The prevalence and prognosis of premature ventricular contractions (PVCs) among individuals without structural heart disease are uncertain. Standard transthoracic echocardiography is a common method in evaluation of underlying cardiovascular disease and is recommended as a diagnostic method in PVC patients. However, it is unclear whether comprehensive echocardiographic examination can identify pathological findings in PVC patients with a normal standard echocardiogram.We included forty consecutive patients with a high PVC burden  and normal findings at a standard echocardiogram and exercise test. All subjects were investigated by a comprehensive echocardiographic examination using parameters usually not included in a routine work-up. We compared the results with 22 age and sex-matched controls.In six additional parameters–global longitudinal strain, right ventricular strain, septal-lateral delay, ventricular-arterial coupling, integrated backscatter and left atrial activation time–a statistically significant difference was shown between PVC patients and controls. Among these parameters, global longitudinal strain had a high reliability between operators.Despite normal findings at standard echocardiography, the PVC group showed signs of impaired heart function when more comprehensive echocardiography parameters were used. All patients had been evaluated at our Arrhythmia Outpatient Clinic by an experienced cardiologist and had undergone exercise test and standard echocardiography between January 2017 and December 2019. All patients had PVC burden established by Holter recording. Exclusion criteria were: previous history of ischemic heart disease, heart failure or other structural heart disease, pathologic result at standard echocardiography or exercise test. The controls were matched on group level for age and sex and were recruited on a voluntary basis.Holter recording was initiated at the hospital and continued at home according to our clinical routine. The data were analysed manually by an experienced physician to ensure accuracy. A normal exercise test was defined as absence of exercise-induced depression of the ST-segment on ECG and absence of exercise-induced ventricular arrhythmia. All patients had a normal age-adjusted exercise capacity.2.1All echocardiographic studies were performed with the patients in the left lateral decubitus position using a commercially available Vivid E9 machine  equipped with a phased array transducer (M5S). A total of 3–5 cardiac cycles in sinus rhythm were recorded. All data were transferred to a dedicated workstation for offline analysis .Normal result at echocardiography was defined as LVEF > 55 % and right ventricular systolic function assessed by tricuspid annular plane systolic excursion (TAPSE) > 17 mm, absence of moderate to severe valve dysfunction, absence of regional wall motion abnormality, normal ventricular dimension, and normal wall thickness. The echocardiographic exams were reviewed by two additional independent and blinded examiners. In case of conflicting evaluations of the echocardiographic findings, the exam was considered normal if two of three examiners assessed the exam as such, and pathologic if two of the three examiners found signs of pathology.Included PVC patients and controls were examined with comprehensive echocardiography, including functional parameters which are not routinely assessed in every echocardiography exam.All the standard echocardiography parameters and Doppler measurements were performed according to the current recommendations LV Global longitudinal strain (GLS) by speckle tracking was calculated from four-, two- and three-chamber apical views. Tracing of the LV endocardium was performed manually, and the thickness of the region of interest (ROI) was adjusted to exclude the papillary muscles and the pericardium. The ROI was also adjusted to exclude the LV outflow tract and the left atrium. Reliable tracking of all myocardial segments throughout the cardiac cycle was confirmed visually. Views were excluded from analysis in case of insufficient tracking.Mechanical dispersion was defined as the standard deviation of time to peak negative strain in 17 LV segments. RV GLS of the free wall and LA strain assessment was performed in concordance to the “How to perform right ventricular strain” paper Ventricular-arterial (VA) coupling was measured as ratio of end-systolic LV volume to Doppler-derived stroke volume .LA activation time was assessed by color-coded tissue Doppler in apical four-chamber view. A fixed ROI of 12 × 5 mm was placed on the lateral LA wall, just above the mitral annulus to acquire the tracing of mechanical activation in this area. The activation time was obtained by measuring the duration of the time delay between the onset of the P-wave on ECG and the peak of the Á -wave on the tissue Doppler tracing. LV diastolic function is assessed according to the latest recommendations from the American Society of Echocardiography and the European Association of Cardiovascular Imaging [15]2.2. Continuous data were checked for normality with Shapiro-Wilk test. If normally distributed, they were compared with t-test; otherwise, they were compared with Mann-Whitney U test. Continuous data are presented as mean ± standard deviation or median and interquartile range (IQR) when appropriate. Nominal data are presented as number of cases (percent).No power calculation was done before inclusion, as this is regarded as a descriptive pilot study. Calculation of mean values was done in Excel . Categorical variables were compared using Chi-squared with Yates’ correction. A two-sided p-value of ≤ 0.05 was considered statistically significantTo determine interobserver variability of the parameters, six PVC patients and ten control subjects were measured by two different investigators, and interclass correlation coefficient for absolute agreement and coefficient of variation were calculated.2.3ClinicalTrials.gov with identifier NCT03370679.The study was approved by the regional ethics committee (DNR 2014/670–31/4) and complied with the Declaration of Helsinki. All participants’ informed consent was obtained in written form. The study is registered at 3A total of 40 patients  and 22 controls  were included. Baseline clinical and echocardiographic characteristics are summarised in 3.1Eleven individuals in the PVC group had a diagnosis of hypertension, and five had paroxysmal atrial fibrillation. However, there was no significant difference in systolic and diastolic blood pressure measured before echocardiography. All participants had a normal systolic LV-function expressed as EF; although, controls had a significantly higher EF. Even E/A ratio was significantly higher in the control group, whereas the median value was above one in both groups.3.2As illustrated in The PVC patients exposed reduced LV elastance  and altered VA-coupling compared to the controls .Integrated Backscatter and LA activation time were also statistically different between the groups. Although, LA mechanical dispersion, LA strain and LA stiffness did not reach the level of significant difference between the groups.Because the PVC group included patients with hypertension and atrial fibrillation we re-ran the analysis for the parameters showing a significant difference after exclusion of such patients. With the exception of LV elastance, all the parameters were confirmed to be significantly different between the two groups.3.3All measurements were not obtained in every patient due to insufficient image quality. LV GLS was obtainable in 29 cases (73 %) and 20 controls (91 %), RV GLS in 27 cases (68 %) and 19 controls (86 %), LA strain in 20 cases (50 %) and 20 controls (91 %), LA stiffness in 20 cases (50 %) and 20 controls (91 %), LV elastance in 39 cases (98 %) and 21 controls (95 %), VA coupling in 39 cases (98 %) and 21 controls (95 %), IBS in 37 cases (93 %) and 21 controls (95 %), LA activation time in 38 cases (95 %) and 21 controls (95 %), and mechanical dispersion in 29 cases (73 %) and 19 controls (91 %).Re-measurements of six to ten randomly selected patients demonstrated a coefficient of variation between 12 and 20 % and inter-class correlation of 0.35 – 0.88 (95 % CI 0.54 ± 0.24), 4In this descriptive pilot study, additional echocardiographic parameters that are commonly not included in routine examination were able to unmask possible signs of subtle myocardial pathology in patients with a high PVC burden and a normal echocardiogram. Evaluation of PVC patients with transthoracic echocardiography (TTE) is recommended in current guidelines and recently published reviews In our study all participants had normal LVEF and RV systolic function (by TAPSE) at standard TTE. When evaluated with GLS, PVC patients showed a significantly lower outcome both for left and right ventricle with a mean LV-GLS of −17.76 %. However, since this value is very close to the conventional cut-off value of −18 %, the clinical value of this difference is debatable and needs further exploration. Speckle tracking-derived GLS is a method for measuring the degree of deformation of the myocardium during the hemodynamic phases and has recently gained ground as a complement to LVEF Functional evaluation in clinical practice has historically tended to focus on systolic ventricular function, as have published studies in the field. However, there is some evidence that PVCs affect diastolic function while systolic function is preserved Ventricular end-systolic elastance is an echocardiographic parameter associated with both systolic and diastolic performance A challenge within echocardiographic diagnostics is to define and secure reproducibility of the measurements, which depends on several factors, including quality of the examination, interpretation of the examiner and biologic variation 4.1No power calculation was done before the study, as it must be regarded as a pilot study. The echocardiographic examinations were carried out by experienced examiners. However, the image quality can be challenging for all measurement, and the calculations were based only on quality secured measurements. As a result some measurements were missing, which prevented us from performing an adequate multivariate analysis.4.2In this study individuals with a high PVC burden and a normal standard echocardiogram showed signs of cardiac dysfunction when evaluated with comprehensive echocardiography. The clinical significance of these findings must be assessed by larger longitudinal studies.5Stiftelsen Hjärta and the Swedish Heart-Lung Foundation (Hjärt-Lungfonden).This study was supported by grants from Stockholm Region, The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RS and KS have no conflict of interest to declare. MR has received consultancy fees from Pfizer, Roche, Zenicor, Medtronic and Janssen. VF has received consultancy fees from Medtronic.


