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.

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.

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study.

Importance: Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. Objective: To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. Design, Setting, and Participants: This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. Exposures: SAVR or TAVR. Main Outcomes and Measures: All-cause and cardiovascular (CV) mortality after aortic valve intervention. Results: Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). Conclusions and Relevance: In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. OBJECTIVES: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. METHODS: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. RESULTS: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. CONCLUSIONS: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

Myocardial Effects of Aldosterone Antagonism in Heart Failure With Preserved Ejection Fraction.

Background Spironolactone may have prognostic benefit in selected patients with heart failure with preserved ejection fraction. This study assessed the myocardial tissue effects of spironolactone in heart failure with preserved ejection fraction. Methods and Results A 1:1 randomized controlled study of 6 months of spironolactone versus control in heart failure with preserved ejection fraction. The primary outcome was change in myocardial extracellular volume fraction by cardiovascular magnetic resonance as a surrogate of diffuse fibrosis. Of 55 randomized patients, 40 (20 women; age, 75.2±5.9 years) completed follow-up (19 treatment, 21 control). A significant change in extracellular volume over the study period was not seen (treatment, 28.7±3.7% versus 27.7±3.4% [P=0.14]; controls, 27.6±3.4% versus 28.3±4.4% [P=0.14]); however, the rate of extracellular volume expansion was decreased by spironolactone (-1.0±2.4% versus 0.8±2.2%). Indexed left ventricular mass decreased with treatment (104.4±26.6 versus 94.0±20.6 g/m2; P=0.001) but not in controls (101.4±29.4 versus 104.0±32.8 g/m2; P=0.111). Extracellular mass decreased by 13.8% (15.1±4.8 versus 13.0±3.4 g/m2; P=0.003), and cellular mass decreased by 8.3% (37.6±10.0 versus 34.3±7.9 g/m2; P=0.001) with spironolactone, but was static in controls. Conclusions Spironolactone did not lead to significant change in extracellular volume. However, spironolactone did decrease rate of extracellular expansion, with a decrease in the mass of both cellular and extracellular myocardial compartments. These data point to the mechanism of action of spironolactone in heart failure with preserved ejection fraction, including a direct tissue effect with a reduction in rate of myocardial fibrosis.

Sex differences in left ventricular remodelling, myocardial fibrosis and mortality after aortic valve replacement.

OBJECTIVES: To investigate sex differences in left ventricular remodelling and outcome in patients undergoing surgical or transcatheter aortic valve replacement (SAVR/TAVR). METHODS: In this multicentre, observational, outcome study with imaging core-lab analysis, patients with severe aortic stenosis (AS) listed for intervention at one of six UK centres were prospectively recruited and underwent cardiovascular magnetic resonance imaging. The primary endpoint was all-cause mortality and secondary endpoint was cardiovascular mortality. RESULTS: 674 patients (425 men, 249 women, age 75±14 years) were included: 399 SAVR, 275 TAVR. Women were older, had higher surgical risk scores and underwent TAVR more frequently (53% vs 33.6%, p<0.001). More men had bicuspid aortic valves (BAVs) (26.7% vs 14.9%, p<0.001) and demonstrated more advanced remodelling than women. During a median follow-up of 3.6 years, 145 (21.5%) patients died, with no significant sex difference in all-cause mortality (23.3% vs 20.5%, p=0.114), but higher cardiovascular mortality in women (13.7% vs 8.5%, p=0.012). There were no significant sex-related differences in outcome in the SAVR or TAVR subgroups, or after excluding those with BAV. Factors independently associated with all-cause mortality were age, left ventricular ejection fraction (LVEF), BAV (better) and myocardial fibrosis detected with late gadolinium enhancement (LGE) in men, and age, LVEF and LGE in women. Age and LGE were independently associated with cardiovascular mortality in both sexes. CONCLUSIONS: Men demonstrate more advanced remodelling in response to a similar severity of AS. The higher cardiovascular mortality observed in women following AVR is accounted for by women having less BAV and higher risk scores resulting in more TAVR. LGE is associated with a worse prognosis in both sexes.

