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.

Myocardial strain analysis of the right ventricle: comparison of different cardiovascular magnetic resonance and echocardiographic techniques.

BACKGROUND: Right ventricular (RV) strain is a useful predictor of prognosis in various cardiovascular diseases, including those traditionally believed to impact only the left ventricle. We aimed to determine inter-modality and inter-technique agreement in RV longitudinal strain (LS) measurements between currently available cardiovascular magnetic resonance (CMR) and echocardiographic techniques, as well as their reproducibility and the impact of layer-specific strain measurements. METHODS: RV-LS was determined in 62 patients using 2D speckle tracking echocardiography (STE, Epsilon) and two CMR techniques: feature tracking (FT) and strain-encoding (SENC), and in 17 healthy subjects using FT and SENC only. Measurements included global and free-wall LS (GLS, FWLS). Inter-technique agreement was assessed using linear regression and Bland-Altman analysis. Reproducibility was quantified using intraclass correlation (ICC) and coefficients of variation (CoV). RESULTS: We found similar moderate agreement between both CMR techniques and STE in patients: r = 0.57-0.63 for SENC; r = 0.50-0.62 for FT. The correlation between SENC and STE was better for GLS (r = 0.63) than for FWLS (r = 0.57). Conversely, the correlation between FT and STE was higher for FWLS (r = 0.60-0.62) than GLS (r = 0.50-0.54). FT-midmyocardial strain correlated better with SENC and STE than FT-subendocardial strain. The agreement between SENC and FT was fair (r = 0.36-0.41, bias: - 6.4 to - 10.4%) in the entire study group. All techniques except FT showed excellent reproducibility (ICC: 0.62-0.96, CoV: 0.04-0.30). CONCLUSIONS: We found only moderate inter-modality agreement with STE in RV-LS for both FT and SENC and poor agreement when comparing between the CMR techniques. Different modalities and techniques should not be used interchangeably to determine and monitor RV strain.

Echocardiography and cardiovascular magnetic resonance based evaluation of myocardial strain and relationship with late gadolinium enhancement.

OBJECTIVES: We sought to: (1) determine the agreement in cardiovascular magnetic resonance (CMR) and speckle tracking echocardiography (STE) derived strain measurements, (2) compare their reproducibility, (3) determine which approach is best related to CMR late gadolinium enhancement (LGE). BACKGROUND: While STE-derived strain is routinely used to assess left ventricular (LV) function, CMR strain measurements are not yet standardized. Strain can be measured using dedicated pulse sequences (strain-encoding, SENC), or post-processing of cine images (feature tracking, FT). It is unclear whether these measurements are interchangeable, and whether strain can be used as an alternative to LGE. METHODS: Fifty patients underwent 2D echocardiography and 1.5 T CMR. Global longitudinal strain (GLS) was measured by STE (Epsilon), FT (NeoSoft) and SENC (Myocardial Solutions) and circumferential strain (GCS) by FT and SENC. RESULTS: GLS showed good inter-modality agreement (r-values: 0.71-0.75), small biases (< 1%) but considerable limits of agreement (- 7 to 8%). The agreement between the CMR techniques was better for GLS than GCS (r = 0.81 vs 0.67; smaller bias). Repeated measurements showed low intra- and inter-observer variability for both GLS and GCS (intraclass correlations 0.86-0.99; coefficients of variation 3-13%). LGE was present in 22 (44%) of patients. Both SENC- and FT-derived GLS and GCS were associated with LGE, while STE-GLS was not. Irrespective of CMR technique, this association was stronger for GCS (AUC 0.77-0.78) than GLS (AUC 0.67-0.72) and STE-GLS (AUC = 0.58). CONCLUSION: There is good inter-technique agreement in strain measurements, which were highly reproducible, irrespective of modality or analysis technique. GCS may better reflect the presence of underlying LGE than GLS.

Treatment of Severe Aortic Valve Stenosis: Impact of Patient Sex and Life Expectancy on Treatment Choice.

