SCMR expert consensus statement for cardiovascular magnetic resonance of patients with a cardiac implantable electronic device.

Cardiovascular magnetic resonance (CMR) is a proven imaging modality for informing diagnosis and prognosis, guiding therapeutic decisions, and risk stratifying surgical intervention. Patients with a cardiac implantable electronic device (CIED) would be expected to derive particular benefit from CMR given high prevalence of cardiomyopathy and arrhythmia. While several guidelines have been published over the last 16 years, it is important to recognize that both the CIED and CMR technologies, as well as our knowledge in MR safety, have evolved rapidly during that period. Given increasing utilization of CIED over the past decades, there is an unmet need to establish a consensus statement that integrates latest evidence concerning MR safety and CIED and CMR technologies. While experienced centers currently perform CMR in CIED patients, broad availability of CMR in this population is lacking, partially due to limited availability of resources for programming devices and appropriate monitoring, but also related to knowledge gaps regarding the risk-benefit ratio of CMR in this growing population. To address the knowledge gaps, this SCMR Expert Consensus Statement integrates consensus guidelines, primary data, and opinions from experts across disparate fields towards the shared goal of informing evidenced-based decision-making regarding the risk-benefit ratio of CMR for patients with CIEDs.

Prevalence, incidence and clinical outcomes of epicardial coronary artery disease among transthyretin amyloidosis cardiomyopathy patients.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described. METHODS AND RESULTS: The prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥ 1-year follow-up was evaluated. The mean age was 78 ± 9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (42%) receiving a positive diagnosis. Among patients with a positive oeCAD diagnosis, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths in the study population, including 5 patients with oeCAD (17%). Fifty-six (42%) patients in the study population required hospitalization, including 10 patients with oeCAD (33%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by univariable regression analysis. CONCLUSIONS: While oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and characteristics are similar to patients without oeCAD.

Improved accuracy and precision with three-parameter simultaneous myocardial T1 and T2 mapping using multiparametric SASHA.

PURPOSE: To develop and validate a three-parameter model for improved precision multiparametric SAturation-recovery single-SHot Acquisition (mSASHA) cardiac T1 and T2 mapping with high accuracy in a single breath-hold. METHODS: The mSASHA acquisition consists of nine images of variable saturation recovery and T2 preparation in 11 heartbeats with T1 and T2 values calculated using a three-parameter model. It was validated in simulations and phantoms at 3 T with comparison to a four-parameter joint T1 -T2 technique. The mSASHA acquisition was compared with MOLLI, SASHA, and T2 -prepared balanced SSFP in 10 volunteers. RESULTS: The mSASHA technique had high accuracy in phantoms compared to spin echo, with -0.2 ± 0.3% T1 error and -2.4 ± 1.3% T2 error. The mSASHA coefficient of variation in phantoms for T1 was similar to MOLLI (0.7 ± 0.2% for both) and T2 -prepared balanced SSFP for T2 (1.3 ± 0.7% vs 1.4 ± 0.3%, adjusted p > .05 for both). In simulations, three-parameter mSASHA had higher precision than four-parameter joint T1 -T2 for both T1 and T2 (46% and 11% reductions in T1 and T2 interquartile range for native myocardium). In vivo myocardial mSASHA T1 was similar to SASHA (1523 ± 18 ms vs 1520 ± 18 ms) with similar coefficient of variation to both MOLLI and SASHA (3.3 ± 0.6% vs 3.1 ± 0.6% and 3.3 ± 0.5% respectively, adjusted p > .05 for all). Myocardial mSASHA T2 was 37.1 ± 1.1 ms with similar precision to T2 -prepared balanced SSFP (6.7 ± 1.7% vs 6.0 ± 1.6%, adjusted p > .05). CONCLUSION: Three-parameter mSASHA provides high-accuracy cardiac T1 and T2 quantification in a single breath-hold with similar precision to MOLLI and T2 -prepared balanced SSFP. Further study is required to both establish normative values and demonstrate clinical utility in patient populations.

Evidence-based cardiovascular magnetic resonance cost-effectiveness calculator for the detection of significant coronary artery disease.

