Mitral regurgitation assessment by cardiovascular magnetic resonance imaging during continuous in-scanner exercise: a feasibility study.

PURPOSE: Exercise imaging using current modalities can be challenging. This was patient focused study to establish the feasibility and reproducibility of exercise-cardiovascular magnetic resonance imaging (EX-CMR) acquired during continuous in-scanner exercise in asymptomatic patients with primary mitral regurgitation (MR). METHODS: This was a prospective, feasibility study. Biventricular volumes/function, aortic flow volume, MR volume (MR-Rvol) and regurgitant fraction (MR-RF) were assessed at rest and during low- (Low-EX) and moderate-intensity exercise (Mod-EX) in asymptomatic patients with primary MR. RESULTS: Twenty-five patients completed EX-CMR without complications. Whilst there were no significant changes in the left ventricular (LV) volumes, there was a significant increase in the LVEF (rest 63 ± 5% vs. Mod-EX 68 ± 6%;p = 0.01). There was a significant reduction in the right ventricular (RV) end-systolic volume (rest 68 ml(60-75) vs. Mod-EX 46 ml(39-59);p < 0.001) and a significant increase in the RV ejection fraction (rest 55 ± 5% vs. Mod-EX 65 ± 8%;p < 0.001). Whilst overall, there were no significant group changes in the MR-Rvol and MR-RF, individual responses were variable, with MR-Rvol increasing by ≥ 15 ml in 4(16%) patients and decreasing by ≥ 15 ml in 9(36%) of patients. The intra- and inter-observer reproducibility of LV volumes and aortic flow measurements were excellent, including at Mod-EX. CONCLUSION: EX-CMR is feasible and reproducible in patients with primary MR. During exercise, there is an increase in the LV and RV ejection fraction, reduction in the RV end-systolic volume and a variable response of MR-Rvol and MR-RF. Understanding the individual variability in MR-Rvol and MR-RF during physiological exercise may be clinically important.

4D Flow Cardiac MR in Primary Mitral Regurgitation.

BACKGROUND: Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established. PURPOSE: To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation. STUDY TYPE: Prospective, single-center, two arm, interventional vs. nonintervention observational study. POPULATION: Forty-four patients (male N = 30; median age 68 [59-75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing "watchful waiting" (WW). FIELD STRENGTH/SEQUENCE: 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots). ASSESSMENT: Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi). STATISTICAL TESTS: Included Student t-test/Mann-Whitney test/Fisher's exact test, Bland-Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05. RESULTS: While Bland-Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement -36 mL to 65 mL), than between 4DF-MR and TTE (bias -8; limits of agreement -106 mL to 90 mL) and PMRI and TTE (bias -23; limits of agreement -105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89). DATA CONCLUSION: This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

Systematic analysis of prophages carried by Porphyromonas gingivalis.

To systematically investigate the prophages carrying in Porphyromonas gingivalis (P. gingivalis) strains, analyze potential antibiotic resistance genes (ARGs) and virulence genes in these prophages. We collected 90 whole genome sequences of P. gingivalis from NCBI and utilized the Prophage Hunter online software to predict prophages; Comprehensive antibiotic research database (CARD) and virulence factors database (VFDB) were adopted to analyze the ARGs and virulence factors (VFs) carried by the prophages. Sixty-nine prophages were identified among 24/90 P. gingivalis strains, including 17 active prophages (18.9%) and 52 ambiguous prophages (57.8%). The proportion of prophages carried by each P. gingivalis genome ranged from 0.5% to 6.7%. A total of 188 antibiotic resistance genes belonging to 25 phenotypes and 46 different families with six mechanisms of antibiotic resistance were identified in the 17 active prophages. Three active prophages encoded 4 virulence genes belonging to type III and type VI secretion systems. The potential hosts of these virulence genes included Escherichia coli, Shigella sonnei, Salmonella typhi, and Klebsiella pneumoniae. In conclusion, 26.7% P. gingivalis strains carry prophages, while the proportion of prophage genes in the P. gingivalis genome is relatively low. In addition, approximately 39.7% of the P. gingivalis prophage genes have ARGs identified, mainly against streptogramin, peptides, and aminoglycosides. Only a few prophages carry virulence genes. Prophages may play an important role in the acquisition, dissemination of antibiotic resistance genes, and pathogenicity evolution in P. gingivalis.

