Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the n = 31) underwent 3 acute 3 T CMR scans (time-point (TP) < 3 h, 24 h and 6 days), including cine, native shortened modified look-locker inversion recovery T1 mapping, T2* mapping and late gadolinium enhancement (LGE). A second group (n = 17) had a single scan at 24 h with an additional T2-weighted sequence to assess the difference in the extent of area-at-risk (AAR) compared to T1-mapping.A first group  and subsequently increased at 6 days (P = 0.041 for TP2 vs.TP3). However, the extent of AAR quantified using T1-mapping did not follow the same course, and no change was detected between TP1&TP2 (P = 1.0) but was between TP2 &TP3 (P = 0.019). In the second group, the extent of AAR was significantly larger on T1-mapping compared to T2-weighted . No change in LGE was detected while microvascular obstruction and intra-myocardial haemorrhage peaked at different time points within the first week of reperfusion.The mean T1 relaxation time The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation. Following reperfusion treatment in patients with ST-segment elevation myocardial infarction (STEMI), there is an abnormal accumulation of water within the injured myocardium which, when depicted using cardiovascular magnetic resonance (CMR) imaging, defines ‘the area at risk’ (AAR) , 2. The severity of oedema beyond the anatomical area of oedema when quantifying the AAR [area and the severity of oedema within AAR. The severity of oedematous reaction post reperfusion, quantified on T2 mapping, followed similar bimodal changes to the anatomical AAR, quantified as percentage of left ventricle (LV) on T2-weighted images [Recently, there has been debate over the stability of oedema /AAR immediately after reperfusion , 7. Data the AAR , 7 In otd images . This ‘rNative T1 mapping can characterise the injured myocardium and has been shown to characterise viable myocardium in the acute setting . The incintensity of oedematous reaction post ischemia/ reperfusion injury do not necessarily track with changes in the extent of the anatomical AAR (percentage of LV). This may provide a better reflection of actual changes in water content and would afford a better understanding of the application of CMR in assessments of acute myocardial injury.Here, we studied patients very early after reperfusion therapy and sought to investigate the temporal changes in AAR, quantified using a T1 mapping technique post STEMI. We hypothesised that bimodal changes in the Patients presenting with STEMI to the Oxford Heart Centre and who underwent primary percutaneous coronary intervention (PCI) were prospectively enrolled as part of the OxAMI Study , 13. Thithe temporal changes cohort). The initial hyper-acute CMR scan was executed under an assent process [single scan cohort, which was performed after 24 h from the presentation  for functional images, native Shortened Modified Look-Locker Inversion recovery (ShMOLLI) T1 mapping for AAR characterisation, [single scan cohort protocol was identical but additionally a T2-weighted (T2-prepared bSSFP) sequence was obtained to compare anatomical AAR between acquired T1 mapping and T2-weighted imaging.CMR was performed on a 3 Tesla scanner . The scan protocol in isation,  T2* mappT1 maps, T2* maps, late gadolinium enhancement (LGE) and bSSFP short axis images were acquired on matching short-axis slices covering the entire LV; only 3 matching short axis slices were acquired for T1 and T2* mapping in the hyper-acute phase targeting the regional wall motion abnormalities as assessed on functional images.Typical acquisition parameters for bSSFP retrospectively gated cine images were TE / TR =1.4/3.2 ms; flip angle 50°; voxel size: 2.4 × 1.8 × 8.0 mm. To shorten the hyperacute scan, the cine sequence at time point (TP)1 were acquired in a single breath hold using real time electrocardiogram (ECG)-triggered and at lower resolution (160 × 72) compared to other time points (224 × 137).T2W was performed using a T2-prep-bSSFP single shot sequence with surface coil correction .ShMOLLI T1 maps were generated from 5 to 7 bSSFP images with variable inversion preparation S2 time as described previously . Typicaln = 5), TE 22.14 ms, FOV = 340 × 225 mm, bandwidth 260 Hz/Px, matrix = 192 × 144, voxel size = 1.8 × 1.8 × 3.0 mm, flip angle 20°.T2* maps were obtained using a gradient echo sequence. Typical imaging parameters were: TR 600 ms, echo numbers (LGE was performed with a T1- weighted segmented inversion recovery gradient echo-phase sensitive-inversion recovery (GRE_PSIR) sequence . LGE images were collected 10–15 min after the administration of 0.1 mmol/kg contrast agent  [Cvi42 image analysis software  was used for image analysis by two experienced operators in CMR image analysis, blinded to CMR timing and measurements of the same patient across three time points. LV volumes and ejection fraction (EF) were assessed from cine bSSFP images. AAR on T1 mapping/ T2-weighted was identified similarly to previous reports using a signal intensity threshold of 2SD above the mean intensity of remote reference region of interest (ROI) placed 180 degree opposite to the injured myocardium with no visible regional wall abnormalities or infarction  , 17. T1 T1 core was defined as a central area within the injured myocardium with T1 value less than 2SD below the mean T1 value of the periphery of AAR as previously described . Since TTo quantify injured myocardium, as depicted by LGE, signal intensity threshold was set at 5 standard deviations above the remote reference myocardium . When prMSI was calculated from 24 h scan using T1 map to derive AAR as previously described .P value < 0.05 was considered statistically significant.Normality of distribution was assessed using the Shapiro-Wilk test. All variables were expressed as mean and ± standard deviation or as median accompanied by interquartile range (IQR) based on normality distribution. Frequencies comparisons were made using Chi square test or Fisher’s exact test, as appropriate while continuous variables were compared by using unpaired T test or Mann-Witney U test where appropriate. Paired t test was used to compare AAR using T1 mapping and T2-weighted in the single scan cohort. To track changes of T1 values over time taking into account repeated measures, generalised mixed model was conducted with time and haemorrhage as fixed effects and subject identification as random effect. This was done given that haemorrhage is known to affect magnetic resonance properties . Post hoA total of 48 patients were included in this study with total of 102 CMR exams. Of these, 31 patients underwent the 3 h hyper-acute CMR scan, followed by 24 h (31 patients) and 6 days (23 patients) CMR scans. These patients formed the temporal changes cohort. The remaining 17 patients underwent a single CMR scan at 24 h . All hyper acute scans were performed between 30 min and 3 h after placing a stent in the culprit artery. No significant arrhythmias were detected during scans acquisition.CMR scans were performed at 1.6 h (1.2–2.4), 25.5 (23.8–26.0) hours and 6.5  days in the temporal changes cohort, compared to a median of 23.5 h (22–28.8) in the single scan cohort (P < 0.001). T1 relaxation time showed significant reduction at 24 h after reperfusion therapy at the second time point (P < 0.001). Subsequently, the T1 value rose to a value similar to that at TP1 and was significantly different from the 24 h scan (P = 0.041)  Table  , and similarly no significant difference between 24 h and 6 days CMR scan (P = 0.1). However, a significant difference was detected when comparing first and third time points (P = 0.004). All remote T1 values were similar to those previously reported in healthy subjects scanned in our department [Unlike the injured myocardium, the remote myocardium had a trend towards reduction in T1 relaxation time over time, nonetheless the absolute difference across the 3 time points was nominal (< 10 ms). There was no significant difference in T1 value between 3 h and 24 h (partment .intensity of the oedema (illustrated above). The changes in the anatomical area or the extent of injured myocardium was also studied and showed no significant change at 24 h, compared to 3 h (P = 1.0). Subsequently, the extent of AAR by T1 