BACKGROUND: Although prior reports have evaluated the clinical and cost impacts of cardiovascular magnetic resonance (CMR) for low-to-intermediate-risk patients with suspected significant coronary artery disease (CAD), the cost-effectiveness of CMR compared to relevant comparators remains poorly understood. We aimed to summarize the cost-effectiveness literature on CMR for CAD and create a cost-effectiveness calculator, useable worldwide, to approximate the cost-per-quality-adjusted-life-year (QALY) of CMR and relevant comparators with context-specific patient-level and system-level inputs. METHODS: We searched the Tufts Cost-Effectiveness Analysis Registry and PubMed for cost-per-QALY or cost-per-life-year-saved studies of CMR to detect significant CAD. We also developed a linear regression meta-model (CMR Cost-Effectiveness Calculator) based on a larger CMR cost-effectiveness simulation model that can approximate CMR lifetime discount cost, QALY, and cost effectiveness compared to relevant comparators [such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA)] or invasive coronary angiography. RESULTS: CMR was cost-effective for evaluation of significant CAD (either health-improving and cost saving or having a cost-per-QALY or cost-per-life-year result lower than the cost-effectiveness threshold) versus its relevant comparator in 10 out of 15 studies, with 3 studies reporting uncertain cost effectiveness, and 2 studies showing CCTA was optimal. Our cost-effectiveness calculator showed that CCTA was not cost-effective in the US compared to CMR when the most recent publications on imaging performance were included in the model. CONCLUSIONS: Based on current world-wide evidence in the literature, CMR usually represents a cost-effective option compared to relevant comparators to assess for significant CAD.

Quantitative technetium pyrophosphate and cardiovascular magnetic resonance in patients with suspected cardiac amyloidosis.

BACKGROUND: Quantitation of myocardial 99m Tc-pyrophosphate activity may have high diagnostic accuracy, but its correlation with disease burden is unknown. We examined the relationship between 99m Tc-pyrophosphate quantitation and cardiac magnetic resonance (CMR) measures in patients with suspected transthyretin cardiac amyloidosis (ATTR-CM) or light chain cardiac amyloidosis (AL-CM). METHODS: Consecutive patients who underwent 99mTc-pyrophosphate imaging and CMR were included. ATTR-CM and AL-CM were diagnosed using standard criteria. 99mTc-pyrophosphate images were assessed with standard parameters and quantified with cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). We assessed the association between 99mTc-pyrophosphate image interpretation and CMR tissue characteristics. RESULTS: Seventy patients were identified, mean age 70.4 ± 11.4 years, with ATTR-CM and AL-CM diagnosed in 22 (31%) and 11 (16%) patients, respectively. In patients with ATTR-CM, there were significant correlations between CPA (r2 = 0.509, P < 0.001) and VOI (r2 = 0.586, P < 0.001) with native myocardial T1 mapping values. Additionally, CPA (adjusted hazard ratio (aHR) 1.04, P = 0.016), VOI (aHR 1.12, P = 0.034), and average myocardial T1 (aHR 1.12, P = 0.025) were associated with incidence of heart failure hospitalization or death. CONCLUSION: CPA and VOI were correlated with CMR measures of myocardial fibrosis in patients with ATTR-CM. 99mTc-pyrophosphate quantitation may have a role in ATTR-CM disease staging, guiding treatment, or following response to therapy.

Right ventricular insertion site fibrosis in a dilated cardiomyopathy referral population: phenotypic associations and value for the prediction of heart failure admission or death.