TNNI3 in the proband boy. This case contributes to our understanding of RCM in children and emphasizes the importance of having AEDs available in public places.Restrictive cardiomyopathy (RCM) is a rare form of heart muscle disease with poor prognosis. Its primary manifestations were caused by systemic or pulmonary circulation congestion. Here, we reported a case of RCM with ventricular fibrillation as initial symptom in a 7-year-old boy. The child suffered cardiac and respiratory arrest suddenly while exercising at school and immediately was given external chest compression and defibrillation by the school’s equipped automatic external defibrillator (AED). The rescue was successful. At the time of the AED discharge, his electrocardiogram (ECG) indicated ventricular fibrillation. Upon further examination, the echocardiogram revealed enlarged bilateral atria, decreased diastolic function and normal ventricular thickness. Genetic analysis identified a heterozygous missense mutation  of  Restrictive cardiomyopathy (RCM), a rare type of cardiomyopathy, is characterized by diastolic dysfunction, enlargement of the left atrium or bilateral atria and normal or nearly normal ventricular thickness –3. TypicTNNI3), alpha tropomyosin (TPM1), titin (TTN), and so on (FLNC), αB-crystallin (CRYAB), and desmin (DES) (Genetic and non-genetic factors contribute to RCM. Pathogenic mutations in over 19 different genes related to RCM have been identified . The majnd so on . Mutatioin (DES) –11. HereA 7-year-old boy was admitted to our emergency department after losing consciousness for an hour. The boy suffered a sudden cardiac and respiratory arrest 1 h ago while exercising at school. He was immediately given external chest compression and defibrillation used AED equipped in the school. As a result, his heartbeat and respiration recovered. When the boy was sent to our hospital, he was conscious and agitated which was alleviated by sedation and intracranial pressure reduction. His vital signs were measured: heart rate 124/min; respiratory rate 25/min; blood pressure 102/55 mmHg. On his physical examination, the liver and spleen were not touched under the ribs and there was no edema in the lower limbs. The boy and his parents were in generally good health and other family members denied a history of syncope, sudden death or cardiomyopathy.1 < –0.04 mm⋅s and biphasic P waves, indicating left atrial enlargement and the chest X-ray revealed an enlarged heart shadow. The echocardiogram showed biatrial enlargement, especially in the left atrium , decreased diastolic function , moderate mitral valve regurgitation and left ventricular ejection fraction of 51.8%. Except for bilateral enlargement, cardiac magnetic resonance (CMR) indicated no abnormalities . The electrocardiogram (ECG) revealed Ptf-Vties see . The ECGties see . TroponiTNNI3 which was not detected in his biological parents and de novo G>A,p.R204H] of novo see . This muand LMNA  were notAccording to the results above, we concluded that the boy was a patient of primary RCM. At present, the vital signs of the boy are stable. We communicated with the parents and suggested installing an implantable cardioverter defibrillator (ICD) for the boy, but the parents refused. We have informed his parents that a heart transplant may be required if the disease progresses further. At present, the boy is being treated with oral diuretics and metoprolol tartrate tablets and he is in outpatient follow-up.Restrictive cardiomyopathy (RCM) is the least common phenotype among pediatric heart muscle diseases. Despite accounting for only about 5% of all diagnosed cardiomyopathies, RCM has the worst prognosis. In children, half of all deaths occurred within 2 years after diagnosis and heart transplantation is frequently the only treatment , 3.TNNI3 gene is the first gene identified to be associated with RCM. The gene is a conserved sequence of cardiac troponin I gene, whose mutation can affect the function of troponin (ACTC1), cardiac myosin binding protein C (MYBPC3), β-myosin heavy chain (MYH7), titin (TTN), troponin T (TNNT2), filamin-C (FLNC), αB-crystallin (CRYAB), desmin (DES), etc.  and low late filling velocity (A wave), mitral inflow E/A ratio > 2.5 . Atrial troponin . As resechain MYH, titin (S), etc. , 17–19. Restrictive cardiomyopathy must be distinguished from constrictive pericarditis (CP), for they have several similarities in clinical symptoms and hemodynamic changes. In addition, pediatric patients with sudden malignant ventricular arrhythmia, syncope attack, adams-stokes syndrome or sudden cardiac death should be alert to cardiac ion channel disease, such as long Q-T syndrome (LQTS), brugada syndrome, catecholaminergic polymorphic ventricular tachycardia(CPVT), etc. , 3. The The boy had never felt discomfortable before and his first symptom was ventricular fibrillation which is rare in RCM. Biatrial enlargement and left ventricular stiffness may contribute to the arrhythmias . This caThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Children’s Hospital Affiliated to Nanjing Medical University. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the minor(s)’ legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.LJ edited the manuscript. JC contributed to samples collection. YQ and SY revised the manuscript. All authors contributed to the article and approved the submitted version.


P < 0.001), improved recovery of left-ventricular developed pressure and dP/dt and reduced left-ventricular end-diastolic pressure in hearts subjected to ischemia–reperfusion. Inhibition of RBC NO synthase with L-NAME or soluble guanylyl cyclase (sGC) with ODQ, and inhibition of cardiac protein kinase G (PKG) abolished the cardioprotective effect. Furthermore, the non-selective purinergic P2 receptor antagonist PPADS but not the P1 receptor antagonist 8PT attenuated the cardioprotection induced by RBCs from STEMI patients. The P2Y13 receptor was expressed in RBCs and the cardioprotection was abolished by the P2Y13 receptor antagonist MRS2211. By contrast, perfusion with PPADS, L-NAME, or ODQ prior to RBCs administration failed to block the cardioprotection induced by RBCs from STEMI patients. Administration of RBCs from healthy subjects following pre-incubation with an ATP analog reduced infarct size from 20 ± 6 to 7 ± 2% (P < 0.001), and this effect was abolished by ODQ and MRS2211. This study demonstrates a novel function of RBCs in STEMI patients providing protection against myocardial ischemia–reperfusion injury through the P2Y13 receptor and the NO–sGC–PKG pathway.Red blood cells (RBCs) are suggested to play a role in cardiovascular regulation by exporting nitric oxide (NO) bioactivity and ATP under hypoxia. It remains unknown whether such beneficial effects of RBCs are protective in patients with acute myocardial infarction. We investigated whether RBCs from patients with ST-elevation myocardial infarction (STEMI) protect against myocardial ischemia–reperfusion injury and whether such effect involves NO and purinergic signaling in the RBCs. RBCs from patients with STEMI undergoing primary coronary intervention and healthy controls were administered to isolated rat hearts subjected to global ischemia and reperfusion. Compared to RBCs from healthy controls, RBCs from STEMI patients reduced myocardial infarct size (30 ± 12% RBC healthy vs. 11 ± 5% RBC STEMI patients, The online version contains supplementary material available at 10.1007/s00395-022-00953-4. CollectST-segment elevation myocardial infarction (STEMI) occurs when coronary arteries are occluded following plaque rupture and thrombi formation that prevents supply of oxygen and nutrient-rich blood to the myocardium which results in myocardial ischemia with subsequent myocardial dysfunction and necrosis . Althoug13 receptor-mediated NO–sGC signaling.In this study, we tested the hypothesis that RBCs from STEMI patients protect the heart from ischemia–reperfusion injury through a mechanism that involves the NO–sGC pathway and purinergic signaling. Using well-established ex vivo techniques with RBCs collected from STEMI patients at admission administered to an isolated rat heart model of ischemia–reperfusion, we demonstrate that RBCs from STEMI patients reduce infarct size and improve post-ischemic cardiac function via a mechanism involving purinergic P2YPatients with STEMI (chest pain and ST-elevation of > 1 mV in two contiguous leads) and planned for primary percutaneous coronary intervention (PCI) at Karolinska University Hospital were eligible for inclusion. Patients received double antiplatelet therapy with aspirin (300–500 mg) and either ticagrelor (180 mg) or clopidogrel (600 mg) in the ambulance or immediately on arrival to the catheterization laboratory. PCI was performed according to the local clinical routine. Age- and sex-matched healthy subjects without a history of cardiovascular disease were included as controls.Male Wistar rats were purchased from Charles River Laboratories  and housed in the Biomedicum animal facility of Karolinska Institutet until 10–15 weeks of age for experiments before use.g and + 4 °C for 10 min, plasma and buffy coat including the top layer of RBCs were discarded to isolate RBCs. After three washing cycles with oxygenated Krebs–Henseleit (KH) buffer , purified RBCs were diluted to a hematocrit of ~ 40% with oxygenated (5% CO2 in O2) KH buffer. This procedure results in the removal of 99% of white blood cells and 98% of platelets [2 saturation of ˃99%. In separate experiments, blood collected from healthy subjects was placed in a refrigerator at + 4 °C for 3 h, 6 h, or 24 h before being washed as above. The RBC-KH buffer suspension was used in the isolated cardiac experiment described below. Samples with hemolysis or clots were excluded.Following catheterization of the radial or femoral artery as part of the coronary angiography procedure of the STEMI patients, whole blood was collected in pre-chilled heparin tubes. A first blood sample of 40 ml was collected before starting the coronary intervention, i.e., before reperfusion. An additional