Coronary angiograms of 41 consecutive TTS patients were retrospectively analyzed to derive angiography-based indices of CMD. Three indices  were calculated based on quantitative flow ratio. CMD was defined as an IMRangio value ≥ 25 units. The correlation between CMD and clinical presentation was then assessed. Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in left anterior descending artery (LAD) than circumflex and right coronary artery with either NH-IMRangio , AngioIMR  or A-IMR . All patients presented CMD with angiography-derived IMR ≥ 25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤ 40%) than in those with preserved ventricular global function . CMD assessed with angiography-derived IMR is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function.Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an “adrenergic storm” upon a susceptible microvascular circulation. The aim of our manuscript was to assess CMD in patients with TTS through the computation of the angiography-derived index of microcirculatory resistance (IMR) and its correlation with clinical presentationThe online version contains supplementary material available at 10.1007/s10554-022-02698-6. Stress cardiomyopathy, known as Takotsubo syndrome (TTS), is a clinical condition that mimics acute myocardial infarction in terms of symptoms (chest pain) and electrocardiographic presentation  although in absence of significative epicardial coronary disease. The typical echocardiographic kinetic pattern  involves a significant portion of myocardium but is usually associated with a modest release of myocardial injury markers –4.Despit. Invasive assessment of CMD in TTS has been previously reported in case reports and small case series [The thermodilution-derived index of microvascular resistance (IMR) is the most commonly used surrogate to invasively assess coronary microvascular dysfunction (CMD) with established diagnostic and prognostic relevance in acute (ACS) and chronic coronary syndromes (CCS) –8 9]. I. I9]. Ite series –12. HoweTo overcome these limitations, the concept of IMR based on angiography has been developed. Angiography-derived IMR is based on the application of computational flow dynamics to the three-dimensional quantitative coronary angiography (QCA)  and it hIn this study we sought to investigate the association of TTS with CMD through the computation of angiography-derived IMR, according to three validated formulas. Secondly, we aimed to assess the correlation of CMD with the clinical presentation. Finally, for the first time we provided a paired comparison of the three major formulas for the computation of IMR derived from angiography.Sixty-five consecutive patients admitted for TTS from January 2018 to August 2021 at the University Hospital of Verona were initially screened for inclusion in this retrospective observational study; between these, 24 patients were excluded because of technically not adequate coronary angiography (CAG) for QFR analysis. TTS diagnosis was defined according to the Revised Mayo Clinic  and InteThe study was conducted in accordance with the ethical principles of the Declaration of Helsinki and all the patients included entered in the prospective clinical registry and provided their written consent for the anonymous collection of the data.For each patient, demographic variables and cardiovascular risk factors were collected at admission. Electrocardiographic (EKG) abnormalities  were collected from the first EKG available. Peak levels of high-sensitivity troponin (hs-cTnT or hs-cTnI) were measured. To compare values of the two different indices of myocardial injury, the value of peak level divided by respective 99th percentile upper reference limit (URL) of the assay  was considered (cTnxURL) according to the international recommendation . CreatinVhyp) were derived [The 3D-QCA analysis and QFR computation were performed by two independent, experienced, trained and certified different investigators  blinded to clinical presentation. A validated software  was used. QFR computation was performed in agreement with the step-by-step procedure validated in previous studies. As per QFR protocol, two angiographic projections at least 25°apart were selected, avoiding foreshortening and overlap between the main vessel and side branches. In each projection, the end-diastolic frame was selected and one anatomical landmark was identified in both as the reference point. Subsequently, the proximal and distal points were selected, while vessel contours were automatically detected and manually corrected if necessary. The software reconstructed a 3D anatomical vessel model without its side branches for the 3D-QCA analysis and QFR computation. Vessel length was automatically calculated by the software, while the number of frames (Nframes) required for contrast dye to travel from the proximal to the distal reference was manually assessed. The frame-acquisition rate was set at 15 frames/second. From these values flow velocity and estimated hyperemic flow velocity  to investigate the incidence of coronary microvascular disfunction in TTS through angiography-derived IMR computation; (2) to assess the correlation of angiography-derived IMR with clinical variables, such as LVEF and laboratory biomarkers; (3) to compare the diagnostic performance of the three different IMR computation formulas in this clinical setting.2 test. NH-IMRangio according to each formula for LAD, left circumflex (LCX) and right coronary (RCA) artery was computed. Angiography-derived IMR ≥ 25 was considered as cut-off for coronary microvascular dysfunction definition. To study the correlation of CMD with clinical and laboratory variables, the highest angiography-derived IMR value between the three vessels was chosen. Correlations were analysed using Pearson test if they presented a normal distribution and Spearman test if they had a non-normal distribution.Clinical and demographic variables are presented as means with standard deviation for continuous variables with normal distribution and as medians with interquartile range for continuous variables with non-normal distribution. The normality of the distribution was assessed by Shapiro–Wilk test and QQ plots analysis. Categorical variables are presented as counts and respective percentages. For continuous variables, they were analysed by t-test or ANOVA in the case of a normal distribution and by Mann–Whitney U-test test in the case of a non-normal distribution. Categorical variables were analysed by Fisher's exact test or χFinal agreement evaluation between the three formulas was conducted according to Bland–Altman plot analysis. Statistical analysis was performed using SPSS 26.0  and Prism 9.0 . A p value < 0.05 was considered statistically significant.2. Most of the patients presented with medical history of arterial hypertension  while only three patients (8.6%) were diabetic and 13 (31.7%) had chronic kidney disease with a global mean CrCl of 64.26 ± 22.4 ml/min. Two patients had previous history of coronary artery disease (CAD) and 8 (18.5%) had documented peripheral artery disease. At admission, most of the patients presented with Killip class one  while three patients (8.1%) presented with cardiogenic shock (Killip class four); five patients (12.8%) required inotropic support and only in one patient mechanical circulatory support with intra-aortic balloon pump was necessary during the hospital stay. One patient (2.6%) had a stroke and died during hospitalization. 11 patients (25.7%) presented with ST-segment elevation, two patients (5.7%) with ST-segment depression and 13 patients (37.1%) with deep T-wave inversion. According to InterTAK diagnostic score, potential emotional or clinical triggers were investigated: in 24 patients (58.5%) a clear physical trigger  was identified, while in nine patients (22%) the trigger was emotional. Mean LVEF at the first echocardiogram was 41.2 ± 10% with 23 patients (56%) presenting with LV dysfunction defined as LVEF < 40%. CAG was performed within 24 h in 27 cases (66%) and within 72 h in 34 cases (83%).The population analyzed was prevalently female (85.7%) with a median age of 76 years (67.5–81.5) and a mean body mass index of 23.1 ± 3.1 kg/mSerial measurements of hs-cTn were collected with median cTnxURL of 123 (20–110). All the clinical variables are reported in Table QFR analysis and angiography-derived IMR calculation was feasible for all the three main vessels in 31 patients (75.6%), while in 39 patients (95%) calculation was feasible for two vessels and in the reminder only LAD was evaluable. Vessel QFR was lower in LAD compared to LCX and RCA respectively . Angiography-derived IMR assessed in the LAD was higher than in LCX and RCA with either NH-IMRangio , Angio-IMR  or A-IMR . CMD defined as an angiography-derived IMR ≥ 25 in at least one territory was present in all the patients. Angiography-derived IMR results are provided in Table Angiography-derived IMR in the LAD territory demonstrated a moderate inverse correlation with LVEF. This was confirmed using all the different formulas . No statistical significant association was observed between mean value of IMR assessed in the three vessels and LVEF .No significant correlation was observed between angiography-derived IMR LAD and hsTnxURL . Angiography-derived IMR in the LAD territory was significantly higher in patients with LVEF ≤ 40% than patients with preserved LVEF .A comprehensive illustration of correlations between angiography-derived IMR, LVEF and hsTnxURL is provided in Fig. There was no statistical difference in assessment of microvascular function between the three formulas for each vessel Fig. . Bland–A1 Coronary microvascular resistance assessed using angiography-derived IMR was significantly augmented in patients presenting with TTS;2 Angiography-derived IMR computed in the LAD territory was inversely correlated with left ventricular systolic function;3 The three formulas showed superimposable performance in assessing angiography-derived IMR.The main findings of our analysis are the following:IMR does not represent a direct measurement of microvascular resistance, but is a derived surrogated index associated with clinical outcome in several clinical settings , 21–25. In TTS the evaluation of microcirculation has reported inconclusive results and no specific IMR cut-off is available. The precise pathophysiology of TTS has not been completely elucidated yet although a number of different mechanisms have been proposed. According to the most accredited rationale, a hyper-activation of the sympathetic nervous system occurs, inducing a neurohormonal catecholaminergic storm. This impacts on pre-existing microvascular abnormalities, determining unbalance between inappropriate α-mediated vasoconstriction and inadequate β2-mediated vasodilation. External microvascular compression due to myocardial oedema and inflammation-related cell accumulation and to increased intracardiac pressures may also contribute to the microvascular perfusion abnormalities , 29. In The invasive study of coronary microvasculature in patients with TTS using IMR has been generally limited to the LAD, due to technical and procedural issues . Nonetheless non-invasive angiography derived IMR calculation allows to easily and rapidly assess the microcirculation status of all the three main epicardial coronary arteries, exploring global microvascular function. In normal coronary arteries, according to the laws of fluid dynamics, resistance increases across the branching structure of the coronary tree, because coronary flow decreases while the driving pressure remains virtually unchanged. Theoretically, IMR values could be influenced by the amount of myocardial mass subtended by the analyzed vessel, similarly to what has been proposed for FFR: this concept have been tested by Mauro Echavarría–Pinto et al., in CAD patients with intermediate stenosis, showing that indeed the amount of myocardium subtending to a coronary stenosis is inversely associated with IMR values . In TTS Interestingly, in our manuscript we showed a moderate correlation between CMD and left ventricular function reduction: while the relevance of such finding in terms of clinical presentation, management and long-term prognosis must be further investigated, concordant results have been publishing by other colleagues. In a recent manuscript by Jordi Sans-Roselló et al., a similar non-invasive microvascular assessment by means of NH-IMRangio derivation was performed in a large cohort of TTS patients. Concordantly to our analysis, a cut-off value of 25 units was chosen for the definition of CMD and a good correlation with LVEF was underlined, together with other variables  not captured by our study .However, to our knowledge, this is the first manuscript evaluating and directly comparing the performance of three different validated formulas for non-invasive angiography-derived IMR computation. IMRangio and its non-hypaeremic counterpart (NH-IMRangio) were the first formulas presented in the field of angiography-derived microcirculatory assessment and those with the largest published literature so far . SubsequFirst of all, the retrospective nature of the analysis and the relative small sample size might have affected the inferential power of the study. Secondly, despite angiography-derived IMR has been validated as a pressure-wire-free alternative to IMR for the evaluation of coronary microvasculature it is indeed only a surrogate of the direct invasive thermodilution assessment, and it has not been extensively validated in TTS patients.Moreover, we applied an angiography derived IMR > 25 units as cut-off that has been shown to be reliable in stable conditions or in the setting of non ST-segment elevation ACS . In the Notably, coronary tortuosity has been reported to be more frequent in TTS as compared to matched controls. This anatomical aspect has been shown to impact both on pressure-wire derived and on angiography-derived epicardial physiology, leading to an underestimation of coronary flow. Whether this condition might have affected also angiography-derived IMR computation can not be excluded, and deserves further analysis. Nonetheless, cases with severe tortuosity were excluded from the analysis.Finally, no data on the long-term trajectory of microvascular function were available: although a progressive recovery together with the LVEF improvement might be expected and has been previously reported, no angiographic follow-up was scheduled as not considered clinically advantageous in this peculiar scenario.This study demonstrated the presence of global dysfunction of the coronary microvasculature in patients with TTS. High values of angiography-derived IMR measured in the LAD territory were associated with TTS presentation with left ventricular systolic dysfunction.Supplementary file1 (DOCX 31 KB)Below is the link to the electronic supplementary material.


