This study is aimed at investigating myocardial multi-directional systolic deformation in hypertensive with different left ventricular ejection fraction (LVEF), and exploring its contribution to LVEF.2), and group C (LVEF < 45%). Two-dimensional strain echocardiography (2DSE) including LV longitudinal strain (SL), radial strain (SR) and circumferential strain (SC) were measured.One hundred and twenty-three patients with primary hypertension (HT) were divided into group A (LVEF ≥ 55%), group B  while SR and SC were reduced only in group B and C . All strain measurements correlated to LVEF, with the strongest correlation in SC  and the second in SL (r = −0.76). The diastolic E/e increased from group A, B to C.SL decreased gradually from group A, B to C (all Left ventricular multi-directional deformation correlated well to LVEF in hypertension and particularly SC, indicating that it was SC, not SL or SR, that makes the prominent contribution to left ventricular pump function. Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced EF (HFrEF) may be different stages of the identical disease . Studies2); group B, “borderline” LVEF and enlarged LV end diastolic volume index  and group C, reduced LVEF (LVEF < 45%).According to 2007 Guidelines for the management of arterial hypertension , hyperte2 for men and LVMI ≥ 110 g/m2 for women [2.Echocardiography was performed in participants using GE VIVID E9 or GE VIVID E7 ultrasound scanner  with GE VIVID E9 or GE VIVID E7 probe (1.7-4.0 MHz). Conventional scans were acquired in standard left ventricular long axis, short axis and apical views. For parasternal short-axis views, three levels of LV were acquired, which were basal level, papillary muscle level and apical level. All echocardiographic measurements were averaged on three heart beats. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and left atrial volume (LAV) were obtained by area-length method in standard apical views (biplane). Left ventricular internal dimension at end diastole and end systole , posterior wall thickness (LVPWT), septal thickness (IVST) and left atrial diameter (LAD) were acquired in parasternal long axis views. Left ventricular mass (LVM) was calculated based on the recently published guidelines . LVEDV, Myocardial strain measurements were performed using 2DSE –13. The Ten patients were randomly-selected to assess interobserver and intraobserver variability in strain measurements. The interobserver variability was calculated as the SD of the difference between the measurements of two independent observers who were blinded to all other patient’s data and expressed as a percent of the average value. The intraobserver variability was calculated as the SD of the difference between the first and second measurements by the same observer at 1-week interval and expressed as a percent of the average value.2 test, and Fisher’s exact tests were used when appropriate. Pearson’s correlation analysis was used to study the relation between two continuous variables. SPSS version 15  was deployed to perform the majority of the statistical operations, where a p value less than 0.05 was considered statistically significant.Continuous data were presented as mean ± standard deviation (SD) or as percentages where appropriate. Comparisons among multiple groups was performed with one-way ANOVA if the data were normally distributed; otherwise, one-way ANOVA on ranks if the data distribution was not normal. Categorical variables were analyzed using χp > 0.05), as shown in Table There was no difference in terms of age or sex among all patients groups and normal controls (p < 0.05); early diastolic e’ velocity decreased and E/e’ ratio increased progressively from NC to group HT-NEF and HT-REF , indicating that it was SC, not SL or SR making the prominent contribution to left ventricular pump function.In the present study, we compared the difference of LV multi-directional strain among patients in three different levels of LVEF, and investigated the correlation and contribution of strain in each direction to global pump function, providing a continuous trend of LV performance in the progression of cardiac dysfunction in hypertension. The major findings were, (1) SL decreased early in the stage of normal LVEF, while SC and SR began to decrease in patients with “borderline” LVEF (45%-55%) and deteriorated with LVEF reduced further. (2) Systolic strains in all directions highly correlated with LVEF, with the strongest correlation in SC . In the early stage of remodeling (concentric remodeling), or before left ventricular function is significantly impaired, SR is preserved or increased in compensation for the decrease in SL , 17. As The present results of SC were in accord with previous studies , 12, 13:A recent study demonstrated that heart failure with normal LVEF had a poorer SC than normal subjects , where “SL was impaired first in the early stage, and deteriorated together with decreased SR and SC with the progression of hypertensive remodeling. The pathological basis of these observations likely lies in hypertension-related fibrosis and myocyte hypertrophy progressing from subendocardial layer to the epicardium , and theThe present study shows a significant correlation between longitudinal, circumferential, radial strain and LVEF. Impaired SL did not appear to impact LVEF because of the compensation of myocardial fibers in the mid and subepicardial layers. In the later stages of hypertension and with LV remodeling, other components of LV strain were also impaired . In our We used 2DSE to reconstruct a 3D LV multi-directional strain, where images were obtained from different heart beats, and some detailed real myocardial dynamic information might be lost through heart motion in the chest in a cardiac cycle. Hence, the results might be less accurate than that of using a real time three dimensional strain. Since some LV short-axis views of apical level were challenging, we did not investigate LV twist, which would also contribute to preserved LVEF. We could not acquire detailed information of patients’ managements and medication of hypertension, for most of them did not have a regular management or they were not able to provide reliable records.Impaired left ventricular longitudinal strain and diastolic dysfunction happened early in patients with normal LVEF in hypertension, while circumferential and radial strains were preserved or increased slightly as a compensation for the decrease in local systolic function, and when all directions of strains were impaired, LVEF decreased together with a deteriorating LV diastolic function. Left ventricular multi-directional deformation correlated well to LVEF in hypertension, particularly SC, indicating that it was SC, not SL or SR making the prominent contribution to left ventricular pump function.


Electrocardiogram (ECG)-gated breath-hold cardiac cine magnetic resonance imaging (MRI) is generally accepted as the gold standard for left-ventricular (LV) volume assessment. However, it may fail in patients with arrhythmia, impaired breath-hold capacity, and poor ECG gating. Recently, sparse real-time (RT) cine using a prototype sequence with sparse sampling and iterative reconstruction has been proposed to accelerate cine MRI . The purpose of this study was to evaluate the diagnostic quality and accuracy of sparse free-breathing (FB) RT cine MRI for the quantification of LV function compared with standard multi-breath-hold cine MRI.3). The image quality, ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and LV mass for sparse FB RT cine and standard cine were compared.50 patients underwent both standard segmented cine MRI (Acc. factor 3) and sparse FB RT cine with a prototype sequence using sparse sampling and iterative reconstruction (acc. factor 12.8) on a clinical 3T MRI scanner . The cine images were obtained in a stack of 8 short-axis slices spanning the entire LV from base to apex ; EDV ; ESV ; SV ; LV mass . The intra-observer and inter-observer agreement for all parameters was good.Sparse FB RT cine MRI evaluates LV function with good accuracy compared with conventional multi-breath-hold cine MRI. For patients with impaired breath-hold capacity, FB RT cine MRI may be clinically useful for quantitative assessment of LV function.


M = 152.90 h) in 47 healthy participants . Diurnally, mean PA for both ankle and wrist and CV of PA for ankle decreased from the first to the second half of daytime (p < 0.05). There were no differences in mean PA between wrist and ankle at any time-period (p > 0.2). CV of ankle PA at daytime was significantly higher than wrist PA (p < .0001). The opposite pattern was observed at nighttime (p < .0001). Pearson correlation analyses were performed to assess the associations between wrist (or ankle) PA and age and BMI. Mean daytime (but not nighttime) activity for wrist and ankle decreased significantly with age (p < .05). PA variability also decreased with age for wrist and ankle during daytime and for ankle during nighttime (p < .05). BMI was negatively associated with wrist daytime PA variability (p < .05). There were no gender effects on activity measures. These findings indicate that wrist and ankle mean PA measures were not significantly different but were significantly different (p < 0.5) for PA variability in both daytime and nighttime. Age-related decreases of PA-mean and variability were observed during daytime in wrist and ankle, whereas higher wrist daytime variability was inversely associated with BMI. These findings provide new insights into PA features in free-living environment, which are relevant for public health and may have implications for clinical assessment of neurodegenerative disorders impacting PA and their interaction with demographics.Physical activity (PA) is associated with various aspects of physical and mental health and varies by age and BMI. We aimed to compare PA measures obtained with wrist and ankle accelerometers and characterize their associations with age and BMI. We assessed PA mean and PA variability (indexed by coefficient of variation (CV)) at daytime and nighttime periods for seven consecutive days ( Physical activity (PA) is associated with a wide range of health outcomes, demographics, developmental stages, and psychological measures , 2. SpecCircadian rhythms influence PA-related biological processes  and behaIt has been suggested that lower extremities’ movement variability and asymmetry of steps length underlie poor balance , which iAccelerometers placed on the extremities or torso objectively and unobtrusively characterize PA by measuring body acceleration in time , 35–39 aHere, we characterized differences of PA mean and variability in healthy individuals between daytime and nighttime periods for lower and upper extremities. We measured PA continuously for seven days using accelerometers positioned on wrist and ankle. The choice of wrist and ankle located monitors was due to evidence showing that PA in body extremities are differently affected by variables such as age and BMI , and thaM = 40.77, SD = 14.91) and BMI varied from 17.6 to 40.5 kg/m2   was two standard deviations above the sample average. Thus, accelerometer data for a final sample of 47 participants  was analyzed. The age range for this sample was 18 to 73 years old (.78) See .Inclusion criterion included older than 18 years of age and the ability to provide written informed consent, approved by the institutional review board at NIH. Exclusion criterion for this subtask, as part of the main neuroimaging study, included past or current DSM-IV or DSM-5 diagnosis of a psychiatric disorder (including substance use disorder), history of head trauma with loss of consciousness for more than 30 minutes, use of psychoactive substances two weeks prior to the study, use of medications that could affect brain function four weeks prior to the study, body weight over 250 kg, any medical problem that would affect brain function, cardiovascular disorders, any clinically significant laboratory finding during screening process, a positive test for drugs and/or pregnancy  at the time of the study. All participants underwent physical examination by a nurse practitioner to ensure there were no physical disabilities, mobility restrictions, or inability to comfortably lie flat on their back for extended periods of time. All participants were provided monetary compensation upon completing the task.n (the number of measurements in the sum) is the sampling frequency times the epoch length in seconds (100 Hz × 60 s), resulting in a total of 6000 samples for every 1-minute bin . Thus, the resulting SVMs for the 1-min bins were divided by 600, so that the resulting numbers have units of 0.1 g . Using MATLAB  software (MATLAB and Statistics Toolbox Release 2012b), 10-min sliding windows with 50% overlap were used to calculate PA’s mean and coefficient of variation (CV = standard deviation/mean) within each window. Our choice of 1-min bins is consistent with prior literature [We used GENEActiv triaxial accelerometers  to record limbs’ acceleration along 3 orthogonal axes. All participants were asked to wear two accelerometer monitors 24 hours continuously for 7 days (sampling rate: f = 100 Hz) and to continue with their regular activities. Consistent with previous studies’ methodology , 52, onend epoch  where, nterature . Moreoveterature .m/s2) during morning hours that continued for consecutive hours (m/s2) at evening hours that continued for several consecutive hours (m/s2) for longer than 20 min continuously during nighttime periods