A precise and accurate assessment of left ventricular (LV) contractility is of utmost importance in terms of prognosis in most cardiac pathologies. Given the limitations of ejection fraction (EF) and global longitudinal strain (GLS) due to their load dependency, a novel imaging tool called myocardial work (MW) has emerged as a promising method for LV performance evaluation. MW is a novel, less load-dependent method based on computation of myocardial strain–arterial blood pressure curves. This method provides a more detailed assessment of segmental and global LV function incorporating the patient’s LV pressure and is derived by brachial artery pressure utilizing an empiric reference curve adjusted to the duration of the isovolumic and ejection phases as determined by echocardiography. The clinical implications of this unique method have been expanding in the last few years, which attest to the robust additive role of MW in routine practice. Left ventricular performance has traditionally been assessed by ejection fraction (EF), which has been demonstrated to be a prognostic parameter in numerous studies ,2,3. HowFollowing this concept, a new echocardiographic tool called myocardial work (MW), which measures the LV pressure–strain relationship through a noninvasive method, has evolved. Work is calculated as force applied over length, while myocardial work is calculated as LV pressure applied over strain, which explains why this method does not calculate the actual LV work but is a valid approximation of it. Russel et al. were the first to develop this tool to assess segmental and global myocardial work by introducing blood pressure with a noninvasive method. In their study, the LV pressure–volume loop correlated well with the pressure–strain loop (PSL) in patients with left bundle branch block (LBBB) and dyssynchrony as well as in patients with ischemic heart disease ,9. The rTraditionally, LV work is evaluated by the pressure–volume relationship, which reflects the myocardial oxygen consumption and eventually the LV performance . The preThe aim of this review is to meticulously describe how to assess MW and all its components in a step-by-step fashion, refer to the normal reference values that have been proposed in previous published studies, and discuss the clinical implications of this method.LV MW is a novel, speckle tracking-based method that evaluates LV work and is estimated by employing brachial artery blood pressure and LV GLS. The profile of the estimated LV pressure curve is calculated using an empiric reference pressure curve that is adjusted according to the duration of the isovolumic and ejection phases as determined by echocardiography. MW is measured from the PSL areas that are constructed from the LV pressure curves combined with strain GLS . The steAttention should be given when calculating LV GLS as there are a few details that may affect the measurement of MW. All apical images should be recorded in 40–80 frames per second (fps) with clear visualization of the endocardial border, and the region of interest (ROI) width should be adjusted in order to cover the whole myocardium and not the pericardium. If the pericardium is included, MW may be underestimated. Conversely, if the ROI width is too narrow, then it is the endocardium that is mainly included, which leads to overestimation of MW .After performing all these steps, the system automatically provides bull’s eye of the global myocardial work index and global work efficiency of the LV with all 17 segments and all values of MW components. Additionally, the application demonstrates the pressure–strain loop that is equal to the GWI of the LV. By choosing a specific segment, we have the ability to compare the global and segmental WI along with their PSL at the same time. The application utilizes the previously defined event timing of the valve opening and closure on the pressure–strain loop and thus separates the different phases of the cardiac cycle isovolumic contraction, ejection time, isovolumic relaxation, and diastolic filling . In the GWI is calculated from mitral valve closure to mitral valve opening, which is the mechanical systole including isovolumic contraction. Constructive work is the work performed during systolic shortening, plus the negative work performed during lengthening in isovolumetric relaxation. The wasted work is the negative work performed during lengthening in systole, plus the work performed during shortening in isovolumetric relaxation. The global work efficiency is the constructive work divided by the sum of constructive and wasted work . All thep < 0.001), EF (p = 0.02), systolic blood pressure (SBP) (p < 0.001), and global radial strain (GRS) (p = 0.004). GCW correlated well with GLS (p < 0.001), SBP (p < 0.001), GRS (p = 0.02), and global circumferential strain (GCS) (p = 0.01). The reference values from the NORRE study are used in routine practice in most echocardiography departments as normal reference values. Another study with healthy subjects from the STAAB cohort [p = 0.001 and 2289 ± 261 vs. 2194 ± 207 mmHg%, p = 0.04, respectively). This is in agreement with the established knowledge that GLS and E’ are much higher in women than in men. In this study, Galli et al. also demonstrated a significant difference between basal, mid, and apical segmental LV work, increasing from base to apex. Likewise, previous studies have demonstrated that segmental strain increases from base to apex [In order to define a parameter as abnormal, a good description of “normal” is essential. Because MW has been developed recently, there have only been a few studies that have included healthy subjects and described the normal values of MW and all of its components. The NORRE study  was the B cohort  analyzedB cohort  also perEstimation of LV systolic function is essential in all cardiac diseases, and EF continues to be the most commonly used parameter. Although speckle tracking echocardiography with GLS provides more detailed information about global and segmental systolic function, giving the opportunity to detect subclinical dysfunction, it remains load-dependent . MW, on In a normal heart, all 17 segments contract at the same time and produce very little wasted work. In diseased hearts with dyssynchronous contraction of LV, bundle branch block, ischemic, or dilated cardiomyopathy, there are segments that lengthen during systole or contract against a closed aortic valve, producing a lot of wasted work.  This expIn the COVID-19 pandemic era, MW has shown better sensitivity in detecting cardiac complications from coronavirus . These cMW was first described and validated in patients undergoing cardiac resynchronization therapy (CRT) . The dysp = 0.004; WMSI, β = 1.32, p = 0.0012). In area under the curve (AUC) analysis, the combination of septal WW and WMSI showed an AUC of 0.86 (0.71–1.0) for CRT response prediction. However, larger studies need to be conducted to establish this hypothesis. Aalen et al. demonstrated that the work difference between septal and lateral wall, combined with the viability detected by cardiac magnetic resonance (CMR), are the parameters to predict CRT responders, with AUC of 0.88 (95% CI: 0.81–0.95), sensitivity of 86%, and specificity of 84% [p = 0.007) and statistically significant reduction in mortality (hazard ratio (HR): 4.76, 95% CI: 1.33–17.12, p = 0.01) compared to patients with lower values [CRT is an important treatment option in heart failure patients, although with limited indications as devices are roughly implanted in patients with bundle branch block (preferably LBBB) and EF < 35% . Howeverr values ,12 also MW has been validated in patients with LBBB undergoing CRT implantation from the very beginning, and since then, all the studies that have been conducted have been convincing about the role of the method in this subgroup of patients. The correlation of MW with mortality rates and prognosis will play an important role in the establishment of the method. Mostly segmental, but also global, values of MW indices, especially wasted and constructive work, should be routinely used when CRT patients are under investigation. However, treatment still cannot be guided by only this echocardiographic parameter. Clinicians should rely on symptoms and ECG findings according to guidelines until large studies have established MW as a strong indicator for CRT implantation.2)  and with NT-pro-BNP levels . Patients with a GWI of < 500 mmHg% had a significantly higher NT-pro-BNP  and a lower peak VO2 (9.5 mL/min/kg ± 2.6) compared to patients with a GWI of > 1000 mmHg%  [p = 0.03), whereas LVEF  and age  were predictors of exercise capacity in patients without LV-DYS [p < 0.0001) and myocardial work efficiency (87 (78–90) vs. 90 (86–95), p < 0.0001). After correction for LV size, EF, and WE, GCW was the only predictor of major adverse cardiovascular events (MACE) (HR: 0.99 (0.99–1.00), p = 0.04). GCW < 910 mmHg identified patients at particularly increased risk of MACE (HR: 11.09 (1.45–98.94), p = 0.002, log-rank test p < 0.0001) [p = 0.0037), GCW (p = 0.025), and GWW (p = 0.047) than insulin treatment or each medication alone 12 months after treatment [As MW is an index of LV performance, we expected it to be investigated in patients with heart failure. However, there have only been a few studies with limited number of patients that have shown MW to be significantly correlated with other echocardiographic and clinical parameters. Hedwig et al. demonstrated a strong correlation between GWI and N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiopulmonary exercise, and established prognostic echocardiographic parameters, such as ESV and EF. In particular, GWI < 500 mmHg% was a predictor of severely impaired LV function, inadequate cardiopulmonary exercise, and increased NT-proBNP levels, all of which are markers of poor prognosis. Patients with GWI < 500 mmHg% had a mean LV end-diastolic volume (LVEDV) of 286.1 ± 100.8 mL, LV ejection fraction (LVEF) of 