Adam K McDiarmid

Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study

BackgroundT1 mapping is a robust and highly reproducible application to quantify myocardial relaxation of longitudinal magnetisation. Available T1 mapping methods are presently site and vendor specific, with variable accuracy and precision of T1 values between the systems and sequences. We assessed the transferability of a T1 mapping method and determined the reference values of healthy human myocardium in a multicenter setting.MethodsHealthy subjects (n = 102; mean age 41 years (range 17–83), male, n = 53 (52%)), with no previous medical history, and normotensive low risk subjects (n=113) referred for clinical cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria for all were absence of regular medication and subsequently normal findings of routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5 Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single midventricular short axis slice and repeated 20 minutes following gadobutrol. Reference values were obtained for native T1 and gadolinium-based partition coefficients, λ and extracellular volume fraction (ECV) in a core lab using standardized postprocessing.ResultsIn healthy controls, mean native T1 values were 950 ± 21 msec at 1.5 T and 1052 ± 23 at 3 T. λ and ECV values were 0.44 ± 0.06 and 0.25 ± 0.04 at 1.5 T, and 0.44 ± 0.07 and 0.26 ± 0.04 at 3 T, respectively. There were no significant differences between healthy controls and low risk subjects in routine CMR parameters and T1 values. The entire cohort showed no correlation between age, gender and native T1. Cross-center comparisons of mean values showed no significant difference for any of the T1 indices at any field strength. There were considerable regional differences in segmental T1 values. λ and ECV were found to be dose dependent. There was excellent inter- and intraobserver reproducibility for measurement of native septal T1.ConclusionWe show transferability for a unifying T1 mapping methodology in a multicenter setting. We provide reference ranges for T1 values in healthy human myocardium, which can be applied across participating sites.

Effect of Left Ventricular Assist Device Implantation and Heart Transplantation on Habitual Physical Activity and Quality of Life

The present study defined the short- and long-term effects of left ventricular assist device (LVAD) implantation and heart transplantation (HT) on physical activity and quality of life (QoL). Forty patients (LVAD, n = 14; HT, n = 12; and heart failure [HF], n = 14) and 14 matched healthy subjects were assessed for physical activity, energy expenditure, and QoL. The LVAD and HT groups were assessed postoperatively at 4 to 6 weeks (baseline) and 3, 6, and 12 months. At baseline, LVAD, HT, and HF patients demonstrated low physical activity, reaching only 15%, 28%, and 51% of that of healthy subjects (1,603 ± 302 vs 3,036 ± 439 vs 5,490 ± 1,058 vs 10,756 ± 568 steps/day, respectively, p <0.01). This was associated with reduced energy expenditure and increased sedentary time (p <0.01). Baseline QoL was not different among LVAD, HT, and HF groups (p = 0.44). LVAD implantation and HT significantly increased daily physical activity by 60% and 52%, respectively, from baseline to 3 months (p <0.05), but the level of activity remained unchanged at 3, 6, and 12 months. The QoL improved from baseline to 3 months in LVAD implantation and HT groups (p <0.01) but remained unchanged afterward. At any time point, HT demonstrated higher activity level than LVAD implantation (p <0.05), and this was associated with better QoL. In contrast, physical activity and QoL decreased at 12 months in patients with HF (p <0.05). In conclusion, patients in LVAD and HT patients demonstrate improved physical activity and QoL within the first 3 months after surgery, but physical activity and QoL remain unchanged afterward and well below that of healthy subjects. Strategies targeting low levels of physical activity should now be explored to improve recovery of these patients.

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/m2; P<0.001), whereas extracellular mass was constant (16.3±2.2 versus 15.3±2.2 g/m2; 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.

Susceptibility-weighted cardiovascular magnetic resonance in comparison to T2 and T2 star imaging for detection of intramyocardial hemorrhage following acute myocardial infarction at 3 Tesla

BackgroundIntramyocardial hemorrhage (IMH) identified by cardiovascular magnetic resonance (CMR) is an established prognostic marker following acute myocardial infarction (AMI). Detection of IMH by T2-weighted or T2 star CMR can be limited by long breath hold times and sensitivity to artefacts, especially at 3T. We compared the image quality and diagnostic ability of susceptibility-weighted magnetic resonance imaging (SW MRI) with T2-weighted and T2 star CMR to detect IMH at 3T.MethodsForty-nine patients (42 males; mean age 58 years, range 35-76) underwent 3T cardiovascular magnetic resonance (CMR) 2 days following re-perfused AMI. T2-weighted, T2 star and SW MRI images were obtained. Signal and contrast measurements were compared between the three methods and diagnostic accuracy of SW MRI was assessed against T2w images by 2 independent, blinded observers. Image quality was rated on a 4-point scale from 1 (unusable) to 4 (excellent).ResultsOf 49 patients, IMH was detected in 20 (41%) by SW MRI, 21 (43%) by T2-weighted and 17 (34%) by T2 star imaging (p =ns). Compared to T2-weighted imaging, SW MRI had sensitivity of 93% and specificity of 86%. SW MRI had similar inter-observer reliability to T2-weighted imaging (κ =0.90 and κ =0.88 respectively); both had higher reliability than T2 star (κ =0.53). Breath hold times were shorter for SW MRI (4 seconds vs. 16 seconds) with improved image quality rating (3.8 ± 0.4, 3.3 ± 1.0, 2.8 ± 1.1 respectively; p < 0.01).ConclusionsSW MRI is an accurate and reproducible way to detect IMH at 3T. The technique offers considerably shorter breath hold times than T2-weighted and T2 star imaging, and higher image quality scores.

