The incidence of Kawasaki disease (KD) is increasing. Indeed, KD has become the most common cause of acquired heart disease in children. Previous studies have well summarized the acute phase left ventricular (LV) systolic dysfunction using speckle tracking echocardiography (STE); however, changes in LV systolic function after long-term follow-up remain unclear.One hundred children with a history of KD, but without coronary artery aneurysms, were enrolled. These children were divided into two subgroups based on the presence or absence of coronary artery dilatation (CAD). The duration of follow-up was > 7 years. The control group consisted of 51 healthy children. The LV myocardial strain were measured by two- and three-dimensional STE.P < 0.05). Global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS) were obtained by 3D STE. Compared to the controls, GLS and GAS decreased in both KD groups (P < 0.05). GCS and GRS decreased in the KD group with CAD, but was unchanged in the KD group without CAD (P < 0.05).Two-dimensional STE not only revealed that LV longitudinal strain decreased in part of segments in both KD groups, but also showed that global strain decreased in the KD group with CAD compared to the controls (LV systolic dysfunction in children with KD and CAD was more severe than KD children without CAD compared to healthy children. This dysfunction can be assessed by LV regional and global myocardial strain using two- and three-dimensional STE. Kawasaki disease (KD) is an acute self-limited vasculitis that affects children, 85% of whom are < 5 years of age . The incThe American Heart Association (AHA) algorithm, which was designed to improve the diagnosis for KD uses echocardiographic evidence of decreased left ventricular (LV) systolic function as supporting criteria . The LV Since 2010 several studies have revealed impaired LV myocardial strain among children with KD in the acute phase using STE , 8, 10. Between February 2017 and February 2018, 100 children with KD  were enrolled in this study for evaluation of LV myocardial strain at Shenzhen Children’s Hospital. All participants had a history of KD and fulfilled the diagnostic criteria for KD [Echocardiographic evaluation was performed in the left lateral recumbent position using a Vivid E9  with M5S and 4-V phased-array matrix transducers. All images and measurements were obtained from standard views according to the recommendations of the American Society of Echocardiography for chamber quantification. All images and datasets were digitally stored.max) and left atrial minimum volume (LAVmin) [Routine 2D echocardiographic images were obtained in the parasternal and LV apical views. The LV end-diastolic dimension and left atrial anteroposterior dimension were obtained in the parasternal long-axis view. The LA boundary was delineated manually in the apical long-axis, four-chamber, and two-chamber views using customized software (details below). The software automatically measured the left atrial maximum volume (LAV(LAVmin) . LV end-Tissue Doppler imaging was performed at the base of interventricular septum , at the lateral wall of the LV  and at the anterolateral wall of the RV. Gain was minimized to obtain clear signals, and images were recorded at 100 mm/s. Myocardial velocity during systole (s’), early diastole (e’), and late diastole (a’) were measured .The mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) were measured by two-dimensional echocardiography–guided M-mode recordings from the apical 4-chamber view as previously recommended –18.Two-dimensional echocardiographic images of three cardiac cycles were obtained at a frame rate of 60–90 frames per second from the LV apical long-axis, four-chamber, and two-chamber views. The images were analyzed offline using customized software . The LV endocardial boundary was manually delineated; the software automatically drew the LV epicardial boundary. The width of the region of interest was manually adjusted when necessary. The software automatically divided the LV myocardium into 17 segments, then generated curves for LV longitudinal strain .The peak systolic strain was defined as the maximum value during the LV systolic phase. The regional longitudinal peak systolic strain was obtained in all 17 segments. In the LV apical long-axis, four-chamber, and two-chamber views, three types of global longitudinal strain (GLS) were obtained  . The sofUsing a phased-array matrix transducer, the LV apical long-axis, four-chamber, and two-chamber views were demonstrated in the 4D mode, then “Large mode” was selected. The entire LV was depicted in the screen. The highest frame rate as possible (> 25 frames/sec) was acquired. The next step involved entering the “full volume mode”, acquiring six cardiac cycles sub-volumes to generate the pyramidal full-volume data set.Four different components of global strain  curves were computed and the area under the curve (AUC) was obtained. A two-tailed P < 0.05 was used to define statistical significance. Statistical analysis was performed using SPSS version 17.0 software.Continuous parameters are expressed as the mean ± standard deviation. Categorial parameters are expressed as frequencies. Differences in continuous parameters among the three groups were analyzed using one-way analysis of variance. Differences in continuous parameters between the two groups were analyzed using independent-sample P > 0.05). The complete KD accounted for 33% in the KD with CAD group, compared with 46% in the KD without CAD group.One hundred children with a history of KD and 51 healthy children were enrolled  (Table P < 0.05). The strain values of the basal anteroseptal segment, basal inferior segment, and mid-anteroseptal segment decreased both in the KD with and without CAD groups, compared to the control group (P < 0.05).For regional strain, the differences among the groups with respect to basal anterior segment, basal anterolateral segment, mid-inferoseptal segment, mid-inferior segment, and all apical segments were not statistically significant (5) Table . CompareP < 0.05) [P = 0.128; mid-anteroseptal segment: P = 0.249).The difference of 2D regional strain occurred in the mid-inferolateral segment and mid-anteroseptal segment which were assigned to the left circumflex coronary artery between the KD with and without CAD groups ( < 0.05) . HoweverP > 0.05). Compared to the control group, GLS_LAX, GLS_A4C, and 2D GLS decreased in the KD with CAD group but was unchanged in the KD without CAD group (P < 0.05). There was a difference between males and females in the KD with CAD group, but no difference in the KD without CAD and control group . GCS and GRS decreased in the KD with CAD group but was unchanged in the KD without CAD group , but also affects the pericardium  , endocarThe Japanese Circulation Society concluded that cardiovascular symptoms in KD patients only appears two decades after the onset of the disease . Thus, aEchocardiography is a fast, noninvasive, and accurate imaging modality to diagnose KD. Meanwhile, follow-up using echocardiography is a convenient method for clinicians. The weakness of 2D STE is that different planes are obtained in different cardiac cycles, whereas 3D STE is able to obtain each plane in the same cardiac cycle. Thus, 3D STE is expected to be a more accurate and sensitive modality to detect subclinical myocardial dysfunction than 2D STE .Our study assessed regional and global LV myocardial strain using 2D STE and 3D STE. For 2D regional strain, we found only the mid-inferolateral and mid-anteroseptal segments decreased in the KD with CAD group compared to the KD without CAD group. For 2D global strain, we found a significant decrease in GLS_A4C, GLS_LAX, and 2D GLS in the KD with CAD group compared to the controls; however, we did not find a difference between the KD without CAD group and the controls using 2D global strain. Then, 3D STE was performed. As might have been expected, we revealed that GLS and GAS decreased in KD without CAD group compared to the controls. We also found 3D GLS to be a better parameter (larger AUC) to detect LV systolic dysfunction than other 3D global strain, which showed that 3D GLS was gradually reduced in the three groups. The reason for the difference between the KD group and the controls is that myocarditis has been well-documented in 50–70% of KD patients in the acute phase with or without CALs , 14, 33.This study had limitations. We did not include KD children with persistent or regressive coronary artery aneurysms. Therefore, the KD children without CAD cannot be compared with the persistent coronary artery aneurysm subgroup or regressive coronary artery aneurysm subgroup. We cannot further verify the hypothesis that the severity of CALs is positively correlated with the degree of LV systolic dysfunction.LV systolic dysfunction of KD children with CAD was shown to be more severe than KD children without CAD compared to healthy children. This dysfunction can be detected by 2D and 3D STE using LV regional and global myocardial strain.Additional file 1: Table S1. Left ventricular myocardial strain using 2D and 3D STE. Table S2. Correlation between longitudinal strain values and the interval from onset to exam (months). Table S3. Reproducibility of 3D global strain.