mapping increased when compared with the second CMR time point (P = 0.019) (Table Injured myocardium as identified on T1 mapping (AAR) was not solely analysed for changes in the P = 0.025)   Table c.P < 0.001) and subsequently stayed the same at 6 days post STEMI (P = 0.99). Similarly, the incidence of T1 core followed similar pattern and 50% of subjects developed T1 core within the injured myocardium at 24 h compared to only 13% at the hyper acute scanning.T1 core area increased significantly after 24 h following STEMI (Enhanced myocardium quantified on LGE sequence was comparable with no significant differences across three time points Table .Table 4DP = 1.0). Subsequently, MVO was significantly reduced  and the reduction was also significant when comparing TP1 vs TP3 (P = 0.02) . IMH remained comparable between 6 days CMR scanning and both 3 h (P = 0.46) and 24 h CMR scanning (P = 0.69)  LGE remained constant within the first week, unlike both MVO and IMH which peaked within the first 7 days.This is the first study to investigate the dynamic changes of highly sensitive T1 mapping immediately post STEMI. The main findings of this study can be summarised as follows: (1) after reperfusion therapy in patients presenting with STEMI, the intensity of oedematous response assessed using T1 mapping on 3 T CMR was not stable and followed bimodal pattern; (2) this bimodal reaction was still evident when excluding ‘T1 core’, which increased in area and, possibly, in prevalence, over time; (3) the Accurate quantification of myocardial area at risk is essential in calculating MSI, which has been used to assess efficacy of applied therapies in patients presenting with STEMI . Timing intensity of the oedematous reaction measured using mapping technique (T1 relaxation time). This implies that the water content of a given volume of myocardium can change, somewhat like a sponge taking water, where changes in water content do not necessitate changes in the overall volume of the sponge. Moreover, we compared the difference between anatomical AAR determined by T1 mapping and T2W imaging and demonstrated that T2W underestimated the injured myocardium 24 h after STEMI. Taking all these observations together, these findings are consistent with the residual water content identified using desiccation method, which can be considered a gold standard. More importantly, it highlights the stability of AAR measured using T1 mapping and would allow the calculation of MSI within the first week.Recently, Fernández-Jiménez et al.  reportedAn area with low T1 relaxation time, termed the ‘T1 core’, within injured myocardium showed some impact on the dynamic changes of AAR. T1 core has been shown to be a significant imaging biomarker to characterise infarcted myocardium and to predict future cardiovascular events . We demoIn this study, patients underwent LGE and T2* mapping sequences at three time points to assess if dynamic changes occur with the first week. Enhanced myocardium showed minimal changes overtime, unlike MVO which appears to peak within the first 24 h. Experimental studies using CMR coupled with blood flow measurement employing microspheres have demonstrated a similar course to our data . MoreoveOur study in vivo in humans lacks histological / tissue validation to confirm findings using T1 mapping technique. We did not compare T2-weighted and T1 mapping at the hyper acute time point given the time constraint to perform lengthy CMR scan immediately after STEMI in potentially unstable patients. However, we validated our finding using a prospective cohort employing both T2-weighted imaging and T1 mapping sequences to measure AAR in humans. In addition, previous reports have demonstrated that T2-weighted imaging may underestimate AAR when compared to desiccation or MDCT , 7. FinaThe intensity of the oedematous reaction post STEMI follows a bimodal pattern; while the extent of AAR does not track the same course and was stable over the first week. This discrepancy has important implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and by tissue desiccation. We conclude that anatomical area at risk may best be quantified using T1 mapping, undertaken in the first week after reperfusion.


Low homoarginine was also related to higher NTproBNP . Lower serum homoarginine is associated with dilatation of the heart and decreased function. Prospective clinical studies should assess if homoarginine supplementation improves cardiac health in subjects with low serum concentrations.Low homoarginine is an independent marker of mortality in heart failure patients and incident cardiovascular events. Whether homoarginine is related with healthier cardiac structure and function is currently unclear. We used data of the population-based “Study of Health in Pomerania” (SHIP-Trend) to assess this relation. Homoarginine was measured in serum using liquid chromatography-tandem mass spectrometry. Linear regression models assessed the relation between homoarginine and several structural as well as functional parameters and N-terminal pro B-type natriuretic peptide (NTproBNP). All models were adjusted for age, sex, body mass index, and renal function. A total of 3113 subjects (median age 48 (25th percentile 37 to 75th percentile 60) years, 46% male) were included. A standard deviation decrease in homoarginine was associated with a larger left ventricular diastolic diameter : 0.2 to 0.5 mm;  For exafrom Arg . Even thfrom Arg ,4.Nevertheless, recent experimental and clinical data indicate a potential role of hArg in cardiovascular disease (CVD), since hArg deficiency or impairment is associated with adverse outcomes ,6,7,8. SVery few clinical studies have explored the relation between circulating hArg and left ventricular cardiac remodeling. Results from the “Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Diastolic Heart Failure” (DIAST-CHF) study showed that low hArg was related with higher NTproBNP and presence of diastolic dysfunction . We aimewww.community-medicine.de.The presented data were derived from the population-based cohort study “Study of Health in Pomerania (SHIP) in Germany” . In brie2), previous myocardial infarction, left ventricular ejection fraction < 40%, atrial fibrillation, extreme values for hArg (<0.995 percentile), and missing data were excluded. The total sample size was 3113 subjects.For the present analysis, individuals with severely impaired renal function (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 mTrained and certified staff used standardized computer-assisted interviews to assess sociodemographic and medical characteristics. Smoking was classified as current smoker, nonsmoker, or former smoker. Previous myocardial infarction was defined as self-reported physician’s diagnosis. Diabetic patients were identified based on the self-reported use of antidiabetic medication  code: A10) in the last 7 days or a glycosylated hemoglobin level >6.5%. All participants underwent an extensive standardized medical examination. Anthropometric measurements included height and weight based on recommendations of the World Health Organization (WHO) . Body ma−1.154 × age−0.203) multiplied by 0.742 for female subjects and expressed as mL/min/1.73 m2 [Fasting venous blood samples were drawn from all subjects in supine position (between 7 am and 4 pm). The eGFR was calculated according to Levey et al. (eGFR = 186 × (plasma creatinine concentration × 0.0113118)/1.73 m2 . Briefly3 − LVDD3)) + 0.6 g as described by Devereux and Reichek [0.725 × weight (kg)0.425) [Two-dimensional, M-mode and Doppler echocardiography were performed using the Vingmed CFM 800A system  as described in detail elsewhere . Measure Reichek ,20. LVM g)0.425) , which lg)0.425) :WT (cm) Transmitral and transcuspid pulsed-wave Doppler were used to record early (E) and late (A) wave ventricular filling velocities. Tricuspid annular plane systolic excursion (TAPSE) is a parameter of right ventricular function. TAPSE was assessed using the four-chamber view in M-mode. Movement of the lateral tricuspid valve was measured from end-diastole to end-systole. Certification examinations for interobserver variations revealed an agreement of >90% .2 test , respectively. First, a linear regression adjusted for sex, age, BMI, and eGFR was fitted to assess the relation