P < 0.05), and the AUC of ROC curves predicting the value of left ventricular function in patients with T2D was 0.723 and 0.628, respectively. With significant positive correlations between MAPSE, s', and the majority of the TAMD parameters (P < 0.05), TAMD, MAPSE, and s' demonstrated high inter- and intra-group agreement using Bland–Altman analyses, and the three had predictive value in assessing left ventricular function in T2D patients by ROC curve. Reduced longitudinal strain and reduced mitral annular displacement were seen in patients with different disease stages of T2D, so the application of aCMQ and TAMD was effective in detecting altered left ventricular function in patients with T2D. aCMQ had higher value in predicting left ventricular function in patients with T2D compared to CMQ for overall longitudinal strain, and the software performed the depiction automatically, reducing manual errors. MAPSE parameters and s ' can replace the TMAD technique for assessing mitral annular motion and was simpler to perform, saving operational time.The global incidence of diabetes and related complications is gradually increasing, with cardiovascular complications being the leading cause of death in the diabetic population. The purpose of this study was to examine left ventricular function in individuals with type 2 diabetes mellitus (T2D) and conduct a feasibility analysis using automated cardiac motion quantification (aCMQ) approach. A total of 150 T2D patients with a history of diabetes mellitus dating back more than 10 years were chosen, and we treated 87 patients with T2D that had been present for less than 15 years as group I, 63 patients with T2D that had been present for more than 15 years as group II, and 50 healthy volunteers as the control group. From the three groups, clinical information, conventional ultrasonography parameters, and mitral annular plane systolic excursion (MAPSE) parameters were gathered. aCMQ technique was used to collect longitudinal strain and circumferential strain in the left ventricle. Tissue motion mitral annular displacement technique (TMAD) in aCMQ was used to collect parameters related to TMAD, and cardiac motion quantification (CMQ) was used to collect two-dimensional global longitudinal strain (2D-GLS) to compare the degree of difference between the aforementioned three groups. The differences between longitudinal strain groups in aCMQ were all statistically significant and gradually decreased with increasing disease duration. Most TMAD parameters were lower in groups I and II than in the control group, and TMAD parameters gradually decreased with increasing disease duration. The results of the LV global longitudinal strain and 2D-GLS using Bland–Altman analyses showed high agreement between and within groups, Pearson correlation analysis showed a significant positive correlation (r = 0.18,  The pathological manifestations of diabetic cardiomyopathy include cardiomegaly, left ventricular hypertrophy, and diffuse myocardial fibrosis2. The mechanism mediating myocardial cell damage in patients with diabetes is a complex composition of enhanced oxidative stress, endoplasmic reticulum stress, myocardial fibrosis, and activation of cardiac cell death pathways3. Altered myocardial energetics is a major risk factor for cardiac cell damage in patients with diabetes. The increased glucose and fatty acid levels lead to lipid deposition in the non-adipose tissues of the heart, resulting in lipotoxicity that exacerbates cellular damage6. Moreover, excessive glucose and fatty acids are used as substrates for the tricarboxylic acid cycle, causing a backlog of electrons in the respiratory chain that can leak and react with molecular oxygen to generate reactive oxygen species (ROS)8. Studies have shown that an increased level of ROS is essential to the pathology of various complications of diabetes9. During the subclinical period of diabetic cardiomyopathy, the manifestations in the heart are cardiac diastolic or systolic dysfunction, with the main triggers of the onset of diabetic cardiomyopathy being insulin resistance and the resulting hyperglycemia10. The common cardiac function evaluation modalities in patients with diabetes include three-dimensional (3D) echocardiography, electrocardiography (ECG), or transesophageal echocardiography, all of which have low sensitivity and can detect only markedly reduced cardiac function or altered cardiac structure in patients with diabetes who have often progressed to advanced stages of the disease. Early detection of altered cardiac function in patients with type 2 diabetes (T2D) is crucial as pharmacological intervention cannot restore impaired cellular function in the later stages of myocardial damage in patients with diabetes. Tools such as tissue Doppler imaging (TDI), strain stratification, and 2- or 3D speckle tracking were commonly used by previous researchers to study left ventricular (LV) function in patients with T2D. Although TDI has a higher sensitivity in assessing local myocardial motions despite the influences of the cardiac preload, afterload, and the heart itself, it is susceptible to angular limitations and machine gain11. Echocardiographic automated cardiac motion quantification (aCMQ) is a technique that can be used to analyze LV systolic function from a strain perspective based on a speckle-tracking technique that enables analysis of the longitudinal and circumferential strain at different LV myocardial segments. Tissue mitral annular displacement (TMAD) is used to assess the maximum displacement of the valve by measuring the absolute motion of the two insertion sites on the mitral annulus and the fixed apical location12. The first purpose of this research was to assess the left ventricular subclinical status of T2D patients of various durations using aCMQ and TMAD techniques. The second goal was to examine the viability of using aCMQ and CMQ to evaluate left ventricular function in T2D patients. The third objective was to investigate the viability of using MAPSE parameters, s', and TAMD parameters to evaluate left ventricular function in T2D patients.The global incidence of diabetes is gradually increasing, and the conditions of chronic hyperglycemia and insulin resistance can result in chronic lesions in various organs including the heart. Patients with diabetes usually experience various complications such as arterial atherosclerosis, diabetic foot, and coronary heart disease. Diabetic cardiomyopathy is one of the complications associated with diabetes and is a type of myocardial damage independent from the heart diseases induced by conditions such as coronary artery disease and hypertension13, and had a history of diabetes for more than 10 years were chosen. All of the patients had been diagnosed by an experienced endocrinologist. There were two groups based on the clinical history of diabetes mellitus: group I, which included 48 females and 39 men, had a mean age of (46.21 ± 5.82) years, ranged in age from 30 to 56, and had a disease duration of 10 to 15 years. In group II, there were 23 men and 40 women, aged 40 to 63, with a mean age of (52.22 ± 6.49) years and a disease duration of more than 15 years. Exclusion criteria for this study were cardiovascular diseases such as hypertension, coronary artery disease, heart failure, congenital heart disease, and heart valve disease; renal diseases such as primary glomerular disease, renal artery stenosis, and uremia; diagnosis of type 1 diabetes; poor-quality images; pregnancy; and malignancy treated using chemo- or radiotherapy. A total of 221 patients with T2D were recruited, and 71 patients with myocardial infarction (n = 8), heart failure (n = 5), hypertension (n = 51), malignancy (n = 1), and poor sonolucency (n = 6) were excluded.150 patients with T2D who had been diagnosed in the Department of Endocrinology of the First Affiliated Hospital of Jinzhou Medical University between January 2021 and July 2022, met the diagnostic standards for type 2 diabetes set forth by the American Diabetes Association (ADA) in 2021P > 0.05). A total of 57 healthy volunteers were recruited with seven excluded because of poor imaging quality.Another 50 healthy volunteers were selected as controls from the same research period, and all were cleared from cardiac and renal diseases, hypertension as well as diabetes by ECG, echocardiography, and tests for blood pressure and biochemical indices. The control group consisted of 24 men and 26 women , which was not statistically significantly different from the diabetic group , body surface area (BSA), heart rate, systolic blood pressure, diastolic blood pressure, gender composition, and smoking status were recorded.Informed consent was obtained from all subjects. The personal information of all subjects was recorded and kept confidential, and the subjects received sufficient written or verbal instructions so that they could object to the use of their data for this study. All investigations were conducted following the principles of the Declaration of Helsinki.A Philips EPIQ 7C color Doppler diagnostic ultrasound system  equipped with an S5-1 sector probe with a bandwidth of 1–5 MHz was used. After 30 min of rest, ECG leads were connected to each subject in all groups who were placed in the left lateral recumbent position, and all subjects were examined with the same diagnostic ultrasound system in the same clinic. All echocardiographic data acquisition and analyses were performed by an experienced sonographer. Before acquiring the images, optimizations were made by adjusting gain or depth based on the quality of the images. Conventional echocardiography was used to measure the interventricular septal thickness (IVST) and LV posterior wall thickness (LVPWT) in the parasternal long axis view of the LV in both groups. Measurements were performed per the guidelines of the American Society of Echocardiography. LVEF, LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) were measured in apical four-chamber views and two-chamber views using the biplane Simpson method. Pulsed Doppler was used to assess the early mitral orifice diastolic flow velocity (E), tissue Doppler was used to measure the peak mitral annular early diastolic motion (e') and the peak mitral systolic motion (s') in the lateral wall, and E/e' was determined. The peak longitudinal mitral annular displacement from end-diastole to end-systole was measured, and the two values were averaged, in an apical 4-chamber view using an M-mode ultrasound-adjusted sampling line placed at the root of the mitral annulus on the lateral wall and septal side of the left ventricle. The 2D dynamic images of apical four-chamber, three-chamber, and two-chamber views, as well as short-axis views at the LV mitral valve, papillary muscle, and apex levels from at least three cardiac cycles were acquired and stored on the diagnostic echocardiographic system. Images from each patient were acquired and stored at least three times so the optimal images could be selected for analysis.All acquired images were imported into Qlab software for offline analysis with an aCMQ plug-in selected. Apical four-chamber, three-chamber, and two-chamber views were selected, and the regions of interest (ROI) were outlined automatically by the software. Further modifications could be made manually on the ROI generated automatically by the software until they were