In adults with severe aortic stenosis, sex and age differences in symptoms and diagnosis may lead to delays in intervention. Choice of intervention partly depends on expected longevity because bioprosthetic valves have limited durability, particularly in younger patients. Current guidelines recommend the following: a mechanical valve in younger adults (aged <50 years) if lifelong anticoagulation is possible and acceptable and a valve-sparing procedure is not possible; surgical mechanical or bioprosthetic aortic valve replacement (SAVR) in adults aged 50-65 years; and transcatheter aortic valve implantation (TAVI) for those aged >80 years based on lower mortality and morbidity compared to SAVR and adequate valve durability. For patients aged 65-80 years, the choice between TAVI and a bioprosthetic SAVR depends on expected longevity, which is greater in women than men, as well as associated cardiac and noncardiac conditions, valvular and vascular anatomy, estimated risk of SAVR versus TAVI and expected complications and patient preferences.

Risk for Increased Mean Diastolic Gradient after Transcatheter Edge-to-Edge Mitral Valve Repair: A Quantitative Three-Dimensional Transesophageal Echocardiographic Analysis.

BACKGROUND: Iatrogenic mitral stenosis is a known limitation of transcatheter edge-to-edge mitral valve repair (TMVr), but determinants of increased postprocedural mean diastolic gradient (MG) are not well defined. The aim of this study was to determine correlates of increased post-TMVr MG or aborted clip implantation due to increased MG. METHODS: Procedural three-dimensional transesophageal echocardiographic (TEE) data sets of 112 patients who underwent TMVr were retrospectively analyzed. Three-dimensional TEE mitral valve area (MVA) planimetry and mitral annular calcification (MAC) were quantified using multiplanar reconstruction. When MAC extension into the mitral leaflets was present, MAC with leaflet calcification (MAC-LC) length was recorded as the maximum distance from the mitral annulus to the most distal leaflet calcification. Increased MG after TMVr, measured on intraprocedural TEE imaging, was defined as ≥5 mm Hg or aborted clip implantation due to increased MG. RESULTS: Baseline MVA was 5.9 ± 1.7 cm2, baseline MG was 2.1 ± 1.2 mm Hg, and MAC-LC length was 4.0 ± 4.5 mm. Thirty-two patients (29%) had increased post-TMVr MG. Risk for increased post-TMVr MG was 86%, 28%, and 14% in patients with baseline MVA < 4.0, 4.0 to 6.0, and >6.0 cm2, respectively (P < .001). In patients with baseline MVA 4.0 to 6.0 cm2, concurrent baseline MG ≥ 4 mm Hg or MAC-LC ≥ 6 mm was associated with higher risk for increased post-TMVr MG (53% vs 12%, P = .002). In patients with baseline MVA < 4.0 and >6.0 cm2, the risk for increased post-TMVr MG was similar in the presence or absence of baseline MG ≥ 4 mm Hg or MAC-LC ≥ 6 mm (P > .05 for both). CONCLUSIONS: Patients with baseline three-dimensional TEE MVA < 4.0 cm2 are at high risk for increased post-TMVr MG. Additionally, patients with borderline MVA (4.0-6.0 cm2) and concurrent MAC-LC length ≥ 6 mm or baseline MG ≥ 4 mm Hg are at moderate risk for increased MG after TMVr.

Regional myocardial strain by cardiac magnetic resonance feature tracking for detection of scar in ischemic heart disease.