between hArg and echocardiographic parameters, as well as NTproBNP continuously. Furthermore, restricted cubic splines [p < 0.05 was considered statistically significant. All statistical analyses were performed in SAS 9.4 . All continuous descriptive characteristics are presented as median and first as well as third quartile unless otherwise indicated.Continuous data are expressed as median and 25th/75th percentile. Nominal data are expressed as percentages. Differences between groups were calculated using Kruskal–Wallis (continuous variables) and χ splines  were use splines , resulti2 and an eGFR of 89 (77 to 102) mL/min/1.73 m2. Diabetes type 2, hypertension, and metabolic syndrome were present in 7%, 40%, and 23% of the study population, respectively. The echocardiographic parameters are grouped according to left and right ventricle, as well as structural and functional parameters.The population characteristics are provided in p < 0.001), LVS  and lower RWT . No relations were found for hArg and LVM, LVMI, PWD, left atrial, and aortic diameter (A one standard deviation (SD) decrease in serum hArg was associated with larger LVD  and FS . No relations were found for hArg and LV diastolic functional parameters , systolic functional , and diastolic functional  parameters .p < 0.01)  .This study assessed the relation between circulating hArg and echocardiographic parameters as well as biochemical parameters of cardiac function in a large general population-based cohort. Our findings support the notion for a positive association of hArg with cardiac health. Specifically, we show that high hArg is related to lower left ventricular thickening, higher ejection fraction, and lower NTproBNP. To our knowledge, this is the first report assessing the relation between circulating hArg and a variety of echocardiographic parameters in more than 3000 subjects with preserved or midrange ejection fraction.Our results are in agreement with previous studies with regards to the inverse association of hArg and NTproBNP. Specifically, in 3305 Caucasian patients who were referred for coronary angiography examination at a tertiary care center in Germany and recruited to the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, hARG and NTproBNP were inversely associated . FurtherWith regard to left ventricular function, our results show a positive association between hArg and LVEF as well as FS. This finding is also supported by the LURIC but not the DIAST-CHF results. Specifically, LURIC patients in the lowest hArg quartile had a LVEF of 54% compared to 64% in the highest quartile . Interesin vivo cardiac function, suggesting a potential role in the pathophysiology of heart disease [l-arginine availability [Even though previous studies reported a relationship of hArg with LV systolic and diastolic function, there is a knowledge gap regarding subclinical LV structural remodeling. However, recent evidence from experimental mouse studies provides a first indication that low hArg may contribute to impaired  disease . In our  disease . Specifilability ,4. Howevlability . Secondllability . To datelability ,8 and helability . Intereslability ,26. A relability . In our Even though SHIP comprises a large and methodologically rigorous regionally representative survey of northern Germany, the findings of our analyses need to be interpreted in the context of several limitations. First, our analysis consisted of middle-aged Europeans living in rural areas. Therefore, we do not know whether our findings are also applicable to other ethnicities or age groups. Second, we used cross-sectional data from one time point. Hence, we do not know whether increases in hArg are also associated with improved left ventricular structure and function. Third, although we used a directed acyclic graph to identify metabolic and cardiovascular confounders for our multivariable models, we cannot exclude the possibility of further residual confounding. Fourth, the clinical interpretation of our results is difficult, as only ten subjects had heart failure with preserved ejection fraction. A recent Mendelian randomization analysis concluded that even though low hArg was associated with an increased risk for future hyperglycemias and abdominal obesity, there was no evidence for any causal relation . Since oOur cross-sectional analyses showed that high levels of circulating hArg in a population-based setting are associated with preferable left ventricular structure and function. We add new information with regards to LV structural remodeling. Of note, we have previously reported serum reference intervals for hArg, allowing the identification of individuals that might benefit from supplementation with hArg to normalize serum concentrations and, in addition, may support cardiac health . Complet


Background: Heart failure (HF) – a very prevalent disease with high morbidity and mortality – usually presents with diastolic dysfunction. Although post-menopause women are at increased risk of HF and diastolic dysfunction, poor attention has been paid to clinically and experimentally investigate this group of patients. Specifically, whether myocardial stiffness is affected by menopause is unknown.Aim: To investigate whether loss of female sexual hormones modifies the Young’s modulus (E) of left ventricular (LV) myocardial tissue in a mouse model of menopause induced by ovariectomy (OVX).Methods: After 6 months of bilateral OVX, eight mice were sacrificed, fresh LV myocardial strips were prepared (∼8 × 1 × 1 mm), and their passive stress–stretch relationship was measured. E was computed by exponential fitting of the stress–stretch relationship. Subsequently, to assess the relative role of cellular and extracellular matrix components in determining OVX-induced changes in E, the tissues strips were decellularized and subjected to the same stretching protocol to measure E. A control group of eight sham-OVX mice was simultaneously studied.Results: E  in OVX mice was ∼twofold lower than in controls . No significant difference between groups was found in E of the decellularized tissue .Conclusion: Loss of female sexual hormones in an OVX model induces a reduction in the passive stiffness of myocardial tissue, suggesting that active relaxation should play a counterbalancing role in diastolic dysfunction in post-menopausal women with HF. Heart failure (HF) is a global health problem associated with high mortality and healthcare system expenditure , 2017. WMoreover, previous data from animal models of ovariectomy (OVX) also provided conflicting results. Some rodent studies reported an increase in ventricular fibrosis , change Diastolic dysfunction – characterized by increased LV end-diastolic pressure – can be caused by either prolongation of active myocardial relaxation or increased myocardial passive stiffness . Main deGiven the clinical importance to further our understanding of the role of menopause in diastolic dysfunction, this study was focused on specifically assessing whether loss of female sexual hormones induces a change in the passive stiffness of LV myocardial tissue in a conventional mouse model of OVX. The passive elastance of myocardial strips from fresh native hearts was measured before and after decellularization to assess the differential contribution of both ECM and cellular components in total LV tissue stiffness in this menopause model.N = 12 and N = 11, respectively). Conventional bilateral OVX was carried out under intraperitoneal ketamine/xylazine (5/10 mg/kg) anesthesia in OVX mice as described in detail elsewhere  randomly distributed into two groups: OVX and sham-operated (SHAM) mice  staining of interstitial collagen in paraffin-embedded 5-μ thick LV tissue sections, as previously described . Images M) was measured. Resting length (L0) of the strip was measured, and its cross-sectional area (A) was computed asFor mechanical measurements, hearts from eight OVX and eight SHAM mice were placed at room temperature in phosphate buffer saline (PBS) (Sigma) immediately after excision. LV wall was excised and a strip of ∼8 × 1 × 1 mm was cut with a scalpel along the long-axis direction and its mass (3). One end of the strip was glued with cyanoacrylate to a hook attached to the lever of a servocontrolled displacement actuator, which allowed us to