overlapping with the outlines of the endocardium and epicardium. When all analyses were finished, the “compute” button was clicked to calculate the longitudinal strain at different LV myocardial segments and generate bull’s-eye charts. In aCMQ, the short-axis views at the LV mitral valve, papillary muscle, and apex levels were analyzed one by one to obtain satisfactory ROI followed by calculating the circumferential strain and generating bull’s-eye charts using the same method described in the longitudinal strain analysis. The apical four-chamber and two-chamber views were loaded into the TMAD plug-in in aCMQ. In the apical four-chamber view, the tracking points were set at the septal site of the mitral annulus with left clicks, the lateral site of the mitral annulus, and the apex to obtain the displacement of the septal annulus toward the apex (AP4MV1), displacement of the lateral annulus toward the apex (AP4MV2), mean displacement of the mitral annulus in a four-chamber view toward the apex (AP4MV Midpt), and proportional displacement of the mitral annulus in a four-chamber view toward the apex (AP4MV Midpt%). In the apical two-chamber view, the three tracing points were placed at the inferior site of the mitral annulus, the anterior site of the mitral annulus, and the apex to yield displacement of the anterior annulus toward the apex (AP2MV1), displacement of the inferior annulus toward the apex (AP2MV2), mean displacement of the mitral annulus in a two-chamber view toward the apex (AP2MV Midpt), and proportional displacement of the mitral annulus in a two-chamber view toward the apex (AP2MV Midpt%). All measurements were repeated three times and averaged.Apical four-chamber views, apical three-chamber views, and apical two-chamber views were imported into the CMQ, and the endocardial border was manually traced at end-diastole and manually adjusted to best match the endocardial position if necessary to derive a two-dimensional overall longitudinal strain.In 30 patients randomly selected from the diabetic group, LVGLS, AP4MV1, s’, MAPSE-mean, and 2D-GLS were analyzed by two independent physicians who were skilled in the use of Qlab software. The two physicians were blinded to each other’s data, and the data collection process was repeated by one of the physicians 1 week later. The inter-observer and intra-observer variability were examined with the Bland–Altman tests.P < 0.05 was considered statistically significant.SPSS 23.0 statistical software was applied for statistical analysis, and the chi-square test was used for the comparison of count data. All measurement data were tested for normality, and those conforming to normal distribution were expressed as mean ± standard deviation, and the F test was used for intergroup comparison between groups, and the LSD-t test was used for two-way comparison between groups. Data that did not conform to a normal distribution are presented as medians and interquartile ranges and were compared using the Kruskal–Wallis rank sum test for differences between groups. Pearson correlation analysis was used to analyze the correlation of TMAD parameters with MAPSE parameters and s'. The area under the ROC curve (AUC) was computed after the receiver operating curve (ROC) of the aCMQ parameters, TMAD parameters, MAPSE parameters, s', and 2D-GLS in predicting left ventricular systolic function of T2D was drawn. The prediction was considered unreliable with minimal diagnostic value when the AUC was < 0.5, some diagnostic value when the AUC was > 0.5, and a high diagnostic value when AUC was > 0.7. A difference with The study was approved by the Ethics Committee of the First Affiliated Hospital of Jizhou Medical University  (202252).The following information was obtained from all participants.P > 0.05). The number of smokers, fasting state glucose, HbA1c, triglycerides, and total cholesterol were higher in group I than in the control group, and the high-density lipoprotein level (HDL) was lower than in the control group (P < 0.05). Age, glucose, glycosylated hemoglobin, low-density lipoprotein level (LDL), triglycerides, and total cholesterol were higher in group II than in the control group, and HDL was lower than in the control group (P < 0.05). Age and LDL were higher in group II than in group I, and the number of smokers was lower than in group I (P < 0.05) . e' was lower in group II than control and group I, and E/e' was higher than control and group I (P < 0.05). LVEF was higher in group II than in control (P < 0.05)  Table .Table 2CP > 0.05). LVGLS, longitudinal strain of the left ventricle in apical two-chamber view (LVAP2LS), longitudinal strain of the left ventricle in apical three-chamber view (LVAP3LS), longitudinal strain of the left ventricle in apical four-chamber view (LVAP4LS), and 2D-GLS in group I were significantly lower than those in the control group (P < 0.05). LVGLS, LVAP2LS, LVAP3LS, LVAP4LS, and 2D-GLS in group II were significantly lower than those in control and group I (P < 0.05). Circumferential strain measured at the basal left ventricular level (SAXMCS) and circumferential strain measured at the apical left ventricular level (SAXACS) were lower in group II than in the control group (P < 0.05). The differences between groups for the remaining parameters were not statistically significant  and the global left ventricular circumferential strain (LVGCS) . AP4MV1, AP4MV Midpt, AP2MV1, AP2MV2, AP2MV Midpt, AP2MV Midpt%, s', MAPSE-SEPTAL, MAPSE-LATERAL, and MAPSE-mean were significantly lower in group II than in group I and the control group (P < 0.05). Both AP4MV2 and AP4MV Midpt% were lower in group II than in the control group (P < 0.05) . MAPSE-LATERAL and AP4MV1, AP4MV2, AP4MV Midpt, AP4MV Midpt%, AP2MV2, AP2MV Midpt, AP2MV Midpt% were positively correlated with each other . MAPSE-mean was correlated with AP4MV1, AP4MV2, AP4MV Midpt, AP4MV Midpt%, AP2MV2, AP2MV Midpt, and AP2MV Midpt% were positively correlated with each other . s' and AP4MV1, AP4MV2, AP4MV Midpt, AP4MV Midpt%, AP2MV1, AP2MV2, AP2MV Midpt% were positively correlated with each other . There was no correlation between MAPSE-LATERAL and MAPSE-mean and AP2MV1 . There was no correlation between s' and AP2MV Midpt . MAPSE-SEPTAL was not correlated with AP4MV1, AP4MV2, AP2MV1, AP2MV Midpt%  (Table P < 0.05) . The differences between SAXBCS and LVGCS groups were not statistically significant (P > 0.05), and only SAXMCS and SAXACS were lower in group II compared with the control group. This indicated that longitudinal strain was more susceptible to change than circumferential strain in the LV of patients with diabetes. It is possible that the LV endocardium, the myocardial fibers of which are predominantly distributed longitudinally, is the first to be damaged by hyperglycemia or free fatty acids, which endows the longitudinal strain with higher statistical significance than circumferential strain28. This result is consistent with the reported findings of many previous studies. For example, a study on cardiac involvement in children with diabetes conducted by Motamedi et al.29 showed lower longitudinal strain in all segments of the heart. Sonaglioni et al.30 suggested that the overall longitudinal strain in the LV of patients with gestational diabetes was significantly lower than that in healthy pregnant women. The statistically significant differences between the AP4MV1, AP4MV Midpt, AP2MV2, AP2MV Midpt, AP2MV Midpt%s', MAPSE-SEPTAL, MAPSE-LATERAL, and MAPSE-mean groups gradually decreased with increasing disease duration. AP4MV2 and AP4MV Midpt% were lower in groups I and II compared with the control group, and AP2MV1 was lower in group II compared with the control group and group I. This could be because impaired cardiomyocyte viability or mitochondrial function in the patients with diabetes increased apoptosis and oxidative stress, which lead to reduced motion of the mitral annulus toward the apex during LV systole compared to that in healthy controls. The results of this study are similar to those reported by Iwakura et al.31.In this study, LVEDV, LVESV, LVPWT, and IVST measured by conventional echocardiography remained within normal values and did not decrease significantly, and only LVEF was lower in group II patients compared with controls, which may be due to the subclinical state of the heart in diabetic patients. Previous studies have shown that in patients with normal LVEF, fibrotic myogenic degeneration of the cardiomyocytes may be a result of the increased oxidative stress, to which LVEF is insusceptible32 discovered reduced left ventricular systolic function despite normal LVEF, demonstrating the viability of MAPSE in assessing left ventricular systolic function and correlating with the findings of the current study. According to our findings, there is a substantial connection between 2D GLS and LVGLS and excellent inter- and intragroup agreement between the two methodologies when measuring overall longitudinal LV strain in patients with T2D using automatic and manual methods. Compared to LVGLS measured mechanically, 2D GLS performed manually was less useful in predicting LV function in individuals with T2D. A comprehensive analysis of the feasibility of the aCMQ technique to assess left ventricular function in patients with T2D was better.We found that most TMAD parameters were significantly and positively correlated with MAPSE parameters and s', and all three Bland–Altman results showed high agreement, and all three had predictive value in assessing left ventricular function in patients with T2D, further suggested that MAPSE parameters and s' can be used as a proxy for TMAD parameters, but s' had a lower value in predicting left ventricular function compared to TMAD and MAPSE parameters. Using MAPSE parameters to analyze patients with Duchenne muscular dystrophy, Panovsk et al.35.We believe that the findings of reduced LV longitudinal strain and mitral annular displacement in patients with T2D by aCMQ and TMAD suggested early myocardial damage in patients with diabetes, and clinicians should be informed to commence early intervention to ameliorate and stop the progression of diabetic cardiomyopathy. Many researchers have noted that exercise could help prevent cardiomyocyte apoptosis, myocardial fibrosis, and oxidative stress, which could moderately delay the development of diabetic myocardial damageThere are certain limitations to this study. First, the application of the aCMQ technique requires a clear depiction of the endocardium. However, in practice, the endocardium can appear unclear because of unavoidable factors such as smoking. In these cases, the endocardium needs to be outlined manually, which may generate operator error and deviations from the true values. Second, mitral valve degeneration or calcification in some patients may have influenced their mitral annular displacement. Finally, because of limited research duration and objective constraints, the patients with T2D selected for this study were regional and few.It is highly feasible for aCMQ and TMAD to evaluate the left ventricular systolic function in patients with T2D and correlate it with the duration of the patient's disease. This can serve as a foundation for the early clinical detection of myocardial damage changes in patients with T2D and for the prompt application of appropriate measures to prevent further development of myocardial injury.