Cardiac reverse remodeling in primary mitral regurgitation: mitral valve replacement vs. mitral valve repair.

BACKGROUND: When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation. METHODS: 83 patients with ≥ moderate-severe MR on TTE were prospectively recruited. 6-min walk tests (6MWT) and CMR imaging including cine imaging, aortic/pulmonary through-plane phase contrast imaging, T1 maps and late-gadolinium-enhanced (LGE) imaging were performed at baseline and 6 months after mitral surgery or watchful waiting (control group). RESULTS: 72 patients completed follow-up (Controls = 20, MVr = 30 and MVR = 22). Surgical groups demonstrated comparable baseline cardiac indices and co-morbidities. At 6-months, MVr and MVR groups demonstrated comparable improvements in 6MWT distances (+ 57 ± 54 m vs + 64 ± 76 m respectively, p = 1), reduced indexed left ventricular end-diastolic volumes (LVEDVi; - 29 ± 21 ml/m2 vs - 37 ± 22 ml/m2 respectively, p = 0.584) and left atrial volumes (- 23 ± 30 ml/m2 and - 39 ± 26 ml/m2 respectively, p = 0.545). At 6-months, compared with controls, right ventricular ejection fraction was poorer post-MVr (47 ± 6.1% vs 53 ± 8.0% respectively, p = 0.01) compared to post-MVR (50 ± 5.7% vs 53 ± 8.0% respectively, p = 0.698). MVR resulted in lower residual MR-regurgitant fraction (RF) than MVr (12 ± 8.0% vs 21 ± 11% respectively, p = 0.022). Baseline and follow-up indices of diffuse and focal myocardial fibrosis (Native T1 relaxation times, extra-cellular volume and quantified LGE respectively) were comparable between groups. Stepwise multiple linear regression of indexed variables in the surgical groups demonstrated baseline indexed mitral regurgitant volume as the sole multivariate predictor of left ventricular (LV) end-diastolic reverse remodelling, baseline LVEDVi as the most significant independent multivariate predictor of follow-up LVEDVi, baseline indexed LV end-systolic volume as the sole multivariate predictor of follow-up LV ejection fraction and undergoing MVR (vs MVr) as the most significant (p < 0.001) baseline multivariate predictor of lower residual MR. CONCLUSION: In primary MR, MVR with chordal preservation may offer comparable cardiac reverse remodeling and functional benefits at 6-months when compared to MVr. Larger, multicenter CMR studies are required, which if the findings are confirmed could impact future surgical practice.

Detrimental Immediate- and Medium-Term Clinical Effects of Right Ventricular Pacing in Patients With Myocardial Fibrosis.

BACKGROUND: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. METHODS: We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing. RESULTS: The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m2; P<0.01) and LV ejection fraction (-5.7±3.4% versus -3.2±2.6%; P=0.02); (2) medium-term RV pacing in patients with fibrosis, compared with those without, was associated with greater changes in LV end-systolic volume index (8.0±10.4 versus -0.6±7.3 mL/m2; P=0.008) and LV ejection fraction (-12.3±7.9% versus -6.7±6.2%; P=0.012); (3) patients with fibrosis did not experience an improvement in quality of life, biomarkers, or functional class after pacemaker implantation; (4) after 6 months of RV pacing, 10 of 50 (20%) patients developed LV ejection fraction <35% and were eligible for upgrade to cardiac resynchronization according to current guidelines. All 10 patients had fibrosis on their preimplant baseline scan and were identified by >1.1 g of fibrosis with 90% sensitivity and 70% specificity. CONCLUSIONS: Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation.

Acute Microstructural Changes after ST-Segment Elevation Myocardial Infarction Assessed with Diffusion Tensor Imaging.

