Carbohydrate antigen 125: a useful marker of congestion, fibrosis, and prognosis in heart failure with preserved ejection fraction.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is a disease associated with high morbidity and mortality, for which it is difficult to identify patients with the poorest prognosis in routine clinical practice. Carbohydrate antigen 125 (CA 125) has been shown to be a potential marker of congestion and prognosis in HF. We sought to better characterize HFpEF patients with high CA 125 levels by using a multimodal approach. METHODS AND RESULTS: We prospectively enrolled 139 HFpEF patients (78 ± 8 years; 60% females) and 25 controls matched for age and sex (77 ± 5 years; 60% females). They underwent two-dimensional echocardiography, cardiac magnetic resonance with late gadolinium enhancement [including extracellular volume (ECV) measurement], and serum measurements of CA 125 level. The primary endpoint of the study was a composite of all-cause mortality or first HF hospitalization. The prognostic impact of CA 125 was determined using Cox proportional hazard models. Median CA 125 levels were significantly higher in HFpEF patients compared with controls [CA 125: 23.5 (14.5-44.7) vs. 14.6 (10.3-21.0) U/mL, P = 0.004]. CA 125 levels were positively correlated with a congestion marker [N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, Pearson's r = 0.37, P < 0.001] and markers of cardiac fibrosis estimated by both ECV (Pearson's r = 0.26, P = 0.003) and fibroblast growth factor 23 levels (Pearson's r = 0.50, P < 0.001). Over a median follow-up of 49 (22-64) months, 97 HFpEF patients reached the composite endpoint. Even after adjustment for the Meta-Analysis Global Group in Chronic risk score, a CA 125 level ≥35 U/mL was still a significant predictor of the composite endpoint [hazard ratio (HR): 1.58 (1.04-2.41), P = 0.032] and more particularly of HF hospitalization [HR: 1.81 (1.13-2.92), P = 0.014]. In contrast, NT-proBNP levels were not an independent predictor. CONCLUSIONS: CA 125 levels were significantly higher in HFpEF patients compared with controls matched for age and sex and were associated with markers of congestion and cardiac fibrosis. CA 125 levels were a strong and independent predictor of HF hospitalization in HFpEF patients. These data suggest a potential value of CA 125 as a biomarker for staging and risk prediction in HFpEF.

Diabetic phenotype and prognosis of patients with heart failure and preserved ejection fraction in a real life cohort.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, with several underlying etiologic and pathophysiologic factors. The presence of diabetes might identify an important phenotype, with implications for therapeutic strategies. While diabetes is associated with worse prognosis in HFpEF, the prognostic impact of glycemic control is yet unknown. Hence, we investigated phenotypic differences between diabetic and non-diabetic HFpEF patients (pts), and the prognostic impact of glycated hemoglobin (HbA1C). METHODS: We prospectively enrolled 183 pts with HFpEF (78 ± 9 years, 38% men), including 70 (38%) diabetics (type 2 diabetes only). They underwent 2D echocardiography (n = 183), cardiac magnetic resonance (CMR) (n = 150), and were followed for a combined outcome of all-cause mortality and first HF hospitalization. The prognostic impact of diabetes and glycemic control were determined with Cox proportional hazard models, and illustrated by adjusted Kaplan Meier curves. RESULTS: Diabetic HFpEF pts were younger (76 ± 9 vs 80 ± 8 years, p = 0.002), more obese (BMI 31 ± 6 vs 27 ± 6 kg/m2, p = 0.001) and suffered more frequently from sleep apnea (18% vs 7%, p = 0.032). Atrial fibrillation, however, was more frequent in non-diabetic pts (69% vs 53%, p = 0.028). Although no echocardiographic difference could be detected, CMR analysis revealed a trend towards higher LV mass (66 ± 18 vs 71 ± 14 g/m2, p = 0.07) and higher levels of fibrosis (53% vs 36% of patients had ECV by T1 mapping > 33%, p = 0.05) in diabetic patients. Over 25 ± 12 months, 111 HFpEF pts (63%) reached the combined outcome (24 deaths and 87 HF hospitalizations). Diabetes was a significant predictor of mortality and hospitalization for heart failure (HR: 1.72 [1.1-2.6], p = 0.011, adjusted for age, BMI, NYHA class and renal function). In diabetic patients, lower levels of glycated hemoglobin (HbA1C < 7%) were associated with worse prognosis (HR: 2.07 [1.1-4.0], p = 0.028 adjusted for age, BMI, hemoglobin and NT-proBNP levels). CONCLUSION: Our study highlights phenotypic features characterizing diabetic patients with HFpEF. Notably, they are younger and more obese than their non-diabetic counterpart, but suffer less from atrial fibrillation. Although diabetes is a predictor of poor outcome in HFpEF, intensive glycemic control (HbA1C < 7%) in diabetic patients is associated with worse prognosis.