Coronary computed tomography angiography (CCTA) has gained a prominent role in the evaluation of coronary artery disease. However, its anatomical nature does not allow the evaluation of the functional repercussion of coronary obstructions. It has been made possible to evaluate Myocardial computed tomography perfusion  recently, based on myocardial contrast changes related to coronary stenoses. Several studies have validated this technique against the anatomical reference method (cardiac catheterization) and other functional methods, including myocardial perfusion scintigraphy and fractional flow reserve. The Myocardial CTP is performed in conjunction with the CCTA, a combined analysis of anatomy and function. The stress phase  can be performed before or after the resting phase (assessment of resting perfusion and coronary arteries), and different acquisition parameters are proposed according to the protocol and type of equipment used. Stressors used are based on coronary vasodilation . Image interpretation, similar to other perfusion assessment methods, is based on the identification and quantification of myocardial perfusion defects. The integration of both perfusion and anatomical findings is fundamental for the examination interpretation algorithm, allowing to define if the stenoses identified are hemodynamically significant and may be related to myocardial ischemia. It is noteworthy that in all these conditions the background for its use rests on its high negative predictive power, making the presence of obstructive disease in the face of a negative test very unlikely.8 Hence the need for invasive coronary angiography in a large number of individuals with clinical presentation or results of noninvasive tests compatible with coronary artery disease, but without obstructive coronary disease, shows a favorable cost-benefit profile using CCTA in these clinical scenario.10Coronary computed tomography angiography (CCTA) was introduced in clinical practice in the end of the last century to promote noninvasive visualization of coronary arteries. Its use proved it an appropriate option for the evaluation of coronary artery disease.11 This limitation would stem mainly from the fact that the positive predictive value of Coronary artery CT is not as high as its negative predictive value, as it is also somewhat limited in characterizing plaques of moderate obstruction, especially when compared to other diagnostic tests.6 This is relevant because the correct management of patients with coronary artery obstruction requires the characterization of the functional impact of stenosis, given that atheromas that do not cause flow reduction should receive maximum clinical treatment, whereas plaques that impact myocardial perfusion could be treated with surgical or percutaneous revascularization even if it promotes a moderate decrease in vessel lumen.15On the other hand, the routine use of CT scan could result in a greater number of invasive procedures, since it would show lesions without clinical manifestation and that would be submitted to interventional treatment.18 the use of hybrid images, combining anatomical and functional findings, has become extremely desirable.4 However, this involves additional costs and time, which often makes this diagnostic workflow impractical. In view of the above, there was a desire to perform myocardial perfusion analyses with the MDCT itself, in the same procedure as the anatomical evaluation. This approach would involve the use of just one piece of equipment, reduced support staff, and reduced time and cost for exams. The initial attempts were made in commercially available equipment and showed favorable results, which confirmed the potential of a combined analysis, providing important data for an appropriate therapeutic management of such cases.20Given the importance of myocardial ischemia detection, either by echocardiography, magnetic resonance imaging, myocardial scintigraphy, or by invasive examinations that include Fractional Flow Reserve (FFR) analysis,23 This favorable scenario led to the development of an international multicenter trial designed to test the validity of a combined analysis of anatomy and perfusion by CT scan with the conventional way of investigating such patients, that is, angiography associated with scintigraphy.24 This study has shown that it is possible to perform combined CT anatomy and perfusion evaluations safely and with very favorable results.24Initial positive expectations were strengthened as technology progressed, including dual energy use, increased detector numbers, and improvements in spatial and temporal resolutions.Nowadays, there are tomographs in Brazil with all characteristics necessary to ensure that such images are generated in accordance with what is described in this document. In addition, similar to what happened with the standardization of coronary angiotomography procedures by the National Agency for Supplementary Health Guidelines, the creation of a document on use is also educational and may hinder the indiscriminate use of diagnostic tests, thus avoiding the waste of resources in situations with no solid scientific evidence of the benefit these could bring.Therefore, the purpose of this paper is to discuss in more depth the characteristics of ischemia CT research, the technological and software prerequisites, and to define which subgroups of patients would benefit from this exam.25 in the 19th century. Images of the heart are taken during iodinated contrast injection to assess its transit through myocardial microcirculation, allowing the construction of an time-attenuation curves in the aorta and myocardium, from which myocardial blood flow (MBF) and myocardial blood volume (MBV) can be defined.26 Based on the principles of the theory of tracer-dilution on CT,27 the higher the concentration of iodinated contrast in the intravascular space and myocardial microcirculation, the greater its attenuation; and the opposite is also true. However, diffusion into the extracellular space increases over time, and after one minute its extracellular concentration is greater than the intravascular.28 Therefore, to obtain an accurate perfusion assessment, images must be acquired right in the beginning of the first contrast pass.Myocardial CTP is based on the principles of the theory of tracer-dilution, first developed by Stewart,26 Another study has shown that first-pass perfusion imaging by helical CT correlates well with myocardial blood flow evaluated by microspheres.29 This study confirmed the feasibility of performing an atherosclerosis and MBF assessment in a single CT scan, with the possibility of quantification and semi-quantitative analysis of perfusion data by attenuation curves. These theoretical considerations were later indorsed in a human clinical study from 2012, which confirmed the accuracy of MDCT assessment to detect coronary obstructions that cause myocardial ischemia.30Thus, in the first-pass imaging approach, the concentration of iodinated contrast is ideally proportional to MBF in a wide range of blood flows. Areas with lower (darker) attenuation upon first contrast passage are classified as hypoperfused territories and are visually and quantitatively evaluated in comparison to adjacent myocardial territories.31 used a canine model to determine the correlation between induced epicardial stenosis and perfusion defects identified by CT, with myocardial perfusion having microspheres as reference. The favorable results encouraged further clinical studies comparing, the additional value of the combination between Coronary computed tomography angiography (CCTA) and Myocardial CTP with the use of CCTA alone. Rocha-Filho et al.22 showed an increase in accuracy in the combined assessment  compared to CCTA alone in the diagnosis of significant coronary stenosis. Adding Myocardial CTP to the strategy improved the accuracy from 0.77 to 0.90 (area under the ROC curve) in detecting stenoses.Although recently inserted in the clinical evaluation, Miocardial CTP has been subject of research for several years. In 2006, George et al.24 This is a multicenter study in which the combined use of CCTA + Myocardial CTP to detect flow-limiting stenoses defined by obstructions >50% associated with perfusion defects was tested, defined by the combination of myocardial perfusion scintigraphy (SPECT-MPI) and cardiac catheterization. When considering all patients, the combination protocol achieved an accuracy of 87% for the definition of disease and 93% when considering only patients with no history of previous coronary disease.Promising data from single-center clinical studies prompted the study CORE320.32 The accuracy of MDCT, defined by the area under the ROC curve, was greater than that of MPC , mainly due to the higher sensitivity of the first method.Data from this same study evaluated the performance of Miocardial CTP alone in the diagnosis of significant stenosis identified by catheterization alone, compared to MPC.33 described the diagnostic performance of MDCT related to other methods of myocardial ischemia analysis, taking invasive coronary FFR as a reference. In a per-patient analysis, Myocardial CTP was shown to have a 93% accuracy in detecting flow-limiting coronary stenosis, while cardiac magnetic resonance and positron emission tomography had similar accuracy . These values were statistically higher when compared to methods traditionally used in myocardial ischemia analysis, such as MPC and stress echocardiography, with accuracy of 82 and 83%, respectively.Although the isolated use of MDCT for myocardial ischemia detection is not the end goal of tomography use, a recent study published by Takx et al.,39 Clinical studies evaluating dynamic Myocardial CTP using invasive FFR as reference have shown good diagnostic performance, with sensitivity and specificity ranging from 88 to 95%, and 74 to 90%, respectively. Although promising, the evaluation of this technique has been performed mainly through small sample unicentric studies, so the potential benefits of its use in relation to static Myocardial CTP need further investigation. Similarly, the use of dual energy in the evaluation of myocardial perfusion finds favorable ground for clinical research. Recent studies have shown promising data in the attempt to detect obstructive coronary artery disease (CAD) (86-94% sensitivity and 74-98% specificity),41 however with data obtained in small samples. A prospective multicenter study to evaluate the use of this technique to identify flow-limiting coronary stenosis using invasive FFR as a reference is underway.42The use of dynamic myocardial perfusion in the detection of myocardial ischemia has shown encouraging results validated by different reference techniques.47 For dynamic stress studies, with follow-up of the first pass of contrast through the myocardium , CT scans with at least 8 cm cover are required, either axially or in shuttle mode. Regarding image post-processing, it is recommended to use specific analysis software that allows segmenting the heart, coding the density of each area of the myocardium by color and displaying the result in a 3D map integrated with the coronary anatomy, or Bull's Eye representation form. Some newer tools allow correction of beam hardening hypo-attenuation, which is common in the inferior/inferolateral walls (from the aorta), septum (from contrast in the right ventricle) and anterior walls (from the ribs). This correction is highly recommended and can be done by probability algorithms48 or by dual energy spectral acquisition with reconstruction of high energy monochrome images.49Any 64-channel or more (4 cm z-axis coverage) CT scan is able to perform coronary angiography, and therefore synchronizes with the electrocardiogram (ECG) and appropriate settings, being also able to study pharmacological-stress myocardial perfusion.A contrast infusion pump, preferably with two heads, is required for dynamic injection of high flow contrast. There is no need for an infusion pump for dipyridamole, but its presence can help optimize and ensure protocol quality. Despite the safety of dipyridamole/adenosine demonstrated in past studies, emergency care supplies regularly present in radiological clinics should be readily available, as well as qualified personnel to use them. Since dipyridamole/adenosine may induce advanced atrioventricular blocks , the presence of percutaneous pacemaker can be helpful. Aminophylline should be ready for infusion after dipyridamole/adenosine administration. Continuous monitoring by ECG of satisfactory quality is indispensable during infusion.50 CTMP imaging techniques vary according to manufacturer and equipment model used. Thus, we warn that for each manufacturer some adjustments should be made for protocol optimization. In addition, we emphasize that the description of patient preparation, techniques of acquisition and use of medications are suggestions based on previous studies and the authors’ experience, and may vary to meet the specific demands and workflows of each institution.Monitoring of coronary artery tomography images, as well as CTMP, should be conducted by a specialized professional.As preparation for the exam, all patients should be fasting for at least four hours and not have caffeinated beverages in the last 24 hours.Patients should be punctured with 18-20 gauge Jelco intravenous catheter in the antecubital vein of the right arm for administration of iodinated contrast. Another IV line in the left arm should be made for infusion of the stressor agent (dipyridamole/adenosine/regadenoson) and aminophylline as dipyridamole antagonist when necessary.24 Although there is a theoretical anti-ischemic effect of nitrates, its use according to steps described above was not relevant to mask perfusion defects under pharmacological stress by tomography, when using SPECT-MPI associated to cardiac catheterization as a reference.24ECG, heart rate and blood pressure should be monitored by the attending physician throughout the examination. Patients with blood pressure above 100 mmHg may receive sublingual nitrate (isosorbide dinitrate [5mg] or propatylnitrate [10mg]), with a minimum interval of 20 minutes for subsequent pharmacological stress, as validated in previous safety profile studies.24 If body mass index (BMI) is < 30 kg/m2 and heart rate (HR) is > 60 bpm, 75 mg oral metoprolol should be administered. If BMI is ≥30 kg/m2 and HR > 60 bpm, oral 150 mg metoprolol should be administered. If HR remains >60 bpm, intravenous metoprolol 5 mg every 5 minutes up to a total of 20 mg may be administered.Patients may receive intravenous or oral metoprolol prior to examination. Although there is no formal guideline for this purpose, the proposal is to use the following scheme used in a previous multicenter study:Regardless of the mode of image acquisition or equipment available, fixed stressor administration protocols are used. In Brazil, stress protocols use mainly dipyridamole (0.56 to 0.84 mg/kg) in 4 minutes, with acquisition in the 6th minute of the beginning of injection or possibly adenosine . Regadenoson can be used as a stressor at a single dose of 0.4 mg intravenous (IV) in a bolus, with stress imaging acquired within 1-2 minutes after injection.The assessment of myocardial perfusion at rest and stress by tomography, as well as the coronary anatomical evaluation, should always be performed in a single protocol. Aiming at a low radiation dose, we always suggest performing resting perfusion study (CCTA study itself) with the usual low-dose protocols available on the device (preferably with dose modulation and/or prospective acquisition), and the protocol under pharmacological stress whenever possible, with a slightly lower radiation dose, but diagnostic quality, always prioritizing prospective acquisition.We encourage the option of the protocol to be used (stress/rest or rest/stress) according to the experience of each center and particular characteristics of each patient or the CT scanner used. 52As an example, we can describe the following acquisition parameters for first-generation 64-channel scanners:Resting study - Retrospective Gating, 70-90 ml of contrast at 5 ml/s injection pump infusion after metoprolol (max. 20 mg), 64 x 0.5 mm or 32 x 0.6 mm collimation, mAs up to 850 depending on gender and weight and Kv of 100 (preferred).Study under pharmacological stress - Retrospective Gating, 60ml contrast at 3ml/s injection pump infusion, peak pharmacological stress acquisition, 32x1.0 mm collimation, 100 mA and 100 Kv (preferred).Devices with latest hardware and state-of-the-art software can take advantage of available technological advances (e.g. prospective acquisition) and be based on a protocol with less radiation and the same diagnostic capability.After iodinated contrast infusion, imaging acquisition can be performed manually as soon as the contrast is visually detected in the left atrium.The rest protocol will simultaneously acquire anatomical image (coronary angiography) and myocardial perfusion. The start and end of acquisition should be programmed based on previously acquired calcium score images, trying to minimize the radiation dose. Acquisition parameters used include 240-320 0.5 mm detectors with 100-120 kV voltage probe, gantry rotation from 0.280 to 0.375 seconds, with prospective ECG trigger.53Intravenous contrast will be infused by pump injection in a biphasic or three-phase protocol: 100% contrast in the first phase, 30% contrast plus 70% saline in the second phase, and 100% saline in the third phase. The contrast dose will be adjusted according to the patient’s weight see .53Contrast injection monitoring must be performed by rapid real-time acquisitions initiated 5 seconds after the start of infusion. An apnea command is to be performed 14 seconds after the start of intravenous contrast infusion. When the contrast density peak reaches 300 UH in the descending aorta, acquisition of resting myocardial perfusion images and coronary angiography by CT will be initiated.53The pharmacological stress protocol will focus on stress myocardial perfusion image. Again, the beginning and end of the acquisition should be programmed based on previously acquired images, calcium score and rest perfusion. Acquisition parameters used include 240-320 0.5 mm detectors with 100-120 kV tube voltage, gantry rotation from 0.280 to 0.375 seconds with a prospective ECG trigger.Following administration of the stressor, a 12-lead ECG should be performed, along with blood pressure and heart rate checks.Different techniques and forms of image acquisition are available and constantly evolving, including dual energy and dynamic acquisition. Although promising, such techniques require further investigation and radiation reduction strategies. Therefore, we will not address the protocols used for such techniques in this document.57 given that the additional value of CT perfusion defects in the absence of atherosclerosis has not been investigated so far.The assessment of CTMP involves a sequence of steps, which must be systematized to produce a result that reflects a physiopathological change or a state of normality. In this approach, initial assessment of CCTA is recommended ,57 givenOnce the CCTA is evaluated and any coronary stenosis and non-interpretable segments  are quantified, the next step is to assess stress and rest myocardial perfusion. At this stage, qualitative and quantitative visual analyses (below) are used to establish the severity and extent of myocardial perfusion deficit, as well as its reversibility.58 myocardial perfusion analysis may be the information required to define obstruction. In this sense, in coronary segments whose evaluation was doubtful for any reason, the presence of myocardial ischemia observed by the Myocardial CTP should strongly suggest significant stenosis.The third step in the process of image interpretation is the reclassification of anatomical findings. Due to potential limitations of luminal assessment by CCTA and the existence of intermediate stenoses,24 i.e. the presence of epicardial obstructions causing myocardial perfusion defects, whether fixed (fibrosis) or reversible (ischemia). This correlation should be performed mainly by multiplanar reconstructions, in order to align each epicardial vessel with its respective myocardial territory, defined by well-established myocardial segmentation models.59 This process should produce a correlation between epicardial stenoses and eventual perfusion defects, whose description should clear and detailed in the final report.The final step in the interpretation process is anatomical-perfusion alignment based on the integration of CCTA and Myocardial CTP findings. This process is essential to define the presence of flow-limiting stenoses,Among the methods used for quantitative evaluation we can mention transmural perfusion ratio (TPR) and summed stress score (SSS), obtained through static acquisition. MBF estimates, although likely to be performed by dynamic myocardial perfusion, will not be addressed in this document.30 and has excellent accuracy to identify perfusion defects after pharmacological stress associated with significant coronary obstruction by invasive coronary angiography.52 TPR less than 0.85 should be considered the cutoff value for identifying ischemic segments.52The TPR is calculated by the average subendocardial density (in Hounsfield Units) divided by the average of the subepicardial density of each myocardial segment. This relationship showed that Myocardial CTP can detect and quantify perfusion defects compared with SPECT,Tomography SSS should be calculated based on the sum of perfusion defect of the 17 segments predefined by the American Heart Association, ranging from a scale of 0-4 for each segment . SSS values for ischemia quantification are: less than 4 normal, between 4 and 8 discrete, between 9 and 13 moderate, and greater than 13 important.Myocardial CTP assessment should be divided into qualitative and quantitative analysis. The report must contain the examiner's visual and subjective impressions, followed by the quantitative assessment (TRP and SSS). The reversibility of perfusion defects is fundamental information and should be addressed in the report, as it reflects the myocardial ischemia itself.60The most important part of the report is the integration of anatomical and perfusion findings. The examiner should clearly define whether there is a correlation between luminal obstructions and perfusion defects, as well as the extent of perfusion defects and reversibility as they define the therapeutic approach.The main elements of the report are expressed in Myocardial perfusion study is advantageous when in conjunction with the anatomical assessment of the coronary arteries, as it benefits from the combined assessment. Thus, it is a limited strategy when considered in isolation, given exposure to ionizing radiation and iodinated contrast, which can be avoided in other diagnostic methods.Because it uses additional doses of radiation and contrast when compared to coronary tomography alone, Myocardial CTP should be used with caution in patients with renal failure or undergoing other examinations employing ionizing radiation over a short time.The use of vasodilatory pharmacological stress should be carefully evaluated in patients with any clinical or hemodynamic instability, as well as in patients with atrioventricular blocks, chronic obstructive pulmonary disease and asthma.As previously mentioned, the use of dynamic perfusion by tomography allows the evaluation of myocardial iodine contrast kinetics, making it possible to quantify MBF. Additionally, the use of dual energy techniques (two x-ray tubes operating simultaneously at different voltages) allows to create an “iodine map” for the quantification of perfusion defects. Although such techniques are already available, further studies are needed to assess the impact of these approaches on clinical decision-making, as well as the increased supply of equipment that allows the use of this technique, which is still scarce in Brazil.61 The most recent data point to an optimal accuracy of this method, and equivalent to the combined assessment CCTA + Myocardial CTP to define flow-limiting stenoses using invasive FFR as a reference.62 Although promising, this technique also faces limitations, such as the impossibility of use in revascularized patients with stents, as well as examinations with motion artifacts/calcification that prevent the proper identification of lumen boundaries to generate the three-dimensional model. Moreover, because it is a technique with specific and hard-availability software and hardware, FFR-CT is still restricted to some centers in the world .Recently, a new approach has emerged in the functional assessment of coronary artery disease by CT, known as CT-derived FFR. Although it uses a completely different technique, it has the same purpose of Myocardial CTP, using routine coronary tomography images without the need for pharmacological stress. Usually, coronary tomography images are transferred to a dedicated computer, where simulations based on computational fluid dynamics are performed, in order to create a three-dimensional model based on the anatomical and physiological characteristics of each patient. This model identifies stenoses and quantifies changes in intracoronary pressures, reflecting the changes found in stenoses invasively assessed by FFR.CCTA combined with stress tomography evaluation of myocardial perfusion is a safe and accurate modality for the simultaneous investigation of coronary obstructions and their repercussions on regional myocardial flow. The positive impact of this approach lies on the value added by the ischemic burden information provided by myocardial perfusion upon CT, a well-established method of anatomical and coronary stenosis assessment, with acceptable doses of radiation and the use of iodinated contrast.