Background Cardiac diffusion tensor imaging (cDTI) allows for in vivo characterization of myocardial microstructure. In cDTI, mean diffusivity and fractional anisotropy (FA)-markers of magnitude and anisotropy of diffusion of water molecules-are known to change after myocardial infarction. However, little is known about regional changes in helix angle (HA) and secondary eigenvector angle (E2A), which reflects orientations of laminar sheetlets, and their association with long-term recovery of left ventricular ejection fraction (LVEF). Purpose To assess serial changes in cDTI biomarkers in participants following ST-segment elevation myocardial infarction (STEMI) and to determine their associations with long-term left ventricular remodeling. Materials and Methods In this prospective study, 30 participants underwent cardiac MRI (3 T) after STEMI at 5 days and 3 months after reperfusion (National Institute of Health Research study no. 33963 and Research Ethics no. REC17/YH/0062). Spin-echo cDTI with second-order motion-compensation (approximate duration, 13 minutes; three sections; 18 noncollinear diffusion-weighted scans with b values of 100 sec/mm2 [three acquisitions], 200 sec/mm2 [three acquisitions], and 500 sec/mm2 [12 acquisitions]), functional images, and late gadolinium enhancement images were obtained. Multiple regression analysis was used to assess associations between acute cDTI parameters and 3-month LVEF. Results Acutely infarcted myocardium had reduced FA, E2A, and myocytes with right-handed orientation (RHM) on HA maps compared with remote myocardium (mean remote FA = 0.36 ± 0.02 [standard deviation], mean infarcted FA = 0.25 ± 0.03, P < .001; mean remote E2A = 55° ± 9, mean infarcted E2A = 49° ± 10, P < .001; mean remote RHM = 16% ± 6, mean infarcted RHM = 9% ± 5, P < .001). All three parameters (FA, E2A, and RHM) correlated with 3-month LVEF (r = 0.68, r = 0.59, and r = 0.53, respectively), with acute FA being independently predictive of 3-month LVEF (standardized ß = 0.56, P = .008) after multivariable analysis adjusting for factors, including acute LVEF and infarct size. Conclusion After ST-segment elevation myocardial infarction, diffusion becomes more isotropic in acutely infarcted myocardium as reflected by decreased fractional anisotropy. Reductions in secondary eigenvector angle suggest that the myocardial sheetlets are unable to adopt their usual steep orientations in systole, whereas reductions in myocytes with right-handed orientation on helix angle maps are likely reflective of a loss of organization among subendocardial myocytes. Correlations between these parameters and 3-month left ventricular ejection fraction highlight the potential clinical use of cardiac diffusion tensor imaging after myocardial infarction in predicting long-term remodeling. © RSNA, 2021 Online supplemental material is available for this article.

Exercise cardiovascular magnetic resonance: feasibility and development of biventricular function and great vessel flow assessment, during continuous exercise accelerated by Compressed SENSE: preliminary results in healthy volunteers.

PURPOSE: Exercise cardiovascular magnetic resonance (Ex-CMR) typically requires complex post-processing or transient exercise cessation, decreasing clinical utility. We aimed to demonstrate the feasibility of assessing biventricular volumes and great vessel flow during continuous in-scanner Ex-CMR, using vendor provided Compressed SENSE (C-SENSE) sequences and commercial analysis software (Cvi42). METHODS: 12 healthy volunteers (8-male, age: 35 ± 9 years) underwent continuous supine cycle ergometer (Lode-BV) Ex-CMR (1.5T Philips, Ingenia). Free-breathing, respiratory navigated C-SENSE short-axis cines and aortic/pulmonary phase contrast magnetic resonance (PCMR) sequences were validated against clinical sequences at rest and used during low and moderate intensity Ex-CMR. Optimal PCMR C-SENSE acceleration, C-SENSE-3 (CS3) vs C-SENSE-6 (CS6), was further investigated by image quality scoring. Intra-and inter-operator reproducibility of biventricular and flow indices was performed. RESULTS: All CS3 PCMR image quality scores were superior (p < 0.05) to CS6 sequences, except pulmonary PCMR at moderate exercise. Resting stroke volumes from clinical PCMR sequences correlated stronger with CS3 than CS6 sequences. Resting biventricular volumes from CS3 and clinical sequences correlated very strongly (r > 0.93). During Ex-CMR, biventricular end-diastolic volumes (EDV) remained unchanged, except right-ventricular EDV decreasing at moderate exercise. Biventricular ejection-fractions increased at each stage. Exercise biventricular cine and PCMR stroke volumes correlated very strongly (r ≥ 0.9), demonstrating internal validity. Intra-observer reproducibility was excellent, co-efficient of variance (COV) < 10%. Inter-observer reproducibility was excellent, except for resting right-ventricular, and exercise bi-ventricular end-systolic volumes which were good (COV 10-20%). CONCLUSION: Biventricular function, aortic and pulmonary flow assessment during continuous Ex-CMR using CS3 sequences is feasible, reproducible and analysable using commercially available software.