Although major advances have occurred lately in medical therapy, ischemic heart failure remains an important cause of death and disability. Viable myocardium represents a cause of reversible ischemic left ventricular dysfunction. Coronary revascularization may improve left ventricular function and prognosis in patients with viable myocardium. Although patients with impaired left ventricular function and multi-vessel coronary artery disease benefit the most from revascularization, they are at high risk of complications related to revascularization procedure. An important element in selecting the patients for myocardial revascularization is the presence of the viable myocardium. Multiple imaging modalities can assess myocardial viability and predict functional improvement after revascularization, with dobutamine stress echocardiography, nuclear imaging tests and magnetic resonance imaging being the most frequently used. However, the role of myocardial viability testing in the management of patients with ischemic heart failure is still controversial due to the failure of randomized controlled trials of revascularization to reveal clear benefits of viability testing. This review summarizes the current knowledge regarding the concept of viable myocardium, depicts the role and tools for viability testing, discusses the research involving this topic and the controversies related to the utility of myocardial viability testing and provides a patient-centered approach for clinical practice. Ischemic heart disease is still the leading cause of morbidity and mortality. There is an increasing number of patients with ischemic cardiomyopathy and heart failure. Coronary artery disease (CAD) is the most important cause of chronic heart failure accounting for two thirds of left ventricular (LV) dysfunction cases . Around LV function is one of the most important prognostic determinants in patients with CAD, impacting survival, hospitalization and quality of life . Long-teThe improved survival after acute coronary syndromes has led to an increased prevalence of ischemic heart failure. The major priority in patients with acute coronary syndromes is to reduce the amount of myocardial necrosis with reperfusion strategies. However, despite early reperfusion, patients are prone to develop myocardial structural alterations that will reduce LV function and will lead to heart failure . Around Although observational studies reported that in patients with myocardial viability, outcomes improved following surgical revascularization, prospective randomized trials have not confirmed the positive interaction between myocardial viability and the effect of revascularization. The recovery of LV function after revascularization is a marker of myocardial viability but is not the most important element, and it does not seem to impact outcomes. Protection of the residual viable myocardium from subsequent acute coronary events and prevention of further deterioration are probably major contributors to improving outcome . HoweverThe role of viability testing in ischemic cardiomyopathy remains controversial, and there are still many unknown elements regarding the interaction between viability, ischemia and treatment in predicting clinical outcomes and prognosis .The aim of this review is to provide a synthesized overview of the current knowledge regarding the concept of viable myocardium and the methodology of myocardial viability testing, to discuss controversies regarding usefulness of viability testing in the management of ischemic heart failure and to describe a potential approach for clinical practice.Extensive research of the literature was performed comprising scientific data regarding myocardial viability, from the concept of viable myocardium to the most important methods of assessing myocardial viability; observational studies and randomized clinical trials on this topic; the prognosis related to myocardial viability; and approaches in the management of patients with ischemic heart failure. Databases such as PubMed, Cochrane Library, Scopus, Web of Science, etc., were researched using keywords and Me-SH terms. The methodology of literature selection is presented in the PRISMA flowchart  Figure . Following an acute ischemic event with abrupt interruption of the blood supply, myocardial necrosis was observed 30 min after ligaturing of the left anterior descending coronary artery in rats . After tMyocardial stunning is a condition defined by reversible LV contractile dysfunction in the presence of a restored coronary flow after a brief period of coronary occlusion. In stunned myocardium, there is a flow–contraction mismatch with restored blood flow but persistent impaired contractility. The recovery of contractile dysfunction occurs spontaneously in a few hours or weeks . The most common settings with stunning myocardium in humans are post-reperfusion after acute myocardial infarction, after cardioplegic arrest during open heart surgery and after exercise-induced ischemia or after coronary artery spasm. Various factors are involved in the pathophysiology of stunned myocardium, such as: oxygen free radicals and/or calcium overload and structural changes of collagen .Hibernating myocardium is defined as a dysfunctional but viable cardiac area with persistently reduced contractility due to reduced coronary blood flow at rest. Myocardial contraction requires a higher amount of energy than that needed for cell survival. Myocardial cells are entering into a state of hibernation, where the energy is used to preserve cellular integrity to the detriment of contractile function ,23. ThisRahimtoola was the first author to describe a significant recovery of myocardial function after revascularization and introduced this concept of viability . HibernaCoronary blood flow at rest is not so severely impaired as the degree of cardiac dysfunction, but rather coronary flow reserve is diminished. Hibernating myocardium may also result from repetitive stunning with progression over time from normal coronary flow with reduced flow reserve to reduced resting coronary flow . The chrAlthough they are described as different entities, this two-setting, stunned and hibernating myocardium can represent different stages of a continuum of LV dysfunction, and chronic, repetitive stunning can lead to myocardial hibernation . The revIn clinical practice, myocardium with contractile dysfunction that recovers contractility with appropriate medical therapy and revascularization is a viable myocardium. An assessment of myocardial viability can be difficult, as viability is not a dichotomous concept, but rather there are different degrees of viability that can vary from total absence of viability to normality . Hibernating myocardium is viable, so in different investigation methods, a conserved cell membrane integrity and metabolic activity, the absence of scar and the presence of contractile reserve can be identified . AvailabThe preservation of LV wall thickness can be evaluated with echocardiography and cardiac magnetic resonance imaging (MRI), while the contractile reserve is investigated with dobutamine stress echocardiography (DSE) and stress cardiac MRI. Myocyte membrane integrity can be evaluated with single-photon emission computed tomography (SPECT) based on radiotracer uptake, and blood perfusion is evaluated with scintigraphy with Thallium (Tha) or technetium (Tc) contrasts, positron emission tomography (PET) and contrast cardiac MRI. PET and cardiac MRI spectroscopy may evaluate metabolic defects of non-viable myocardium. Late gadolinium hyper-enhancement (LGE) and T1 mapping cardiac MRI can depict myocardial fibrosis and scar. Diagnostic technique should have a good spatial resolution since necrotic myocardium and viable myocardium may coexist in the same segment of LV wall. Cardiac MRI is, from that point of view, the imaging diagnostic tool of choice.The traditional definition of viable myocardium implies the recovery of myocardial function after revascularization. As a consequence, imaging tools that evaluate reserve contractility as DSE and stress cardiac MRI will possess a higher positive predictive value and specificity, but lower sensitivity in identifying viable myocardium, than methods that are evaluating cell membrane integrity such as SPECT, or metabolic activity such as PET, which have higher sensitivity and negative predictive value but a lower specificity . A meta-analysis of 158 studies confirmed that PET had the highest sensitivity and negative predictive values, and DSE the highest specificity and positive predictive values at a segmental level . Echocardiography represents an available and inexpensive diagnostic tool able to provide information on myocardial viability. At rest, echocardiography can establish LV ejection fraction (LVEF), can detect the presence of wall motion abnormalities and allows measurements of wall thickness and LV size. Myocardial cell necrosis and fibrosis are leading to a thinning of the LV wall. Echocardiography can evaluate the thinning of the LV in akinetic or dyskinetic segments, and an increased refraction may indicate fibrosis. The presence of end-diastolic thickness at rest below 5 mm associated with akinesia or dyskinesia is a sign of non-viable myocardium ,35.A myocardial wall thickness over 5 mm in end-diastole is an indicator of a viable myocardium with a sensitivity of 100% but with a low specificity of 28%. A severely dilated LV can reflect the presence of non-viable myocardium, an increased end-systolic volume being correlated with poor LV function improvement after revascularization. An LV end-systolic volume > 130 mL can predict a higher rate of cardiac events after revascularization even in the presence of metabolically viable myocardium ,36. EchoDSE has an established role for the evaluation of hibernating and stunned myocardium and can help in identifying those patients with ischemic cardiomyopathy that are suitable for revascularization. DSE has low risk, and is a quick and non-invasive investigation that implies no radiation, so is the most widely used technique for detecting myocardial viability . DSE can evaluate the contractile reserve in the viable myocardium and predict functional recovery after revascularization. However, even in the absence of contractile reserve, myocardial viability may exist. In patients with a low amount of viable myocardium, revascularization may not be followed by contractility recovery, but LV remodeling can be avoided . DobutamAn initial improvement of contractility indicating viability, followed by a later worsening due to ischemia, is a biphasic response characteristic for hibernating myocardium. A biphasic response has a reported sensitivity of 60% and a specificity of 88% in predicting the recovery of contractile function after revascularization . The secCompared to SPECT and PET, DSE has a greater specificity (81% vs. 73%) but a lower sensitivity (84% vs. 90%) for the detection of myocardial viability ,45,46.Myocardial contrast echocardiography can assess microvascular integrity with a contrast agent, and perfusion defects are indicators of the no-reflow phenomenon associated with remodeling and poor outcome . MicrovaKorosoglou et al. performed a study to compare myocardial contrast echocardiography with DSE and with combined Tc 99m SPECT and FDG-18 PET for the evaluation of myocardial viability. Myocardial contrast echocardiography showed 86% sensitivity and 43% specificity to predict myocardial function recovery, nuclear imaging had 90% sensitivity and 44% specificity and DSE had 83% sensitivity and 76% specificity . MyocardAn accurate test for the evaluation of regional myocardial deformation is speckle-tracking echocardiography . By evalThe SPECT permits the concomitant evaluation of perfusion and contractility at both global and segmental levels. The sensitivity of the method is 87% and specificity 65% in predicting the recovery of contractility after revascularization ,53.In SPECT imaging, a viable myocardium is characterized by the presence of cardiomyocyte with cellular membrane integrity that uptakes a radionuclide-labeled tracer. An uptake of >50% tracer activity of the maximum uptake of a normal segment is used to identify viable myocardium, and an uptake less than 30% is indicative of non-viable myocardium. in an uptake between 30 and 50% of tracer activity, a partial viable myocardium is identified. The most commonly used radiotracers in SPECT myocardial perfusion imaging are Thallium 201 and Technetium 99m. When rest perfusions’ defects are detected, and the viability of myocardium is questionable, stress perfusion imaging may be performed. A worsening defect