BACKGROUND: Although cardiac magnetic resonance (CMR) can accurately quantify global left ventricular strain using feature tracking (FT), it has been suggested that FT cannot reliably quantify regional strain. We aimed to determine whether abnormalities in regional strain measured using FT can be detected within areas of myocardial scar and to determine the extent to which the regional strain measurement is impacted by LV ejection fraction (EF). METHODS: We retrospectively studied 96 patients (46 with LVEF ≤ 40%, 50 with LVEF > 40%) with coronary artery disease and a late gadolinium enhancement (LGE) pattern consistent with myocardial infarction, who underwent CMR imaging (1.5T). Regional peak systolic longitudinal and circumferential strains (RLS, RCS) were measured within LGE and non-LGE areas. Linear regression analysis was performed for strain in both areas against LVEF to determine whether the relationship between strain and LGE holds across the LV function spectrum. Receiver-operating curve (ROC) analysis was performed in 33 patients (derivation cohort) to optimize strain cutoff, which was tested in the remaining 63 patients (validation cohort) for its ability to differentiate LGE from non-LGE areas. RESULTS: Both RLS and RCS magnitudes were reduced in LGE areas: RLS = -10.4 ± 6.2% versus -21.0 ± 8.5% (p < 0.001); RCS = -10.4 ± 6.0% versus -18.9 ± 8.6%, respectively (p < 0.001), but there was considerable overlap between LGE and non-LGE areas. Linear regression revealed that it was partially driven by the natural dependence between strain and EF, suggesting that EF-corrected strain cutoff is needed to detect LGE. ROC analysis showed the ability of both RLS and RCS to differentiate LGE from non-LGE areas: area under curve 0.95 and 0.89, respectively. In the validation cohort, optimal cutoffs of RLS/EF = 0.36 and RCS/EF = 0.37 yielded sensitivity, specificity and accuracy 0.74-0.78. CONCLUSION: Abnormalities in RLS and RCS within areas of myocardial scar can be detected using CMR-FT; however, LVEF must be accounted for.

Contrast-enhanced echocardiographic measurement of longitudinal strain: accuracy and its relationship with image quality.

The importance of left ventricular (LV) global longitudinal strain (GLS) is increasingly recognized in multiple clinical scenarios. However, in patients with poor image quality, strain is difficult or impossible to measure without contrast enhancement. The feasibility of contrast-enhanced GLS measurement was recently demonstrated. We sought to determine: (1) whether contrast enhancement improves the accuracy of GLS measurements against cardiac magnetic resonance (CMR) reference, (2) their reproducibility compared to non-enhanced GLS, and (3) the dependence of accuracy and reproducibility on image quality. We prospectively enrolled 25 patients undergoing clinically indicated CMR imaging who subsequently underwent transthoracic echocardiography (TTE) with and without low-dose contrast injection (1-2 mL Optison/3-5 mL saline IV, GE Healthcare). GLS was measured from both non-contrast and contrast-enhanced images using speckle tracking (EchoInsight, Epsilon Imaging). These measurements were compared to each other and to CMR reference values obtained using feature tracking (SuiteHEART, NeoSoft). Inter-technique comparisons included linear regression and Bland-Altman analyses. A random subgroup of 15 patients was used to assess inter- and intra-observer variability using intra-class correlation (ICC). Contrast-enhanced GLS was in close agreement with non-enhanced GLS (r = 0.95; bias: - 0.2 ± 1.5%). Both inter-observer (ICC = 0.88 vs. 0.82) and intra-observer variability (ICC = 0.91 vs. 0.88) were improved by contrast enhancement. The agreement with CMR was better for contrast-enhanced GLS (r = 0.87; bias: 1.1 ± 2.2%) than for non-enhanced GLS (r = 0.80; bias: 1.3 ± 2.7%). In 12/25 patients with suboptimal TTE images that rendered GLS difficult to measure, contrast-enhanced GLS showed better agreement with CMR than non-enhanced GLS (r = 0.88 vs. 0.83) and also improved inter-observer (ICC = 0.83 vs. 0.76) and intra-observer variability (ICC = 0.88 vs. 0.82). In conclusion, contrast enhancement of TTE images improves the accuracy and reproducibility of GLS measurements, resulting in better agreement with CMR, even in patients with suboptimal acoustic windows. This approach may aid in the assessment of LV function in this patient population.

Validation of non-contrast multiple overlapping thin-slab 4D-flow cardiac magnetic resonance imaging.