The injury of the left ventricle (LV) during anticancer therapy has long been recognized, and guidelines recommend a specific set of parameters for determination of LV impairment. The influence of anticancer therapy on the right ventricle (RV) has been insufficiently investigated, and there are only a few studies that have considered the effect of radiotherapy on RV remodeling. On the other hand, large number of patients with different types of cancers located in the chest are treated with radiotherapy, and the negative clinical effects of this treatment such as accelerated coronary artery disease, valve degeneration and heart failure have been documented. The anatomical position of the RV, which is in the front of the chest, is responsible for its large exposure during radiation treatment, particularly in patients with left-sided breast and lung cancers and mediastinal cancers . For the same reason, but also due to its anatomical complexity, the RV remains under-investigated during echocardiographic examination, which remains the cornerstone of cardiac imaging in everyday practice. In the last decade many new echocardiographic imaging techniques that enable better evaluation of RV structure, function and mechanics appeared, and they have been used in detection of early and late signs of RV injuries in oncological patients. These investigations are related to some important restrictions that include limited numbers of patients, used parameters and imaging techniques. Many questions about the potential impact of these changes and possible predictions of adverse events remain to be evaluated in future large longitudinal studies. The current body of evidence indicates an important role of radiotherapy in RV remodeling, and therefore, the aim of this review is to summarize currently available data regarding RV changes in patients with various oncological conditions and help clinicians in the assessment of possible cardiac damage. Radiotherapy is a very important part of anticancer therapy in a large number of oncological patients. However, it may be related with cardiac damage in cancers with chest localization—such as breast, lung, esophageal and mediastinal cancers including lymphomas—as well as some pediatric cancers such as lymphoma, thymoma and teratoma. The influence of radiotherapy is difficult to differentiate from chemotherapy-induced effects, as they are commonly used together and their individual effects are difficult to evaluate.Chemotherapy is known to induce early cardiotoxicity, whereas radiotherapy has been considered to be more related to late cardiac damage. However, the use of novel imaging methods, primarily in echocardiography, has enabled the early detection of cardiac impairment in oncological patients treated with radiotherapy . Novel cThe PubMed database was searched for all articles published in English up to 31 October 2022. Studies were identified by using the following terms: “right ventricle”, “cancer”, “radiotherapy”, “strain”, “systolic function”, “longitudinal strain” and “echocardiography”. The number of studies investigating the relationship between radiotherapy and RV remodeling is scarce, and the number of included patients is very limited. However, the majority of these studies indicate significant changes in RV systolic function and mechanics not only during long-term follow-up, but also in a period of few weeks and months after exposure to this type of therapy. The aim of this article is to summarize data about RV structural, functional and mechanical remodeling in patients with different types of cancer in order to help clinicians in treating and following up with these patients.The cornerstone responsible for almost all cardiac changes found in radiation-induced heart disease is tissue fibrosis that is related to micro- and macrovascular injury. Microvascular injury is related to myocardial fibrosis, pericardial fibrosis and decreased capillary density. These changes induce LV remodeling and changes in diastolic and systolic function, as well as pericardial effusion and constriction. Macrovascular injury is associated more with accelerated coronary atherosclerosis, which induces acute and chronic myocardial ischemia.Cellular damage induces vasodilation and vascular permeability even after a few minutes of ionizing radiation. Impaired endothelial cells release adhesion molecules and growth factors responsible for the acute inflammatory response that includes the secretion of inflammatory cytokines  and interleukins (IL) including IL-1, IL-6 and IL-8) . The mosThe classical hallmarks of radiation-induced heart disease (RIHD) include the following: fibrosis and calcification of the aortic root and the aortomitral curtain that can lead to progressive stenosis of the aortic and mitral valves; ostial coronary stenosis; myocardial atrophy; and widespread pericardial adhesions and thickening ultimately leading to intractable and inoperable pericardial constriction. However, one should be aware of the possibility that the presence of cancer itself has a potentially negative influence on RV functioning and mechanics, as we reported in a cohort of patients with different types of solid cancers .Interestingly, similar mechanisms responsible for RIHD might induce changes in cardiac metabolism, myofibril disorganization, imbalance among protein synthesis and degradation, cellular apoptosis and ultrastructural changes of cardiomyocytes that altogether may trigger cancer-induced cardiac dysfunction. The interaction between inflammation, oxidative stress, sympathetic system hyperactivity and vasoactive cytokines that induces myocyte damage may be related with cancer-induced RV impairment.Breast cancer is the most common cancer in women, and improved diagnostics and adjuvant therapies have significantly improved survival rates in these patients. Adjuvant radiotherapy has an important role in anticancer therapy of these patients. However, cardiac exposure is known to be associated with adverse cardiovascular effects including impairment in cardiac function and mechanics, but also valvular damage as well as advanced coronary artery disease. Therefore, it is very important to provide short- and long-term follow-up for these patients in order to provide timely diagnosis and treatment of radiation-induced heart disease. There is an obvious difference in cancer location, and the cardiac exposure is essentially different between left- and right-sided breast cancer.A study that investigated 49 patients with left-sided breast cancer did not find significant differences in conventional parameters of RV systolic and diastolic function before and approximately 40 days after radiotherapy, with the exception of tricuspid annular plane systolic excursion—TAPSE—which was significantly reduced after radiotherapy was applied . The samn = 60) who experienced short- and long-term TAPSE reduction had left-sided breast cancer. RV systolic function deterioration was not found in patients with right-sided breast cancer (n = 20) during short- and long-term follow-up. Investigators additionally studied ultrasound tissue characterization 34 ± 11 days after radiotherapy in these patients and found elevated echodensity in the RV free wall and in the septum in patients with left-sided breast cancer, whereas there were no changes in patients with right-sided breast cancer [The same research group provided a 3-year study of 80 patients with left- and right-sided breast cancer treated with radiotherapy and reported a significant short-term reduction in TAPSE, but not in other parameters of RV systolic function (s’) or diastolic function (E/e’) . The majt cancer . RV and t cancer .p = 0.06), whereas after 12 months, global longitudinal RV function was significantly reduced . The reduction in RV longitudinal strain was mostly caused by a decrease in apical strain, which is concomitantly the field that receives the highest radiation dose. Nevertheless, different receptors are present in the three myocardial layers, as well as in various cardiac segments, which might also be the reason for the unique response of each myocardial region .A small study that used cardiac magnetic resonance and followed 20 patients with breast cancer for 12 months showed impairment in RV mechanics that started early after radiotherapy application . Namely,RV diastolic parameters were not deteriorated in women with breast cancer treated with radiotherapy compared to controls, whereas RV structure was mostly not investigated ,11,12,13The largest echocardiographic investigations in this field studied surviving patients with hematological malignancies that were treated during childhood. They provided comprehensive data regarding RV remodeling in both genders and very long follow-up periods (>10 years), which is very different from studies performed in patients with breast cancer that included only women and had significantly shorter monitoring.n = 149) or in combination with radiotherapy (n = 40), whereas only small portion of patients (n = 18) was treated with only mediastinal radiotherapy. Even though all three groups had significantly lower values of RV systolic function  and RV free-wall strain, patients treated only with mediastinal radiotherapy had a trend of lower values than other patients [A study included 246 survivors of childhood lymphoma and acute lymphoblastic leukemia, mean 21.7 years after diagnosis, and 211 matched controls [2) and radiation (cut-off: 30 Gy). The patients who received both anthracycline therapy and radiation >30 Gy were found to have the worst RV systolic function  and RV longitudinal mechanics  [Another large study involved 274 lymphoma survivors who were followed for 13 ± 6 years and separated patients into those who were treated only with anthracyclines and those who were treated with anthracyclines plus radiotherapy, as well as 222 control subjects . Moreove strain) . However strain) .The authors also investigated the relationship between RV remodeling and functional capacity, evaluated by a cardiopulmonary exercise test (peak oxygen consumption—peak VO2) . TAPSE, RV thickness was 14% lower in patients compared with control subjects. Patients had significantly smaller RV mid and basal diameters and RV end-diastolic areas. Considering the fact that the numerical values were small, the authors concluded that there were no clinically important differences in RV morphology between the observed groups . RV diasThere are some evident limitations of these investigations. Namely, a long-term follow-up without echocardiographic assessment in the meantime cannot provide evidence that radiotherapy and/or chemotherapy were the only causes of RV remodeling, as in the meantime these patients developed comorbidities that also might induce changes in RV structure, function and mechanics. Even though the majority of well-known comorbidities  were not very prevalent in these patients’ populations and were included in the multivariable analysis, it is difficult to completely exclude their influence. The patients were not regularly followed, and therefore it is not clear when RV remodeling started. It is possible that it began much earlier, but it can be also hypothesized that RV deterioration was gradual and progressive.There is a substantial lack of data about the effect of radiotherapy on RV remodeling in patients with other types of cancers. A study that included 70 patients with esophageal cancer, central lung cancer, thymoma and left breast cancer showed that TAPSE and the Tei index were sensitive indicators for the early detection of right heart injury after RT for thoracic tumors . NeverthA small study that investigated the influence of low-dose radiotherapy in patients with lung and esophageal cancer found a significant reduction in TAPSE . The limChen et al. investigated 128 inoperable patients with stage III non-small-cell lung cancer (NSCLC) before and after concurrent chemoradiotherapy that included platinum agents  and radiotherapy with a median dose of 64.5 Gy that was administered over 5–7 weeks . The comRadiotherapy remains an important part of anticancer therapy in various types of cancers, and its impact on cardiac structure, function and mechanics is very important, as these parameters showed significant sensitivity in recognizing subclinical cardiac damage and excellent prediction of cardiovascular and overall morbidity and mortality. The available studies, although not sufficient, provide evidence about RV functional changes in radiotherapy-treated cancer patients, which should be enough to justify the inclusion of RV parameters in routine echocardiographic examinations (basic and follow-ups) in all cancer patients. Follow-up should start shortly after radiotherapy, but is has to be prolonged for decades after therapy is completed. A limited number of studies revealed the large significance and clinical importance of RV longitudinal strain determination, which seems to be more sensitive in detection of RV injury than conventional echocardiographic parameters; it is also associated proportionally with the amount of radiation that RV myocardium received and is a good predictor of all-cause mortality ,18. The The role of RV longitudinal strain should be particularly emphasized in the early detection of RIHD. The effect of radiotherapy has been more extensively investigated regarding LV multidirectional strain, particularly global longitudinal strain (GLS). However, available studies show that RV GLS is a more reproducible and sensitive method for the detection of subclinical cardiac impairment than TAPSE, FAC and s’ . NeverthThe importance of CMR in the detection of RV impairment in cancer patients has been poorly investigated, and it is difficult to provide recommendations based on the available data. However, if we examine the existing guidelines related to multimodality imaging in patients treated with radiotherapy for the LV, we may recommend CMR in situations when echocardiographic images are of limited quality or when additional information is required . Routine CMR for evaluation of the RV in oncological patients is not recommended due to its low availability, its costs and the limited number of healthcare professionals with the required level of expertise for this kind of examination.The duration of follow-up in oncological patients treated with radiotherapy should last as long as possible, at least 5–20 years after radiation exposure, but preferably decades after radiation because studies showed that deterioration in LV and RV function remains for more than two decades after therapy, perhaps even longer; however, studies with longer follow-up periods are not available . MoreoveCurrently available data show that the RV cannot be considered an insignificant cardiac chamber and has to be involved in the routine echocardiographic evaluation of patients with cancer treated with chemotherapy or radiotherapy. The effect of cancer itself should be also carefully considered at the baseline examination, before anticancer therapy is initiated, as some evidence about RV remodeling in untreated patients shows that chemo- and radiotherapy are not solely responsible for RV injury. The type of treatment (chemotherapy with or without radiotherapy or isolated radiotherapy) is also very important for RV remodeling because the cumulative dosage of medications and radiation has a determinant role in RV damage. An increasing body of evidence implies that RV involvement in cancer-related cardiotoxicity is very frequent, but its impact on outcomes should be established in large prospective investigations. These studies should also provide information about whether some cardioprotective therapy should be used in patients undergoing radiotherapy with or without chemotherapy in order to prevent potential cardiac remodeling.


Extracellular vesicles (EVs) were investigated as potential biomarkers associated with heart failure (HF) pathophysiology in patients undergoing elective coronary artery bypass surgery characterized by HF phenotype.n = 19) or reduced ejection fraction  were studied and compared to patients with normal left ventricular function (n = 42). EVs in plasma samples collected from the coronary sinus, an arterial line, and from the right atrium were analyzed by flow cytometry. We studied EVs of presumed cardiomyocyte origin [EVs exposing Connexin-43 + Caveolin-3 (Con43 + Cav3) and Connexin-43 + Troponin T (Con43 + TnT)], of endothelial origin [EVs exposing VE-Cadherin (VE-Cad)] and EVs exposing inflammatory markers [myeloperoxidase (MPO) or pentraxin3 (PTX3)].Patients with preoperative proxy-diagnoses of HF types i.e., preserved  were similar in all three patient groups.Median concentrations of EVs exposing Con43 + TnT and Con43 + Cav3 were approximately five to six times higher in coronary sinus compared to radial artery indicative of cardiac release. Patients with HFrEF had high trans-coronary gradients of both Con43 + TnT and Con43 + Cav3 EVs, whereas in HFpEF the profile indicates myocardial stress with less myocardial injury.Con43 + TnT and Con43 + Cav3 EVs are released over the heart indicating cardiomyocyte origin. In HFrEF the EV release profile is indicative of myocardial injury and myocardial stress with elevated  The study patients were divided into three HF phenotypes according to EF, see below.Heart failure (HF) is a severe and common condition with high cost to society , 2. Sinctrans-coronary concentration gradients. The patients underwent clinical evaluation, blood sampling for routine blood tests, electrocardiogram (ECG), and transthoracic echocardiography prior to surgery. According to the results of echocardiography and NT-proBNP concentrations, patients were divided into three phenotypes with respect to EF: i.e., HFpEF, (EF ≥ 45% and objective criteria for HFpEF), HFrEF (EF < 45%), or normal LV function, according to a previously described algorithm (This is an exploratory sub-study of the CABG PREFERS study  which inlgorithm . As not Patients were further divided into three groups based on the extent of CAD on the preoperative coronary angiography: left main stenosis (LMS), three-vessel disease (3-VD), and one- or two-vessel disease (1- or 2-VD) , 10.See Supplementary data for more details on echocardiography and HF phenotyping.Anesthesia was induced with propofol and fentanyl, further maintained with sevoflurane in oxygen/air, additional doses of fentanyl, and subsequently a continuous propofol infusion during ECC. Muscle relaxation was achieved with atracurium or rocuronium before endotracheal intubation.g for 15 min to obtain platelet poor plasma. After centrifugation, samples were loaded on a Hamilton Microlab STARlet liquid handling robot  and aliquoted into 300 μL REMP tubes  uniquely labeled with QR codes. Aliquoted REMP tubes were foil-sealed with a Brooks CSP8 sealer  and immediately stored at −80°C. Time from blood sampling to −80°C freezer was <2 h.All patients were in a fasting state. Blood sampling for EV measurement was performed during the initial phase of the surgical procedure before cardiopulmonary bypass and before entering extracorporeal circulation and heparinization. Blood was sampled using a syringe and carefully drawn from an indwelling catheter in the radial artery, from the right atrium through a central venous catheter, and from the coronary sinus through a 12 French retrograde catheter. Blood samples were then immediately dispensed in a tube containing sodium citrate and centrifuged at 20°C at 2,000 × sinus coronarius and radial artery were calculated and are expressed as trans-coronary gradients . A positive trans-coronary concentration gradient can indicate release of EVs over the heart and/or a reduced EV clearance, a negative gradient can indicate reduced release and increased uptake/and or degradation of EVs over the heart, and/or release of EVs from the lung tissue/pulmonary vasculature.We defined EVs measured by flow cytometry as vesicles between ∼0.3 and 0.9 μm (previously known as microvesicles/particles). Differences in EV concentrations between plasma samples from Fluorescent labeled antibodies toward Connexin-43 , TroponiAs an additional potential cardiomyocyte marker we measured EVs exposing N-Cadherin (N-Cad) .To study the vascular endothelium EVs exposing VE-cadherin (VE-Cad) were measured .For inflammation EVs exposing myeloperoxidase (MPO) –17 or PeSee n) and/or proportions. The following statistical tests have been used: Mann–Whitney test for comparison of two groups of independent variables, Kruskal–Wallis test for comparison of >2 groups of independent variables, and Wilcoxon signed rank test for comparison of two groups of dependent variables. Correlations were studied with Spearman’s rank correlation coefficient. A p-value <0.05 was considered statistically significant.Continuous variables are expressed as mean value and standard deviation (SD), or median value and interquartile range (IQR) or percentiles, as appropriate, while categorical variables are expressed with number of cases .The CABG PREFERS study was approved by the Stockholm Ethical Review Board, Sweden (2013/1869-31/1) and was conducted according to International Conference on Harmonization and Good Clinical Practice guidelines and compliant with the Declaration of Helsinki.Oral and written informed consent was obtained from all study participants, all included between January 2014 and June 2017.The present sub-study included patients where central blood samples were available. For logistic reasons, central blood sampling could not always be performed in all patients included in the CABG PREFERS study. Samples from the coronary sinus and radial artery were available in 81 patients, and for all three sampling locations  in 80 patients.The median age was 71 years, and 88% were men . A largeAround 70% of patients were on antiplatelet agents and 12% on oral anticoagulants. More than 60% of patients were on beta-adrenoreceptor antagonists, and 81% on statin therapy. Less than 1/3 of patients had other HF medication, such as angiotensin-converting enzyme inhibitors, angiotensin II-receptor antagonists and/or mineralocorticoid receptor antagonists. Seven percent of patients were on diuretics (furosemide), and this was equally distributed between HF phenotypes.See trans-coronary gradients for Con43 + TnT and Con43 + Cav3 EVs indicating cardiac release. There were positive but much smaller trans-coronary gradients also for VE-Cad EVs, PTX3 EVs, and MPO EVs, while for N-Cad EVs the trans-coronary concentration gradients were negative suggesting uptake or degradation of EVs over the heart, or perhaps a small release of N-Cad EVs from the lung tissue/pulmonary vasculature. Transcoronary gradients for all extracellular vesicles are shown in top panel of We found positive trans-coronary gradients of Con43 + TnT and Con43 + Cav3 EVs , LVEF , LAVI , E/é , and TR V-max .As illustrated in r = 0.41; p < 0.001), LVEF , LAVI , and LVMI , and there was a correlation of borderline significance between Con43 + TnT EVs and TR V-max .Also Con43 + TnT EVs and echocardiographic parameters were correlated: GLS .Furthermore, Con43 + Cav3 as well as Con43 + TnT EVs concentrations correlated significantly with preoperative NT-pro-BNP concentrations . In contrast, Con43 + Cav3 EV concentrations did not differ significantly between CAD disease groups, as there was a pronounced inter-patient variability in the concentration gradients of this EV type in patients with 1- or 2-VD . In fact, the median concentration gradient for MPO EVs was negative in patients with 1- or 2-VD  in HFpEF and HFrEF, respectively].The median MPO-EV concentration was almost two times higher in the right atrium compared to in the radial artery or coronary sinus, and right atrium concentrations were slightly higher in HFpEF compared to HFrEF [median concentrations 1157 vs. 929 vesicles/μL  Con43 + TnT and Con43 + Cav3 EV concentrations were elevated in coronary sinus compared to radial artery, (b) the Con43 + TnT and Con43 + Cav3 EV profile was different in patients with HFrEF compared to those with HFpEF, (c) the coronary sinus concentrations of Con43 + TnT and Con43 + Cav3 EVs correlated significantly with echocardiographic and laboratory markers of HF. Our data indicate that the EV phenotype exposing Con43 + TnT and Con43 + Cav3 are released from cardiomyocytes. The EV release associates with markers of HF functional severity.trans-coronary gradient of Con43 + TnT EVs found in the HFpEF patients is in line with a recent study where it was shown that circulating troponin was a biomarker for future HFrEF but not for HFpEF, thus supporting our results  and it is unlikely that this passage should influence EV levels significantly.trans-coronary EV release profile is different between HF phenotypes with HFrEF being associated with a pronounced release of EVs reflecting myocardial injury. In HFpEF, on the other hand, there is a clear stress-induced release of EVs but much lower release of myocardial injury-related EVs. Con43 + TnT and Con43 + Cav3 EVs are rapidly cleared over the pulmonary circulation, likely due to uptake and degradation in the pulmonary vasculature. As EVs may transfer biological information and have distant effects, future studies on EVs released from cardiomyocytes and its effects on the cardiopulmonary system in HF, as well as other types of cardiovascular diseases, are warranted.Con43 + TnT and Con43 + Cav3 EVs are released over the heart and associate with HF and signs of myocardial stress, suggesting involvement of stretch-activated pathways leading to cardiomyocyte EV release. The The 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 Stockholm Ethical Review Board, Sweden. The patients/participants provided their written informed consent to participate in this study.HW, FM, and HP: conceptualization. HW, FM, HP, MC, DM, and MEk: formal analysis and methodology. HW, HP, FM, and DM: investigation, validation, visualization, and wrote manuscript—original draft preparation. HW, HP, FM, MEk, DM, CH, CL, UL, MKr, MC, PL, and BP: review and editing of manuscript. All authors contributed to the article and approved the submitted version.


Simpson's rule is generally used to estimate cardiac volumes. By contrast, modern methods such as Virtual Reality (VR) utilize mesh modeling to present the object's surface spatial structure, thus enabling intricate volumetric calculations. In this study, two types of semiautomated VR models for cardiac volumetric analysis were compared to the standard Philips dedicated cardiac imaging platform (PDP) which is based on Simpson's rule calculations.This retrospective report examined the cardiac computed tomography angiography (CCTA) of twenty patients with atrial fibrillation obtained prior to a left atrial appendage occlusion procedure. We employed two VR models to evaluate each CCTA and compared them to the PDP: a VR model with Philips-similar segmentations (VR-PS) that included the trabeculae and the papillary muscles within the luminal volume, and a VR model that only included the inner blood pool (VR-IBP).Comparison of the VR-PS and the PDP left ventricle (LV) volumes demonstrated excellent correlation with a Simpson's rule and polygon summation algorithms produce similar results in normal morphological LVs. However, this correlation failed to emerge when applied to RVs and irregular chambers.The findings suggest that the polygon summation method is preferable for RV and irregular LV volume and function calculations.  Virtual reality; Polygon summation; Volumetric analysis; Heart chambers. TVirtual reality (VR) imaging may be a viable alternative for cardiac volumetric analysis. It allows for comprehensive visualization of complex anatomical structures such as those present in congenital heart defects and may contribute to perioperative planning and interventions , 11, 12.Compared to other methods, semiautomated VR segmentation is quick, accurate, and less prone to inter-observer variability. Thus, this methodology may facilitate additional assessments in complex anatomical environments , 19. The22.1This retrospective study was conducted in a single center. The dataset was derived from the records of adult patients followed at the Sheba Medical Center (SMC) Heart Institute between 2017 and 2019. All the patients in the cohort underwent a dedicated CCTA scan. The study protocol was approved by the SMC institutional review board. The participants’ informed consent was waived since the data were retrieved without identificatory information from medical records. Data treatment adhered to the principles of Good Clinical Practice (GCP).2.2CCTA was performed using retrospective gating utilizing a 256-slice scanner  with 70 ml of intravenous non-ionic contrast medium  followed by 40 ml of saline flush (at an injection rate of 4–5 ml/s). The CCTA data were reconstructed using a dedicated platform ; Philips Healthcare). Volumetric analysis was conducted using the best available diastolic phase that represented 80%–90% of the R-R interval.The VR simulated heart models were created retrospectively based on the same CCTA data collected for each patient. Images were uploaded as Digital Imaging and Communications in Medicine (DICOM) files into D2P® software  for cardiac chamber segmentation. The mesh files were converted into stereolithography (STL) format files that describe 3D objects’ surface geometry. The operator was able to see the resulting segmentation in a stereoscopic view using a dedicated system .2.3For the volumetric analysis, each heart was evaluated in the same phase using three different analysis methods. The first implemented the Phillips dedicated cardiac CT imaging platform (PDP) , and the2.4The Philips software automatically reconstructed the analyzed ventricles, and their volumes were measured. The dedicated cardiac CT imaging platform segmented the inner ventricular area. The measurements included the ventricular trabeculae and both chambers' papillary muscles, as is common practice . The bas2.5Segmentations based on the outer surfaces of the two ventricles were performed using the D2P® segmentation software. The tissue segmentations were done semi-automatically with two different defined segmentation borders. The first segmentation was the Philips-similar VR segmentation (VR-PS), which included the trabeculae and the papillary muscles within the luminal volume, which produced a smooth edge similar to the Philips platform segmentation A. The sea is the area of the triangle, and In practice, when using the D2P® segmentation, a 3D mesh is created of the cavity's outer surface consisting of triangular and polygonal elements that create a phantom of the chosen ventricle A and 3B.Note that the order of vertices matters here, as it yields the positivity or negativity of each part of the summation.2.6We examined the correlations between the VR chamber's volumetric measurements and the Phillips dedicated cardiac CT imaging platform (PDP), which is considered the gold standard for volumetric measurements. The concordance between the variables was evaluated using Lin's Concordance Correlation Coefficient (ed (MSE) , 24, 25.ed (MSE) , 27. A p3The database was composed of the records of 20 adult patients  with a mean age of 83.4 years (±13.0 years). Their demographics and associated comorbidities are presented in c) between the VR-PS and the PDP LV volume measurements was 0.983 . The B&A plots showed very good agreement, with a mean difference of 4.19 mm3 ± 6.04  and a MSE of only 52.16 mm6 . The B&A plots showed good agreement with a mean difference of 1.26 mm3 ± 17.31  and a MSE of 284 mm6 , p < 0.001 . The RV volume measurements differed by -8.89 cm3 , p < 0.05 . Shapiro-Wilk tests indicated that all outcomes were normally distributed.Comparison of the VR-IBP and VR-PS volume measurements revealed that the VR-IBP measurements were significantly smaller. The LV volumes differed by -18.18 cm4In the earliest days of 3D anatomical assessment and imaging computation, radiologists used geometric shapes such as planes, spheres, ellipsoids, and truncated cones to define organs and cavities. These structures were used to model the external contours of the human body and the structure of individual organs. These geometrically simple and easy-to-comprehend phantoms were ideal for the primitive computer technology of the time , 29, 30.Cardiac function comprehension and 3D anatomical assessments of its chambers: Simpson's rule has been shown to be an effective tool for estimating cardiac chamber volumes and functions [unctions , 33, 34.unctions . This meunctions , 37.3D VR imaging, unlike the voxel summation method, uses advanced tetrahedron volume summation to estimate chamber volumes. 3D VR is a convenient, fast, and efficient method of assessing complex cardiac structures . SeveralThe comparison of the LV volumes calculated by the Phillips dedicated cardiac imaging platform (PDP) and those calculated by the VR-Philips-similar segmentation (VR-PS) showed that in the LV there was an excellent Automated 3D segmentation of complex anatomical structures may be inaccurate as a result of low contrast differences, missing edges, and/or low signal-to-noise ratios . Because5This study was performed on a selected population of adult patients’ hearts awaiting left atrial appendage occlusion. Further evaluation needs to be performed on younger patients with anatomically normal, hypertrophic and affected hearts (as seen after myocarditis), and with congenital heart defects in order to establish the superiority of one method over the other. Moreover, it was also assumed the calculation of all the volumes by both modalities were correct, as it was impossible to evaluate the inner blood pool by other techniques.6Cardiac chamber analysis is currently based on voxel area summation using Simpson's equation. The findings here suggest that polygon summation is a feasible and accurate method for cardiac volume assessment which may be preferable for RV and irregular LV volume and function calculations.David Yogev and Shai Tejman-Yarden: Conceived and designed the experiments; Performed the experiments; Wrote the paper.Orly Goitein: Conceived and designed the experiments; Contributed reagents, materials, analysis tools or data; Wrote the paper.Omer Feinberg: Conceived and designed the experiments; Analyzed and interpreted the data.Yisrael Parmet: Analyzed and interpreted the data; Wrote the paper.Shay Ilouz: Performed the experiments; Wrote the paper.Tomer Goldberg, Netanel Nagar, Dor Freidin, Oliana Vazgovsky, Sumit Chatterji, Yishay Salem and Uriel Katz: Contributed reagents, materials, analysis tools or data; Wrote the paper.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Data will be made available on request.The authors declare no conflict of interest.No additional information is available for this paper.