on stress imaging (indicating ischemia) can suggest viable myocardium. A preserved wall motion and thickening of the myocardium at rest, or improving of segmental contractility on post-stress gated imaging is an important marker of the absence of a transmural scar . Thallium 201 is a cationic radionuclide isotope analog of potassium. The initial myocardial uptake of Thallium 201 is determined by rest coronary blood flow, but the subsequent uptake in the next 4–24 h is produced by ”refill and redistribution” of the tracer, depending on cellular membrane integrity ,41. the Hibernating myocardium will appear as a perfusion defect, determined by reduced rest coronary blood flow on initial images, but in 4–24 h imaging, the uptake will become normal due to the redistribution of Thallium 201 (with or without reinjection). The sensitivity in detecting viable myocardium may increase in the late 24 h reinjection/redistribution protocol versus 4 h early redistribution protocol .A quarter of fixed defects on reinjection Images are reversible on nitrate/reinjection images, improving the identification of myocardial viability . Technetium (Tc) 99m compounds have a greater photonic energy and lower half-life than Thallium, being better detected by SPECT gamma cameras. Tc 99m-sestamibi and Tc 99m-tetrofosmin are lipophilic with cardiac affinity and are distributed in the myocardial cells proportional with coronary flow. Technetium enters in the myocardial cells through passive diffusion via the cell and mitochondrial membrane. Its fixation is more than 90% in the mitochondria and depends on the presence of the mitochondrial metabolic activity and maintenance of the polarity of the transmembrane potential. Redistribution is not produced, and Tc remains inside the cell. Technetium compounds are very good in the evaluation of coronary blood flow because no redistribution occurs, but it is impossible to differentiate between hypo fixation due to reduced coronary flow or cellular necrosis. It is essential to measure relative levels of activity in different myocardial regions, with Tc 99m-sestamibi activity being inversely correlated with the amount of fibrosis. Activity cutoff points above 50–55% predicted the functional recovery of myocardium after revascularization ,57.A perfusion defect at rest is myo”ardi’l infarction or hibernating myocardium. If the perfusion defect is correlated with the presence of wall motion and thickening on gated imaging (rest or post-stress), and there is a worsening of perfusion defect at stress, this indicates a hibernating myocardium. Although Thallium is considered superior in myocardial viability assessment due to its redistribution, different studies showed similar sensitivity and specificity in detecting viable myocardium for both tracers and in predicting functional recovery after revascularization . SPECT is more available and cheaper than PET, but the absence of tracer uptake does not confirm non-viable myocardium, while the normal uptake of radiotracer confirms viability. A thinned viable myocardium can sometimes be characterized on SPECT imaging as non-viable due to poor resolution, and DSE may detect the absence of contractile reserve in thinned non-fibrotic myocardial segments mislabeling a viable or partially viable myocardium as non-viable .The low spatial resolution Is affecting the accuracy of diagnosis. SPECT can detect about half of non-viable segments with involvement of less than 50% of wall thickness detected by LGE cardiac MRI . New isoPET implies the comparison of myocardial perfusion and myocardial metabolism to assess myocardial viability . The maiFDG imaging can detect myocardial viability with a high sensitivity of 92%, a lower specificity of 63%, a positive predictive value of 74% and a negative predictive value of 87% ,53.The main disadvantages are low availability and high cost, the complex and long protocol, interference of FDG uptake by medication (levothyroxine), diabetes, age, sex, heart failure and inability to identify small subendocardial necrosis. Advantages of PET over SPECT are considered as follows: superior spatial resolution, less radiation exposure and quick and absolute quantification of myocardial perfusion. A superior diagnostic accuracy is revealed for PET in the detection of myocardial viability versus other imaging tools .Cardiac MRI can evaluate myocardial viability with various techniques that will assess the metabolic, structural, functional alterations, tissue characteristics and cellular viability. It is the ideal imaging technique for the evaluation of myocardial viability. It can identify and quantify the extent of the scar tissue, myocardial perfusion, wall thickness and segmental wall motion, LV ejection fraction, ventricular volumes and contractile reserve with dobutamine stress . It is aMembrane cellular damage and impaired micro perfusion can be detected with contrast-enhanced MRI. The most commonly used contrast agents are gadolinium-based, and are rapidly moving through the vascular space before entering to intercellular space. In heathy myocardial cells, gadolinium respects the intracellular space. The detection of myocardial perfusion defects using first pass gadolinium-enhanced MRI after an acute myocardial infarction indicates no-reflow and non-viable myocardium, and revascularization is not leading to the recovery of contractile function ,63,64. TSeveral clinical studies revealed the recovery of function in the viable ventricular wall detected by LGE ,67,68. TCardiac MRI is a simple, reproductible, and safe method, that has high accuracy for detecting viable myocardium. The good spatial resolution permits the detection of the extent of the viability alteration in the ventricular wall and clearly distinguishes between viable and non-viable myocardium . Due to In areas with LGE < 50% of segmental thickness, or with akinetic and thinned myocardium, the contractile reserve with a low dose of dobutamine will be evaluated . A signiThe volume fraction of the extracellular space can be evaluated based on native and post-contrast T1 images, a technique that can help in predicting myocardial function recovery ,74. A neBy combining multiple viability parameters, end-diastolic segmental thickness, LGE, and contractile reserve, an increased sensitivity and specificity are obtained in detecting viable myocardium (<50% LGE with contractile reserve), partial viable myocardium , or non-viable myocardium  ,76. Any residual viable myocardium may benefit from revascularization, because even if there was no significant contractile recovery after revascularization, the improved outcome was observed in the surgical arm of the STICH trial .The large-scale implementation of cardiac MRI for viability evaluation is limited, being an expensive and less available method, with a few contraindications  .In contrast, in enhanced cardiac computed tomography (CT), the contrast agent directly evaluates extracellular volume dimensions by interference with an X-ray beam, but due to a molecule with a reduced size of the iodine contrast dye, the optimal imaging time is shorter. Multi-row detector CT has greater spatial resolution and can accurately evaluate the myocardial and microvascular structure. Compared with LGE-cardiac MRI, the lower contrast-to-noise ratio represents a limitation. More extensive studies are necessary regarding the potential of multi-energy CT in myocardial viability assessment ,79.Coronarography and intravascular imaging can evaluate the morphology and function of the coronary vessels and the myocardium. Elements that are indicating a myocardium with preserved viability are: a distal TIMI  grade III flow, myocardial blush of contrast, the presence of a collateral flow, and a significant proximal coronary stenosis. Myocardial contractility improvements after dobutamine or nitroglycerine also reflect myocardial viability. Coronary artery pressure and velocities can be measured invasively during adenosine-induced hyperemia. The fractional flow reserve during hyperemia is influenced by the severity of the coronary artery stenosis but also by the magnitude of the area of viable myocardium supplied by the stenotic coronary and the collateral vessels. The fractional flow reserve distal to a stenosis is lower in the presence of a viable myocardium, and the improvement after revascularization predicts myocardial contractility recovery  ,80.In viable myocardium, the coronary microvascular bed is preserved and has normal resistance. Myocardial blood flow is reduced in infarcted myocardium due to microvascular dysfunction. The degree of microvascular impairment is a predictor of myocardial contractility recovery after revascularization in acute myocardial infarction. Several parameters can evaluate microvascular resistance as: coronary flow reserve, index of microcirculatory resistance, and hyperemic microvascular resistance. While coronary flow reserve is affected by the presence of epicardial coronary artery stenosis, the other two parameters reflect better microcirculatory dysfunction and are more specific for myocardial viability evaluation . The indPathologic Q waves were traditionally attributed to transmural ischemia and thought to represent necrotic scarred myocardial tissue. On succeeding investigation, it was revealed that the presence of the Q wave has a poor correlation with the absence of myocardial viability, and low accuracy for myocardial viability detection compared with other imaging tests with a reduced sensitivity (65%) and specificity (69%) ,84. ST segment elevation in infarct-related leads and reciprocal ST depression during an exercise stress test have similar sensitivity and specificity for viability detection (84% and 100%) . The norThere is no recommendation for a specific imaging modality for viability testing in the current guidelines , but CMRDifferent imaging modalities are reported to have different performance characteristics for the detection of myocardial viability. However, pooled data from a large number of patients enrolled in 105 studies revealed similar accuracy for SPECT, PET, and DSE, with higher sensitivity for PET and SPECT-Tl 201-rest-redistribution and a higher specificity for DES . LGE carViable myocardium can be identified by different imaging techniques, but its prognostic outcome after revascularization is still controversial.Several studies have addressed this issue, mainly retrospective, observational studies with incomplete control of confounding factors. The results of these observational studies revealed improved LV function in patients with viable myocardium after revascularization and sustained the utility of myocardial viability assessment in clinical practice. Due to a non-randomized design, it is probably that the results at viability assessment determined the decision of revascularization, leading to important selection bias. Furthermore, there were important contemporary advancements in the medical treatment of heart failure and in the revascularization techniques, so the extrapolation of these data to contemporary medical practice is difficult .Several observational studies revealed an improved outcome after revascularization in patients with ischemic heart failure and a significant amount of viable myocardium. The greater the area of viable myocardium, the better the result of revascularization. The optimal threshold for the area of viable myocardium is 25.8% for PET-FDG and 38.7% for SPECT . A signip < 0.001). This meta-analysis concluded that testing for myocardial viability in patients with significant ischemic LV dysfunction can identify patients at increased risk, a risk that can be reduced with revascularization, with the magnitude of benefit increasing with the severity of LV dysfunction. This would be very important when deciding on revascularization in this challenging category of patients. Furthermore, patients with non-viable myocardium who underwent surgical revascularization had a higher mortality than patients with viable myocardium, meaning that for patients without myocardial viability, medical therapy is the preferred option [Revascularization was compared to medical therapy in patients with severe CAD and LV dysfunction, evaluated for myocardial viability in a meta-analysis of 24 observational studies published by Allman et al. They followed-up with 3.088 patients, with LV ejection fraction (of 32 ± 8 %), during 25 ± 10 months. In patients with viable myocardium, revascularization was correlated with a 79.6% decrease in annual mortality, and there was a direct relationship between the severity of LV dysfunction and the importance of benefits after revascularization (p < 