were excluded from the data. To characterize the impact of first and second halves of daytime on PA, we segmented the daytime period into two equal parts (for each day), and mean and CV of PA for wrist and ankle for the first half (P1) and for the second half (P2) were calculated separately.Real time of activity was calculated by the sum of minutes from start time of monitor wear. The average PA mean and CV across all windows that corresponded to daytime  were calculated individually and guided by time: we manually identified for each day increased activity for both wrist and ankle .Non-wear time was manually excluded from the analysis when either wrist or ankle showed no activity  PA, and age and BMI at daytime and nighttime. Two-sample t-tests were used to assess the effects of gender on age, BMI and PA measures. All statistical tests were performed against a two-tailed alternative and considered significant at p < 0.05.To assess mean PA and variability of participants at sleep and wake cycles, we estimated mean and CV measures for ankle and for wrist for all time periods . Paired t-tests showed no difference in daytime between mean PA of wrist  and ankle : t(46) = 0.09, p = .93; nor in the nighttime between mean PA of wrist  and ankle : t(46) = 1.15, p = .26  than wrist CV : t(46) = 8.99, p < .0001, whereas at nighttime ankle CV  was lower than wrist CV : t(46) = 11.44, p < .0001 (Paired  < .0001 .r(45) = .68, p < .000 (r(45) = .15, p = .32 (r(45) = .21, p = .16 (r(45) = .61, p < .0001  = -.35, p = .02 (r(45) = -0.37, p = .01 (r(45) = -.31, p = .03 and for wrist r(45) = -.33, p = .02 (r(45) = -.40, p = .005  = -.34, p = .021 (r(45) = .17, p = .25.The only significant correlation with BMI was for wrist CV during daytime p = .021 . Howeverp = .851) and age (p = .983) between males and females. In addition, there were no gender effects of PA mean and CV for wrist or ankle at any period, p > 0.1  than at daytime P2 : t(46) = 2.46, p = .02; similarly, wrist mean PA was higher at daytime P1  than daytime P2 : t(46) = 2.21, p = .03. When comparing mean PA of wrist and ankle at daytime P1, no differences were found between ankle  and wrist : t(46) = 0.45, p = .65. Similarly, at daytime P2, mean PA of ankle  did not differ from wrist mean PA : t(46) = 1.14, p = .26.  than at daytime P2 : t(46) = 2.82, p = .007, however, no differences in wrist PA CV were found between daytime P1  and daytime P2 : t(46) = 1.23, p = .22. Comparisons of PA CV between wrist and ankle at daytime P1 revealed that PA CV of ankle  was higher than wrist : t(46) = 8.94, p < .0001. Similarly, at daytime P2, PA CV of ankle  was higher than wrist : t(46) = 7.37, p < .0001. . In contrast, intra-subject variability, as quantified by CV, differed significantly between wrist and ankle: at daytime, the ankle had higher PA variability than the wrist; whereas at nighttime, wrist PA had greater variability. For diurnal patterns, we found that mean PA was significantly reduced between the first and second halves of the daytime period. We also showed that mean and variability of both wrist and ankle PA during daytime were negatively associated with age. Although we predicted a negative association between mean PA and BMI, we only observed a negative BMI association with wrist PA variability during daytime, for which the significance was affected by an outlier .The current study was performed in a free-setting environment and participants engaged in their regular diurnal and nightly behaviors. Daily activities such as walking may require high involvement of ankle and wrist, while other behaviors such as desk or domestic activities may require higher contribution from upper limbs. Here, we show no difference of PA mean between wrist and ankle for either daytime or nighttime in healthy subjects. Thus, it appears that gross movements that engage both upper and lower extremities dominate the small magnitude movements that might differently engage the upper over the lower extremities . This was also supported by the high correlation between mean wrist and mean ankle PA in daytime  showing In contrast, we found differences in intra-subject variability of PA between ankle and wrist as a function of daytime and nighttime  periods . High anIn addition to sleep-wake cycles, time-of-day has been recognized as a key factor for the interaction of PA with neurological and cardiovascular systems . For exaAs suggested by previous research, we found that mean PA of the lower and upper limbs decreased by age but only at daytime. After accounting for the effects of mean , we found that CV also significantly decreased with age during daytime. These findings suggest that age may impact both overall but also patterns of activity. Although there is evidence that movement variability increases in association with age-related neurodegenerative disorders, such as Parkinson’s disease , we showContrary to our hypothesis, we did not find an association between BMI and mean PA. This could also reflect the limited statistical power due to the small sample size in our study. Nevertheless, we found a significant negative association between wrist PA variability and BMI during daytime, such that the higher the BMI the lower the PA wrist variability. This association might be driven by a reduced probability of shifting between activities as a function of BMI, though this effect was not seen in ankle PA variability in our sample. Further studies are needed to determine the differential sensitivity to BMI for wrist versus ankle monitors for movements in lower versus upper extremities.The present results suggest that quantitative assessment of mean PA only requires one accelerometer device on one body location for healthy controls. However, monitoring the variability in movement as seen in motor disorders like Parkinson’s or other age-related neurodegenerative disorders might benefit from monitoring activity in both body extremities.S1 FileExcel file containing acceleration raw data in 0.1 g units (m/s^2) for 47 participants included in all analyses. Column A indicates subject number. Columns B-E contain mean and CV data of ankle at daytime and nighttime. Columns F-I contain wrist mean and CV data for daytime and nighttime. Columns J-M contain demographics data, including gender, age, and BMI of participants.(XLSX)Click here for additional data file.


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 . 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 . 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. Microvascular obstruction (MVO) and intra-myocardial haemorrhage (IMH) as detected by cardiovascular magnetic resonance (CMR) are established independent adverse prognostic markers following reperfused ST-elevation myocardial infarction (STEMI). The presence of MVO has been associated with ‘no re-flow’ on coronary angiography after revascularisation . IMH is Myocardial systolic function after STEMI is conventionally assessed by calculating left ventricular ejection fraction (EF) from left ventricular volumes –5. HowevThis study aimed to investigate the association of FT derived peak global longitudinal strain (GLS), peak global circumferential strain (GCS), peak global radial strain (GRS), peak global longitudinal strain rate (GLSR), peak global circumferential strain rate (GCSR) and peak global radial strain rate (GRSR) with the presence of MVO, IMH and adverse LV remodelling in acute reperfused STEMI.2, haemodynamic instability  and con therapy . HealthyThe study protocol was approved by the National Research Ethics Service (12/YH/0169) and complied with the Declaration of Helsinki and all patients gave written informed consent.Coronary angiography and revascularisation were performed in a standard fashion as per current best practice guidelines . TIMI flAll patients underwent CMR imaging at 3.0 T  within 3 days (median 2 days) of their index presentation and were invited to attend a further CMR study at 3 months. CMR imaging used a dedicated 32-channel cardiac phased array receiver coil. Cine imaging was performed using a balanced steady-state free precession (SSFP) pulse sequence with a spatial resolution of 1.6 × 2.0 × 10 mm and 40 phases per cardiac cycle. 4-chamber, 2-chamber and LV short axis stack cine imaging were acquired for strain analysis using the same spatial and temporal resolution.T2 weighted (T2w) and T2* imaging were performed using the ‘3-of-5’ approach by acquiring the central 3 slices of 5 parallel short-axis slices spaced equally from mitral valve annulus to LV apical cap . 0.1 mmoCine, T2w, T2* and LGE images were evaluated offline using commercially available software . Left ventricular volumes and EF were analyzed from cine images using standard methods . InfarctStrain analysis was performed in a semi-automated manner using Circle Cardiovascular Imaging Inc., Calgary, Canada cvi42 v5.1  was performed on demographic and CMR parameters. Post-hoc univariate analysis was performed by using Tukey test . Step-wiForty-three acute STEMI patients met the inclusion criteria. Demographics of patients and ten healthy volunteers are shown in Table Left ventricular EF, left ventricular end-systolic volume (LVESV), GLS, GCS, GRS and GRSR were significantly altered in infarct patients versus healthy volunteers  Fig. . Stroke On linear regression analysis, using all the demographics and imaging variables including infarct size, GLS demonstrated the strongest association with presence of MVO or IMH  Table . The areThirty-four of the 43 patients underwent 3 month follow up CMR; six patients declined further follow-up and in three patients the scan quality of cines on follow up was not suitable for FT analysis. Demographics parameters  and baseline CMR parameters  were not significantly different in the nine patients who did not attend for follow-up scans compared with the overall study population (p > 0.1). All 34 follow up scans showed complete resolution of MVO and IMH. As compared to baseline, relative improvement in EF was 19 ± 24.5%. Of all the baseline CMR parameters , LVESVi  and GLS  demonstrated the strongest correlation with improvement in EF at follow-up scan. GCS  and GRS  also demonstrated good correlations with improvement in EF at follow-up.Out of 34 patients with follow-up data, 6 (17%) patients demonstrated adverse left ventricular remodelling. From all CMR baseline parameters, GLS demonstrated the strongest diagnostic performance in predicting adverse LV remodelling   are altered significantly in patients with MVO or IMH (p < 0.05). MVO and IMH affect predominantly the sub-endocardium, where most of the longitudinal myocardial fibres are located. It is thus plausible that GLS is the strongest predictor of MVO and IMH as shown in our study. GLS also demonstrated modest diagnostic performance to predict adverse LV remodelling at follow-up more than any other deformation parameter. In this study, the volume of MVO and infarct size were more strongly associated with GCS than GLS Table . These rIt is acknowledged that strain examination is more readily available by echocardiography than CMR. All modern echocardiographic systems come with strain packages , 32. EarOur findings have possible clinical implications as FT-strain analysis can be performed rapidly from standard cine CMR images and allows the detection of the functional effects of MVO and IMH without the need for additional CMR tissue characterisation techniques (T2W and T2*) and analysis methods. From our one-center experience, the time for total left ventricular strain analysis by CMR FT is approximately 7 min. As demonstrated, a cut off value of −13.7% for GLS detects MVO or IMH with a sensitivity of 76% and specificity of 77.8%. GLS can potentially predict the presence of MVO or IMH early after PPCI for STEMI. MVO and IMH are independent histopathological and cardiac imaging markers of adverse prognosis and we speculate that their early detection from routinely acquired CMR cines may help tailor appropriate pharmacological interventions or guide stem cell therapy. Patients with known allergy to gadolinium-based contrast agents or patients with end-stage renal failure may also benefit from this technique.In this study, we excluded patients who were unstable post-PPCI . These patients are more likely to represent a higher risk group with an adverse prognosis. In our study population, the majority of patients with MVO had IMH and only one patient with MVO had no IMH. Hence, the data on GCS for IMH detection should be interpreted with caution.Another important limitation of our study was that 9 of 43 patients did not have follow-up CMR scans. This may have introduced transfer bias although the two groups were not different for demographic and standard CMR parameters.In our study, at follow-up, only 6 (17%) patients had adverse LV remodelling and hence the demonstrated diagnostic performance of GLS to predict remodelling should be interpreted with caution.In the present study, only global parameters of strain were investigated. Assessment of regional left ventricular strain parameters by CMR FT demonstrates regional variations and their clinical role remains very speculative .Myocardial deformation changes adversely in patients with acute STEMI. Baseline GLS by FT-analysis of cine CMR is strongly associated with the presence of MVO or IMH and could be used as surrogate functional imaging marker of these acute myocardial pathological changes in patients with acute STEMI. Baseline GLS demonstrated stronger association with adverse LV remodelling than other CMR parameters.