sample of 40 ml was collected at the end of the procedure, i.e., after reperfusion. The blood samples were stored at + 4 °C in a refrigerator for up to 6 h before being used in functional experiments (see below). Blood samples from healthy control subjects were collected from an antecubital vein. Following the separation of blood components by centrifugation at 1000latelets  and O2 s2O) at 37 °C [Wistar rats were anesthetized with pentobarbital sodium  and heparinization . The hearts were excised and placed in ice-cold KH buffer. The ascending aorta was then quickly cannulated and perfused with oxygenated KH buffer in a retrograde manner at a constant pressure , the non-selective purinergic P1 receptor antagonist 8-phenyltheophylline , the non-selective purinergic P2 receptor antagonist pyridoxal phosphate-6-azo tetrasodium salt hydrate , or the P2Y13 receptor antagonist MRS2211 . In separate experiments, the isolated rat heart was perfused with KH buffer containing vehicle, L-NAME, ODQ, PPADS or the selective inhibitor of cyclic guanosine monophosphate (cGMP)-dependent protein kinase  for 10 min before ischemia, after which suspension with RBCs from STEMI patients was given to the heart at the onset of ischemia. Suspension with RBCs from healthy controls was incubated as described above with vehicle, the cell-permeable analog of ATP α-β-methylene ATP  or the combination of mATP and ODQ, PPADS or MRS2211. The oxygenated RBC suspension was then given to the isolated Langendorff-perfused heart at the onset of global myocardial ischemia without an additional washing step (see below). In additional experiments, hearts subjected to 10 min of global ischemia were given KH buffer containing cGMP  at the onset of ischemia after which the heart was collected for immunofluorescence (see below). All experiments including pharmacological interventions were performed with the vehicle as control and using RBCs from the same patient. The concentrations used above were based on pilot studies and previous publications [The suspension with RBCs from patients with STEMI was incubated with one of the following for 20 min at 37 °C: vehicle [dimethyl sulfoxide, (DMSO) 5 µmol Litor 1H-  oxadiazoications , 35, 44.Global ischemia was induced by clamping the inflow tube, and 3 ml of RBC-KH suspension was administered to the heart via a sidearm connected to the ascending aorta at the onset of ischemia. The duration of global ischemia was 25 min, and during this period, the pre-incubated RBCs were present in the coronary circulation. Reperfusion, which rinsed away the RBCs, was initiated by releasing the clamp and was maintained for 60 min. Previous detailed investigations have revealed that human RBCs can be administered to the isolated rat heart without affecting cardiac functional recovery per se , 45.At the end of reperfusion, hearts were frozen at − 20 °C and sectioned into 1 mm-thick slices from the apex to the base, stained with triphenyltetrazolium chloride for 15 min, and fixed in 4% formaldehyde for 18 h. Necrotic negatively stained myocardium was measured using Adobe Photoshop Elements 2019 Edition by an investigator blinded to group allocation [13 receptor, isolated RBCs (1%) were incubated on glass coverslips overnight at 37ºC in Roswell Park Memorial Institute Medium (RPMI) as described elsewhere [13 , a rabbit polyclonal anti-P2Y13 , or with a proper matched control , followed by incubation with the secondary antibody Alexa-Fluor™ 488-conjugated goat anti-rabbit  at room temperature for 1 h.For the detection of P2Ylsewhere . RBCs we® plus; Thermo Fisher Scientific, Waltham, MA, USA). At least 12 slides containing ~ 4 tissue cross-Sects. (5 μm thick) from each animal were examined. Sections were deparaffinized in xylene and rehydrated in graded ethanol. For antigen retrieval, slides were subjected to high-pressure boiling in citrate buffer (pH 6.0). Heart cross-sections were permeabilized with 0.3% Triton X-100 for 10 min, blockade with goat serum , and incubated overnight (+ 4 °C) with the following primary antibodies: a rabbit polyclonal anti-phosphorylated vasodilator-stimulated phosphoprotein (pVASP)  and a mouse monoclonal anti-sarcomeric alpha-actinin antibody . Specific labeling was detected with an Alexa-Fluor™ 488 goat anti-rabbit  or an Alexa-Fluor™ 594 goat anti-mouse , respectively. Cell nuclei were counterstained with Hoechst dye . To confirm the specificity of antibodies, isotype controls were used as negative controls . Fields were captured with the fluorescence microscope equipped with an × 40 objective lens and an × 10 eyepiece , digitized, and analyzed .For the detection of PKG-dependent phosphorylation of vasodilator-stimulated phosphoprotein (pVASP), Langendorff-perfused rat hearts were collected after 30 min of stabilization and 10 min of ischemia followed by 1 min of reperfusion. The hearts were then perfused with 4% formaldehyde and fixed for 24 h at room temperature, dehydrated in graded ethanol , embedded in paraffin, sectioned using a microtome, and mounted on coated glass slides . Data are unless otherwise stated presented as mean ± standard deviation (SD). Infarct size is presented as mean ± SD and individual data points. P < 0.05 was considered as statistically significant.LVDP and dP/dt are presented as the percentage of recovery during reperfusion from baseline levels. LVEDP is expressed in absolute value. Normal distribution of data was analyzed using D’Agostino and Pearson normality test. Differences between two groups were analyzed by paired or unpaired Student’s Study subject characteristics are shown in Table Baseline pre-ischemic cardiac function and heart rate of all the isolated rat hearts are shown in Supplementary Table 1.First, we investigated the functional role of RBCs from patients with STEMI on cardiac post-ischemic functional recovery and infarct size. Administration of RBCs from patients with STEMI in Langendorff-perfused rat hearts significantly improved post-ischemic recovery of LVDP Fig. a and dP/Next, we investigated the mechanisms by which RBCs from STEMI patients improve cardiac post-ischemic recovery. To test whether the protective effect involves the NO–sGC pathway, RBCs from STEMI patients were pre-incubated with the NOS inhibitor L-NAME before being given to the isolated heart. L-NAME significantly attenuated the improvement in post-ischemic recovery induced by RBCs from STEMI patients and increased infarct size Fig. a, b. In 13 receptor is expressed in human RBCs [13 receptor is abundantly expressed in RBCs from STEMI patients and healthy controls  on recovery of left ventricular developed pressure (LVDP) in isolated rat hearts subjected to global ischemia-reperfusion. Recovery of LVDP in heart following administration of red blood cells (RBCs) from STEMI patients (STEMI RBC) (a) before (n=35) or after (n=25) reperfusion; (b) with (n=16), or without (n=19) hypertension; (c) with (n=8), or without (n=27) type 2 diabetes (T2D); (d) with (n=5), or without (n=30) dyslipidemia compared to that in heart given RBCs from healthy controls (H RBC) (n=23). Post-ischemic LVDP is presented as percentage recovery from baseline. Data are presented as mean ± SD. Statistical differences were analyzed with 2-way ANOVA including all time points (JPG 2694 KB)Supplementary file2 Fig. 2 Effect of baseline medication on recovery of LVDP in isolated rat hearts subjected to global ischemia-reperfusion. Recovery of LVDP following administration of RBCs from STEMI patients (STEMI RBC) treated (a) with ticagrelor (n=28) and clopidogrel (n=7); (b) with (n=14) or without (n=21) angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB); (c) with (n=7) or without (n=28) calcium channel inhibitor . Post-ischemic LVDP is presented as percentage recovery from baseline. Data are presented as mean ± SD. Statistical differences were analyzed with 2-way ANOVA including all time points (JPG 2357 KB)Supplementary file3 Fig. 3 Effect of duration between RBCs collection and experimental determination of recovery of LVDP in isolated hearts subjected to global ischemia-reperfusion. Recovery of LVDP following administration of RBCs from healthy subjects (H RBC) after placing for 3 h (n=7), 6 h (n=8) or 24 h (n=7) at +4°C. Post-ischemic LVDP is presented as percentage recovery from baseline. Data are presented as mean ± SD. Statistical differences were analyzed with 2-way ANOVA including all time points (JPG 655 KB)Supplementary file4 Fig. 4 Post-ischemic recovery of LVDP in hearts perfused (p) with vehicle (n=7), L-NAME (n=6) or ODQ (n=6) in KH buffer prior to administration of RBCs from STEMI patients. Post-ischemic LVDP is presented as percentage recovery from baseline. Data are presented as mean ± SD (JPG 716 KB)Supplementary file5 Fig. 5 Post-ischemic recovery of LVDP in hearts given RBCs from healthy subjects (H RBC) that were incubated with (a) L-NAME (n=6), (b) ODQ (n=5) or (c) KT5823 (n=6). Post-ischemic recovery of LVDP in hearts (d) perfused with KT5823 (n=5) prior to administration of RBCs from healthy subjects. Post-ischemic LVDP is presented as percentage recovery from baseline. Data are presented as mean ± SD (JPG 2503 KB)Supplementary file6 Representative immunofluorescence images showing P2Y13 receptor expression in RBCs from four different (a) patients with STEMI and (b) healthy subjects. Immunoreactivity was visualized using Alexa FluorTM 488 antibody  (JPG 2628 KB)Supplementary file7 Post-ischemic recovery of LVDP in heart perfused (p) with vehicle (n=7) or PPADS (n=6) in KH buffer prior to administration of RBCs from STEMI patients (STEMI RBC). Post-ischemic LVDP is presented as percentage recovery from baseline. Data are presented as mean ± SD (JPG 659 KB)Supplementary file8 Fig. 8 Post-ischemic recovery of LVDP in hearts given RBCs from healthy subjects (H RBC) that were incubated with (a) PPADS (n=5) or (b) MRS2211 (n=5). Post-ischemic LVDP is presented as percentage recovery from baseline. Data are presented as mean ± SD (JPG 1271 KB)Supplementary file9 (DOCX 17 KB)Below is the link to the electronic supplementary material.