21.3 ± 5.7%, and stroke volume (SV) of 45.9 ± 11.6 mL, while patients with GWI > 1000 mmHg% had a LVEDV of 147.9 ± 39.6 mL, LVEF of 42.6 ± 4.8%, and SV of 70.9 ± 14.3 mL. GWI also showed significant correlation with peak oxygen consumption (peak VO/min/kg) . Shrub et LV-DYS . The res 0.0001) . MW and reatment .Even though the results from the aforementioned studies are promising, all of them are of low value and cannot provide safe conclusions about the use of MW in HF patients. In a recently published study, for the first time, Wang et al. included 508 HF patients with EF < 40%. Although this was a single-center study, the results should be taken into serious consideration as MW was associated with the prognosis of patients. MW correlated with HF hospitalizations and all-cause mortality. In particular, patients with GMW < 750 mmHg% were associated with a significantly higher risk of all-cause death and HF hospitalization  than patients with GMW > 750 mmHg%. These results expand the use of MW in patients with EF <40% and provide safe use of MW for not only segmental but also global values instead of EF and GLS for estimation of patient survival and rates of future hospitalization .p < 0.001), GWE (93% (89–95%) vs. 96% (96–97%), p < 0.001), and GWI (1534 ± 551 vs. 1929 ± 473 mmHg%) were significantly reduced, while GWW (104 mmHg% (66–137 mmHg%) vs. 71 mmHg% (49–92 mmHg%), p < 0.001) was increased in hypertrophic cardiomyopathy (HCM) patients. Segmental differences of CW were observed among different phenotypes of HCM, and GCW was associated with adverse events [p < 0.001). Galli et al. also found that GCW was significantly reduced in HCM . No difference was observed in GWW  and EF (63 ± 13 vs. 6 ± 4% p = 0.17) between the two groups. GCW was the only predictor of myocardial fibrosis as confirmed by CMR, and in particular, a value of 1623 mmHg% showed good sensitivity and decent specificity  [p < 0.001 for all comparisons), and the average increase of GWI in exercise was more pronounced in controls ) than in CA patients ) and in the basal segments of LV than in the apical ones (p < 0.001). Furthermore, GWI identified patients with poor exercise capacity and increased levels of surrogate prognostic markers [MW can also be beneficial in evaluation of cardiomyopathies. In a previous study, it was demonstrated that mean GCW , and it was the most powerful predictor of significant CAD (AUC: 0.786). A cut-off value of 1810 mmHg% predicted significant CAD with a sensitivity and specificity of 92 and 51%, respectively [p < 0.01) [Assessment of patients with coronary artery disease is challenging when there are no wall motion abnormalities (WMA). Echocardiography relies on subjective methods with eyeball assessment of segmental and global myocardial dysfunction and ischemia detection. Even in stress echocardiography, there is no objective measurement that can prove ischemia rather than evaluation of WMA. MW is a promising tool that has demonstrated better sensitivity and accuracy compared to EF and GLS in detecting patients with single- or multivessel coronary artery disease (CAD). GWI was found to be significantly reduced in severe CAD patients compared to those without CAD (ectively . Meimoun < 0.01) . In STEM < 0.01) . Finally < 0.01) .MW has been assessed in valvular heart disease with promising results. Jain et al.  added thp < 0.001) rather than peak aortic pressure , which overestimated the LVSP. The authors concluded that MW is feasible and reliable in AS patients.In another study, in AS patients, it was demonstrated that HF symptoms correlated well with the MW values. New York Heart Association (NYHA) III–IV patients had more impaired GWI and GCW , which rEven though these studies show promising data for evaluation of AS patients using MW, the results should be taken into careful consideration as Russel et al.  incorporp = 0.03) and GLS (p = 0.01), severe MR with effective regurgitant orifice area (EROA) > 30 mm2 (p = 0.02), and preserved LV performance with higher GWI (p = 0.006) and GCW (p = 0.003). However, when ΔLVESV was evaluated, as the true indicator of reverse remodeling, GCW was the only parameter that predicted reverse remodeling. A cut-off value of GCW > 846 mmHg% was associated with 10% LVESV reduction with a sensitivity and specificity of 79 and 74%, respectively [MW has also been evaluated in HFrEF patients with concomitant severe functional mitral regurgitation (MR) treated with MitraClip . The basectively . Again, ectively ,52,53. Tectively  to detecMW has already been investigated recently in right ventricle (RV) and seems to correlate better than other conventional echocardiography parameters with invasive stroke volume and stroke volume index . HoweverTraditionally, LV stroke work is the amount of energy that the heart converts to work during systole when pumping blood into the aorta. LV work is measured invasively with the pressure–volume loop, which demonstrates changes in intraventricular volume and pressure during a normal cardiac cycle. This work is affected by the size of the ventricle and both the preload and afterload. In large ventricles, the volume increases and the ventricle consequently contracts with greater pressure. Preload is important in assessing the contractile properties of the ventricle as it reflects the tension of the muscle when it starts to contract. Afterload is also important as it represents the work that the ventricle must generate to pump the blood to the aorta during systole.Myocardial work was developed as an index of the work performed by the myocardium as it ejects blood during systole and is considered as a less load-dependent method compared to EF and GLS for assessment of LV performance. The protocol of this method involves only the afterload and in particular the systolic aortic pressure, which is equal to the systolic LV pressure in the absence of LVOT and aortic valve gradients. It needs to be mentioned that the protocol does not include the afterload that comes from arterial stiffness, vascular resistance, and reflection waves. In aortic stiffness, reflection waves come earlier into the systole and augment the afterload. This is closely related to LV diastolic dysfunction, ischemia, increased LV mass, and decreased deformation (GLS) . The preEven if MW measures the LV work during systole, end-diastolic LV pressure, which reflects the preload, is also important in LV work assessment. MW takes as granted that, in normal hearts, LVEDP is very low (2–3 mmHg) and does not affect the overall pressure–strain loop area. This means that the method should be restricted to patients with normal functional state of circulation and normal filling pressures of the ventricle. In the future, preload should be taken into account in the MW methodology in order to include all patients suffering from right ventricular pressure and volume overload conditions. Atrial fibrillation should also be taken into consideration as preload changes and MW may lead to inconclusive results from cycle to cycle. For the moment, as MW agrees with invasive methods for measuring LV stroke work and has been validated under several conditions, we accept the method as a more precise index of LV systolic performance. We should not forget that a meta-analysis of 24 studies showed alterations of GLS values in different afterload conditions . As GLS AS and LVOT obstruction (LVOTO) is another contraindication for this method. The addition of the mean transaortic gradient to the brachial systolic pressure in AS cases has not been extensively validated. Even though several small studies showed good correlation with invasive measurements, we can only assume that this practice is correct. In HCM with LVOTO, there are no available data, so MW is not recommended for LV performance evaluation.MW does not take into account anatomic variations, which may lead to limitations. Wall thickness, LV curvature, and radius are not accounted for in the protocol as they may alter the wall stress applied on the segments and consequently the segmental and global work. 4D application that includes all myocardial layers from endocardium to epicardium, LV mass, work produced from circumferential direction, and area strain may eliminate false results that come from geometric assumptions. Patients with normal ventricles without concentric or eccentric hypertrophy and severe remodeling are at the moment considered to be ideal candidates for application of this method.Further development of the method to enable it to come closer to true cardiac physiology as well as validation by large cohort studies will establish the method in routine practice. A direct comparison between GLS and MW in different cardiac diseases and the association of this new marker with the prognosis of patients would enhance its role in LV assessment. Treatments that are guided by GLS evaluation, such as in cardio-oncology patients, may benefit most by a more accurate evaluation of the toxic results of chemotherapeutic drugs. Research will prove the effectiveness of this method.Finally, it has to be mentioned that MW is a diagnostic tool exclusively supported by General Electric (GE) machines. This limits the number of patients that can be evaluated with this method and restricts the ability to compare the results of the same patient with products from different vendors.MW is a feasible, reproducible, and thus reliable method for noninvasive measurement of LV performance. Clinical indications of this method have expanded rapidly in the light of some studies demonstrating the correlation of MW with invasive stroke work and its role as a prognostic marker for survival and hospitalizations, especially in HF patients. Because there are several limitations to this method, it is recommended to be used above and beyond EF and GLS for routine cases or as a research tool. Larger multicenter studies that include a broad spectrum of cardiac diseases will determine the added value of MW in LV performance assessment.


