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.

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.

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 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.

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.

Effect of cellular and extracellular pathology assessed by T1 mapping on regional contractile function in hypertrophic cardiomyopathy.

BACKGROUND: Regional contractile dysfunction is a frequent finding in hypertrophic cardiomyopathy (HCM). We aimed to investigate the contribution of different tissue characteristics in HCM to regional contractile dysfunction. METHODS: We prospectively recruited 50 patients with HCM who underwent cardiovascular magnetic resonance (CMR) studies at 3.0 T including cine imaging, T1 mapping and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association model segment thickness, native T1, extracellular volume (ECV), presence of LGE and regional strain (by feature tracking and tissue tagging) were assessed. The relationship of segmental function, hypertrophy and tissue characteristics were determined using a mixed effects model, with random intercept for each patient. RESULTS: Individually segment thickness, native T1, ECV and the presence of LGE all had significant associations with regional strain. The first multivariable model (segment thickness, LGE and ECV) demonstrated that all strain parameters were associated with segment thickness (P < 0.001 for all) but not ECV. LGE (Beta 2.603, P = 0.024) had a significant association with circumferential strain measured by tissue tagging. In a second multivariable model (segment thickness, LGE and native T1) all strain parameters were associated with both segment thickness (P < 0.001 for all) and native T1 (P < 0.001 for all) but not LGE. CONCLUSION: Impairment of contractile function in HCM is predominantly associated with the degree of hypertrophy and native T1 but not markers of extracellular fibrosis (ECV or LGE). These findings suggest that impairment of contractility in HCM is mediated by mechanisms other than extracellular expansion that include cellular changes in structure and function. The cellular mechanisms leading to increased native T1 and its prognostic significance remain to be established.

The impact of trans-catheter aortic valve replacement induced left-bundle branch block on cardiac reverse remodeling.

BACKGROUND: Left bundle branch block (LBBB) is common following trans-catheter aortic valve replacement (TAVR) and has been linked to increased mortality, although whether this is related to less favourable cardiac reverse remodeling is unclear. The aim of the study was to investigate the impact of TAVR induced LBBB on cardiac reverse remodeling. METHODS: 48 patients undergoing TAVR for severe aortic stenosis were evaluated. 24 patients with new LBBB (LBBB-T) following TAVR were matched with 24 patients with a narrow post-procedure QRS (nQRS). Patients underwent cardiovascular magnetic resonance (CMR) prior to and 6 m post-TAVR. Measured cardiac reverse remodeling parameters included left ventricular (LV) size, ejection fraction (LVEF) and global longitudinal strain (GLS). Inter- and intra-ventricular dyssynchrony were determined using time to peak radial strain derived from CMR Feature Tracking. RESULTS: In the LBBB-T group there was an increase in QRS duration from 96 ± 14 to 151 ± 12 ms (P < 0.001) leading to inter- and intra-ventricular dyssynchrony (inter: LBBB-T 130 ± 73 vs nQRS 23 ± 86 ms, p < 0.001; intra: LBBB-T 118 ± 103 vs. nQRS 13 ± 106 ms, p = 0.001). Change in indexed LV end-systolic volume (LVESVi), LVEF and GLS was significantly different between the two groups (LVESVi: nQRS -7.9 ± 14.0 vs. LBBB-T -0.6 ± 10.2 ml/m2, p = 0.02, LVEF: nQRS +4.6 ± 7.8 vs LBBB-T -2.1 ± 6.9%, p = 0.002; GLS: nQRS -2.1 ± 3.6 vs. LBBB-T +0.2 ± 3.2%, p = 0.024). There was a significant correlation between change in QRS and change in LVEF (r = -0.434, p = 0.002) and between change in QRS and change in GLS (r = 0.462, p = 0.001). Post-procedure QRS duration was an independent predictor of change in LVEF and GLS at 6 months. CONCLUSION: TAVR-induced LBBB is associated with less favourable cardiac reverse remodeling at medium term follow up. In view of this, every effort should be made to prevent TAVR-induced LBBB, especially as TAVR is now being extended to a younger, lower risk population.

Post-procedural myocardial infarction following surgical aortic valve replacement and transcatheter aortic valve implantation.

