Abstract Objectives In the setting of reperfused acute myocardial infarction (AMI), the authors sought to compare prediction of contractile recovery by infarct extracellular volume (ECV), as measured ...by T1-mapping cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) transmural extent. Background The transmural extent of myocardial infarction as assessed by LGE CMR is a strong predictor of functional recovery, but accuracy of the technique may be reduced in AMI. ECV mapping by CMR can provide a continuous measure associated with the severity of tissue damage within infarcted myocardium. Methods Thirty-nine patients underwent acute (day 2) and convalescent (3 months) CMR scans following AMI. Cine imaging, tissue tagging, T2-weighted imaging, modified Look-Locker inversion T1 mapping natively and 15 min post–gadolinium-contrast administration, and LGE imaging were performed. The ability of acute infarct ECV and acute transmural extent of LGE to predict convalescent wall motion, ejection fraction (EF), and strain were compared per-segment and per-patient. Results Per-segment, acute ECV and LGE transmural extent were associated with convalescent wall motion score (p < 0.01; p < 0.01, respectively). ECV had higher accuracy than LGE extent to predict improved wall motion (area under receiver-operating characteristics curve 0.77 vs. 0.66; p = 0.02). Infarct ECV ≤0.5 had sensitivity 81% and specificity 65% for prediction of improvement in segmental function; LGE transmural extent ≤0.5 had sensitivity 61% and specificity 71%. Per-patient, ECV and LGE correlated with convalescent wall motion score (r = 0.45; p < 0.01; r = 0.41; p = 0.02, respectively) and convalescent EF (p < 0.01; p = 0.04). ECV and LGE extent were not significantly correlated (r = 0.34; p = 0.07). In multivariable linear regression analysis, acute infarct ECV was independently associated with convalescent infarct strain and EF (p = 0.03; p = 0.04), whereas LGE was not (p = 0.29; p = 0.24). Conclusions Acute infarct ECV in reperfused AMI can complement LGE assessment as an additional predictor of regional and global LV functional recovery that is independent of transmural extent of infarction.
Among patients with suspected coronary heart disease (CHD), rates of invasive angiography are considered too high.
To test the hypothesis that among patients with suspected CHD, cardiovascular ...magnetic resonance (CMR)-guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines-directed care and myocardial perfusion scintigraphy (MPS)-guided care in reducing unnecessary angiography.
Multicenter, 3-parallel group, randomized clinical trial using a pragmatic comparative effectiveness design. From 6 UK hospitals, 1202 symptomatic patients with suspected CHD and a CHD pretest likelihood of 10% to 90% were recruited. First randomization was November 23, 2012; last 12-month follow-up was March 12, 2016.
Patients were randomly assigned (240:481:481) to management according to UK NICE guidelines or to guided care based on the results of CMR or MPS testing.
The primary end point was protocol-defined unnecessary coronary angiography (normal fractional flow reserve >0.8 or quantitative coronary angiography QCA showing no percentage diameter stenosis ≥70% in 1 view or ≥50% in 2 orthogonal views in all coronary vessels ≥2.5 mm diameter) within 12 months. Secondary end points included positive angiography, major adverse cardiovascular events (MACEs), and procedural complications.
Among 1202 symptomatic patients (mean age, 56.3 years SD, 9.0; women, 564 46.9% ; mean CHD pretest likelihood, 49.5% SD, 23.8%), number of patients with invasive coronary angiography after 12 months was 102 in the NICE guidelines group (42.5% 95% CI, 36.2%-49.0%), 85 in the CMR group (17.7% 95% CI, 14.4%-21.4%); and 78 in the MPS group (16.2% 95% CI, 13.0%-19.8%). Study-defined unnecessary angiography occurred in 69 (28.8%) in the NICE guidelines group, 36 (7.5%) in the CMR group, and 34 (7.1%) in the MPS group; adjusted odds ratio of unnecessary angiography: CMR group vs NICE guidelines group, 0.21 (95% CI, 0.12-0.34, P < .001); CMR group vs the MPS group, 1.27 (95% CI, 0.79-2.03, P = .32). Positive angiography proportions were 12.1% (95% CI, 8.2%-16.9%; 29/240 patients) for the NICE guidelines group, 9.8% (95% CI, 7.3%-12.8%; 47/481 patients) for the CMR group, and 8.7% (95% CI, 6.4%-11.6%; 42/481 patients) for the MPS group. A MACE was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group (adjusted hazard ratios: CMR group vs NICE guidelines group, 1.37 95% CI, 0.52-3.57; CMR group vs MPS group, 0.95 95% CI, 0.46-1.95).
In patients with suspected angina, investigation by CMR resulted in a lower probability of unnecessary angiography within 12 months than NICE guideline-directed care, with no statistically significant difference between CMR and MPS strategies. There were no statistically significant differences in MACE rates.
Clinicaltrials.gov Identifier: NCT01664858.
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.
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).
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.
To investigate the pharmacology and potential clinical utility of splenic switch-off to identify understress in adenosine perfusion cardiac magnetic resonance (MR) imaging.