Structural and Functional Correlates of Gradient-Area Patterns in Severe Aortic Stenosis and Normal Ejection Fraction.

OBJECTIVES: The authors sought to characterize the functional and structural myocardial phenotypes of patients with moderate-to-severe aortic stenosis (AS) and to determine whether severe paradoxical low-gradient AS (LG-AS) is specifically associated with left ventricular (LV) remodeling and fibrosis. BACKGROUND: Recently, it was suggested that severe paradoxical LG-AS is a more advanced form of AS, with greater reduction of longitudinal deformation, adverse LV remodeling, and more interstitial fibrosis. METHODS: The study population includes 147 patients with moderate-to-severe AS and a normal LV ejection fraction, and 75 normal control subjects. They prospectively underwent 2-dimensional speckle-tracking echocardiography and cardiac magnetic resonance to evaluate myocardial deformation, LV remodeling, and age- and sex-adjusted extravascular volume fraction (ECV, %). Among AS patients, 18 had moderate AS, 74 had severe high-gradient AS (HG-AS), and 55 had severe paradoxical LG-AS. RESULTS: Reduced longitudinal and circumferential deformation was observed in 21% and 6% of the AS patients, respectively. Multivariate analyses identified increased ECV (ß = 1.99; p = 0.001) and the absence of normal LV geometry (ß = -1.37; p = 0.007) and as independent predictors of reduced longitudinal deformation. Increased ECV was an independent predictor of reduced circumferential deformation (ß = 2.19; p = 0.001). Over a median follow-up of 29 months, reduced longitudinal deformation (hazard ratio: 0.82; p = 0.023) and higher transvalvular gradients (hazard ratio: 1.05; p < 0.001) increased the risk of death or need for aortic valve replacement. LV hypertrophy was more frequently observed among patients with severe HG-AS (65%) than among the other AS patients (14%; p < 0.001). On average, ECV was within normal limits and did not differ among gradient-area subgroups. When present, increased ECV was associated with reduced longitudinal deformation. CONCLUSIONS: This study's data show that patients with severe paradoxical LG-AS less frequently display reduced longitudinal deformation, LV hypertrophy, or myocardial fibrosis than patients with HG-AS. Also, interstitial fibrosis only occurs when reduced longitudinal deformation and severe HG-AS are present together. Finally, this study suggests that reduced longitudinal deformation and higher transvalvular gradients adversely affect patients' outcomes.

Heart failure with preserved ejection fraction in Belgium: characteristics and outcome of a real-life cohort.

BACKGROUND: Due to aging of the population and the increase of cardiovascular risk factors, heart failure and preserved ejection fraction (HFpEF) is a rising health issue. Few data exist on the phenotype of HFpEF patients in Belgium and on their prognosis. OBJECTIVES: We describe clinical characteristics and outcomes of Belgian HFpEF patients. METHODS: We prospectively enrolled 183 HFpEF patients. They underwent clinical examination, comprehensive biological analysis and echocardiography, and were followed for a combined outcome of all-cause mortality and first HF hospitalisation. RESULTS: Belgian patients with HFpEF were old (78 ± 8 years), predominantly females (62%) with multiple comorbidities. Ninety-five per cent were hypertensive, 38% diabetic and 69% overweight. History of atrial fibrillation was present in 63% of population, chronic kidney disease in 60% and anaemia in 58%. Over 30 ± 9 months, 55 (31%) patients died, 87 (49%) were hospitalised and 111 (63%) reached the combined outcome. In multivariate Cox analysis, low body mass index (BMI), NYHA class III and IV, diabetes, poor renal function and loop diuretic intake were independent predictors of the combined outcome (p < .05). BMI and renal function were also independent predictors of mortality, as were low haemoglobin, high E/e' and poor right ventricular function. CONCLUSION: Belgian patients with HFpEF are elderly patients with a high burden of comorbidities. Their prognosis is poor with high rates of hospitalisation and mortality. Although obesity is a risk factor for developing HFpEF, low BMI is the strongest independent predictor of mortality in those patients.