MicroRNAs are highly investigated for their role in the pathogenesis of cardiovascular diseases. Nevertheless, evidence for clinical implementation is still lacking. In our systematic review, we evaluated the potential of microRNAs as pathophysiological and diagnostic biomarkers of heart failure. We identified 72 differentially expressed microRNA molecules among groups of heart failure patients and control groups by searching the PubMed database. We did not identify a substantial overlap of differentially expressed microRNAs among different studies; only five microRNAs  were differentially expressed in more than one included study. Gene set enrichment analysis, based on the gene targets of microRNAs presented in the included studies, showed that gene targets of differentially expressed microRNAs were enriched in the MAPK, TGFβ, PI3K-Akt, and IL-2 signaling pathways, as well as apoptosis pathway, p53 activity regulation, and angiogenesis pathway. Results of our systematic review show that there is currently insufficient support for the use of any of the presented microRNAs as pathophysiological or prognostic biomarkers in the clinical setting. Heart failure is a major cause of morbidity and mortality worldwide. The prevalence of heart failure is on the rise, and it has been estimated that it will grow further and reach 10% of the general population in 2030 . The serMicroRNAs (miRNAs) are small (~22 nucleotides long) endogenous non-coding RNAs that play an important role by regulating post-transcriptional gene expression. They act to either inhibit the translation of messenger RNA or to induce the degradation of specific mRNA –8. MiRNADifferentially expressed miRNA patterns were found to be associated with various pathophysiological mechanisms of heart failure, such as cardiac remodeling, hypertrophy, apoptosis, and hypoxia –32. The In this review, we aim to provide an overview of current scientific support for the use of miRNAs as pathophysiological and diagnostic biomarkers for heart failure.The literature search was conducted in the PubMed database until August 2019, using the following terms: (“MiRNAs” OR “microRNAs”) AND (“heart failure” OR “HF”) in the title/abstract. We limited our search to articles written in English. The “AND” operator was used to create all possible combinations of selected terms. The literature search was conducted independently by two authors (AP and KP) who reached consensus on all of the research papers.Research papers were initially retrieved as title and abstract and screened for eligibility. All selected research papers were then retrieved as complete manuscripts and checked for compliance with inclusion and exclusion criteria. We included human studies meeting the following criteria: (1) heart failure diagnosis based on clinical features and confirmed with echocardiography; (2) the patients had measured specific miRNA expression level at the time of heart failure exacerbation/follow up examination; (3) case–control study design; (4) qPCR, real-time PCR, microarray, and RNAseq are acceptable methods to evaluate the expressions of miRNAs. The exclusion criteria applied to the studies were as follows: (1) patients had received medications before blood/serum samples were collected; (2) heart failure as an immediate consequence of acute myocardial infarction; (3) heart failure studied only on subpopulations of patients, i.e., diabetics; (4) research papers that were not focused on heart failure but were focused only on the specific pathophysiological mechanism leading to heart failure ; and (5) the same cohort was already studied in other research papers. Newcastle-Ottawa quality assessment scale  was usedUsing miRTarBase (release 8.0 beta), we identified all known gene targets for selected miRNAs that were differentially expressed in the research papers included in the systematic review . We thenThrough the initial keyword search, we retrieved 1,165 research papers. The further selection process is presented in The Newcastle-Ottawa questionnaire was applied to assess the quality of the included studies . The mosThe majority of included studies (17/18 RT-qPCR studies) provides information on performed normalization. However, there was a discrepancy in the normalization methods (exogenous or endogenous controls) and selected control microRNAs. The most commonly used control microRNAs were U6 snRNA, i.e., in seven studies , 29, 32 By searching miRTarBase , we idenWe identified 72 differentially expressed miRNAs among groups of heart failure patients and control groups with a systematic review. Among 72 differentially expressed miRNAs, only 5 miRNAs, namely, miR-1228, miR-122, miR-423-5p, miR-142-3p, and exosomal miR-92b-5p were differentially expressed in more than one included study.Two studies found increased levels of miR-1228 and miR-122 in patients with heart failure , 26. VogStudies by Tijsen et al. and Fan et al. found miR423-5p to be significantly increased in heart failure patients compared to healthy controls and speculated that miR423-5p could be a significant predictor of heart failure diagnosis , 32. TheThe results regarding the differential expression of miR142-3p were conflicting , 31. VolWu et al. investigated the role of serum exosomal miR-92b-5p in two different subpopulations of heart failure patients (patients with heart failure with reduced ejection fraction and patients with dilated cardiomyopathy caused by acute heart failure). They found increased expression levels of exo-miR-92b in both patient subgroups compared to control groups. Both studies also found miR-92b to be positively related to the left atrium diameter, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension and negatively related to left ventricular ejection fraction and left ventricular fractional shortening , 23. DueThrough a thorough assessment of previously published studies, we established that the evidence of the magnitude of effect and certainty of the evidence, contextual factors including improvement of the predictive diagnostic value of investigated miRNAs, and pathophysiological action of miRNA in heart failure are still poorly investigated at present. Similarly, analytical and clinical validity, as well as clinical utility, have not been assessed yet , 47. TheBased on the results of this systematic review, it is evident that none of the miRNAs could be considered to be used as a biomarker in the clinical setting. Therefore, we performed gene set enrichment analysis on 2,558 genes that were defined as targets of 72 differentially expressed miRNAs to investigate if there are any common enriched pathways related to pathophysiological processes of heart failure. We found support for an association of pathway enrichment results with heart failure for MAPK signaling pathway, TGFβ signaling pathway, PI3K-Akt signaling pathway, IL-2 signaling pathway, apoptosis pathway, p53 activity regulation, and angiogenesis pathway.Cardiac angiogenesis, especially of microvasculature, in the setting of pathological cardiac hypertrophy, is insufficient to maintain adequate perfusion. Impaired production of NO from dysfunctional endothelial cells is one of the most researched pathophysiological mechanisms that impair angiogenesis . Inhibitin vitro (Mitogen-activated protein kinase (MAPK) signaling cascades are considered to be important regulators of cardiac hypertrophic response –53. Numein vitro –57. Furtin vitro –57. Myocin vitro .Several studies have already linked different miRNAs with the PI3K-Akt pathway –61. Two The results of previously published studies on the effects of IL-2 on heart-related pathologies are inconsistent. On the one hand, plasma levels of IL-2 were shown to be elevated in patients with acute myocardial infarction, angina pectoris, and dilated cardiomyopathy, while on the other hand, there are reports that suggest a potential therapeutic effect of IL-2 in the setting of acute myocardial infarction , 64.TGFβ was found to be involved in cardiac remodeling . SpecifiWe discovered that many of the most enriched pathways were associated with different types of cancer, especially prostate cancer, colorectal cancer, and chronic myeloid leukemia. This discovery is not all that surprising since more than 50% of the miRNA genes are located in regions associated with cancer .The systematic evaluation of diagnostic and prognostic values of miRNA presented in this study has some limitations due to different subpopulations of patients with various heart failure phenotypes across different studies, a small number of patients per study, and different technical approaches for miRNA identification and analysis . Furthermore, inferrals about a pathophysiological mechanism based on pathway analysis of circulating microRNA should be made with caution since heart tissue was not analyzed directly. Reporting bias may exist to some extent because we only included research papers written in English or because only positive results were published.The results of our systematic review on the role of miRNAs as pathophysiological and diagnostic biomarkers of heart failure show that there is currently insufficient support for the use of any of the presented miRNAs in the clinical setting. Gene set enrichment analysis showed that gene targets of differentially expressed miRNAs were enriched in pathways playing an important role in the MAPK, TGFβ, PI3K-Akt, PDGF, and IL-2 signaling pathways, as well as, apoptosis pathway, p53 activity regulation, and angiogenesis pathway. To establish the definite value of miRNAs as pathophysiological and diagnostic markers, future experimental studies employing the same methodological design and performed on large sample sizes are needed.The datasets generated for this study are available on request to the corresponding author.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Accumulation of excess body fluid and autonomic dysregulation are clinically important characteristics of acute decompensated heart failure. We hypothesized that transthoracic bioimpedance, a noninvasive, simple method for measuring fluid retention in lungs, and heart rate variability, an assessment of autonomic function, can be used for detection of fluid accumulation in patients with acute decompensated heart failure.We aimed to evaluate the performance of transthoracic bioimpedance and heart rate variability parameters obtained using a fluid accumulation vest with carbon black–polydimethylsiloxane dry electrodes in a prospective clinical study .with fluid and without fluid groups, respectively.We computed 15 parameters: 8 were calculated from the model to fit Cole-Cole plots from transthoracic bioimpedance measurements , and 7 were based on linear  and nonlinear  analysis of heart rate variability. We compared the values of these parameters between 3 participant data sets: control , baseline , and discharge . We used several machine learning approaches to classify participants with fluid accumulation (baseline) and without fluid accumulation (control and discharge), termed 0; difference in extracellular-intracellular resistance, R0 – R∞, and tissue heterogeneity, α) and 3 heart rate variability  parameters were found to be the most discriminatory between groups (patients with and patients without heart failure). R0 and R0 – R∞ had significantly lower values for patients with heart failure than for those without heart failure , indicating that a higher volume of fluids accumulated in the lungs of patients with heart failure. A cubic support vector machine model using the 5 parameters achieved