Antibodies to citrullinated protein antigens have been linked to altered left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA). Serum reactivity to several citrullinated protein/peptide antigens has been identified in RA, which are detectable years before RA onset and in individuals who may never develop RA. Among community-living individuals without heart failure (HF) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated associations between serum reactivity to citrullinated protein/peptide antigens, LV mass, LV ejection fraction (LVEF), and incident HF.th percentile cut-off in MESA. Number of EHR antibody responses to citrullinated protein/peptide antigens were summed for each participant (range 0–28). LV mass(g) and LVEF(%) were measured on cardiac MRI. Associations between EHR antibodies and LV mass and LVEF were evaluated using linear regression. Cox proportional hazards models were used to evaluate associations between EHR antibodies and incident HF during 11 years of follow-up, adjusting for age, gender, race/ethnicity, smoking status, systolic blood pressure, use of anti-hypertensive medications, self-reported arthritis, IL-6, body surface area, and estimated glomerular filtration rate.Among 1232 MESA participants, we measured serum reactivity to 28 different citrullinated proteins/peptides using a multiplex bead-based array. Each antibody was defined as having extremely high reactivity (EHR) if >95Mean age was 65±10, 50% were female, 40% were White, 21% were Black, 26% were Hispanic/Latino, and 14% were Chinese. Twenty-seven percent of MESA participants had extremely high reactivity to ≥ 1 citrullinated protein/peptide antigen. In fully adjusted analysis, every additional EHR antibody was significantly associated with 0.1% lower LVEF . No association was observed with LV mass  = 0.13±0.15 (p = 0.37)). Neither the presence nor number of EHR antibodies was associated with incident HF during follow-up ).Greater number of extremely highly reactive antibodies was associated with lower LVEF, but not with LV mass or incident HF. Thus, serum reactivity to citrullinated protein/peptide antigens was associated with subtle subclinical changes in myocardial contractility, but the significance in relation to clinically apparent HF is uncertain. Among individuals with rheumatoid arthritis (RA), risk for heart failure is 70% higher compared to the general population . Given tGeraldino-Pardilla and colleagues investigated associations between individual antibodies to citrullinated protein antigens (ACPA) and left ventricular structure and function in RA patients . They foACPA are known to become detectable several years before clinical manifestation of RA, and are also detectable in some seemingly healthy individuals who do not develop RA. ACPA reactivity to several different citrullinated and non-citrullinated proteins/peptides has been identified in RA as well as during the ‘preclinical’ period of RA –21. SeruThe Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-center prospective cohort study that enrolled 6814 participants from six field centers across the US  to evaluate race/ethnic differences in risk factors for subclinical and clinical CVD. This study started in July 2000–2002 and included individuals who were Black, Chinese, Hispanic/Latino, and White Americans and were aged ≥ 45 years with no clinically apparent CVD. Individuals were excluded if they had clinical CVD, including physician-diagnosed myocardial infarction, angina, stroke, transient ischemic attack, or heart failure; use of nitroglycerine; or current atrial fibrillation, or had undergone a procedure related to CVD. During clinic visits, participants underwent an extensive physical exam, with computed tomography (CT) and magnetic resonance (MR) imaging, had fasting blood drawn and stored, and completed questionnaires. More extensive details regarding study design, methods, examinations, and data collection have been previously published . All resOur study population consisted of participants in the MESA Abdominal Aortic Calcium Ancillary Study, which collected abdominal CT scans on 1968 individuals randomly selected from 5 of 6 MESA field centers  between August 2002 and September 2005. Characteristics between this ancillary study cohort and the overall MESA cohort did not differ. Among these 1968 individuals, 1647 had complete measurements for all antibodies measured.We used MRI data from the baseline exam. In merging the MRI data with the antibody and clinical data, 415 were missing MR images. Thus, combining individuals with complete antibody data, complete MRI data, and complete covariate data totaled to 1232 for our analysis dataset.™  bead-based autoantibody assay in which antigens are conjugated to spectrally-distinct beads. Protein antigens are coupled to beads using N-hydroxysuccinimide ester chemistry, and peptide antigens synthesized with C- terminal biotin (by Fmoc chemistry) and coupled to avidin-coated beads. Pooled beads are mixed with serum samples and diluents and incubated at room temperature. After washing, anti-human IgG antibody conjugated to phycoerythrin (PE) was added to the dyed beads and incubated at room temperature. After another wash, the bead mixture was passed through a laser detector  that identified beads based on the fluorescence of the dyes. The amount of antibody bound to each bead was determined by the fluorescence of PE. This assay has yielded highly reproducible results with 7-fold intra-assay coefficient of variance (CV) of 0.9–6.8% and 14-fold inter-assay CV ranging from 5.9–19.5% (over 90% of beads yielding inter-assay variances of < 12%) [A multiplex platform  used autf < 12%) .Measurements of rheumatoid factor (RF) IgM and IgG as well as anti-cyclic citrullinated peptide (anti-CCP2) antibodies had previously been measured in MESA, and were evaluated in parallel with antibodies to citrullinated and non-citrullinated proteins/peptides in this current investigation . Inter- Our main outcome variables were left ventricular (LV) mass, measured in grams, and left ventricular (LV) ejection fraction, measured as a percent. These variables were based on measurements from MRI which followed a protocol based on the fast gradient echo MRI pulse sequence to obtain images of the heart . BrieflyWe also investigated associations between serum reactivity to citrullinated protein/peptide antigens and incident heart failure. These events were adjudicated by a committee in MESA, and included both definite and probable heart failure, defined by heart failure symptoms, and by physician diagnosis with medical treatment. Specifically, definite and probable heart failure required clinical symptoms, e.g., shortness of breath, and signs e.g., edema since asymptomatic disease was not an endpoint. Probable heart failure required a physician diagnosis and medical treatment for heart failure. Definite heart failure required pulmonary edema/congestion on chest x-ray and/or dilated ventricle or poor LV function by echocardiography or ventriculography, or evidence of LV diastolic dysfunction , 31.Standardized questionnaires were used to collect participant demographics, ethnicity, medical history, self-reported arthritis, and medication usage including use of anti-hypertensive medications. Cigarette smoking was classified as never, current, or former, and was dichotomized in analyses to ‘ever’ versus ‘never.’2). Body surface area (BSA) was calculated using the Mostellar formula [2 [Resting blood pressure was measured three times in the seated position using a Dinamap automated sphygmanometer, and the average of the second and third readings was used for this analysis. Height and weight were measured with participants wearing light clothing and no shoes. Body mass index (BMI) was calculated as weight (kg)/height . Average analytic coefficient of variation for this assay was 9.3%.th percentile cutoffs, where individuals in the top 5% of each individual antibody were considered having extremely high reactivity to that antigen. Then we categorized individuals as having extremely high reactivity (EHR) or within normal reactivity (WNR) for antibodies to citrullinated proteins/peptides; and