Fibroblast growth factor 23: a biomarker of fibrosis and prognosis in heart failure with preserved ejection fraction.

AIMS: Besides regulating calcium-phosphate metabolism, fibroblast growth factor 23 (FGF-23) has been associated with incident heart failure (HF) and left ventricular hypertrophy. However, data about FGF-23 in HF and preserved ejection fraction (HFpEF) remain limited. The aim of this study was to assess the association between FGF-23 levels, clinical and imaging characteristics, particularly diffuse myocardial fibrosis, and prognosis in HFpEF patients. METHODS AND RESULTS: We prospectively included 143 consecutive HFpEF patients (78 ± 8 years, 61% female patients) and 31 controls of similar age and gender (75 ± 6 years, 61% female patients). All subjects underwent a complete two-dimensional echocardiography and cardiac magnetic resonance with extracellular volume (ECV) assessment by T1 mapping. FGF-23 was measured at baseline. Among the patients, differences in clinical and imaging characteristics across tertiles of FGF-23 levels were analysed with a trend test across the ordered groups. Patients were followed over time for a primary endpoint of all-cause mortality and first HF hospitalization and a secondary endpoint of all-cause mortality. Median FGF-23 was significantly higher in HFpEF patients compared with controls of similar age and gender (247 [115; 548] RU/mL vs. 61 [51; 68] RU/mL, P < 0.001). Among HFpEF patients, higher FGF-23 levels were associated with female sex, higher incidence of atrial fibrillation, lower haemoglobin, worse renal function, and higher N terminal pro brain natriuretic peptide levels (P for trend < 0.05 for all). Regarding imaging characteristics, patients with higher FGF-23 levels had greater left atrial volumes, worse right ventricular systolic function, and more fibrosis estimated by ECV (P for trend < 0.05 for all). FGF-23 was moderately correlated with ECV (r = 0.46, P < 0.001). Over a mean follow-up of 30 ± 8 months, 43 patients (31%) died and 69 patients (49%) were hospitalized for HF. A total of 87 patients (62%) reached the primary composite endpoint of all-cause mortality and/or first HF hospitalization. In multivariate Cox regression analysis for the primary endpoint, FGF-23 (HR: 3.44 [2.01; 5.90], P < 0.001) and E wave velocities (HR: 1.01 [1.00; 1.02], P = 0.034) were independent predictors of the primary composite endpoint. In multivariate Cox regression analysis for the secondary endpoint, ferritin (HR: 1.02 [1.01; 1.03], P < 0.001), FGF-23 (HR: 2.85 [1.26; 6.44], P = 0.012), and ECV (HR: 1.26 [1.03; 1.23], P = 0.008) were independent predictors of all-cause mortality. CONCLUSIONS: Fibroblast growth factor 23 (FGF-23) levels were significantly higher in HFpEF patients compared with controls of similar age and gender. FGF-23 was correlated with fibrosis evaluated by ECV. High levels of FGF-23 were significantly associated with signs of disease severity such as worse renal function, larger left atrial volumes, and right ventricular dysfunction. Moreover, FGF-23 was a strong predictor of poor outcome (mortality and first HF hospitalization).