Feasibility and reproducibility of a cardiovascular magnetic resonance free-breathing, multi-shot, navigated image acquisition technique for ventricular volume quantification during continuous exercise.

BACKGROUND: Cardiovascular magnetic resonance (CMR) image acquisition techniques during exercise typically requires either transient cessation of exercise or complex post-processing, potentially compromising clinical utility. We evaluated the feasibility and reproducibility of a navigated image acquisition method for ventricular volumes assessment during continuous physical exercise. METHODS: Ten healthy volunteers underwent supine cycle ergometer (Lode) exercise CMR on two separate occasions using a free-breathing, multi-shot, navigated, balanced steady-state free precession cine pulse sequence. Images were acquired at 3-stages, baseline and during steady-state exercise at 55% and 75% maximal heart rate (HRmax), based on a prior supine cardiopulmonary exercise test. Intra-and inter-observer variability and inter-scan reproducibility were derived. Clinical feasibility was tested in a separate cohort of patients with severe mitral regurgitation (n=6). RESULTS: End-diastolic volume (EDV) of both LV and RV decreased during exercise at 55% and 75% HRmax, although a reduction in RVEDV index was only observed at 75% HRmax. Ejection fractions (EF) for both ventricles were significantly higher at 75% HRmax compared to their respective baselines (LVEF 68%±3% vs. 58%±5%, P=0.001; RVEF 66%±4% vs. 58%±7%, P=0.02). Intra-observer and inter-observer reproducibility of LV parameters was excellent at all 3-stages. Although measurements of RVESV were more variable during exercise, the reproducibility of both RVEF and RV cardiac index was excellent (CV <10%). Inter-scan LV and RV ejection fraction were highly reproducible at all 3 stages, although inter-scan reproducibility of indexed RVESV was only moderate. The protocol was well tolerated by all patients. CONCLUSIONS: Exercise CMR using a free-breathing, multi-shot, navigated cine imaging method allows simultaneous assessment of left and right ventricular volumes during continuous exercise. Intra- and inter-observer reproducibility were excellent. Inter-scan LV and RV ejection fraction were also highly reproducible.

[Effect of serum IgA/C3 and glomerular C3 staining on clinical prognosis in patients with IgA nephropathy].