subsequently counted the number of EHR antibodies for each individual (range 0–28).We classified each antibody using 95For descriptive statistics comparing continuous variables between individuals with extremely high reactivity and within normal reactivity to citrullinated proteins/peptides, we used Student’s t-tests or Wilcoxon rank-sum tests for normally and non-normally distributed variables, respectively; and chi-square tests to compare categorical variables. For the cross-sectional analysis of EHR antibodies with LV mass and ejection fraction and LV end systolic and diastolic volume, we used analysis of covariance (ANCOVA). For the association between number of EHR antibodies and LV mass and ejection fraction, and LV end systolic and diastolic volume, we used multivariable linear regression. For Anti-CCP2, RF-IgA, and RF-IgM antibodies, we log-transformed these autoantibody concentrations and analyzed them per standard deviation (SD) change in multivariable linear regression.For our longitudinal analysis investigating associations of EHR, anti-CCP2, RF-IgA, and RF-IgM antibodies with incident heart failure, we considered their follow-up time from August 2002 until an event or until December 2014, and used Cox proportional hazards regression.All analyses were adjusted for age, gender, race/ethnicity, smoking status, systolic blood pressure, use of anti-hypertensive medications, self-reported arthritis, IL-6, body surface area (BSA) and estimated glomerular filtration rate (eGFR). We tested for the effect of gender and race/ethnicity on associations between EHR antibodies and LV structure and function as well as incident HF. SAS version 9.4  was used for statistical analysis, and p-values < 0.05 were considered statistically significant.Among the 1647 MESA participants included in this study, the average age was 65 ± 10, 40% were White, and 50% were women. There were 444 (27%) who had extremely high reactivity to at least 1 citrullinated protein/peptide antigen, and 1203 (73%) who had within normal reactivity to all 28 citrullinated proteins/peptides. We found no significant differences between MESA participants with extremely high reactivity versus within normal reactivity except that those with at least 1 EHR response to a citrullinated antigen were more likely to have detectable anti-CCP2 antibodies and had higher IL-6 concentrations .th, 75th percentile) number of EHR antibodies was 2 . When evaluating the 362 individuals with at least 1 EHR antibody response to a citrullinated protein/peptide antigen, the number of EHR antibodies were associated with lower LV EF. In fully adjusted analysis of this cohort, each additional EHR antibody response to a citrullinated antigen was associated with 0.1% lower left ventricular ejection fraction . Among the 362 with at least 1 EHR antibody response to a citrullinated protein/peptide antigen, greater number of EHR antibodies was not significantly associated with LV mass (p = 0.37). There were also no significant associations between the number of EHR antibodies with left ventricular end diastolic and end systolic volumes  were significantly associated with LV ejection fraction  had extremely high reactivity to at least 1 citrullinated protein/peptide antigen. Compared to those who had within normal reactivity to citrullinated protein/peptide antigens, those with extremely high reactivity to at least 1 citrullinated antigen had similar LV mass and LVEF . Among t volumes . In suppfraction .In parallel assessment of anti-CCP2, RF-IgA, and RF-IgM antibodies with LV mass and LVEF, we found that neither anti-CCP2, RF-IgA, nor RF-IgM antibodies were associated with LV mass or LV ejection fraction in fully adjusted analysis . With reWe next evaluated the associations of extremely highly reactive antibody responses with risk of incident heart failure. Among the 1641 participants with antibody measurements at baseline, 69 participants experienced incident HF during 10.7 ± 2.4 years mean follow-up. We found no significant associations between EHR vs WNR antibody responses with incident HF. Among the subset with 1 or more EHR antibody response to a citrullinated protein/peptide antigen, we also found no association between the number of EHR antibodies and incident heart failure . In addiIn this multi-ethnic community-dwelling population of individuals without CVD, extremely high reactivity to RA-related citrullinated protein/peptide antigens was detected in approximately one-third (27%) of the cohort. These individuals appeared markedly similar in respect to demographics and clinical characteristics compared to those who had within normal reactivity to citrullinated protein/peptide antigens, but had higher concentrations of anti-CCP2 antibodies and the inflammatory biomarker, IL-6. Among those who had extremely high reactivity to ≥1 citrullinated protein/peptide antigen, the number of these EHR antibodies was associated with lower left ventricular ejection fraction, but not with left ventricular mass, nor with incident heart failure over 11 years of follow-up. Neither extremely high reactivity to citrullinated antigens nor the number of EHR antibodies were significantly associated with left ventricular end systolic or diastolic volume. We suspect EHR antibodies to citrullinated protein/peptide antigens could contribute to subtle subclinical changes in the myocardium that are associated with lower EF, but given absent associations with incident heart failure, the clinical consequences of these associations are uncertain.Extremely high reactivity to citrullinated protein/peptide antigens was present in 27% of MESA participants, which suggests that these individuals may have an underlying level of autoantibody-related inflammation. Prior studies in first-degree relatives of patients with RA have shown that having RA-related autoantibodies is associated with higher concentrations of inflammatory biomarkers including IL-6, as confirmed in our study . First d48–65 arg2 v1 cyclic, Histone 2A, and Histone 2B were also associated with lower LV ejection fraction, suggesting that antibodies to histones, citrullinated and non-citrullinated, may play a role in left ventricular function and warrant further investigation. Given that prior work has shown serum reactivity to citrullinated and non-citrullinated proteins/peptides in the preclinical phase of RA [Among the subset of 362 of individuals who had extremely high reactivity to ≥1 citrullinated protein/peptide antigen, the number of EHR antibodies was significantly associated with lower left ventricular ejection fraction. The number of EHR antibodies, however, was not associated with greater LV mass, nor with incident heart failure. Supplemental analysis of individual antibodies to citrullinated and non-citrullinated antigens affirmed no associations with LV mass; and demonstrated an association of anti-citrullinated Histone 2B with LV ejection fraction. Three of the non-citrullinated antigens, Filaggrin se of RA –21, it iTo better understand our finding of an association of greater number of EHR antibodies with lower left ventricular ejection fraction, we investigated associations of EHR antibodies with left ventricular end systolic and diastolic volumes. We found that neither having extremely high reactivity nor the number of EHR antibodies were significantly associated with these parameters, but the marginally significant association between number of EHR antibodies and left ventricular end systolic volume suggests that there are subtle ventricular changes that could lead to a lower ejection fraction. Further, our evaluation of anti-CCP2, RF-IgM, and RF-IgA antibodies revealed that neither RF-IgM nor RF-IgA were associated with any of the cardiovascular structural outcomes, nor incident HF. Anti-CCP2 was, however, inversely associated with LV end diastolic and systolic volumes.To our knowledge, this is the first large-scale evaluation of the relationship of serum reactivity to citrullinated protein/peptide antigens with cardiovascular structure and function in a community-living population, not selected for having autoimmune disease or among relatives of those affected by