First aid is to give immediate first aid to patients who have suffered accidental injuries or sudden diseases before the emergency medical personnel arrive at the scene or are sent to the hospital for treatment; myocardial infarction is a severe and emergency of coronary heart disease. It is often because of coronary atherosclerosis, plaque rupture, bleeding, or thrombosis, which leads to the acute and complete occlusion of the coronary arteries and acute necrosis of the myocardium. This article aims to investigate the effectiveness of a stratified emergency care team assisted by multidisciplinary first aid knowledge in acute myocardial infarction first aid, hoping to reduce the probability of acute myocardial infarction through first aid and nursing care. Business process reengineering is a management idea that reached its heyday in the 1990s and is usually defined as achieving workflow and productivity through the reorganization and optimization of corporate strategies, value-added operational processes, and the systems, policies, organizations, and structures that support them. This article first outlines the concepts and steps of medical image registration, analyzes the characteristics of current medical image registration methods, and uses the two most commonly used medical registration methods today; in this study, the BPR theory was used to construct the AMI emergency care process in the hospital, which effectively reduced the emergency delay time of AMI patients, improved the patient's emergency response, and increased the efficiency of emergency nurses' rescue work. The experimental results in this paper show that the sensitivities of the first four groups of ST↑III > II, ST ↓ aVL > I, STV3 ↓ /STIII↑≤1.2, STI ↓ ≥0.05 mV are 82.1%, 80%, 75.3%, and 60.3%, respectively. Their sensitivities are relatively close, both are greater than 50%; among them, ST↑III > II has the highest sensitivity, which is 80%. In terms of specificity, ST↑III > II, ST ↓ aVL > I, STV3 ↓ /STIII↑≤1.2, and STI ↓ ≥0.05 mV were 82.1%, 89.2%, 82.7%, and 65.2%, respectively. ST ↓ ≥0.05 mV has the lowest specificity, and ST ↓ aVL > I has the highest specificity. Myocardial infarction is one of the most fatal and disabling diseases with the highest risk; so, its greatest harm can be said to be death. Myocardial infarction, also called myocardial infarction, is mainly caused by partial necrosis of myocardium due to ischemia caused by interruption of blood flow. Due to the continuous development of the economy, the pace of life is getting faster and faster, and the pressure of life is getting heavier. Overwork has become a common phenomenon nowadays. Excessive exertion brings about an increase in myocardial oxygen consumption, plaque rupture, and myocardial infarction. In recent years, there have been more and more cases of myocardial infarction, and the age of the onset group is getting younger and younger. The continuous enhancement of these characteristics requires that we urgently need to find an effective way to reduce the mortality rate of acute myocardial infarction. With the improvement of people's living standards and people's attention to improving the quality of life, the mastery of first aid knowledge has become a new trend at the moment. If the patient can be treated with emergency treatment in time, this can save the patient's life to a large extent and delay the deterioration of the condition. In particular, for sudden heart diseases such as acute myocardial infarction, if effective first aid can be given in time, doctors can be left with time for rescue. Therefore, combining the stratified emergency care team assisted by the knowledge of the department and the acute myocardial infarction first aid will have a huge effect on patients with acute myocardial infarction, thereby reducing the mortality rate. Myocardial infarction is one of the most common diseases that endanger human health. The World Health Organization pointed out that in the past few decades, the understanding of myocardial infarction has been continuously deepened, and the mortality rate under treatment has decreased significantly, with the mortality rate of hospitalized patients reaching 11.9%. Although some progress has been made in myocardial infarction in recent years, many detection techniques are only adapted to a certain stage. Combining the stratified first-aid care team assisted by the knowledge of departmental first aid and acute myocardial infarction first aid is of great practical significance for improving survival and treatment. Advances in diagnostic techniques, its electrocardiogram, are currently developed from surface electrocardiograms to intracardiac electrophysiological electrograms. Intravascular ultrasonography can also be done to determine the type of thrombus and the condition of the lesion.n = 16) and non-STEMI (NSTEMI) (n = 16) subtypes were associated. Similar to other studies, 9565 expressed transcripts were detected, including several known platelet-rich markers (such as PPBP and OST4). RNA-seq data is closely related to independently determined platelet expression data. It also shows the enrichment of platelet-related pathways , as well as actin-related and posttranscriptional processes [μg/m3 increase in PM2.5 concentration (with a lag of 1 day) is associated with an increase in the risk of EDV [n = 35) and group B (n = 25). The 12-lead ECG timing teletransmission system was sent to the chest pain center before the patients in group A were transferred to the hospital, while the patients in group B did not. The median time from door to balloon in group A was significantly shorter than that in group B . The median length of hospital stay in group A was significantly shorter . Experiments have proved that the 12-lead ECG real-time remote transmission system is beneficial to the prehospital diagnosis of STEMI [The implementation of full-time stratified nursing can effectively improve the quality of nursing. After systematic training, the nursing staff can effectively improve their first aid skills and can accurately judge the changes in the condition and implement rescue measures. Although some progress has been made in myocardial infarction in recent years, many detection techniques are only adapted to a certain stage. Therefore, the combination of the stratified emergency care team assisted by the knowledge of departmental first aid in the first aid of acute myocardial infarction is still the current research focus. Noris et al. studied isolated spontaneous platelet aggregation (SPA) in platelet-rich plasma from 37 patients with acute myocardial infarction. It occurs in subjects who receive heparin after streptokinase therapy and rarely occurs in patients who have not received streptokinase or heparin therapy and in patients who have received streptokinase therapy alone. Research on patients receiving heparin therapy for deep vein thrombosis suggests that SPA may come from adenosine diphosphate released by platelets during sample processing. Therefore, Noris P suggested that heparin infusion may promote platelet activation in vitro, and this mechanism is effective in patients with acute myocardial infarction receiving thrombolytic therapy . Eicher rocesses . Shah etN + n regional collaborative rapid treatment system established by multiple PCI hospitals as the core. In this study, many hospitals are covered, and the geographical scope is very broad, allowing a more comprehensive analysis of acute myocardial infarction.At present, most of the research on the emergency system is a single center; in short, it is a research on a regional collaborative rapid treatment system with a PCI hospital as the core . TherefoWith the continuous development of the economy and the increasing aging, cardiovascular disease has become one of the major causes of mortality. According to WHO statistics, there are currently about 500 million people suffering from cardiovascular diseases in the world, while more than 300 million people in China . This daAcute myocardial infarction is an acute myocardial ischemic heart disease, including ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction . The maiIn order to obtain the image information of myocardial infarction, data collection of the entire image is required. Connect each point of the image to make the diagnosis information more accurate . Define a, b) represents the floating image point. where  represents the gray value of the target point, g represents the displacement function of the image, and y represents the change function of the pixel value. The premise of pixel value transformation is spatial transformation, but this transformation does not occur under any circumstances. The main job of parameter conversion is to determine the coincidence point. Coincidence point refers to a large point (or control point of each level) that has coordinates of two coordinate systems at the same time. In the formal image space conversion, we need to determine the conversion process, especially the parameter conversion. Find the corresponding relationship between the parameters, and the main operation process is shown in Projection transformation is the process of transforming the coordinates of one map projection point into the coordinates of another map projection point. Research the theory and method of coordinate transformation of projected point. The transformation of the search space includes global transformation, local transformation, and semilocal transformation. The semilocal transformation can be divided into rigid body transformation, affine transformation, projection transformation, and nonlinear transformation , 21. Theα represents the strain of the rigid body transformation, Qa represents the rotation angle, and Qb represents the displacement that occurs in the horizontal and vertical directions.Affine transformation, also known as affine mapping, means that in geometry, a vector space is transformed into another vector space by performing a linear transformation followed by a translation. The affine transformation is converted from the rigid body transformation. It adds scaling and miscutting on the basis of rotation and translation. All in all, two degrees of freedom are added on the basis of rigid body transformation . The funs11, s12, s21, s22, Qa, Qb represents the parameter change point, which can be determined by three points on any straight line.The biggest feature of projection transformation is that it can convert straight lines into straight lines, but it cannot keep it balanced. This application is more common in registration between multi-dimensional images . The funThe degrees of freedom of projection transformation include rotation, shearing, scaling, and translation, which can be determined by any three points that are not collinear. Linear transformation uses polynomial functions to map straight lines into straight lines . NonlineThe thin plate spline is obtained by the researchers through the results of scattered data, and it is also one of the most used methods in medical imaging. Thin-plate spline interpolation is a kind of interpolation method and is a commonly used 2D interpolation method. The function expression is as follows:Among them,e2 represents the stiffness parameter. When e2 is close to zero, the load is close to the point load. When e2 shows an increasing trend, the load becomes smoother. Loads refer to external forces and other factors that cause internal forces and deformations of structures or components or conventionally refer to various direct actions that are applied to engineering structures to produce effects on engineering structures or components. When the load is zero, the thin plate is in a stable state, so that the surface will not rotate. Solve the equations to get the coefficients, and the thin plate can undergo arbitrary deformation at the mark definition point . (10)A=AA represents the area of the image. V. Among them, Sn represents the basis function of the n-th S-spline.where In information theory, mutual information can be used to express the size and relevance of the amount of information in the system. The function expression is as follows:C and D represent two images, Ec, Ed represents the probability distribution, and Ecd represents the joint probability distribution. Among them, U represents normalized information, C and D represent two images, and C, D represents the gray value of the image at point . Among them, c ∈ C, d ∈ D, ec(c), ed(d) represents the independent distribution probability of the system, ecd represents the joint distribution probability, L(C), L(D) represents the entropy of C and D, and L represents the joint entropy.Among them, According to the survey of relevant data, if the heart stops beating within 4 minutes and effective first aid can be obtained, the patient has a half chance of surviving. Once rescue is carried out after 10 minutes, the probability of survival of the patient is very small, less than 1% . TherefoAt present, the teaching of first aid knowledge in China is basically based on textbooks. However, these teaching methods cannot simulate the real situation and cannot create a sense of crisis in the first aid scene; so, the teaching effect is not very good . The emeThe most common feature of patients with acute myocardial infarction is chest pain, and coronary stenting can effectively alleviate this condition. However, there are still many problems in the care of acute myocardial infarction in China. The common ones are unclear division of labor, chaotic emergency scenes, error-prone, and waste of resources. Through literature research, the nursing process in medical institutions in Western