Overall, CPCs were detected in 53 enrolled fetuses, and the remainder were enrolled as controls (n = 47). Pathological findings, such as echogenic intracardiac focus (EIF), ductal spasm, atrial septal defect (ASD), pericardial effusion, cardiomyopathy, and congenital heart disease were found in neither group. In the CPC group, two mild and six trivial cases of tricuspid regurgitation (TR) were detected. In the controls, five cases of trivial TR were identified. In conclusion, the presence of CPCs was not associated with significant functional or structural fetal cardiac abnormalities, which may be due to altered developmental mechanisms.Choroid plexus cysts (CPCs) are often transient and benign findings observed in pregnancy screenings. This study aimed to examine the association between the frequency of congenital heart diseases and the detection of CPCs. In this prospective case-control study, pregnant mothers with no predisposing risk factors for the development of fetal cardiac abnormalities were eligible for entry. Based on the presence or absence of CPCs on ultrasound, the enrolled fetuses were divided into two groups. All patients ( Choroid Plexus Cysts (CPCs) refer to small, fluid-filled structures originating from the lateral ventricles of the fetal brain. These cysts result from the accumulation of cerebrospinal fluid (CSF) in the villi and may resolve with increasing gestational age . Most coThe widespread use of ultrasonography (US) for the detection of fetal abnormalities has also resulted in the more detailed documentation of fetal structural variations. Although the majority of these variations may be part of the natural process of fetal development, others were shown to be of pathologic significance . PrenataAssessment of fetal cardiac function is a routine component of pregnancy ultrasound screening . CardiacDespite the concern regarding the association between the development of CPCs and structural anomalies in affected fetuses, available data are sparse and inconclusive. In addition, and to the best of our knowledge, no previous study has investigated the association between CPCs and the development of fetal cardiac anomalies. To address this issue, we designed and performed this study to evaluate the necessity of fetal heart echocardiography in fetuses with CPCs.This prospective case-control study enrolled pregnant mothers admitted to Rasoul-Akram and Akbarabadi Hospitals  between 31 August 2020 and 21 September 2021. Prior to enrollment and after receiving adequate information on the process and purpose of the study, all eligible participants were required to sign a written informed consent. This study was approved by the Ethics Committee of Iran University of Medical Sciences (IR.IUMS.FMD.REC.1399.687). Singleton pregnant mothers of 18–35 years of age and gestational age (GA) of 18–36 weeks were eligible for enrollment. All the mothers referred for echocardiography, due to presence of CPCs, were asked to provide a complete normal profile of screening tests such as serum screening tests and amnio synthesis prior to enrollment. If such documents were not provided by the mothers, they were excluded from the study. Furthermore, fetuses with abnormal US findings in the first trimester or abnormal US findings at the time of enrollment and mothers with a history of fetal cardiac abnormality, congenital heart diseases in first-degree relatives, chronic disease or continuous use of medication, previous abortion(s) or chromosomal abnormality in previous pregnancies were excluded from the study. Eventually, we excluded participants that used assistant reproductive technology to become pregnant; Since it was already demonstrated that such methods could increase the risk of adverse pregnancy outcomes such as CHD . Then, fTo minimize anticipation bias, all echocardiographic evaluations were performed by a single specialist using a Phillips Affinity 70C system  equipped with a multi-frequency C6-2MHz transducer. Apical, long, and short axis, left ventricular outflow tract (LVOT), right ventricular outflow tract (RVOT), sagittal, and three vessels’ views were assessed. In compliance with the guidelines for fetal echocardiography, edited by the Fetal Echocardiography Guidelines Committee, all subjects were evaluated using the M-Mode, two-dimensional and conventional Doppler echocardiography. Left side cardiac output (LCOP) and Right-side cardiac output (RCOP) were calculated in accordance with the formulas below: Diastolic filling period (DFP) was calculated as the ratio of total diastolic inflow time to the total cardiac cycle duration for both ventricles. The total diastolic filling time was calculated from the beginning of the E-wave to the end of the A-wave. The total cardiac cycle duration was measured from the beginning of any E-wave to the next E-wave’s beginning. Doppler echocardiography was used to measure the MPI  of the right and left ventricles based on the following: isovolumic contraction time (ICT) + isovolumic relaxation time (IRT) divided by ejection time (ET). Doppler time intervals were measured from the mitral inflow and left ventricular outflow, tricuspid inflow, and right ventricular outflow.Echocardiography was employed to explore anatomical abnormalities and measure cardiac function indices (CFI). In addition to the monitoring of the fetal heart rhythm, valvular function, especially that of the tricuspid valve, was also evaluated.t-test, while the Mann–Whitney U test was used to compare nonparametric data. To check the equality of the variance to perform t-test, Levene’s test was used. In the case of qualitative data, the Chi-square test was employed for the purpose of comparison. The p-values < 0.05 were regarded as statistically significant. Statistical analysis was performed using SPSS software version 20 for Windows .Quantitative variables are expressed as mean and standard deviation (mean ± SD), and if the variable lacks normal distribution, median and regarded range were implemented. The qualitative data are presented as frequencies and percentages. To assess for normality, the Kolmogorov–Smirnov test was employed. The comparison of normally distributed data was performed using the In this study, a total of 53 cases and 47 controls were enrolled . In the p-value = 0.43). The echocardiography results for both groups are represented in The echocardiography indices are summarized in t-test. Overall, only the TAPSE index  was found to be statistically different between the two groups.Left ventricular posterior wall thickness at diastole (LVPWD), interventricular septum thickness at end-diastole (IVSD), right ventricular wall thickness, and tricuspid annular plane systolic excursion (TAPSE) exhibited non-normal distribution and were assessed using the Mann–Whitney U test. Normally distributed indices were compared using the The current study reported that fetuses with isolated CPCs did not exhibit a higher risk for developing fetal cardiac anomalies. To control for the risk of fetal and congenital anomalies, we enrolled a group of fetuses with isolated CPCs. Moreover, we provided a normal profile of hemodynamic indices in fetuses with CPCs.CPCs were first observed in the US and described in 1984 and were regarded as normal during development . The forThe correlation between persistent CPCs and various chromosomal abnormalities was suggested. Of these, the association with hydronephrosis and aneuploidies, particularly in trisomy 18 and less in trisomy 21, was investigated more extensively; in addition, an increased frequency of aneuploidy was reported in association with large (> 1 cm) and bilateral CPCs and advanced maternal age (>32 years) ,7. The cNonetheless, Norton et al., who retrospectively examined infants with congenital heart disease, expressed that the prevalence of choroid plexus cysts was 26%, compared to the 12% observed in the controls. However, a noticeable correlation was seen between the presence of CPCs and congenital heart disease and hydronephrosis. Therefore, they proposed non-invasive US screening of the heart and kidney in CPC-positive fetuses . ContrarIn our study, the CFI was similar between the two groups, suggesting normal cardiac development despite the presence of CPCs. Overall, the presence of CPCs was not associated with the development of either structural or functional cardiac disorders. This study corroborates previous research that isolated choroid plexus cysts have no clinical significance and are not considered pathological findings.Tricuspid regurgitation  may be associated with congenital heart diseases, such as tricuspid valve dysplasia, pulmonary atresia, or atrioventricular canal anomalies or it may be an isolated finding without clinical significance. Messing et al. classified mild tricuspid regurgitation as a benign fetal finding at various stages of pregnancy with an overall prevalence of 83.4% . In a suA major limitation of this study is the limited sample pool; enrollment of larger populations may aid in detecting more minute differences between the cases and controls. A number of analyses, such as investigating the relationship between sizes and numbers and sides of the cysts, were not performable due to lacking data. In addition, the outbreak of COVID-19 completely hampered the postpartum follow-up of the neonates. Nevertheless, and to the best of our knowledge, this study was the first study that focused on the echocardiographic parameters of the fetus heart with CPCs.To conclude, the development of CPCs was not associated with structural and functional anomalies. The findings of this study suggest that CPCs, in the absence of previous familial and clinical risk factors, are not associated with the development of fetal heart diseases, and no further screening appears to be necessary for such settings.


Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the LV function as measured by tissue Doppler imaging (TDI) and its association with BPD-PH. We retrospectively assessed prospectively acquired clinical and echocardiographic data from 77 preterm infants born between 2011 and 2013. We characterized the LV function by measuring systolic and diastolic myocardial velocities , isovolumetric relaxation time (IVRT), and myocardial performance index with TDI at three time periods from 32 and 36 weeks, postmenstrual age through one year of age. We also measured post systolic motion (PSM), a marker of myocardial dysfunction that results from asynchronous movement of the ventricular walls, and not previously described in preterm infants. Patients were stratified into groups according to BPD severity and the presence of PH and compared over time. Conventional TDI measures of the LV function were similar between groups, but the septal PSM was significantly prolonged over the first year of age in patients with BPD-PH. PSM provides a novel objective way to assess the hemodynamic impact of lung and pulmonary vascular disease severity on LV function in preterm infants with BPD and PH. Birth at extreme prematurity abruptly challenges the underdeveloped cardio–respiratory systems. The lungs must perform a gas exchange with a decreased surface area of both alveoli and pulmonary vasculature while the heart remodels due to the substantial hemodynamic changes associated with prematurity and its effects on its developmental programming ,2,3. TheWhile the prognosis of the BPD and PVD/PH is linked to RV function, the contribution of the immature left ventricle (LV) performance towards the BPD-PH phenotype is not as well characterized in this high-risk population. Premature birth limits the cell population available to support myocardial maturation and affects ventricular performance in preterm born infants . SpecifiNormal LV function requires coordinated sequential electrical activation and mechanical contraction patterns in the longitudinal, radial, and circumferential planes. Tissue Doppler imaging (TDI) derived post systolic motion (PSM), occurring during isovolumic relaxation, is a distinctive myocardial velocity pattern of LV longitudinal motion. This has been utilized in adults to detect serious myocardial dysfunction with abnormal and asynchronous movement of the ventricular walls that provides insight into both longitudinal contraction patterns and electrical stimulation ,12. TDI Our group has previously demonstrated that BPD-PH adversely impacts contraction patterns in the circumferential–longitudinal plane   with theClinicalTrials.gov: NCT01435187) site at Washington University School of Medicine/Saint Louis Children’s Hospital between August 2011 and November 2013. Details of the PROP study design have been comprehensively described elsewhere [For this exploratory study, we performed a post-hoc analysis on data from preterm infants enrolled through the Prematurity and Respiratory Outcomes Program  consensus definition  by utiliTransthoracic echocardiograms were performed at three time points over the first year of age in the preterm infant: 32 and 36 weeks PMA, and one year CA. The timings of the echocardiograms were selected to avoid the early postnatal period of clinical and cardiopulmonary instability and early mortality associated with extreme preterm birth . We perfWe assessed the LV function offline from TDI derived longitudinal myocardial velocities from the apical four-chamber view. We measured the velocity of muscle movement of a single point along the myocardial wall at both the lateral and septal side of the mitral valve annuli from the base to apex in systole, and the reverse in diastole . The lonWe assessed PSM, also referred to as post systolic velocity, after termination of the s’ wave and prior to the onset of the e’ wave . PSM occp < 0.05. The independent effect of the risk factors for BPD and PH, including gestational age, gender, total oxygen days, length of hospital stay, perinatal factors, common neonatal morbidities , and presence of a patent ductus arteriosus (PDA) beyond 32 weeks PMA on PSM were also accounted for in the analysis. Due to the lack of data regarding the relationship between demographic and clinical characteristics with PSM, and the exploratory nature of this study, we used data from our previous work in premature infants and ventricular performance studies to estimate the sample size, assuming an alpha of 0.05, where 20 subjects per group would provide 99% power to detect 20% differences in echocardiographic measures between groups [®  9.4 version.Categorical level data are described as numbers and percentages, and continuous level data as medians and interquartile ranges. Normally distributed demographics, clinical parameters, and echocardiographic variables between groups were examined by a one-way analysis of variance (ANOVA), and group differences were compared through post-hoc testing using Tukey honestly significant difference testing. Non-normally distributed variables determined by the Shapiro-Wilk test were examined by chi-square, and independent samples by the Kruskal–Wallis one-way ANOVA. Relationships between outcome variables were examined using the univariate (Pearson product correlation coefficient), and standardized linear regression analyses with Bonferroni adjustment for multiple correlations were used to refine the ability to predict LV and septal PSM. The univariate analysis was used to determine the best predictors to enter in the model (significant correlation > 0.4), and then backward step-wise regression was performed to assess the independent effect of gestational age, gender, race, total oxygen days, length of stay, and common neonatal morbidities known to impact cardiopulmonary development  ,18,25, wn groups ,18,25. Ap < 0.01 for both). There were no differences in maternal complications between the three groups. Group I required fewer days of postnatal steroids, had less mechanical ventilation and oxygen therapy days, and shorter lengths of NICU  stays compared to Groups II and III. Other than the difference in IVH (intraventricular hemorrhage) rate, the clinical data and postnatal complications were similar between Groups II and III. In this study, none of the preterm infants received inotropes, inhaled nitric oxide, or other pulmonary vasodilators at any time point in the first year of age. Additionally, none of the preterm born infants were on respiratory support at one year CA. Finally, all preterm born infants received caffeine from birth through 34 weeks PMA, and none received it beyond 34 weeks PMA. Of the 11 in the BPD-PH Group III, 4 (36%) had mild BPD, 5 (45%) had moderate BPD, and 2 (18%) had severe BPD  were classified in Group I, with no or mild BPD, 33 (43%) were in Group II with moderate or severe BPD, and 11 (14%) were in Group III with BPD-PH. Maternal and infant demographic and clinical characteristics for the preterm cohorts are summarized in vere BPD . None ofp < 0.001 for all measures). LV lateral and septal wall a’ remained stable in all three groups from 32 weeks PMA to one year CA. LV lateral and septal wall MPI decreased from 36 weeks PMA to one year CA (p < 0.001 for measures). LV lateral IVRT was increased in Group III at 32 and 36 weeks PMA and was similar between all groups at one year CA. Septal IVRT was increased in Group III at all times points over the first year of age.Comparisons of LV lateral and septal wall TDI measures between groups over time are presented in p > 0.05 for all time points), and also remained stable from 32 weeks to one year CA , but similar between all three groups at one year CA; LV lateral wall PSM remained stable from 32 weeks to 36 weeks PMA, but significantly decreased from 36 weeks PMA to one year CA within Group III (p < 0.01) . PSM remained stable from 32 weeks to one year CA within Group III  and moderate-severe, ) and compared to Group I and Group II, respectively. Within these 11 patients in Group III, there were no statistical differences between PSM based on the severity of the PH or the degree of BPD. Finally, there was significant correlation between IVRT and PSM for the lateral and septal walls . We observed high intra- and inter- observer reliability for both lateral and septal wall PSM   A. Septalroup III B. The sameasure) .p < 0.01), and LV e’/a’, and MPI were lower in the term control cohort compared to all three preterm groups.PSM was not present in the term infants. Septal wall e’, a’, s’, e’/a’, and MPI were similar between all preterm groups and term control infants at one year of age. Septal IVRT was the same between Groups I, II, and the term control population, but significantly higher when compared between Group III and the term controls . LV e’ an = 15) of infants with no difference between the three groups . A PDA was present on the echocardiogram at 36 weeks PMA in 10% (n = 8) of infants with no difference between the three groups . There were no PDAs present at one year CA. There were no differences in conventional TDI measures of PSM based on the presence of a PDA, adjusted for gestational age, sex, PDA size, diagnosis of BPD, and late PH . Similarly, there was no difference in measures at 32 and 36 weeks PMA or 1 year CA between groups, and those that required medical  and/or surgical intervention  to augment closure of the PDA. None of the infants had their PDA closed with a transcatheter device as this study was performed prior to the availability of the transcatheter device at our center.A patent ductus arteriosus (PDA) was present on the echocardiogram at 32 weeks PMA in 19%  as a marker of abnormal myocardial motion and synchrony and showed that those individuals with the severe BPD-PH phenotype had a significantly higher magnitude of septal wall PSM values that presented at 32 weeks PMA and persisted through one year of age. Interestingly, there were no differences over the first year of age in conventional systolic and diastolic tissue Doppler derived velocity measures based on the severity of BPD or presence of PH. The developmental patterns of PSM suggest that prematurity-related cardiorespiratory diseases impact LV myocardial function, reflected by abnormal longitudinal contraction patterns and asynchronous movement of the ventricular walls.Premature birth impacts LV development and growth, predisposing this population to long-term cardiovascular risk ,10. The In adults, PSM has been observed in situations created by ischemia or changes in loading conditions with abnormal motion of the myocardium secondary to ventricular asynchrony ,12. AlthThe challenge in BPD-PH is for the RV to remain hemodynamically coupled to a compliant pulmonary arterial circulation. With the increased awareness of the impact that LV dysfunction has on the RV-PA interactions , it has There is an increasing body of literature on the use of TDI in preterm infants that focuses on diseases in the transitional period and the neonatal period, but with less emphasis beyond . Poon etGiven the clinical importance of earlier detection of PH in preterm infants with severe BPD , advancen = 2) of infants were on mechanical ventilation at 32 weeks PMA and 3% (n = 1) of the infants at 36 weeks PMA. There were no infants on respiratory support at one year CA. We were unable to properly investigate the effect of mechanical ventilation on PSM changes because all of the mechanically ventilated infants at 32 weeks and 36 weeks PMA developed BPD. Although several studies have explored RV TDI measures in BPD and PH patients [The implications of this study need to be understood within the context of its limitations. Although this is the first longitudinal study to track PSM in preterm infants, and only the second study to track TDI mechanics to one year of age in preterm infants, the small sample size and exploratory nature of the post-hoc study design limit the strong associations that can be made with this measure. The sample size calculation allowed for a univariate analysis to determine the best predictors to enter in the model and then backward step-wise regression to assess the independent effect of common perinatal confounders; however, casualty cannot necessarily be proven from the retrospective, nonrandomized design. None of the infants required pulmonary vasodilator therapy or inotropic support, suggesting that the PH in this cohort was relatively well controlled. Although the PSM findings may not be representative of critically ill neonates requiring more aggressive support for their PH or cardiovascular status, we can only hypothesize that the alterations with PSM and impact of LV performance may be even more pronounced with more severe phenotypes of PH. Future large-scale prospective studies are evolving to answer these questions . We assepatients ,51,52,53patients , future In this exploratory post-hoc analysis, we demonstrated for the first time in preterm born individuals that PSM is present and is a sensitive measure of abnormal LV performance in premature infants with varying degrees of cardiopulmonary disease in infants over the first year of age. Although conventional echocardiographic parameters have suggested that LV longitudinal function in premature infants has persevered, we have shown that LV function is indeed abnormal as demonstrated by the presence of PSM. PSM also correlated with IVRT on both the lateral and septal side of the LV and may provide further insight into recognized LV diastolic dysfunction in preterm infants. The presence of abnormal septal motion might also serve as a marker of the impact of disease severity on ventricular function in a population of infants with a high prevalence of cardio-pulmonary disease. The developmental patterns of PSM suggest that prematurity-related cardiorespiratory diseases impact myocardial function, reflected by abnormal longitudinal contraction patterns and asynchronous movement of the ventricular walls. Future prospective studies are now needed to track PSM throughout the ages in preterm born individuals to characterize its natural progression in both health and disease. Adequately powered prospective studies are required to better understand the role of post systolic motion as a marker of systolic and diastolic dysfunction in premature infants with different BPD phenotypes.