BACKGROUND: Cardiac magnetic resonance (CMR) flow quantification is typically performed using 2D phase-contrast (PC) imaging of a plane perpendicular to flow. 3D-PC imaging (4D-flow) allows offline quantification anywhere in a thick slab, but is often limited by suboptimal signal, potentially alleviated by contrast enhancement. We developed a non-contrast 4D-flow sequence, which acquires multiple overlapping thin slabs (MOTS) to minimize signal loss, and hypothesized that it could improve image quality, diagnostic accuracy, and aortic flow measurements compared to non-contrast single-slab approach. METHODS: We prospectively studied 20 patients referred for transesophageal echocardiography (TEE), who underwent CMR (GE, 3 T). 2D-PC images of the aortic valve and three 4D-flow datasets covering the heart were acquired, including single-slab, pre- and post-contrast, and non-contrast MOTS. Each 4D-flow dataset was interpreted blindly for ≥moderate valve disease and compared to TEE. Flow visualization through each valve was scored (0 to 4), and aortic-valve flow measured on each 4D-flow dataset and compared to 2D-PC reference. RESULTS: Diagnostic quality visualization was achieved with the pre- and post-contrast 4D-flow acquisitions in 25% and 100% valves, respectively (scores 0.9 ± 1.1 and 3.8 ± 0.5), and in 58% with the non-contrast MOTS (1.6 ± 1.1). Accuracy of detection of valve disease was 75%, 92% and 82%, respectively. Aortic flow measurements were possible in 53%, 95% and in 89% patients, respectively. The correlation between pre-contrast single-slab measurements and 2D-PC reference was weak (r = 0.21), but improved with both contrast enhancement (r = 0.71) and with MOTS (r = 0.67). CONCLUSIONS: Although non-contrast MOTS 4D-flow improves valve function visualization and diagnostic accuracy, a significant proportion of valves cannot be accurately assessed. However, aortic flow measurements using non-contrast MOTS is feasible and reaches similar accuracy to that of contrast-enhanced 4D-flow.

Prevalence of mitral annular disjunction in patients with mitral valve prolapse and severe regurgitation.

Mitral annular disjunction (MAD) is routinely diagnosed by cardiac imaging, mostly by echocardiography, and shown to be a risk factor for ventricular arrhythmias. While MAD is associated with mitral valve (MV) prolapse (MVP), it is unknown which patients with MAD are at higher risk and which additional imaging features may help identify them. The value of cardiac computed tomography (CCT) for the diagnosis of MAD is unknown. Accordingly, we aimed to: (1) develop a standardized CCT approach to identify MAD in patients with MVP and severe mitral regurgitation (MR); (2) determine its prevalence and identify features that are associated with MAD in this population. We retrospectively studied 90 patients (age 63 ± 12 years) with MVP and severe MR, who had pre-operative CCT (256-slice scanner) of sufficient quality for analysis. The presence and degree of MAD was assessed by rotating the view plane around the MV center to visualize disjunction along the annulus. Additionally, detailed measurements of MV apparatus and left heart chambers were performed. Univariate logistic regression analysis was performed to determine which parameters were associated with MAD. MAD was identified in 18 patients (20%), and it was typically located adjacent to a prolapsed or flail mitral leaflet scallop. Of these patients, 75% had maximum MAD distance > 4.8 mm and 90% > 3.8 mm. Female gender was most strongly associated with MAD (p = 0.04). Additionally, smaller end-diastolic mitral annulus area (p = 0.045) and longer posterior leaflet (p = 0.03) were associated with greater MAD. No association was seen between MAD and left ventricular size and function, left atrial size, and papillary muscle geometry. CCT can be used to readily detect MAD, by taking advantage of the 3D nature of this modality. A significant portion of MVP patients referred for mitral valve repair have MAD. The presence of MAD is associated with female gender, smaller annulus size and greater posterior leaflet length.

Cardiac Sarcoidosis: A Picture May Be Worth a Thousand Words, But Do We Need More?

See Article Okasha et al.

Machine Learning-Based Three-Dimensional Echocardiographic Quantification of Right Ventricular Size and Function: Validation Against Cardiac Magnetic Resonance.