autoimmunity. The inclusion of men and women, diverse race/ethnicity, high quality assessment of cardiac structure by MRI, and adjudication of clinical HF events during long-term follow-up are additional strengths. The study also has important limitations. We utilized MRI data from the baseline exam which was 2 years prior to Exam 2/3 where antibodies were measured, so we cannot conclude that extremely high reactivity to citrullinated protein/peptide antigens leads to myocardial changes, and instead only report that there were associations between antibodies to citrullinated proteins/peptides and myocardial function. Further, we did not have a formal diagnosis of RA for study participants. Due to the unknown RA status of MESA participants, we were not able to establish cut-offs for antibody positivity using receiver operating characteristic (ROC) curves, and instead followed the 95% cutoff for extremely high reactivity as defined in the 1987 American College of Rheumatology Criteria . Thus, iIn conclusion, approximately 27% of community-living individuals have serum reactivity to citrullinated protein/peptide antigens. These individuals appear similar in terms of demographic and clinical characteristics to those who have within normal reactivity to citrullinated antigens, with the exception of greater prevalence of anti-CCP2 antibodies and higher concentrations of the inflammatory biomarker IL-6. Overall, persons with extremely high reactivity to at least 1 citrullinated protein/peptide antigen had similar cardiac structure in terms of LVEF and LV mass, and similar risk for HF compared to those with normal reactivity to citrullinated protein/peptide antigens. Among the subset of 27% who had EHR antibodies, a greater number of EHR antibodies was independently associated with lower LVEF, however this did not appear to translate to higher risk of HF during approximately 11 years of follow-up. Further research is warranted to determine whether addressing autoimmune-related cardiovascular risk prior to clinical symptoms can prevent cardiac structural changes, particularly among those with greater number of EHR antibodies.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


The study objective was to explore the feasibility and safety of totally endoscopic resection of a left ventricular tumor through small chest incisions without robotic assistance.Four patients with a left ventricular tumor  underwent surgery with peripheral cardiopulmonary bypass. The mean age of patients was 58 ± 15 years. There were 3 female patients and 1 male patient. Through 3-port incisions in the right chest, pericardiotomy, bicaval cannulation, cardiac arrest, and atriotomy, left ventricular tumor resection was performed under thoracoscopy.All patients had successful resections. The cardiopulmonary bypass and aortic crossclamp times were 110 ± 14 minutes and 58 ± 19 minutes, respectively. The length of stay in the intensive care unit was 38 ± 27 hours. There were no mortalities or complications in this cohort. Patients were discharged 7 days after the operation. Transthoracic echocardiography showed that the cardiac tumor was completely removed without any residue 3 months after surgery.Totally endoscopic left ventricular tumor resection without a robotically assisted surgical system is feasible and reproducible. This technique could minimize surgical trauma and achieves complete tumor resection.  Totally endoscopic left ventricular tumor resection without a robotically assisted surgical system is feasible and reproducible.The feasibility and safety of total thoracoscopic resection of ventricular tumors, especially left ventricular tumors, have not been reported. We concluded that totally endoscopic left ventricular tumor resection without a robotically assisted surgical system is feasible and reproducible. This approach may be beneficial for the visualization and thrombectomy of a left ventricular thrombus.,Cardiac tumors are a rare group of diseases. Common benign cardiac tumors include mucinous tumors, papillary fibroelastoma, rhabdomyomas, fibroma, and lipoma.This study was approved by the Institutional Review Board of Qilu Hospital of Shandong University –215). All participants provided written informed consent for publication of their study data. From June 2021 to February 2022, 4 patients with left ventricular tumors from the Department of Cardiovascular Surgery were included for this study. The inclusion and exclusion criteria are listed next.(1) The pedicle of tumor was located in the left ventricle, and the diameter of the tumor was smaller than that of the mitral annulus. (2) Pulmonary arterial systolic pressure measured by echocardiography was 60 mm Hg or less. (3) There was no history of lung disease or operations on the right chest. (4) There were no other cardiovascular diseases or chronic illnesses. (5) Preoperative chest computed tomography (CT) scan showed no diaphragmatic eventration or transverse heart position. (6) Preoperative CT scan showed no atherosclerosis of the aortoiliac tree.Patients unable to meet all of the selection criteria or unable to provide informed consent were excluded from this study. Baseline characteristics and perioperative data of the patients who underwent ventricular tumor resections are shown in After induction of general anesthesia, a left-sided double-lumen endotracheal tube was placed to allow for single-lung ventilation. The respiration rate was set between 18 and 30 breaths/min, and the arterial oxygen saturation rate was maintained at greater than 97%.The patient was positioned in the supine position with the right side of the body elevated to 15° to 20°. After systemic heparinization, the right femoral artery and vein were accessed through an oblique incision along the inguinal crease. Bicaval venous drainage (26F or 28F)  was inserted through the right femoral vein into the inferior and superior vena cavae. The bypass circuit was completed by positioning a catheter (20F or 24F)  in the abdominal aorta through the right femoral artery.2 catheter, traction line, left heart drainage tube, upper- and lower-chamber cannulae, left heart cannula, perfusion cannula, pericardial, and atrial traction lines  were made on the right side of the chest . Port 1 on lines . A plaston lines  and 2.FiOnce the 3 ports were secured, unilateral left lung ventilation started simultaneously, and a pericardiotomy near the mediastinum was performed. Then, 3 to 4 sutures were placed to suspend the bottom half of pericardium only . Ready-t2O. Bedside chest radiographic analysis was routinely performed in the ICU to exclude complications in the lungs. Furosemide (1 mg/kg administered intravenously once daily) and methylprednisolone (0.5 mg/kg administered intravenously once daily) were used in all patients to prevent pulmonary edema. Mechanical ventilation was ceased once the patient's hemodynamics, arterial blood gas results, and spontaneous respiration stabilized. Patients were encouraged to perform respiratory exercises and have regular coughs. Routine postoperative care was provided when patients were transferred from the ICU, and patients were encouraged to get out of bed early.Before surgical intervention, education and counseling were provided to all participants on surgical techniques, possible clinical outcomes, potential complications, and postoperative self-care measures. Preoperative CT is necessary to exclude relative or absolute contraindications to thoracoscopic cardiac surgery such as history of previous surgery on the right lung, adhesions, diaphragmatic eventration, transverse heart position, and poor cardiac function. Lung function tests were routinely performed on all patients before the operation. The lungs were inflated every 20 minutes during the operation. After the operation, patients were monitored in the intensive care unit (ICU) overnight and received low-frequency, high-volume mechanical ventilation with a peak end-expiratory pressure of 3 to 5 cm HSPSS 23 software  was used for statistical analysis. Quantitative variables are expressed as mean ± standard deviation.Resections were successfully conducted in all patients. The total