Non-ST-elevation myocardial infarction (NSTEMI) has a less severe ratio of acute coronary syndromes compared with ST-segment elevation myocardial infarction (STEMI), arising from complete occlusion of a major coronary artery. The name implies a syndrome that does not exhibit the dramatic ST-elevation seen in the traditional 12-lead ECG in chest pain patients with a confirmed diagnosis of STEMI. The crucial clinical significance of NSTEMI is that delay in diagnosis can lead to increased morbidity, risk of arrhythmia, and death. It was recently reported that atrial fibrillation (AF) correlates with the risk rise of myocardial infarction (MI), although the mechanism underlying this association is currently unknown. Does atrial fibrillation with decompensated heart failure (DHF) get complicated with NSTEMI? In this article, we describe the case of a 77-year-old male patient diagnosed and admitted as NSTEMI complicated by DHF. Atrial fibrillation (AF) is more of an electrical complication. It is observed mainly in patients with acute myocardial infarction (AMI). According to the literature, the incidence ranges from 6% to 19% -3.Various studies have shown that there is a link between atrial fibrillation and increased mortality  as well as adverse events like a cerebrovascular accident (CVA) and heart failure (HF) ,4-6. It Non-ST-elevation myocardial infarction (NSTEMI), as the name implies, is myocardial infarction. NSTEMI is frequently associated with ST-segment depression and T wave changes but can occur with normal ECG. Typically, chest pain patients without significantly abnormal ST elevation are closely monitored until other examinations confirm an acute infarction. A typical confirmation is elevated troponin levels. It is also worth mentioning that troponin elevation indicates injury to the myocardial cells, which may be triggered by inflammation trauma, tachycardia, ischemia, strenuous exercise, release or infusion of catecholamines, renal failure, or imbalance in the autonomic nervous system .Atrial fibrillation is considered a significant public health concern owing to its rising prevalence and strong association with poor prognosis. Currently, there are at least 2.7 to 6.1 million individuals with AF in the United States, and there are indications that this figure may double by 2050 -12. AF, Atrial fibrillation with decompensated heart failure (DHF) is believed to be complicated by NSTEMI. We describe the case of a 77-year-old male patient diagnosed and admitted as NSTEMI complicated by DHF.A 77-year-old male patient was presented to the emergency department with shortness of breath since early morning. The patient had reported a reduction in his urine output recently. He denied any chest pain, palpitation or dizziness, no fever, or significant respiratory symptoms, or lower limb swelling. The patient had been admitted to the hospital because of acute onset shortness of breath associated with orthopnea and paroxysmal nocturnal dyspnea. The patient was known to have diabetes mellitus type II, hypertension, paroxysmal atrial fibrillation on warfarin, osteoarthritis of the knee, multiple myeloma (IgA Kappa) stage III B, recurrent anemia, requiring blood transfusion, previous admissions with volume overload, and end-stage renal disease on peritoneal dialysis.We took the patient’s vitals and obtained the following results: Temperature 36.3°C , respiration rate (RR) 20 breaths per minute, blood pressure 115/89, oxygen saturation (SpO2) 98%, weight 70 kg.General examination revealed that the patient was in a state of consciousness, oriented, looking well, and not in distress. Cardiovascular examinations first and second heart sounds were normal and showed no added sound. Chest examination revealed bilateral basal fine scattered crepitus. Examination of the abdomen showed it was soft, lax, no tenderness. Lower limb examination revealed mild pitting edema of both limbs from the toes up to the whole of both legs, without any signs of deep venous thrombosis. Figure Aspirin treatment was stopped, and warfarin resumed with bridging heparin. The international normalized ratio (INR) has been followed daily until the day of discharge. Upon discharge, the patient’s condition had significantly improved with a drastic reduction of the troponin T Table , with heMyocardial infarction is one of the most common health conditions in developed, developing, and underdeveloped nations. The occurrence of atrial fibrillation in an acute myocardial infarction setting is, therefore, a common phenomenon. Many studies have reported high immediate, long-term, or short-term mortality and even thromboembolic conditions such as ischemic heart disease, ischemic stroke, and atrial fibrillation, reduced quality of life, and reduced capacity to exercise in patients with acute myocardial infarction complicated by atrial fibrillation ,4-6,16.There are a couple of explanations that account for the absence of abnormal ST elevation in acute myocardial infarction. Among these are the possibilities that the patient may be having relatively small infarcts in areas that are not strongly sensed by the lead fields of the 12-lead ECG or probably due to the slow development of the infarct. This also does not imply that the QRS waves and ST-T waves of the ECG do not undergo dynamic changes during the infarct’s time course. At the cellular level, acute ischemia triggers changes in amplitude of action potential, as well as the duration, sloping, or triangularization of the plateau, and in many cases, reduced action potential upstroke velocity in the cells that have been affected. As such, the ECG reveals a dynamic progression of changes in slope and ST level as well as morphology and amplitude of T wave, alongside a widened QRS as a consequence of conduction slowing - all with varying time course and magnitude. All of these may present in NSTEMI, although in a more subtle form than in ST-segment myocardial infarction, in which there are definite elevations of ST segments. As such, any method that is sensitive to changes in QRS and ST-waveform or quantitates them should improve the sensitivity of the infarction test and also reduce the time required for the diagnosis of the syndrome.The results and analysis from this study, according to findings from recent studies that atrial fibrillation is a risk factor for myocardial infarction . But morIt is also worth mentioning that there may be more mechanisms that contribute to the development of congestive heart failure in patients experiencing non-ST elevation acute coronary syndromes (ACS). Diabetes and advancing age are established, independent, and very powerful risk factors for atherosclerosis development, and there is the possibility that the association observed between diabetes and age and the risk of chronic heart failure (CHF) development may be due to a serious underlying disease of the coronary artery in these patients. But then, both diabetes and advancing age are also associated with diastolic dysfunction, and this may play a role in association with the development of CHF .Atrial fibrillation is associated with a high risk of incident myocardial infarction. This association differs based on the MI type. Atrial fibrillation increases the risk of NSTEMI but does not influence STEMI. Once two or more critically cardiac diseases have been diagnosed simultaneously, they must be treated side-by-side on time, as highlighted in the case report with anticoagulation, close monitoring, and AF treatment considering AMI at intervals.