Right Ventricular Global Longitudinal Strain and Outcomes in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Right ventricular (RV) strain has emerged as an accurate tool for RV function assessment and is a powerful predictor of survival in patients with heart failure with reduced ejection fraction. However, its prognostic impact in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. The aim of this study was to compare the prognostic value of RV global longitudinal strain (RVGLS) by two-dimensional speckle-tracking echocardiographic (STE) imaging in patients with HFpEF against conventional RV function parameters. METHODS: Patients with HFpEF were prospectively recruited, and 149 of 183 (81%) with analyzable STE RVGLS images constituted the final study population (mean age, 78 ± 9 years; 61% women), compared with 28 control subjects of similar age and sex. All control subjects and 120 patients also underwent cardiac magnetic resonance imaging. Patients were followed up for a primary end point of all-cause mortality and first heart failure hospitalization, and Cox regression analysis was performed. RESULTS: Mean STE RVGLS was significantly altered in patients with HFpEF compared with control subjects (-21.7 ± 4.9% vs -25.9 ± 4.2%, P < .001). STE RVGLS correlated well with RV ejection fraction by cardiac magnetic resonance (r = -0.617, P < .001). Twenty-eight patients with HFpEF (19%) had impaired STE RVGLS (>-17.5%). During a mean follow-up period of 30 ± 9 months, 91 patients with HFpEF (62%) reached the primary end point. A baseline model was created using independent predictors of the primary end point: New York Heart Association functional class III or IV, hemoglobin level, estimated glomerular filtration rate, and the presence of moderate or severe tricuspid regurgitation. Impaired STE RVGLS provided significant additional prognostic value over this model (χ2 to enter = 7.85, P = .005). Impaired tricuspid annular plane systolic excursion and fractional area change, however, did not. CONCLUSIONS: In patients with HFpEF, impaired RVGLS has strong prognostic value. STE RVGLS should be considered for systematic evaluation of RV function to identify patients at high risk for adverse events.

Relative Contribution of Afterload and Interstitial Fibrosis to Myocardial Function in Severe Aortic Stenosis.

OBJECTIVES: The present study aimed at investigating the respective contribution of afterload and myocardial fibrosis to pre- and post-operative left ventricular (LV) function by using stress-strain relationships. BACKGROUND: Separating the effect of myocardial dysfunction and afterload on pump performance has important implications for the prognosis and management of patients with severe aortic stenosis (AS). METHODS: A total of 101 patients with isolated severe AS (57% men; mean age 71 years) and 75 healthy control subjects underwent resting 2-dimensional and speckle-tracking echocardiography to measure global circumferential strain (GCS) and global longitudinal strain (GLS), as well as end-systolic wall stress (ESWS). Normal stress-strain relationships were constructed using control subjects' data and fitted to linear regression. End-systolic stress-strain indexes (the number of SDs from the mean regression line) were used as an afterload-independent index of myocardial function and compared with myocardial fibrosis, measured on transmural myocardial biopsies harvested at the time of surgery. RESULTS: GCS and GLS were afterload-dependent in both control subjects and patients. The GLS-ESWS relationship of patients was shifted downward compared with control subjects. Patients with reduced pre-operative end-systolic stress-strain indexes exhibited larger degrees of interstitial myocardial fibrosis than patients without (3.8 ± 2.9% vs. 8.3 ± 6.3%, p < 0.001; and 4.9 ± 4.4% vs. 9.5 ± 6.4%; p < 0.001, for GLS and GCS, respectively). By multivariate analysis, pre-operative end-systolic stress-strain indexes were the only predictors of post-operative longitudinal and circumferential end-systolic stress-strain indexes (ß = 0.49 and ß = 0.60, respectively; p < 0.001). CONCLUSIONS: Myocardial strains are afterload-dependent. In patients with severe AS, pre-operative stress-strain indexes allow identification of patients with increased myocardial fibrosis and predict the extent of functional recovery after aortic valve replacement.

FGF23: Clinical usefulness and analytical evolution.

Fibroblast Growth Factor 23 (FGF23) is a key hormone for the regulation of phosphate homeostasis. Over the past decades, FGF23 was the subject of intense research in the fields of nephrology and the cardiology. It presents a remarkable correlation with well-established biomarkers of cardiovascular disorders in both chronic kidney disease (CKD) and heart failure (HF) patients. The interest of FGF23 lies in its early-onset in the primary course of CKD as well as in the incremental prognosis information it conveys in both CKD and HF. Different types of assays of FGF-23 testing exist, those targeting the intact form (iFGF23), the other one detecting terminal fragments (cFGF23). The issue is still pending which assay suits best for clinical use. Recently, the implementation of this biomarker on multianalyzer platforms, on which other markers of phospho-calcic balance are set up, allows a rapid turn-around-time and a potential financial gain. However, despite the good analytical performances of the automated methods, there is a poor harmonization between assays. The introduction of an international certified reference material should standardize the measurement and improve the harmonization of results from different laboratories. A deeper understanding of physio-pathological mechanisms and processing of FGF-23 should reinforce its clinical indications and might also identify new therapeutic targets for the treatment of CKD and HF.