BACKGROUND: Dilated cardiomyopathy (DCM) is increasingly recognized as a heterogenous disease with distinct phenotypes on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging. While mid-wall striae (MWS) fibrosis is a widely recognized phenotypic risk marker, other fibrosis patterns are prevalent but poorly defined. Right ventricular (RV) insertion (RVI) site fibrosis is commonly seen, but without objective criteria has been considered a non-specific finding. In this study we developed objective criteria for RVI fibrosis and studied its clinical relevance in a large cohort of patients with DCM. METHODS: We prospectively enrolled 645 DCM patients referred for LGE-CMR. All underwent standardized imaging protocols and baseline health evaluations. LGE images were blindly scored using objective criteria, inclusive of RVI site and MWS fibrosis. Associations between LGE patterns and CMR-based markers of adverse chamber remodeling were evaluated. Independent associations of LGE fibrosis patterns with the primary composite clinical outcome of heart failure admission or death were determined by multivariable analysis. RESULTS: The mean age was 56 ± 14 (28% female) with a mean left ventricular (LV) ejection fraction (LVEF) of 37%. At a median of 1061 days, 129 patients (20%) experienced the primary outcome. Any abnormal LGE was present in 306 patients (47%), inclusive of 274 (42%) meeting criteria for RVI site fibrosis and 167 (26%) for MWS fibrosis. All with MWS fibrosis showed RVI site fibrosis. Solitary RVI site fibrosis was associated with higher bi-ventricular volumes [LV end-systolic volume index (78 ± 39 vs. 66 ± 33 ml/m2, p = 0.01), RV end-diastolic volume index (94 ± 28 vs. 84 ± 22 ml/m2 (p < 0.01), RV end-systolic volume index (56 ± 26 vs. 45 ± 17 ml/m2, p < 0.01)], lower bi-ventricular function [LVEF 35 ± 12 vs. 39 ± 10% (p < 0.01), RV ejection fraction (RVEF) 43 ± 12 vs. 48 ± 10% (p < 0.01)], and higher extracellular volume (ECV). Patient with solitary RVI site fibrosis experienced a non-significant 1.4-fold risk of the primary outcome, increasing to a significant 2.6-fold risk when accompanied by MWS fibrosis. CONCLUSIONS: RVI site fibrosis in the absence of MWS fibrosis is associated with bi-ventricular remodelling and intermediate risk of heart failure admission or death. Our study findings suggest RVI site fibrosis to be pre-requisite for the incremental development of MWS fibrosis, a more advanced phenotype associated with greater LV remodeling and risk of clinical events.

Cardiovascular toxicity of PI3Kα inhibitors.

The phosphoinositide 3-kinases (PI3Ks) are a family of intracellular lipid kinases that phosphorylate the 3'-hydroxyl group of inositol membrane lipids, resulting in the production of phosphatidylinositol 3,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. This results in downstream effects, including cell growth, proliferation, and migration. The heart expresses three PI3K class I enzyme isoforms (α, ß, and γ), and these enzymes play a role in cardiac cellular survival, myocardial hypertrophy, myocardial contractility, excitation, and mechanotransduction. The PI3K pathway is associated with various disease processes but is particularly important to human cancers since many gain-of-function mutations in this pathway occur in various cancers. Despite the development, testing, and regulatory approval of PI3K inhibitors in recent years, there are still significant challenges when creating and utilizing these drugs, including concerns of adverse effects on the heart. There is a growing body of evidence from preclinical studies revealing that PI3Ks play a crucial cardioprotective role, and thus inhibition of this pathway could lead to cardiac dysfunction, electrical remodeling, vascular damage, and ultimately, cardiovascular disease. This review will focus on PI3Kα, including the mechanisms underlying the adverse cardiovascular effects resulting from PI3Kα inhibition and the potential clinical implications of treating patients with these drugs, such as increased arrhythmia burden, biventricular cardiac dysfunction, and impaired recovery from cardiotoxicity. Recommendations for future directions for preclinical and clinical work are made, highlighting the possible role of PI3Kα inhibition in the progression of cancer-related cachexia and female sex and pre-existing comorbidities as independent risk factors for cardiac abnormalities after cancer treatment.

Left atrial vortex size and velocity distributions by 4D flow MRI in patients with paroxysmal atrial fibrillation: Associations with age and CHA2 DS2 -VASc risk score.