stretch the strip and to measure the stretched length (L) and the applied force (F) . The other strip end was glued to a fixed hook  was defined asL0 was measured again and 10 more cycles were acquired. Tissue stiffness was characterized by its Young’s modulus (E) defined as dσ/dλ. E was computed at 20% stretch (λ = 1.2) by exponentially fitting the stress–stretch (σ-λ) curve .LV myocardial strips were initially pre-conditioned by applying cyclical stretch at a frequency of 0.2 Hz and maximum stretch of 50% for 10 cycles. After measuring E in fresh native samples, each strip was decellularized as described in detail elsewhere . Brieflyt-tests. Mann–Whitney U tests were used for skewed data. A p-value < 0.05 was considered statistically significant.Group data were computed as mean ± SE. The OVX vs. SHAM differences in body, heart, and uterine weights, and E were assessed by p = 0.016) higher in OVX (2.04 ± 0.20) than in SHAM (1.00 ± 0.21).The OVX surgical procedure was effective as indicated by a considerable reduction in uterine weight and, as expected, OVX mice significantly increased body weight whereas heart weight did not change Figure . CollageE = 11.7 ± 1.8 kPa and 22.1 ± 4.4 kPa, respectively (p < 0.05). However, the stiffness of decellularized LV myocardial strips was not significantly different (p = 0.58) in OVX compared to SHAM: E = 31.4 ± 12.05 and 40.9 ± 11.5, respectively  are warranted. A non-significant change in passive stiffness was observed in decellularized LV myocardial tissue. Noteworthy, the decellularized tissue was stiffer than the fresh native tissue (Figure To assess myocardial passive stiffness, we measured tissue mechanics of fresh LV myocardial strips. This approach allowed us to directly characterize tissue stiffness thereby avoiding the geometric assumptions required when tissue mechanics is determined from pressure–volume measurements in the whole ventricular cavity . Tissue e Figure , which ce Figure .Loss of female sexual hormones has been considered a possible cause of ECM fibrosis, and hence of potential increase in passive stiffness, by accumulation and remodeling of collagen. However, the evidence available is conflicting since both increase and no change in collagen deposits after OVX have been reported . AlthougAlthough elderly women are more likely to develop pronounced diastolic dysfunction than men , this stThe experimental procedures were approved by the Ethics Committee of Animal Experimentation of the University of Barcelona following the local and European regulations in force.NF and DN conceived the work and designed the experiments. IJ, MT, and BF carried out most experiments and data analysis. JM-A, RF, and IA contributed to analyze and interpret the data. All authors discussed the work and finally contributed to writing the manuscript final version drafted by NF and DN.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


There is increasing recognition of a specific diabetic cardiomyopathy beyond ischemic cardiomyopathy, which leads to structural and functional myocardial abnormalities. The aim of this review is to summarize the recent literature on diagnostic findings and prognostic significance of non-invasive imaging including echocardiography, nuclear imaging, computed tomography and cardiovascular magnetic resonance in diabetic cardiomyopathy. The high incidence and prevalence of heart failure (HF) in individuals with type 2 diabetes (T2D) is well-established. Observational studies have shown an association between diabetes and risk of HF, as well as a link between worse glycaemic control and HF . In diabNon-invasive imaging has the ability to provide important pathophysiological insights into the processes that lead to development of DCM. The aim of this review is to summarize the literature on the diagnostic and prognostic use of non-invasive imaging techniques in DCM.Measurement of left ventricular ejection fraction (LVEF) by echocardiography remains the first-line technique for evaluation of DCM. Diabetes is a highly prevalent comorbidity in patients with HF , indepenT2D has been strongly associated with adverse LV remodeling, most commonly concentric in nature. In several longitudinal cohort studies T2D has been independently associated with increased LV mass ,9,10. AsDiastolic dysfunction has also been frequently characterized as one of the key echocardiographic findings in DCM. An early small study of 46 asymptomatic males with T2D found that diastolic dysfunction, defined as either abnormal relaxation or pseudonormalisation of left ventricular filling, assessed by transmitral pulse wave velocity imaging (E/A) and pulmonary venous recordings, was present in over half of the patients . A largeMore recently, advanced echocardiography methods such as strain imaging using speckle-tracking have identified subclinical alterations in systolic myocardial function in patients with T2D and preserved LVEF  . Strain GLS also appears to have prognostic significance. In one study of 172 asymptomatic patients with T2D, reductions in GLS at baseline have been associated with higher LV end-systolic volumes and LV relative wall thickness, as well as reduced likelihood of a decrease in LV volumes at three years . ExtendiAlthough the majority of studies have focused on the left ventricle, reduced left atrial GLS has also been reported in T2D patients ,29. ReduThere has also been some evidence that DCM is associated with alterations in left ventricular function during exercise or stress echocardiography. Similar to the general population, identification of epicardial CAD using stress echocardiography has prognostic significance ,35. TherStress echocardiography may also provide some additional prognostic information. Measurement of coronary flow reserve (CFR), which in the absence of flow-limiting epicardial coronary artery stenosis is reflective of microvascular disease, was found to be associated with major adverse cardiovascular events in T2D patients with suspected angina and non-obstructed coronary arteries on invasive angiography . SimilarOverall, echocardiography is the workhorse for clinical assessment of cardiac structure and function, and provides excellent temporal resolution for evaluation of subclinical LV dysfunction using strain and diastolic function. It has a wealth and depth of long-term prognostic information, and comprehensive echocardiography should certainly be considered as a key part of the evaluation of DCM.The most common use of nuclear medicine in non-invasive CV imaging is for ischemia testing. Stress testing using single-positron emission computed tomography (SPECT) has been the most widely studied modality and has been shown to have similar diagnostic accuracy in T2D patients compared to non-T2D for detection of significant CAD compared to invasive angiography . As withAlterations in CFR can also be detected by nuclear imaging, and similar to echocardiography, even asymptomatic T2D patients with normal coronary arteries demonstrate reduced CFR compared to controls measured during technetium sestamibi scanning . MyocardPET may also provide some useful information on other parameters. Rijzewijk et al. reported that T2D patients who underwent PET scanning displayed a reduction in myocardial glucose uptake and increases in fatty acid uptake and oxidation, although these were not correlated with LV diastolic function . A recenNuclear imaging remains widely used, particularly in ischemia assessment where its diagnostic and prognostic value has been extensively validated. There is no evidence to suggest that the prognostic value of nuclear imaging is any different in T2D patients compared to non-T2D. Nuclear imaging also allows assessment of myocardial blood flow, and some assessment of metabolism, which might provide further pathophysiological insights into DCM.The main use of cardiac computed tomography (CCT) is for non-invasive visualization of coronary arteries. CCT offers unparalleled anatomical delineation of cardiac structures compared to other non-invasive imaging methods. The majority of CCT studies have focused more on identification of CAD than DCM, however CCT may play an important role in confirming DCM by excluding significant CAD as a cause for HF. As in non-T2D populations, the presence of significant