0.0009). The risk of death increased in parallel with the amount of hibernating myocardium in patients who remained on medical therapy. At a level of 10% of hibernating myocardium, the benefits of medical and revascularization therapies were similar. Revascularization therapies had a progressively greater benefit as the amount of hibernating myocardium increased [One of the most important prospective observational studies was performed by Ling et al. on a number of 648 patients with ischemic cardiomyopathy, with a mean LV ejection fraction of 31%, with PET perfusion, and metabolic imaging testing. Early revascularization was accomplished in 33% of them, and they were followed-up for all-cause mortality as a primary endpoint. After a period of 2.8 years, the study observed a significant interaction between revascularization, the amount of hibernating myocardium, diabetes, and outcome  study, the Surgical Treatment for Ischemic Heart failure (STICH) study, and more recently, the REVIVED BCIS2 trial. p = 0.16), suggesting no benefit for FDG-PET testing [p = 0.019). At 5 years of follow-up, there were still no significant differences between the two arms of study, but in the subgroup of patients that followed the PET-guided therapy, a significant reduction in the primary endpoint was registered  [The PARR-2 study was a randomized controlled trial that evaluated the role of viability testing on clinical outcomes. The trial enrolled patients with severe LV dysfunction and suspected CAD proposed for revascularization or transplantation and randomized to FDG-PET imaging (218 patients) or standard of care (212 patients). The primary endpoint was a composite of cardiac death, myocardial infarction, or recurrent hospitalization. At 1 year, it was registered in 30% of patients in the FDG-PET arm vs. 36% in the standard of care arm  . Approxi= 0.042) .In the Ottawa-FIVE study, a post-hoc analysis from PARR-2, a significant benefit from PET guided management was revealed in an experienced heart failure center . The outp = 0.12). Cardiovascular death  and cardiovascular death and hospitalization  were significantly reduced in the CABG group. From 602 patients assigned in the OMT group, 17% crossed over to CABG before the end of the follow-up period. After excluding crossover, CABG was found to reduce significantly all-cause mortality . Failure to show a difference in all-cause mortality may also be explained by early mortality in the CABG group correlated with the surgical intervention. A sub-study from the STICH trial evaluated the role of viability testing and revealed no interaction between myocardial viability and outcomes. In total, 601 patients were tested for myocardial viability. The original protocol was that all the patients should undergo viability testing, but this was an impediment for recruitment, so the protocol was revised, and the myocardial viability assessment became optional, with either SPECT or DSE. SPECT myocardial perfusion imaging used a 17-segment model and viability was defined if >11 segments were viable based on relative tracer activity. For DSE, a 16-segment model was used, and viability was defined if >5 segments with hypo-akinesia at rest proved contractile reserve with dobutamine. From the patients who underwent a myocardial viability test, 487 patients were considered viable , and 114 patients were considered non-viable  [The Surgical Treatment for Ischemic Heart Failure (STICH) study was designed to investigate the role of CABG for the revascularization of patients with severe LV dysfunction . This prnt CABG) . The viap = 0.003), but in a multivariate model only a trend  to a reduced rate of mortality plus cardiovascular hospitalization was observed  [Myocardial viability was associated with a reduced overall rate of death in a univariate analysis  . The con 0.3903) . A lot of explanations were found for these surprising results: (a) STICH included patients with angina rather than heart failure symptoms; (b) the benefit of viability testing was difficult to assess due to the reduced number of patients without viable myocardium (19%); (c) the baseline characteristics, medical, and interventional therapy in the viability group were different compared to the main trial population and were not representative for the ischemic cardiomyopathy population at large; (d) a high percentage of patients who underwent viability testing were with one vessel disease (25.3%), most probably patients with non-ischemic cardiomyopathy and incidental CAD, who were not expected to benefit from revascularization; and (e) a viability assessment was conducted with SPECT and DSE, at the discretion of the physicians, while in contemporary practice, these were replaced by PET and cardiac MRI. At 10 years of follow-up, the STICHES study found improved survival in the surgical arm, but again no interaction between myocardial viability and outcomes was proved, and furthermore better outcomes were independent of LV systolic function recovery . p =0.96) over a median period of 3.4 years follow-up. LV ejection fraction, which was 27.0% in both treatment groups at baseline, was no different between the two treatment approaches at 6 and 12 months. Quality of life favored the group with PCI at 6 and 12 months, but at 24 months no significant differences were seen [The REVIVED-BCIS2 trial was the first study with randomized evidence on PCI for ischemic cardiomyopathy. It was a prospective multi-center, open label, randomized controlled trial that randomized 700 patients with severe CAD, LV ejection fraction < 35%, and myocardial viability in ≥4 dysfunctional segments to either PCI with complete revascularization encouraged or to medical therapy alone. The primary endpoint was a composite of all-cause mortality or hospitalization for heart failure and occurred in 37.2% in the PCI group and in 38% in the OMT group  did not find a survival benefit in revascularized patients with ischemic heart failure versus conservative therapy. The HEART was terminated earlier due to poor recruitment; it was an underpowered study that showed no significant benefit in patients with ischemic heart failure, with LV ejection fraction ≤ 35%, and a significant proportion of viable myocardium who underwent revascularization compared to those on medical therapy alone .p = 0.02). Patients with severe LV dysfunction of ischemic etiology and viable myocardium detected by LGE cardiac MRI had significantly higher mortality without revascularization compared to those with complete revascularization . The interaction between myocardial viability by LGE cardiac MRI and revascularization significantly predicted survival in ischemic heart failure with low ejection fraction [Multiple studies proved better accuracy for LGE cardiac MRI in detecting myocardial viability, but the investigation was not available in PARR2 and STICH. Cardiac MRI is superior compared to SPECT and PET in detecting myocardial viability ,107. Kuhfraction . In animal studies, it was demonstrated that the presence of viable non-revascularized myocardium was correlated with poor prognosis due to an increased risk of electrical instability leading to sudden cardiac death . HibernaAnother small retrospective study was performed in a single center on patients with severe LV dysfunction (ejection fraction ≤ 35%), with a luminal narrowing of ≥50% in at least one major coronary artery, and myocardial viability tested using FDG-PET. Fifty-three patients underwent CABG and were divided in two groups: one with scar burden ≥ 10% (n = 30) and another with scar burden < 10% (n = 23). In patients with substantial scar amount, the presence of hibernating myocardium was followed by a functional recovery after revascularization, but this was not translated into survival benefit. The viability guided therapeutic strategy was not correlated with improved clinical outcome. The study confirmed that surgical coronary revascularization led to structural and functional improvement vs. medical therapy alone, but these improvements were independent of the baseline viability status. No benefits on survival, or major adverse cardiac and cerebrovascular events were observed between the groups with CABG vs. medical therapy alone. The authors concluded that, at least in part, this was explained by the high peri-operative mortality correlated with CABG, and possibly surgical revascularization is sometimes not enough to improve micro-circulation in the ischemic area, for the salvation of hibernating myocardium .The results regarding the usefulness of myocardial viability tests remained inconclusive after analyzing thirty-two non-randomized (4328 patients) and four randomized (1079 patients) studies, in a systematic review and meta-analysis that compared medical treatment versus revascularization, in patients with viable and non-viable myocardium. Patients with viable myocardium but also without viable myocardium appeared to benefit from revascularization . AnotherResults are awaited from AIMI-HF, an ongoing multi-center randomized trial and registry that evaluates the outcomes of patients with ischemic left ventricular dysfunction (EF < 45%) managed with advanced imaging methods (PET or cardiac MRI) compared to standard cardiac imaging (SPECT). The study is expected to enroll 1511 patients and follow them for at least 2 years. The composite primary outcome is cardiac death, myocardial infarction, resuscitated cardiac arrest, or cardiac hospitalization. A demonstration of viability detection is not mandatory for study enrollment, but its detection will influence the management and will be an important secondary analysis .The outcome after revascularization of hibernating myocardium is still an area of debate since the results of the randomized clinical trials are not supporting the findings from previous observational studies. Furthermore, the usefulness of viability testing prior to the revascularization procedure became unclear after publishing the results from the STICH trial and REVIVED BCSI2 ,117. However, the follow-up of patients from the STICH trial after 20 years of enrollment showed a trend for better survival in the group of patients with viability, compared to the non-viable group, and once again assessing myocardial viability came into focus . ImagingYet, what is clear is that patients with severe LV remodeling, lower ejection fraction, larger LV volume, and more extensive CAD are more likely to benefit from surgical revascularization. These patients are at the highest risk for future acute coronary events, will tolerate less a new event, and will benefit more after CABG.It seems that improvement of the LV function is not the only mechanism, and is not the most important mechanism for improved outcomes after CABG . A relatThe risk of death from heart failure in patients with ischemic LV dysfunction is clearly correlated to LV ejection fraction, but sudden arrhythmic or ischemic deaths are not. In the Digitalis Intervention Group trial, after analyzing the connection between LV ejection fraction and mechanism of death in 7788 patients (69% of them with ischemic heart failure), a near-linear relationship was demonstrated between LV ejection fraction and death from worsening heart failure, but the risk of death due to arrhythmic events was constant across the spectrum of reduced LV ejection fraction . Sudden Reduction in LV volume and sphericity after revascularization are also important prognostic factors beyond the improvement of regional wall thickening and of LV ejection fraction ,134.The risk associated with CABG will determine the final decision of surgical revascularization. PCI has a lower procedural risk, but the benefits of interventional revascularization in patients with ischemic cardiomyopathy need to be further evaluated. No improvement in regional LV function was observed in the randomized studies of chronic total occlusion PCI, even in the presence of viable myocardium; however, these were not addressed to patients with severe LV systolic dysfunction ,136. MorFurthermore, the presence of extensive viability has been shown to predict the response to various treatment methods, such as pharmacological ,138, andThe available data suggest that revascularization is reducing mortality in patients with ischemic heart failure that have a substantial amount of viable myocardium. The benefits of revascularization in patients without a substantial amount of viable myocardium remain unclear. The treatment effect of CABG in STICH was independent of viability status, with similar reductions in sudden cardiac death and heart failure. It is probably appropriate to recommend CABG in patients with ischemic cardiomyopathy