In addition, the native T1 values were negatively correlated with free thyroxine (FT4)  and were positively correlated with TSH . Furthermore, left ventricular diastolic function estimated by the peak filling rate (PFR) was significantly lower in patients with TSH levels ≥10 µIU/mL than that in the controls (p < 0.05). In conclusion, diffuse myocardial injuries were present in SHT, and T1 mapping may be a useful tool for evaluating mild myocardial injuries in SHT at an early stage. Our study is the first to confirm myocardial injuries in SHT patients using T1 mapping.Subclinical hypothyroidism (SHT) is a common disorder that may represent early thyroid dysfunction and is related to adverse cardiovascular events. However, myocardial injuries induced by SHT are difficult to detect. Our previous study demonstrated that the cardiac magnetic resonance (CMR) myocardial longitudinal relaxation time (T1) mapping technique is a useful tool for assessing diffuse myocardial injuries in overt hypothyroidism patients. This study was designed to detect whether diffuse myocardial injuries were present in SHT by using the T1 mapping technique. We found that SHT participants had significantly increased native T1 values within four segments of the left ventricle (all  The overall prevalence of SHT in the general population varies from 4~20% and is particularly higher in women over sixty years old2. It is most often caused by chronic lymphocytic thyroiditis (goitrous Hashimoto’s thyroiditis and atrophic thyroiditis), an autoimmune disorder of the thyroid gland3, and progresses to overt hypothyroidism (HT) in approximately 5~8% of cases annually4. SHT is generally divided into two categories according to the TSH level: mild SHT (TSH between 4.5 and 10 µIU/mL) and severe SHT (TSH above 10 µIU/mL)5. Most patients with SHT have few or no typical hypothyroid symptoms. The thyroid and the cardiovascular system are closely related, both in physiological and pathological conditions6, and the adverse consequences of overt thyroid disease for the heart are well known. Indeed, mild forms of thyroid disease and even thyroid hormone variations within the physiological range have been linked to adverse cardiovascular effects, such as impaired diastolic relaxation and reduced exercise capacity7. In recent years, subclinical thyroid dysfunction has received increasing attention. The results of a 12-year study showed that heart failure events were increased in SHT patients without previous cardiovascular risks8. Because the potential risk factors are similar to those of HT10, some experts believe that SHT is an independent predictor for cardiovascular disease and that the risk is related to age and increased levels of TSH11.Subclinical hypothyroidism (SHT) is a very common endocrine disorder characterized by an elevated serum thyroid-stimulating hormone (TSH) concentration, but normal values of free thyroxine (FT4) and biologically active free triiodothyronine (FT3) in serum12. Therefore, when HT is present, cardiovascular function tests are typically indicated to determine whether overt cardiovascular disorders are also present, even for patients with SHT. The effects of mild thyroid hormone deficiency on the cardiovascular system have been extensively researched over the last several decades; however, most studies have focused on systolic/diastolic dysfunction. The mechanisms eliciting cardiac dysfunction in SHT are incompletely understood, but they are thought to be mediated in part by fibrosis resulting from the production of extracellular matrix proteins. Specifically, thyroid hormone deficiency can cause the accumulation of extracellular collagen and mucopolysaccharide substances in the myocardial interstitium, leading to myocardial fiber swelling, myocardial fibrosis, and myocardial oedema and then diffuse interstitial space expansion.In adults, thyroid hormone influences cardiac performance, including myocardial contractility, stroke volume, heart rate, vascular function and others, through genomic and non-genomic effects, thus causing changes in cardiac structure and function14, establishing whether mild alterations of thyroid function induce myocardial injuries is important. The available evidence for the presence of myocardial tissue effects due to SHT has not been considered sufficient to warrant treatment of these subjects according to the most recent guidelines5. On the other hand, once a negative tissue effect is identified in an SHT patient, early aggressive treatment may have a favourable effect on cardiovascular morbidity and mortality15. However, the interstitial changes induced by mild thyroid hormone deficiency occur more diffusely throughout the extracellular space of the myocardium and are commonly detected by histology, which poses challenges for clinical diagnosis. Currently, a novel, validated longitudinal relaxation time (T1) mapping cardiac magnetic resonance (CMR) can be used to quantitatively assess the full range of myocardial injuries in HT that are not readily detectable by conventional CMR16. We previously evaluated diffuse myocardial injuries at baseline by CMR T1 mapping and found significantly increased native T1 values in overt HT patients, indicating myocardial interstitium fibrosis and oedematous lesions in the HT heart17. To our best knowledge, no similar studies have been conducted in the SHT population.Given the high prevalence of SHT in the general population, and that the treatment of mild thyroid hormone deficiency is controversialTherefore, this study was undertaken to detect and quantify myocardial injuries by means of T1 mapping in SHT. In addition, we investigated the relationships of both T1 values and thyroid function with LV cardiac function in these patients.2) = body weight (kg)/height (m)2, and BSA (m2) = 0.007184 × height (cm)0.725 × weight (kg)0.425. Furthermore, cardiac magnetic resonance (CMR) imaging was performed. This study followed the Declaration of Helsinki guidelines and was approved by the Medical Ethics Committee of Beijing Chaoyang Hospital. All subjects provided written informed consent and ethical approval was granted for all study procedures.All research was performed in our hospital between September 2015 and March 2016. Twenty SHT patients  with Hashimoto’s thyroiditis who were not taking levothyroxine and were between 18 and 49 years of age were invited to participate. SHT was defined as: an increased TSH level (≥4.94 µIU/mL); normal serum FT4 level; and positive anti-thyroid peroxidase (anti-TPO) antibodies. The presence of elevated anti-TPO antibodies predicts progression to overt hypothyroidism, a clear risk factor for heart disease, reflecting the importance of establishing this autoimmune phenomenon. Thyroid function should be reassessed after one month to rule out the laboratory errors or transient anomalies. Patients with known hypertension, heart disease, diabetes, liver or kidney failure, chronic pulmonary disease, tumour, adrenal insufficiency, obesity, pregnancy, connective tissue diseases, claustrophobia or metal implants were not included. Sixteen subjects  with no documented medical history and matched for sex and age formed the healthy control group. All subjects’ vital signs and general data were recorded, including sex, age, height, body weight, blood pressure and heart rate, and their thyroid function and biochemical indexes were measured. Body mass index (BMI) and body surface area (BSA) were calculated using the following formulas: BMI , creatinine and cardiac troponin I (cTNI) levels were determined by electrochemiluminescence immunoassay (ECLIA) using an Abbott Architect i2000 . The reference intervals for FT3, FT4, TSH, cTNI and creatinine were 1.71–3.71 pg/ml, 0.7–1.48 ng/dL, 0.35–4.94 μIU/ml, 0–0.09 ng/ml and 53.0–115.0 μmol/l respectively. Total cholesterol (TC), low density lipoprotein cholesterol (LDLC), and high density lipoprotein cholesterol (HDLC) were determined using a Dade-Behring Dimension RXL Autoanalyzer . The reference intervals for TC, LDLC, and HDLC were 3.62–5.7 mmol/l, 1.81–3.36 mmol/l and 1.03–1.55 mmol/l respectively.All examinations were performed on a 3 T Tim Trio System scanner . CMR included cine and non-contrast T1 mapping. Cardiac volumes assessment was achieved via whole-heart coverage using gapless short-axis slices. Cardiac cines were acquired with a series of single breath-hold balanced steady-state free precession images including multiple short-axis stacks. The echo time (TE) was 1.5 ms; repetition time (TR) 3.0 ms; flip angle 50°; slice thickness was 6 mm with a 2 mm gap.18 were generated from the same short-axis images as previously published. Typical acquisition parameters were: TE/TR: 1.07/2.14 ms, flip angle: 35°, matrix size: 192 × 144, field of view: 340 × 255 mm, slice thickness: 6 mm, 107 phase-encoding steps, interpolated pixel size: 0.9 × 0.9, GRAPPA: 2, 24 reference lines, cardiac delay time TD: 500 ms, 206 ms acquisition time for single image, and phase partial Fourier 6/8.For the evaluation of diffuse myocardial injuries, Modified Look-Locker Inversion recovery (MOLLI) T1 maps19: LV mass (LVM), LV end-diastolic volume (EDV), LV end-systolic volume (ESV), peak ejection time (PET), peak filling time (PFT), peak ejection rate (PER), and peak filling rate (PFR). The heart rate (HR) was measured during the MRI procedure. All volumetric indexes and function parameters were normalized to the BSA. The LVM index (g/m2) was calculated by multiplying the difference between the epicardial and endocardial end-diastolic indexed volumes by the density of the myocardial tissue (1.05 g/mL). Analyses of the T1 relaxation maps were performed directly on the maps as described in a previous study20. Short-axis images were automatically contoured to outline the endocardium and epicardium. To quantify the T1 values, manual contouring was used to define the regions of interest (ROIs) in the anterior, septal, inferior and lateral segments of the LV myocardium on the mid-ventricular short- axis slices. Shimming and center frequency adjustments were performed to generate images free from off-resonance artifacts. All quantitative analyses of all CMR images were performed by two operators unaware of the subjects’ clinical information and the results of other diagnostic tests.All MR images and maps analysis were performed offline using Argus software  according to the Society for Cardiovascular Magnetic Resonance guidelines for reporting MR examinationsp < 0.05 was considered statistically significant. All data analyses were conducted using SPSS Statistics .Continuous data were tested for normality using the Kolmogorov-Smirnov test. Normal distribution data were expressed as means ± standard deviation (SD) and abnormal distribution data were expressed as medians (25th and 75th percentiles). The comparison between the two groups utilized unpaired Student t-test, or Mann-Whitney U test (nonparametric test). Multiple comparisons were performed by One-way ANOVA, with post hoc testing as appropriate. Correlations of variables were determined by Spearman or Pearson’s analysis. All of the statistical tests were two-tailed and p > 0.05). FT3 levels in the SHT patients were slightly lower compared with those in the controls , but the difference did not reach statistical significance. The TSH level was significantly higher in the SHT group comparison with that in the control group . Notably, although they remained within the normal range, the FT4 levels of the SHT patients were significantly lower than those in the controls , indicating thyroid hormone deficiency.A total of 36 subjects were evaluated during the study period, including 20 patients with SHT and 16 controls. The baseline characteristics of the two groups are reported in Table p = 0.026), suggesting poor cardiac filling in individuals with early thyroid hormone deficiency.  (Table p < 0.05). However, no significant differences in T1 values were observed between the mild SHT subgroup and the control group   in the LV, native MOLLI showed significantly higher myocardial T1 values in the SHT patients compared with those in the healthy controls  Table ; Table 55) Table .Table 4TNative MOLLI Fig.  showed sp = 0.003)   Fig. , and a s02) Fig. . These fThis was the first study in which the index of myocardial injury (fibrosis and oedema) was evaluated in patients with subclinical hypothyroidism. There are several important findings in our study: SHT patients have significantly longer native myocardial T1 times compared to those of healthy controls, which is consistent with the presence of diffuse interstitial myocardial fibrosis. Furthermore, the extent of this fibrosis was correlated with the levels of FT4 and TSH, suggesting a hormone link between diffuse myocardial injuries and abnormal thyroid function. In addition, the patients with severe SHT were affected by diastolic dysfunction as evidenced by a significantly reduced PFR compared to that in the controls. The patients with TSH levels between 4.5 and 10 µIU/ml were not affected by myocardial injury.21. Previous ultrasonic studies have shown that the mitral diastolic peak late velocity (Amax), mitral diastolic early inflow deceleration time and isometric relaxation time (IRT) were significantly higher in SHT patients versus those in controls22, all of which are parameters of left ventricular diastolic function. Importantly, impaired diastolic function often precedes systolic dysfunction in HT patients. Additionally, SHT is regarded as an independent risk factor of coronary heart disease (CHD)24.The effect of altered thyroid function is apparent in clinical practice by the cardiovascular alterations observed in patients with SHT25. Despite thyroid hormones within the normal range, SHT should be considered a mild form of thyroid failure, in which impaired diastolic relaxation has also been documented26. However, no evidence is available to support the presence of tissue effects due to altered thyroid function in SHT patients. T1 mapping is a previously histologically validated CMR technique that can provide information regarding myocardial injury in different ventricular regional segments27. CMR with T1 mapping quantification allows detection of coexisting functional and textual abnormalities of the myocardium that are partially undetectable by conventional CMR in patients with mild thyroid hormone deficiency. Our research demonstrated by quantification that diffuse myocardial injuries could be detected in SHT even in the absence of clinical symptoms for the first time. Meanwhile, myocardial abnormalities were associated with disease severity in patients with SHT.CMR is currently the most accurate and reproducible technique for evaluating cardiac volumes and function due to its excellent image resolution and intrinsic tissue contrast. Previous research utilizing CMR reported that only cardiac dysfunction, such as typical diastolic dysfunction, was induced by thyroid hormone deficiency in patients with overt HT28. Thyroid hormones modulate the expression and function of several enzymes and proteins involved in cardiac performance. Thyroid hormone deficiency can result in reduced calcium reuptake into the sarcoplasmic reticulum during diastole and increased hyaluronan in the myocardial interstitium, which can impair diastolic filling. An age-related decline in LV diastolic function should also be considered. However, no difference in age was found between the SHT patients and the controls in our study.The cellular mechanisms by which thyroid hormones act on diastolic cardiac function are complex. In animal experiments, SHT in adult hamsters resulted in thinning of myocardial artery, decrease myocardial cells and extensive fibrosis29. Therefore, a mild decrease in the serum FT4 concentration within the normal range could cause the TSH level to increase beyond its normal range. Most experts believe that an elevated serum TSH concentration is a marker of true thyroid hormone deficiency. Dr. Sellitti detected clear TSH receptor (TSHR) mRNA expression in a pig’s heart by RT-PCR technology. Dr. ZhaoJiajun reported that the heart was the target organ of TSH because he identified the presence of functional TSHRs in the ventricular tissue cells of mice. However, the mechanism of the characteristically elevated serum TSH level in SHT in the induction of cardiac damage is not yet clear.Further analysis confirmed the negative relationship between thyroid hormone deficiency and myocardial injuries. The serum TSH level changes logarithmically with arithmetic changes in the serum concentration of FT430. The relative levels of fibrosis varied markedly between the severe SHT patients and the controls in our study, which may partially account for the decreased PFR, thus explaining the impaired ventricular filling at an early stage. Moreover, MRI-derived indexes of LV diastolic filling revealed abnormalities of myocardial relaxation only in patients with severe SHT and not in those with mild SHT in our research. The cardiac effects of subtle thyroid dysfunction, such as mild SHT, are less clear. In a recent study, CMR was used to evaluate 30 women with mild SHT (TSH: 3.7–8.7 µIU/ml) due to Hashimoto’s thyroiditis and 20 matched control subjects. The EDV was significantly decreased and systolic performance was altered in these mild SHT patients31. Furthermore, no significant differences were observed, but significant overlap of native T1 times was identified between the mild SHT patients and the control subjects, implying a limited extent of diffuse myocardial fibrosis in mild SHT. The relationship between native myocardial T1 times and diastolic dysfunction has been described in overt HT patients in our previous study17. However, we did not observe a significant correlation between T1 values and PFR in this study, which is regarded as a reflection of LV diastolic filling. This result may be due to differences in the numbers and conditions of the patients enrolled.In previous studies, impaired LV diastolic function is the most consistent finding in patients with SHT as confirmed by Doppler echocardiography, TDE, CMR and radionuclide ventriculography (RNV)33. Whether levothyroxine could be cardiotoxic is also controversial. Previous animal experiments have shown that in adult hamsters with SHT, thyroid hormone replacement therapy could prevent myocyte loss, reverse left ventricular remodeling, and improve coronary flow34. Furthermore, in a rat myocardial infarction-heart model, Martin Gerdes’ group found that thyroid hormone replacement therapy attenuated atrial remodeling and reduced atrial fibrillation inducibility35. In clinical practice, early detection of myocardial lesions is critical to the timing of treatment. Based on the natural course of the disease, oral L-thyroxine replacement therapy is recommended for SHT patients with TSH levels >10 µIU/ml29. For SHT patients with TSH levels <10 µIU/ml, the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) both agree that the decision to treat should be tailored to each individual patient without any standardization. A study from the Cleveland Clinic Preventative Cardiology Clinic showed that untreated patients with TSH levels greater than 6.1 µIU/ml had higher all-cause mortality36. Another study on adults with atrial fibrillation (AF) with or without levothyroxine treatment showed that levothyroxine treatment decreased the mortality risk in women with AF and reported that the treatment seemed to be safe37. According to our study, we found that severe SHT was associated with obvious myocardial injuries by T1 mapping CMR and should be treated. This conclusion is consistent with clinical treatment guidelines. For mild SHT, if T1 values increase obviously, we suggest that timely treatment should be applied. Therefore, the ability to non-invasively evaluate diffuse fibrosis in SHT is likely to enhance our understanding of the pathogenesis and disease progression. Additionally, T1 quantification can be used for early detection and can serve as a screening tool before overt myocardial changes manifest. The age of SHT patients should also be mentioned. With increasing age, the range of normal TSH levels may be wider. Therefore, elderly individuals with mild TSH elevations may not actually qualify as subjects with subclinical hypothyroidism. The patients in our study were young and may benefit from CMR to detect SHT-induced cardiac dysfunction.Currently, oral L-thyroxine replacement therapy for SHT patients is controversial because the benefits of this therapy vary across different situationsOur study was a single-center study with a relatively small number of enrolled patients. Furthermore, since the time at which the active pro-fibrotic state manifests in the myocardium of patients with SHT is uncertain, serial imaging using T1 mapping techniques over a patient’s lifetime may provide crucial information regarding the timing of this process. However, our conclusions require a study with a larger sample size for further confirmation.38. Therefore, early detection of myocardial injuries caused by SHT is particularly important. Our study confirmed the presence of myocardial injuries in patients with SHT using T1 mapping for the first time, especially in those with severe SHT. The data summarized in this paper strongly support treatment of these patients. As an emerging tool, CMR T1 mapping can help us detect subclinical myocardial lesions earlier and provide a basis for individual treatment plans. We believe that this technique has good clinical application value and may be more common in the near future.SHT has an insidious onset without typical symptoms and increases the incidence of adverse cardiovascular events. Several important cardiovascular risk factors may improve with L-T4 replacement therapy


Characterizing myocardial mechanical properties is valuable in understanding cardiomyopathy with and without clinical heart failure (HF). We sought to examine the incremental value of strain assessment in patients with left ventricular systolic dysfunction without HF (LVSD), HF with reduced ejection fraction (HFrEF), LV diastolic dysfunction without HF (LVDD) and HF with preserved EF (HFpEF) during routine cardiac MR (CMR) evaluation.All study participants were enrolled prospectively to undergo CMR in a 1.5 T scanner. HF was diagnosed with clinical manifestations and elevated BNP (>400 pg/ml) or NT-BNP (> 900 pg/ml). Patients with myocardial infarction and severe mitral regurgitation were excluded. LVSD was defined as having LVEF < 50%. LVDD was determined by echocardiographic criteria or by elevated LV filling pressure assessed during cardiac catheterization. Myocardial circumferential strain (CS) and strain rate (CSR) were taken as the average of basal, mid and apical CS and CSR of the CMR cine images using feature tracking . The longitudinal strain (LS) and strain rate (LSR) were analyzed in 4-chamber view.Mean LVEF was 26 ± 10% for HFrEF (N = 16) and 35 ± 8% for LVSD (N = 14). The average CS was lowest in HFrEF (-8 ± 3%) followed by LVSD (-9 ± 3%) compared to normal (-17 ± 2%) (N = 11) (p < 0.001). In contrast, CS was largely unaltered in LVDD (-15 ± 4%) (N = 14) and in HFpEF (-18 ± 3%) (N = 10). While HFrEF demonstrated lowest LS (-6 ± 3%) which was followed by LVSD (-9 ± 2) and HFpEF (-9 ± 3%) when compared to normal (-14 ± 2%) (p < 0.001), LVDD did not show significant LS reduction (-14 ± 2%). Findings of CSR and LSR were similar to CS and LS, respectively (both p < 0.001). The early diastolic relaxation rate in the circumferential direction dropped by ~50% in HFrEF and LVSD but it was largely unchanged in HFpEF and LVDD. However, LVDD demonstrated significantly enhanced late diastolic relaxation rate (45 ± 15%) compared to normal (22 ± 9%) (p < 0.001) whereas other groups did not.In contrast to reduced CS and LS in HFrEF and LVSD, HFpEF is characterized by preserved CS but markedly reduced LS. While LVDD has preserved CS and LS it is associated with heightened late diastolic relaxation rate. Identifying these distinctive myocardial mechanical features can be an important addition to CMR evaluation of cardiac function and tissue characteristics.