Objective: To investigate the effects of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio and glomerular C3 staining on clinical prognosis in patients with IgA nephropathy. Methods: From January 1st, 2007 to December 30th, 2016, a total of 519 patients with biopsy-proven IgA nephropathy (IgAN) in West China Hospital were retrospectively reviewed and divided into four groups based on serum IgA/C3 ratio and glomerular C3 staining: group A with IgA/C3 ratio ≥3.046 (median) and glomerular C3 staining ≥2 (n=151), group B with IgA/C3 ratio ≥3.046 and glomerular C3 staining<2 (n=109), group C with IgA/C3 ratio<3.046 and glomerular C3 staining ≥2 (n=119), and group D with IgA/C3 ratio<3.046 and glomerular C3 staining<2 (n=140). Clinical data, pathological characteristics and the primary endpoint [≥ 50% decline in estimated glomerular filtration rate (eGFR) and/or end-stage renal disease (ESRD)]were collected. Clinical prognosis and relevant risk factors were analyzed among the four groups. Results: Totally, 519 patients (298 males, 57.4%) with an average age of (33.6±10.9) years were recruited and followed up for (43.4±21.6) months. The rate of complete remission plus partial remission was 74.2% (112/151), 74.3% (81/109), 72.3% (86/119), 81.4% (114/140) in group A, B, C, D, respectively. Meanwhile, The rate of ESRD was highest in group A (14.6% vs 9.2%, 13.4%, 8.6%). Renal outcome (patients reached the endpoint) was worse in group A and C compared with group B and D (15.2%, 16.0 vs 8.3%, 7.9%). Moreover, 80-month renal survival rate was significantly worse in group A (84.8%) than that in group B and D (91.7% and 92.1%), but no statistical significant difference was found between group A and B (P(AB)=0.085; P(AD)=0.028). There was no significant difference of renal survival rate between group A and C (84.8% vs 84.0%, P=0.896). Multivariate Cox model showed that hypertension (HR=2.753, 95%CI: 1.452-5.217, P=0.002), serum creatinine (HR=1.011, 95%CI: 1.008-1.014, P<0.001), and tubular atrophy/interstitial fibrosis (T1/T2) (HR=6.595, 95%CI: 3.107-13.999, P<0.001) were independent predictors of poor renal survival. Conclusion: Serum IgA/C3 ratio and glomerular C3 staining are predictors of renal clinical prognosis in patients with IgA nephropathy.

Regression of Left Ventricular Mass in Athletes Undergoing Complete Detraining Is Mediated by Decrease in Intracellular but Not Extracellular Compartments.

BACKGROUND: Athletic cardiac remodeling can occasionally be difficult to differentiate from pathological hypertrophy. Detraining is a commonly used diagnostic test to identify physiological hypertrophy, which can be diagnosed if hypertrophy regresses. We aimed to establish whether athletic cardiac remodeling assessed by cardiovascular magnetic resonance is mediated by changes in intracellular or extracellular compartments and whether this occurs by 1 or 3 months of detraining. METHODS: Twenty-eight athletes about to embark on a period of forced detraining due to incidental limb bone fracture underwent clinical assessment, ECG, and contrast-enhanced cardiovascular magnetic resonance within a week of their injury and then 1 month and 3 months later. RESULTS: After 1 month of detraining, there was reduction in left ventricular (LV) mass (130±28 to 121±25 g; P<0.0001), increase in native T1 (1225±30 to 1239±30 ms; P=0.02), and extracellular volume fraction (24.5±2.3% to 26.0±2.6%; P=0.0007) with no further changes by 3 months. The decrease in LV mass was mediated by a decrease in intracellular compartment volume (94±22 to 85±19 mL; P<0.0001) with no significant change in the extracellular compartment volume. High LV mass index, low native T1, and low extracellular volume fraction at baseline were all predictive of regression in LV mass in the first month. CONCLUSIONS: Regression of athletic LV hypertrophy can be detected after just 1 month of complete detraining and is mediated by a decrease in the intracellular myocardial compartment with no change in the extracellular compartment. Further studies are needed in athletes with overt and pathological hypertrophy to establish whether native T1 and extracellular volume fraction may complement electrocardiography, echocardiography, cardiopulmonary exercise testing, and genetic testing in predicting the outcome of detraining.

[Epidemiological survey of mental disorders in the rural left behind elderly aged 60 years and older in Gansu].

Objective: To investigate the prevalence, demographic characteristics and social life function of mental disorders in the rural left behind elderly aged 60 years and older in Gansu. Methods: Between November 2017 and June 2018, a multi-stage stratified cluster sampling method was used to randomly select the rural left behind elderly aged 60 years and older in Gansu, and totally 6 000 elderly were enrolled. By using the extended general health questionnaire (GHQ-12) and the American Handbook for Diagnosis and Statistics of Mental Disorders (DSM-Ⅳ) Axis Ⅰ Disorders Formal Clinical Examination Patient Edition, all the included subjects were screened and diagnosed. Functional status was assessed by the Global Assessment Function scale (GAF). Statistical analysis of the prevalence of various mental illnesses, as well as the differences in the prevalence of different gender, marital status and age groups was performed. Results: Totally, 6 000 subjects completed the survey. The adjusted current prevalence of any mental disorder was 20.11% (95%CI 17.70%-22.85%). The six most prevalent specific disorders were major depressive disorder (9.20%), pain disorder (2.71%), mood disorder due to the body condition (2.08%), generalized anxiety disorder (1.99%), anxiety disorder not otherwise specified (1.15%) and dysthymic disorder (0.84%). The lifetime prevalence of mental disorders was 20.54% (95%CI 18.40%-23.39%). The overall current prevalence of mental disorders was higher in women (242.89‰) than in men (119.55‰), and the unmarried (248.37‰) was higher than those married (187.53‰). There was no significant difference in the prevalence of mental disorders among different age groups (P>0.05). The GAF score of mental disorders was 56±11, and 71.82% was moderate to severe functional impairment. Conclusions: The prevalence of mental disorders is high in rural left-behind population aged 60 years and over in Gansu Province. Major depression is a condition that deserves special attention.