obstructive CAD is associated with adverse cardiovascular outcomes. In asymptomatic individuals, a large meta-analysis of 10 studies including 5012 individuals with T2D reported that the presence of both obstructive CAD (≥50% stenosis) and non-obstructive were significantly associated with adverse events, as was the extent of CAD . T2D patBeyond assessment of the coronary arteries however, there have been few large studies assessing the role of CCT in DCM. It is possible to measure ventricular function using CCT, although given the ionizing radiation dose, other methods such as echocardiography are preferred . PerfusiThe main role of CCT in DCM is in providing a non-invasive method to exclude significant CAD as the underlying aetiology. Given that most guidelines do suggest that high-risk patients such as those with T2D should undergo invasive coronary artery assessment, CCT does not play a huge role in assessment of DCM. It may, however, be valuable in those unable to undergo invasive coronary angiography or cardiac magnetic resonance imaging, or in those whose echocardiographic images are sub-optimal.Cardiovascular magnetic resonance imaging (CMR) is becoming increasingly utilized to provide further pathophysiological insight into myocardial structure and function. As well as being the gold-standard for measurement of left ventricular volumes, function and mass, CMR also has unique tissue characterization properties which have helped shed light on the patterns and prevalence of DCM, some of which have also been shown to be prognostically significant.The most widely studied CMR technique is that of late gadolinium enhancement (LGE). This technique is usually performed by taking CMR images 10–15 min after the injection of intravenous gadolinium contrast agents. Gadolinium is an extracellular contrast agent, and therefore in normal healthy myocardium where there is very little extracellular space, no gadolinium remains, and the myocardium appears black. In areas where there is extracellular space , the myocardium appears white due to the gadolinium contrast . The preLGE techniques are predominantly only able to identify focal areas of fibrosis. More recently, there has been intense interest in measuring diffuse myocardial fibrosis using T1 mapping techniques . T1 mapp1H) MRS, reflecting cardiac steatosis which is present even in individuals with preserved LVEF [31P (phosphorus) MRS [31P MRS is a non-invasive measure of myocardial energetics which is reduced in individuals with T2D, correlates with impaired perfusion and oxygenation, coronary microvascular dysfunction, diastolic dysfunction and subclinical systolic impairment [Magnetic resonance spectroscopy (MRS) imaging has also been utilized to demonstrate increased myocardial triglyceride content in T2D using proton (ved LVEF . This strus) MRS . Indeed,pairment .CMR has also been used to identify epicardial adipose tissue (EAT), which is associated with T2D and insulin resistance. EAT has been associated with reduced systolic strain in DCM  and periIn this review the main non-invasive imaging techniques used in clinical practice have been summarized. Nevertheless, many of the advanced techniques discussed such as speckle-tracking echocardiography, PET and cardiovascular magnetic resonance are not routine used by clinicians and are limited to research. It is likely, as more prognostic data becomes available, that these techniques are used more in the future. In particular, some of the changes identified in DCM using these techniques  may become treatment targets and require monitoring using advanced non-invasive imaging. With the increasing interest in CMR T1 mapping techniques, there will almost certainly be prognostic data on diffuse myocardial fibrosis in DCM, and whether therapies can be developed to reduce this fibrosis. There is also increasing focus on combining imaging techniques, either in cluster analysis (to identify patients with similar phenotypes who might have differing prognosis and respond to treatment differently)  or alongT2D patients are at significantly increased risk of CV events compared to the general population. Beyond CAD, T2D itself appears to be associated with a number of myocardial structural and functional changes leading to DCM and HF. Non-invasive imaging techniques can play a key role in identification of these changes even prior to the development of overt HF . Figure


The pathophysiology of cardiovascular disease in CKD is under investigation but to date, treatment options are limited. Blood pressure control and statins have the strongest supportive evidence.A 30 year old asymptomatic male with stage 3 chronic kidney disease (CKD) secondary to Focal Segmental Glomerulosclerosis was found to have features of CKD associated cardiomyopathy including left ventricular hypertrophy (LVH) and focal sub-endocardial scarring on cardiac magnetic resonance imaging. There was also a significantly raised CT coronary calcium score and evidence of non-flow limiting coronary artery disease (CAD) on a CT coronary angiogram. Early stage CKD is a major risk factor for cardiovascular risk causing myocardial hypertrophy and fibrosis and coronary artery atheroma. Cardiovascular risk begins to increase from an eGFR of around 75ml/min/1.73m The leading cause of death in patients with end-stage renal disease (ESRD) is cardiovascular disease.2 and heavy proteinuria . There was no significant past medical history. He was hypertensive (164/72) but not obese. His total cholesterol was 5.3 mmol/l and triglycerides 1.10 mmol/l. He was started on losartan with initial adequate blood pressure (BP) control (129/84) but continued to have proteinuria. A renal biopsy showed focal segmental glomerulosclerosis (FSGS). A cardiac magnetic resonance (CMR) scan demonstrated concentric LVH with a maximal segmental wall thickness of 16 mm in the basal septum and an elevated left ventricular mass of 108 g/m2 . Systolic function was good with an ejection fraction of 61% and 3D global longitudinal strain (GLS) of −15.06%. There was however, hypokinesia of the mid-inferior and inferolateral segments without associated thinning. Following administration of intravenous gadolinium contrast there was focal sub-endocardial late enhancement in the basal and mid-inferior segment corresponding with the segments of hypokinesia  of 57 ml/min/1.73 mesia see . These f,,The high prevalence of cardiovascular disease in ESRD was identified in the 1970s early after the introduction of dialysis and was found to be the result of left ventricular disease (CKD-associated cardiomyopathy) and accelerated atherosclerosis.et al.E/e′ was increased.E/e′ is the ratio of mitral early filling maximal velocity to early myocardial relaxation velocity of the lateral mitral annulus and is an index of left atrial pressure. More recently, the application of T1 mapping CMR has allowed better characterization of the myocardium than with standard late gadolinium enhancement inversion recovery imaging. In a small cross-sectional study, Edwards et al.et al.In early stage CKD, left ventricular mass is frequently elevated and the reported prevalence of LVH by echocardiography is 32%.While novel techniques allow further insights into the structural changes seen with CKD-associated cardiomyopathy the pathophysiology of CKD-associated cardiomyopathy remains complex and multifactorial. To date, there is evidence supporting a disordered renin–angiotensin aldosterone system, altered calcium and phosphate metabolism (causing high levels of fibroblast growth factor 23 and parathyroid hormone) and hypertension.Early stage CKD is probably also an independent risk factor for CAD.et al.,Management of CAD in CKD is challenging due to a lack of evidence.This young patient already has evidence of both CKD-associated cardiomyopathy with LVH and scarring and premature CAD with a possible previous MI. He is asymptomatic and none of these abnormalities were evident on routine clinical examination or ECG. There are no current guidelines on screening patients with early stage CKD for cardiac disease but this case should serve to remind all nephrologists of the need to be vigilant; subjects with early stage CKD are usually far more likely to die of premature cardiovascular disease (13-fold) than to progress to ESRD.