In stable coronary artery disease (CAD), accurate ischemia detection enables targeted revascularization, which improves clinical outcomes. Myocardial blood volume (MBV) may be a better ischemia marker than myocardial blood flow. Adenosine stress and rest T1-mapping is a novel gadolinium-free CMR technique that reflects changes in MBV through its water content. We hypothesized that different myocardial tissues in CAD patients and controls have distinctive T1-responses to adenosine, enabling ischemia detection without gadolinium agents.CAD patients  and normal controls  underwent CMR at 1.5T to assess for LV function (cine), ischemia (adenosine stress/rest first-pass perfusion) and viability . These were compared with novel adenosine stress/rest T1-mapping performed using ShMOLLI. T1 values of different myocardial tissues  were estimated using manually placed regions of interest (ROI). ROI for infarcts were placed in the infarct core, carefully referenced to LGE and cine. ROI for ischemic myocardium were placed in regions corresponding to reversible perfusion defects on first-pass imaging, downstream significant angiographic coronary stenosis, and without evidence of LGE. ROI for remote myocardium were placed in areas free from perfusion defects, infarctions, upstream angiographic stenosis or wall motion defects.Normal controls showed normal resting myocardial T1 952 ± 18 ms) and positive T1-reactivity of ~6% from baseline during adenosine stress . Younger and older controls showed similar resting T1  and T1-reactivity . In CAD patients, infarcted myocardium exhibited the highest resting T1 of all myocardial tissues , with no T1-reactivity (0.2 ± 0.8%). Ischemic myocardium displayed higher resting T1 than normal controls , with no T1-reactivity (0.2 ± 0.7%). Remote myocardium of CAD patients (non-ischemic/non-infarcted) showed normal resting T1 (954 ± 13 ms), with blunted T1-reactivity  compared to normal controls  myocardium of CAD patients, compared to controls, may deepen our understanding of CAD pathophysiology. Stress/rest T1-mapping has the potential to become a powerful diagnostic and risk stratification tool for CAD.


Myocardial T1 mapping holds promise for non-invasive evaluation of diffuse fibrosis. Nevertheless, the widely used cardiac T1 mapping techniques, including MOLLI and SASHA, are generally not applicable to patients with implanted cardiac devices, such as implantable cardioverter defibrillators (ICDs) and pacemakers, due to large off-resonance induced by the device and the associated banding artifacts when using bSSFP readouts. We sought to develop and validate an improved technique for accurate myocardial T1 mapping in patients with implanted cardiac devices.3. The BLESSPC fitting algorithm recently described by Shao et al.  was applied to the reconstruction of T1 maps.Recent work by Rashid et al.  demonstrates the use of a wideband adiabatic inversion pulse in late gadolinium enhancement (LGE) MRI to remove hyper-intensity image artifacts during myocardial scar imaging of patients with cardiac devices. In this work, we incorporate a similar wideband inversion pulse to a MOLLI sequence based on FLASH readouts, using a M0-(1)-5-(1)-3-(1)-1 acquisition scheme shown in Figure Wideband FLASH-MOLLI was evaluated using 8 phantom studies and validated in 10 healthy volunteers and 5 patients with ICDs using a 1.5T MR scanner. The effects of off-resonance frequency variation, heart rate variation, and presence of ICD on T1 estimation accuracy were investigated using phantom studies. To mimic ICD-induced image artifacts, the ICD generator was attached to the body coil and close to the left shoulder of healthy volunteers. The original FLASH-MOLLI sequence using a 3-(3)-3-(3)-5 acquisition scheme was used to image one healthy volunteer (before and after ICD attachment) and in one patient with ICD for comparison.Wideband FLASH-MOLLI generated consistent T1 values over a wide range of off-resonance frequencies Figure  and showThis study demonstrates the feasibility of using wideband FLASH-MOLLI for accurate myocardial T1 mapping in patients with implanted cardiac devices through mitigation of image artifacts associated with conventional T1 mapping techniques.


The evolution of T1ρ and of other endogenous contrast methods  in the first month after reperfused myocardial infarction (MI) is uncertain. We conducted a study of reperfused MI in pigs to serially monitor T1ρ, T2 and T1 relaxation, scar size and transmurality at 1 and 4 weeks post-MI.n = 10) and 4 weeks (n = 5). Semi-automatic FWHM  thresholding was used to assess scar size and transmurality and compared to histology. Relaxation times and contrast-to-noise ratio were compared in healthy and remote myocardium at 1 and 4 weeks. Linear regression and Bland-Altman was performed to compare infarct size and transmurality.Ten Yorkshire swine underwent 90 min of occlusion of the circumflex artery and reperfusion. T1ρ, T2 and native T1 maps and late gadolinium enhanced (LGE) cardiovascular magnetic resonance (CMR) data were collected at 1 week (T1 = 7.0 ± 3.5 (1 week) and 6.9 ± 2.4 (4 week), CNRT1ρ = 12.0 ± 6.2 and 12.3 ± 3.2, and CNRT2 = 8.0 ± 3.6 and 10.3 ± 5.8. Infarct size was not significantly different for T1ρ, T1 and T2 compared to LGE (p = 0.14) and significantly decreased from 1 to 4 weeks (p < 0.01). Individual infarct size changes were ∆T1ρ = −3.8%, ∆T1 = −3.5% and ∆LGE = −2.8% from 1 – 4 weeks, but there was no observed change in infarct size for T2 or histologically.Relaxation time differences between infarcted and remote myocardial tissue were ∆T1 (infarct-remote) = 421.3 ± 108.8 (1 week) and 480.0 ± 33.2 ms (4 week), ∆T1ρ = 68.1 ± 11.6 and 74.3 ± 14.2, and ∆T2 = 51.0 ± 10.1 and 59.2 ± 11.4 ms. Contrast-to-noise ratio was CNRT1ρ was highly correlated with alterations left ventricle (LV) pathology at 1 and 4 weeks post-MI and therefore it may be a useful method endogenous contrast imaging of infarction.The online version of this article (doi:10.1186/s12968-017-0332-z) contains supplementary material, which is available to authorized users. Ischemic heart disease is an enormous health and economic burden and the most common cause of death throughout the world . A devasT1ρ (“T-one-rho”) CMR has recently emerged as an endogenous contrast method for quantitative imaging of myocardial injury –13. T1ρ We conducted a serial study of reperfused infarction in pigs to monitor T1ρ at 1 and 4 weeks post-MI. The objectives were to compare T1ρ relaxation time changes in ischemic tissue with native T1, T2 and LGE and associate each with infarct size and transmurality. Finally, imaging results were correlated with fibrosis using histological data.n = 10) were procured for this study. During all procedures, sedation was induced with intramuscular ketamine, endotracheal intubation was performed, and the animal was maintained with a mixture of isoflurane 1-2% and oxygen with a ventilator tidal volume of 20 mL/kg . Anesthesia and animal temperature was closely monitored for the duration of surgical and imaging procedures to maintain a constant physiologic state. Arterial access was obtained at the carotid artery for measurement of intraventricular pressure . Venous access was obtained at the internal jugular veins for administration of medication. After each procedure, the animal was weaned from anesthesia and transported to the recovery room. Upon completion of the terminal CMR study, the animal was returned to the operating room for euthanasia and tissue harvest.Yorkshire swine (n = 5) and II, a 4-week terminal study (n = 5). Furthermore, five animals  underwent a baseline CMR immediately prior to coronary artery occlusion. The experimental model was chosen to emulate human post-percutaneous coronary intervention ischemia injury. All the animals of the 4 week group underwent both 1 and 4 week CMR. Figure Ten pigs underwent 90 min of coronary artery occlusion and were randomized into two groups: group I, a 1-week post-MI terminal study  with 40 mT/m gradient and 12 channel RF receiver arrays. Intraventricular pressure was interfaced to physiological monitoring software and filtered to facilitate dual respiratory and cardiac gating . All 2D images were acquired in the short-axis during breath-holding and 3D with dual cardiac and respiratory gating. Breath-holding was performed by temporarily disabling the animal ventilator.x – SLy - 180y – SL-y - 90-x) [1 = 500 Hz, spatial resolution = 1.4 × 1.4 mm2, slice thickness = 6 mm, flip angle = 70°, TE = 1.45 ms, TR = 2.9 ms, NSeg = 55, bandwidth = 900 Hz/pixel, linear k-space phase encoding ordering, parallel imaging with acceleration factor = 2, 34 reference k-space lines obtained in a separate heartbeat, and four heartbeats for T1 relaxation between shots. The T1ρ amplitude was set at the highest available within scanner specific absorption rate limits (B1 = 500 Hz).2D T1ρ single-shot balanced steady-state free precession (bSSFP) sequences were performed using a spin echo, spin lock (SL) T1ρ pulse cluster (90 - 90-x) , 15. T1ρx – 180y – 90-x) bSSFP sequence and 8 images were acquired with different contrast times TE = 2, 10, 18, 26, 34, 42, 50 ms using the same readout as with the T1ρ images.2D T2 maps were obtained using a single-shot T2 prepared  . Other p2, slice thickness = 6 mm.Retrospective, short axis, multi-slice cine CMR was performed with a temporal resolution = 40 ms, flip angle = 70°, bandwidth = 940 Hz/pixel, spatial resolution = 1.1 × 1.1 mm2, flip angle = 50°, TE = 1.6 ms, TR = 3.2 ms. slice thickness = 2 mm, and parallel imaging acceleration factor = 2 [The animals received a 0.1 mmol/kg intravenous injection of gadolinium contrast for LGE imaging . Imaging was performed 10 minutes after injection of contrast agent using an inversion time (TI) scout sequence to determine the inversion time to null myocardial tissue signal. LGE CMR was obtained using a 3D multishot phase-sensitive inversion recovery (PSIR) bSSFP sequence at spatial resolution = 1.2 × 1.2 mmctor = 2 .After ex vivo CMR, the heart was flash-frozen using liquid nitrogen in a 4.5 L cryogenic container . The heart was sectioned into uniformly thick short axis slices using a commercial-grade prosciutto slicer  obtaining slices of uniform thickness of approximately 2 mm to be matched to CMR studies. Slices were submerged in a PBS solution with 0.1 M triphenyl tetrazolium chloride (TTC) and incubated at 50 ° C for 15 min . Slices Cine CMR image series were used to calculate indexed LV mass (Mass), wall thickness (WT), end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and cardiac output (CO). Epi- and endocardial contours were drawn manually at ED and ES (excluding papillary muscles) using standard techniques  , 20.For all images, scar size was assessed using full width at half maximum (FWHM) thresholding in a mid-LV slice with visible enhancement on LGE (QMass) . FWHM thScar transmurality was computed as the ratio of hyperintense (infarct) to non-enhanced myocardium (%) in a mid-ventricular short axis slice. The myocardium was divided into six circumferential wedges and transmurality was reported for anterolateral and posterolateral segments in which infarction was observed (two of six