Additional Prognostic Value of 2D Right Ventricular Speckle-Tracking Strain for Prediction of Survival in Heart Failure and Reduced Ejection Fraction: A Comparative Study With Cardiac Magnetic Resonance.

OBJECTIVES: This study sought to compare the prognostic value of 2-dimensional (2D) right ventricular (RV) speckle tracking (STE) against cardiac magnetic resonance (CMR) RV ejection fraction (EF) and feature tracking (FT) and conventional echocardiographic parameters on overall and cardiovascular (CV) survival in patients with heart failure with reduced EF (HFrEF). BACKGROUND: Prior works showed that RV systolic function predicts prognosis in HFrEF. 2D RVSTE had recently been proposed as new echocardiographic method to evaluate RV dysfunction. METHODS: A total of 266 patients with HFrEF (mean LVEF 23 ± 7%, 60 ± 14 years of age; 29% women) underwent RV function assessment using CMR and 2D echocardiography and were followed for a primary endpoint of overall death and secondary endpoint of CV death. RESULTS: Average CMR-RVEF was 42 ± 15%, average STE RV global longitudinal strain (STE-RVGLS) was -18.0 ± 4.9%, and average CMR-FT-RVGLS was -11.8 ± 4.3%. After a median follow-up of 4.7 years, 102 patients died, 84 of a CV cause. RVEF, FT-RVGLS, tricuspid annulus plane systolic excursion (TAPSE), fractional area change (FAC), and STE-RVGLS were significant univariate predictors of overall and cardiac death. In multivariate Cox regression, age, ischemic etiology, diabetes, New York Heart Association functional class III to IV, and beta-blocker treatment were independent clinical predictors of overall mortality. CMR-RVEF (chi-square to enter = 3.9; p < 0.05), FT-RVGLS (chi-square to enter 3.7; p = 0.05), FAC (chi-square to enter 6.2; p = 0.02), and TAPSE (chi-square to enter = 4.1; p = 0.04) provided additional prognostic value over these baseline parameters, but the additional predictive value of STE-RVGLS (chi-square to enter = 10.8; p < 0.001) was significantly (p < 0.05) higher than the other tests. Additional hazard ratio to predict overall mortality was 2.5 (95% confidence interval [CI]: 1.6 to 3.9) for STE-RVGLS <-19%, 2.15 (95% CI: 1.34 to 3.43) for TAPSE >15 mm, 1.6 (95% CI: 1.02 to 2.49) for FAC >39%, 1.93 (95% CI: 1.25 to 2.99) for RVEF >41%, and 1.87 (95% CI: 1.10 to 3.19) for CMR-FT-RVGLS <-15%. CONCLUSIONS: 2D RVGLS provides strong additional prognostic value to predict overall and CV mortality in HFrEF, with higher predictive value than CMR-RVEF, CMR-FT-RVGLS, TAPSE, or FAC. This supports use of STE-RVGLS to identify higher-risk HFrEF patients.

Associations and prognostic significance of diffuse myocardial fibrosis by cardiovascular magnetic resonance in heart failure with preserved ejection fraction.