Clinical evaluation of two dark blood methods of late gadolinium quantification of ischemic scar.

BACKGROUND: Late gadolinium enhancement (LGE) imaging was validated for diagnosis and quantification of myocardial infarction (MI). Despite good contrast between scar and normal myocardium, contrast between blood pool and myocardial scar can be limited. Dark blood LGE sequences attempt to overcome this issue. PURPOSE: To evaluate T1 rho (T1 ρ)-prepared dark blood sequence and compare to blood nulled (BN) phase sensitive inversion recovery (PSIR) and standard myocardium nulled (MN) PSIR for detection and quantification of scar. STUDY TYPE: Prospective. POPULATION: Thirty patients with prior MI. FIELD STRENGTH/SEQUENCE: Patients underwent identical 1.5 T MRI protocols. Following routine LGE imaging, a slice with scar, remote myocardium, and blood pool was selected. PSIR LGE was repeated with inversion time set to MN, to BN, and T1 ρ FIDDLE (flow-independent dark-blood delayed enhancement) in random order. ASSESSMENT: Three observers. Qualitative assessment of confidence scores in scar detection and degree of transmurality. Quantitative assessment of myocardial scar mass (grams), and contrast-to-noise ratio (CNR) measurements between scar, blood pool, and myocardium. STATISTICAL TESTS: Repeated-measures analysis of variance (ANOVA) with Bonferroni correction, coefficient of variation, and the Cohen κ statistic. RESULTS: CNRscar-blood was significantly increased for both BN (27.1 ± 10.4) and T1 ρ (30.2 ± 15.1) compared with MN (15.3 ± 8.4 P < 0.001 for both sequences). There was no significant difference in CNRscar-myo between BN (55.9 ± 17.3) and MN (51.1 ± 17.8 P = 0.512); both had significantly higher CNRscar-myo compared with the T1 ρ (42.6 ± 16.9 P = 0.007 and P = 0.014, respectively). No significant difference in scar size between LGE methods: MN (2.28 ± 1.58 g) BN (2.16 ± 1.57 g) and T1 ρ (2.29 ± 2.5 g). Confidence scores were significantly higher for BN (3.87 ± 0.346) compared with MN (3.1 ± 0.76 P < 0.001) and T1 ρ (3.20 ± 0.71 P < 0.001). DATA CONCLUSION: PSIR with inversion time (TI) set for blood nulling and the T1 ρ LGE sequence demonstrated significantly higher scar to blood CNR compared with routine MN. PSIR with TI set for blood nulling demonstrated significantly higher reader confidence scores compared with routine MN and T1 ρ LGE, suggesting routine adoption of a BN PSIR approach might be appropriate for LGE imaging. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:146-152.

Feasibility study of a single breath-hold, 3D mDIXON pulse sequence for late gadolinium enhancement imaging of ischemic scar.