operation time was 196 ± 23 minutes. The CPB and aortic crossclamp times were 106 ± 12 minutes and 49 ± 10 minutes, respectively. The length of stay in the ICU was 38 ± 27 hours. There were no mortalities and no major complications such as bleeding, stroke, renal failure, and wound infection in this cohort. Patients were discharged from the hospital in an average of 7 days after the operation. Transesophageal echocardiography immediately after the operation and 30 days after operation showed that the cardiac tumor was completely removed without any residue .Figure 5Cardiac tumors are a rare condition of the heart. As the disease progresses, some benign tumors grow into the chambers causing obstruction of blood flow and heart valve dysfunction, and can lead to acute embolism or even sudden cardiac death if the tumor is partially or completely dislodged.Surgeries are the most common and effective way to treat cardiac tumors. However, with the development of medical technology and the concept of minimally invasive surgery, conventional sternotomy has been no longer overwhelmingly dominant. Small incision approach, total endoscope techniques, and even the da Vinci surgical robot can be used to achieve perfect radical treatment for certain diseases in cardiac surgery.13,Total thoracoscopic cardiac surgery such as thoracoscopic closure of ventricular septal defect and atrial septal defect has been performed for many years.,In this study, we reported 4 cases of total thoracoscopic-assisted left ventricular tumor resection, including 1 case of lipoma, 1 case of papillary fibroelastoma, and 2 cases of myxoma. In all patients, complete resections of the tumor were achieved without serious complications such as death or embolism. A critical factor in the successful surgical treatment of cardiac tumor was optimized exposure of the operating field. To fully expose the tumor for surgical manipulation, we chose to cut through the interatrial groove, with all instruments entering the left ventricle through the fully exposed mitral orifice. One of the advantages of thoracoscopy is that it could allow a near panoramic view of the left ventricle through the mitral valve orifice. By doing this, the anatomic position and morphology of the tumor could be visualized more clearly. The ventricular tissue near the apex of the heart could be clearly determined, thus allowing the operator to locate the origin of the tumor for precise excision. On the other hand, this approach may be beneficial for the visualization of left ventricular thrombus. Patients with a myocardial infarction are at high risk of developing an intracardiac appendage thrombi at the left ventricular apex.2 slowly in the intraoperative field to prevent air embolism after aortic opening.We have summarized the following technical points:First, minimally invasive cardiac endoscopic surgery could be conducted only in a few hospitals because of technical requirements. Moreover, most surgeons in general have not been trained sufficiently in the more complex minimally invasive cardiac endoscopic procedures. Thus, total thoracoscopic cardiac surgeries have not been commonly performed or have become the standard procedure. It has been reported that minimally invasive procedures increased the duration of CPB due to the learning curve and technical complexity.We have preliminarily shown that total thoracoscopic surgical resection is feasible and reproducible, and we have achieved complete ventricular tumor resection successfully with this procedure.The authors reported no conflicts of interest.Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.The


Levosimendan (LS) has been progressively used for the treatment of patients developing acute as well as chronic or advanced cardiac dysfunction. It has proven to be a better inotropic agent than its counterparts in terms of its ability to increase the cardiac output in an acutely or chronically decompensated heart without an increase in the myocardial oxygen demand. The purpose of this systematic review, which was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020, was to determine the efficacy and advantages of utilizing LS in patients with both acute and chronic heart failure. We collected and reviewed articles, including clinical trials, literature reviews, randomized and non-randomized control trials, case-control and cohort studies, and systematic reviews and meta-analyses published between January 1, 2012, and November 27, 2022. The databases that were used to collect these articles included Pubmed, Pubmed Central, Cochrane Library, and Google Scholar. After applying appropriate filters, a total of 143 reports were identified from these four databases. They were further screened and subjected to quality assessment tools which finally yielded 21 studies that were included in this systematic review. This review provides strong evidence that the pharmacological properties and different mechanisms of action of LS give it an upper hand over other inotropic agents for its successful administration in patients with either acute or advanced cardiac failure, which consists of left as well as right ventricular failure, either individually or in combination. Heart failure (HF) is a long-term clinical condition that can be brought on by problems with the heart valves, pericardium, myocardium, or endocardium. It can also happen as a result of certain metabolic imbalances . PatientOne of the main causes of AHF is acute coronary syndrome (ACS), which typically occurs in conjunction with severe myocardial dysfunction and damage as well as arrhythmia . HoweverThere is a greater need for new therapeutic approaches that can slow or prevent clinical progression and prevent hospitalization outside of the drug and device therapy recommended by guidelines because many patients with AHF and chronic HF have few specific therapeutic options, and these options frequently fail to slow disease progression . PatientThe early 1990s saw the development of LS in Finland, and it was only in 2001 that it was made prescription-only ,10-17. TThe pharmacokinetics of LS is another factor that sets it apart, especially the way that a long-acting active metabolite known as OR-1896 forms in the intestines through a reduced acetylation pathway . While hLS has been researched for potential application in a range of therapeutic contexts, such as the management of AHF, patients with low cardiac output, and high-risk cardiac surgery. Along with right ventricular failure, cardiogenic shock (CS), septic shock, and takotsubo cardiomyopathy, it has also shown early encouraging outcomes in a number of other disorders requiring inotropic support ,17. TheMethodsLS use in patients with acute and/or severe cardiac failure is the subject of this systematic review, which aims to investigate and evaluate it. This systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations.Search StrategyA thorough literature search of databases such as Pubmed, Pubmed Central (PMC), Cochrane Library, and Google Scholar was done. The search was generated using keywords such as "heart failure," "cardiac failure," "left ventricular failure," "right ventricular failure," "congestive heart failure," "left ventricular systolic dysfunction," "acute cardiac failure," "decompensated cardiac failure," "advanced cardiac failure," "postural nocturnal dyspnea," "dyspnea on exertion," "orthopnea," "Levosimendan," "inodilator," and "calcium sensitizing inotrope" and combining them using the BOOLEANs “AND” and “OR.” A mesh strategy was used to narrow down the published articles. Table Eligibility RequirementsBased on the following participant, intervention, and outcome characteristics, the studies were chosen for inclusion:Participants: Adult and geriatric populations (>= 18 years) of all ethnicities and genders with signs of early, AHF, and AdHF were chosen for studies.Intervention: Use of LS in the abovementioned population.Outcomes: LS administration appears to be effective in symptomatically improving or halting the progression of de-compensation in patients with HF, according to studies.Inclusion and Exclusion CriteriaAdditionally, the following inclusion