BACKGROUND: Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk. PURPOSE: To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores. STUDY TYPE: Prospective clinical. POPULATION: Patients with PAF (n = 45, 46 ± 14 years) and healthy controls (n = 15, 54 ± 9 years) were enrolled. MRI SEQUENCES: 3T standardized cardiac MRI protocol inclusive of 4D flow MRI. ASSESSMENT: Flow analysis planes were prescribed at each pulmonary vein. Velocity distribution analysis and vortex size quantification by the Lambda2 (λ2 ) method were performed in the LA. STATISTICS: Pearson or Spearman's correlation coefficients, r, were calculated to identify relationships between 4D flow-derived LA parameters and age, LA/LV function, and CHA2 DS2 -VASc stroke risk score. Univariate and multivariate determinants of stroke risk were assessed using linear regressions. To compare parameters within multiple groups, one-way analysis of variance or Kruskal-Wallis was used. RESULTS: LA vortice sizes were observed in all subjects using λ2 showing inverse correlations with peak pulmonary vein inflow velocities (P < 0.05), and positive correlations with LA volume (P < 0.05). Vortex size was elevated in PAF at all phases of the cardiac cycle, being most prominent at end early diastole (3.98 ± 1.84 cm3 vs. 6.93 ± 3.11 cm3 , P = 0.001). Velocity distribution analysis showed a greater incidence of flow stasis among patients with PAF (P < 0.05). In univariate regression, vortex size was associated with the CHA2 DS2 -VASc risk score at peak systole (0.457 ± 0.038, P ≤ 0.001). However, in multivariate regression age was the dominant determinant of stroke risk (0.348 ± 0.012, P = 0.006). DATA CONCLUSION: This study demonstrated that LA vortex size is increased among low-risk patients with PAF and is associated with the CHA2 DS2 -VASc risk score. Age remained the dominant determinant of stroke risk. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:871-884.

Layer-specific strain in patients with heart failure using cardiovascular magnetic resonance: not all layers are the same.

BACKGROUND: Global longitudinal strain (GLS), most commonly measured at the endocardium, has been shown to be superior to left ventricular (LV) ejection fraction (LVEF) for the identification of systolic dysfunction and prediction of outcomes in heart failure (HF). We hypothesized that strains measured at different myocardial layers (endocardium = ENDO, epicardium = EPI, average = AVE) will have distinct diagnostic and predictive performance for patients with HF. METHODS: Layer-specific GLS, layer-specific global circumferential strain (GCS) and global radial strain (GRS) were evaluated by cardiovascular magnetic resonance imaging (CMR) feature tracking in the Alberta HEART study. A total of 453 subjects consisted of healthy controls (controls, n = 77), at-risk for HF (at-risk, n = 143), HF with preserved ejection fraction (HFpEF, n = 87), HF with mid-range ejection fraction (HFmrEF, n = 88) and HF with reduced ejection fraction (HFrEF, n = 58). For outcomes analysis, CMR-derived imaging parameters were adjusted with a base model that included age and N-terminal prohormone of b-type natriuretic peptide (NT-proBNP) to test their independent association with 5-year all-cause mortality. RESULTS: GLS_EPI distinguished all groups with preserved LVEF (controls - 16.5 ± 2.4% vs. at-risk - 15.5 ± 2.7% vs. HFpEF - 14.1 ± 3.0%, p < 0.001) while GLS_ENDO and all GCS (all layers) were similar among these groups. GRS was reduced in HFpEF (41.1 ± 13.8% versus 48.9 ± 10.7% in controls, p < 0.001) and the difference between GLS_EPI and GLS_ENDO were significantly larger in HFpEF as compared to controls. Within the preserved LVEF groups, reduced GRS and GLS_EPI were significantly associated with increased LV mass (LVM) and LVM/LV end-diastolic volume EDV (concentricity). In multivariable analysis, only GLS_AVE and GRS predicted 5-year all-cause mortality (all ps < 0.05), with the strongest association with 5-year all-cause mortality by Akaike Information Criterion analysis and significant incremental value for outcomes prediction beyond LVEF or GLS_ENDO by the likelihood ratio test. CONCLUSION: Global strains measured on endocardium, epicardium or averaged across the wall thickness are not equivalent for the identification of systolic dysfunction or outcomes prediction in HF. The endocardium-specific strains were shown to have poorest all-around performance. GLS_AVE and GRS were the only CMR parameters to be significantly associated with 5-year all-cause mortality in multivariable analysis. GLS_EPI and GRS, as well as the difference in endocardial and epicardial strains, were sensitive to systolic dysfunction among HF patients with normal LVEF (> 55%), in whom lower strains were associated with increased concentricity.

Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis.

BACKGROUND: The tolerability and utility of combination doxycycline and ursodeoxycholic acid (ursodiol) amyloid fibril disruption therapy for transthyretin cardiac amyloidosis (ATTR CA) in clinical practice is poorly described. METHODS AND RESULTS: We report the clinical experience of 53 ATTR CA patients treated with doxycycline and ursodiol. Six patients (11%) did not tolerate the therapy owing to dermatologic and gastrointestinal effects. Of those remaining, the median follow-up was 22 months (range 8-30), mean age was 71 ± 11years, 41 (87%) were male, and 42 (89%) had wild-type and 5 (11%) mutant ATTR. Five patients (11%) died during follow-up. There was no significant change in New York Heart Association (NYHA) functional class, cardiac biomarkers, or echocardiographic parameters during follow-up. Left ventricular (LV) global longitudinal systolic strain (GLS) improved in 16 patients (38%) (-12 ± 4% to -17 ± 4%; P < .01). Patients whose LV GLS improved were significantly younger and had lower NYHA functional class, troponin-T, N-terminal pro-B-type natriuretic peptide (BNP), and baseline LV GLS levels compared with those whose LV GLS did not improve. Troponin-T improved in follow-up for patients whose LV GLS improved (35 ± 21 to 20 ± 14 ng/L; P = .06). CONCLUSIONS: Doxycycline and ursodiol therapy for treatment of ATTR CA was tolerable and was associated with stabilized markers of disease progression. LV GLS improved in patients with less advanced disease.

Utilizing wall shear stress as a clinical biomarker for bicuspid valve-associated aortopathy.

PURPOSE OF REVIEW: Bicuspid aortic valve (BAV) results from fusion of two adjacent aortic valve cusps, and is associated with dilatation of the aorta, known as BAV-associated aortopathy, or bicuspid aortopathy. Bicuspid aortopathy is progressive, increasing the risk of life-threatening clinical events, such as aortic dissection. Regular monitoring and timely intervention with prophylactic surgical resection of the proximal aorta is recommended. RECENT FINDINGS: Aortopathy is heterogeneous among patients. Studies have shown that different flow patterns lead to specific phenotypes of aortopathy. Although not uniform, BAV morphology affects flow patterns. Recent work has demonstrated the role of wall shear stress (WSS) in driving aortopathy, and it is suggested that individualized WSS 'heat maps' can be used for clinically monitoring patients with BAV. WSS has the potential to be an imaging biomarker for directing resection timing, surgical strategies, and postsurgical follow-up care. SUMMARY: Finding and validating noninvasive hemodynamic biomarkers of aortic risk to assist in the management of BAV patients is of clinical importance. Herein, we will review the latest findings pertaining to the utility of WSS as a specific biomarker of risk for BAV patients with aortopathy.

Three-dimensional thoracic aorta principal strain analysis from routine ECG-gated computerized tomography: feasibility in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Functional impairment of the aorta is a recognized complication of aortic and aortic valve disease. Aortic strain measurement provides effective quantification of mechanical aortic function, and 3-dimenional (3D) approaches may be desirable for serial evaluation. Computerized tomographic angiography (CTA) is routinely performed for various clinical indications, and offers the unique potential to study 3D aortic deformation. We sought to investigate the feasibility of performing 3D aortic strain analysis in a candidate population of patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Twenty-one patients with severe aortic valve stenosis (AS) referred for TAVR underwent ECG-gated CTA and echocardiography. CTA images were analyzed using a 3D feature-tracking based technique to construct a dynamic aortic mesh model to perform peak principal strain amplitude (PPSA) analysis. Segmental strain values were correlated against clinical, hemodynamic and echocardiographic variables. Reproducibility analysis was performed. RESULTS: The mean patient age was 81±6 years. Mean left ventricular ejection fraction was 52±14%, aortic valve area (AVA) 0.6±0.3 cm2 and mean AS pressure gradient (MG) 44±11 mmHg. CTA-based 3D PPSA analysis was feasible in all subjects. Mean PPSA values for the global thoracic aorta, ascending aorta, aortic arch and descending aorta segments were 6.5±3.0, 10.2±6.0, 6.1±2.9 and 3.3±1.7%, respectively. 3D PSSA values demonstrated significantly more impairment with measures of worsening AS severity, including AVA and MG for the global thoracic aorta and ascending segment (p<0.001 for all). 3D PSSA was independently associated with AVA by multivariable modelling. Coefficients of variation for intra- and inter-observer variability were 5.8 and 7.2%, respectively. CONCLUSIONS: Three-dimensional aortic PPSA analysis is clinically feasible from routine ECG-gated CTA. Appropriate reductions in PSSA were identified with increasing AS hemodynamic severity. Expanded study of 3D aortic PSSA for patients with various forms of aortic disease is warranted.

