P < 0.001) increased risk of the end-point event compared with those with SVR ≤ 320.89 (kPa s/L). Similarly, patients with SVR > 169.94 (kPa s/L) at discharge faced a risk elevated by 6.57 times (P = 0.002) relative to those with SVR ≤ 169.94 (kPa s/L). In HF patients with permanent AF, SVR measured by ICG emerges as an independent risk factor and clinical predictor for HF deterioration-related readmission within 180 days after discharge. Higher SVR levels, both upon admission and at discharge, correlate with an incremental rehospitalization risk.Heart failure (HF) and permanent atrial fibrillation (AF) interact mutually, exacerbating hemodynamic effects and causing adverse outcomes and increased healthcare costs. Monitoring hemodynamic indicators in patients with these comorbidities is crucial for effective clinical management. Transthoracic impedance cardiography (ICG) has been widely employed in assessing hemodynamic status in clinical settings. Given the limited research on the prognostic significance of ICG parameters in HF with permanent AF, we undertook this study. A total of 66 HF patients with permanent AF were included in this retrospective study, and the primary outcome was rehospitalization due to worsening HF within 180-day post-discharge. Cox regression analysis was performed to explore the connection between ICG-evaluated parameters and the outcome risk. Receiver operating characteristic (ROC) curve analysis determined the optimal cutoff values of risk factors, subsequently applied in plotting Kaplan Meier (KM) survival curves. Multivariate Cox regression analysis revealed that systemic vascular resistance (SVR) both on admission and at discharge independently predicted rehospitalization for worsening HF. ROC analysis established optimal SVR cutoff values: 320.89 (kPa s/L) on admission and 169.94 (kPa s/L) at discharge  0.831, respectively, sensitivity 90%, specificity 55.6%, AUC 0.742). KM survival curves analysis showed that patients with SVR > 320.89 (kPa s/L) on admission had an 8.14-fold ( Heart failure (HF) has been a growing public health issue. Despite marked reductions in HF-related mortality rates, rehospitalization owing to recurrent HF deterioration remains prevalent worldwide. Some studies , 2 have Inflammation, oxidative stress, and neuroendocrine abnormalities related to HF contribute to AF while ongoing AF worsens left ventricular function and HF progression. HF triggers increased left atrial pressure, affecting atrial function and causing hemodynamic imbalance , 8, raisThe Swan–Ganz floating catheter  is globaIn recent years, ICG has played an essential role in guiding medical therapy for acute and chronic HF –23, in cWe reviewed the patients with HF and permanent AF admitted to the Cardiology Department of Aoyang Hospital Affiliated to Jiangsu University from January 2021 to December 2022 and ultimately included 66 subjects  classification of cardiac function ≥ 3, and no improvement in symptoms with oral pharmacotherapy. This study was approved by the Medical Ethics Committee of our institution ((2021) Ethics Approval No. 010), and written informed consent was waived because of the retrospective nature.The following data were collected through the hospital database: demographic information, medical history, physical examination, blood tests, including N-terminal pro-B-type natriuretic peptide (NT-pro BNP), high-sensitivity cardiac troponin (HS-cTn), creatinine clearance evaluated by Cockcroft–Gault formula, total bilirubin, serum albumin, hemoglobin, D-Dimer, thyroid-stimulating hormone (TSH), blood sodium, serum total cholesterol, serum triglyceride, low-density lipoprotein. Arterial pressure, rhythm type, mean ventricular rate determined by 24-h ambulatory monitoring, left atrial transverse diameter, left atrial volume index, left ventricular end-diastolic diameter, left ventricular ejection fraction (LVEF) measured by transthoracic echocardiography, and medication prescriptions at discharge were gathered. The post-discharge end-point event was collected through retrospective medical records until December 2022. Data were checked and entered collaboratively by two investigators.ICG is non-invasive, relying on varying electrical impedance in various tissues and water contents of the human body. In one cardiac cycle, impedance value changes with the blood volume and flow rate in thoracic vessels. Analyzing thoracic impedance shifts help determine hemodynamic parameters of blood movement . Notablyt test for continuous variables, the Chi-square or Fisher’s exact test for categorical variables, and the Mann–Whitney U test for non-normally distributed variables. Cox regression analysis examined the relationship between the end-point event and parameters. Variables (P < 0.05) were included in multivariate analysis. Receiver-operating characteristic (ROC) curves established cutoff values for rehospitalization prediction. Kaplan–Meier (KM) analysis assessed the prognostic value, and significance was set at P < 0.05. Data were analyzed using SPSS version 25 and plotted with GraphPad Prism version 9.3 and R version 4.2.2.Continuous variables with normal distribution were expressed as means ± standard deviation, while non-normally distributed variables as medians and interquartile ranges (IQRs); categorical variables were presented