an accuracy of 92% for with fluid and without fluid group classification. The transthoracic bioimpedance parameters were related to intra- and extracellular fluid, whereas the heart rate variability parameters were mostly related to sympathetic activation.Among the 15 parameters, 3 transthoracic bioimpedance (extracellular resistance, RThis is useful, for instance, for an in-home diagnostic wearable to detect fluid accumulation. Results suggest that fluid accumulation, and subsequently acute decompensated heart failure detection, could be performed using transthoracic bioimpedance and heart rate variability measurements acquired with a wearable vest. Heart failure is estimated to affect more than 25 million people worldwide and over 6 million people in the United States -4. AcuteTransthoracic bioimpedance can measure intrathoracic volume, a surrogate biomarker of pulmonary edema -13. For Traditionally, various types of electrodes have been used for transthoracic bioimpedance and ECG measurements using fluid accumulation vests: adhesive Ag-AgCl electrodes, which often result in skin irritation and are often misaligned when positioned; textile electrodes, which need to be wetted prior to every use; and recently proposed reusable carbon black–polydimethylsiloxane (PDMS) dry electrodes ,20. In oThere are several studies ,21 that In this prospective clinical study  to examine the performance of transthoracic bioimpedance and heart rate variability measured using carbon black–PDMS electrodes embedded in fluid accumulation vests for detection of acute decompensated heart failure, we hypothesized that (1) participants without acute decompensated heart failure should have resistance measurements that are higher than those of participants with acute decompensated heart failure at the time of admittance to the hospital; (2) participants with acute decompensated heart failure at the time of discharge from hospital should have smaller amount of accumulated lung fluid and therefore higher resistance measurements than those of participants with acute decompensated heart failure at the time of admission; and (3) autonomic function assessed by heart rate variability would provide additional information about the dysregulation of heart failure patients, hence, it would detect acute decompensated heart failure.A total of 93 hospitalized individuals were prospectively enrolled in our observational study at the University of Massachusetts Medical Center. We acquired recordings from participants with acute decompensated heart failure taken within the first few hours of hospital arrival (baseline) and taken prior to discharge from hospital (discharge). We also acquired recordings from a group of patients without acute decompensated heart failure (control). All participants gave written informed consent before participating in the study, in accordance with the Declaration of Helsinki. The protocol was approved by the institutional review board of the University of Massachusetts Memorial Hospital (docket number H00014714).The CONSORT diagram in For this study, we used Philips prototype fluid accumulation vests , which p0R to represent the extracellular fluid, in parallel with a resistance IR to represent intracellular fluid, and a capacitance mC to represent cell membranes [f=0 Hz will pass around all cells, and the total resistance is equal to the resistance from the extracellular fluid only, 0R. At the other extreme, when the frequency is infinite, f=∞, the current will pass through the cells, and the total resistance can be calculated as the parallel circuit of 0R and IR,Transthoracic bioimpedance is a noninvasive method that measures the impedance of the tissue at a series of frequencies. A small alternating current, typically ranging from 100 µA to 10 mA, is injected into the tissue via electrodes, while the voltage drop is measured as the output. By applying Ohm’s law, the resistance of the body tissue can be calculated. Biological tissue is typically modeled with a resistance embranes . ElectriIR can be represented aswhere If we measure impedance for frequencies between these two extreme cases, we obtain an arc-like Cole-Cole plot in the impedance plane -27. The The parameters of the model can be extrapolated from a set of measurements made at a predefined set of frequencies. The exponent α represents the heterogeneity of the tissue in the model. For each frequency, the real (resistance) and imaginary (reactance) part of the electrical impedance is estimated. The Taubin algorithm  is used 0R is obtained as the x-axis intercept at the far right side of the Cole-Cole plot, while the value of ∞R is the x-axis intercept at the far left side of the same plot. The frequency that corresponds to the upper point of the circle is called the resonance frequency, cf,fitting error was calculated as the sum of the square error at the optimal parameters. We calculated 8 transthoracic bioimpedance measurements in this study: 0R, IR, ∞R, 0R – ∞R, cf, mC, α, and fitting error.The sum of the square error is minimized in the fitting process. The To compute heart rate variability parameters, 4 minutes of clean ECG data were extracted from each 5-minute recording of ECG acquired simultaneously with transthoracic bioimpedance measurements. Noise and motion artifacts were removed from the ECG signals using a bandpass filter (0.05 Hz-40 Hz). The R peaks were detected using a validated algorithm ,33. SegmWe computed the indices of low frequencies of heart rate variability (low-frequency components of heart rate variability: 0.045 Hz to 0.15 Hz), high frequencies of heart rate variability (high-frequency components of heart rate variability: 0.15 Hz to 0.4 Hz), and the indices normalized to the total power of heart rate variability  . Indicest tests following rejection of an ANOVA null hypothesis [P value<.05 was considered statistically significant for ANOVA and Dunn tests.The normality of each parameter was tested using the Kolmogorov-Smirnov test -36. We tpothesis . A P valpatients without fluid (control and discharge groups) and participants with increased fluid in the lungs, termed patients with fluid (baseline group)Statistical analysis of the differences between groups provides insight into the suitability of the measures of transthoracic bioimpedance and heart rate variability to detect fluid accumulation, which is used as an indication of heart failure exacerbation. However, measurement results have nonlinear characteristics and cannot be completely described with linear statistical methods. Hence, we used nonlinear methods such as machine learning to examine 15 features derived from transthoracic bioimpedance and heart rate variability for classification between groups . Furthermore, participants in the discharge group were partially recovered, so they could be considered similar to the participants in control group. We tested the feasibility of classifying participants without fluid accumulation in the lung, termed k-nearest neighbor classifier (k=1) [For these classification analyses, 3 algorithms were used: support vector machines , a k-neaer (k=1) , and decer (k=1) . Cubic, We approached 90 patients with heart failure who were eligible, and 43 were enrolled in this study. Out of the 43 enrolled participants, we were able to collect data from 28 participants with heart failure; 23 were included in the baseline group , and 17 were included in the discharge group . Only 12 participants were included in both baseline and discharge groups. There were several reasons for the lower number of participants in the discharge group: (1) in some cases, the recordings were of poor quality (n=14); (2) some participants (n=5) were lost to follow-up ; (3) some participants (n=7) could not provide the second recording owing to illness or refusal.We enrolled 50 participants without acute decompensated heart failure  in the control group. Of the recordings taken on the 50 enrolled participants 32 of them were usable. It should be noted that participants from both groups were well matched with respect to age.P=.70; sex: P=.70; race: P=.52). Participants with acute decompensated heart failure were more likely to have a history of cardiovascular disease risk factors , prior heart failure (P<.001), and atrial fibrillation (P<.001). All transthoracic bioimpedance and heart rate variability parameters were found to be normally distributed, except for low-frequency components of heart rate variability and high-frequency components of heart rate variability.The demographic and medical characteristics of study participants are shown in 0R and 0 – R∞R, for the baseline group had statistically significantly lower values than those for the control group, with P=.006 and P=.001, respectively. Even though values of these 2 parameters for the discharge group were higher than those for the baseline group, there were no statistically significant differences . Possible reasons could be the lower number of participants in the discharge group , and one possibility is that, at the time of discharge, some of the participants still had excess fluid in their lungs. The parameter α for the baseline group had statistically significantly higher values than those of the control group (P=.003),We compared values of 15 parameters from transthoracic bioimpedance and heart rate variability measurements between participants in control, baseline, and discharge groups . As can P=.02; discharge: P=.13) and normalized high-frequency components of heart rate variability  had significantly higher values than those for the control group. Normalized low-frequency components of heart rate variability exhibited a significantly lower value in the discharge group, when compared to those in the control group (P=.01). None of the other parameters of heart rate variability exhibited significant differences between groups.As for the heart rate variability parameters, for the baseline and discharge groups, high-frequency components of heart rate variability . Incorporating the heart rate variability parameters improved the accuracy of most models. The quadratic support vector machine model achieved 75% accuracy using 8 parameters . As for patients without fluid/patients with fluid classification, the overall best model was the cubic support vector machine, which achieved an accuracy of 92% using 6 parameters .In this prospective observational study, we successfully trained machine learning models to classify participants with and without fluid accumulation using parameters obtained with a fluid accumulation vest, specifically transthoracic bioimpedance and heart rate variability parameters. We achieved a cross-validation accuracy of 92% using a cubic support vector machine model. The transthoracic bioimpedance parameters that contributed to this accuracy were related to intra- and extracellular fluid, whereas the heart rate variability parameters were mostly related to sympathetic activation. Our results suggest that the transthoracic bioimpedance and heart rate variability signals acquired with a wearable vest with carbon black–PDMS dry electrodes are suitable for detecting fluid accumulation and can potentially help with prediction and management of clinical worsening in heart failure patients.0R and 0 – R∞R resistances in the baseline group  than those in the control group , with P values of .006 and .001, respectively. This suggests that participants in the baseline group had higher fluid volumes retained in the lungs than participants in the control group did. Moreover, the same parameters 0R and 0 – R∞R for discharge participants  were higher than those for the baseline participants. However, this difference did not reach statistical significance . Since predischarge assessments could not be performed in all participants, our findings may be attributable to a relatively small sample size. Alternatively, significant variability in the amount of intrathoracic fluid remaining before discharge may also explain our findings.In the past, transthoracic bioimpedance has been used for lung fluid abnormality detection ,15. In tBioimpedance is a proven biomarker of acute decompensated heart failure. Our group previously performed a clinical study of 106 hospitalized patients discharged after an admission for acute decompensated heart failure. Participants were sent home with a fluid accumulation vests and we determined that it was feasible to measure transthoracic bioimpedance on a daily basis . We alsoP=.02; at discharge: P=.13) and normalized high-frequency components of heart rate variability parameters  were significantly higher in acute decompensated heart failure participants when compared to control participants without acute decompensated heart failure. This is possibly the result of more labored breathing exhibited by the participants with acute decompensated heart failure [P=.06; at discharge: mean 19.2, SD 51.3 P=.09). The activation of the sympathetic nervous system is a known countermeasure of the body aiming to restore cardiac output in the case of heart failure [As for the heart rate variability, high-frequency components of heart rate variability . This is in agreement with the between-group statistical differences, in which this parameter was found to be the most sensitive to heart failure. Using the set of transthoracic bioimpedance parameters only, machine learning models were able to provide moderate classification accuracy for both types of classification: an accuracy of 68% was found for 3-class classification (control/baseline/discharge classification) model, and an accuracy of 82% was found for 2-class models (patients without fluid/patients with fluid classification), which are acceptable performances, considering that the bottom line accuracy for 3- and 2-class models are 33% and 50%, respectively. However, adding heart rate variability parameters (the model was trained with transthoracic bioimpedance and heart rate variability parameters together) further increased the accuracy of the models. The control/baseline/discharge classification, with 75% accuracy, was acceptable. Furthermore, 92% accuracy for classifying of patients without fluid and patients with fluid suggested the feasibility of such an algorithm to potentially detect the healthy condition (control group) or recovering  of a patient from excess fluid accumulation. This model used parameters from transthoracic bioimpedance , as well as parameters from heart rate variability . The transthoracic bioimpedance parameters that were included are related to intra- and extracellular fluid, whereas the heart rate variability parameters are mostly related to the sympathetic activation. This finding is useful in developing in-home diagnostic tools that can detect or predict fluid accumulation in heart failure participants.In the machine learning classifications, Statistical analysis and machine learning analysis showed similar results for a reduced set of features. For instance, extracellular resistance and low-frequency components of heart rate variability exhibited significant differences between non–heart failure (control) and heart failure groups (baseline and discharge), and these features were present in the most accurate model for fluid accumulation detection. However, other features including intracellular resistance, cell membrane capacitance, principal dynamic mode index of parasympathetic function, and mean heart rate did not exhibit significant differences between groups but were relevant for improving accuracy of the machine learning algorithms.As for the limitations of the study, many recordings were not usable, mostly in the acute decompensated heart failure group. This is related to technical issues with the fluid accumulation vests, which can be partially attributed to the carbon black–PDMS electrodes. From the 28 participants with acute decompensated heart failure, we obtained reliable measures from only 23 participants at baseline and from 17 participants at discharge. We obtained data from both baseline and discharge for only 12 participants. Even in the control group, we collected usable data from only 32 out of the 50 participants. In some instances, applying a layer of hydrating lotion helped with data collection. This limitation could potentially diminish the clinical use of the device and must be addressed in the near future. A more robust hardware design, tailored to match the impedance of the carbon black–PDMS electrodes, is a potential improvement. Configurations that enable collection of transthoracic bioimpedance data from several locations on the thorax could help the quality and usability of the data, as accumulation of fluid does not occur always in the same location. Furthermore, given the limited data set, we have reported leave-one-subject-out cross-validation accuracy, and the results cannot be interpreted as conclusive concerning the efficacy of the transthoracic bioimpedance device and features derived from it. Instead, the results can be interpreted as promising, based on the validation of the transthoracic bioimpedance and its associated features and machine learning. A larger testing data set is required for further evaluation of transthoracic bioimpedance to allow for more definite conclusions about its efficacy.There are several potential clinical applications of transthoracic bioimpedance measurements in patients with heart failure. Wearable technologies such as fluid accumulation vests could allow for rapid point-of-care diagnostics that could be used in the emergency setting to help identify heart failure decompensation. In addition, fluid accumulation vest measurements in different clinical states such as decompensated heart failure, predischarge, and in outpatient setting, could be used to establish a profile for a given patient that could improve diagnostic certainty and guide treatment. Moreover, triaging medical severity is a necessary and time-consuming step of the patient care process, but this is often difficult due to limitations in both the number of available medical personnel and individual provider time.The device and algorithm in this study can be used in a longitudinal study with patients with heart failure, extending monitoring into the home. The system could be used to monitor a patient’s fluid accumulation daily and generate early warnings of heart failure decompensation, provide guidance on therapeutic changes to improve quality of life, and reduce heart failure readmissions. Alternatively, the system can be used to monitor either the discharge readiness of a patient from the hospital or the home treatment regime effectiveness on the patient. Wearable sensors such as the fluid accumulation vest can potentially provide an ideal avenue for patient monitoring over time, allowing for rapid action in response to acute decompensation. Garments integrating vital sign sensors have been utilized in acute medical settings to monitor patients with high medical risk profiles . In addiP=.006; P=.001, respectively), and 3  showed statistically significantly higher values  for participants with acute decompensated heart failure at hospital admission than those for participants in the control group. A significant difference in the sympathetic control  was observed between acute decompensated heart failure participants at the time of discharge and the control participants. Transthoracic bioimpedance and heart rate variability exhibited promising results for classifying participants with excess intrathoracic fluid versus those with normal intrathoracic fluid. Further clinical studies will be undertaken to refine our approach and determine the optimal application of this monitoring technology in acute medical settings.The main goal of this study was to evaluate the performance of biologically relevant parameters measured by a fluid accumulation vests with carbon black–PDMS dry electrodes. In our clinical study (SHIELD), transthoracic bioimpedance and heart rate variability parameters were considered for statistical analysis and discrimination between patients with nonacute decompensated heart failure and acute decompensated heart failure. As expected, our results show that among the 15 parameters, 2 (extracellular resistance and intracellular-extracellular difference in resistance) showed statistically significantly lower values (


Background: Acromegaly is a rare disease that requires modern treatment to decrease the risk of mortality, mainly from vascular diseases. Identifying acromegalic patients with increased cardiovascular risk is challenging. Speckle-tracking echocardiography (STE) is a modern, well-validated, and reproducible method of assessing left ventricular longitudinal deformation and providing a sensitive assessment of myocardial contractility. We hypothesized that STE may be useful in evaluating subclinical dysfunction of the left heart in acromegalic patients, especially when a left ventricle (LV) assessment is completed with STE of the left atrium (LA).Purpose: To assess the diagnostic value of speckle-tracking echocardiography in identifying the occurrence of LV and LA functional impairment in patients with acromegaly, in comparison to patients without this rare pituitary disease.Methods: Echocardiographic assessments of LV and LA function using the new STE method were performed in 60 subjects: 30 acromegalic (ACRO group) patients and a CONTROL group with 30 patients matched in terms of age, gender, systolic/diastolic pressure, and history of hypertension for at least 12 months.Results: The ACRO group, compared to the CONTROL group, presented: (1) higher left ventricular mass  and, in consequence, more frequent LV hypertrophy ; (2) impaired LV systolic function measured by both left ventricular ejection fraction (LVEF)  and global longitudinal strain (GLS) ; (3) greater LA anteroposterior diameter  and indexed left atrial volume ; and (4) impaired echocardiographic strain parameters corresponding with LA function.Conclusions: Acromegaly, even in young patients with good blood pressure control, may be associated with left ventricular hypertrophy and subclinical impairment of the left ventricular and left atrial mechanical function, which may be identified by speckle-tracking echocardiography. Further research in this area is necessary to clarify the prognostic value of these phenomena. Acromegaly is a chronic disease caused by growth factor (GH) hypersecretion. This rare pituitary disorder has some characteristic external appearance features. Unfortunately, they develop slowly and gradually, which is the cause of the relatively late diagnosis, usually after about 5–10 years and typically when the patient is around 40 years of age . NowadayIt is worth remarking that although standard echocardiography used to be the traditionally applied technique to evaluate diastolic and systolic LV dysfunction, more recent studies encourage the use of new methods such as speckle-tracking echocardiography (STE). This modern, well-validated, and reproducible technique to assess LV longitudinal deformation offers a more sensitive assessment of myocardial contractility. Evaluating global