Silent cerebral infarction and cognitive function following TAVI: an observational two-centre UK comparison of the first-generation CoreValve and second-generation Lotus valve.

OBJECTIVE: To compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve (Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA). DESIGN: A prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up. SETTING: University hospitals of Leeds and Leicester, UK. PATIENTS: 66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015. MAIN OUTCOME MEASURES: Incidence of new cerebral microinfarction and objective decline in neurocognitive performance. RESULTS: All underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains. CONCLUSIONS: There was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.

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.

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.

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.

Myocardial Scar and Mortality in Severe Aortic Stenosis.

BACKGROUND: Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS: In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS: Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). CONCLUSIONS: In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.

Cardiovascular magnetic resonance assessment of 1st generation CoreValve and 2nd generation Lotus valves.

OBJECTIVES: We sought to compare using serial CMR, the quantity of AR and associated valve hemodynamics, following the first-generation CoreValve (Medtronic, Minneapolis, MN) and the second-generation Lotus valve (Boston Scientific, Natick, MA). BACKGROUND: Aortic regurgitation (AR) following Transcatheter Aortic Valve Replacement (TAVR) confers a worse prognosis and can be accurately quantified using cardiovascular magnetic resonance (CMR). Second generation valves have been specifically designed to reduce paravalvular AR and improve clinical outcomes. METHODS: Fifty-one patients (79.0 ± 7.7 years, 57% male) were recruited and imaged at three time points: immediately pre- and post-TAVR, and at 6 months. RESULTS: CMR-derived AR fraction immediately post-TAVR was greater in the CoreValve compared to Lotus group (11.7 ± 8.4 vs. 4.3 ± 3.4%, P = 0.001), as was the frequency of ≥moderate AR (9/24 (37.5%) versus 0/27, P < 0.001). However, at 6 months AR fraction had improved significantly in the CoreValve group such that the two valve designs were comparable (6.4 ± 5.0 vs 5.6 ± 5.3%, P = 0.623), with no patient in either group having ≥moderate AR. The residual peak pressure gradient immediately following TAVR was significantly lower with CoreValve compared to Lotus (14.1 ± 5.6 vs 25.4 ± 11.6 mmHg, P = 0.001), but again by 6 months the two valve designs were comparable (16.5 ± 9.4 vs 19.7 ± 10.5 mmHg, P = 0.332). There was no difference in the degree of LV reverse remodeling between the two valves at 6 months. CONCLUSION: Immediately post-TAVR, there was significantly less AR but a higher residual peak pressure gradient with the Lotus valve compared to CoreValve. However, at 6 months both devices had comparable valve hemodynamics and LV reverse remodeling.

Cardiovascular magnetic resonance measures of aortic stiffness in asymptomatic patients with type 2 diabetes: association with glycaemic control and clinical outcomes.

BACKGROUND: We aimed to investigate in patients with type 2 diabetes whether aortic stiffness is: (i) associated with glycaemic control, (ii) associated with adverse outcomes and (iii) can be reversed on treatment with RAAS inhibition. METHODS: Patients with type 2 diabetes (N = 94) and low vascular risk underwent assessment of cardiovascular risk and CMR assessment of ascending aortic distensibility (AAD), descending aortic distensibility (DAD) and aortic pulse wave velocity (PWV). Of these patients a subgroup with recent onset microalbuminuria (N = 25) were treated with renin-angiotensin-aldosterone system (RAAS) inhibition and imaging repeated after 1 year. All 94 patients were followed up for 2.4 years for major adverse cardiovascular disease (CVD) events including myocardial infarction detected on late gadolinium enhancement CMR. RESULTS: Ascending aortic distensibility, DAD and PWV all had a significant association with age and 24 h systolic blood pressure but only AAD had a significant association with glycaemic control, measured as HbA1c (Beta - 0.016, P = 0.04). The association between HbA1c and AAD persisted even after correction for age and hypertension. CVD events occurred in 19/94 patients. AAD, but not DAD or PWV, was associated with CVD events (hazard ratio 0.49, 95% confidence interval 0.25-0.95, P = 0.01). On treatment with RAAS inhibition, AAD, but not DAD or PWV, showed significant improvement from 1.51 ± 1.15 to 1.97 ± 1.07 10-3 mmHg-1, P = 0.007. CONCLUSIONS: Ascending aortic distensibility measured by CMR is independently associated with poor glycaemic control and adverse cardiovascular events. Furthermore it may be reversible on treatment with RAAS inhibition. AAD is a promising marker of cardiovascular risk in asymptomatic patients with type 2 diabetes and has potential use as a surrogate cardiovascular endpoint in studies of novel hypoglycaemic agents. Clinical trials registration https://clinicaltrials.gov/ct2/show/NCT01970319.