countries is divided into three categories: cardiovascular care, chest pain emergency care, and emergency care. It does not treat acute myocardial infarction as a major prescribed nursing process. In the first aid part of the hospital management process, the value specifies information such as the emergency environment, patient evaluation, and clinical records . HoweverNursing of acute myocardial infarction is very important and affects the prognosis of patients. General routine nursing measures include observing the patient's condition, finding out the discomfort in time, and assisting the patient to take medicine, eat, drink water, and defecate. The current nursing process for acute myocardial infarction is still in the development stage. The subject of inquiry lacks pertinence, which is not much different from the ordinary nursing process, and the process is not detailed enough. For example, the establishment of full-time nurses in the emergency department and systematic training of nurses can improve the nursing ability of acute myocardial infarction, which indeed improves the nursing level of acute myocardial infarction to a certain extent, but the complete nursing process has not yet been implemented. In view of these conditions, it is not difficult to find that the current acute myocardial infarction care process lacks specificity and cannot adapt to acute myocardial infarction emergency care; nursing responsibilities cannot be fulfilled, reliance on experience is strong, and resources are wasted; the model is outdated and cannot keep up with the development of chest pain centers , 32.According to the definition of acute myocardial infarction, the subjects of this investigation need to have the following characteristics: myocardial loss or ventricular wall displacement phenomenon, abnormal troponin detection, presenting symptoms of acute myocardial ischemia, coronary angiography,; and coronary thrombosis . The ageAccording to the data in According to the data in According to the data in According to the data in According to the data in According to the data in In a controlled experiment on changes in left ventricular ejection fraction of patients with acute myocardial infarction, there was no significant difference between the two groups of patients before the intervention. After two months of intervention, no recovery advantage was seen. At the third month of the intervention, the ejection fraction of the control group was 51, while the ejection fraction of the experimental group was 64. The recovery status of the experimental group was significantly better than that of the control group.According to the data in Cardiac enzymes are a general term for a variety of enzymes present in the myocardium, including aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase isoenzymes. According to the data in According to the data in First aid is the meaning of emergency treatment, which means that when any accident or emergency occurs, the rescuer, before the arrival of the medical staff, according to the principle of medical care, temporarily and appropriately conducts preliminary rescue and treatment for the wounded and sick by using the materials available on site. In the context of medical treatment, this article is combined with the current developing economy. The purpose is to study the effect of a stratified emergency care team assisted by multidisciplinary first aid knowledge in the first aid of acute myocardial infarction, hoping to reduce the probability of acute myocardial infarction through first aid and nursing. In this paper, the BPR theory is used to construct the AMI emergency care process in the hospital, which effectively reduces the emergency delay time of AMI patients, improves the patient's emergency response, and improves the efficiency of emergency nurses' rescue work. Overall, the following tasks are mainly completed: (1) the calculation knowledge of medical image registration is introduced, its evolution process is introduced in detail, and the image conversion process is briefly explained. (2) The relevant knowledge of emergency medicine was collected and sorted, and the necessary database was established to save time for the emergency process. (3) After measuring the energy consumption of the preliminary plan, the exercise rehabilitation plan for patients after acute myocardial infarction is finally formed, which provides a blueprint for the timely rehabilitation of patients.


In the pooled population, by adjusting for systolic blood pressure, GLS, E/e’ ratio and left atrial volume index, age was independently associated with GCW (β = 0.748) and GWI (β = 0.685) (both p < 0.0001) and HR with GWW  and GWE . Conclusions: In healthy subjects age shows a mild influence on GCW. HR exerts an independent negative impact on GWW and GWE: the higher HR the greater wasted work and lower myocardial efficiency.Background: The influence of age and gender on strain-imaging-derived myocardial work (MW) was recently investigated in healthy subjects. No information is available on the impact of heart rate (HR) on MW. Methods: 177 healthy subjects  underwent an echo-Doppler exam, including quantification of global longitudinal strain (GLS). Cuff blood pressure was used as a surrogate of left ventricular peak pressure to estimate global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). Statistical analyses were performed according to age and HR tertiles. Results: GWW was higher in the third HR tertile, i.e., ≥74 bpm (74.7 ± 33.6 mmHg %) than in the first HR tertile (<66 bpm) (61.0 ± 32.5 mmHg %) ( The progressive advancement of cardiac ultrasound has led to large clinical use of two-dimensional 2D) speckle tracking echocardiography (STE). Global longitudinal strain (GLS), in particular, allows quantifying the degree of left ventricular (LV) longitudinal dysfunction beyond ejection fraction (EF). The utilization of GLS is promoted by the echocardiographic scientific societies ,2, also D speckleMore recently, according to the assumption that the invasively determined LV pressure–volume loop reflects stroke work ,10,11,12Determinants of MW and its components in healthy subjects have already been investigated by the multicenter EACVI NORRE Study. It provided evidence on the absence of a strong influence of age and sex on MW and also highlighted the association of both global work index (GWI) and GCW with systolic BP . The pre2), and smoke habit. Sinus tachycardia (HR > 100 bpm) and age < 18 years were the main exclusion criteria. Subjects with a history of coronary artery disease and previous acute myocardial infarction, stroke, transient ischemic events, more than mild valvular heart diseases, congestive heart failure, primary cardiomyopathies, congenital heart diseases, systemic diseases, active or previous history of cancer, pharmacological therapies, any kind of resting electrocardiographic abnormalities and echocardiograms of poor quality, were also excluded.The study population included 177 consecutive healthy adult subjects, prospectively recruited on a voluntary basis from January to December 2018. The informed consent of each participant was collected. No subject had cardiovascular risk factors, such as arterial hypertension (BP > 140/90 mmHg), dyslipidemia , diabetes mellitus (fasting glycaemia > 100 mg/dL), obesity . By using this software and according to standardized procedures , cuff syThe patient-specific LV pressure curve is built by adjusting the standard LV pressure curve to the duration of isovolumic and ejection phases defined by the timing of valvular events (marked by previously recorded Doppler imaging) B. StrainOn the other hand, wasted work (mmHg %) computed as the sum of the energy spent for the lengthening in systole and shortening in isovolumic relaxation, correspond to energy loss spent during ineffective work expressed by the formula:The ratio between the constructive work and the sum of constructive and wasted work represents myocardial work efficiency (%):Global values are obtained as averages from all segmental values of MW parameters, including GWI, GCW, GWW, and GWE.2 distribution with computation of exact p value by the Monte Carlo method. Participants were divided into tertiles of age and HR, and analyses were performed by using post-hoc inter-group Bonferroni test. Correlation between continuous variables was tested by Pearson’s correlation coefficient. Multivariable linear regression analyses were performed to examine the independent correlates between MW components and both demographic and echocardiographic variables. Collinearity was considered acceptable and regression model stable for variance inflation factor less than 3. Reproducibility tests of chosen variables (MW work components) were determined by measuring average intra-class correlation coefficients (ICC) and their 95% confidence intervals (CI). Average ICC > 0.80 were considered to be optimal. The null hypothesis was rejected at two-tailed p < 0.05.All statistical analyses were performed by the SPSS software, release 12 . The normal distribution of continuous variables was tested by the Kolmogorov–Smirnov test. All data were expressed as mean ± standard deviation (SD). Descriptive statistics were obtained by one factor ANOVA and χp = 0.10), GCW , GWW  and GWE . The univariate analyses showed the following significant relations: age with GCW , systolic BP with GWI , GCW  and GWW , diastolic BP with GWI (r = 0.33) and GCW (r = 0.34) (both p < 0.0001), HR with GWW  and GWE . GWI was also related with E/e’ ratio  and left atrial volume index , GCW with EF , E/e’ ratio  and left atrial volume index . ( 0.005). .p < 0.01), whereas GWW and GWE did not differ among the three tertiles. According to HR tertiles, subjects with HR ≥ 74 bpm had higher GWW than subjects with HR < 66 bpm (p < 0.02). The impact of age and HR on MW parameters are represented in the explicatory clinical case comparison in p > 0.01).p < 0.0001). The interobserver ICC were: GLS = 0.92 (95% CI = 0.73–0.97), GWI = 0.93 (95% CI = 0.78–0.98), GCW = 0.95 (95% CI = 0.84–0.98), GWW = 0.94 (95% CI = 0.82–0.98), GWE = 0.89 (95% CI = 0.68–0.97) .By testing the MW components reproducibility in a subgroup of 30 healthy subjects, the Intra-observer ICC were the following: GLS = 0.97 (95% CI = 0.92–0.99), GWI = 0.95 (95% CI = 0.86–0.98), GCW = 0.99 (95% CI = 0.99–1.00), GWW = 0.97 (95% CI = 0.89–0.99), GWE = 0.95 (95% CI = 0.84–0.98) . This data is in line with results provided from the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study which included 4965 participants aged 30–79 years. The authors found that GCW, GWW, and GWE were not affected by sex, BMI and age below the 45 years, whereas linear increase with GWW was evident above the age cut-off The concept that myocardial oxygen consumption increases and myocardial efficiency decreases with the heart beat increase is well known. To the best of our knowledge, the present study is the first to confirm the significant impact of HR on some MW components, i.e., GWI, GWW and GWE by applying the non-invasive, strain-imaging-derived technology. In particular, GWW was substantially increased in the third HR tertile (HR ≥ 74 bpm) and HR was positively and independently associated with GWW in the pooled population. Although the myocardial efficiency was not significantly reduced in the third HR tertile, in the multiple regression analyses HR was also inversely associated with GWE, which is indirectly derived from the ratio of GCW and GWW . Of inteThe main limitation is intrinsic to the utilized methodology which replaces central (aortic) with cuff BP. Systolic BP varies throughout the arterial tree and cuff systolic BP is slightly overestimated in comparison with the corresponding brachial BP, with a variable inter-individual disparity ,33. The This is a study performed on a series of healthy individuals and the results cannot be transferred to patients with cardiac diseases. GWW is only a small fraction of global MW and the impact of its HR-related changes does not appear to be clinically relevant on myocardial efficiency of our healthy population. Accordingly, the study of relationships between HR and MW components needs to be extended to the spectrum of pathologic conditions, in particular heart failure and coronary artery disease. Moreover, the data of the present study refers to a relatively small sample size of the healthy population, with a limited number of elderly subjects, collected in a single-center enrollment and should be therefore extended to larger populations. The exclusion of subjects with sinus tachycardia, a pre-defined requirement for recruitment, can also have influenced the statistical impact of HR in the analyses performed. Accordingly, while the cumulative R2 of the multivariable models assessing GWI and GCW explained a large variance proportion (79 and 85% respectively), the cumulative R2 of GWW and GWE models were relatively small (0.18 and 0.16 respectively). It is likely that other covariates—not investigated in the present study—could exert additional influence on MW components.Elevated HR at rest is a well-known indicator of cardiovascular outcome in heart failure with reduced EF . One-beaThe current investigation provides evidence that HR, and to a lesser extent age, should be considered when assessing strain-imaging-derived MW in the human heart. In particular, failure to adjust for HR may lead to inappropriate interpretation of MW data obtained. Further studies could be addressed to evaluate the effects of cardiac drugs producing changes of both BP and HR on MW and demonstrate possible reflections of these changes on the therapeutic management of cardiac patients.