as frequency and percentage (%). Statistical tests included the The study included 66 HF patients with permanent AF. Of these, 30 with worsening HF were readmitted within 180 days (readmission group), while 36 were not , Chronotropy , CI , and multivariate analysis confirmed the unique efficacy of SVR . In addition, SVR at discharge was significantly associated with the end-point event , even after adjusting for the significant variable CI in univariate analysis .As shown in Table P < 0.001). Meanwhile, employing the designated cutoff value to divide subjects into distinct groups, the KM survival analysis was performed using the log-rank test  compared with those with SVR ≤ 320.89 (kPa s/L). Interestingly, an SVR value of 169.94 (kPa s/L) at discharge was the optimal cutoff level to predict rehospitalization for worsening HF, presenting 90% sensitivity and 55.6% specificity with an AUC of 0.742 . Survival analysis suggested that patients with SVR > 169.94 (kPa s/L) at discharge faced a 6.57-fold increased risk of the end-point event  in contrast to those with SVR ≤ 169.94 (kPa s/L).ROC analysis of the SVR to predict readmission for HF exacerbation revealed Fig.  that theest Fig. . PatientThis study found that SVR, both on admission and at discharge, emerged as an independent risk factor and predictor of rehospitalization for worsening HF within 180-day post-discharge in HF patients with permanent AF. Moreover, patients with elevated SVR faced an increased risk of readmission stemming from HF aggravation within this period. To the best of our knowledge, this is the first study demonstrating the utility of ICG parameter SVR as a straightforward marker and predictive risk factor for 180-day rehospitalization in patients with HF and permanent AF.Reducing rehospitalization for HF and AF patients is vital for better outcomes and cost control. For this purpose, it is essential to identify high-risk groups and implement interventions. Currently, there is an ongoing inquiry into the rehospitalization risk for HF and AF patients. However, compared to the previous studies –35, new  P ≥ 450 pg/ml and TFC ≥ 40.1/kΩ, excluding AF patients. Hao‐Chih et al. [2 to increased HF readmission and all-cause death based on nocturnal impedance measurements. The observation did not include SVR, affecting comparability. A cohort study [Limited research has explored the relationship between non-invasive hemodynamic parameters and the prognosis of HF and AF. Some studies have focused on cardiac death as the end-point event. For instance, Andrius et al. reported  that chrrt study  tied expDynamic changes in vascular tone are another critical component in worsening HF pathogenesis. Heightened sympathetic activation and vasoconstrictor substances release, common in deteriorating HF, intensify arterial constriction, then increase SVR. Increased afterload triggers a rise in left ventricular pressure, enhancing ventricular wall stress, worsening myocardial ischemia, causing myocardial injury, deteriorating left ventricular pump performance, and elevating the likelihood of severe cardiac events –54. TeerSVR pertains to the level of hindrance encountered by blood flow within the vessels of the circulatory system. The elevation of SVR stems from a multifaceted interplay of factors, including vasoconstriction, heightened vascular wall thickness, augmented blood viscosity, reduced vascular elasticity, vascular endothelial dysfunction, disturbances in the neuroendocrine system, and inflammatory responses within the vascular wall, among others. These underlying pathophysiological mechanisms may interact to contribute to the escalation of SVR.Cardiovascular diseases directly or indirectly raise SVR by affecting these mechanisms. For instance, the diminished cardiac function activates the sympathetic nervous and renin–angiotensin–aldosterone systems, causing vasoconstriction, water retention, and increased blood volume, elevating resistance . HyperteIn our study, the exclusion of various hemodynamically impactful diseases and the presence of comparable baseline data, including blood pressure and relevant resistance-affecting medications, minimized external influences on SVR, enabling a direct evaluation of the link between HF with AF and SVR. Since we did not specify the cardiac etiology of the enrolled population, we cannot ascertain whether different cardiac causes might affect SVR measurement in our study. Further research on this aspect would also hold significant value.Our conclusions quantified the linkage between SVR and rehospitalization within 180 days for HF patients with permanent AF. This insight may aid clinicians in identifying high-risk readmissions, optimizing treatment plans, strengthening outpatient follow-up, and even ultimately reducing adverse events—an essential contribution of this study.This study has limitations: small sample size, all Chinese participants, HF types, some comorbidities excluded, and retrospective design impact generalization. Prospective multi-center research with a large sample is needed to further validate the prognostic value of SVR in different HF and permanent AF cases.In conclusion, our findings show a strong link between elevated SVR measured by ICG and a 180-day readmission risk for worsening HF in cardiac insufficiency patients with permanent AF.