On multivariate analysis, LAVImin , anterior infarction , and abnormal diastolic function  were independent predictors of METs ≤ 8. On Kaplan–Meier analysis, METs ≤ 8 (p = 0.01) and abnormal diastolic function (p = 0.04) were associated with MACEs (median follow-up 2.3 years). METs ≤ 8 was an independent predictor of MACEs . Conclusions: Following first-ever STEMI, increased LAVImin, anterior infarction, and abnormal diastolic function were independent predictors of reduced exercise capacity. Furthermore, reduced exercise capacity was an independent predictor of MACEs. These results highlight important prognostic and therapeutic implications related to abnormal diastolic function in STEMI patients that are distinct from those with LV systolic impairment.Background: Abnormal left ventricular systolic and diastolic function and reduced exercise capacity are associated with worse prognosis following ST-elevation myocardial infarction (STEMI). However, evidence is lacking on the determinants of exercise capacity following STEMI. We sought to determine the impact of systolic and diastolic dysfunction on exercise capacity and outcomes following first-ever STEMI. Methods: In a retrospective analysis of 139 consecutive STEMI patients who had a transthoracic echocardiogram following STEMI and completed exercise treadmill testing, the primary outcome was to identify clinical and echocardiographic determinants of exercise capacity, and the secondary outcome was to identify determinants of major adverse cardiac events (MACEs). Results: Mean number of metabolic equivalents (METs > 8) was used as a cut-off. Age, female sex, anterior infarction, abnormal diastolic function, minimum left atrial indexed volume (LAVI Exercise capacity following acute ST-segment elevation myocardial infarction (STEMI) has been used as a surrogate marker and a predictor of poor outcomes ,2,3. SpeAlthough left ventricular ejection fraction (LVEF) is a well-established predictor of mortality after myocardial infarction, LVEF per se does not predict exercise capacity, as reported both in patients after myocardial infarction and in unselected patients ,7. Only Exercise treadmill testing (ETT) and estimation of metabolic equivalents (METs) are used in cardiac rehabilitation for STEMI patients. METs achieved at ETT have been demonstrated to be an independent predictor of cardiac morbidity and mortality in a variety of unselected patients ,3,10,11 Our aim was to examine the clinical and echocardiographic determinants of exercise capacity defined by METs achieved by ETT, following first-ever STEMI. We additionally sought to determine the prognostic value of METs achieved for a composite of cardiovascular morbidity and mortality. We hypothesised that measures of abnormal diastolic function may be more significant determinants of reduced exercise capacity as compared with systolic function.This was a retrospective cohort study of consecutive patients with first-ever STEMI, presenting between November 2015 and 2017 to Westmead Hospital, Sydney, Australia, a tertiary referral centre.Patients were included if fulfilling prespecified eligibility criteria based on having received standard of care for STEMI patients at our centre. Eligible patients were aged ≥18 years, admitted with first-ever STEMI, had a transthoracic echocardiogram (TTE) performed following the incident event, and subsequently attended cardiac rehabilitation at our centre. All included patients had exercise capacity assessed by an ETT. Patients in atrial fibrillation at the time of TTE, with greater than moderate valvular regurgitation, with severe mitral annular calcification, or with previous valve replacement/repair were excluded from the analysis as diastolic function in these groups cannot be accurately graded .The primary objective was to identify clinical and systolic and diastolic echocardiographic parameters that were determinants of exercise capacity at ETT during cardiac rehabilitation. The secondary objective was to determine the prognostic significance of reduced exercise capacity at ETT with major adverse cardiac events (MACEs), defined as the composite endpoint of cardiovascular hospitalisation for recurrent angina, acute coronary syndrome (ACS), heart failure, arrhythmias, and cardiovascular mortality (death related to cardiovascular causes or sudden death).Prespecified demographic and clinical data were retrospectively collected from electronic medical records. Data were extracted from New South Wales Health Information Exchange by the WSLHD Clinical Analytics and Performance Unit on 30 July 2019, and outcomes were collected until 29 March 2019 . Prespecified echocardiographic parameters were measured from a comprehensive TTE performed following index presentation with STEMI. All TTEs were reanalysed for this study by an investigator blinded to patient, clinical, and ETT details and outcomes. Overall diastolic function was graded and individual parameters of diastolic function  were evaluated. Diastolic grade was determined according to 2016 guidelines  by two iSafety of early ETT in STEMI patients has been previously reported by our cardiac rehabilitation program . Exercis2 for maximum [2 for minimum left atrial indexed volumes [METs were dichotomised according to the mean METs achieved as ≤8 and >8  METs). Age was categorised as ≤59 years and >59 years based on the mean age of the group, and gender was categorised as male and female. Smoking status was divided into three groups: current smoker, former smoker, and never smoked. Left atrial indexed volume was dichotomised based on cut-offs from expert consensus and previous studies: ≥34 mL/m maximum  and ≥18  volumes ,17. LVEF volumes . Tricusp volumes . Territop-values ≤ 0.05 were considered statistically significant. Sample distributions of demographics and clinical characteristics at baseline were examined using descriptive statistics. Continuous and categorical variables were expressed as mean ± SD and number (%) respectively. For univariate analyses, two-sample t-tests for continuous variables or χ2 tests of independence for categorical variables were performed to determine associations between METs and clinical and echocardiographic factors. Clinical factors included age, gender, body mass index (BMI), waist circumference, STEMI territory (by ECG criteria), diabetes, smoking status, symptom onset to table time and TIMI III flow , days until cardiac rehabilitation from STEMI, and serum creatinine. Echocardiographic parameters of diastolic function assessed included transmitral parameters , mitral annular tissue Doppler parameters (average e’ velocity and E/e’ ratio), indexed left atrial volume (maximum and minimum), and peak tricuspid regurgitant velocity; overall diastolic function was graded as normal or abnormal as described in p-values < 0.05 on univariate analyses were included in the multivariable logistic regression model for exercise capacity. Backward elimination was conducted to select the final predictive model for METs ≤ 8. The criterion for the removal of the candidate predictor variables from the multivariable model was set at p < 0.10. Cumulative incidence of MACEs was estimated by the Kaplan–Meier method and compared between groups by the log-rank test. For univariate analysis of MACEs, a Cox regression analysis was performed on the variables included in the final multivariable model for METs ≤ 8, in addition to METs achieved. Variables found to have p-values < 0.05 on univariate analyses were included in the multivariable Cox regression model for MACEs.SPSS Statistics version 24.0 for Windows  was used for analysis; This study was approved by the Western Sydney Local Health District (WSLHD) Human Research Ethics Committee (AU RED LNR/17/WMEAD/192) and conformed to the provisions of the Declaration of Helsinki. Data from this research were completely deidentified and reported only as combined totals.One hundred thirty-nine consecutive eligible patients (November 2015–2017) were assessed. Just over half the patients had an anterior infarction . Most were treated with percutaneous coronary intervention (PCI) , 4/139 (2.9%) had coronary artery bypass grafting, and 9/139 (6.5%) received medical therapy only. Most received dual antiplatelet therapy , 4/139 (2.9%) received single antiplatelet therapy with anticoagulation, and 2/139 (1.4%) received triple therapy . Time from symptom onset to TIMI III flow was available for 107/139 (77.0%) of patients and was 418.9 (SD 698.6) minutes. TIMI III flow was not achieved in 6/139 (4.3%) of patients, and 26/139 (18.7%) did not have symptom onset recorded. Time from symptom onset to table was recorded for 113/139 (81.3%) patients with a mean of 381.2 (SD 675.8) minutes. Most were on appropriate secondary prevention medication at discharge—137/139 (98.6%) were on statin therapy, 116/139 (83.5%) were on beta blockers, and 94/139 (67.6%) were on angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers.LVEF was calculated for all patients ; mean LVmin) , left atrial maximum indexed volume (LAVImax) , and E/e’ . METs achieved had a significant positive correlation with E velocity . There was no significant correlation with LVEF . Further analyses were performed to determine independent predictors of reduced exercise capacity ).METs achieved had a significant inverse correlation with left atrial minimum indexed volume (LAVIp < 0.001). Increasing age, presence of anterior infarction, abnormal diastolic function, and individual diastolic function variables (lower average e’ and higher E/e’) were associated with METs ≤8. Additionally, LAVImin ≥ 18 mL/m2 (p = 0.01) was associated with METs ≤ 8, but LAVImax > 34 mL/m2 (p = 0.15) was not. LVEF < 52% was not associated with METs ≤ 8 (p = 0.15).Individual parameters of diastolic function including transmitral E and A velocity, E/A ratio, deceleration time, e’ velocities, E/e’, and LA maximum and minimum volume were compared between groups based on METs achieved . The nummin , and average E/e’ (e’ velocity was colinear with E/e’ ratio and not included in the multivariate model). Sex was not included as 91.4% were male. LAVImin , anterior infarction , and abnormal diastolic function  were independent predictors of reduced exercise capacity.Multivariate logistic regression  was perfp = 0.01; p = 0.04; min or anterior infarction with MACEs.The mean follow-up from TTE was 718 (SD 324) days, and there were 86 cardiac events including 2 deaths (both due to end-stage heart failure) in a total of 29 patients. The diagnoses of first MACE presentation are presented in p = 0.02) and abnormal diastolic function (p = 0.04) were associated with MACEs. On multivariate analysis , METs ≤ 8 was an independent predictor of MACEs .On univariate Cox regression analysis, METs ≤ 8  In this STEMI cohort, a reduced number of METs (<8) was an independent predictor of a composite of nonfatal and fatal MACEs.The main findings for our study are as follows: (1) Following first-ever STEMI, exercise capacity was reduced in approximately two-thirds of patients to ≤8 METs. (2) LAVImin is often altered before the development of enlarged LAVImax [n = 2867) cross-sectional study of patients undergoing exercise echocardiography [Evaluation of diastolic function is complex