While the role of inflammation in acute coronary events is well established, the impact of inflammatory-mediated vulnerability of coronary plaques from the entire coronary tree, on the extension of ventricular remodeling and scaring, has not been clarified yet.The present manuscript describes the procedures of the VIABILITY trial, a descriptive prospective single-center cohort study. The main purpose of this trial is to assess the link between systemic inflammation, pan-coronary plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree), myocardial viability and ventricular remodeling in patients who had suffered a recent ST-segment elevation acute myocardial infarction (STEMI). One hundred patients with STEMI who underwent successful revascularization of the culprit lesion in the first 12 hours after the onset of symptoms will be enrolled in the study. The level of systemic inflammation will be evaluated based on the serum biomarker levels  in the acute phase of the myocardial infarction (MI) and at 1 month. Pan-coronary plaque vulnerability will be assessed based on serum biomarkers known to be associated with increased plaque vulnerability (V-CAM or I-CAM) and at 1 month after infarction, based on computed tomographic angiography analysis of vulnerability features of all coronary plaques. Myocardial viability and remodeling will be assessed based on 3D speckle tracking echocardiography associated with dobutamine infusion and LGE-CMR associated with post-processing imaging methods. The study population will be categorized in 2 subgroups: subgroup 1 - subjects with STEMI and increased inflammatory response at 7 days after the acute event (hs-CRP ≥ 3 mg/dl), and subgroup 2 - subjects with STEMI and no increased inflammatory response at 7 days (hs-CRP < 3 mg/dl). Study outcomes will consist in the rate of post-infarction heart failure development and the major adverse events (MACE) rate.VIABILITY is the first prospective study designed to evaluate the influence of infarct-related inflammatory response on several major determinants of post-infarction outcomes, such as coronary plaque vulnerability, myocardial viability, and ventricular remodeling. In the latest years, introduction of coronary care units and large-scale implementation of networks for emergency myocardial revascularization, as well as development of reperfusion and pharmacological therapies, led to a significant decrease in mortality rates following AMI. However, the high incidence of post-infarction heart failure is still affecting the long-term outcomes of these patients. Predictors for CHF following an AMI include preexistent heart failure, traditional cardiovascular risk factors , previous myocardial infarction (MI) with or without revascularization, rhythm disturbances during the acute phase of the coronary event, delayed revascularization times, multivessel coronary artery disease (CAD), enhanced inflammatory response, or no-reflow phenomenon after revascularization.–9Congestive heart failure (CHF) as a long-term complication following AMI, although having a relatively low incidence in the primary percutaneous coronary intervention (PCI) era, is an important predictor of mortality and morbidity, at the same time leading to increased health-care costs and decreased quality of life.,10–12Multiple coinciding pathophysiological mechanisms may lead to heart failure after AMI, both during the index event and later on. These include myocardial necrosis and stunning, inflammation, reperfusion injury, microvascular obstruction, fibrosis and remodeling. CHF during the acute phase of an acute coronary syndrome results from a combination of myocardial necrosis and stunning, as well as ischemic  and arrhythmic complications. Later onset of CHF arises as a consequence of myocardial scarring and remodeling.–16The major aim of the urgent revascularization in ST-elevation myocardial infarction (STEMI) is to save myocardial tissue from death and necrosis, in order to recover viable myocardium. Despite a timely revascularization of the epicardial culprit coronary artery, a significant proportion of patients do not present the typical signs for a successful reperfusion, this being defined as the no-reflow phenomenon. Various mechanisms have been incriminated in an attempt to provide an explanation for this phenomenon, including microvascular embolization, endothelial dysfunction due to an exaggerated inflammatory response, or reperfusion injury. The consequences of this phenomenon are expansion of the infarct size, life-threatening arrhythmias, early development of CHF, and enhanced ventricular remodeling and dilation. Diagnosis of no-reflow can be achieved in the catheterization laboratory, during the revascularization procedure, or via imaging techniques such as gadolinium contrast magnetic resonance, contrast echocardiography or nuclear imaging. Atheromatous plaques develop and progress due to a chronic non-resolving inflammatory process that occurs at the site of an endothelial injury caused by turbulent blood flow. The atherosclerotic lesions can evolve in a silent manner for a number of years without causing an acute event. However, some plaques become unstable by acquiring several phenotypic changes  which make them prone to rupture.,20 Several studies have shown that vulnerable plaques are associated with an enhanced inflammatory response, which causes overexpression of the vulnerability features, with consequent rupture and thrombosis.–22 Furthermore, myocardial injury triggers an inflammatory cascade, which is persistent during the first 3 to 5 days following the acute event, having a benefic reparatory effect. The persistence of an elevated systemic inflammation after AMI after day 3 to 5 has deleterious effects, stimulating the process of left ventricular remodeling and evolution towards CHF. Moreover, the enhanced inflammation secondary to myocardial ischemia, may lead to vulnerabilization of additional atherosclerotic plaques thorough the vascular system, which might explain increased rates of acute coronary and cerebrovascular events in patients that have already suffered an AMI.,24,25It is well-known that one of the major factors that trigger an AMI is the systemic inflammation, which has a direct influence on coronary plaque vulnerability.The exact influence of various pathophysiological mechanisms, such as no-reflow phenomenon or increased inflammatory response on a pan-coronary level, on the process of ventricular remodeling is not fully understood. Understanding the complex heterogenous interaction of these components could help to identify patients at a higher risk for developing heart failure, as well as subsequent coronary and cerebrovascular events, after they have already suffered an AMI.The present manuscript describes the procedures of the VIABILITY trial, a descriptive prospective single-center cohort study which intends the assessment of the link between systemic inflammation, pan-coronary plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree), myocardial viability and ventricular remodeling in patients who had suffered a recent STEMI.1.2primary objective consists in the evaluation of the relationship between coronary inflammation-mediated plaque vulnerability, myocardial viability and ventricular remodeling in the post-infarction period.The secondary objectives of the study are:The (1)to assess the effect of systemic