and exclusion standards were added: papers were only taken into consideration if they were written entirely in English, free full-text articles published within the previous 10 years, randomized control trials (RCTs), non-RCTs, case series, and case reports; cohort studies; case-control studies; systematic reviews; literature reviews; and meta-analyses. Animal studies weren’t considered for this systematic review.ResultsUsing the search strategies and appropriate filters, a total of 143 articles were identified from the databases, as mentioned above, within the last 10 years . The screened articles, after the removal of duplicates and irrelevant records, were subjected to quality assessment by using quality assessment tools such as AMSTAR 2 , the Jadad scale (for RCTs and non-RCTs), SANRA (for narrative review articles), the JBI quality appraisal checklist (for case series and case reports), and the Newcastle-Ottawa checklist (for case-control and cohort studies). An overview of the screening process is presented in the PRISMA chart, as shown in Figure The studies included in this systematic review are summarized in Table DiscussionWhen conventional therapy was deemed insufficient and inotropic support was deemed appropriate, LS was initially approved in Sweden in 2000 for the short-term treatment of severely decompensated chronic HF . The mecThe current indication for LS as a short-term treatment for acutely decompensated severe chronic HF is supported by clinical trial data, from which a number of noteworthy characteristics were extracted and explained diagrammatically in Figure Pharmacokinetics of LSWith a pKa of 6.2 and a half-life of around one hour, LS is a weak acid and a moderately lipophilic molecule . The cheThe majority of the drug's metabolism occurs at one of its nitrile groups via glutathione conjugation, followed by amino acid cleavage and cyclization or acetylation ,23. HowTypically, the infusion is started at 0.1 g/kg/min and raised to 0.2 g/kg/min for 24 hours as long as the systolic blood pressure (SBP) remains constant for the first two to three hours. A 24-hour break between infusions is advised for patients with AHF . To reduLS in AHFAHF is a circumstance in which the signs and symptoms of HF suddenly appear or get worse, and it must be classified as a life-threatening medical illness that necessitates immediate assessment and treatment and frequently ends with the patient getting hospitalized . FindingTraditional adrenergic inotropes and phosphodiesterase (PDE)-3 inhibitors are sometimes linked to increased mortality, arrhythmias, or other safety problems, according to a number of clinical trials and meta-analyses undertaken over the past 25 years ,17. In In patients with obvious signs of pulmonary edema and excessive PCWP who do not respond appropriately to vasodilation, LS is recognized for its greater ability to decrease PCWP and right atrial pressure compared to other inotropes like dobutamine ,10,26. AThe key to resolving the issue of AHF lies in understanding the pathophysiology that causes it. Because AHF results from fluid redistribution, increased left ventricular pressure, and vasoconstriction with increased venous return, it is a phenotype that responds well to therapy with vasodilators . AHF cauLS in AHF or CS Secondary to ACSAHF in the setting of ACS is an urgent issue that necessitates quick detection and care, not the least of which is the possibility that AHF will progress into CS. Age, a previous myocardial infarction (MI), or chronic HF are risk factors for the development of AHF in ACS, as are diabetes, hypertension, and the female sex . AHF is The safety of LS was examined in the Randomized Study on the Safety and Effectiveness of Levosimendan in Patients with Left Ventricular Failure after an Acute Myocardial Infarction (RUSSLAN), a placebo-controlled, double-blind, parallel-group, randomized study with 504 patients enrolled in five days after an index infarction ,28. In tAccording to current expert advice on the use of LS in AHF complicating ACS, it can be thought about as a potential substitute for adrenergic medications in all patients who have had chronic beta-blocker therapy or in those whose urine production is insufficient after taking diuretics . In addiLS in AHF Secondary to Septic ShockModern definitions of sepsis include an infection that causes at least one organ to malfunction due to an uncontrolled host inflammatory response. Septic cardiomyopathy (SCM), which results in de novo AHF as a result of cardiac depression, can also arise from sepsis in addition to the intrinsic distributive shock brought on by vascular hypo-reactivity and autonomic dysfunction . MyocardFor the recovery of a sufficient cardiac output and the delivery of peripheral oxygen, inotropic support is recommended . DespiteA 24-hour infusion of either LS (0.2 g/kg/min) or dobutamine (5 g/kg/min) was randomly assigned to 28 septic patients with chronic left ventricular dysfunction following 48 hours of standard treatment in a trial to determine the effectiveness of LS in treating septic myocardial depression . When coLS in Chronic or AdHFHospitalizations for refractory HF patients are common because of clinical worsening . Acute-oThe presently acknowledged mechanism for the onset and progression of HF is cardiac remodeling . Pro-infEvidence suggests that people with AdHF will live longer and require fewer hospital stays with intermittent use of LS . AccordiLeft ventricular dysfunction is the most frequent cause of right ventricular failure, and bi-ventricular dysfunction has a poorer prognosis than pure left ventricular dysfunction . Right vLimitationsThis systematic review encounters certain limitations. As mentioned before, LS has been in clinical use since 2000, but the majority of the information gathered in this review has been included in the articles, studies, and clinical trials that have been published in the last 10 years. In addition, only the free full-text articles available across various databases have been used for this review. Publications in languages other than English were rejected during the screening process. Studies with minors , including the pediatric population, as the subjects, were not included in this review; thus, the congenital heart conditions leading to HF have not been discussed in this systematic review. Studies in which animal models have been used to test the efficacy and safety of LS have been excluded from the review. Drug interactions and side effects of LS have not been explained in this review. Lastly, the use of LS during cardiac surgeries has not been taken into consideration while describing the pharmaceutical benefits of the drug.This systematic review proves the efficacy of LS in patients with AHF and AdHF. Although LS itself has a very short half-life, its active metabolite, which has similar pharmaceutical properties as that of the original drug, has a much longer half-life and is hence primarily responsible for carrying out the actions of LS. Various mechanisms of action of this drug include a positive inotropic effect independent of cAMP activity, a vasodilatory effect owing to the opening of the K-ATP channels in the smooth muscles, and the prevention of ischemic or re-perfusion myocardial injury by its action on K-ATP channels in the mitochondria of the cardiac muscles. It is by virtue of these properties that LS has been increasingly used in patients with AHF, both de novo and secondary to other conditions, and for the treatment of chronic or AdHF, as it has proved to be a better option for these patients compared to other inotropes such as dobutamine. This review has very clearly marked and explained the use of LS in both acute and chronic cardiac failure and gathered enough evidence to support this statement from various clinical studies and trials performed in the last decade. Suggestions for future research include clinical trials to study interactions of LS with other classes of drugs, such as antibiotics, anti-psychotics, anesthetics, and anti-arrhythmic agents, clinical trials for using LS in the pediatric population with congenital heart conditions leading to HF in adult life.