During acute myocardial infarction (AMI), the electrophysiological changes are clearly visible on the 12-lead electrocardiogram (ECG), and are as such, an important diagnostic tool in human cardiology. Similar to humans, changes are seen on the ECG in both pigs and dogs, but so far, this has not been studied in horses, despite equine cardiology being a growing field. This study aimed to investigate the ECG changes seen with a 12-lead ECG in a horse with induced myocardial infarction. The ECG changes observed in this case report were comparable to other species with AMI and showed similar patterns throughout the different phases of occlusion. The results could, therefore, indicate that a 12-lead ECG can be used to detect signs of ischemic heart disease, such as AMI, in horses, while they also potentially elucidate certain translational connections between human and veterinary medicine.During acute myocardial infarction (AMI), the ischemia and necrosis of the infarcted tissue result in local electrophysiological changes, which bring about deviations of the ST segment and T wave. In this case report, the aim was to investigate whether these changes could be detected with a 12-lead electrocardiogram (ECG) during acute occlusion of the coronary artery in a 15-year-old Standardbred mare . The left anterior descending (LAD) coronary artery was occluded using an angioplasty balloon catheter guided through the carotid artery. Two coronary occlusions of 30 min were induced, separated by a 10-min reperfusion phase. AMI led to ST deviations and T-wave amplitude changes . The ST segment almost returned to the baseline during the reperfusion phase. The ECG changes seen after the infarction were comparable to those reported in other species with AMI, suggesting that the 12-lead-ECG can potentially be used to detect signs of myocardial infarction in horses. In human medicine, the 12-lead electrocardiogram (ECG) is an important diagnostic tool for the detection of arrhythmias, cardiac hypertrophy and myocardial infarction (MI) . Acute tIn equine medicine, ECG recordings are generally used to detect arrhythmias, and often only one to three leads is used . RecentlA 15-year-old Standardbred mare was scheduled for euthanasia  and included in this study. Before including this horse in the study, a full clinical examination, blood sample and resting ECG were performed. The horse was sedated and anesthetized as previously described and placed in dorsal recumbency ; the horDuring the procedure, a 12-lead ECG , with the electrodes placed according to the recently published 12-lead method, the “Copenhagen method”  Figure A, was reThe sum of ST deviations (STD) at the baseline was 0.35 mV, and two minutes following the first occlusion, clear ST deviations were visible with a sum of 1.19 mV. During reperfusion, the ST deviations returned to the baseline with a sum of 0.31 mV. Two minutes into the second occlusion, an even more pronounced STD of 1.98 mV was observed . The ST-The baseline sum of the T-wave amplitude was 6.58 mV, and two minutes into the first occlusion, the sum was 9.25 mV. Five minutes after the reperfusion, the sum of the T-wave amplitude changes was 9.50 mV, and two minutes into the second occlusion, the sum was 9.65 mV .During the reperfusion phase, after the second occlusion, the horse developed ventricular fibrillation and asystole while under anesthesia. Post-mortem examination of the heart confirmed occlusion of the proximal LAD.In this study, we showed that acute occlusion of a coronary vessel and subsequent transmural AMI in a horse resulted in ST deviation changes in anatomically related ECG leads.Research on equine myocardial infarction (MI) is very limited , and to During transmural AMI, diastolic injury currents and increased extracellular potassium concentrations lead to ST elevation and high T-wave amplitudes . BipolarIn our study, the ST segment was elevated in leads II, III and aVF, while ST-segment depression was seen in V3 and V4. The positions of the ECG leads when using the Copenhagen method resulted in coverage of the LAD perfused area, mainly by leads II, III and aVF. In humans, these leads face the inferior parts of the heart (diaphragmatic surface mainly formed by the right ventricle) and are largely used in diagnostics for occlusion of the right coronary artery [In horses, the precordial leads are placed around the chest to cover all chambers of the heart. The altered lead positioning, and distance from the electrodes to the heart and thickness of the equine myocardium, may lead to findings other than those expected based on human procedures . In thisIn humans, the precordial ECG leads are placed close together on the chest to provide good anatomical coverage of the anterior, left-lateral and segmental wall segments . The posterior wall and right-sided segments are clearly underrepresented, and transmural AMI in these regions is often only diagnosed indirectly by ST depression in the leads facing away .In human cardiology, an ST-segment change of at least >0.1 mV in two adjacent leads is diagnostic for AMI . In thisThe ST-segment changes and their dynamics were similar to those in other species with induced AMI . The T-wDetection of myocardial damage depends not only on the electrode position but also on factors such as the distance from the damaged tissue, intervening structures and the strength of a wavefront, which will influence the electrocardiographic appearance and are thus considered limitations that impact the utility of the technique. To support the ECG findings and provide a deeper understanding of the myocardial tissue damage, measurements of biomarkers such as troponin could have been taken. Furthermore, a thorough postmortem examination of the horse including the use of histopathology could have provided more valuable information on specific tissue damage in the myocardial area vascularized by the LAD. It is worthy of note that the size of the infarct made in this case study was large, and therefore, was expected to result in different and probably more severe electrocardiographic findings compared to clinical cases. The study setup in this case report did not allow for a possible clinical evaluation of the horse following the AMI.The results of this study demonstrate that AMI of the magnitude induced can be detected with a body-surface ECG with the lead placement used here. The difference in the leads suggests that the infarcted area could potentially be located and diagnosed in horses using the 12-lead Copenhagen method for ECG. As the horse did not recover from anesthesia, the long-term effect of myocardial infarction on the horse could not be studied. Since only one horse was included in this case study, whether the ECG changes apply to all horses still needs further investigation with larger study populations.