BACKGROUND: Late gadolinium enhancement (LGE) imaging is well validated for the diagnosis and quantification of myocardial infarction (MI). 2D LGE imaging involves multiple breath-holds for acquisition of short-axis slices to cover the left ventricle (LV). 3D LGE methods cover the LV in a single breath-hold; however, breath-hold duration is typically long with images susceptible to motion artifacts. PURPOSE/HYPOTHESIS: To assess a single breath-hold 3D mDIXON LGE pulse sequence for image quality and quantitation of MI. STUDY TYPE: Prospective. POPULATION: Ninety- two patients with prior MI. FIELD STRENGTH/SEQUENCE: 1.5T cardiac MRI protocol using both conventional 2D phase sensitive inversion recovery and 3D mDIXON LGE imaging 10 minutes following contrast administration in random order to avoid bias. ASSESSMENT: Data were analyzed qualitatively for image quality (three observers). Quantitative assessment of myocardial scar mass (full-width half-maximum), scar transmurality, and contrast-to-noise ratio measurements were performed. Time for 2D and 3D LGE imaging was recorded. STATISTICAL TESTS: Paired Student's t-test, Wilcoxon rank test, Cohen κ statistic, Pearson correlation, linear regression, and Bland-Altman analysis. RESULTS: Image quality scores were comparable between 3D and 2D LGE (1.4 ± 0.6 vs. 1.3 ± 0.5; P = 0.162). 3D LGE was associated with greater scar tissue mass (3D: 18.9 ± 17.5 g vs. 2D: 17.8 ± 16.2 g P = 0.03), although this difference was less pronounced when scar tissue was expressed as %LV mass (3D: 13.4 ± 9.9% vs. 2D: 12.7 ± 9.5% P = 0.07). For 3D vs. 2D scar mass there was a strong and significant positive correlation; Bland-Altman analysis showed mean mass bias of 1.1 g (95% confidence interval [CI]: -5.7 to 7.9). Segmental level agreement of scar transmurality between 3D and 2D LGE at the clinical viability threshold of 50% transmurality was excellent (κ = 0.870). 3D image acquisition (15.6 ± 1.4 sec) was just 5% of time required for 2D images (311.6 ± 43.2 sec) P < 0.0001. DATA CONCLUSION: Single breath-hold 3D mDIXON LGE imaging allows quantitative assessment of MI mass and transmurality, with comparable image quality, in vastly shorter overall acquisition time compared with standard 2D LGE imaging. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1437-1445.

Left ventricular thrombus formation in myocardial infarction is associated with altered left ventricular blood flow energetics.

Aims: The main aim of this study was to characterize changes in the left ventricular (LV) blood flow kinetic energy (KE) using four-dimensional (4D) flow cardiovascular magnetic resonance imaging (CMR) in patients with myocardial infarction (MI) with/without LV thrombus (LVT). Methods and results: This is a prospective cohort study of 108 subjects [controls = 40, MI patients without LVT (LVT- = 36), and MI patients with LVT (LVT+ = 32)]. All underwent CMR including whole-heart 4D flow. LV blood flow KE wall calculated using the formula: KE=12 ρblood . Vvoxel . v2, where ρ = density, V = volume, v = velocity, and was indexed to LV end-diastolic volume. Patient with MI had significantly lower LV KE components than controls (P < 0.05). LVT+ and LVT- patients had comparable infarct size and apical regional wall motion score (P > 0.05). The relative drop in A-wave KE from mid-ventricle to apex and the proportion of in-plane KE were higher in patients with LVT+ compared with LVT- (87 ± 9% vs. 78 ± 14%, P = 0.02; 40 ± 5% vs. 36 ± 7%, P = 0.04, respectively). The time difference of peak E-wave KE demonstrated a significant rise between the two groups (LVT-: 38 ± 38 ms vs. LVT+: 62 ± 56 ms, P = 0.04). In logistic-regression, the relative drop in A-wave KE (beta = 11.5, P = 0.002) demonstrated the strongest association with LVT. Conclusion: Patients with MI have reduced global LV flow KE. Additionally, MI patients with LVT have significantly reduced and delayed wash-in of the LV. The relative drop of distal intra-ventricular A-wave KE, which represents the distal late-diastolic wash-in of the LV, is most strongly associated with the presence of LVT.

CMR quantitation of change in mitral regurgitation following transcatheter aortic valve replacement (TAVR): impact on left ventricular reverse remodeling and outcome.