segments). Scar transmurality <5% in a segment was excluded as noise.Motion correction was used to align T1ρ and T2 images using optical flow estimation of the image deformations . T1 and ∆TX=TXinf–TXrem and TXinf (TXrem) was the mean relaxation time in the infarcted (remote) tissue and σ(TXrem) was the standard deviation of the relaxation times observed in remote myocardium [Contrast-to-noise ratio (CNR) was calculated for T1ρ, T2 and native T1:ocardium .t-test.Descriptive statistics were reported as mean ± standard deviation (SD). Comparison of statistical means was performed using 2-way analysis of variance. Correlations were assessed with Pearson’s r. Bland-Altman testing was performed to test for mean bias and variation between imaging methods . Pairwiss = 10) survived the 90 min ischemia and reperfusion study to their terminal CMR at 1 or 4 weeks. At 4 weeks post-MI, there was a 13.4 ± 5.4% reduction in EF compared to baseline and associated with a 22.7 ± 8.0 mL increase in ESV and a 24.2 ± 14.1 mL increase in EDV. End diastolic wall thickness decreased by 4.0% after 4 weeks (p < 0.05) and ΔWT and ΔLVEDV between baseline and 4 weeks were correlated . Additional details are reported in Table All pigs s = 0 surviveHyperintense regions were observed at the lateral wall on all T1ρ, T2, and T1 maps and in LGE images at 1 and 4 weeks, consistent with ischemic injury to the circumflex coronary circulation  and 12.3 ± 3.2 (4 week), CNRT2 = 8.0 ± 3.6 and 10.3 ± 5.8 and CNRT1 = 7.0 ± 3.5 and 6.9 ± 2.4.As illustrated in Fig. ss = 0.14) and, among animals who underwent both 1 and 4 week CMR, significantly decreased from 1 to 4 weeks (s < 0.01). Individual infarct size changes were ΔT1ρ = −3.8%, ΔT1 = −3.5% and ΔLGE = −2.8% from 1 to 4 weeks , good correlation for T1 and LGE  and poor correlation for T2 and LGE   and was unchanged from 1 to 4 weeks (p = 0.15).Infarct transmurality was not significantly different for T1ρ, T1 and T2 compared to LGE (p < 0.001), T1 and LGE  and moderate correspondence between T2 and LGE   T1ρ values had higher relaxation time-dependent change than T2 and contrast-to-noise ratio compared to T1 and T2 in the infarcted myocardium; (2) there was a decrease in infarct size from 1 to 4 weeks on T1ρ, T1 and LGE CMR; and (3) T1ρ infarct size was better correlated with LGE than T1 or T2 and that T2 in particular was poorly correlated. Improved infarct contrast-to-noise ratio on T1ρ may explain the better correlation with LGE and histological infarct size and transmurality than T1 and T2.T1ρ is increased in acute and chronic myocardial infarction , 11, 13,Furthermore, while T2 and native T1 are believed to be biomarkers for myocardial edema in the area-at-risk after acute MI , recent T2 had reduced correlation with LGE as compared to T1ρ and T1, which may be partly explained by differences in the way post-infarction hemorrhage affects endogenous contrast. Degradation of hemoglobin byproducts in the hemorrhage in T2 and T2* CMR studies in patients and animals contribute to increased magnetic susceptibility-induced dephasing on CMR , 28. Acc1. As the amplitude B1 approaches zero, T1ρ approaches T2 . In our comparison of T1ρ, T2 and T1, we used identical readout sequences to eliminate a major cause of measurement variation. In addition, we matched the time between adjacent T2 or T1ρ preparations (4 heartbeats) and discarded the first scan because of variations in T1 recovery between preparations.Another reason for the poor T2 agreement with LGE is that different methods of preparation may give different T2, e.g. preparations with adiabatic refocusing pulses instead of a non-selective Hahn spin echo . The freInfarct size is expected to decrease from sub-acute to chronic post-infarction times . T1ρ, T1We found that T1ρ and T1 infarct transmurality was correlated with LGE CMR at 1 and 4 week post-MI. However, differences in T1ρ infarct transmurality might be explained by the varying acquisition times in the cardiac cycle. Although infarct size is not influenced by cardiac cycle, scar transmurality (derived from LGE CMR) has shown to vary between end-diastolic and end-systolic assessment . LGE MR T1ρ CMR is increased in myocardial infarction compared to T2 and has improved contrast-to-noise ratio compared to T1 and T2. Infarct size and transmurality on T1ρ and native T1 endogenous contrast was correlated with LGE CMR and thus may be useful as endogenous contrast CMR methods in ischemic patients who cannot receive contrast agents.


Left ventricular (LV) diastolic function can be evaluated by echocardiographic indices of LV relaxation/restoring forces, diastolic compliance, and filling pressure. By using a combination of indices, diastolic function can be graded and LV filling pressure estimated with high feasibility and good accuracy. Evaluation of diastolic function is of particular importance in patients with unexplained exertional dyspnea or other symptoms or signs of heart failure which cannot be attributed to impaired LV systolic function and to assess filling pressure in patients with heart failure and reduced LV ejection fraction. Furthermore, grading of diastolic dysfunction can be used for risk assessment in asymptomatic subjects and in patients with heart disease. Left ventricular systolic function is evaluated clinically by measuring left ventricular (LV) ejection fraction (EF) and more recently by strain imaging as a supplementary method. Evaluation of LV diastolic function is more challenging, and a number of different noninvasive approaches have been proposed. Recently, important consensus was reached regarding use of echocardiography to assess diastolic function , and twoE) and smaller atrial-induced velocity (A) was disturbed in arterial hypertension and in specific heart diseases. In hypertension and in myocardial infarction, there was E/A reversal and reduced deceleration rate of early filling . Finally, atrial contraction causes late diastolic filling, giving rise to the A-velocity.During isovolumic relaxation, LV pressure falls rapidly, and when it has declined below atrial pressure, a pressure gradient is established between the atrium and the ventricle, the mitral valve opens, and the ventricle fills rapidly, giving rise to the ity Fig. . During L-velocity is not entirely clear, but it is associated with elevated LV diastolic pressure and impaired myocardial relaxation . The. TheS) wD-velocity coincides with the transmitral E-velocity, and its magnitude is determined by essentially the same factors that modify mitral E. In normal individuals, the pulmonary venous S is usually higher than D. With advanced LV diastolic function which is characterized by elevated mitral E-velocity, there is typically elevated D velocity, and for reasons explained in the previous paragraph, there is reduced S-velocity. Therefore, the S/D ratio is usually <1 in patients with heart failure and elevated LV filling pressure. Young healthy subjects with excellent LV relaxation may also have S/D < 1, but in contrast to patients with advanced diastolic dysfunction, there is not a marked Ar. With increasing LV diastolic pressure, which leads to reduction in operative LV compliance, atrial contraction pushes an increasing volume of blood back into the more compliant pulmonary veins, and this is evident as increase in peak value and duration of Ar . Pr. Pr18]. Left ventricular diastolic compliance is a lumped parameter and is determined not only by LV myocardial compliance, but also by elastic properties of extraventricular structures (pericardium and lungs) and by right ventricular diastolic pressure. The term LV chamber compliance is often used rather than just LV compliance, with the latter referring to myocardial compliance. Because the LV pressure–volume relationship is curvilinear, chamber compliance is a function of the operative LV diastolic pressure. As an example, elevation of LV diastolic pressure by volume loading, which moves the LV pressure–volume coordinate to a steeper part of the pressure–volume curve, causes reduction in chamber compliance in a ventricle which is entirely normal. Therefore, reduced chamber compliance does not necessarily mean there has been a change in myocardial elastic properties. Figure E and tall A. The pattern of pseudonormalized filling (grade II) has flow velocities similar to a normal heart and is identified by reduced e′. The pattern with tall E with short deceleration time (<150 ms), combined with small A and E/A > 2 is named restrictive filling (grade III) and is associated with reduced LV diastolic compliance [E deceleration time and degree of diastolic dysfunction is nonlinear; therefore, in mild diastolic dysfunction dominated by impaired relaxation, there is prolongation of E deceleration time because of ongoing relaxation during flow deceleration. Importantly, in young healthy individuals with high mitral E, there is often a deceleration time <150 ms. Therefore, a short deceleration time should not be used as a standalone index of reduced LV compliance. Healthy people, however, do not have a large Ar, which is typical for ventricles with reduced compliance as discussed below.Different mitral filling patterns are displayed in Fig. mpliance  Fig. 8)E and talA velocity and is typically combined with accentuation and prolongation of the pulmonary vein Ar [Ar exceeds the duration of mitral A by >30 ms, it is consistent with elevated LV end-diastolic pressure. The limitations of A duration difference as an index of diastolic compliance include atrial mechanical failure and suboptimal quality of the pulmonary venous flow signal. Furthermore, even in patients with severe diastolic dysfunction, a large Ar may be absent when there is prolonged atrioventricular conduction or tachycardia, so that atrial contraction takes place before diastolic pulmonary venous flow (D) is completed. In these cases, the difference in A duration does not reflect LV filling pressure.Reduction in LV chamber compliance is also reflected in attenuation and abbreviation of the transmitral vein Ar , 8. WhenE deceleration time together with a small and abbreviated mitral A and a large Ar of long duration are consistent with reduced LV compliance.Thus, a short mitral 2 is considered enlarged [Whereas Doppler-derived diastolic indices reflect LV filling pressures at the time of measurement, LA volume reflects the cumulative (chronic) effect of LV filling pressures over time in patients who are in sinus rhythm and do not have mitral disease, anemia, or other high-output states. LA volume >34 mL/menlarged . There iMore recently, global LA strain by two-dimensional (2D) speckle tracking echocardiography was introduced as a promising supplementary marker of LV filling pressure. Elevated LA pressure is associated with low values for LA reservoir strain. The incremental value of measuring LA strain remains to be defined, but preliminary data from smaller studies are promising.In patients with heart failure symptoms and normal LVEF, the finding of LV hypertrophy favors HFpEF as diagnosis. After introduction of strain imaging by speckle tracking echocardiography, it became apparent that patients with normal LVEF may have mildly reduced LV systolic function by