inflammation on the structural remodeling process of the left ventricle (LV) following an AMI and(2)to evaluate the impact of local inflammatory response on pan-coronary plaque vulnerability in the post-infarction period.22.1VIABILITY is a prospective, non-randomized, cohort study, carried out in a single-center, which aims to assess the link between systemic inflammation, pan-coronary plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree), myocardial viability and ventricular remodeling in patients with recent STEMI.2.2Declaration of Helsinki. Each subject will provide sign written informed consent before randomization process.The VIABILITY clinical study is approved by the local Ethics Committee for Scientific Research of the University of Medicine and Pharmacy of Tirgu-Mures, Romania  and the Ethics Committee for Scientific Research of the Cardio Med Medical Center Tirgu Mures, Romania . All study procedures will be conducted according to the 2.3VIABILITY will be a single-center, observational, non-randomized study including 100 patients with STEMI who underwent successful revascularization of the culprit lesion in the first 12 hours after the onset of symptoms.2.3.1Patients with STEMI treated by primary PCI within the first 12 hours after the onset of symptoms;2;Body mass index (BMI) under 40 kg/mSigned written informed consent;Subject at age of majority.2.3.2Documented ACS within last month before randomization;Patient disapproval to provide written informed consent;Intolerance to iodine contrast agent;Conditions associated with contraindication for CMR examination;Women during pregnancy or lactation period;Women able to procreate without any contraceptive usage;2) or acute renal injury that requires hemodialysis;Chronic kidney disease , financed by the European Union and the Romanian Government through the Ministry of Education and Research, which was selected for funding in a national competition for research grants, following an international peer-review selection process.2.5This study will enroll 100 patients with STEMI meeting the inclusion criteria. Study subjects will be distributed in 2 groups: group 1 – patients with STEMI and increased inflammatory response at 7 days after the acute event (hs-CRP ≥ 3 mg/dl) and group 2 - subjects with STEMI and no increased inflammatory response at 7 days (hs-CRP <3 mg/dl).2.6Medical records, physical exam, laboratory analysis: complete blood count (CBC), biochemistry, levels of high sensitivity C-reactive protein (hs-CRP), MMPs, IL6, NT-pro-BNP, adhesion molecules;electrocardiogram (ECG);TTE with morphological measurements, assessment left ventricular systolic and diastolic performance, speckle tracking echo, Dobutamine viability test;LGE-CMR with the evaluation of myocardial scar and fibrosis, ventricular function and remodeling index;Angiographic Computed Tomography (Angio-CT) with assessment of coronary plaque vulnerability  and myocardial perfusion.2.6.1Routine biochemistry and CBC analysis will be performed at the main laboratory of the Emergency Clinical County Hospital of Tirgu-Mures, immediately after randomization. Inflammatory status (hs-CRP levels) will be evaluated at 7 days after the acute cardiac event via immunoturbidimetric assay. Adhesion molecules , matrix metalloproteinase 9, and interleukin-6 serum levels will be evaluated using enzyme linked immunosorbent assay. Serum inflammatory biomarkers will be analyzed in Advanced Medical and Pharmaceutical Research Center of the University of Medicine and Pharmacy Tirgu-Mures, Romania. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels will be evaluated at randomization and at the last follow-up visit, at the main laboratory of the Emergency Clinical County Hospital of Tirgu-Mures by electrogenerated chemiluminescence.2.6.2Transthoracic echocardiographic (TTE) assessment will be performed at first and last follow-up visit in all patients. Evaluation of cardiac diameters and volumes, systolic and diastolic performance of LV, speckle tracking, and Dobutamine viability test will be conducted with a Vivid E9 ultrasound system , with the patient turned slightly on his left side, according to American College of Echocardiography indications. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricle ejection fraction (LVEF) will be evaluated using the Simpson's method, on the basis of images obtained from apical four chamber view. All measurements will be calculated as an average from 3 heart cycles.2.6.3All cardiac magnetic resonance images will be acquired with the use of a 1.5T Siemens Magnetom Aera equipment. The structure and function of the LV will be assessed by cine acquisitions in the long axis, 2-chamber and 4-chamber view respectively, as well as short axis, from the mitral plain through the apex. Short axis cine images will also be used for assessment of LV mass, LVEF, end-diastolic and end-systolic volumes of the LV. The LGE-CMR will be used to evaluate the myocardial scar, degree of fibrosis and the remodeling process of the LV. The images will be acquired during the diastolic phase of the cardiac cycle, by using the same views as for cine imaging, respectively short and long axis views, but after a 10 minutes delay after gadolinium intravenous injection. Imaging data post-processing will be conducted with the use of Medis Q Mass 8.1 software , by manually tracing the epicardium and endocardium. The analysis of the delayed signal intensity (DSI) will be conducted in 10 to 12 successive short-axis LGE slices. Image segmentation will use an automated hyper-enhancement threshold, and myocardial regions with a slow washout kinetic will be considered as fibrotic areas. The volume of the epicardial adipose tissue will be measured by a semiautomatic protocol for image post-processing, using automatic tracing and manual adjustments for epicardial layers.2.6.4Coronary Computed Tomographic Angiography associated with complex post-processing will be used for assessment of pan-coronary plaque vulnerability , myocardial perfusion and for quantification of epicardial fat volume, using a 128-slices dual-source computer tomography (CT) scanner  and the work station Siemens Syngo Via Frontier – Coronary Plaque Analysis platform , available in the Laboratory of Advanced Research in Cardiac Multimodal Imaging of the Cardio Med Medical Center, Targu Mures, Romania.2.7VIABILITY study will be conducted from March 2019 to March 2021.2.8primary outcome of the study refers to the incidence of post-infarction heart failure development, defined as the rate of re-admission in the hospital for heart failure or by a significant decrease in the ejection fraction (<45%).The Secondary outcomes of the study are represented by rate of re-hospitalization rates, rate of repeated revascularization and major adverse events (MACE) rates, including cardiovascular death or stroke.2.92.9.1Achieve written informed consent form all patients.Check all inclusion/exclusion criteria.Record demographic information, medical records, cardiovascular risk factors.Perform and record physical examination and 12-lead ECG.Laboratory analysis .2D TTE/speckle tracking.2.9.2hs-CRP assessment2.9.3Angio-CT .LGE-CMR .Dobutamine stress echocardiography/speckle tracking (viability).2.9.4Record results of physical exam, medical records, ECG2D TTE2.9.5Record results of physical exam, medical records, ECG2D TTEEnd-point assessment2.9.6Medical