based on the extent of their CAD, rather than on the viability testing . FurtherThe relationship between myocardial viability and revascularization is further studied in the ongoing trial IMAGE-HF : a prospective study that will compare the effect of an advanced imaging technique such as PET and cardiac MRI on clinical outcomes of patients with ischemic heart failure compared to those using standard care, including SPECT .There are still many unknown elements regarding the interaction between ischemia and viability in predicting both clinical outcomes and treatment effects.Myocardial hibernation is induced by recurrent episodes of inducible ischemia, and the reversal of hibernation depends on two factors: resolution of ischemia and a viable myocardium that is able to recover. The recovery of dysfunctional myocardium is most likely to occur in territories with both inducible ischemia and viability. There are a few observational data that support these findings, respectively, a greater diagnostic accuracy if both contractile reserve and ischemia are demonstrated via a biphasic response on DSE, versus the demonstration of contractile reserve alone ,110. In Patients with ischemic LV dysfunction have, in general, a multi-vessel complex CAD, so probably they have a large ischemic burden on functional testing. Hibernating myocardium itself is an adaptive response to ischemia, but the ability to demonstrate inducible ischemic contractile dysfunction may be limited, and it is difficult to evaluate ischemia when the myocardium is thinned or partially scarred .Patients with ischemic LV dysfunction and important inducible ischemia have poorer outcomes. The benefits of revascularization are greater in those with more extensive ischemia in observational studies . HoweverThe role of ischemia in selecting patients with ischemic LV dysfunction for revascularization is controversial. Observational studies observed that low-dose DSE allowed the risk stratification of outcome after revascularization . Some stA sub-study of the ISCHEMIA trial evaluated the relation between inducible ischemia and the effect of revascularization on clinical outcomes, in patients with heart failure and a mid-range ejection fraction, and revealed improved results with revascularization vs. pharmacological treatment . The valIn clinical practice, most of the patients undergo coronarography as an initial investigation, followed directly by angioplasty or they are sent to CABG, so the majority of them are not evaluated regarding myocardial viability. If the evidence for the importance of viability testing will increase, then development of viability tests that can be used as adjunctive to coronarography will improve the management of these patients .Pharmacological therapy can improve the balance between myocardial oxygen consumption and demand, can diminish myocardial ischemia and restore contractile function, and can reduce the risk of recurrent ischemic and arrhythmic events. Beta-blockers are reducing heart rate and myocardial oxygen consumption; increasing diastole and improving coronary perfusion; and decreasing the risk of arrhythmia, recurrent myocardial infarction, and sudden death . In the Angiotensin converting enzyme inhibitors (ACE), angiotensin receptor blockers, and aldosterone receptor antagonists are reducing LV end-diastolic volume, LV pressure, and wall stress, and are improving subendocardial flow. These drugs can reduce mortality and the risk of heart failure hospitalization and improve symptoms . Angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter-2 inhibitors reduce the worsening of heart failure, cardiovascular and all-cause mortality, and improve heart failure symptoms and quality of life ,150,151.Obviously, the pharmacological treatment has a key role in the management of patients with ischemic heart failure and should not be neglected even if patients are referred for revascularization. On the other hand, there is an interaction between pharmacological therapy, revascularization, and viability, so controlling for their individual effect is very difficult in clinical trials. An experimental approach to the treatment of hibernating myocardium is to consider regenerative techniques by injecting stem cells  into models of myocardial ischemia, that can lead to the improvement of myocardial contractility .Randomized trials are needed, which consider the scope of viability testing more broadly, not simply if there is viable myocardium or not, but also to evaluate the amount or the percentage of the myocardium that is viable and to determine a relation between the amount of viable but dysfunctional myocardium and the response to revascularization therapy. There is a persisting debate regarding myocardial viability testing due to the controversial results observed in prospective randomized studies. Viability assessments continue to have a role in several clinical circumstances but should always be just one of the factors implied in the decision of revascularization. The severity of LV adverse remodeling and dysfunction, the probability of successful revascularization, the anatomical characteristics of the coronary arterial bed, comorbidities, and surgical or interventional risk should be taken into account as well. Patients with ischemic cardiomyopathy and reduced ejection fraction are at a high risk of future cardiovascular events. When myocardial viability testing reveals the presence of viable myocardium, an improved outcome is expected by the coronary revascularization of the anatomically corresponding coronary artery ,100,101.Viability testing imaging tools are evaluating different aspects of the myocardium, but it is obvious that viable myocardium cannot be categorized in a dichotomized fashion, and imaging modalities must reveal the physiologic complexities of viable and ischemic myocardium ,55.Current ESC guidelines recommend a class IIb level of evidence B for non-invasive stress imaging  for the evaluation of myocardial viability in patients with CAD, suitable for revascularization . ACC AHAIn patients with ischemic heart failure with a LV ejection fraction moderately or severely reduced, with significant perfusion defects, but without moderate or severe ischemia, with multiple important comorbidities and/or poor coronary anatomy, viability testing is required. In patients with severe angina, with significant ischemia, with critical left main CAD and good coronary anatomy, with normal or mildly reduced ejection fraction, and no comorbidities, viability testing is not needed . The type of imaging test will be selected based on availability, local experience, specific advantages of each method, and clinical setting . In patiWhen the patients have left main CAD or severe proximal three-vessel disease, we should avoid DSE, and in patients with renal failure or implanted metallic devices, we should avoid LGE cardiac MRI.A patient with angina, with myocardial ischemia, with partial or viable myocardium on echocardiography or SPECT with low-intermediate procedural risk will benefit from coronary revascularization. However, a patient with severe heart failure, with severely dilated and remodeled LV, with akinetic and thinned myocardium on echocardiography and absent of radiotracer uptake at SPECT, with Q waves on ECG, and without angina will have a better outcome with medical and device therapy.A dysfunctional myocardium is a continuum starting from early hibernation with minimal remodeling and no scar, to an intermediate stage of partial viable thinned myocardium, and at the end myocardial scar and fibrosis . If the The following clinical approach can be considered for the management of patients with ischemic heart failure with moderately or severely reduced ejection fraction .When choosing between PCI or CABG, CABG is preferred in patients with multi-vessel complex CAD and in patients with diabetes due to improved outcomes and survival ,157.European revascularization guidelines have as a class I level of evidence B the recommendation for CABG in patients with ischemic cardiomyopathy and multi-vessel disease . PCI canHeart failure guidelines also sustain guideline directed therapy and CABG in selected patients with LV ejection fractions of ≤35% ,160.All these recommendations are based on consensus opinion and the results from the STICHES extension study that revealed an improved survival at 10 years in patients with CABG plus OMT versus OMT alone ,161. WheRegarding interventional revascularization, after the first results of the REVIVED BCIS trial, no additional benefit over OMT was demonstrated in patients with severe CAD impaired LV function and viable myocardium ,104.However, the optimization of medical therapy should always play a key role in the management of all these patients because for medical therapy there is strong evidence that it is working. OMT can improve contractile function in viable segments independent of revascularization. Myocardial viability testing in the management of ischemic LV dysfunction remains controversial. Although multiple imaging tests can detect viable myocardium, cardiac MRI and PET whenever available should be preferred, due to their increased sensitivity and higher spatial resolution. Viability imaging continues to play a role in the highest risk patients with ischemic cardiomyopathy. Patients with very low ejection fraction, with three-vessel disease amenable for revascularization, large LV end-systolic volume, and ischemic mitral regurgitation may benefit from viability testing. CABG will lead to better outcomes in patients with large areas of hibernating myocardium, but when selecting a patient for revascularization, multiple factors should be considered. Patients with ischemic cardiomyopathy, with large areas of non-viable myocardium, may have better outcomes with medical therapy combined with device therapies. It remains unclear if patients without a certain amount of viable myocardium have no benefits after surgical revascularization. Further prospective trials of revascularization in patients with ischemic cardiomyopathy, with different amounts of viable myocardium, are needed to better define the value of identifying myocardial viability.


Chagas disease (CD) is a neglected infectious disease associated with early mortality and substantial disability. Three-dimensional speckle tracking (3D STE) may play a role in the evaluation of CD. We aim to characterize new echocardiographic variables in patients with CD and to assess the hypothesis that 3D STE may predict outcomes. Seventy-two patients with CD were included. Clinical and conventional 2D and 3D STE analysis were performed. Patients were followed up for 60 months. Clinical events were defined as hospitalization for heart failure, complex ventricular arrhythmias, heart transplant and all-cause death. Seventy-two patients were recruited and enrolled in three groups: left ventricular ejection fraction (LVEF) < 0.40 ; 0.40 ≤ LVEF ≤ 0.50  and LVEF > 0.50 . After a Cox model analysis, the top predictors of composite endpoints were 2D LV global longitudinal strain (GLS) ≤ − 11.3% (AUC = 0.87), 2D LV global circumferential strain (GCS) ≤  − 10.1% (AUC = 0.79), 3D LV GLS ≤ − 13% (AUC = 0.82), 3D LV area strain ≤ − 16% (AUC = 0.81) and right ventricle (RV) GLS ≤ − 17.2% (AUC = 0.78). Patients with CD and mrLVEF were morphologically similar to the rLVEF patients despite the benign evolution as the pLVEF group. RV GLS, 2D LV GLS, 2D LV GCS, 3D LV GLS, and 3D LV area strain are strong predictors of 60 months outcomes in patients with CD. Nowadays, more than a century after its description, it still remains associated with early mortality and substantial disability. Nevertheless, in recent decades, CD has increased worldwide and has become a health problem in non-endemic countries as a result of the migration of infected people3.Chagas disease (CD) is an endemic and neglected infectious disease, first described in 1909 by Carlos Chagas6.CD is characterized by two well established phases: an acute and a chronic phase. Approximately 20 to 40% of patients with CD will develop chronic Chagas cardiomyopathy (CCM), which is the most important and severe form of CD. Mortality due to CCM is closely related to the extent of cardiac function impairment and can be attributed to heart failure (HF), conduction disturbances, ventricular arrhythmias and sudden death and/or thromboembolism. CCM carries higher mortality risk than ischemic or idiopathic dilated cardiomyopathies8. In this context, echocardiography consists of a very useful tool not only for evaluation of LV function, but also for the analysis of other variables that can add incremental information