global longitudinal strain. Therefore, LV strain imaging represents a supplementary test which is useful when echocardiographic indices of diastolic function are inconclusive and it is not clear whether the patient suffers from heart disease. Reduced global longitudinal strain provides support in favor of heart disease as underlying mechanism of symptoms.e′, E/e′, LA volume index, and peak tricuspid regurgitation velocity were positive [Diastolic dysfunction is present in arterial hypertension, diabetes mellitus, obesity, and in a large number of cardiovascular disorders often at a preclinical stage, and is part of normal aging. Diastolic dysfunction may be graded as illustrated in Fig. positive . This reE is <50 cm/s combined with E/A < 1 is that a low E implies a small transmitral pressure gradient. The combination with E/A < 1 confirms that E is low also when compared with A. When E is tall and much higher than A, it implies a high transmitral gradient, which in turn implies high LA pressure. One exception is young healthy individuals, who may have negative early diastolic pressure and therefore high gradient and tall E with normal LA pressure. For intermediate mitral filling patterns, the recommendation is to use E/e′, LA volume, and peak TR velocity in combination  on top of elevated minimum LV diastolic pressure (suggested by low e′) means high LA pressure. Large LA reflects long-term effect of elevated LA pressure. High TR regurgitation velocity implies high pulmonary artery systolic pressure. It was recently confirmed in two large multicenter studies that this algorithm can identify patients with elevated filling pressure with high feasibility and good accuracy [When the purpose of the study is to determine whether a patient has elevated LV filling pressure, the ASE/EACVI guideline recommends using the algorithm presented schematically in Fig. ion Fig. . The reaaccuracy , 3.A common misinterpretation of the ASE/EACVI guideline  is that When evaluating patients with potential HFpEF, one should always search to exclude diseases such as valve disease, coronary artery disease, pericardial disease, and right-sided heart disease before it is concluded that a patient suffers from HFpEF. Furthermore, since LV diastolic pressure may be entirely normal at rest in HFpEF, a noninvasive and sometimes invasive diastolic stress test is recommended when there is inconsistency between symptoms of heart failure and echocardiographic findings at rest , 24. ImpWhen pulmonary hypertension is observed in combination with signs of LV disease, it is consistent with elevated LV filling pressure. Pulmonary artery systolic pressure can be estimated in most patients by continuous wave Doppler of tricuspid regurgitation velocity and an estimate of right atrial pressure.When the tricuspid velocity cannot be imaged or the peak of the velocity is not well defined, pulmonary artery acceleration time may be used as an index of elevated pulmonary artery pressure and is measured with high feasibility as the time interval between the onset and peak pulmonary arterial systolic flow velocity . Values In patients with unexplained exertional dyspnea or other symptoms or signs of heart failure which cannot be attributed to reduced LV systolic function or to diseases such as coronary artery disease, valve disease, pulmonary vascular disease, lung disease or other diseases.To determine if LV filling pressure is elevated in patients with heart failure and reduced LV ejection fraction when considering adjustment of diuretics or other heart failure medication.Grading of diastolic function can be used for risk assessment in asymptomatic subjects and in patients with heart disease.Left ventricular diastolic function can be evaluated by measuring indices of LV relaxation, restoring forces, diastolic compliance, and filling pressure. By using a combination of indices, diastolic function can be graded and LV filling pressure estimated with high feasibility and good accuracy regardless of level of systolic function. Evaluation of diastolic function should be considered in the following clinical settings:


The majority (60%) of left ventricular (LV) stroke volume (SV) is generated by longitudinal shortening causing apical atrioventricular plane displacement (AVPD) in systole. The remaining SV is caused by radial inward motion of the epicardium both in the septal and the lateral wall. We aimed to determine if these longitudinal, septal and lateral contributions to LVSV are changed in patients with chronic myocardial infarction (MI).n = 20) or right coronary artery  and healthy controls (n = 20) were examined with cardiovascular magnetic resonance (CMR). AVPD was quantified in long axis cine CMR images and LV volumes and dimensions in short axis cine images.Patients with a chronic (>3 months) ST-elevation MI in the left anterior descending  and RCA-MI  compared to controls (15 ± 0 mm). However, the longitudinal contribution to SV was unchanged for both LAD-MI  and RCA-MI  compared to controls (64 ± 2%). The preserved longitudinal contribution despite decreased absolute AVPD was a results of increased epicardial dimensions (p < 0.01 for LAD-MI and p = 0.06 for RCA-MI). In LAD-MI the septal contribution to LVSV was decreased (5 ± 1%) compared to both controls  and patients with RCA-MIs . The lateral contribution was increased in LAD-MI patients (44 ± 3%) compared to both RCA-MI  and controls .AVPD was decreased both in patients with LAD-MI (11 ± 1 mm, Longitudinal shortening remains the principal component of left ventricular pumping in patients with chronic MI even when the absolute AVPD is decreased. Myocardial infarction (MI) leads to decreased left ventricular function due to the necrosis of myocytes and subsequent replacement with fibrous tissue and is the most common etiology to heart failure . CardiacCardiovascular magnetic resonance imaging has the ability to quantify the amount of stroke volume (SV) generated by longitudinal function by combining the measurements of the AVPD and the short-axis area of the left ventricle encompassed by the AVPD, and express this as a percentage of SV , 11. In n = 20, age 59 ± 3 years, 17 males) or the right coronary artery (RCA) territory  were studied. Time from MI to CMR examination had to be >3 months for patients to be eligible for inclusion. Exclusion criteria were left bundle branch block, MI within more than one coronary territory, previous cardiac surgery with opening of the pericardium and significant pericardial effusion or valvular disease. Patient characteristics are listed in Table This retrospective, cross-sectional study was approved by the Regional ethical committee in Lund and written informed consent was obtained from each subject. Patients with ST-elevation myocardial infarction (STEMI) in the left anterior descending (LAD) territory  to acquire end-expiratory breath held images in the supine position with ECG-triggering. Cine images for LV function were obtained covering the entire heart in the short-axis plane, including both ventricles and atria of the heart using a balanced steady state free precession sequence. Imaging parameters were typically: acquired temporal resolution of 47 ms reconstructed to 30 time phases per cardiac cycle, repetition time 3 ms, echo time 1.4 ms, flip angle 60°, slice thickness 8 mm with no slice gap and SENSE factor of 2. Long-axis images were acquired in the left ventricular two chamber, left ventricular outflow tract and four-chamber planes.LGE images for infarct quantification were acquired using a 3D inversion-recovery gradient-recalled echo sequence in the short-axis plane 10–20 min after intravenous administration of 0.2 mmol/kg gadolinium-based MR contrast medium. Typical sequence parameters were: repetition time 4 ms, echo time 1.3 ms, flip angle 15°, slice thickness 8 mm, in-plane resolution 1.6 × 1.6 mm with inversion time set to null non-infarcted myocardium.All image analysis was done using the software Segment version 1.9 . DelineaThe longitudinal contribution to LVSV Fig.  was calcThe radial contribution to LVSV was defined as the volume difference caused by the inward displacement of the epicardial border of the LV from end-diastole to end-systole and was subdivided into the septal and lateral contributions. The ventricular septum was defined as between the RV insertion points according to the American Heart Association standardization of myocardial segmentation . The LV P < 0.05 are considered statistically significant. Internal validations of the measurements are reported as the sum of the longitudinal, septal and lateral contributions to stroke volume, which in theory should be 100%. Inter- and intra-observer variability and the internal validation were calculated as bias ± standard deviation (SD).All statistical analysis was performed using Graphpad Prism v 6.05 . Comparisons between the three groups were done with 1-way ANOVA with Tukey’s multiple comparison test. Comparisons between patients for infarct size were done with unpaired t-tests and relationships between continuous variables were tested with Spearman correlation analysis. Results for continuous variables are presented as mean ± standard error of the mean (SE) and results with r = 0. 75, p < 0.001 and ESV = 7.78xIS-1.6, r = 0.82, p < 0.001. Ejection fraction had a negative correlation with IS, EF = −1.18xIS-0.8, r = 0.79, p < 0.001. Altogether, patients with MI in the LAD vessel territory had larger volumes and lower EF compared to both patients with RCA-MI and controls (Table p < 0.001). RCA-MI patients also had larger EDV and lower EF compared to controls). Atrioventricular plane displacement was decreased in both LAD-MI (11.0 ± 0.7 mm) and RCA-MI (13.0 ± 0.9 mm) compared to controls  but did not differ between the patient groups (p = 0.08). The epicardial short-axis areas used for calculation of AVPD contribution to SV were increased in infarct patients (p < 0.01) but in the subanalysis, LAD-MI had larger epicardial areas compared to controls (p < 0.01) while RCA-MI did not reach significance (p = 0.06).Parameters of LV size and function for the study groups are presented in Table Figure p = 0.08 for LAD and p = 0.09 for RCA) (Table p < 0.01) (Table p < 0.001) and RCA-MI (p < 0.05) compared to controls  but not in RCA-MI  patients. However, there was no correlation between infarct size and longitudinal contribution to LVSV in LAD-MI  or RCA-MI  patients. Furthermore, infarct size did not correlate to septal contributions to LVSV in LAD-MI , or in RCA-MI , or lateral contributions to LVSV in LAD-MI  or in RCA-MI .Longitudinal contribution to LVSV was numerically lower in patients compared to controls but this difference did not reach statistical significance (A) Table , Fig. 3.1) Table , Fig. 4.ls Table , Fig. 5.2 and for AVPD 0.5±1.0 mm. Intraobserver variability of AVPD in 20 patients analyzed >3 months apart, was 0.3 mm ± 0.7 mm.Internal validation of the measurements by adding the longitudinal, septal and lateral contributions to stroke volume showed 107 ± 16% for LAD-MI, 104 ± 8% for RCA-MI and 103 ± 9% for controls. Interobserver variability for average epicardial areas used for calculation of longitudinal contribution was −0.7±1.7 