Quantitative deformation analysis differentiates ischaemic and non-ischaemic cardiomyopathy: sub-group analysis of the VINDICATE trial.

Aims: To test the hypothesis that patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) have different torsion and strain parameters, and compare to healthy, age-matched controls. VINDICATE investigated efficacy of high-dose vitamin D on patients with heart failure (HF) secondary to left ventricular (LV) systolic dysfunction of any aetiology. It is important to differentiate ICM and NICM as treatment and prognosis varies significantly. Cardiovascular magnetic resonance (CMR) reliably determines aetiology of HF and tissue tagging techniques are recognized as the reference standard measures of strain and torsion. Methods and results: Fifty three patients (31 ICM, 22 NICM) from VINDICATE and 25 controls underwent CMR at 3.0T, including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization. CMR data were analysed blinded, by quantitatively reporting circumferential strain and torsion from tagged images and global longitudinal strain from feature tracking. HF patients had larger ventricles indexed to body surface area, lower left ventricular ejection fraction (LVEF), LV torsion, twist, and strain parameters compared to controls. There were no significant differences between ICM and NICM in age, blood pressure, heart rhythm, or NYHA status. There was no significant difference in LV dimensions, EF, and strain parameters between ICM and NICM. NICM patients had significantly lower LV twist (6.0 ± 3.7° vs. 8.8 ± 4.3°, P = 0.023) and torsion (5.9 ± 3.5° vs. 8.8 ± 4.7°, P = 0.017) compared to ICM. Conclusion: Twist, torsion, and strain are reduced in HF patients compared to controls. Torsion and twist are significantly lower in patients with NICM compared to ICM, despite similar volumetric dimensions, circumferential and longitudinal strain parameters, and LVEF.

Extra-cellular expansion in the normal, non-infarcted myocardium is associated with worsening of regional myocardial function after acute myocardial infarction.

BACKGROUND: Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI). METHODS: Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h-72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre-/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT). RESULTS: From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, -1.78 ± 9%, -2.9 ± 10.9%, respectively; P < 0.001). Normal segments which demonstrated deterioration in wall thickening at follow-up showed significantly increased Δ ECV compared with normal segments with preserved wall thickening at follow up (1.82 ± 6.05% versus -0.10 ± 6.88%, P < 0.05). CONCLUSION: Following reperfused STEMI, normal myocardium demonstrates subtle expansion of the extracellular volume at 3-month follow up. Segmental ECV expansion of normal myocardium is associated with worsening of contractile function.

Diabetes Mellitus, Microalbuminuria, and Subclinical Cardiac Disease: Identification and Monitoring of Individuals at Risk of Heart Failure.

BACKGROUND: Patients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure. We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease. METHODS AND RESULTS: In a case-controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR >2.5 mg/mol in males and >3.5 mg/mol in females, ≥2 measurements, no previous renin-angiotensin-aldosterone therapy, 50 ACR-ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography. Thirty ACR+ve patients underwent further testing after 1-year treatment with renin-angiotensin-aldosterone blockade. Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P=0.0002) and in ACR+ve than ACR-ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P=0.004). ACR+ve patients also had lower E' measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P=0.04) and elevated high-sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L (P=0.05). Rate of silent myocardial ischemia or infarction were not influenced by ACR status. Renin-angiotensin-aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P=0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P=0.01) but no changes in diastolic function or high-sensitivity cardiac troponin T levels. CONCLUSIONS: Asymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high-sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin-angiotensin-aldosterone blockade. Increased risk in these patients may be mediated by subclinical changes in tissue structure and function. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01970319.