records, physical exam, laboratory analysis ;ECG.TTE with morphological measurements, assessment left ventricular systolic and diastolic performance, speckle tracking echo, Dobutamine viability test.LGE-CMR with the evaluation of myocardial scar and fibrosis, ventricular function and remodeling index.Angio-CT with assessment of coronary plaque vulnerability  and myocardial perfusion.All study procedures are illustrated in Figure 2.10One hundred patients with STEMI who underwent successful revascularization of the culprit lesion within the first 12 hours after the onset of symptoms will be enrolled in this study. On the basis of the persistence of systemic inflammation at 7 days after the acute event patients will be allocated into 2 subgroups. Stat Mate 2.0 software was used in order to establish the sample size of the study. According to this computation, a sample size of 50 subjects per group presents a 90% power to detect an increase in major adverse CV events rates proportion of 3.28, with a significance level  of 0.05 (2-tailed). Therefore, the study population was established at 100 subjects.2.11Graph Pad in Stat 3.10 software  will be used in order to perform all the statistical analysis, using a level of significance of 5%. Normality tests will be performed in order to check all study data. Categorical variables will be interpreted with Pearson Chi-Square test and being presented as numerical or percentage values respectively. Continuous variables will be presented in the form of a mean value +/- SD and will be compared using the Student test for variables with gaussian distribution and Mann–Whitney test for variable with non-gaussian distribution.3This manuscript presents the protocol of a clinical study, conducted in a single center, with the purpose to analyze the link between systemic inflammation, pan-coronary plaque vulnerability, myocardial viability and remodeling in patients who had suffered a recent STEMI. According to histological studies, prone-to-rupture plaques present significant differences as compared with stable obstructive coronary plaques. Those high-risk plaque features associated with the presence of acute coronary syndrome (ACS) have been defined by a series of Angio-CT studies and include larger plaque volume, plaque with low attenuation, positive remodeling, large plaque burden, spotty calcium, and napkin-ring sign. Ruptured plaques, the main cause of MIs, proved to have fibrous caps that contain elevated levels of proteases, including metalloproteinases (MMPs). Histologic studies provide strong associative evidence that MMPs promote plaque vulnerability in humans. Similarly, two overexpression studies give a clear evidence of plaque disruption in the presence of high MMP-9 levels, that are thought to influence the rates of atherogenesis and the stability of atherosclerotic plaques.,30It is well-known that one of the major factors that trigger an AMI is the systemic inflammation, which has a direct influence on coronary plaque vulnerability, usually related to decreased structural stability.Therefore, one of the study objectives will be to investigate the impact of local inflammatory response, assessed by inflammatory biomarkers and adhesion molecules, on pan-coronary plaque vulnerability based on vulnerability features determined via coronary CT angiography, following an AMI.Patients with AMI who survive the acute event very often present significant deterioration of their clinical status with progression towards heart failure, which is directly linked to the extent of myocardial injury and the remodeling process starting immediately after infarction. At the same time, 20% of patients surviving an AMI present a recurrent cardiovascular event in the following 12 months, as a result of increased systemic inflammation triggered by the infarction, which leads to vulnerabilisation of other atheromatous plaques from all the circulatory system in the post-infarction period. While the role of inflammation in acute coronary events is well established, the impact of inflammatory-mediated vulnerability of coronary plaques from the entire coronary tree on the extension of ventricular remodeling and scaring has not been elucidated so far.,31 Based on multivariate analyses, a series of previous studies reported a severe inflammatory response, expressed by serum CRP levels >20 mg/dl, as an independent strong predictor of subacute cardiac rupture and ventricular aneurysm. Furthermore, a prospective study has demonstrated an association between inflammation and LV remodeling, as the group of patients with peak CRP level above the median had a greater increase in LV volumes both at 2 weeks and at 6 months.Inflammatory response triggered by MI leads to appropriate infarct healing process and cardiac repair. Despite its beneficial effect, inflammatory reaction present in post AMI phase is a double-edged sword that in association with a vulnerable plaque, vulnerable blood and vulnerable myocardium can lead to catastrophic events, causing postinfarction remodeling and heart failure. At a clinical level, infarct size proved to be an independent prognostic factor for heart failure, arrhythmic events, and cardiac mortality. In PROTECTION AMI CMR study, the infarct size evaluated by LGE-CMR on day 3 to 5 proved to be the most robust independent predictor of late LVEF and adverse LV remodeling, at 90 days post STEMI. Negative remodeling, based on the cut-off value of >20% left ventricle end-diastolic (LVED) dilatation at 6 months follow-up, proved to have prognostic importance in 2 large multicenter trials. Moreover, in a study conducted by Haeck et al, NT-proBNP proved to be the strongest independent predictor of LV function, assessed by CMR imaging, in patients with STEMI undergoing PCI. As smaller previous studies have reported, admission levels of NT-proBNP above 260 pg/ml proved to be in a strong correlation with LV remodeling and impaired cardiac function during long-term follow-up.In recent studies, CMR parameters, including infarct size assessed by LGE, have been extensively evaluated in predicting late LV function in patients with AMI undergoing primary percutaneous intervention (PCI), providing powerful surrogate markers of outcomes.4The primary contribution of the VIABILITY trial will be to elucidate the consequence of infarct-related inflammatory response on several major determinants for post-infarction outcomes, such as coronary plaque vulnerability, myocardial viability, and ventricular remodeling.Submission to ethical committee was performed by Mirabela Morariu. The radiologist responsible for CMR imaging interpretation is Mihaela Ratiu. Morariu Mirabela, Sándor M. Szilágyi and Theodora Benedek will perform data statistical analysis.Conceptualization: Morariu Mirabela, Diana Opincariu, Roxana Hodas, Ciprian Rezus, Andras Mester, Istvan Kovacs, Szilágyi László, Imre Benedek.Data curation: Theodora Benedek, Kovacs Istvan.Formal analysis: Andras Mester, Theodora Benedek.Investigation: Theodora Benedek, Monica Chitu.Methodology: Mirabela Morariu, Opincariu Diana, Elena Rezus, Imre Benedek, Theodora Benedek.Resources: Imre Benedek.Supervision: Imre Benedek, Theodora Benedek.Visualization: Andras Mester.Writing – original draft: Morariu Mirabela, Diana Opicariu, Roxana Hodas, Dan Pasaroiu, Noemi Mitra, Andras Mester, Dan Georgescu, Imre Benedek.All the authors approved the final manuscript.