and provide newer clinical perspectives for patients with CCM14.Despite the crucial importance of an adequate risk profile evaluation for therapeutic guidance, until now, prognostic markers have limited value16. It is well established in literature that endocardial fibers, arranged longitudinally, are the first to undergo functional damage. Hence, longitudinal myocardial strain has been considered the best predictor of cardiac events in patients with HF, in comparison to left ventricular ejection fraction (LVEF) and Tissue Doppler data16.More recently, techniques as three-dimensional (3D Echo) and speckle tracking echocardiography (STE) have become very useful and promising tools for the evaluation of cardiac mechanics, allowing a more precise and quantitative measurement of the global and regional myocardial longitudinal, radial and circumferential strainNevertheless, literature data are scarce concerning cardiac mechanics evaluation by 3D STE, particularly in patients with CD. The present study aims to clinically characterize new echocardiographic variables concerning cardiac mechanics according to LVEF and evaluate its role in the prediction of clinical outcomes in patients with CD.2), hepatic failure, atrial fibrillation or frequent arrhythmias, coronary artery disease, patients with pacemakers, pregnancy and chronic obstructive pulmonary disease. This was a convenience sample because 3D STE is very sensitive technique and may be influenced by several clinical conditions.Eight hundred and eight patients with CD from the Cardiomyopathies and Heart Failure Clinics of a tertiary cardiological center were evaluated. Seventy-two consecutive patients with CD were recruited based on the following criteria: seropositivity for CD in two distinct laboratory tests  in sinus rhythm without other documented etiology. The exclusion criteria were age under 18 or beyond 70-years old, uncontrolled systemic arterial hypertension, diabetes mellitus, hypothyroidism, renal failure .All studies were performed using the Vivid E9  with dedicated transthoracic transducers. Comprehensive conventional (2D Echo) and 3D Echo were performed according to joint recommendations from the American Society of Echocardiography5. Patients did not receive specific pharmacological treatment for T.cruzi infection. Composite endpoints were defined as hospitalization for heart failure (HF), complex ventricular arrhythmias (ventricular fibrillation and sustained ventricular tachycardia), heart transplant and death.All patients were followed up 60 months. All patients were clinically evaluated by an assistant physician every 3 months or whenever necessary. Holter monitoring was assessed annually for each patient or whenever necessary. Patients were treated according the Brazilian Guidelines for CD2) or the Fisher exact test, when appropriate. A two-tailed p value of 0.05 was considered significant.Continuous numeric variables were expressed as mean ± standard deviation (SD). Normally distributed data were compared using a 2-sample Student’s t-test and 1-way analysis of variance. Non-normally distributed data were compared with Mann–Whitney U test and Kruskal–Wallis test. Categorical variables were expressed as frequency (percentage) and were compared using the chi-square test  and Bland–Altman analysis. Intraobserver variability was assessed by having one observer re-measuring after 30 days. Another observer blinded to the first observer’s measurements evaluated the randomly selected exams for interobserver variability analysis. To determine the optimal cutoff value of prognostic STE parameters for predicting composite endpoints, mortality and hospitalization for heart failure, receiver-operating characteristic (ROC) curves were used.Survival curves according to the LVEF were obtained in a Kaplan–Meier analysis and compared using the log-rank test. Uni and multivariate Cox regression models were used for estimations of the predictors of outcomes.Eight-hundred and eight medical electronic reports of patients with CD followed in the single center where the study was performed were analyzed. Seventy-two patients were recruited according to the inclusion and exclusion criteria. The great majority of patients were excluded due to uncontrolled hypertension, diabetes mellitus, irregular cardiac rhythm, hypothyroidism and renal failure. Patients were enrolled in three groups: patients with LVEF < 0.40  (N = 32); patients with LVEF ≥ 0.40 and ≤ 0.50  (N = 10); patients with LVEF > 0.50  (N = 30).Clinical, anthropometric and electrocardiographic data are described in Table Bilateral cardiac chambers dimensions were larger in the rLVEF in comparison to the group with pLVEF. LV diastolic and systolic indexed volumes were greater in the group rLVEF than in the other groups. Thus, in these patients, LV indexed volumes were more accurate to distinguish the groups according to the LVEF than LV diameters and absolute volumes. Tricuspid annular plane systolic excursion (TAPSE) was the only RV systolic function parameter able to distinguish the groups. Septal e´ and lateral e´ velocities on Tissue Doppler were lower while E/e´ ratios were greater in the group rLVEF in G1 when compared to the other groups.2D STE data are shown in Table LV Peak systolic CS and LV displacement were lower in the group rLVEF in comparison to the group pLVEF. With exception of LV basal displacement, there were no differences regarding LV peak systolic CS and displacement between the groups rLVEF and mrLVEF. RV GLS and free wall strain were similar between the groups with mrLVEF and pLVEF.3D Conventional Echo and STE parameters are shown in Table All patients were followed up for 60 months. Composite endpoints , survival and hospitalization for heart failure Kaplan Meyer curves are shown in Fig. In the overall patients, bilateral cardiac remodeling was associated with composite endpoints. Larger atrial and ventricular diameters and volumes (absolute or indexed) as well as reduced biventricular function evaluated by 2D and 3D Echo, reduced velocities at tissue Doppler and increased E/e´ ratio were associated with composite endpoints. 2D LV GLS, 2D LV GCS, RV GLS, 3D LV GLS and 3D LV area strain were the strongest predictors of composite endpoints Table .Table 5PAs for composite endpoints, bilateral cardiac remodeling was associated with mortality. Larger atrial and ventricular diameters and volumes (absolute or indexed) as well as reduced LV and RV function (TAPSE) evaluated by 2D and 3D Echo, reduced velocities at tissue Doppler and increased E/e´ ratio were associated with death from all causes and hospitalization for heart failure. Interestingly, RV S´ wave, FAC were not associated with overall mortality.2D LV GLS, 2D LV GCS, RV GLS, 3D LV GLS and 3D LV area strain were the strongest predictors of death from all causes and hospitalization for HF Table .Receiver-operator characteristic (ROC) curves of the strong predictors of cardiovascular events were built for the 5 years of follow up Fig. . The cutThere is known collinearity between the LVEF obtained from the conventional 2D Echo evaluation and the cardiac mechanic parameters derived from the STE analysis and 3D Echo data. Also, it was observed non-linear relation of LVEF according to the patients´ age. So, we presented the estimated relation of STE analysis and 3D Echo data individually adjusted for age and cubic natural splines of LVEF Table .Table 7EFor prediction of death, LVDD and LVSD evidenced incremental value over LVEF; for prediction of hospitalization, 2D GLS, LA diameter, 3D LA indexed volume and LV DD evidenced incremental value over LVEF and for composite endpoints, LVDD and LVSD evidenced incremental value over LVEF.The intraobserver and interobserver reproducibility of most of the STE parameters was excellent, as reflected by high CCC  3D conventional and 2D STE analysis in mrLVEF were anatomically and functionally similar to rLVEF; (2) RV GLS, 2D LV GLS, 2D LV GCS, 3D LV GLS, and 3D LV area strain were strong predictors of outcomes in patients with CD, with superior value to other conventional parameters provided by cardiac dimensions, Tissue Doppler indexes or TAPSE and fractional area change for prediction of overall mortality or composite endpoints.To the best of our knowledge, this is the first study to evaluate 3D conventional and strain analysis in patients with CD from normal LVEF up to reduced LVEF. So far, only 2D STE parameters have been described in different stages of CD and most studies evaluated patients with normal LVEF21. In other published investigation, only regional LV longitudinal strain was reduced in indeterminate form of CD with pLVEF that is in concordance with our results. Also, in a recent study, with patients in different CCM stages, 2D LV GLS was the more accurate measurement regarding stage A differentiation from the stages B, C, and D25. However, reports of 2D LV GLS in CD are conflicting and still remain a controversial issue. To explain the abnormal strain, myocarditis and inflammatory infiltrate was found in 15% and 37% respectively of indeterminate phase26. In another publication, in 60.6% of patients with indeterminate phase, it was found abnormalities like fiber degeneration, volume changes, interstitial edema, inflammatory infiltrates and fibrosis27. Besides, it was reported even in patients with Chagas disease with preserved or minimally impaired ventricular function cardiac fibrosis in 3% and 11% respectively using late gadolinium enhancement on cardiac magnetic resonance (CMR)28. Moreover, some studies support the use of 2D LV GLS in surveillance providing a window of opportunity for early intervention and preventing heart failure patients.Our results are in disagreement with previous studies suggesting that in patients with the indeterminate form of CD with pLVEF, global and segmental longitudinal systolic strain is reduced compared with healthy subjects, thus indicating that it could be a sensitive technique to detect early myocardial damagePatients with indeterminate form of CD are defined as patients seropositive for CD but with normal electrocardiogram and normal LVEF. These patients have a very benign clinical course that may be compared with matched cohorts of patients without cardiac disease. Some studies suggest that these patients may have subclinical of subtle cardiac disease that may be identified with STE techniques. Nevertheless, in our study we did not confirm these findings making it necessary more studies to determine the practical use of STE in these patients. These controversial data may be due to the limited number of studies and patients for this purpose allied with the ongoing developing state of echocardiographic techniques.28. It was reported in reduced and mid-range LVEF HF patients similar natriuretic peptide elevated levels, and neuroendocrine profile. However, cardiac troponin values in mid-range LVEF HF patients are intermediate to those with reduced and preserved LVEF HF patients. On other hand, studies on endomyocardial biopsies from CD patients showed that the clinical evolution of the disease was correlated with a continuous progression of fiber destruction, fibrosis, myocardial inflammation, and a reduction in performance2. These findings may indicate that, possibly, patients with CD mrLVEF could be sharing with rLVEF some pathophysiological mechanisms related to 3D conventional Echo and 2D STE parameters but for all characteristics. In fact, a recent meta-analysis concluded that significant differences in hospitalization and mortality were detected between mildly or mid-range heart failure and the other subtypes of heart failure including diverse etiologies but not included CD29. Nevertheless, CD is a very peculiar etiology that is not included in the studies. Herein, there is an extreme paucity of data concerning patients with mildly or mid-range Chagas heart disease and no study so far evaluated 3D cardiac mechanics in patients with mrLVEF and CD.In our study, 3D conventional Echo and 2D STE parameters evidenced similar results comparing rLVEF and mrLVEF. Hitherto, the pathophysiology of rLVEF and mrLVEF heart failure patients is incompletely understood and, consequently, the reasons for this finding are unclear. In other etiologies, mrLVEF patients may include a heterogeneous population with patients that partially recovered the cardiac function under guidelines-directed medical treatment, or patients that have not yet evolved to rLVEF, or patients that never will follow to rLVEF. Previously, we reported improvement in CCM under guidelines-directed medical treatment30. After adjustment for LVEF, there were no differences in STE values between Chagas Disease cardiomyopathy and idiopathic cardiomyopathy in reduced LVEF. 2D LV GLS was a strong predictor of adverse events, incremental to LVEF and E/e' ratio in dilated cardiomyopathy that included also chagasic etiology. No absolute values for 2D LV GLS indicating high risk are established, but a value of 2D LV GLS of − 12% has been suggested representing severe systolic dysfunction and adverse prognosis30. Our findings are in concordance with this value and a value of 2D LV GLS lower than − 11.4% was associated with composite endpoints. 