This study aimed to report the clinical outcomes of continuous flow left ventricular assist device implantation in end-stage chronic heart failure patients with a history of surgical left ventricular restoration.n = 3), posterior restoration procedure (n = 2), and septal anterior ventricular exclusion (n = 1).We retrospectively identified 190 patients undergoing continuous flow left ventricular assist device implantation at our center from November 2007 to April 2020. In total, six patients underwent continuous flow left ventricular assist device implantation after various types of surgical left ventricular restoration procedures, including endoventricular circular patch plasty  was successfully implanted in all patients. During a median follow-up of 48 months , no death was documented, which means that overall survival after left ventricular assist device implantation was 100% at any time point. Finally, three patients received heart transplantation  and the other three patients are still awaiting heart transplantation .Continuous flow left ventricular assist device (Jarvik 2000, In our series, continuous flow left ventricular assist device implantation after surgical left ventricular restoration was safe and feasible, even if an endoventricular patch was used, and effective for bridge to transplant strategy.The online version contains supplementary material available at 10.1007/s11748-023-01917-8. Surgical ventricular restoration (SVR) has been developed for patients with end-stage heart failure which is refractory to guideline-directed heart failure therapy in Japan, the United States of America, and Europe, owing to a shortage of donors –4. SVR pThe landmark Surgical Treatment for Ischemic Heart Failure (STICH) trial showed no benefit of SVR from the standpoint of the overall survival in ischemic heart disease. However, some researchers believe that the STICH trial may have failed to show an improvement in survival by SVR because the surgery did not make the ventricle small enough , 6. A smHowever, some patients may develop heart failure after successful SVR at later follow-up . This phDuring the past decades, a continuous flow left ventricular assist device (Cf-LVAD) therapy has been a treatment option in advanced heart failure, with improving outcomes around the world , 10. In However, an efficacy and feasibility of VAD therapy were barely investigated, due to scarce clinical experience, and there are no clear recommendations for patients with a prior history of SVR , 15. Cf-The aim of the present study was to review our experience with cf-LVAD therapy in patients with a prior SVR and provide clinical outcome and follow-up data, including mortality and adverse events.This single-center study was approved by Institutional Ethics Committee of the University of Tokyo (3031-). We incThe SVR procedures, including endoventricular circular patch plasty (EVCPP), septal anterior ventricular exclusion (SAVE), and posterior restoration procedure (PRP), were selected and performed based on the affected region of the ventricle and the surgeon’s preference in other hospitals –5. A DacAll LVAD implantation procedures were performed via median sternotomy or left thoracotomy (LT) on cardiopulmonary bypass (CPB) on a beating heart. CPB is established by aortic cannulation in the ascending aorta or the proximal arch and venous cannulation via the SVC and IVC. In the LT approach, skin-incision in the sixth intercostal space was performed after establishing CPB through femoral artery and vein cannulation. First, an LVAD inflow cannula was implanted. The optimal position of the LVAD inflow cannula was estimated by finger palpation or using epicardial echocardiography. Subsequently, coring of the left ventricular wall was performed by avoiding the sutured line created at the previous SVR procedure. An LVAD apical cuff was sutured onto the cored hole. An outflow graft was sutured end-to-side to the proximal ascending aorta in cases with a median sternotomy approach, or the descending aorta in the case of the LT approach. A pump pocket or space was created according to the size of each device and the anatomical position of the cored area.p value of < 0.05 was considered statistically significant. All statistical analyses were performed using R .Results are expressed as mean ± standard deviation (SD) or as median + 25th–75th percentile interquartile range for continuous variables and frequency and percentage for categorical variables, as appropriate. The Friedman test was used to compare the three paired groups with nonparametric nature of data. Data for survival and freedom from cardiac events and all-cause death were derived using a Kaplan–Meier method; comparisons were made using a log-rank test. A two-sided n = 5) and ischemic cardiomyopathy (n = 1). Previously performed SVR was classified into three types composing of the EVCPP procedure (n = 3), PRP procedures (n = 2), and SAVE procedure (n = 1). All SVR procedures were performed through a median sternotomy. At the time of the cf-LVAD implantation, the patients had a median INTERMACS level 3 (IQR: 2–3). Only one patient (INTERMACS level 2) required intra-aortic balloon pumping before cf-VAD implantation, while the other five patients required no temporary mechanical circulatory support. Additionally, all patients required high-dose inotropes, but no patient needed intubation. Baseline characteristics at cf-LVAD implantation are shown in Table A total of six patients  with a history of SVR surgery, who underwent cf-LVAD implantation in our institution due to recurrent severe heart failure were included in the study. The median interval between SVR and cf-LVAD implantation was 70 months (IQR: 46–101 months). Based on the clinical/medical history and muscle biopsy histology, the etiologies of cardiomyopathies consisted of idiopathic dilated cardiomyopathy , and only one patient (patient No. 4) had LVESVI under 70 ml/m2. The median mean pulmonary capillary wedge pressure (PCWP) was 24 mmHg , and five patients (except patient No. 5) had higher values than 20 mmHg. The median cardiac index (CI) was 1.7 L/min/m2 , and all patients had CI values lower than 2.2 L/min/m2. The median pulmonary vascular resistance (PVR) was 4.3 Wood units , and three patients  had PVR ≥ 4.0 Wood units.The values of thoracic echocardiography and right heart catheterization before cf-LVAD implantation are summarized in Table n = 2), HM2 (n = 1), EVAHEART II (n = 1), DuraHeart (n = 1), and HVAD (n = 1), respectively] and the concomitant valve surgery are described in Table All patients underwent cf-LVAD implantation as BTT strategy. First, one patient (No. 1) underwent cf-LVAD implantation with left thoracotomy due to strong adhesion of the left ventricular anterior lesion caused after the SAVE operation. Median sternotomy was chosen for the other five patients because of severe focal adhesion of the left ventricular apical or posterior region. Implanted devices [Jarvik 2000 , at least 2 cm apart from the sutured line created in the EVCPP procedures and the optimal left ventricle-apical portion in the PRP and SAVE procedures. Removal of the implanted Dacron Patch or additional left ventricle plasty was not performed. No patient experienced any perioperative complications such as re-thoracotomy or cardiac tamponade. Various type of VAD associated complications were observed in all patients during a follow-up, but, due to no major sequelae, any patient was not excluded from a heart transplantation candidate Table . Three pThe hemodynamic value was determined at pre-LVAD implantation, 1 month post-VAD-implantation, and during the late follow-up after LVAD implantation  who had VAD implants  . After aWhile removal of the endoventricular Dacron patch may be effective in improving the position of the inflow cannula, it is not always necessary for LVAD implantation . We did Leaving the Dacron patch in place seems to have some advantages. First, the LVAD implantation is performed with a beating heart in the routine fashion. Therefore, the surgical procedure is not complicated and is quicker. Second, myocardium damage can be reduced. This can reduce the frequency of postoperative atrial or ventricular arrhythmia, and may decrease the risk of right heart failure. Third, the left ventricular hole after the removal of Dacron patch is too large and the tissue around the hole is fragile. Therefore, there may be difficulty in controlling the bleeding around the inflow cannula. For these reasons, we routinely performed both intraoperative transoesophageal and epicardial echocardiography in all cases in order to determine the optimal position of the inflow cannula. As a result, we could perform cf-LVAD implantation in a safe fashion (Supplement 1).Careful attention should be paid while deciding the appropriate surgical strategy. If preoperative TTE and chest CT with contrast show signs of wedge thrombus around the apical area or Dacron patch, removing the Dacron patch and Fontan stitch may be a choice of optimal surgical strategy for an inspection of the left ventricular cavity.There are several limitations to our study. This was a retrospective, single-center study with a limited number of patients. Even though this study does not provide generalized statements, we were still able to report good outcomes for this cohort.Supplementary file1 (DOCX 16 KB)Below is the link to the electronic supplementary material.