AIMS: Myocardial injury assessed using cardiac biomarker release is ubiquitous following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI), preventing accurate discrimination between focal myocardial infarction (MI) and global injury. Cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) imaging was used to compare rates of new MI following SAVR and TAVI. METHODS AND RESULTS: Identical CMR scans were obtained at baseline and six months post procedure in ninety-six patients undergoing SAVR (n=39) and TAVI (n=57). The rate of new MI was greater following SAVR than TAVI (SAVR, n=10 [26%] vs. TAVI, n=3 [5%], p=0.004). Infarct mass was similar between groups (SAVR 1.1±0.6 vs. TAVI 2.0±1.4 g, p=0.395). New MI did not impact on change in LV ejection fraction (SAVR:LGE[+]2.2±4.7 vs. LGE[-]0.9±8.0%, p=0.437, TAVI:LGE[+]-0.9±6.0 vs. LGE[-]2.0±7.8%, p=0.420). Thirty-four patients (60%) in the TAVI group had non-revascularised coronary artery disease (CAD) at the time of TAVI, of whom three (9%) had new MI. CONCLUSIONS: MI is an infrequent complication of TAVI but is more common following SAVR. Infarct size is small following both procedures. The low new infarct rate in TAVI, especially in the context of high rates of non-revascularised CAD, strengthens data from previous studies suggesting that coronary revascularisation pre-TAVI may be unnecessary.

The role of left ventricular deformation in the assessment of microvascular obstruction and intramyocardial haemorrhage.

In the setting of acute ST-elevation myocardial infarction (STEMI), it remains unclear which strain parameter most strongly correlates with microvascular obstruction (MVO) or intramyocardial haemorrhage (IMH). We aimed to investigate the association of MVO, IMH and convalescent left ventricular (LV) remodelling with strain parameters measured with cardiovascular magnetic resonance (CMR). Forty-three patients with reperfused STEMI and 10 age and gender matched healthy controls underwent CMR within 3-days and at 3-months following reperfused STEMI. Cine, T2-weighted, T2*-imaging and late gadolinium enhancement (LGE) imaging were performed. Infarct size, MVO and IMH were quantified. Peak global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS) and their strain rates were derived by feature tracking analysis of LV short-axis, 4-chamber and 2-chamber cines. All 43 patients and ten controls completed the baseline scan and 34 patients completed 3-month scans. In multivariate regression, GLS demonstrated the strongest association with MVO or IMH (beta = 0.53, p < 0.001). The optimal cut-off value for GLS was -13.7% for the detection of MVO or IMH (sensitivity 76% and specificity 77.8%). At follow up, 17% (n = 6) of patients had adverse LV remodeling (defined as an absolute increase of LV end-diastolic/end-systolic volumes >20%). Baseline GLS also demonstrated the strongest diagnostic performance in predicting adverse LV remodelling (AUC = 0.79; 95% CI 0.60-0.98; p = 0.03). Post-reperfused STEMI, baseline GLS was most closely associated with the presence of MVO or IMH. Baseline GLS was more strongly associated with adverse LV remodelling than other CMR parameters.

Relationship between cardiac deformation parameters measured by cardiovascular magnetic resonance and aerobic fitness in endurance athletes.

BACKGROUND: Athletic training leads to remodelling of both left and right ventricles with increased myocardial mass and cavity dilatation. Whether changes in cardiac strain parameters occur in response to training is less well established. In this study we investigated the relationship in trained athletes between cardiovascular magnetic resonance (CMR) derived strain parameters of cardiac function and fitness. METHODS: Thirty five endurance athletes and 35 age and sex matched controls underwent CMR at 3.0 T including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization (SPAMM). CMR data were analysed quantitatively reporting circumferential strain and torsion from tagged images and left and right ventricular longitudinal strain from feature tracking of cine images. Athletes performed a maximal ramp-incremental exercise test to determine the lactate threshold (LT) and maximal oxygen uptake (V̇O2max). RESULTS: LV circumferential strain at all levels, LV twist and torsion, LV late diastolic longitudinal strain rate, RV peak longitudinal strain and RV early and late diastolic longitudinal strain rate were all lower in athletes than controls. On multivariable linear regression only LV torsion (beta = -0.37, P = 0.03) had a significant association with LT. Only RV longitudinal late diastolic strain rate (beta = -0.35, P = 0.03) had a significant association with V̇O2max. CONCLUSIONS: This cohort of endurance athletes had lower LV circumferential strain, LV torsion and biventricular diastolic strain rates than controls. Increased LT, which is a major determinant of performance in endurance athletes, was associated with decreased LV torsion. Further work is needed to understand the mechanisms by which this occurs.

Acute Reverse Remodelling After Transcatheter Aortic Valve Implantation: A Link Between Myocardial Fibrosis and Left Ventricular Mass Regression.