and not determined by a single parameter. Current guidelines use a combination of several parameters to grade diastolic dysfunction . Diastol LAVImax . Previou LAVImax ,6,8. How LAVImax . Similar LAVImax . The str LAVImax . Additio LAVImax . This mamin was an independent predictor of exercise capacity. A recent study did demonstrate the effect of left atrial dilatation on exercise capacity [min as a marker for exercise capacity following STEMI. LAVImax was not associated with exercise capacity, which suggests that LAVImin may be a more sensitive marker of elevation of left ventricular filling pressures. Previous studies have demonstrated that LAVImin is more strongly associated with diastolic dysfunction and increased LV filling pressures than LAVImax [min would occur prior to an increase in LAVImax. As reported recently, enlarged LAVImin with normal LAVImax has intermediate prognostic value, worse than patients with normal LAVImin and LAVImax but improved compared to those with both enlarged LAVImin and LAVImax in patients with myocardial infarction [Although the prognostic significance of left atrial size and function has been demonstrated in heart failure and other conditions ,22, datacapacity ; however LAVImax ,24, in pfarction .LV systolic function evaluated by LVEF is a predictor of mortality in STEMI patients . A recenExercise capacity has been previously correlated to early complete revascularisation in STEMI patients ; howeverOur study showed reduced exercise capacity to be an independent predictor of MACEs. This is consistent with other studies where the number of METs achieved was an independent predictor of cardiac morbidity and mortality in various clinical settings ,10,12, iThis study has some limitations. Firstly, this was a single-centre retrospective study with a relatively small number of patients and low event rates. Nonetheless, our results are novel and clinically important as a ‘proof of concept study’ and merit further investigation with larger studies. Secondly, peak troponin as a biochemical marker of infarct size was not assessed as the pathology testing at our hospital capped measurement of high-sensitive troponin I at 40,000 ng/L, preventing assessment of peak levels. Thirdly, details on pre-existing diastolic dysfunction are lacking to determine whether diastolic dysfunction was present prior to STEMI or developed after STEMI. However, determining pre-existing diastolic function would not be possible given this was a cohort of first-ever STEMI of which the timing is unpredictable. We also did not perform analysis of patient medications given the relatively high use of appropriate therapy. Fourthly, this was a retrospective study, and hence advanced echocardiographic measurements such as strain analysis could not be evaluated. Finally, <10% of our STEMI study population was female, which is lower compared to Australian registry data   and thusmin, anterior infarction, and abnormal diastolic function were independent predictors of exercise capacity and superior to clinical variables and other echocardiographic parameters including LVEF, demonstrating the impact of abnormal diastolic function on exercise capacity in STEMI patients. Furthermore, reduced exercise capacity was an independent predictor of MACEs, demonstrating the prognostic value of this relatively easy to obtain parameter in STEMI patients undergoing cardiac rehabilitation. Although our data require confirmation in larger prospective studies, the results highlight important implications for monitoring and surveillance of STEMI patients with diastolic dysfunction distinct from those with LV systolic impairment.In patients who underwent ETT following first-ever STEMI, LAVI


Immediate reperfusion of the infarct-related vessel by primary percutaneous coronary intervention (PCI) is the cornerstone of treatment for patients with ST-elevation myocardial infarction (STEMI) to limit myocardial injury , 2. Seven = 448 patients) reported reduced rates of cardiac death and hospitalization for heart failure after additional RIC [n = 696 STEMI patients) also indicate a prevention of post-infarction heart failure after RIC in combination with ischemic post-conditioning (via repetitive brief interruptions of coronary blood flow immediately after reperfusion) [n = 5401) on clinical outcomes  [Remote ischemic conditioning (RIC) is one of the most innovative and promising approaches in this regard. Brief cycles of transient ischemia and reperfusion applied to an organ or tissue remote from the heart resulted in reduced myocardial damage in experimental models of acute myocardial infarction , 5. In tonal RIC , and therfusion) , 8. Howeization) , 11.12 inhibitors in patients with STEMI [In this issue of the journal, Yu Zheng and colleagues present the rationale and design of the intelligent “Internet-Plus”-based full disease cycle remote ischemic conditioning (i-RIC) trial . This clth STEMI . HoweverIn conclusion, despite sobering results in the most recent RIC studies, RIC should not yet be abandoned and deserves further clinical evaluation. The i-RIC trial pursues some innovative approaches and will provide novel insights into the clinical value of RIC in patients with STEMI. In addition, experimental studies are required to elucidate the underlying mechanism and signal pathways of RIC in order to improve conditioning protocols and patient selection.


This article reviews the most relevant literature published in 2021 on the role of cardiovascular imaging in cardiovascular medicine. Coronavirus disease 2019 (COVID-19) continued to impact the healthcare landscape, resulting in reduced access to hospital-based cardiovascular care including reduced routine diagnostic cardiovascular testing. However, imaging has also facilitated the understanding of the presence and extent of myocardial damage caused by the coronavirus infection. What has dominated the imaging literature beyond the pandemic are novel data on valvular heart disease, the increasing use of artificial intelligence (AI) applied to imaging, and the use of advanced imaging modalities in both ischaemic heart disease and cardiac amyloidosis. Graphical Abstract).Cardiovascular imaging continues to play an important role in improving risk stratification and management in patients with cardiovascular disease. In 2021, coronavirus disease 2019 (COVID-19) continued to impact the healthcare landscape, resulting in reduced access to hospital-based cardiovascular care for acute presentations, including reduced routine diagnostic cardiovascular testing. However, imaging has also facilitated the understanding of the presence and extent of myocardial damage caused by the coronavirus infection. What has dominated the imaging literature beyond the pandemic are novel data on valvular heart disease, the increasing use of artificial intelligence (AI) applied to imaging, and the use of advanced imaging modalities in both ischaemic heart disease and cardiac amyloidosis (CA) (1 Cardiovascular computed tomography (CCT) has been used successfully as a non-invasive alternative for both morphologic assessment, such as for left atrial appendage imaging in lieu of transoesophageal echocardiography,2 or computed tomography coronary angiography (CTCA) in lieu of invasive coronary angiography (ICA), effectively screening patients in whom revascularization is immediately required versus those who can be safely deferred until the acute pressures on global healthcare systems have lessened.3The effect of the COVID-19 pandemic on cardiovascular imaging has been profound.et al.4 characterized myocardial injury using cardiac magnetic resonance (CMR). They identified myocarditis-like myocardial injury in 26% of patients, myocardial ischaemia and infarction in 22% of patients, and dual pathology (ischaemic and non-ischaemic) in 6% of patients. Also, the large majority of patients (89%) has a normal left ventricular (LV) systolic function [ejection fraction (EF) 67 ± 11%], providing evidence that myocardial injury during the COVID-19 infection can be detected but it has limited extent and minimal functional consequence.The topic of myocardial injury caused by the COVID-19 infection had a prominent presence in both the scientific literature and in the media, on occasion causing concerns among physicians and members of the public regarding the extent to which the COVID-19 could affect the heart including in patients with mild symptoms not requiring hospitalization. In a multicentre UK study of 140 patients hospitalized with the COVID-19 infection and concomitant troponin rise, Kotecha Figure 1).5Results from the Magnetic Resonance Imaging in Acute ST-Elevation Myocardial Infarction (MARINA-STEMI) study explored the impact of the COVID-19 pandemic and associated public health restrictions on infarct severity and myocardial tissue damage. The study demonstrated a significant increase in myocardial damage assessed by CMR such as larger infarct size, more extensive microvascular obstruction, higher rate of intramyocardial haemorrhage, as well as a lower LVEF  is an established technique to detect inducible myocardial ischaemia. A recent ABCDE protocol has been proposed which includes the analysis of the B lines by lung ultrasound (Step B), LV contractile reserve (Step C), coronary flow velocity reserve (CFVR) (Step D), and the heart rate reserve (Step E), in addition to the standard regional wall motion assessment. This extended protocol aims at capturing the various sources of vulnerability of patients with coronary artery disease (CAD), such as pulmonary congestion, myocardial impaired contractility, coronary microvascular dysfunction, and cardiac autonomic unbalance. Ciampi 9 tested the prognostic value of the echocardiographic assessment of CFVR in 1600 women with angina pectoris and no obstructive CAD. It demonstrates for the first time the independent association between CFVR and the composite endpoint of cardiovascular mortality, myocardial infarction, heart failure (HF), stroke, and coronary revascularization. This relatively simple and readily available technique could be therefore used in this patient population to diagnose coronary microvascular dysfunction, improve risk stratification, and identify patients eligible for intensified preventive treatment such as statins.The iPOWER study10 demonstrated 36% had a zero CACS, of which 2% had a obstructive disease, 2% had visually assessed adverse plaques, and 13% had a low-attenuation plaque burden (>4%). Myocardial infarction occurred in 41 patients, 10% of whom had a zero CACS.The role of coronary artery calcium scoring (CACS) as an independent risk factor for major adverse cardiac event (MACE) is well established, especially in patients aged >50 years; however, it is not without limitation, especially in those with a CACS of zero. Recent data from the SCOT-HEART groupβ, −0.02; 95% CI, −0.03 to −0.01; P = 0.001), fibro-fatty plaque , greater progression of high-density calcium plaque , and 1K plaque . When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, the statin therapy was not associated with a change in overall calcified plaque volume  but was associated with a transformation towards more dense calcium, which in turn was associated with less plaque progression.11The