BACKGROUND: Three-dimensional echocardiography (3DE) allows accurate and reproducible measurements of right ventricular (RV) size and function. However, widespread implementation of 3DE in routine clinical practice is limited because the existing software packages are relatively time-consuming and skill demanding. The aim of this study was to test the accuracy and reproducibility of new machine learning- (ML-) based, fully automated software for three-dimensional quantification of RV size and function. METHODS: Fifty-six unselected patients with a wide range of RV size and function and image quality, referred for clinically indicated cardiac magnetic resonance (CMR) imaging, underwent a transthoracic 3DE exam on the same day. End-systolic and end-diastolic RV volumes (ESV, EDV) and ejection fraction (EF) were measured using the ML-based algorithm and compared with CMR reference values using Bland-Altman and linear regression analyses. RESULTS: RV function quantification by echocardiography was feasible in all patients. The automatic approach was accurate in 32% patients with analysis time of 15 ± 1 seconds and 100% reproducible. Endocardial contour editing was necessary after the automated postprocessing in the remaining 68% patients, prolonging analysis time to 114 ± 71 seconds. With these minimal adjustments, RV volumes and EF measurements were accurate in comparison with CMR reference (biases: EDV, -25.6 ± 21.1 mL; ESV, -7.4 ± 16 mL; EF, -3.3% ± 5.2%) and showed excellent reproducibility reflected by coefficients of variation <7% and intraclass correlations ≥0.95 for all measurements. CONCLUSIONS: The new ML-based 3DE algorithm provided accurate and completely reproducible RV volume and EF measurements in one-third of unselected patients without any boundary editing. In the remaining patients, quick minimal editing resulted in reasonably accurate measurements with excellent reproducibility. This approach provides a promising solution for fast three-dimensional quantification of RV size and function.

Aortic Stenosis: Changing Disease Concepts.

Aortic stenosis (AS) occurs in almost 10% of adults over age 80 years with a mortality about 50% at 2 years unless outflow obstruction is relieved by aortic valve replacement (AVR). Development of AS is associated with anatomic, clinical and genetic risk factors including a bicuspid valve in 50%; clinical factors that include older age, hypertension, smoking, diabetes and elevated serum lipoprotein(a) [Lp(a)] levels; and genetic factors such as a polymorphism in the Lp(a) locus. Early stages of AS are characterized by focal areas of leaflet thickening and calcification. The rate of hemodynamic progression is variable but eventual severe AS is inevitable once even mild valve obstruction is present. There is no specific medical therapy to prevent leaflet calcification. Basic principles of medical therapy for asymptomatic AS are patient education, periodic echocardiographic and clinical monitoring, standard cardiac risk factor evaluation and modification and treatment of hypertension or other comorbid conditions. When severe AS is present, a careful evaluation for symptoms is needed, often with an exercise test to document symptom status and cardiac reserve. In symptomatic patients with severe AS, AVR improves survival and relieves symptoms. In asymptomatic patients with severe AS, AVR also is appropriate if ejection fraction is < 50%, disease progression is rapid or AS is very severe (aortic velocity > 5 m/s). The choice of surgical or transcatheter AVR depends on the estimated surgical risk plus other factors such as frailty, other organ system disease and procedural specific impediments.

Outcomes of asymptomatic adults with combined aortic stenosis and regurgitation.

BACKGROUND: The outcomes of patients with mixed aortic valve disease (MAVD; concurrent aortic stenosis [AS] and aortic regurgitation [AR]) and its optimum management are undefined. The aim of this study was to evaluate the natural history of MAVD. METHODS: Between 2000 and 2005, 524 asymptomatic adults (mean age, 66 ± 14 years; 306 men) were identified who had mixed AS and AR, who did not undergo early intervention with surgery. The severity of AS and AR was defined using American Society of Echocardiography guideline criteria. Patients were followed over 5.5 ± 3.1 years. RESULTS: Aortic valve replacement (AVR) was performed in 349 patients (67%), and 88 (17%) died. Angina, dyspnea, or syncope developed in 292 patients (84%) before AVR; baseline left ventricular mass and the severity of AS and AR were independent predictors of progression to AVR in the overall group. Survival was associated with younger age (hazard ratio, 1.08; P < .001) and valve replacement (hazard ratio, 0.61; P = .02). Most patients with MAVD in the moderate category progressed to severe AS or AR by the time of surgery (n = 51 [27%]); symptoms were the main indication in 22 patients. In this group, AVR was associated with age, left ventricular function, valve area, and the change in peak gradient over follow-up. In patients with moderate MAVD, coronary artery disease was present in 38 (20%) at baseline and developed in 21 (21%) during follow-up but was not associated with surgery. The average time to an event (AVR or death) in patients with MAVD was 4 years. CONCLUSIONS: Careful surveillance of patients with MAVD is warranted, bearing in mind the composite severity of both AS and AR and their combined hemodynamic effects.