Acute Infarct Extracellular Volume Mapping to Quantify Myocardial Area at Risk and Chronic Infarct Size on Cardiovascular Magnetic Resonance Imaging.

BACKGROUND: Late gadolinium enhancement (LGE) imaging overestimates acute infarct size. The main aim of this study was to investigate whether acute extracellular volume (ECV) maps can reliably quantify myocardial area at risk (AAR) and final infarct size (IS). METHODS AND RESULTS: Fifty patients underwent cardiovascular magnetic resonance imaging acutely (24-72 hours) and at convalescence (3 months). The cardiovascular magnetic resonance protocol included cines, T2-weighted imaging, native T1 maps, 15-minute post-contrast T1 maps, and LGE. Optimal AAR and IS ECV thresholds were derived in a validation group of 10 cases (160 segments). Eight hundred segments (16 per patient) were analyzed to quantify AAR/IS by ECV maps (ECV thresholds for AAR is 33% and IS is 46%), T2-weighted imaging, T1 maps, and acute LGE. Follow-up LGE imaging was used as the reference standard for final IS and viability assessment. The AAR derived from ECV maps (threshold of >33) demonstrated good agreement with T2-weighted imaging-derived AAR (bias, 0.18; 95% confidence interval [CI], -1.6 to 1.3) and AAR derived from native T1 maps (bias=1; 95% CI, -0.37 to 2.4). ECV demonstrated the best linear correlation to final IS at a threshold of >46% (R=0.96; 95% CI, 0.92-0.98; P<0.0001). ECV maps demonstrated better agreement with final IS than acute IS on LGE (ECV maps: bias, 1.9; 95% CI, 0.4-3.4 versus LGE imaging: bias, 10; 95% CI, 7.7-12.4). On multiple variable regression analysis, the number of nonviable segments was independently associated with IS by ECV maps (ß=0.86; P<0.0001). CONCLUSIONS: ECV maps can reliably quantify AAR and final IS in reperfused acute myocardial infarction. Acute ECV maps were superior to acute LGE in terms of agreement with final IS. IS quantified by ECV maps are independently associated with viability at follow-up.

The utility of global longitudinal strain in the identification of prior myocardial infarction in patients with preserved left ventricular ejection fraction.

Prior myocardial infarction (MI) is associated with increased mortality and is prevalent in certain high risk patient groups. Electrocardiogram may be used in diagnosis, however, sensitivity is limited, thus non-invasive imaging techniques may improve diagnosis. We investigated whether global longitudinal strain (GLS) and longitudinal strain parameters are reduced in patients with prior MI but preserved left ventricular ejection fraction (LVEF). The study included 40 clinical patients with prior MI occurring >3 months previously (defined as subendocardial hyperenhancement on late Gadolinium enhancement imaging) with LVEF ≥ 55% and 40 controls matched for age and LVEF. GLS, global longitudinal strain rate (GLSR) and early diastolic longitudinal strain rate (GLSRe) were measured from cine imaging feature tracking analysis. Presence of wall motion abnormality (WMA) and minimum systolic wall thickening (SWT) were calculated from cine imaging. GLS was -17.3 ± 3.7% in prior MI versus -19.3 ± 1.9% in controls (p = 0.012). GLSR was -88.0 ± 33.7%/s in prior MI versus -103.3 ± 26.5%/s in controls (p = 0.005). GLSRe was 76.4 ± 28.4%/s in prior MI versus 95.5 ± 26.0%/s in controls (p = 0.001). GLS accurately identified prior MI [AUC 0.662 (95% CI 0.54-0.785) p = 0.012] whereas WMA [AUC 0.500 (95% CI 0.386-0.614) p = 1.0] and minimum SWT [AUC 0.609 (95% CI 0.483-0.735) p = 0.093] did not. GLS, GLSR and GLSRe are reduced in prior MI with preserved LVEF. Normal LVEF and lack of WMA cannot exclude prior MI. Prior MI should be considered when reduced GLS, GLSR or GLSRe are detected by non-invasive imaging.