Fragmented QRS complexes after acute myocardial infarction are independently associated with unfavorable left ventricular remodeling.

BACKGROUND: Recovery of left ventricular ejection fraction (LVEF) after acute myocardial infarction (MI) is not universal and is difficult to predict. Fragmented QRS (fQRS) complexes are thought to be markers of myocardial scar. We hypothesized that fQRS complexes on 12­lead surface ECGs during the initial post-MI period would be associated with adverse LV remodeling over the following year. METHODS: Change in LVEF between the early (0-2 month) and later (2-12 month) post-MI periods was assessed in two independent cohorts of post-MI patients with initial LV dysfunction. A decline or no recovery in LVEF (ΔLVEF ≤0%) was used as a primary outcome. fQRS complexes were measured on 12­lead ECGs within a week of acute MI. A subset of patients underwent cardiac magnetic resonance imaging (CMR) for scar quantification. RESULTS: Of 705 patients in the combined cohort, 27% experienced the primary outcome (average ΔLVEF of -4%). fQRS complexes were associated with a two-fold higher risk of no LVEF recovery, independent of prior MI or CABG, baseline LVEF, MI location and QRS duration or axis. Of 113 patients undergoing CMR, fQRS was associated with increased peri-infarct zone late gadolinium enhancement (13 ±â€¯5% vs 11 ±â€¯4%, p = 0.02), but not core infarct. CONCLUSIONS: Despite contemporary post-MI therapy, >1 in 4 patients will show a decline in LVEF during follow-up. Fragmented QRS complexes on 12­lead surface ECG early post-MI may be a valuable marker of unfavorable LV remodeling and correlate to increased peri-infarct scar on CMR imaging.

Objective criteria for septal fibrosis in non-ischemic dilated cardiomyopathy: validation for the prediction of future cardiovascular events.

BACKGROUND: Expert subjective reporting of mid-wall septal fibrosis on late gadolinium enhancement (LGE) images has been shown to predict major cardiovascular outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). This study aims to establish objective criteria for non-experts to report clinically relevant septal fibrosis and compare its performance by such readers versus experts for the prediction of cardiovascular events. METHODS: LGE cardiovascular magnetic resonance (CMR) was performed in 118 consecutive patients with NIDCM (mean age 57 ± 14, 42 % female) and the presence of septal fibrosis scored by expert readers. CMR-naive readers performed signal threshold-based LGE quantification by referencing mean values of remote tissue and applying these to a pre-defined anatomic region to measure septal fibrosis. All patients were followed for the primary composite outcome of cardiac mortality or appropriate implantable cardioverter-defibrillator (ICD) therapy. RESULTS: The mean LVEF was 32 ± 12 %. At a median follow-up of 1.9 years, 20 patients (17 %) experienced a primary composite outcome. Expert visual scoring identified 55 patients with septal fibrosis. Non-expert septal fibrosis quantification was highly reproducible and identified mean septal fibrosis burden for three measured thresholds as follows; 5SD: 2.9 ± 3.6 %, 3SD: 6.9 ± 6.3 %, and 2SD: 11.1 ± 7.5 % of the left ventricular (LV) mass, respectively. By ROC analysis, optimal thresholds for prediction of the primary outcome were; 5SD: 2.74 % (HR 8.7, p < 0.001), 3SD: 6.63 % (HR 5.7, p = 0.001) and 2SD: 10.15 % (HR 6.1, p = 0.001). By comparison, expert visual scoring provided a HR of 5.3 (p = 0.001). In adjusted analysis, objective quantification by a novice reader (>5SD threshold) was the strongest independent predictor of the primary outcome (HR 8.7) and provided improved risk reclassification beyond LVEF alone (NRI 0.54, 95 % CI 0.16-0.92, p = 0.005). CONCLUSIONS: Novice readers were able to achieve superior risk prediction for future cardiovascular events versus experts using objective criteria for septal fibrosis in patients with NIDCM. Patients with a septal fibrosis burden >2.74 % of the LV mass (>5SD threshold) were at a 9-fold higher risk of cardiac death or appropriate ICD therapy versus those not meeting this criteria. As such, this study validates reproducible criteria applicable to all levels of expertise to identify NIDCM patients at high risk of future cardiovascular events.