Cryptogenic stroke (CS) is associated with a high rate of recurrences and adverse outcomes at long-term follow-up, especially due to its unknown etiology that often leads to ineffective secondary prevention. Asymptomatic atrial fibrillation (AF) could play an important pathophysiological role. Some studies have pointed to left atrial (LA) and left ventricular (LV) systolic and diastolic dysfunction as surrogate markers of AF. The aim of the study is to evaluate the relationship between echocardiographic parameters of LA and LV function, and the occurrence of AF revealed by continuous ECG monitoring in a cohort of patients with CS.Single-center prospective cohort study. Seventy-two patients with CS with insertable cardiac monitors (ICM) underwent transthoracic echocardiography (TTE). TTE was focused on LA and LV function, including both standard and longitudinal strain-derived parameters. All detected AF episodes lasting more than 2 min were considered.p = 0.005, and adjusted OR = 0.69, CI 95% 0.46–0.95, p = 0.041, respectively).Continuous ECG monitoring revealed subclinical AF in 23 patients (32%) at an average of 6.5 months after ICM implantation. Many echocardiographic parameters, indicating LA volume and LV systolic/diastolic function, were significantly associated with the occurrence of AF, suggesting the worst atrial function in the AF group. Furthermore, multivariable regression analysis revealed that peak atrial contraction strain and left ventricular strain were independently associated with AF (adjusted OR = 0.72, CI 95% 0.48–0.90, In patients with CS, LA and LV strain analysis add predictive value for the occurrence of AF over clinical and morpho-functional echocardiographic parameters. Impaired booster pump strain and LV longitudinal strain are strong and independent predictors of AF. About 8SC score  portend SC score , echocarSC score , 13, eveSC score , 15. MorSC score –18, can SC score , 20.Some studies have pointed LA dysfunction as a surrogate predictor of hidden AF in patients with CS, but the assessment of incident AF was heterogeneous, mostly based on clinical follow-up, and were more frequently short-term, with a small percentage of patients implanted with cardiac loop recorder , 22. ThiThe aim of this study was to evaluate the relationship between echocardiographic parameters, indicating LA and LV function, and the occurrence of AF revealed by continuous ECG monitoring after CS. Particularly, we investigated the predictive value of LA strain and function and LV diastolic function for the detection of AF episodes.This is a single-center prospective cohort study. We enrolled consecutive patients from March 2016 to September 2020 who were admitted to the Neurological Clinic of Santissima Annunziata Hospital of Chieti with the diagnosis of CS. The etiology was determined by the neurologist according to Trial of Org 10172 in Acute Stroke Treatment's (TOAST's) classification . Standard echocardiographic parameters were recorded and measured while blinded to cardiac monitoring findings (G. B.) and according to the recommendations of international guidelines , includiBoth apical views were optimized in terms of orientation, depth, and gain to avoid LA foreshortening and to visualize the entire LA throughout the cardiac cycle. Five cardiac cycles of each plane were stored in cine loop format in order to subsequently select the images of better quality for off-line speckle-tracking analysis.With these parameters we then calculated volumetric LA function as follows:Passive LA emptying fraction (LAPEF) (in %): 100 · [LAV max × LAV Pre-A]/LAV max;Active LA emptying fraction (LAAEF) (in %): 100 · [LAV Pre-A × LAV min]/LAV Pre-A;Total LA emptying fraction (LATEF) (in %): 100 · [LAV max × LAV min]/LAV max.® Vector Velocity Imaging (VVI) Longitudinal version 2.0, with the onset of QRS complex used as the zero-reference point (R-R gating). LA endocardial border was manually traced in both A4-C and A2-C views, delineating a region of interest (ROI) composed by six segments for each view. Then, after the segmental tracking quality analysis and the eventual manual adjustment of the ROI, the longitudinal strain curves were generated by the software for each atrial segment. The resulting atrial strain curve provided 2 peaks consistent with reservoir and contractile strain /American Society of Echocardiography (ASE)'s consensus document . Strain e strain . LA conte strain , and peae strain , 16. Pase strain . In these strain . In the e strain .Patients without interpretable images were excluded from the study. If more than two segments were excluded in a projection, the investigation was deemed unsatisfactory. In all patients, conventional and strain parameters were obtained in sinus rhythm at baseline and without significant valvular heart disease at time of the exam.Reproducibility of strain measures were confirmed by two physicians  in order to minimize interpersonal variability. The reproducibility was tested while blinded in a random sample of 15 patients, according to a recent practical guideline .Long term cardiac monitoring was obtained in all the study patients for up to 3 years by the Reveal LINQ™  ICM. The device was implanted subcutaneously on the thoracic surface. We considered for the analysis all detected AF episodes, defined as an irregular supraventricular rhythm with absence of P waves and variable R-R interval lasting more than 2 min. All recorded AF episodes were evaluated and confirmed by an expert cardiologist (M. F.). AF burden was considered as the number of AF episodes recorded by ICM lasting more than 2 min.t-test and chi-squared test were used to compare means and frequencies of clinical and echocardiographic covariates between groups of subjects with or without AF revealed at ICM. Covariates were screened in univariate models by logistic regression to test AF prediction. Then, a multivariable logistic regression analysis was performed to identify independent predictors by selecting covariates with a p-value <0.10 at univariate analysis. Kaplan-Meier analysis was performed using Log-rank test in order to compare AF probabilities between patients with or without impaired LVLS and PACS, with discriminative cut-off values for each variable deriving from ROC curve analysis. A ROC analysis was also performed by combining LVLS and PACS. At this scope, a binary logistic regression has been run to generate a probability variable of AF with LVLS and PACS as covariates. Then, a ROC curve was generated by using the probability as the test variable and AF as dependent variable.Categorical variables are described as absolute frequencies and percentages. Continuous variables are presented as mean values ± standard deviation (SD), their associated 95% confidence intervals (CI), or as median and interquartile range (IQR), as appropriate. Normality of variable distributions was tested by the Kolmogorov–Smirnov test. The unpaired Student's r) and intraclass correlation coefficient (ICC), while agreement was visually assessed by Bland–Altman Plot for inter-operator reproducibility  . ICM wer2DS2-VASc score, which was significantly higher in AF group  and for prevalence of hypercholesterolemia, which was significantly higher in no-AF group   . In our A comparison of LA and LV strain between an AF patient and no-AF patient is shown in Multivariable regression analysis revealed that PACS and LV strain were the only parameters independently associated with AF .p = 0.005; p = 0.041; Receiver-operating characteristic (ROC) curve analysis showed that PACS had the best diagnostic performance  and HR 5.6 (95% CI 2.2–14.3) respectively, log-rank p = 0.003) and 0.69 (p = 0.004), respectively, and ICC was 0.74 and 0.61, respectively. Intra-observer correlation of PALS and PACS were expressed as Spearman's r of 0.7 (p = 0.004) and 0.7 (p = 0.004), respectively, and ICC was 0.76 and 0.78, respectively.PALS and PACS showed good inter and intra-observer correlation. Inter-observer correlation of PALS and PACS were expressed as Spearman's r of 0.70  and one non-cardiovascular death were reported. Two recurrent strokes occurred in the AF group. In the first patient, the second stroke occurred before the implantation of ICM and consequently before the detection of AF. After the beginning of oral anticoagulation, no further strokes were detected. In the second patient, the additional stroke occurred under oral anticoagulation with dabigatran 110 mg bis in die (BID) after a de-escalation from dabigatran 150 mg BID driven by minor bleeding. After the second stroke, dabigatran 150 mg BID was restored, and no further strokes were detected. No major life-threatening or intracranial bleeding were reported in the entire study cohort.There is an increasing interest in the potential role of subclinical AF in patients with CS. After several trials and confirmed by real-world data , last GuAmong them, PACS and LVLS were the strongest and independent predictors of AF occurrence. PACS has been recently associated with AF in patients with CS without LA enlargement and emerged as a new useful echocardiographic parameter for the prediction of AF in this cohort of patients .The value of this parameter, above LA sizing measurements, stands on the capability to detect even initial alteration of LA contractile function . Accordiper se, but age-related morpho-functional LA and LV dynamic changes are more important in this setting. CHA2DS2-VASc score was higher in patients who developed AF compared with those who did not, as previously observed in a population-based cohort of 22,179 middle-aged individuals  in subclinical AF remains a matter of debate, in the last ESC Guidelines , the useFurther large series studies are needed to address clinical implications of the predictive value of echocardiographic parameters, including PACS and LVLS, for the occurrence of AF. Since the research of hidden AF is crucial in patients with CS and can lead to an adequate therapeutic regimen, availing of predictive parameters of subclinical AF might indicate patients worthy of receiving long-term ICM. Furthermore, LA and LV strain is useful to find out the atrial myopathy and dysfunction related to AF and often preceding the occurrence of the arrhythmia. Therefore, these echocardiographic parameters can be exploited to identify higher risk patients in which the research of AF is strongly recommended, including patients with CS, but also in other high-risk clinical settings.To our knowledge, this is the largest study with the totality of CS population monitored using ICM. In fact, most studies were conducted on patients monitored with conventional methods, while only one enrolled 56 patients with CS monitored with ICM .There are some limitations in this study. First, this is a single-center study with a small sample size. Therefore, a correlation of clinical and echocardiographic variables with hard clinical events was not possible. Moreover, since the ICM here used requires at least 2 min of AF to be detected, episodes <2 min could have been missed, while definition of AF now accounts for episodes lasting more than 30 s with absence of P waves and variable R-R interval. Furthermore, 15 patients were unable to attend a clinical visit, and follow-up data were collected by a phone questionnaire. Finally, for some strain data, only A4-C view results are presented because of the better quality of the images. However, although in most studies, the 2D-global longitudinal strain was calculated as the average of