cmThis study has shown that longitudinal shortening remains the principal contributor to LV stroke volume in patients with chronic MI even when the absolute AVPD is decreased. This is mainly explained by the LV dilatation after an MI causing a larger short-axis epicardial area. The presence and degree of LV dilatation showed a correlation with infarction size. The three-dimensional intrinsic movement of the myocardium during the cardiac cycle is complex. However, when viewing the LV from the epicardial border, the movement is simpler, comprising of a longitudinal shortening and a radial inward motion , 13, 18.Of note, the SV and heart rate, were unchanged in MI patients compared to the age-matched controls. Thus, cardiac output was similar in patients and controls. The longitudinal contribution did not differ between infarcts in the LAD or RCA territory. Septal contribution to SV, however, was decreased and lateral contribution increased in patients with MI in the LAD compared to controls. These findings are as expected from the localization of LAD-MI in the anterior and septal walls Fig. . Thus, tOur findings of preserved longitudinal contribution to LVSV are in line with the results of a previous study in patients with dilated cardiomyopathy . In bothWe did not find any relationship between MI size and regional contributions to LVSV. This may be due to a limited patient population and larger studies may be needed to shed further light on a possible relationship. Larger sized myocardial infarction results in worse remodeling and reduced ejection fraction at follow up, and because of the larger myocardium at risk in anterior LAD-MI these are related to worse remodeling . This waThe reason for using the epicardial area of the LV to calculate the AVPD contribution to SV has been previously described and validated , 11. SimThe mean longitudinal contribution to LVSV on a group level did not differ from controls but the study of individual patients show differences in how LV remodeling after an MI affect cardiac pumping. Fig. In patients with MI a decreased AVPD is associated with worse prognosis  and receAutomatic software for AVPD tracking exists and can be used to minimize user dependency of the AVPD measurements –24. In aIn this study, only patients with chronic MI were included. Thus, the results cannot be directly transferred to acute STEMI or non-STEMI. Further studies are needed to show if there is an effect on the different contributions to LVSV in acute MI and non-STEMI patients. Detailed coronary angiography data was not available in all patients, due to the retrospective nature of the study. Thus, we could not assess the procedural features in cases of percutaneous coronary interventions and the potential impact of the amount of vessel disease. Neither was time from pain onset to reperfusion during the STEMI available in this study and potential impact of remote ischemic preconditioning cannot be assessed.The patient number in this study is limited and larger patient numbers may be needed to study the relationship between contribution of the different components of LV pumping to LVSV and infarct size. Of note, there was a numerically lower longitudinal AVPD contribution to SV in patients compared to controls, however this did not reach statistical significance. Further studies will show if this difference is statistically significant in larger patient materials. We did not include the effect of MI on RV function that may be seen in RCA-MI when part of the RV diaphragm wall sometimes is infarcted. Furthermore, in cases where the septum bulges to the RV during systole due to LV infarction, this movement will contribute to RV pumping. The effects of MI on the longitudinal, septal and lateral RV function may therefore be of interest for future studies. Finally, in this study we did not discriminate the contribution of the anterior, lateral and inferior wall of the LV in this study but combined them to one parameter called lateral contribution, which was compared with its septal counterpart. This was done to decrease the risk of type I errors due to a high number of comparisons in each subject.Chronic MI in the LAD and RCA vessel territory does not change the internal relationship between the contributions to overall LV pumping of longitudinal (≈60%) as compared to radial (≈40%) pumping. Although the overall contribution to SV of radial pumping did not change, MI within the LAD vessel territory caused a decrease in the septal component of radial pumping which seems to be compensated by an increase in its lateral component.


Left ventricular ejection fraction (LVEF) late after arterial switch operation (ASO) is often normal. However, some studies have shown increased indexed end diastolic volume (iEDV) and ventricular mass when compared to healthy controls. We sought to identify LV morphological differences between patients with transposition of the great arteries (TGA post ASO) and matched healthy control subjects. We hypothesised that besides a mere increase in ventricular volume, characteristic shape features can be associated with LV morphology post ASO. Ventricular shape being difficult to quantify using traditional morphometrics, a novel, validated non-parametric statistical shape modelling framework (SSM) was used to analyse 3D anatomical models without the need for landmarking.shape vector, which numerically describes 3D shape features most associated with either of the groups. Size effects due to differences in BSA were removed. Results were visualised by deforming the computed mean LV shape along the shape vector from low values for the control group towards high values for the ASO group. Differences were assessed using non-parametric Mann-Whitney-U test. Correlations between shape features and CMR volumetric data  were assessed using Pearson's correlation. Significance was assumed at p < .05.Cardiovascular magnetic resonance (CMR) data from 18 patients post ASO and 18 age-matched healthy control subjects  were analysed. Institutional review board approved the study; all patients/carers signed informed consent. 3D geometric LV surface models were manually reconstructed from the CMR data  and constituted the input for the SSM. Based on the 36 LV input shapes, the mean LV shape and its deformations towards each patient anatomy were computed , implying distinct morphological differences in LV shape Figure . 3D shapUsing a SSM framework based on CMR, distinct 3D shape features could be associated with LV morphology post ASO. Moreover, those shape features were linked with higher iEDV. Such advanced post-processing of CMR data could lead to identifying previously unknown 3D shape features of cardiac anatomy that distinguish healthy and diseased subjects, thereby constituting novel shape biomarkers for improved CMR-based diagnosis.


Magnetic resonance (MR) imaging has become an important diagnostic tool for the detection of impaired myocardial motion, which has been considered as a common consequence of most ischemic or non-ischemic heart diseases. Both cine DENSE and TPM have been independently adopted to delineate abnormal regional myocardial motion patterns for the estimation of the progression of cardiovascular diseases or for the evaluation of individual cardiovascular responses to treatments. However, although the similarities and differences between cine DENSE and TPM are well understood from a technical point of view, the interchangeability of those two imaging techniques in cardiovascular risk stratification is still not fully understood. The aim of the present study was to test the hypothesis that clinical metrics derived from cine DENSE and TPM are correlated for characterizing regional myocardial motion.This study complied with HIPAA regulations. Thirteen healthy volunteers and 4 asymptomatic recipients of heart transplant (HTx) were recruited following the approval of the institutional review board (IRB). For each participant, two-dimensional (2D) cine DENSE and TPM were performed at basal, midventricular and apical locations at the left ventricle (LV) with the short-axis view. DENSE-derived myocardial metrics, including peak radial strain (Err), circumferential strain (Ecc), first principal strain (E1), second principal strain (E2) and twist were measured and correlated with TPM-derived indices, including peak radial velocity (Vr), circumferential velocity (VΦ) and time to peak (TTP) in systole and diastole using Pearson correlation coefficient (r).DENSE and TPM data were successfully acquired in 17 participants and resulted in 51 data points  for comparisons. On a per-slice basis, peak Err had moderate correlations with peak Vr in systole  and in diastole . Peak E1 was moderately associated with Vr-sys  and Vr-dia . Peak twist was moderately correlated with peak VΦ in diastole . See figures DENSE and TPM can provide correlated clinical metrics for quantitatively characterizing regional myocardial motion from different technical aspects.


In the early stages of some cardiovascular diseases (CVDs), myocardial ischemia only occurs in a limited area. Thus, accurate detection of regional myocardial perfusion abnormalities is important for diagnosis. Recently, myocardial perfusion using MRI has become a promising non-invasive method to evaluate myocardial ischemia in CVDs. However, the reproducibility of MRI for assessment of regional perfusion has not been studied. This knowledge gap could affect the use of Cardiac MR in clinical practice. To address this clinical need, we evaluate the reproducibility of MRI perfusion in 12 healthy volunteers.12 healthy volunteers  were recruited after IRB approval. Written informed consent was obtained. MRI scans were performed at 1.5 T . Each participant underwent two cardiac MRI perfusion scans (steady-state free precession) with the same protocols separated by a 2-week interval. Perfusion data were acquired at base, mid, and apex levels of the left ventricle (LV) after injection of a single dose gadopentetate dimeglumine . Motion Correction Imaging was used to account for cardiac and respiratory motion. The parameters were as follows: FOV = 360 × 360 mm2, Slice thickness = 8 mm, TR/TE/flip angle = 168/1.14 ms/12degree. Measurements = 60The images were transferred to a computer (Siemens Leonardo Syngo) for analysis using ARGUS software. A single reviewer drew the borders (endo and epi) of the LV at each slice for each study. The peak signal intensity, slope of the signal change, and time to peak perfusion (TTP) were evaluated in individual myocardial segments (based on AHA-16-segment model).(COV). Bland-Altman plots were also applied to show inter-study variations.The reproducibility of peak signal intensity, slope, and TTP was assessed using intraclass correlation coefficient (ICC) and coefficient of variation Cardiac MR was successful in 12 volunteers twice and resulted in 192 pairs of data points for each of the three parameters. As summarized in Table Cardiac MR is a reproducible technique for quantitative assessment of segmental myocardial perfusion at rest during quiet breathing. However, technical improvements in image acquisition and processing are needed to further lower its inter-study variability.