Dear readers,The annual scientific meeting of the Heart Rhythm Society was held recently in New Orleans, during which many important presentations were given. Atrial fibrillation continues to be an important topic, and various studies on pulsed-field ablation were discussed. Another area of growing interest is left bundle branch area pacing (LBBAP), which has become a popular technique for conduction system pacing. Three studies covering this topic were presented at the late-breaking clinical trial sessions during HRS 2023.1 that enrolled 1,778 patients who met criteria for cardiac resynchronization therapy (CRT). LBBAP was performed in 797 patients, while biventricular pacing was performed in 981. The primary outcome was a composite of time to death or heart failure hospitalization. During a mean follow-up of 33.2 ± 15.5 months, the primary outcome rate was significantly lower in the LBBAP group compared to the biventricular pacing group .The first and largest study was an observational multicenter investigation completed by Vijayaraman et al.2 was a multicenter prospective non-randomized trial that enrolled 371 patients. The primary safety outcome was the occurrence of acute and long-term procedure-related complications, and secondary outcomes included improvements in New York Heart Association (NYHA) functional class and electrocardiographic and echocardiographic parameters. LBBAP was performed in 128 patients, while biventricular pacing was performed in 243. At a median follow-up of 340  days, LBBAP was superior to biventricular pacing.The second study by Diaz et al.3 that enrolled 100 patients randomized to conduction system or biventricular pacing. The primary endpoint was the change in left ventricular ejection fraction at 6 months post-implantation, while secondary endpoints included changes in echocardiographic measurements, NYHA functional class, 6-min walk distance, quality of life, QRS duration, and CRT response. At 6 months of follow-up, conduction system pacing was associated with a greater improvement in left ventricular ejection fraction compared to biventricular pacing .The third late-breaking clinical trial was a randomized controlled study also completed by Vijayaraman et al.4 could represent the beginning of a radical shift in CRT. LBBAP appears to be a simpler and less-challenging procedure and, more importantly, is associated with greater improvements in ejection fraction and survival. The results of these studies will need to be confirmed by larger randomized controlled studies, which are underway.These three studies, in addition to other small, previously published ones,The Journal of Innovations in Cardiac Rhythm Management.I hope that you enjoy reading this issue of Sincerely,md, fhrs, faccMoussa Mansour, Editor in ChiefThe Journal of Innovations in Cardiac Rhythm ManagementMMansour@InnovationsInCRM.comDirector, Atrial Fibrillation ProgramJeremy Ruskin and Dan Starks Endowed Chair in CardiologyMassachusetts General HospitalBoston, MA 02114


Ventricular septal rupture (VSR) is a rare but well‐known mechanical consequence of an acute myocardial infarction (AMI). Even in the later stages of re‐perfusion therapy, the result of VSR remains poor. Our aim is to assess the site and size of VSR in relation to the severity of cardiac failure.From January 2016 to December 2022, a total of 71 patients with a diagnosis of post‐myocardial infarction VSR were admitted to the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Data records were retrospectively included in this registry. In all patients, clinical and echocardiographic data were gathered, and statistical analyses were performed.p = .016), LVEF (p = .012), AMI site (p = .001), and affected coronary vessel (p = .004). Prodromal angina (p = .041), intra‐aortic balloon pump (p = .002), affected coronary vessels (p = .020), pro‐BNP (p = .000), and LVEF (p = .017) were predictors of the severity of heart failure.A total of 71 consecutive patients (mean age: 66.27 ± 8.88 years); 50.7% male, 49.3% female, with (M:F) ratio of almost (1:1). Left ventricular ejection fraction (LVEF) was (48.55 ± 10.44%) on echocardiography, and apical VSR was the most common site (69.0%). Overall, the VSD site was strongly related to the VSD size (Diabetes mellitus is a common risk factor for post‐myocardial infarction VSR. VSR site and size had no relation to the severity of heart failure. A presentation with prodromal angina predicted severe heart failure and a worse prognosis. BACKGROUND: VSR is an uncommon but well‐recognized mechanical complication of AMI. The outcome of VSR remains poor even in the era of re‐perfusion therapy. PURPOSE: Our aim is to assess the site and size of ventricular septal rupture in relation to the severity of cardiac failure. METHODS: 71 patients with a diagnosis of post‐myocardial infarction ventricular septal rupture were retrospectively included in this registry. RESULTS: On echocardiography, the left ventricular ejection fraction was 48.55%, and the most frequent location of VSR was apical. Overall, the VSD site was strongly related to the VSD size. Prodromal angina, IABP, affected coronary vessels, pro‐BNP, and LVEF were predictors of the severity of heart failure. CONCLUSIONS: Diabetes mellitus is a common risk factor for post‐myocardial infarction ventricular septal rupture. VSR site and size had no relation to the severity of heart failure. A presentation with prodromal angina predicted severe heart failure and a worse prognosis. Participants signed the patient permission form after a thorough description of the projects' aims, advantages, and even potential risks.Any patient admitted for AMI who exhibited evidence of VSR on urgent cardiac catheterization or had hemodynamic compromise on echocardiography was considered for inclusion. Patients who did not survive their first hospital visit were not included; this included those who were rushed in for emergency cardiac catheterization but were unable to undergo it. Clinical symptoms and an elevation of serum troponin‐T >0.1 mg/dL were used to diagnose AMI, and an electrocardiographic (ECG) showing >2 mm ST‐segment elevation in the precordial leads or >1 mm ST‐segment elevation in the limb leads was also considered diagnostic. We reviewed all of the patients' medical records and analyzed their clinical profiles, therapies , and final results. Each patient's clinical hemodynamics were derived from the earliest available vital signs.2.3All patients who were diagnosed with AMI in the ER underwent immediate cardiac catheterization. The major goal of the coronary angiograms given to all patients was to initiate a primary intervention. Some patients also had a left ventriculogram before echocardiographic confirmation. The level of obstruction was used to describe coronary artery disease (CAD). No narrowing of more than 20% showed that there was no CAD. Nonobstructive coronary artery disease was diagnosed when there was at least one lesion with a narrowing of more than 20% but less than 70%. Obstructive CAD was described as stenosis of more than 70% or stenosis of the left main artery of more than 50% that affected one, two, or three vessels.2.4All of the patients had an echocardiogram, and VSR was confirmed by transthoracic and/or transesophageal techniques within an average of 4 h and 36 min (up to 13 h and 51 min) of being admitted to the hospital. Color Doppler showed that there was a left‐to‐right backflow, which meant that the ventricular septum was broken. A transthoracic echocardiogram was used to find where the VSR was located. The VSR was found in the apical septum and the middle of the septum. Either the Quinonez method or Simpson's method with two planes