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.

Single bolus versus split dose gadolinium administration in extra-cellular volume calculation at 3 Tesla

BackgroundDiffuse myocardial fibrosis may be quantified with cardiovascular magnetic resonance (CMR) by calculating extra-cellular volume (ECV) from native and post-contrast T1 values. Accurate ECV calculation is dependent upon the contrast agent having reached equilibrium within tissue compartments. Previous studies have used infusion or single bolus injections of contrast to calculate ECV. In clinical practice however, split dose contrast injection is commonly used as part of stress/rest perfusion studies. In this study we sought to assess the effects of split dose versus single bolus contrast administration on ECV calculation.MethodsTen healthy volunteers and five patients ( 4 ischaemic heart disease, 1 hypertrophic cardiomyopathy) were studied on a 3.0 Tesla (Philips Achieva TX) MR system and underwent two (patients) or three (volunteers) separate CMR studies over a mean of 12 and 30 days respectively. Volunteers underwent one single bolus contrast study (Gadovist 0.15mmol/kg). In two further studies, contrast was given in two boluses (0.075mmol/kg per bolus) as part of a clinical adenosine stress/rest perfusion protocol, boluses were separated by 12 minutes. Patients underwent one bolus and one stress perfusion study only. T1 maps were acquired pre contrast and 15 minutes following the single bolus or second contrast injection.ResultsECV agreed between bolus and split dose contrast administration (coefficient of variability 5.04%, bias 0.009, 95% CI −3.754 to 3.772, r2 = 0.973, p = 0.001)). Inter-study agreement with split dose administration was good (coefficient of variability, 5.67%, bias −0.018, 95% CI −4.045 to 4.009, r2 = 0.766, p > 0.001).ConclusionECV quantification using split dose contrast administration is reproducible and agrees well with previously validated methods in healthy volunteers, as well as abnormal and remote myocardium in patients. This suggests that clinical perfusion CMR studies may incorporate assessment of tissue composition by ECV based on T1 mapping.

Myocardial Extracellular Volume Estimation by CMR Predicts Functional Recovery Following Acute MI

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.

Reciprocal ECG change in reperfused ST-elevation myocardial infarction is associated with myocardial salvage and area at risk assessed by cardiovascular magnetic resonance

Objective ST-elevation acute myocardial infarction (STEMI) is frequently associated with reciprocal ST depression in contralateral ECG leads. The relevance of these changes is debated. This study examined whether reciprocal ECG changes in STEMI reflect larger myocardial area at risk (AAR) and/or infarct size. Design Patients were stratified by presence of reciprocal change on the presenting ECG, defined as ≥1 mm ST depression in ≥2 inferior leads for anterior STEMI, or ≥2 anterior leads for inferior STEMI. Infarcted tissue was defined on late enhancement and AAR on T2-weighted cardiovascular magnetic resonance (CMR). Setting Patients with reperfused first STEMI underwent CMR within 3 days of presentation. Main outcome measures In addition to AAR and infarct mass, myocardial salvage was calculated as (AAR mass—infarct mass) and salvage index as myocardial salvage/AAR mass. Results Thirty-five patients were analysed (n=35). Patients with reciprocal ECG changes (n=19) had higher AAR mass than those without (42 g vs 29 g, p<0.001), and higher myocardial salvage (27 g vs 9 g, p<0.001) and myocardial salvage index (61% vs 17%, p<0.001) but similar infarct size (16 g vs 20 g, p=0.3) and ejection fraction (43% vs 45%, p=0.5). Conclusions STEMI patients with reciprocal ECG changes have larger AAR, higher myocardial salvage and salvage index than those without. Reciprocal changes appear to be a marker of increased ischaemic myocardium at risk and indicate the potential for increased salvage with emergency revascularisation. Reciprocal changes showed no relationship to infarct size, which may be influenced by ischaemia time and other treatment factors.

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

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 (&bgr;=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.

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: http://www.clinicaltrials.gov. Unique identifier: NCT01970319.