2D LV GCS is not well established as a predictor of outcomes because 2D LV GLS is the most robust parameter for this purpose but in our study, a value of 2D LV GCS lower than − 10.1% was also associated with composite endpoints.Our findings that RV GLS, 2D LV GLS, 2D LV GCS, 3D LV GLS, and 3D LV area strain were strong predictors of outcomes in patients with CD are in concordance with an increasing number of studies that have suggested that 2D LV GLS is superior to LVEF as a measure of LV function and as a predictor of mortality and cardiac events in other etiologies, mainly ischemic cardiac diseaser = 0.70, p < 0.001) and GLS  regarding the percentage of fibrosis. Nevertheless, after multiple linear regression analysis, the 2D LV GLS were no longer a predictor of myocardial fibrosis. So, the authors concluded in this study that 2D LV GLS has no incremental value to left ventricular ejection fraction assessed by conventional echocardiography in the prediction of myocardial fibrosis in patients with Chagas disease31.The value of 2D LV GLS as a predictor of outcomes relies on the hypothesis that this parameter reflects changes in the myocardial interstitium yielding information regarding the extent of myocardial fibrosis as suggested by findings in patients with mitral regurgitation and hypertrophic cardiomyopathy. In another study, both GLS and ejection fraction were significant predictors of myocardial fibrosis. It was observed a high correlation with both ejection fraction assessed by echocardiography (32. In concordance in our study, RV GLS was also a strong predictor of outcomes. Values of RV GLS under − 17.2% and − 14.9% were associated with composite endpoints and mortality, respectively. Similarly, an RV GLS under − 19% was related to all-cause or cardiovascular mortality in rLVEF patients with ischemic, hypertensive or idiopathic cardiomyopathies32. As shown in previous studies in other etiologies and potentially also for CCM, RV GLS and RV free wall LS have performed better than conventional parameters for the prediction of outcomes. This may be probably because the use of the longitudinal strain for RV as for LV evaluation allows the analysis of the deformation of the endocardial fibers, which might be more sensitive to reduced coronary perfusion and increased wall stress and are usually affected earlier in myocardial diseases.In respect to the RV GLS, several studies showed that this parameter provides strong additional prognostic value to predict overall and cardiovascular mortality in rLVEF patients with other etiologies, essentially ischemic cardiac disease. The predictive value was even higher than parameters evaluated by CMR as RV ejection fraction and RV strain33. Particularly, 3D LV area strain is a very promising index that quantifies endocardial area change, integrating longitudinal and circumferential deformation, allowing a more detailed evaluation of the different types of myocardial fibers and enabling a better understanding of the pathophysiology of cardiomyopathies33. In a recent meta-analysis that aimed to determine normal ranges of 3D Strain, the authors reported that the mean value of 3D LV GLS was 19.1%, ranging from 15.8 to 23.4% among the studies34. In our study, 3D LV GLS values and 3D LV area strain under − 13% and − 10%, were associated with composite endpoints and mortality, respectively.Concerning 3D analysis, our findings that 3D LV GLS and 3D LV area strain are strong predictors of outcomes in CCM suggest a very innovative clinical application for this technique. Until now, some studies evaluated the prognostic value of 3D Strain in a variety of clinical scenarios including valvular heart disease, ischemic heart disease and chronic renal failure, showing that the reduction of 3D values was associated with poor outcomesThe use of new technologies for better understanding CD presents a great potential for clinical application. The evaluation of cardiac mechanics can be performed non-invasively, with practically no risk. Our study suggests that 2D and 3D strain analysis should be added to the comprehensive evaluation of patients with CD and rLVEF for prognostication. Our findings reinforce and extend previous studies´ results showing that RV GLS, 2D, and 3D STE may provide additional information for better risk assessment of these patients with high feasibility and good intra and interobserver variability.Although the application of strain imaging has yet not been included in clinical practice guidelines, it is likely to become a useful application when evaluating patients with CD.14.In our study, it was observed high feasibility of 2D and 3D strain analysis in all the groups. Despite the significant LV dilatation, especially in the group with rLVEF, which could limit the analysis of all LV segments, the feasibility was close to 100%. These findings demonstrate the great applicability of this technique, even in patients with extensive ventricular remodeling and/or presence of abnormalities in the apical region, very frequent in patients with CDThe finding of better correlation of RV GLS, 2D LV GLS, 2D LV GCS, 3D LV GLS, and 3D LV area strain with outcomes than conventional 2D and 3D Echo conventional indexes in patients with CD provides important and potentially incremental information that may contribute to the establishment of cutoff values for different degrees of LV dysfunction and prognosis in addition to the already established values of LVEF. Therefore, we hypothesize that, eventually, the analysis of biventricular longitudinal strain could add incremental data regarding mortality and composite endpoints, predicting outcomes in patients with CD, as previously described, shedding light on complexes mechanisms of cardiomyocytes contraction imbalance and pathophysiology of patients with Chagas cardiomyopathy as a useful tool for prognostication.Thereby, cardiac mechanics provide more refined and accurate information related to cardiac dysfunction and derangement than conventional parameters expressed by morphological variables as cardiac diameters and volumes and LVEF and might be related to myocardial fibrosis as evaluated by CMR but with expressive lower cost, mainly considering the economic issues in the developing countries, where CD is more prevalent.Due to the high prevalence of unknown or poorly controlled hypertension, in addition to diabetes mellitus and hypothyroidism, the vast majority of patients could not be included in this study, limiting the final number of patients. However, this extreme caution is mandatory when evaluating new techniques, without definite cutoff values and clinical applications. The small number of patients is a limitation as well as the fact that this was a single-center study. Also, there was an imbalance between the three groups analyzed because the study included a convenience sample. Another limitations concern the limited availability of specific equipment besides more substantial time to acquire the datasets and perform all the measurements. Currently, conventional 3D Echo and 3D STE are available in a very limited number of research centers of echocardiography. Besides, both techniques require a learning curve and expertise until an adequate examination is possible. Nowadays, there is still inter-vendor variability in 3D STE measurements and spatial and temporal resolution are not yet adequate to perform reliable segmental analysis. Finally, there still considerable interobserver variability of 3D strain measurements but that was not a limitation in this study.Patients with CD and mrLVEF presented anatomic and functional characteristics more similar to the CD and rLVEF despite the benign clinical evolution similar to patients with pLVEF. RV GLS, 2D LV GLS, 2D LV GCS, 3D LV GLS, and 3D LV area strain are strong predictors of outcomes in patients with CD. These findings suggest that 2D and 3D strain yields a potential incremental value for clinical decision guidance in patients with Chagas heart Disease.Supplementary Information.


Brugada syndrome (BrS) is an autosomal-dominant condition mainly caused by defects in sodium channels causing ST-segment elevation in electrocardiograms (ECGs) in the V1 and V2 precordial leads, with ventricular tachyarrhythmias due to premature ventricular contractions, which increases the risk of sudden cardiac death. BrS usually presents in adulthood, with an average age of presentation of 41 years.In this article, we describe a case of BrS diagnosed in a 36-year-old male having sudden cardiac arrest with no comorbidities such as hypertension, diabetes mellitus, smoking, or any valvular disease history. We then explain the ECG-based diagnosis, signs and symptoms, presentation at the emergency department, and treatment options. Brugada syndrome (BrS) is a rare serious autosomal-dominant genetic arrhythmogenic disorder characterized by an electrocardiogram pattern of right bundle branch block (RBBB), ST-segment elevation (>2mm) in anteroseptal chest leads (V1-V3), and inverted T-waves in conjunction with an increased incidence of ventricular tachyarrhythmias and sudden cardiac death (SCD) in patients with a structurally normal heart. Approximately 20%-25% of patients with BrS have a genetic mutation in the SCN5A gene that causes a functional reduction in cardiac sodium channels resulting in a decreased influx of sodium into myocytes. BrS is diagnosed by characteristic electrocardiogram findings, significant events , and other investigations . Clinical presentation of BrS is related to recurrent life-threatening ventricular arrhythmia, self-terminating ventricular tachycardia, and documented idiopathic ventricular fibrillation increases the risk of SCD. The overall prevalence of BrS is estimated to be two to five in 1000 people, with a higher prevalence seen in Southeast Asia. It has a male preponderance, with a male-to-female ratio of 8-10:1. In most patients, symptoms manifest in the third or fourth decade of life, but the disease can occur at any age. The only effective and long-term treatment of BrS is the management of ventricular tachyarrhythmias with an automatic implantable cardioverter defibrillator (AICD). In an acute setting, the administration of appropriate antiarrhythmics  and beta sympathomimetics  is life-saving.We present herein the case of a 36-year-old male who presented to the Emergency Department (ED) with typical cardiac chest pain with substernal pressure, radiating to the left arm, nausea, tachycardia, acute anxiety, sweating, and later-developed syncope. The patient was thrombolysed with Streptokinase in the ED, as he was misdiagnosed with acute anterior wall myocardial infarction based on an initial electrocardiogram (ECG). Immediately after thrombolysis, the patient developed polymorphic ventricular tachycardia (VT), and CPR was started. He was successfully DC cardioverted with 13 shocks @ 270 J, and treatment started with vasopressors, Lidocaine, magnesium sulfate, and calcium gluconate. A 6Fr central venous sheath was passed into the internal jugular vein. After initial stabilization, the patient’s repeat ECG spontaneously showed coved ST elevation in leads V1 and V2  with or without quinidine, which is a cardiac sodium channel blocker that stabilizes cardiac sodium channels to resolve the ST segment elevation ,9.Non-pharmacological approaches toward the acute arrhythmias or electrical storm in BrS include defibrillation and/or resuscitation if needed, and cessation of any arrhythmogenic drugs if suspected of having a role in the causation of the arrhythmias. ICD implantation in patients with BrS is reserved for those who present with aborted sudden death or severe symptoms such as seizure, syncope, or nocturnal dyspnea .The majority of BrS patients are diagnosed after SCD occurs in their family or after SCAs in people with low risk with no previous history of VT . ECG-based methods are best for diagnosing BrS at earlier stages in undiagnosed cases prior to the development of fatal arrhythmias. Genetic testing  of such families can also help in the prevention of BrS-induced ventricular arrhythmia by using prophylactic ICD placement.