Transcatheter mitral therapies offer treatment options to selected patients who are unable to undergo open procedures due to prohibitive surgical risk. Data detailing the design and structure of transcatheter mitral services to ensure appropriate patient selection and tailored management strategies is lacking. We report our initial experience of developing and running a purpose-built transcatheter mitral service. The nature and number of referral sources, the multi-disciplinary make-up of the dedicated Mitral Heart Team and the use of integrative imaging assessment with incorporation of computational solutions are discussed. In addition, a summary of the clinical decision-making process is presented. This report sets out a framework from which future clinics can evolve to improve and streamline the delivery of transcatheter mitral therapies. The application of the Heart Team to facilitate transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis is now established in routine clinical practice with well-defined patient pathways . It is aA one-stop TMV clinic was run by five Cardiologists. The first two (RR and JH) were imaging cardiologists (echocardiography and cardiac CT) with experience in managing patients with complex valve disease and heart failure, and the third, fourth and fifth were structural interventional cardiologists  with experience in transcatheter aortic and mitral therapies. Discussion at a Mitral Heart Team meeting comprising of a heart failure/imaging specialist, cardiac surgeon and interventional cardiologist was undertaken for all patients entering the TMT pathway. If treatment was indicated, but surgical options were deemed high risk, then assessment in the TMV clinic was organized. For other patients a clinic review was arranged to ensure transcatheter options were explored prior to resorting to medical therapy alone or palliation. Following approval for review, patients were seen in a purpose-designed, specialist TMV clinic. Integral to the clinic was the availability of a spectrum of TMVT devices. These comprised  transcatAs awareness of the TMV clinic grew, there was a rapid increase in referrals which was only interrupted by the Coronavirus-19 pandemic . The cliBaseline characteristics are recorded in There are several important observations from our experience in establishing a dedicated TMV service. The proportion of patients receiving comprehensive TMVT assessment increased from 9 in 2017 to 41 in 2021, despite a significant downturn in 2020 and early 2021 due to the COVID-19 pandemic, signaling a growing awareness and demand for the service. Moreover, participation in the clinic resulted in definitive procedural management for 46.8% of these patients. A modest increase in transcatheter therapy was noted, reflecting similar (but amplified) trends from US registry data . Our datThe structure of our TMVs model was strategically designed to streamline the clinical decision-making process. Patients were often referred once symptomatic with substantial baseline comorbidity and frailty equating to poor physiological reserve. In such cases, rapid assessment and treatment is vital. To achieve this, we positioned a mix of specialists in the clinic as an entry point to the pathway with same day diagnostics for the majority of patients. We believe this bestowed greater referrer confidence in the clinic and increased referrals to the service. The incorporation of MV surgeons earlier in the pathway increased surgical confidence in the TMV clinic, enabling bilateral referral pathways with MV surgeons operating on patients initially deemed to be at high surgical risk, and patients who were not ideal for surgery being referred to the TMV clinic. The positioning of an imaging specialist at the fulcrum of the pathway enabled faster decision making and facilitated access to bioengineering solutions for pre-procedural planning and modeling.Management of MR is complex, and a multitude of factors are considered when deciding the optimum management strategy . ClinicaThe means to assessing patient symptomatic status and lesion severity are well-established, however interpreting these findings in the context of concurrent cardiac comorbidity is vital. MR  is frequently accompanied by concurrent significant tricuspid regurgitation (TR). In the COAPT cohort, greater than moderate TR conferred an additional mortality and morbidity risk . TherefoTreatment of concurrent coronary artery disease (CAD) is another important factor in the management of MR, and particularly relevant in ischaemic MR, and warrants address prior to definitive valve treatment . Within Whilst primary mitral regurgitation (PMR) requires treatment of the valve by repair or replacement once thresholds are met, pharmacotherapy is a core component of secondary mitral regurgitation (SMR) management. Within our cohort, 30% patients received optimum medical therapy, with one patient additionally receiving cardiac resynchronisation therapy (CRT). Optimisation of medical therapy yields improvements in LV function, severity of mitral regurgitation and LV geometry . This haTreatment strategy is dependent upon the accurate delineation of anatomic suitability. Careful assessment using transthoracic and/or transoesophageal echocardiography is indicated. Aside from important but generic information on the LV/RV volumes and function, valuable information impacting feasibility for TMVT is obtained. This includes coaptation height, tenting area, leaflet tethering, calcification, posterior leaflet height, annulus geometry and valve area. Important anatomical criteria along with cautions for different TMVT are included in Assessment of surgical risk presented an additional challenge when administering the TMV service. Within our institution, surgical risk was estimated by Heart Team consensus, as suggested in ESC guidance . In our TRAnscatheter MItral (TRAMI) registry, revealed that centers performing TEER in <25 patients/year had comparable in-hospital mortality to those performing >25 procedures/year and that this was the case with cut-offs at 10 and 50 procedures a year . PL holds a Wellcome Trust Senior Research Fellowship (209450/Z/17/Z).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.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.


CME CREDIT TM by reading this case and reviewing the video quizzes embedded. Then follow the link to obtain CME credit.Earn free AMA PRA Category 1 Credit Figure 1, and chest x-ray (CXR) showed a slightly increased cardiothoracic ratio with clear lung fields.A 60-year-old man had undergone mechanical mitral valve replacement in 2012 due to mitral valve prolapse complicated by infective endocarditis. He has a history of atrial fibrillation, for which he underwent pulmonary vein isolation with mitral isthmus ablation in March 2020. He presented 1 year later with a 4-week history of exertional dyspnea and fatigue. Vital signs were within normal limits. Physical exam was remarkable for a mechanical S1 click on cardiac auscultation. His medication regimen included coumadin, aspirin 81 mg daily, amiodarone 200 mg daily, and rosuvastatin 10 mg daily. Laboratory workup was unremarkable except for a slightly subtherapeutic international normalized ratio (INR) of 2.3 and a mildly elevated brain natriuretic peptide (BNP) of 150 pg/mL. An electrocardiogram (ECG) is shown in What is the most likely cause of dyspnea in this patient?Myocardial infarctionProsthetic valve dysfunctionCongestive heart failurePulmonary embolismRequires more investigationFigure 1) showed a normal sinus rhythm with Q waves in leads II and III, and aVF and inverted T wave in leads V4, V5, and V6. Theoretically, all of the above are possible causes of dyspnea in this patient; however, none of the aforementioned answers will fit perfectly with the clinical presentation. Although the patient presents with subtherapeutic INR and mildly elevated BNP, the patient is euvolemic on exam, CXR does not show signs of congestion, and he had crisp mechanical heart sounds that make mitral valve prosthesis dysfunction and congestive heart failure unlikely. ECG showed Q waves in the inferior territory suggesting an old myocardial infarction, but the patient denies any history of known myocardial infarction or chest pain. Additionally, the troponin was negative. Pulmonary embolism would be highly unlikely in an anticoagulated patient. To further evaluate his symptoms, transthoracic echocardiography (TTE) was done (Videos 123).12-lead ECG  with an ejection fraction (EF) in the 40% to 45% range and a lateral wall pseudoaneurysm (Videos 23). Video 2 shows a narrow neck opening from the posterolateral wall to the aneurysm, while Video 3 demostrates free passage of the ultrasound contrast from the LV to the pseudoaneurysm. Doppler recordings indicated normal function of the mechanical mitral valve (not shown).TTE showed a mildly impaired left ventricular (LV) systolic function  confirmed the TTE findings and demonstrated a large bilobed posterolateral LV pseudoaneurysm measuring up to 7.8 cm in length. Coronary CT angiography showed mild coronary atherosclerosis but no significant stenosis.A cardiac computed tomography (CT) scan Cardiac fluorodeoxyglucose positron emission tomography (FDG-PET)Coronary angiographyAll of the aboveVideo 5). There was no extra cardiac FDG uptake to suggest inflammation. Cardiac magnetic resonance (CMR) can define anatomy, measure LV volume, and assess myocardial viability. CMR showed a basal–mid-lateral wall myocardial infarction with contained rupture resulting in a large (8.1 × 3.9 cm) LV pseudoaneurysm (Video 6). Interestingly, coronary angiography was normal.Cardiac fluorodeoxyglucose-positron emission tomography (FDG-PET) is a noninvasive imaging modality that differentiates normal myocardium from scarred myocardium by lack of FDG uptake. The patient underwent FDG-PET and it did not show FDG uptake in the pseudoaneurysm  or obstructive coronary artery disease.The patient had mitral isthmus ablation 1 year prior to this presentation. In preparation for the ablation, the patient had a cardiac CT that did not show a pseudoaneurysm .The patient underwent resection of a bilobed pseudoaneurysm and repair with placement of a Hemashield dacron patch (MAQUET Cardiovascular LLC). There was extensive expansion of the pseudoaneurysm beyond the initial point of rupture. The total diameter of the aneurysm was 7.2 cm and the orifice measured approximately 4 × 3 cm. CMR 1 week post repair showed a thin myocardial repair graft at the mid-inferolateral segment of the LV with mild biventricular dysfunction (2 Myocardial infarction, cardiac surgery, trauma, and infections are well-recognized causes of ventricular pseudoaneurysms. Of all cardiac surgeries, mitral valve replacement and aneurysmectomy carry the highest risk.3 The site of the pseudoaneurysm is primarily related to the etiology. Post-myocardial infarction pseudoaneurysms often occur in the inferior or posterolateral wall and less commonly at the apex. Postoperative pseudoaneurysms are usually in the posterior subannular region after mitral surgery, right ventricular outflow tract after congenital heart surgery, and in the subaortic region and/or aortomitral intervalvular fibrosa after aortic valve replacement.3Ventricular pseudoaneurysm results from rupture of the myocardium that is walled off by pericardium, fibrous tissue, or hematoma. It lacks true myocardium or endocardium in its wall and typically has a narrow neck.3 On the contrary, “true aneurysms” have all layers of the myocardium but they are thinned out, scarred, or fibrotic. Additionally, the neck is wide and most commonly occurs at the ventricular apex or anterior wall.4 Our patient had a pseudoaneurysm related to a posterolateral infarction that likely resulted from spasm in the left circumflex artery during mitral isthmus ablation.1 To our knowledge, this is the first reported LV pseudoaneurysm resulting from mitral isthmus ablation.Meanwhile, endocarditis can be complicated by pseudoaneurysm at the aortomitral intervalvular fibrosa.3 On exam, 70% of patients will have a murmur, most likely to-and-fro in character.2 Almost all patients with pseudoaneurysm will have an abnormal ECG, most commonly in the form of nonspecific changes or an old infarct. However, 20% of patients will have ST-segment elevation.2 TTE is a reasonable first step for diagnosing pseudoaneurysms. Nonetheless, CT or CMR better define the extent of the aneurysm and can assist in surgical planning. Surgery is the preferred approach because medical management carries a 50% mortality risk, while surgical perioperative mortality is less than 10%.6 More recently, percutaneous closure has shown promising results in high-risk surgical candidates.7Patients with LV pseudoaneurysms present with a wide spectrum of symptoms ranging from being completely asymptomatic to sudden cardiac death.Mitral isthmus radiofrequency ablation can cause injury in the left circumflex artery territory.Multimodality imaging is essential to determine the etiology and anatomy of pseudoaneurysms.Surgery is the treatment of choice in patients with ventricular pseudoaneurysms.