Splenic switch-off was ...assessed in perfusion cardiac MR examinations from 100 patients (mean age, 62 years age range, 18-87 years) by using three stress agents (adenosine, dobutamine, and regadenoson) in three different institutions, with appropriate ethical permissions. In addition, 100 negative adenosine images from the Clinical Evaluation of MR Imaging in Coronary Heart Disease (CE-MARC) trial (35 false and 65 true negative; mean age, 59 years age range, 40-73 years) were assessed to ascertain the clinical utility of the sign to detect likely pharmacologic understress. Differences in splenic perfusion were compared by using Wilcoxon signed rank or Wilcoxon rank sum tests, and true-negative and false-negative findings in CE-MARC groups were compared by using the Fisher exact test.
The spleen was visible in 99% (198 of 200) of examinations and interobserver agreement in the visual grading of splenic switch-off was excellent (κ = 0.92). Visually, splenic switch-off occurred in 90% of adenosine studies, but never in dobutamine or regadenoson studies. Semiquantitative assessments supported these observations: peak signal intensity was 78% less with adenosine than at rest (P < .001), but unchanged with regadenoson (4% reduction; P = .08). Calculated peak splenic divided by myocardial signal intensity (peak splenic/myocardial signal intensity) differed between stress agents (adenosine median, 0.34; dobutamine median, 1.34; regadenoson median, 1.13; P < .001). Failed splenic switch-off was significantly more common in CE-MARC patients with false-negative findings than with true-negative findings (34% vs 9%, P < .005).
Failed splenic switch-off with adenosine is a new, simple observation that identifies understressed patients who are at risk for false-negative findings on perfusion MR images. These data suggest that almost 10% of all patients may be understressed, and that repeat examination of individuals with failed splenic switch-off may significantly improve test sensitivity.
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.
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.
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/m2, P < .001) and a smaller indexed LV end-diastolic volume (87.3 ± 17.5 vs 101.2 ± 28.6 mL/m2, 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/m2, 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.
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.
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.
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.
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.
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.
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.
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).
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).
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).
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.
Abstract Objective The response of the RV following treatment of aortic stenosis is poorly defined, reflecting the challenge of accurate RV assessment. Cardiovascular magnetic resonance (CMR) is the ...established reference for imaging of RV volumes, mass and function. We sought to define the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon RV function in patients treated for severe aortic stenosis using CMR. Methods A 1.5T CMR scan was performed preoperatively and 6 months postoperatively in 112 (56 TAVI, 56 SAVR; 76 ± 8 years) high-risk severe symptomatic aortic stenosis patients across two UK cardiothoracic centres. Results TAVI patients were older (80.4 ± 6.7 vs. 72.8 ± 7.2 years, p < 0.05) with a higher STS score (2.13 ± 0.73 vs. 5.54 ± 3.41%, p < 0.001). At 6 months, SAVR was associated with a significant increase in RV end systolic volume (33 ± 10 vs. 37 ± 10 ml/m2 , p = 0.008), and decrease in RV ejection fraction (58 ± 8 vs. 53 ± 8%, p = 0.005) and tricuspid annular plane systolic excursion (22 ± 5 vs. 14 ± 3 mm, p < 0.001). Only 4 (7%) SAVR patients had new RV late gadolinium hyper-enhancement with no new cases seen in the TAVI patients at 6 months. Longer surgical cross-clamp time was the only predictor of increased RV end systolic volume at 6 months. Post-TAVI, there was no observed change in RV volumes or function. Over a maximum 6.3 year follow-up, 18(32%) of TAVI patients and 1(1.7%) of SAVR patients had died (p = 0.001). On multivariable Cox analysis, the RV mass at 6 m post-TAVI was independently associated with all-cause mortality (HR 1.359, 95% CI 1.108–1.666, p = 0.003). Conclusions SAVR results in a deterioration in RV systolic volumes and function associated with longer cross-clamp times and is not fully explained by suboptimal RV protection during cardiopulmonary bypass. TAVI had no adverse impact upon RV volumes or function.
Background
It is often stated that heart disease is underdiagnosed in COPD. Evidence for this statement comes from primary studies, but these have not been synthesised to provide a robust estimate of ...the burden of undiagnosed heart disease.
Methods
A systematic review of studies using active diagnostic techniques to establish the prevalence of undiagnosed major cardiac comorbidities in patients with COPD was carried out. MEDLINE, Embase, Scopus and Web of Science were searched for terms relating to heart failure (specifically, left ventricular systolic dysfunction (LVSD), coronary artery disease (CAD) and atrial fibrillation), relevant diagnostic techniques and COPD. Studies published since 1980, reporting diagnosis rates using recognised diagnostic criteria in representative COPD populations not known to have heart disease were included. Studies were classified by condition diagnosed, diagnostic threshold used and whether participants had stable or exacerbated COPD. Random-effects meta-analysis of prevalence was conducted where appropriate.
Results
In general, prevalence estimates for undiagnosed cardiac comorbidities in COPD had broad confidence intervals, with significant study heterogeneity. Most notably, a prevalence of undiagnosed LVSD of 15.8% (11.1–21.1%) was obtained when defined as left ventricular ejection fraction <50%. Undiagnosed CAD was found in 2.3–18.0% of COPD patients and atrial fibrillation in 1.4% (0.3–3.5%).
Conclusion
Further studies using recent diagnostic advances, and investigating therapeutic interventions for patients with COPD and heart disease are needed.