BACKGROUND: Increased myocardial fibrosis may play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology. The study aim was to evaluate the presence, associations, and prognostic significance of diffuse fibrosis in HFpEF patients compared to age- and sex-matched controls. METHODS: We prospectively included 118 consecutive HFpEF patients. Diffuse myocardial fibrosis was estimated by extracellular volume (ECV) quantified by cardiovascular magnetic resonance with the modified Look-Locker inversion recovery sequence. We determined an ECV age- and sex-adjusted cutoff value (33%) in 26 controls. RESULTS: Mean ECV was significantly higher in HFpEF patients versus healthy controls (32.9 ± 4.8% vs 28.2 ± 2.4%, P <  0.001). Multivariate logistic regression showed that body mass index (BMI) (odds ratio (OR) =0.92 [0.86-0.98], P = 0.011), diabetes (OR = 2.62 [1.11-6.18], P = 0.028), and transmitral peak E wave velocity (OR = 1.02 [1.00-1.03], P = 0.022) were significantly associated with abnormal ECV value. During a median follow-up of 11 ± 6 months, the primary outcome (all-cause mortality or first heart failure hospitalization) occurred in 38 patients. In multivariate Cox regression analysis, diabetes (hazard ratio (HR) =1.98 [1.04; 3.76], P = 0.038) and hemoglobin level (HR = 0.81 [0.67; 0.98], P = 0.028) were significant predictors of composite outcome. The ECV ability to improve this model added significant prognostic information. We then developed a risk score including diabetes, hemoglobin and ECV > 33% demonstrating significant prediction of risk and validated this score in a validation cohort of 53 patients. Kaplan-Meier curves showed a significant difference according to tertiles of the probability score (P <  0.001). CONCLUSION: Among HFpEF patients, high ECV, likely reflecting abnormal diffuse myocardial fibrosis, was associated with a higher rate of all-cause death and first HF hospitalization in short term follow up. TRIAL REGISTRATION: Characterization of Heart Failure With Preserved Ejection Fraction. TRIAL REGISTRATION NUMBER: NCT03197350 . Date of registration: 20/06/2017. This trial was retrospectively registered.

Improvements of Myocardial Deformation Assessment by Three-Dimensional Speckle-Tracking versus Two-Dimensional Speckle-Tracking Revealed by Cardiac Magnetic Resonance Tagging.

BACKGROUND: In prior work, the authors demonstrated that two-dimensional speckle-tracking (2DST) correlated well but systematically overestimated global longitudinal strain (LS) and circumferential strain (CS) compared with two-dimensional cardiac magnetic resonance tagging (2DTagg) and had poor agreement on a segmental basis. Because three-dimensional speckle-tracking (3DST) has recently emerged as a new, more comprehensive evaluation of myocardial deformation, this study was undertaken to evaluate whether it would compare more favorably with 2DTagg than 2DST. METHODS: In a prospective two-center trial, 119 subjects (29 healthy volunteers, 63 patients with left ventricular dysfunction, and 27 patients with left ventricular hypertrophy) underwent 2DST, 3DST, and 2DTagg. Global, regional (basal, mid, and apical), and segmental (18 and 16 segments per patient) LS and CS by 2DST and 3DST were compared with 2DTagg using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. Test-retest reproducibility of 3DST and 2DST was compared in 48 other patients. RESULTS: Both global LS and CS by 3DST agreed better with 2DTagg (ICC = 0.89 and ICC = 0.83, P < .001 for both; bias = 0.5 ± 2.3% and 0.2 ± 3%) than 2DST (ICC = 0.65 and ICC = 0.55, P < .001 for both; bias = -5.5 ± 2.5% and -7 ± 5.3%). Unlike 2DST, 3DST did not overestimate deformation at the regional and particularly the apical levels and at the segmental level had lower bias (LS, 0.8 ± 2.8% vs -5.3 ± 2.4%; CS, -0.01 ± 2.8% vs -7 ± 2.8%, respectively) but similar agreement with 2DST (LS: ICC = 0.58 ± 0.16 vs 0.56 ± 0.12; CS: ICC = 0.58 ± 0.12 vs 0.51 ± 0.1) with 2DTagg. Finally, 3DST had similar global LS, but better global CS test-retest variability than 2DST. CONCLUSIONS: Using 2DTagg as reference, 3DST had better agreement and less bias for global and regional LS and CS. At the segmental level, 3DST demonstrated comparable agreement but lower bias versus 2DTagg compared with 2DST. Also, test-retest variability for global CS by 3DST was better than by 2DST. This suggests that 3DST is superior to 2DST for analysis of global and regional myocardial deformation, but further refinement is needed for both 3DST and 2DST at the segmental level.

Head-to-Head Comparison of Global and Regional Two-Dimensional Speckle Tracking Strain Versus Cardiac Magnetic Resonance Tagging in a Multicenter Validation Study.

