0.03 to 2.59). When using a 10% threshold for a dichotomous result for presence or absence of significant ischaemia, there was moderate agreement between the methods (κ = 0.58, P < 0.0001). CONCLUSION: 2D high resolution and 3D whole heart myocardial perfusion stress CMR are comparable for detection of ischaemia. 2D high resolution gives higher values for myocardial ischaemic burden compared with 3D whole heart, suggesting that 2D high resolution is more sensitive for detection of ischaemia.

The impact of dark-blood versus conventional bright-blood late gadolinium enhancement on the myocardial ischemic burden.

PURPOSE: In perfusion cardiovascular magnetic resonance (CMR), ischemic burden predicts adverse prognosis and is often used to guide revascularization. Ischemic scar tissue can cause stress perfusion defects that do not represent myocardial ischemia. Dark-blood late gadolinium enhancement (LGE) methods detect more scar than conventional bright-blood LGE, however, the impact on the myocardial ischemic burden estimation is unknown and evaluated in this study. METHODS: Forty patients with CMR stress perfusion defects and ischemic scar on both dark-blood and bright-blood LGE were included. For dark-blood LGE, phase sensitive inversion recovery imaging with left ventricular blood pool nulling was used. Ischemic scar burden was quantified for both methods using >5 standard deviations above remote myocardium. Perfusion defects were manually contoured, and the myocardial ischemic burden was calculated by subtracting the ischemic scar burden from the perfusion defect burden. RESULTS: Ischemic scar burden by dark-blood LGE was higher than bright-blood LGE (13.3 ± 7.4% vs. 10.3 ± 7.1%, p < 0.001). Dark-blood LGE derived myocardial ischemic burden was lower compared with bright-blood LGE (15.6% (IQR: 10.3 to 22.0) vs. 19.3 (10.9 to 25.5), median difference -2.0%, p < 0.001) with a mean bias of -2.8% (95% confidence intervals: -4.0 to -1.6%) and a large effect size (r = 0.62). CONCLUSION: Stress perfusion defects are associated with higher ischemic scar burden using dark-blood LGE compared with bright-blood LGE, which leads to a lower estimation of the myocardial ischemic burden. The prognostic value of using a dark-blood LGE derived ischemic burden to guide revascularization is unknown and warrants further investigation.