Left atrial (LA) function is a marker of prognosis in patients with heart failure. The prognostic implications of an improvement in LA function in addition to an improvement in left ventricular (LV) function after cardiac resynchronization therapy (CRT) implantation are unknown. This study aimed to evaluate the prognostic value of a significant change in LA reservoir strain (RS) and/or LV global longitudinal strain (GLS) after initiation of CRT.P < 0.001). On multivariable analysis, complete reverse remodelling  was associated with the lowest risk of mortality.LARS and LVGLS were measured with speckle-tracking echocardiography. Significant improvement in LARS and LVGLS was defined as a percentage change of +5% and +20% at 6 months after CRT implantation, respectively. Patients were divided into three groups: no significant reverse remodelling (no improvement in LARS and LVGLS), incomplete reverse remodelling (improvement in LARS or LVGLS), and complete reverse remodelling (improvement in LARS and LVGLS). The primary endpoint was all-cause mortality. A total of 923 patients  were included, of which 221 (24%) had complete reverse remodelling, 414 (45%) incomplete reverse remodelling, and 288 (31%) no significant reverse remodelling. Five-years’ mortality was 24%, 29%, and 36% for patients with complete, incomplete, and no significant reverse remodelling, respectively (Patients with complete reverse remodelling have a lower mortality risk than those showing incomplete or no significant reverse remodelling. The use of integrated LA and LV deformation imaging may improve risk-stratification of CRT recipients.  Accordingly, the aims of this study were (i) to quantify changes in LA reservoir strain (LARS) and LV GLS after CRT and (ii) to assess the prognostic implications of a significant change in LARS, LV GLS or both, 6 months after initiation of CRT.1 were included from an ongoing single-centre registry at the Leiden University Medical Center in The Netherlands. Clinical and echocardiographic data were obtained from the departmental electronic medical record  and retrospectively analysed. An ischaemic aetiology of HF was defined by the presence of significant coronary artery disease on invasive coronary angiography. Quality of life was evaluated with the Minnesota Living with Heart Failure Questionnaire. Renal function was quantified by estimating the glomerular filtration rate with the Modification of Diet in Renal Disease Study (MDRD) equation. The study complies with the Declaration of Helsinki and was approved by the Institutional Review Board. Considering the retrospective nature of the study and all data being handled anonymously, the Medical Ethical Committee waived the need of patient written informed consent.Patients with HF who underwent CRT implantation according to prevailing guideline recommendations,11 Right ventricular end-systolic and end-diastolic areas were traced in a focused right ventricular apical view according to current recommendations.11 Tricuspid annular plane systolic excursion was measured on M-mode recordings of the lateral tricuspid annulus in a right ventricular-focused view.11 Right ventricular peak systolic pressure was derived from the peak velocity of the tricuspid regurgitant jet according to the Bernoulli equation, adding the right atrial pressure (estimated by the inspiratory collapse and diameter of the inferior vena cava).11 The severity of mitral and tricuspid regurgitation was graded using a multiparametric approach, as recommended by current guidelines.12 Speckle tracking LV GLS was averaged from 17 LV segments, and measured from apical views .13 The region of interest was traced manually and adjusted to the myocardial thickness. Speckle tracking LA strain was measured on the apical four-chamber view, according to current guidelines with the onset of the QRS complex used as the zero-reference point.15 The endocardium of the LA wall was traced manually and corrected by adjusting the region of interest or the width of the contour, excluding the pulmonary vein ostia and LA appendage . LARS was chosen over LA conduit strain and LA contractile strain because it shows a good correlation with LA wall fibrosis on magnetic resonance imaging,16 reflects atrial compliance and can still be assessed in patients with atrial fibrillation.14 Both LV GLS and LARS are represented as absolute (i.e. positive) values.All patients underwent transthoracic echocardiography before CRT implantation in the left lateral decubitus position with commercially available ultrasound equipment . ECG-triggered echocardiographic data were stored digitally in a cine-loop format for offline analysis using EchoPAC version 203 . LV volumes, LVEF and LA volumes were measured using the Simpson’s biplane method.CRT implantation was performed according to a standard approach, i.e. insertion of the right atrial and ventricular leads via the subclavian or cephalic veins. Before insertion of the LV lead, coronary sinus venography was performed. The LV pacing lead was then introduced into the coronary sinus through an 8 Fr guiding catheter, and positioned in a posterior or posterolateral vein, if possible. Defibrillator functionality was included in most (96%) of the implanted devices. CRT recipients were followed up at regular intervals at the HF outpatient clinic, at which time the device was interrogated. Atrioventricular and interventricular delays were empirically set at 120–140 and 0 ms, respectively. CRT optimization was performed during follow-up visits at the discretion of the treating physician.Figure 2). The prognostic value of these thresholds was confirmed by Kaplan–Meier survival analysis and differences between groups were analysed using the log-rank test . The study cohort was subsequently divided into three groups: (i) no significant reverse remodelling (change in LV GLS <20% and change in LARS <5%); (ii) incomplete reverse remodelling ; and (iii) complete reverse remodelling (change in LV GLS ≥20% and change in LARS ≥5%) .In order to divide the study population into groups according to the degree of LV GLS/LARS change in response to CRT, spline curve analysis was performed. Spline curves were fitted to visualize the relation between the hazard ratio (HR) of all-cause mortality and the echocardiographic parameter in question, i.e. percentage change in LV GLS or LARS 6 months after CRT implantation. Based on this analysis, a 20% change in LV GLS and a 5% change in LARS were identified as optimal cut-off values  , which is linked to the governmental death registry database. Follow-up data were complete for all patients.post hoc analysis when normally distributed, whereas the Kruskal–Wallis test was used to compare continuous variables that did not follow a normal distribution. Categorical variables were compared using the Pearson χ2 test. A spline curve analysis was performed to assess the HR for all-cause mortality across a range of LV GLS and LARS values . A change in LV GLS of +20% and a change in LARS of +5% were identified, based on mortality excess (i.e. in which the predicted HR was ≥1). The inter- and intra-observer variabilities of LARS measurement were assessed by calculating the intra-class correlation coefficient on 20 randomly selected patients. The intra-class correlation coefficients for inter- and intra-observer variability were 0.94  and 0.95 , respectively. The intra-class correlation coefficients for inter- and intra-observer variability of LV GLS have been published previously,17 with an intra-class correlation coefficient for inter- and intra-observer variability of 0.92  and 0.97 , respectively, showing excellent agreement. Event-free survival curves were generated using the Kaplan–Meier method and differences between the three groups  were analysed using the log-rank test. To assess the association of different groups of LV GLS and LARS change with all-cause mortality, uni- and multivariable Cox proportional hazard models were constructed. For both uni- and multivariable analyses, HRs with 95% CIs were calculated. To inspect for multicollinearity, the Pearson correlation coefficient was calculated between continuous variables, assuming no significant multicollinearity when the correlation coefficient was <50%. In addition, the variation inflation factor was also calculated, assuming no significant multicollinearity when this value was <5. To investigate the incremental value of significant change(s) in LV GLS and/or LARS over clinical and conventional echocardiographic parameters to predict outcome, likelihood ratio testing was performed, for which the change in global chi-square values was calculated and reported. A two-sided P-value <0.05 was considered statistically significant. Statistical analysis was performed using SPSS for Windows, version 25.0  and R version 4.0.1 .Continuous data are presented as mean ± standard deviation when normally distributed and as median and interquartile range when not normally distributed. Categorical data are presented as frequencies and percentages. Continuous variables were compared using the analysis of variances test with Bonferroni’s Table 1, while Table 2 summarizes the echocardiographic data for the overall population. An ischaemic aetiology of HF was present in 539 (58.4%) patients. The mean LV GLS and median LARS at baseline were 7.6 ± 3.4% and 12.7 (7.8–18.4)%, respectively.A total of 923 patients  were included. Baseline clinical characteristics are shown in At 6 months after CRT implantation, 288 (31.2%) patients showed no significant reverse remodelling, while 414 (44.9%) showed incomplete reverse remodelling and 221 (23.9%) showed complete reverse remodelling. Of the 414 individuals with incomplete reverse remodelling, a significant improvement in LV GLS without a significant change in LARS was seen in 270 (65.2%) patients, while 144 (34.8%) patients showed a significant change in LARS but not in LV GLS. The Pearson correlation coefficient for the relative change in LARS and LV GLS (expressed as continuous variables) was 0.153, whereas the variation inflation factor was 1, assuming no significant multicollinearity between both variables.Table 1). In addition, patients with complete reverse remodelling had larger LV ESV, lower LVEF and more impaired LV GLS and LARS at baseline, compared with the other two groups (Table 2).Patients with complete reverse remodelling were more likely to be female with a non-ischaemic HF aetiology, more likely to be in sinus rhythm and had a longer QRS duration at