the A4-C, A2-C, and A3-C views, the A4-C view is considered adequate to obtain strain measures when the echocardiographic acoustic window is limited .In about one-third of patients with CS, ICM revealed subclinical AF episodes. In these patients, LA and LV strain analysis adds predictive value for the occurrence of AF over clinical and other morpho-functional echocardiographic parameters. Impaired booster pump strain and left ventricular longitudinal strain are strong and independent predictors of AF.The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Institutional Ethics Committee of G. d'Annunzio University/Santissima Annunziata Hospital of Chieti. The patients/participants provided their written informed consent to participate in this study.GB and GR contributed to the conception and design of the work. GB, FR, CD'A, and FP contributed to the acquisition and analysis of data for the work. GB, FR, SG, GR, and SP contributed to the interpretation of data. GB and FR drafted the manuscript. MD, MF, SP, SG, and GR critically revised the manuscript. All authors gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy.FR: speaker/consultant fee from Boehringer Ingelheim, Daiichi Sankyo. SP: speaker/consultant fee from Astra Zeneca, Bayer. GR: speaker/consultant fee from Astra Zeneca, Bayer, BMS-Pfizer, Boehringer Ingelheim, Daiichi Sankyo. The remaining 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Heart failure (HF) is a clinical syndrome caused by various etiologies that results in systolic and diastolic cardiac dysfunction with congestion. While evaluating HF and planning for treatment, physicians utilize various laboratory tests, including electrocardiography, diverse imaging tests, exercise testing, invasive hemodynamic evaluation, or endomyocardial biopsy. Among these, cardiac imaging modalities and biomarkers are the mainstays during HF diagnosis and treatment. Recent developments in non-invasive imaging modalities, such as echocardiography, computed tomography, magnetic resonance imaging, and nuclear imaging, have helped us understand the etiology, pathophysiology, and hemodynamics of HF, and determine treatment options and predict the outcomes. Due to the convenience of their use and potential impact on HF management, biomarkers are increasingly adopted in our clinical practice as well as research purpose. Natriuretic peptide is the most widely used biomarker for the diagnosis of HF, evaluation of treatment response, and prediction of future outcomes. Other cardiac biomarkers to evaluate the pathophysiological mechanisms of HF include myocardial injury, oxidative stress, inflammation, fibrosis, hypertrophy, and neurohormonal activation. Because HF results from complex cardiac disorders, it is essential to assess the disease status multidimensionally. The proper utilization of multimodality imaging and cardiac biomarkers can improve the quality of patient management and predict clinical outcomes in HF in the era of personalized medicine. Heart failure (HF) is a clinical syndrome caused by various etiologies, resulting in systolic and diastolic cardiac dysfunction with congestion ,2,3,4,5.The recently proposed HF definition suggests that HF is a clinical syndrome with current or prior symptoms and/or signs caused by a structural and/or functional cardiac abnormality  and corroborated by at least one of the following: elevated natriuretic peptide levels; objective evidence of cardiogenic pulmonary or systemic congestion by diagnostic modalities, such as imaging  or hemodynamic measurement  at rest or with provocation  . FinallyThe first step of imaging in HF is determining the signs of congestion by chest X-ray. According to the recent HF guidelines, the HF can be classified through transthoracic echocardiography (TTE). ,3,4 In HConventional 2-dimensional TTE (2D TTE) is widely used to evaluate chamber size, systolic function, and diastolic function . RegionaLung ultrasound is an additive tool to evaluate heart failure status in a couple of minutes using general cardiac transducer by echocardiography (3.5 to 5.0 MHz) ,24. The The use of cardiac computed tomography (CCT) is rapidly increasing. In addition to coronary artery evaluation, anatomical and functional evaluation of various cardiac structures are available with higher resolution when applying the retrospective protocol ,19,26,27Nuclear imaging is a frequently used non-invasive functional imaging technique. Single positron emission computed tomography (SPECT) with ²⁰¹Thallium chloride or ⁹⁹mTechnetium-sestamibi can assess cell membrane integrity and mitochondrial function, as well as myocardial perfusion. Myocardial perfusion can also be assessed with ¹³N-ammonia and ⁸²Rubidium-PET ,16,27. PCardiac magnetic resonance (CMR) is helpful for evaluating myocardial function and anatomical evaluation. Both T1 and T2 imaging sequence variations allow for the assessment of myocardial inflammation and edema as frequently seen in myocarditis or inflammatory cardiomyopathies ,31. The With the development of novel HF medications, biomarkers have emerged as a helpful guide in the management of HF. Various biomarkers have been developed for diagnosis, management, and prognostication. The most widely adopted biomarkers for diagnosis, management, and prognostication are natriuretic peptides . Many other biomarkers have been developed to evaluate pathophysiological processes related to HF, such as myocardial insult, neurohormonal activation, myocardial inflammation, and remodeling. Some of these biomarkers have already been utilized in clinical practice . However, other biomarkers are still in research or are only used to evaluate pathophysiological mechanisms of specific types of HF. Likewise, for the imaging modalities, a multidimensional strategy with different biomarkers is required in each step of HF management .(1)B-type natriuretic peptidesNatriuretic peptides are synthesized by the brain, heart, and other organs. In the heart, these hormones are provoked by atrial and ventricular distention and neurohormonal stimulations in response to HF. BNP is originally recognized in the brain but is discharged predominantly from the ventricles of the heart in reaction to volume expansion and overload . ProBNP The negative predictive value of both BNP and NT-proBNP is 96%  and 99% , respectively, to exclude acute decompensated HF. In patients with an outpatient clinic, the negative predictive value remained high  . PhysiciBased on recent guidelines, angiotensin receptor/neprilysin inhibitor (ARNI) has become a mainstay of HFrEF treatment ,39. In a(2)Atrial natriuretic peptideSimilar to B-type natriuretic peptides, atrial natriuretic peptide (ANP) also increases in response to myocardial wall stress. It is the first hormone isolated from the heart as a potent natriuretic/diuretic and hypotensive factor, which induces profound natriuresis/diuresis, hypotension, and inhibition of aldosterone secretion . Since t(3)High-sensitivity troponinp = 0.008), and more time in low hsTn (≤10.9 pg/mL) was also associated with a lower cardiovascular event rate after adjustment  [High-sensitivity troponin (hsTn) is a representative biomarker for myocardial injury in patients with myocardial infarction or acute myocarditis. Elevated serum concentrations of hsTn are also frequently observed in patients with various stages of HF despite the absence of coronary artery obstruction. The release of cardiomyocyte cell membrane blebs during myocardial wall stress may be the reason for elevated troponin levels in HF. Elevated serum concentrations of hsTn are associated with adverse clinical outcomes and cardiac remodeling in HF ,50,51. I= 0.008) .(4)Myeloperoxidasep = 0.02) [p < 0.0001) [Myeloperoxidase (MPO) is a biomarker released by activated neutrophils and monocytes in response to oxidative stress during inflammation. The depletion of vascular nitric oxide and promotion of low-density lipoprotein oxidation in endothelial cells are the major contributors. Increased serum MPO concentration is associated with poor outcomes in HF, and it is more pronounced when combined with BNP ,54. Incr = 0.02) . Higher (5)Uric acidUric acid is a marker of cell stress that predicts HF onset. A high uric acid level predicts a higher incidence of HF and an increased risk of adverse events . A previIn HF, activation of the sympathetic nervous system results in elevated norepinephrine concentration, which is responsible for increased heart rate, myocardial contraction, peripheral vascular resistance, and energy expenditure. Increased plasma concentrations of norepinephrine are associated with increased cardiovascular risk . In adva(1)Adrenomedullinp = 0.002), similar to NT-proBNP [Although the fundamental mechanism is not fully understood, the endogenous vasodilator adrenomedullin (ADM) helps in the diagnosis of HF. Mid-regional propeptide (MR-proADM), which is a precursor of ADM, can be measured due to the short half-life of ADM. High MR-proADM is related to HF diagnosis and is helpful in diagnosis, independent of the NT-proBNP levels. Furthermore, the MR-proADM level is an independent predictor of death . AnotherT-proBNP .(2)Arginine vasopressinThe antidiuretic and vasoactive hormone arginine vasopressin (AVP) is released from the hypothalamus in response to changes in plasma osmolality and blood volume . In seve(3)Endothelin-1In response to inflammation, neurohormonal activation, and vascular shear stress, endothelin-1 (ET-1) is released by the vascular endothelium . It is r(1)Tumor necrosis factor, interleukin-6Inflammatory biomarkers, such as tumor necrosis factor (TNF), soluble TNF receptors, and interleukin-6 (IL-6) are also related with the HF outcome. In chronic HF, inflammatory markers are related to increased mortality ,62 Micro(2)Soluble suppression of tumorigenicity 2p < 0.001) and acute HF  above and beyond NT-proBNP [Under myocardial or vascular strain conditions, a member of the IL-1 receptor family, ST2, is released. Among the two types of ST2 isoforms (ST2 ligand and soluble ST2), soluble ST2 (sST2) has a more critical role in myocardial and vascular remodeling, fibrosis, and atherosclerosis . The conT-proBNP . When coT-proBNP . The rolT-proBNP . The benT-proBNP . The chaT-proBNP .(3)Galectin-3Galectin-3 is a macrophage lectin product that is associated with tissue fibrosis. In HF, galectin-3 plays an essential role in LV remodeling. The concentration of galectin-3 is linked to outcomes such as death and HF hospitalization, and when it is combined with NT-proBNP, the risk prediction accuracy improves . However(4)Matrix metalloproteinasesDuring the development and progression of HF, cardiac extracellular matrix remodeling is a critical pathway through degradation of collagen and other matrix proteins by collagenases, matrix metalloproteinases (MMP), and by tissue inhibitors of metalloproteinases (TIMP) . An imba(5)Growth/differentiation factor-15p < 0.001) and first morbid event  [Growth differentiation factor-15 (GDF-15) is also known as macrophage inhibitory cytokine-1 (MIC-1) due to its inhibitory function of macrophage activation. It is a part of the transforming growth factor beta (TGF-β) cytokine superfamily . It regu< 0.001) .The use of diverse imaging modalities and biomarkers for the management of HF has evolved tremendously. Echocardiography and natriuretic peptides are the most effective tool throughout the HF. However, the appropriate use of different imaging modalities and biomarkers is key to successful treatment . Physici