BACKGROUND: Despite widespread use to characterize and refine prognosis, validation data of two-dimensional (2D) speckle tracking (2DST) echocardiography myocardial strain measurement remain scarce. METHODS AND RESULTS: Global and regional subendocardial peak-systolic Lagrangian longitudinal (LS) and circumferential strain (CS) by 2DST and 2D-tagged (2DTagg) cardiac magnetic resonance imaging were compared against sonomicrometry in a dynamic heart phantom and among each other in 136 patients included prospectively at 2 centers. The ability of regional LS and CS 2DST and 2DTagg to identify late gadolinium enhancement was compared using receiver operating characteristics curves. In vitro, both LS-2DST and 2DTagg highly agreed with sonomicrometry (intraclass correlation coefficient [ICC], 0.89 and ICC, 0.90, both P<0.001 with -3±2.8% and 0.34±4.35% bias, respectively). In patients, both global LS and global CS 2DST agreed well with 2DTagg (ICC, 0.89 and ICC, 0.80; P<0.001); however, they provided systematically greater values (relative bias of -37±27% and -25±37% for global LS and global CS, respectively). On regional basis, however, ICC (from 0.17 to 0.81) and relative bias (from -9 to -98%) between 2DST and 2DTagg varied strongly among segments. Ability to discriminate infarcted versus noninfarcted segments by late gadolinium enhancement was similarly good for regional LS 2DTagg and 2DST (area under the curve, 0.66 versus 0.59; P=0.08), while it was lower for CS 2DST than 2DTagg (area under the curve, 0.61 versus 0.75; P<0.001). CONCLUSIONS: The high accuracy against sonomicrometry and good agreement of global LS and global CS by 2DST and 2DTagg confirm the overall validity of 2DST strain measurement. Yet, higher intertechnique segmental variability and lower ability for detecting infarct suggest that 2DST strain estimates may be less performant on regional than on global basis.

Age and sex corrected normal reference values of T1, T2 T2* and ECV in healthy subjects at 3T CMR.

BACKGROUND: Myocardial T1, T2 and T2* imaging techniques become increasingly used in clinical practice. While normal values for T1, T2 and T2* times are well established for 1.5 Tesla (T) cardiovascular magnetic resonance (CMR), data for 3T remain scarce. Therefore we sought to determine normal reference values relative to gender and age and day to day reproducibility for native T1, T2, T2* mapping and extracellular volume (ECV) at 3T in healthy subjects. METHODS: After careful exclusion of cardiovascular abnormality, 75 healthy subjects aged 20 to 90 years old (mean 56 ± 19 years, 47% women) underwent left-ventricular T1 (3-(3)-3-(3)-5 MOLLI)), T2 (8 echo- spin echo-imaging) and T2 * (8 echo gradient echo imaging) mapping at 3T CMR (Philips Ingenia 3T and computation of extracellular volume after administration of 0.2 mmol/kg Gadovist). Inter- and intra-observer reproducibility was estimated by intraclass correlation coefficient (ICC). Day to day reproducibility was assessed in 10 other volunteers. RESULTS: Mean myocardial T1 at 3T was 1122 ± 57 ms, T2 52 ± 6 ms, T2* 24 ± 5 ms and ECV 26.6 ± 3.2%. T1 (1139 ± 37 vs 1109 ± 73 ms, p < 0.05) and ECV (28 ± 3 vs 25 ± 2%, p < 0.001), but not T2 (53 ± 8 vs 51 ± 4, p = NS) were significantly greater in age matched women than in men. T1 (r = 0.40, p < 0.001) and ECV (r = 0.37, p = 0.001) increased, while T2 decreased significantly (r = -0.25, p < 0.05) with increasing age. T2* was not influenced by either gender or age. Intra and inter-observer reproducibility was high (ICC ranging between 0.81-0.99), and day to day coefficient of variation was low (6.2% for T1, 7% for T2, 11% for T2* and 11.5% for ECV). CONCLUSIONS: We provide normal myocardial T2, T2*,T1 and ECV reference values for 3T CMR which are significantly different from those reported at 1.5 Tesla CMR. Myocardial T1 and ECV values are gender and age dependent. Measurement had high inter and intra-observer reproducibility and good day-to-day reproducibility.