baseline, compared with the other two groups (P = 0.178), whereas the percentage change in LARS was 46 ± 8% vs. 10 ± 5%, respectively (P < 0.001).Of the 340 patients with moderate or severe MR at baseline, 200 (59%) patients showed significant improvement in MR severity (reduction of ≥1 grade) at follow-up, whereas 140 (41%) patients showed no significant improvement (reduction of <1 grade). The percentage change in LV GLS for MR improvers vs. non-improvers was 43 ± 10% vs. 24 ± 8%, respectively (P < 0.001) . Patients with complete reverse remodelling showed significantly lower mortality rates compared with those with incomplete reverse remodelling and no significant reverse remodelling . On multivariable analysis, incomplete reverse remodelling  and complete reverse remodelling  were independently associated with better outcomes (Table 3). There was no interaction between the percentage difference in LV GLS and change in LV ESV with outcome  or the percentage difference in LARS and change in LV ESV with outcome .After a median follow-up of 91 (49–138) months, 546 (59.2%) patients died. Five-year mortality rates were 36%, 29%, and 24% for patients with no significant reverse remodelling, incomplete reverse remodelling, and complete reverse remodelling, respectively (P < 0.001) as well as a percentage change in LV GLS  were both independently associated with all-cause mortality on the multivariable Cox regression analysis.Of interest, when looking at the percentage change in LARS and LV GLS expressed as continuous variables, a percentage change in LARS  and various clinical parameters, likelihood ratio testing was performed. The baseline model comprised all covariates used in the multivariable Cox regression analysis, i.e. age, sex, arterial hypertension, diabetes mellitus, dyslipidaemia, ischaemic aetiology for HF, estimated glomerular filtration rate, New York Heart Association class III–IV, baseline LV ESV, baseline left atrium volume index, baseline LV GLS, baseline LARS, and tricuspid annular plane systolic excursion.In order to investigate the incremental prognostic value of change in LV GLS and LARS, in addition to the conventional definition of CRT response  .Addition of the conventional definition of CRT response (≥15% reduction in LV ESV) to the baseline clinical model showed incremental prognostic value (P < 0.001) . A third model, including both a significant improvement in LV GLS and LARS (change in LV GLS ≥20% and change in LARS ≥5%), provided further incremental prognostic value (P < 0.001) .Next, addition of a significant change in LV GLS (change in LV GLS ≥20%) to the baseline clinical model and ≥15% reduction in LV ESV, yielded incremental prognostic value (The main findings of this study are summarized as follows: (i) patients with complete reverse remodelling (significant improvement in both LARS and LVGLS) after CRT implantation have better outcomes than patients showing incomplete reverse remodelling (significant improvement in LARS or LVGLS) or no significant reverse remodelling (no significant improvement in LARS and LVGLS) and (ii) an integrated assessment of changes in LARS and LV GLS has incremental prognostic value over conventional echocardiographic indices of LV reverse remodelling.19 The use of LV ESV to define CRT response however, has some limitations: (i) it does not adequately reflect active myocardial deformation and (ii) a reduction in LV ESV may occur without the recruitment of contractile reserve, which has been associated with better outcomes in patients receiving CRT.20 Myocardial strain imaging by speckle tracking echocardiography at least partially overcomes these limitations, and its use in characterizing CRT response is supported by outcome data. In a study of 761 HF patients, Pouleur et al.3 demonstrated that CRT resulted in a significant improvement in LV function assessed by LV GLS and this improvement translated into better outcomes. In addition, van der Bijl et al.17 demonstrated that patients showing a significant improvement in LV GLS but not in LV ESV had better long-term outcomes when compared with patients showing no improvement in LV GLS and LV ESV. The results of this study further support the use of LV GLS in patients receiving CRT and show the incremental value of LV GLS to predict outcomes over conventional echocardiographic parameters of CRT response.The echocardiographic definition of CRT response is most commonly defined as ≥15% reduction in LV ESV at 6 months after device implantation.4 and may impose an additional volume overload on the thin-walled LA, leading to LA structural remodelling.21 LA remodelling is accompanied by an increase in interstitial fibrosis of the atrial wall, leading to a progressive reduction in LA compliance. Reduced LA compliance in turn, not only decreases LV preload (and therefore LV cardiac output)22 but also unfavourably increases the pulsatile load on the pulmonary circulation, contributing to the development of post-capillary pulmonary hypertension and right ventricular-pulmonary arterial uncoupling.24 LA electrical and structural remodelling also enhances the risk of developing atrial fibrillation22 which has been associated with poor outcomes in HF.25 CRT has the potential to reverse many of these deleterious effects on the LA. The initiation of CRT significantly reduced LA volume in a study of 107 patients with HF.7 Moreover, LA reverse remodelling after CRT has been associated with a significant reduction in the risk of incident atrial arrhythmias,26 as well as a reduction in the occurrence of HF hospitalization or death.27LV diastolic dysfunction is a common finding in HF with reduced LVEF and may lead to elevated LV filling pressures, which increase LA afterload. In addition, functional mitral regurgitation is frequently found in HF patients,28 Furthermore, LARS is a functional parameter and has shown a good correlation with LA compliance. LARS has also shown a good correlation with the extent of atrial fibrosis on cardiac magnetic resonance imaging.16 The prognostic impact of a significant change in LARS after CRT implantation, however, has not been extensively evaluated in CRT recipients. In a study of 30 patients undergoing CRT implantation, Valzania et al.8 showed an improvement of LARS in CRT responders, with concomitant improvement in LV systolic and diastolic function. In a limited cohort of CRT recipients, Dokuni et al.9 investigated the effects of CRT on LARS and demonstrated an association between improved LARS after CRT and better outcomes.Although the beneficial effect of CRT on LA volume is well described, LA functional changes occur well before LA dilatation occurs.et al.9 indeed demonstrated that CRT recipients show impaired LA reservoir function in parallel with LA dyssynchrony, becoming more pronounced as the QRS complex broadens. This shows that LA and LV (dys)function are closely linked in CRT candidates. In patients with impaired LA reservoir function, CRT may therefore have the potential to improve LA function by reversing LV dyssynchrony and subsequently, LA dyssynchrony. The results of the present study underscore the importance of evaluating both LA and LV function by showing that complete left-sided reverse remodelling is associated with better outcomes compared with incomplete reverse remodelling or no significant reverse remodelling.Because the LA is anchored by the pulmonary veins, the major determinant of LA expansion is the systolic descent of the atrioventricular plane towards the apex, which is mainly driven by LV longitudinal function. Impaired LV longitudinal function and loss of LV synchrony, which is typically seen in CRT candidates, may therefore have a negative impact on LA synchrony and LA reservoir function. Dokuni 29 As such, patients with contractile reserve, may initially have lower LA and LV strain values, but show the ability to have a more pronounced improvement in LA and LV strain values after CRT implantation. Additional studies however, are needed to confirm this hypothesis.Interestingly, patients who showed complete reverse remodelling initially had lower LA and LV strain values. This might at least partly be explained by the recruitment of contractile reserve. The presence of contractile reserve in CRT candidates has been demonstrated with dobutamine stress-echocardiography and was associated with better outcomes.30 For example, more recently introduced HF treatments, such as sodium-glucose co-transport 2 inhibitors and angiotensin-neprilysin inhibitors have shown promising effects on LV longitudinal function.32 In patients with atrial fibrillation, maintenance of sinus rhythm by pharmacological therapy or catheter ablation may improve LA reverse remodelling.33 In patients with significant residual mitral regurgitation after CRT implantation, percutaneous mitral valve repair represents another potential approach to improve LA function.34 However, whether these strategies will translate into better clinical outcomes in CRT recipients, requires prospective, randomized trials.The assessment of LARS and LV GLS after CRT implantation may allow the identification of a subgroup of CRT recipients who might otherwise be classified as responders by conventional criteria, but who will nevertheless experience suboptimal outcomes. The identification of such patients may argue for more intensive follow-up and allow the institution of therapies to optimize the effects of CRT, especially on LA and LV mechanics.In addition, although we often use a reduction in LV ESV ≥15% to define an echocardiographic response to CRT, this study shows that assessing the change in LARS and LV GLS shows incremental prognostic value over this parameter. Whether LARS and LV GLS should replace the well-established parameter of a ≥15% reduction in LV ESV however, requires further research.This study is subject to the limitations of its single-centre, retrospective, and observational design. Patients who died during the first 6 months after CRT implantation could not be included, and may have caused survival bias. LARS and LV GLS are vendor-dependent parameters, which cannot be compared directly between different platforms, and the thresholds of LARS and LV GLS used to define a CRT response in this study may not be generalizable to all patient populations. The duration of echocardiographic follow-up (6 months) disallows conclusions on whether LARS will potentially improve even further in some CRT recipients. Data on HF hospitalizations were not available. Mortality was ascertained by review of hospital records, linked to the governmental death registry database, which does not include granular detail on cardiac vs. non-cardiac mortality.Improvement in LV GLS and/or LARS at 6 months post-CRT is independently associated with a lower risk of mortality. Patients with complete reverse remodelling have the lowest mortality risk when compared with patients showing incomplete or no significant reverse remodelling. This supports the use of integrated LA and LV deformation imaging to assess CRT response and may aid in the refinement of risk-stratification of patients treated with CRT.European Heart Journal - Cardiovascular Imaging online.J.S. received funding from the European Society of Cardiology (ESC Training Grant App000064741).Conflict of interest: The Department of Cardiology, Heart Lung Center, Leiden University Medical Centre received research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. J.J.B. received speaker fees from Abbott Vascular. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare. V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD, and Novartis. The remaining authors have nothing to disclose.The data underlying this article will be shared on reasonable request to the corresponding author.jeac042_Supplementary_DataClick here for additional data file.