BACKGROUND: Despite the wealth of data showing the positive effects on cardiac reverse remodelling in the long-term, the immediate effects of transcatheter aortic valve implantation (TAVI) on the left ventricle are yet to be comprehensively described using cardiovascular magnetic resonance imaging. Also, the link between myocardial fibrosis and acute left ventricular (LV) mass regression is unknown. METHODS: Fifty-seven patients with severe aortic stenosis awaiting TAVI underwent paired cardiovascular magnetic resonance scans before and early after the procedure (4 [interquartile range, 3-5] days). LV mass, volume, and function were measured. Late gadolinium enhancement (LGE) imaging was performed to assess for the presence of and pattern of myocardial fibrosis. RESULTS: After the procedure, 53 (95%) patients experienced an immediate (10.1 ± 7.1%) reduction in indexed LV mass (LVMi) from 76 ± 15.5 to 68.4 ± 14.7 g/m2 (P < 0.001). Those with no LGE experienced the greatest LVMi regression (13.9 ± 7.1%) compared with those with a midwall/focal fibrosis pattern LGE (7.4 ± 5.8%) and infarct pattern LGE (7.2 ± 7.0%; P = 0.005). There was no overall change in LV ejection fraction (LVEF; 55.1 ± 12.1% to 55.5 ± 10.9%; P = 0.867), however a significant improvement in LVEF was seen in those with abnormal (< 55%; n = 24; 42%) baseline LVEF (43.2 ± 8.9 to 46.7 ± 10.5%; P = 0.027). Baseline LVMi (P = 0.005) and myocardial fibrosis (P < 0.001) were strong independent predictors of early LVMi regression. CONCLUSIONS: LV reverse remodelling occurs immediately after TAVI, with significant LV mass regression in the total population and an improvement in LVEF in those with preexisting LV impairment. Those without myocardial fibrosis at baseline experience greater LV mass regression than those with fibrosis.

A Novel and Practical Screening Tool for the Detection of Silent Myocardial Infarction in Patients With Type 2 Diabetes.

OBJECTIVE: Silent myocardial infarction (MI) is a prevalent finding in patients with type 2 diabetes and is associated with significant mortality and morbidity. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) is the most validated technique for detection of silent MI, but is time-consuming, costly, and requires administration of intravenous contrast. We therefore planned to develop a simple and low-cost population screening tool to identify those at highest risk of silent MI validated against the CMR reference standard. METHODS: A total of 100 asymptomatic patients with type 2 diabetes underwent electrocardiogram (ECG), echocardiography, biomarker assessment, and CMR at 3.0T including assessment of left ventricular ejection fraction and LGE. Global longitudinal strain from two- and four-chamber cines was measured using feature tracking. RESULTS: A total of 17/100 patients with no history of cardiovascular disease had silent MI defined by LGE in an infarct pattern on CMR. Only four patients with silent MI had Q waves on ECG. Patients with silent MI were older (65 vs 60, P = .05), had lower E/A ratio (0.75 vs 0.89, P = .004), lower GLS (-15.2% vs -17.7%, P = .004), and higher amino-terminal pro brain natriuretic peptide (106 ng/L vs 52 ng/L, P = .003). A combined risk score derived from these four factors had an area under the receiver operating characteristic curve of 0.823 (0.734-0.892), P < .0001. A score of more than 3/5 had 82% sensitivity and 72% specificity for silent MI. CONCLUSIONS: Using measures that can be derived in an outpatient clinic setting, we have developed a novel screening tool for the detection of silent MI in type 2 diabetes. The screening tool had significantly superior diagnostic accuracy than current ECG criteria for the detection of silent MI in asymptomatic patients.

Sex-related differences in left ventricular remodeling in severe aortic stenosis and reverse remodeling after aortic valve replacement: A cardiovascular magnetic resonance study.

BACKGROUND: Cardiac adaptation to aortic stenosis (AS) appears to differ according to sex, but reverse remodeling after aortic valve replacement has not been extensively described. The aim of the study was to determine using cardiac magnetic resonance imaging whether any sex-related differences exist in AS in terms of left ventricular (LV) remodeling, myocardial fibrosis, and reverse remodeling after valve replacement. METHODS: One hundred patients (men, n = 60) with severe AS undergoing either transcatheter or surgical aortic valve replacement underwent cardiac magnetic resonance scans at baseline and 6 months after valve replacement. RESULTS: Despite similar baseline comorbidity and severity of AS, women had a lower indexed LV mass than did men (65.3 ± 18.4 vs 81.5 ± 21.3 g/m(2), P < .001) and a smaller indexed LV end-diastolic volume (87.3 ± 17.5 vs 101.2 ± 28.6 mL/m(2), P = .002) with a similar LV ejection fraction (58.6% ± 10.2% vs 54.8% ± 12.9%, P = .178). Total myocardial fibrosis mass was similar between sexes (2.3 ± 4.1 vs 1.3 ± 1.1 g, P = .714), albeit with a differing distribution according to sex. After aortic valve replacement, men had more absolute LV mass regression than did women (18.3 ± 10.6 vs 12.7 ± 8.8 g/m(2), P = .007). When expressed as a percentage reduction of baseline indexed LV mass, mass regression was similar between the sexes (men 21.7% ± 10.1% vs women 18.4% ± 11.0%, P = .121). There was no sex-related difference in postprocedural LV ejection fraction or aortic regurgitation. Sex was not found to be a predictor of LV reverse remodeling on multiple regression analysis. CONCLUSIONS: There are significant differences in the way that male and female hearts adapt to AS. Six months after aortic valve replacement, there are no sex-related differences in reverse remodeling, but superior reverse remodeling in men as a result of their more adverse remodeling profile at baseline.