Recent Advances in Cardiovascular Imaging Relevant to the Management of Patients with Suspected Cardiac Amyloidosis.

Cardiac amyloidosis is a form of infiltrative cardiomyopathy typically presenting with progressive heart failure. The clinical presentation and morphological findings often overlap with other cardiovascular diseases, and frequently results in misdiagnosis and consequent under-reporting. Cardiovascular imaging is playing an increasingly important diagnostic and prognostic role in this referral population, and is reducing the reliance on endomyocardial biopsy as a confirmatory testing. Advancements across multiple cardiac imaging modalities, including echocardiography, magnetic resonance imaging, nuclear imaging, and computed tomography, are improving diagnostic accuracy and offering novel approaches to sub-type differentiation and prognostication. This review explores recent advancements in cardiac imaging for the diagnosis, typing, and staging of cardiac amyloidosis, with a focus on new and evolving techniques. Emphasis is also placed on the promise of non-invasive cardiac imaging to provide value across the spectrum of this clinical disease, from early disease identification (prior to the development of increased wall thickness) through to markers of advanced disease associated with early mortality.

Max-IDEAL: a max-flow based approach for IDEAL water/fat separation.

PURPOSE: To propose a novel approach to water/fat separation using a unique smoothness constraint. THEORY AND METHODS: Chemical-shift based water/fat separation is an established noninvasive imaging tool for the visualization of body fat in various anatomies. Nevertheless, B0 magnetic field inhomogeneities can hamper the water/fat separation process. In this work, B0 variations are mapped using a convex-relaxed labeling model which produces a coarse estimate of the field map, while considering T2* decay during the labeling process. Fat and water components are subsequently resolved using T2*-IDEAL. An adaptive spatial filtering (ASF) was introduced to improve the robustness of the estimate. The method was tested on cardiac and abdominal datasets from healthy volunteers and nonalcoholic fatty liver disease (NAFLD) patients. RESULTS: Out of 168 cardiac and abdominal images, only 1 case has shown water/fat swaps that can hinder the clinical interpretation of the underlying anatomy. CONCLUSION: This work demonstrates a new water/fat separation approach that prevents the occurrence of water/fat swaps, by means of a unique smoothness constraint. Incorporating T2* effect in the labeling procedure and including the ASF processing enhance the robustness of the proposed approach and permit the procedure to handle abrupt B0 variations within the field of view.

High-resolution 3-dimensional late gadolinium enhancement scar imaging in surgically corrected Tetralogy of Fallot: clinical feasibility of volumetric quantification and visualization.