concept of reduced atherosclerotic risk with increased densification of calcium  has also been a topic of debate in 2021 and is further supported in a multi-institutional cohort study of 857 patients who underwent serial CTCA, 2 or more years apart, with quantitative coronary plaques assessment throughout the entire coronary artery tree. The statin therapy was associated with volume decreases in low-attenuation plaque .12Combining all the available data that can be accrued in a CTCA study in 2021  is increasingly making CTCA an attractive, non-invasive imaging tool that is highly capable of identifying vulnerable patients who would most benefit from preventative therapies .13 Compared to patients with preserved CFC, those with the lowest CFC had the highest mortality risk (2.3 vs. 14%) and this risk was reduced with revascularization. A second study including 623 patients showed an association between the ischaemic burden derived by quantitative MBF data with 15O-water PET and MACE. They showed that patients with an ischaemic burden of at least 24% of the LV mass had worse outcomes than those with a lower ischaemic burden . In multivariable modelling, a high ischaemic burden was prognostically incremental over pre-imaging variables.14 Two additional studies expanded the prognostic value of quantitative MBF with PET to patients with systemic inflammatory disorders without overt obstructive CAD, suggesting a prognostic association between systemic inflammation, diffuse atherosclerosis and coronary microvascular dysfunction.16Two new studies confirmed and expanded the role of quantitative position emission tomography (PET) for risk stratification in patients with suspected or known CAD. One large study including 5274 patients showed that the integration of stress myocardial blood flow (MBF) and flow reserve, termed coronary flow capacity (CFC), as quantified by et al.17 sought to leverage the power of molecular characterization of atherosclerotic plaques with hybrid CTCA and 18F-sodium fluoride (18F-NaF) PET/CT and prognostication using an AI-based survival model in patients with CAD. The study reports incremental value of quantitative 18F-NaF PET/CT over quantitative CT-based plaque analysis for the prediction of myocardial infarction .Kwiecinski et al.18 developed a CMR virtual native enhancement (VNE) imaging technology using AI to identify myocardial fibrosis without the need of a contrast agent. This new method was validated in 1348 patients with hypertrophic cardiomyopathy undergoing both late gadolinium enhancement (LGE) imaging post-contrast administration and VNE imaging. There was a good correlation between the two methods and the VNE had significantly better image quality than the LGE. Importantly, as the VNE images can be produced in <1 s, using this technology can significantly shorten a routine CMR protocol of cine and tissue characterization to 15 min.Artificial intelligence continues to shape the applications of advanced cardiovascular imaging into more efficient and precise tools. Zhang 19Meanwhile, ML algorithms such as applied in the peri-coronary fat attenuation index (FAI) have shown significant promise in identifying those at risk of cardiovascular events, and when used as part of a cardiovascular risk assessment tool that integrates standardized FAI mapping together with clinical risk factors and plaque metrics, is now shown to provide robust individualized cardiovascular risk prediction.et al.20 assessed in almost 300 patients the relationship between TR severity and the composite endpoint of death and HF hospitalization in order to identify the threshold values of vena contracta width (VCW), effective regurgitant orifice area (EROA), regurgitant volume (RegVol), and regurgitant fraction (RegFr) to define low, intermediate, and high-risk TR. The obtained partition values  were lower than in current recommendations and may prevent the underestimation of TR severity, allowing patients to be treated earlier. Fortuni et al.21 studied 1129 patients with significant TR and found that although VCW < 7 mm performed well in stratifying the prognosis of patients with moderate vs. severe TR, EROA > 80 mm2 could better differentiate the risk of patients with more than severe TR. Based on these observations, VCW and EROA were combined into a novel algorithm to classify TR into three clinically meaningful categories: moderate, severe, and torrential, with the last one being independently associated with worse prognosis.The grading of tricuspid regurgitation (TR) is currently based on 2D echocardiographic parameters, its cut-off values were never or poorly validated and they tend to capture only a limited range of regurgitation severity. The increasing awareness of the negative prognostic impact of TR and the introduction of new transcatheter valvular interventions, have raised the interest to improve TR grading. Muraru et al.22 showed that atrial MR (when compared with ventricular MR) is characterized by lower leaflet remodelling and less leaflet tethering (with ‘flattened’ annular shape) but with similar MR severity, suggesting the potential role of different therapeutic strategies for these two distinct secondary MR types . In primary MR, there is increasing evidence on arrhythmic mitral valve prolapse and its association with malignant ventricular arrythmias, particularly in the presence of mitral annular disjunction (MAD), as recently demonstrated in a large cohort (n = 595).23 MAD, as assessed by echocardiography, was independently associated with long-term increased arrhythmic events but without excess mortality.New important insights into mitral regurgitation (MR) have also been published this year. The concept of ‘atrial’ MR has been introduced for patients with secondary MR but normal LV dimension and function, typically observed in patients with atrial fibrillation or HF with preserved EF. Using three-dimensional transoesophageal echocardiography in 135 patients with secondary MR, Uno et al.24 used ML in a large cohort of 440 patients with severe aortic stenosis from 13 centres to identify prognostically important CMR markers of myocardial remodelling and myocardial fibrosis in AS. They demonstrated that myocardial fibrosis (LGE percentage and extracellular volume of distribution) and biventricular remodelling (right ventricle EF and LV-indexed LV end-diastolic function) were the top predictors of survival in AS. The authors proposed combining these four imaging biomarkers into a score that could identify patients at high risk of mortality post-aortic valve replacement (post-AVR) and have the potential to optimizing the decision of AVR.As the interest in myocardial involvement in valvular heart disease continues to grow, Kwak et al.25 investigated whether myocardial flow reserve (MFR) and stress MBF are associated with LV structure and function derangements, and whether these parameters improve after AVR. They demonstrated that in patients with aortic stenosis without obstructive CAD, MBF, and MFR were associated with adverse myocardial remodelling, including markers of myocardial injury and wall stress.Zhou 18F-FDG PET/CT was associated with moderately high sensitivity and specificity  and a high positive predictive value (92%) but a low negative predictive value (47%). Importantly, a positive 18F-FDG PET/CT scan correctly reclassified 57% of possible to definite pulmonary prosthetic valve endocarditis.26Finally, inflammation/infection imaging was used to diagnose infective endocarditis in pulmonary prosthetic valves. A multicentre registry of 66 children and adults with congenital heart disease reported that the use of et al.27 demonstrated in the largest population to date (n = 615) of patients newly diagnosed with cardiac AL amyloidosis, baseline GLS was associated with mortality independently of standard biomarker-based criteria. Most importantly, only patients with a complete haematological response showed a significant improvement in GLS during follow-up, and an absolute improvement of GLS of 2% together with a cardiac biomarker response (decrease in proBNP) identified the subgroup of patients with the best survival. These data support the systematic measure of GLS in these patients in order to improve risk stratification and fine-tune therapy.Global longitudinal strain (GLS) by speckle tracking echocardiography has increasingly been validated as a sensitive tool of LV dysfunction in different clinical scenarios, showing an incremental diagnostic and prognostic value particularly in patients with preserved LVEF. As cardiac involvement is a major determinant of prognosis in amyloid light chain (AL), Cohen 99mTc-SPECT imaging for the differentiation between transthyretin amyloidosis (ATTR) and AL amyloidosis.28 In a large cohort of AL patients, the study reported that 99mTc-DPD uptake was present in 39% of patients but only 10% overall had Grade 2–3 cardiac uptake—threshold used to define the presence of ATTR amyloidosis. The data highlight the importance of ruling out AL amyloidosis in patients with 99mTc uptake. The other study described the accuracy of absolute quantification of 99mTc retention using advanced hardware.29 It found that all quantitative markers correlated with structural remodelling in CA. This approach opens an opportunity for early detection of CA, which is thought to be important to improve success of novel therapies.Two important studies expanding the role of nuclear molecular imaging in CA were published this year. One study addressed the question of the specificity of et al.30 demonstrated how CMR identified no mass in 25%, pseudomass in 16%, thrombus in 16%, benign tumour in 17%, and malignant tumour in 23% of patients. Patients with CMR diagnoses of pseudomass and benign tumour had similar mortality to those with no mass, whereas those with malignant tumour [hazard ratio (HR) 3.31 (2.40–4.57)] and thrombus [HR 1.46 (1.00–2.11)] had greater mortality.The use of CMR in assessing myocardial masses is well established, but there is a paucity of data on its diagnostic accuracy and prognostic role. In a multicentre study of 903 patients with cardiac masses undergoing CMR for further characterization, Shenoy et al.31 investigated the role of quantitative MBF with PET to understand maladaptive myocardial responses in hypertension, demonstrating that a lower stress myocardial flow indexed to myocardial mass (flow–mass ratio) to account for metabolic demand was independently associated with abnormal LV remodelling and with a higher risk of HF hospitalization and death in patients with hypertensive heart disease .Brown Conflict of interest: C.B.-D. is the chief executive officer (part-time) of the Society for Cardiovascular Magnetic Resonance; speaker's fees from Circle Cardiovascular Imaging, Bayer and Siemens Healthineers, she also participated in the medical advisory board of Bayer. N.A.-M. received speaker fees from GE Healthcare and Abbott Vascular; she also participated in the Medical Advisory Board of Philips Ultrasound. E.N. is the Secretary of the Society of Cardiovascular Computed Tomography; speaker fees from Siemens Healthineers, educational consultancy from GE, consultancy with Terarecon Inc, and advisory board of Caristo diagnostics. M.D.C. has none to declare.