were used to figure out the left ventricular ejection fraction (LVEF).2.5By reviewing the patient's medical records, we were able to learn about their demographic traits, medical co‐morbidities , medical acuity , the location of the infarction, the site and size of the septal rupture, and the peak cardiac enzymes. Prodromal angina is defined as typical chest pain bouts lasting 30 min or longer that occur within 24 h of the AMI's onset (either at rest or with exertion).2.6The primary outcome was clinical correlation between the apex and middle VSR, defined as any factor that can differentiate the apical from the middle VSR based on clinical and statistical points. The secondary outcome was the indicators of severity of heart failure, defined as factors that can predict the severity of heart failure based on the clinical classification of cardiac failure and statistical analysis. The New York Heart Association classification of heart failure Table  can be u2.7SD). Categorical variables were expressed as percentages of the sample. The comparison between apical VSR and middle VSR was performed by an independent sample test (Whitney U test) and the Chi‐square test using Yates correction and Fisher's exact test for continuous and categorical variables, respectively. A two‐tailed p < 0.05 was used to indicate statistical significance.Continuous variables were summarized as mean plus or minus the standard deviation (3SD was (66.2 ± 8.88) years old with  were males and  where females gave rise to (M:F) ratio almost equal (1.02:1). A total of 40 patients (56.3%) had diabetes mellitus, which was a common risk factor for post‐myocardial infarction VSR, followed by hypertension, which was found in . A total of 26 patients (36.6%) were on dialysis. Smoking and a history of cerebrovascular accident were presented in 14 patients (19.7%) and 7 patients (9.9%), respectively. HDL was low in 21 patients (29.6%), and LDL was high in 17 patients (23.9%) . The majority of patients at the time of diagnosis were Killip class III  or IV . Extensive anterior  and anterior  myocardial infarctions were the most common locations of myocardial infarction. The apical VSR  was the most common VSR location, while there were 22 patients (31.0%) with the middle VSR. The average LVEF was (48.5 ± 10.4%).A total of 25 patients (35.2%) were supported by IABP , followed by the right coronary artery (RCA) at n = 9, 12.7%). A revascularization procedure was performed in 65 patients. Among them,  patients received PCI, and  patients received thrombolysis  was the most common location for culprit lesions (p = .012); a lower LVEF predicted severe heart failure. There was a significant difference in the size of the VSR among the two groups, which was smaller in the apical group than that in the middle one . The location of the myocardial infarction had a significant difference among the two groups with a p value was (p = .001). This strong variance showed that the apical VSR almost always comes with the anterior wall myocardial infarction, while the middle VSR mostly comes with the inferior wall myocardial infarction. The affected coronary artery vessel was almost the left anterior descending coronary artery (LAD) in the apical group, while the left anterior descending coronary artery (LAD) and the RCA were the most common in the middle group with a significant difference was (p = .004) (Table From Table 4) Table .n = 2, 2.82% vs. n = 23, 32.4%, p = .002), while mechanical support with extra corporeal membrane oxygenation (ECMO) had a marginally significant difference (p = .056). Prodromal angina had also a significant difference between classes II, III, and IV with a p value was . Pro‐BNP had also a strong variance between the 3 classes of heart failure, with a p value was (p = .000), which indicated that the higher the Pro‐BNP value, the more severe the heart failure. And last, the LVEF was significantly different among the 3 classes of heart failure (p = .017), which predicted that the lower the LVEF, the higher the stage of heart failure . Here we describe the relationship between VSR and heart failure based on the clinical classification. There were no patients in class I; only 3 patients were in class II; 22 patients were in class III; and 46 patients were in class IV. As it is shown in Table re Table .4While reading the research conclusions, individual points are worth pointing out. First, modern reperfusion strategies and more potent antiplatelet therapies have modified the epidemiology of VSR complicating AMI.Second, necropsy studies of patients experiencing fatal AMI have frequently demonstrated that VSR occurs as a consequence of a transmural infarction.Age, gender, Killip class, NYHA class, and pro‐BNP had no significant variance between the two groups , which indicated no correlation between these factors and the site of the VSR. There was a significant difference in the size of the VSR among the two groups, which was smaller in the apical group than that in the middle one. LVEF can be used as an indicator to differentiate between apical and middle VSR, as it was lower in the apical VSR than that in the middle one, unless the size of the middle VSR was >10 mm, which is common as it is mentioned above, with a significant p value. The site of the AMI and the affected coronary artery were also significant. The apical and middle VSR can be roughly clinically differentiated from each other by the site of the AMI that appears on the ECG paper, the apical VSR most commonly coming with the extensive anterior AMI followed by anterior AMI, while the middle VSR was mostly coming with the inferior myocardial infarction followed by the anterior one; the left anterior descending (LAD) coronary artery was mostly coming with the apical VSR while the RCA was not uncommon with the middle VSR.This study confirmed that age, gender, site, and size of the VSR had no significance, which indicated that these factors were not affecting the severity of heart failure. Mechanical support with the IABP and ECMO were significant and marginally significant, respectively. Case reports and other small retrospective studies demonstrate that the use of IABP improves survival following VSR until surgical repair.Our findings suggest that both IABP and EMCO provide survival advantages through preoperative hemodynamic support and postoperative advantages with the use of EMCO. Individuals who had prodromal angina frequently have a stage III or IV NYHA classification, so prodromal angina revealed significant variation and anticipated the severity of heart failure. The left anterior descending (LAD) coronary artery almost always takes place with stage IV heart failure, followed by the RCA, as proved in previous studies. Pro‐BNP had also a great variance between the 3 classes of heart failure, which indicated that the greater the Pro‐BNP value, the more severe the heart failure. And last, the LVEF was significantly different among the 3 classes of heart failure, which predicted that the lower the LVEF, the higher the stage of heart failure.51.There is no relationship between the site and size of the VSR and the severity of heart failure.2.Presentation with prodromal angina indicates more severe heart failure and a worse prognosis.3.Certain factors  can give a clue to the site of the VSR.4.Mechanical support with IABP and ECMO, prodromal angina, affected coronary arteries, pro‐BNP, and LVEF are directly proportionate to the severity of heart failure.5.Diabetes mellitus is a common risk factor for post‐myocardial infarction VSR.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare no conflicts of interest.Supporting information.Click here for additional data file.