BACKGROUND: The extent of surgical scarring in Tetralogy of Fallot (TOF) may be a marker of adverse outcomes and provide substrate for ventricular arrhythmia. In this study we evaluate the feasibility of high resolution three dimensional (3D) late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) for volumetric scar quantification in patients with surgically corrected TOF. METHODS: Fifteen consecutive patients underwent 3D LGE imaging with 3 Tesla CMR using a whole-heart, respiratory-navigated technique. A novel, signal-histogram based segmentation technique was tested for the quantification and modeling of surgical scar. Total scar volume was compared to the gold standard manual expert segmentation. The feasibility of segmented scar fusion to matched coronary CMR data for volumetric display was explored. RESULTS: Image quality sufficient for 3D scar segmentation was acquired in fourteen patients. Mean patient age was 32.2 ± 11.9 years (range 21 to 57 years) with mean right ventricle (RV) ejection fraction (EF) of 53.9 ± 9.2% and mean RV end diastolic volume of 117.0 ± 41.5 mL/m². The mean total scar volume was 11.1 ± 8.2 mL using semi-automated 3D segmentation with excellent correlation to manual expert segmentation (r = 0.99, bias = 0.89 mL, 95% CI -1.66 to 3.44). The mean segmentation time was significantly reduced using the novel semi-automated segmentation technique (10.1 ± 2.6 versus 45.8 ± 12.6 minutes). Excellent intra-observer and good inter-observer reproducibility was observed. CONCLUSION: 3D high resolution LGE imaging with semi-automated scar segmentation is clinically feasible among patients with surgically corrected TOF and shows excellent accuracy and reproducibility. This approach may offer a valuable clinical tool for risk prediction and procedural planning among this growing population.

Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy.

BACKGROUND: The presence and extent of late gadolinium enhancement (LGE) has been associated with adverse events in patients with hypertrophic cardiomyopathy (HCM). Signal intensity (SI) threshold techniques are routinely employed for quantification; Full-Width at Half-Maximum (FWHM) techniques are suggested to provide greater reproducibility than Signal Threshold versus Reference Mean (STRM) techniques, however the accuracy of these approaches versus the manual assignment of optimal SI thresholds has not been studied. In this study, we compared all known semi-automated LGE quantification techniques for accuracy and reproducibility among patients with HCM. METHODS: Seventy-six HCM patients (51 male, age 54 ± 13 years) were studied. Total LGE volume was quantified using 7 semi-automated techniques and compared to expert manual adjustment of the SI threshold to achieve optimal segmentation. Techniques tested included STRM based thresholds of >2, 3, 4, 5 and 6 SD above mean SI of reference myocardium, the FWHM technique, and the Otsu-auto-threshold (OAT) technique. The SI threshold chosen by each technique was recorded for all slices. Bland-Altman analysis and intra-class correlation coefficients (ICC) were reported for each semi-automated technique versus expert, manually adjusted LGE segmentation. Intra- and inter-observer reproducibility assessments were also performed. RESULTS: Fifty-two of 76 (68%) patients showed LGE on a total of 202 slices. For accuracy, the STRM >3SD technique showed the greatest agreement with manual segmentation (ICC = 0.97, mean difference and 95% limits of agreement = 1.6 ± 10.7 g) while STRM >6SD, >5SD, 4SD and FWHM techniques systematically underestimated total LGE volume. Slice based analysis of selected SI thresholds similarly showed the STRM >3SD threshold to most closely approximate manually adjusted SI thresholds (ICC = 0.88). For reproducibility, the intra- and inter-observer reproducibility of the >3SD threshold demonstrated an acceptable mean difference and 95% limits of agreement of -0.5 ± 6.8 g and -0.9 ± 5.6 g, respectively. CONCLUSIONS: FWHM segmentation provides superior reproducibility, however systematically underestimates total LGE volume compared to manual segmentation in patients with HCM. The STRM >3SD technique provides the greatest accuracy while retaining acceptable reproducibility and may therefore be a preferred approach for LGE quantification in this population.

Simplifying cardiovascular magnetic resonance pulse sequence terminology.

We propose a set of simplified terms to describe applied Cardiovascular Magnetic Resonance (CMR) pulse sequence techniques in clinical reports, scientific articles and societal guidelines or recommendations. Rather than using various technical details in clinical reports, the description of the technical approach should be based on the purpose of the pulse sequence. In scientific papers or other technical work, this should be followed by a more detailed description of the pulse sequence and settings. The use of a unified set of widely understood terms would facilitate the communication between referring physicians and CMR readers by increasing the clarity of CMR reports and thus improve overall patient care. Applied in research articles, its use would facilitate non-expert readers' understanding of the methodology used and its clinical meaning.