Patients with coronary artery disease (CHD) are prone to early myocardial ischemia; early diagnosis of myocardial ischemia is of great significance in judging disease progression and guiding clinical intervention. However, reports on the accuracy of dynamic electrocardiogram (ECG) in the diagnosis of myocardial ischemia in patients with CHD are inconsistent. The purpose of the current meta-analysis was to analyze the efficacy of ECG in the diagnosis of myocardial ischemia attack in CHD.  Chinese database  and English database  were searched. A study on the collection of dynamic ECG in the diagnosis of myocardial ischemic attack of coronary heart disease to extract data and calculate sensitivity (Sen), specificity (Spe), positive likelihood ratio (+LR), negative likelihood ratio (- LR), and diagnostic odds ratio (DOR). Draw summary receiver operating characteristic curves (SROC), and calculate area under curve (AUC). Stata 15 software was used for meta-analysis. P < 0.05).  Twenty-seven literatures were included in this study. Meta-analysis results showed that Sen = 0.78 (95% CI: 0.73~0.82), Spe = 0.76 (95% CI: 0.68~0.82), +LR = 2.79 (95% CI: 2.17~3.59), −LR = 0.33 (95% CI: 0.27~0.40), AUC = 0.84 (95% CI: 0.80~0.87), and DOR = 9.66 (95% CI: 6.13~15.21). Subgroup analysis showed that the sensitivity of 12-lead ECG was higher than that of 3-lead ECG. The sensitivity and specificity of ST segment and QTc interphase changes were higher than those of ST segment changes alone ( Dynamic ECG has high application value in the diagnosis of myocardial ischemia attack of coronary heart disease. But it is difficult to achieve a satisfactory level of use alone. ST segment combined with QTc interval observation can improve the diagnostic accuracy. Synchronous observation of ST segment and QTc interval can improve the diagnostic efficiency. Coronary atherosclerotic heart disease is short for coronary heart disease (CHD). It is myocardial ischemia, hypoxia, and necrotizing heart disease caused by coronary artery stenosis or occlusion which seriously affects acute coronary syndrome (ACS). ACS can be caused in severe cases. In China, the death rate ranks first among all kinds of cardiovascular diseases. And it still shows an upward trend in recent years .With the development of coronary atherosclerosis, myocardial ischemia and cardiac events may occur in patients with CHD. Early diagnosis of myocardial ischemia is of great significance in judging disease progression and guiding clinical intervention  . CoronarThe literature inclusion criteria are as follows: (1) type of study: diagnostic test of dynamic ECG for myocardial ischemic attack in patients with coronary heart disease; (2) subjects: patients with CHD, patients with suspicious CHD, patients with suspected coronary heart disease with myocardial ischemia, suspected coronary heart disease patients with asymptomatic myocardial ischemia (SMI), and suspected patients with acute coronary syndrome; (3) diagnostic methods: 12-lead or 3-lead dynamic ECG; the gold standard was CAG or myocardial perfusion imaging (MPI); and (4) outcome index: the number of true positive (TP), false positive (FP), false negative (FN), and true negative (TN) was described.The literature exclusion criteria are as follows: (1) repeatedly published papers, which are included in the literature with the largest sample size; (2) intervention study; (2) reviews, abstracts, and conference papers; (4) nonmyocardial ischemic attack ones are not included , or the healthy people were used as the control group; (5) case report; (6) unable to get full text; (7) incomplete data or data error; (8) literature other than Chinese and English; and (9) low-quality literature.Search English and Chinese electronic databases; Chinese databases include China National Knowledge Internet (CNKI), Wanfang Database, and VIP database. English databases include PubMed, Web of Science, Embase, SinoMed, and Cochrane Library. The search period is from January 2010 to December 2021. The keywords are as follows: Coronary Heart Disease, Myocardial Ischemia, Holter/dynamic electrocardiogram/DEG/dynamic ECG/continuous electrocardiogram/continuous ECG/Ambulatory ECG/Ambulatory electrocardiography, and Diagnosis. Search for MeSH-related terms and combination of subject words and free words.Literature screening was conducted independently by two researchers. The data of the included literature shall be extracted and resolved through negotiation when there is divergence. Develop data collection forms, including authors, years of publication, research objects, testing methods, diagnostic criteria, gold standards, and diagnostic efficiency. The same literature describes the data with the highest diagnostic efficiency under different diagnostic criteria.QUADAS-2 scale was used to evaluate the quality of literature . There aStata 15 software was used for data analysis. ROC graph is drawn to determine whether threshold effects exist. When there is a threshold effect, only SROC is fitted and the AUC is calculated. If there is no threshold effect, the heterogeneity caused by the nonthreshold effect is further judged. In the absence of heterogeneity, the fixed effect model was used. Random effect model is used when heterogeneity exists. Calculate the combined sensitivity (Sen), specificity (Spe), positive release ratio (+LR), and negative release ratio (-LR). Draw the SROC curve, and calculate the AUC. Metaregression was used to analyze whether there were differences in diagnostic efficacy among different diagnostic criteria, gold standards, and leads. Draw a Deek funnel diagram to see if it is symmetrical. Deek's test was used to determine whether there was publication bias or not.A total of 27 literatures were included in this study with 3747 cases in total. Literature screening process is shown in The result of literature quality evaluation is shown in Meta-analysis showed that Sen combined with Spe combined = 0.78 (95% CI: 0.73-0.82) and Spe combined = 0.76 (95% CI: 0.68-0.82) for the diagnosis of myocardial ischemia attack in CHD ; +LR = 2The DOR forest map of dynamic ECG diagnosis of CHD myocardial ischemia attack is shown in vs. 3-lead), diagnostic criteria , and gold standard (CAGVSMPI), the patients were divided into two groups and subgroups were analyzed. The results showed that there was no statistical difference (P > 0.05) between Sen merger and Spe merger among different gold standards. Spe in the 12-lead group was significantly higher than that in the 3-lead group (P < 0.05). There was no significant difference in the combination of Spe (P > 0.05). The combination of Sen and Spe in the ST+QTc interval change group was significantly higher than that in the ST segment change group (P < 0.05). (According to the number of dynamic ECG leads (12-lead < 0.05). .The funnel diagram of Deek is shown in Myocardial ischemia attack is an important event in the progression of coronary heart disease. It may suggest that the prognosis is poor and the risk of cardiac events is increased . At presAt present, it is considered that the value of using dynamic ECG alone is limited, and there is a certain gap between it and other methods such as stress dynamic CT myocardial perfusion imaging . This stThis study showed that the detection method and diagnostic basis of dynamic ECG can affect its diagnostic efficacy in myocardial ischemia. The diagnostic sensitivity of 12 leads was significantly higher than that of 3 leads. Combined observation of ST segment and QTc interval can effectively reduce missed diagnosis and misdiagnosis and improve the accuracy of diagnosis of myocardial ischemia. At present, the commonly used clinical dynamic ECG includes 12 leads and 3 leads, of which the former is more commonly used. Three-lead dynamic ECG continuously monitors cardiac activity through V1, V3, and V5 and simulates the electrical activity of the anterior wall of the ventricle. 12-lead dynamic ECG can be used to determine the occurrence time of myocardial ischemia by contrast scanning of ST segment trend map. The shape of ST segment and QTc interval were dynamically observed, and the interactive three-dimensional color trend map of 12-lead ST segment was provided. It can assist clinic to grasp the characteristics of ST segment changes during myocardial ischemic attack . Compare2+ flow occurred in myocardial action potential interphase. These phenomena were manifested as prolonged QT and QTc interval on dynamic ECG [During acute myocardial ischemia, parasympathetic activation occurs and catecholamines are released into the blood. Abnormal Caamic ECG . TherefoIn conclusion, dynamic ECG is effective in the diagnosis of myocardial ischemic attack in CHD. But it is difficult to reach a satisfactory level by using it alone. Other inspection methods should be applied jointly. 12-lead dynamic ECG and combined observation of ST segment and QTc interval changes can improve the diagnostic efficiency. However, this study has some limitations. It is mainly reflected in the following aspects: (1) the literature included is mainly in Chinese and less in English, so the representativeness may be insufficient; (2) there are few high-quality literatures, and conclusion extrapolation may be limited.