longitudinal strain (GLS) may help to identify patients with subclinical LV systolic dysfunction. More and more new studies have revealed the importance of this method as a diagnostic tool allowing assessment of the prognosis in many cardiological and non-cardiological diseases –10. Our We hypothesize that STE may be useful in evaluating subclinical dysfunction of the left heart in acromegalic patients, especially when LV assessment is completed with STE of the left atrium (LA). This latter concept has arisen from reports that proved the role of STE in detecting LA dysfunction in several cardiovascular diseases –14. For We assessed 33 patients with acromegaly qualified for causal treatment at the Military Institute of Medicine, Poland, between 2016 and 2019 (ACRO group), diagnosed on the basis of standard hormonal criteria: an increased level of GH, increased insulin-like growth factor 1 (IGF-1), failure to suppress serum GH levels to <0.4 mcg/L during oral glucose tolerance test (OGTT), and positive pituitary MRI findings. One patient from the ACRO group was excluded from the final analysis due to the diagnosis of a significant type 2 atrial septal defect, and two patients were excluded due to non-acceptable ultrasound image quality, excluding the possibility of measuring the strain value.The comparative control group consisted of 30 patients matched in terms of age, gender, systolic/diastolic pressure, and history of hypertension for at least 12 months.The exclusion criteria for both groups included coronary artery disease, LVEF <50%, stroke/transient ischemic attack in anamnesis, pulmonary embolism in anamnesis, chronic obstructive pulmonary disease in severe stadium, respiratory failure, a condition after a head injury, and pregnancy.All patients underwent two-dimensional echocardiography using a high-quality echocardiograph . Echocardiography was performed using all standard views. All measurements of LV and LA dimensions were made in accordance with the current guidelines of the European Society of Echocardiography . The staTo assess LV diastolic function, we measured waves E and A of the mitral inflow velocity, recorded using pulsed wave Doppler from the apical 4-chamber view, the ratio between peak early (E) and late (A) diastolic LV filling velocities, the velocity waves (e′ and a′) of the mitral annulus septal, and the lateral regions recorded using tissue Doppler imaging (TDI). When calculating E/e′ ratio, the average value of the septal and lateral mitral annulus velocities was used. Left ventricular diastolic dysfunction (LVDd) was diagnosed according to the current guidelines .Global and regional longitudinal two-dimensional (2D) LV and LA strain was analyzed with the speckle-tracking technique using GE EchoPAC software.Left ventricular global longitudinal strain (GLS) was assessed with the use of automated function imaging software. Two basal points were selected at the level of the mitral annulus and the third point at the apex detection of the tracked area to carry out the assessment semi-automatically with the possibility of manual adjustments. The LV walls were divided into six segments in each apical view, and tracking quality and strain value were assessed for each LV segment. The mean global longitudinal peak systolic strain was calculated for each view. The mean of these values was the value of GLS.For the analysis of LA strain, apical 4- and 2-chamber view images were obtained using conventional 2D gray scale echocardiography during breath hold. The frame rate was set between 60 and 80 frames per second. This technique is recommended by the Expert Consensus Statement . The recThe intraobserver variability of PALS 4CH, PALS 2CH, PACS 4CH, and PACS 2CH was assessed in 20 randomly selected patients. Intraobserver variability coefficients were calculated using images independently recorded on two different occasions by the same investigator. The intraclass correlation coefficient together with the mean difference (95% CI) of two measurements in Bland–Altman analysis, divided by the mean of those two measurements and given as percentages, was calculated for intraobserver variability.t-test/Mann–Whitney U-test for continuous variables and chi-squared or Fisher's exact test for categorical variables. A p-value of <0.05 was considered statistically significant.Statistical analysis was performed using Statistica 12.0 . The distribution and normality of the data were assessed using the Kolmogorov–Smirnov test. The categorical variables were presented as absolute and relative frequencies (percentages), and continuous variables were presented as means ± standard deviation (SD). The ACRO and CONTROL groups were compared in terms of clinical, echocardiographic, and hemodynamic parameters with the use of the Student's Thirty patients in the ACRO group  had acceptable ultrasound image quality and were included in the final analysis. The CONTROL group comprised 30 patients . There were no significant differences between the groups in terms of gender, age, concomitant diseases, or pharmacotherapy for arterial hypertension (AH), which was the only cardiovascular disease in most patients. Acromegalic patients had a higher resting heart rate (HR) compared to the CONTROL group . In both groups, blood pressure was well controlled . Five patients in the ACRO group were diagnosed with diabetes mellitus (DM) type 2, which was well controlled. Moreover, the duration of DM 2 was less than a year, and patients were treated either with a low dose of only one antidiabetic drug—metformin (three patients)—or diet alone (two patients). The duration of DM 2 was determined on the basis of medical history or laboratory test. For three patients, we had the fasting glucose result obtained 9–12 month earlier, and for the other two patients, the history of antidiabetic treatment was <12 months. None of the patients in either group had chronic kidney disease, coronary artery disease, atrial fibrillation (AF), stroke in anamnesis, or pulmonary diseases. The detailed baseline clinical characteristics of both groups and the average GH and IGF-1 levels measured in the acromegalic patients are presented in 2, p < 0.001) and, in consequence, more frequent LV hypertrophy . The occurrence of LVDd, measured according to the standard parameters, tended to be higher in the ACRO group, but the difference reached only borderline statistical significance . Patients in the ACRO group had lower e′ septal value , but no differences were noted for e′ lateral value  and E/e′ ratio . Acromegaly was also related to impaired LV systolic function. There were differences between the ACRO and the CONTROL group both in the assessment of LVEF  and GLS ]: 18.5% (13.0–22.9%) vs. 19.8   see . Even af.02) see .p = 0.003) and indexed LAV (LAVI) . The repeatability of the LA strain measurements was very high. The intraclass correlation coefficient for intraobserver variability of LA strains was as follows: for PALS A4C−0.99, PALS A2C−0.98, PACS A4C−0.99, and PACS A2C−0.98. The mean difference divided by the mean of two measurements for intraobserver variability was as follows: for PALS A4C−0.4% (−1.1–2.0%), PALS A2C−0.6% (−1.6–2.8%), PACS A4C−0.2% (−3.7–6.6%), PACS A2C−0.5% (−3.1–4.1%).Our study revealed that STE may be useful in evaluating subclinical dysfunction of the left heart in acromegalic patients. We confirmed the clinical value of STE in LV assessment and revealed even more expressed impairment of LA deformation. To our knowledge, this is the first such report. The comparison of relatively young acromegalic patients, seemingly without tangible cardiological burden, to controls without acromegaly enabled the identification of strongly expressed heart abnormalities.An elevated level of GH in acromegaly stimulates the liver to synthesize increased levels of IGF-1. Both GH and IGF-1 may cause acromegalic morphological and functional changes, either directly by affecting myocyte growth and contractility or indirectly by affecting peripheral vascular resistance, which modifies extracellular volume and neurohormonal activity , 20. Botp < 0.01). Di Bello et al. , we revealed that they present more pronounced LV systolic and diastolic dysfunction than hypertensive patients and healthy individuals . Patiento et al.  found tho et al. , which eo et al. .2; p < 0.001).The most important novelty of our work concerns the LA dysfunction in the ACRO group. We evaluated LA morphology and its several important functions: (1) as a booster pump during late ventricular diastole (PACS), (2) as a reservoir for the inflow volume received from the pulmonary veins during ventricular systole and isovolumic relaxation (PALS), and (3) as a passive conduit during early ventricular diastole and diastasis (CALS) . The ACREven more impressive are the results of the LA strain parameters. Patients with acromegaly presented significantly lower LA global PALS, PACS, and CALS as well as separately averaged values observed in 4- and 2-chamber views (PALS/PACS A4C and PALS/PACS A2C). This indicates a significant impairment of the LA function in all its phases: as the reservoir, conduit, and booster pump. We did not find another study that assessed LA function in acromegalic patients by using 2-dimensional STE (2D-STE). Kormányos et al.  evaluateLA pathologies are robust predictors of adverse cardiovascular outcomes such as stroke, congestive heart failure, and cardiovascular death , 28. JusTwo-dimensional STE analysis allows assessment of both the LV and LA deformation profile during an entire cardiac cycle. This method, which closely follows LV and LA physiology, is also relatively quick and easy to perform . The useWe realize that the small sample size is a limitation of this study. However, it should be borne in mind that acromegaly is a rare disease. On the other hand, the strength of our results lies in the fact that we recruited acromegalic subjects with no other serious chronic cardiovascular diseases apart from AH. The duration of hypertension, which was not investigated in detail, might potentially confound the results. Our study mainly involved young and middle-aged patients, and our results should not be extrapolated to the general population. Another limitation of our study is the fact that five subjects with acromegaly were burdened with DM type 2. However, all of them were successfully treated with low doses of oral antidiabetic drugs. Finally, it is worth mentioning that the role of STE in the assessment of LA deformation dynamics is still not well established. This new echocardiographic method was initially developed for LV function assessment and only recently has it been applied to assess LA deformation.Acromegaly, even in young patients with good blood pressure control, may be associated with left ventricular hypertrophy and subclinical impairment of the left ventricular and left atrial mechanical function, which may be identified by speckle-tracking echocardiography. Further research in this area is necessary to clarify the prognostic value of these phenomena.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by The Ethics Committee of the Military Institute of Medicine in Warsaw. The patients/participants provided their written informed consent to participate in this study.BU-Ż conceived the concept of the study. BU-Ż and PK contributed to the study design. BU-Ż, AJ, PW, and GZ organized the database. PK performed the statistical analysis. BU-Ż and PK wrote the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a past co-authorship with one of the authors GZ.