Athletic Cardiac Adaptation in Males Is a Consequence of Elevated Myocyte Mass.

BACKGROUND: Cardiac remodeling occurs in response to regular athletic training, and the degree of remodeling is associated with fitness. Understanding the myocardial structural changes in athlete's heart is important to develop tools that differentiate athletic from cardiomyopathic change. We hypothesized that athletic left ventricular hypertrophy is a consequence of increased myocardial cellular rather than extracellular mass as measured by cardiovascular magnetic resonance. METHODS AND RESULTS: Forty-five males (30 athletes and 15 sedentary age-matched healthy controls) underwent comprehensive cardiovascular magnetic resonance studies, including native and postcontrast T1 mapping for extracellular volume calculation. In addition, the 30 athletes performed a maximal exercise test to assess aerobic capacity and anaerobic threshold. Participants were grouped by athleticism: untrained, low performance, and high performance (O2max <60 or>60 mL/kg per min, respectively). In athletes, indexed cellular mass was greater in high- than low-performance athletes 60.7±7.5 versus 48.6±6.3 g/m(2); P<0.001), whereas extracellular mass was constant (16.3±2.2 versus 15.3±2.2 g/m(2); P=0.20). Indexed left ventricular end-diastolic volume and mass correlated with O2max (r=0.45, P=0.01; r=0.55, P=0.002) and differed significantly by group (P=0.01; P<0.001, respectively). Extracellular volume had an inverse correlation with O2max (r=-0.53, P=0.003 and left ventricular mass index (r=-0.44, P=0.02). CONCLUSIONS: Increasing left ventricular mass in athlete's heart occurs because of an expansion of the cellular compartment while the extracellular volume becomes relatively smaller: a difference which becomes more marked as left ventricular mass increases. Athletic remodeling, both on a macroscopic and cellular level, is associated with the degree of an individual's fitness. Cardiovascular magnetic resonance ECV quantification may have a future role in differentiating athlete's heart from change secondary to cardiomyopathy.

The effect of changes to MOLLI scheme on T1 mapping and extra cellular volume calculation in healthy volunteers with 3 tesla cardiovascular magnetic resonance imaging.

BACKGROUND: Diffuse myocardial fibrosis may be quantified with magnetic resonance (MR) by calculating extracellular volume (ECV) fraction from native and post-contrast T1 values. The ideal modified look-locker inversion recovery (MOLLI) sequence for deriving T1 values has not been determined. This study aims to establish if systematic differences exist between suggested MOLLI schemes. METHODS: Twelve phantom gels were studied with inversion recovery spin echo MR at 3.0 tesla to determine reference T1. Gels were then scanned with six MOLLI sequences (3s)3b(3s)5b; 4b(3s)3b(3s)2b; 5b(3s)3b with flip angles of both 35° and 50° at a range of heart rates (HRs). In 10 healthy volunteers MOLLI studies were performed on two separate occasions. Mid ventricular native and post contrast T1 was measured and ECV (%) calculated. RESULTS: In phantoms, the co-efficient of variability at simulated HR [40-100] with a flip angle of 35° ranged from 6.77 to 9.55, and at 50° from 7.71 to 11.10. T1 was under-estimated by all MOLLI acquisitions. Error was greatest with longer T1, and increased as HR increased. The 10 volunteers had normal MR studies. Native T1 time was similar for all acquisitions but highest with the 5b(3s)3b 35° scheme (1,189.1±33.46 ms). Interstudy reproducibility was similar for all MOLLIs. CONCLUSIONS: The 5b(3s)3b MOLLI scheme agreed best with reference T1, without statistical difference between the six schemes. The shorter breath-hold time of 5b(3s)3b scheme may be preferable in clinical studies and warrants further investigation.