Current echocardiographic data reporting the impact of concomitant mitral regurgitation (MR) on outcome in patients who undergo transcatheter aortic valve replacement (TAVR) are conflicting. Using cardiovascular magnetic resonance (CMR) imaging, this study aimed to assess the impact of MR severity on cardiac reverse remodeling and patient outcome. 85 patients undergoing TAVR with CMR pre- and 6 m post-TAVR were evaluated. The CMR protocol included cines for left (LV) and right ventricular (RV) volumes, flow assessment, and myocardial scar assessment by late gadolinium enhancement (LGE). Patients were dichotomised according to CMR severity of MR fraction at baseline ('non-significant' vs 'significant') and followed up for a median duration of 3 years. Forty-two (49%) patients had 'significant MR' at baseline; they had similar LV and RV size and function compared to the 'non-significant MR' group but had greater LV mass at baseline. In those with significant MR at baseline, 77% (n = 32) had a reduction in MR post-TAVR, moving them into the 'non-significant' category at 6-months, with an overall reduction in MR fraction from 34 to 17% (p < 0.001). Improvement in MR was not associated with more favourable cardiac reverse remodeling when compared with the 'non-improvers'. Significant MR at baseline was not associated with increased mortality at follow-up. Significant MR is common in patients undergoing TAVR and improves in the majority post-procedure. Improvement in MR was not associated with more favourable LV reverse remodeling and baseline MR severity was not associated with mortality.

Impact of Age and Diastolic Function on Novel, 4D flow CMR Biomarkers of Left Ventricular Blood Flow Kinetic Energy.

Two-dimensional (2D) methods of assessing mitral inflow velocities are pre-load dependent, limiting their reliability for evaluating diastolic function. Left ventricular (LV) blood flow kinetic energy (KE) derived from four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) may offer improvements. It remains unclear whether 4D LV blood flow KE parameters are associated with physiological factors, such as age when compared to 2D mitral inflow velocities. Fifty-three healthy volunteers underwent standard CMR, plus 4D flow acquisition. LV blood flow KE parameters demonstrated good reproducibility with mean coefficient of variation of 6 ± 2% and an accuracy of 99% with a precision of 97%. The LV blood flow KEiEDV E/A ratio demonstrated good association to the 2D mitral inflow E/A ratio (r = 0.77, P < 0.01), with both decreasing progressively with advancing age (P < 0.01). Furthermore, peak E-wave KEiEDV and A-wave KEiEDV displayed a stronger association to age than the corresponding 2D metrics, peak E-wave and A-wave velocity (r = -0.51 vs -0.17 and r = 0.65 vs 0.46). Peak E-wave KEiEDV decreases whilst peak A-wave KEiEDV increases with advancing age. This study presents values for various LV blood flow KE parameters in health, as well as demonstrating that they show stronger and independent correlations to age than standard diastolic metrics.

Left ventricular blood flow kinetic energy after myocardial infarction - insights from 4D flow cardiovascular magnetic resonance.

BACKGROUND: Myocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment. METHODS: Forty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEiEDV. In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups. RESULTS: LV KEiEDV was higher in controls than in MI patients (8.5 ± 3 µJ/ml versus 6.5 ± 3 µJ/ml, P = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEiEDV were lower in MI (P < 0.05). In logistic-regression analysis, systolic KEiEDV (Beta = - 0.24, P < 0.01) demonstrated the strongest association with the presence of MI. In multiple-regression analysis, infarct size was most strongly associated with in-plane KE (r = 0.5, Beta = 1.1, P < 0.01). In patients with preserved LV ejection fraction (EF), minimal and in-plane KEiEDV were reduced (P < 0.05) and time difference to peak E-wave KE propagation during diastole increased (P < 0.05) when compared to controls with normal EF. CONCLUSIONS: Reduction in LV systolic function results in reduction in systolic flow KEiEDV. Infarct size is independently associated with the proportion of in-plane LV KE. Degree of LV impairment is associated with TD of peak E-wave KE. In patient with preserved EF post MI, LV blood flow KE mapping demonstrated significant changes in the in-plane KE, the minimal KEiEDV and the TD. These three blood flow KE parameters may offer novel methods to identify and describe this patient population.