Right ventricular dysfunction impacts the prognosis of various heart diseases. We set-out to examine which right ventricular functional parameters after STEMI and NSTEMI have prognostic value. Of 297 eligible participants, 266 (149 STEMI and 117 NSTEMI) completed follow-up. All patients underwent Grace score and 2D-echocardiography within 24 h. Outcome was defined as occurrence of Major Adverse Cardiovascular events (MACE), such as death, recurrent ischaemia, arrhythmia, reinfarction, stroke or heart failure, within 30 days. Patients were categorized into patients with MACE and patients without MACE.In STEMI-patients, compared to those without MACE, patients with MACE experienced higher grace score, left ventricle (LV) end-systolic volume, LV end-systolic dimension and wall motion score index values, but lower tricuspid annular plane systolic excursion, right ventricle (RV) fractional area change, Tricuspid S’ wave peak systolic velocity and LV ejection fraction. Nevertheless, in NSTEMI-patients, those with MACE exhibited higher left atrial volume index values, but lower tricuspid annular plane systolic excursion, RV fractional area change, S’ wave peak systolic velocity and LVEF. Right ventricular fractional area change < 37.5%, tricuspid annular plane systolic excursion < 15.8 mm and Tricuspid S’ peak systolic velocity < 9.67 cm/s are independent predictors of MACE within first 30 days after STEMI and NSTEMI. Compared to the conclusive data on the role of LV in various heart disease, the available information regarding the RV function and its role in heart diseases particularly acute myocardial infarction (AMI), is limited but outlined its significant contribution . A link The association between right ventricular functional parameters and STEMI –7, but nThis is a prospective non-randomized study. Approval was obtained from hospital ethics committee. Patients who were admitted with AMI to our CCU from April 2014 to December 2016 were eligible to be enrolled. Consent was obtained from eligible participants. Those with co-morbidities such as renal failure, hepatic failure, cor-pulmonale, dilated cardiomyopathy, connective tissue diseases, pulmonary hypertension, pulmonary embolism, previous MI, permanent pacemaker or right ventricular infarction were excluded.Of 297 patients, 266 (89.56%) completed the follow up, of whom 117 (43.98%) had NSTEMI and 149 (56.02%) experienced STEMI. In patients with STEMI, 83 of 149 (55.70%) and 66 of 149 (44.30%) had anterior AMI and inferior AMI, respectively. All participants underwent clinical examination  and blood tests including plasma creatinine, blood glucose, and serum hemoglobin values. Grace risk score was calculated. Echocardiography and tissue Doppler were performed, within the first 24 h of the event, using Vivid 3 . Data acquisition was performed at a depth of 16 cm in the parasternal and apical views using a 3.5-MHz transducer.The LV end-systolic volume (LV ESV) and end-diastolic volume (LV EDV) were assessed by biplane Simpson method from the apical 4- and 2-chamber views tracing the LV endocardial-blood pool interface at end-systole and end-diastole. Echocardiographic measurements were performed by expert blinded operator. LV ejection fraction (LVEF) was calculated (EF = EDV − ESV/EDV), using the biplane Simpson method. Tricuspid annular plane systolic excursion (TAPSE) was measured in the M-mode view, in the RV free wall as total displacement of the RV base from end-diastole to end-systole. RVFAC was obtained by tracing the RV end-diastolic area (RVEDA) and end-systolic area (RVESA) in the apical 4-chamber view using the formula (RVEDA − RVESA)/RVEDA × 100. RV basal diameter is the maximal transverse dimension in the basal one-third of RV inflow at end-diastole in the RV-focused view. Tricuspid S’ peak systolic velocity: pulsed-wave DTI at tricuspid annulus, obtained from the apical approach with parallel alignment of Doppler beam with RV free wall longitudinal excursion. LAVI was performed using the LA areas and lengths through tracing of LA endocardial borders in both the apical four- and two-chamber views. As LAV is dependent on gender, indexing to BSA was performed to abolish confounding.Patients were followed up for 30 days after AMI event and adverse outcome was defined as occurrence any of the major adverse cardiovascular events (MACE) events during the follow up. MACE events include death, hospitalization for recurrent ischemia, reinfarction, hospitalization for heart failure, arrhythmias requiring hospital management, ischemic stroke. Patients were classified into “patients with MACE” group (patients who experienced any of the MACE events within first 30-days period after AMI) and “patients without MACE” group.Statistical methods: The sample size was calculated with margin of error accepted at 5% and a degree of confidence of 95%. The population size was considered infinite and the response distribution was set at 25%. All statistical calculations were performed using SPSS 22. Descriptive data was presented as mean and Standard Deviation (SD). P value < 0.05 was considered significant. Student t-test was used to compare the mean of clinical, laboratory and doppler variables between the groups. Variable which were significant by t-test, were examined as predictors of the outcome, by using univariate regression analysis. This was followed by multivariate logistic regression analysis to determine the independent predictors of the outcome. Receiver operator characteristic analysis was used to determine the cutoff values for TAPSE, RVFAC and S’ peak systolic velocity.In total 266 patients were examined, mean (SD) age 61.19 (7.97) years. Of these 266 individuals, 181 (68%) were male, 79 (29.7%) have diabetes mellitus, 74 (7.2%) were smokers, 66 (24.8%) experienced hypertension and 19 (7.1%) exhibited positive family history of sudden cardiac death. The difference between patients with MACE and those without MACE in terms of clinical and laboratory data, Grace risk assessment score and doppler parameters is illustrated in Tables In these 266 patients, univariate regression analysis showed a significant association between MACE and LVEF, LAVI, TAPSE, RVFAC, S’ wave peak systolic velocity, LV ESV and Grace score (p < 0.05). However, by using multivariate regression, LVEF , TAPSE (p = 0.009), RVFAC (p = 0.012) and S’ wave peak systolic velocity (p = 0.001) remained significant as independent predictor for the adverse outcomes.Of 266 patients, 149 (56.02%) had STEMI and 117 (43.98%) experienced NSTEMI. In those with STEMI, MACE occurred in 51 of 149 (34.22%) patients; arrythmia required admission [7 (4.70%)], hospitalization for recurrent ischemia [5 (3.35%)], recurrent infarction , cardiogenic shock [4 (2.68%)], stroke [2 (1.34%)] and death [23 (15.44%)]. However, in those with NSTEMI, MACE events were reported in 55 of 117 (47%); arrythmia require hospital management [11 (9.4%)], hospitalization for recurrent ischemia [7 (6%)], reinfarction [6 (5.1%)], hospitalization for heart failure [5 (4.3%)], cardiogenic shock [5 (4.3%)] and death [21 (17.9%)].Table The link between MACE events and echocardiography parameters and doppler values was examined. In patients with STEMI, by using univariate regression, MACE was significantly associated with Grace score, TAPSE, S’ wave peak systolic velocity, RVFAC, LVEF, LV ESV, LV ESd and WMSI  . However, by using multivariate regression analysis, only TAPSE, S’ wave peak systolic velocity and RVFAC remained significant . Similarly, in those with NSTEMI, using univariate regression analysis showed that there was a significant association between the adverse outcome and LVEF, TAPSE, RVFAC, S’ wave peak systolic velocity and LAVI , notably this association was not documented with Grace score, LV ESV, LVESd or WMSI . However, by using multivariate regression analysis, LVEF , TAPSE (p = 0.001), RVFAC (p = 0.001) and S’ wave peak systolic velocity (p = 0.008) remained significant as independent predictor for the adverse outcomes.By the end of the first 30 days post AMI, the overall MACE events were noticed in 64.8% of patients who have RV dysfunction (n = 54) (defined as RVFAC < 35%), but only in 33.5% of patients with normal RV function (n = 212) post AMI .Receiver operator characteristic (ROC) analysis was used to examine the cutoff of various variables and their sensitivity and specificity in predicting the adverse outcome. We have noted that the TAPSE cutoff value was 15.8 mm, with area under the curve (AUC) 0.803, 95% CI (0.749–0.859), sensitivity of 79.3% and specificity 75.1%. The cutoff value for RVFAC was 37.5%, with AUC 0.783), 95% CI (0.727–0.839), sensitivity 72.6% and specificity 73.7%. S’ peak systolic velocity cutoff value was 9.67 cm/s, AUC 0.783, 95% CI (0.670–0.797), 73% sensitivity and 65.0% specificity), (Additional file In the current study, we have demonstrated the right ventricular functional parameters within the first 24 h from AMI and their relation to MACE in those presented with STEMI or NSTEMI. In STEMI and NSTEMI patients; a link has been observed between RV dysfunctional parameters such as RVFAC, TAPSE and S’ peak systolic velocity and occurrence of MACE events within the first 30 days after AMI. In patients with STEMI and NSTEMI, individuals with MACE had lower TAPSE, RVFAC, S’ wave peak systolic velocity and LVEF values than those without MACE. However, they experienced higher Grace score, LVESd, LVESV and WMSI values, in patients with STEMI, and higher LAVI values in those with NSTEMI.Emerging evidence suggests that the right ventricular dysfunction is an important predictor of cardiac events and mortality in multiple cardiac diseases , 8. In tIn this cohort of patients, we have found that right ventricular dysfunction occurs in individuals with inferior as well as anterior infarction, in accordance with previous studies , 4, 9. IWe noted a link between MACE event and RV dysfunctional parameters such as RVFAC and TAPSE. Similarly, the association between RVFAC or TAPSE and adverse outcome has been reported in previous study, in patients with AMI . In patiIn this cohort of patients, TAPSE and RVFAC are independent predictors for MACE after STEMI, in accordance with the previous studies , 10. IntCompared to patients without MACE, patients with MACE had lower TAPSE, RVFAC, S’ wave peak systolic velocity and LVEF values, in patients with STEMI and NSTEMI. However, they experienced higher Grace score, LVESV, LVESd and WMSI values in patients with STEMI, and higher LAVI values in those with NSTEMI.In STEMI and NSTEMI patients; RV dysfunctional parameters in terms of RVFAC < 37.5%, TAPSE < 15.8 mm and S’ peak systolic velocity < 9.67 cm/s are independent predictors of MACE events within the first 30 days after AMI. These parameters should be used in clinical settings to identify those with high risk.Single center-based study.Data regarding the invasive catheterization was not available for all patients.Additional file 1: Fig. S1. ROC curve for TAPSE, RVFAC, S’ peak systolic velocity.


The Journal of Innovations in Cardiac Rhythm Management, Donnelly et al. provide a comprehensive review of ventricular arrhythmias arising from the left ventricular papillary muscles and the techniques used for mapping and ablation.1In this issue of When premature ventricular contraction or ventricular tachycardia ablation fails from an endocardial approach, patients are often sent to specialized centers for consideration for epicardial mapping and ablation. Yet, in many instances, the site of origin of the ventricular arrhythmia is as far away from the epicardium as is anatomically possible: the intracavitary structures, specifically the papillary muscles.Figure 1, both papillary muscles are predominantly lateral structures. Further, the moderator band in the right ventricle is a frequent site of ventricular arrhythmia origin and has highly variable size and right ventricular free wall insertion sites.As a field, to both enhance our individual skills and improve procedural success rates, we must return to the basics. Without understanding the beauty and complexity of cardiac anatomy, procedural skills can only reach a certain threshold. For instance, many expect the posteromedial papillary muscle to be septal. However, as can be seen in An in-depth understanding of anatomy doesn’t preclude the need to have technical skill, but, without adequate anatomic knowledge, even the most technically skilled operators will still be at risk for a high rate of procedural failure.Technical failures are sometimes unavoidable, but every effort should be made to ensure cognitive failures do not occur.