P < 0.001 for both) from patient presentation. CoDE-ACS used as a clinical decision support system has the potential to reduce hospital admissions and have major benefits for patients and health care providers.Although guidelines recommend fixed cardiac troponin thresholds for the diagnosis of myocardial infarction, troponin concentrations are influenced by age, sex, comorbidities and time from symptom onset. To improve diagnosis, we developed machine learning models that integrate cardiac troponin concentrations at presentation or on serial testing with clinical features and compute the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) score (0–100) that corresponds to an individual’s probability of myocardial infarction. The models were trained on data from 10,038 patients (48% women), and their performance was externally validated using data from 10,286 patients (35% women) from seven cohorts. CoDE-ACS had excellent discrimination for myocardial infarction , performed well across subgroups and identified more patients at presentation as low probability of having myocardial infarction than fixed cardiac troponin thresholds (61 versus 27%) with a similar negative predictive value and fewer as high probability of having myocardial infarction (10 versus 16%) with a greater positive predictive value. Patients identified as having a low probability of myocardial infarction had a lower rate of cardiac death than those with intermediate or high probability 30 days (0.1 versus 0.5 and 1.8%) and 1 year (0.3 versus 2.8 and 4.2%;  A clinical decision support system for diagnosis of myocardial infarction, based on machine learning models that use a single measurement of high-sensitivity troponin, outperforms clinical guidelines that use fixed cardiac troponin thresholds for diagnosis. These pathways are now recommended by national and international clinical practice guidelines, but they have some important limitations13. First, they use fixed troponin thresholds for all patients, which do not account for age, sex or comorbidities that are known to influence cardiac troponin concentrations17. Second, they are based on specific time points for serial testing, which can be challenging to apply consistently in busy emergency departments18. Third, they categorize patients as low, intermediate or high risk of myocardial infarction based on troponin thresholds alone and do not consider other important information, such as the time of symptom onset or findings on the electrocardiogram19. Finally, although these pathways perform well to rule out myocardial infarction, identifying those with the condition is more challenging, and the performance of the 99th percentile diagnostic threshold is inconsistent in men and women, in older patients and in those with comorbidities24. In this study, we hypothesized that machine learning approaches to integrate cardiac troponin as a continuous measure and clinical features known to influence concentrations may provide a more individualized approach to assess probability and improve the diagnosis of myocardial infarction.High-sensitivity cardiac troponin assays have enabled the adoption of accelerated diagnostic pathways for the assessment of patients with symptoms suggestive of acute myocardial infarction25, we evaluated the diagnostic performance of guideline-recommended cardiac troponin thresholds and developed a clinical decision support system called the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) that uses machine learning models to calculate the probability of myocardial infarction for an individual patient. We then externally validated the diagnostic performance of CoDE-ACS and compared performance with guideline-recommended pathways to demonstrate how it could be used in clinical practice.In a prespecified analysis of the High-Sensitivity Troponin in the Evaluation of Patients with Suspected Acute Coronary Syndrome (High-STEACS) trial11 following review of all clinical information and investigations by two clinicians independently, with a third reviewer providing consensus if there was disagreement. The diagnostic outcome was prespecified and included all patients with an adjudicated diagnosis of type 1, 4b or 4c myocardial infarction without ST-segment elevation during the index hospital admission. Models to estimate the probability of myocardial infarction were trained separately in consecutive patients with and without myocardial injury at presentation, defined as a cardiac troponin I concentration above or below the sex-specific 99th percentile upper reference limit on the first measurement. In 6,239 and 3,799 patients with and without myocardial injury at presentation, the final adjudicated diagnosis after serial cardiac troponin measurements was type 1, 4b or 4c myocardial infarction in 3,094 and 132 patients, respectively.The derivation cohorts together were composed of 10,038 patients  with possible myocardial infarction presenting to 1 of 10 secondary or tertiary care hospitals in Scotland , 99.3–99.8) . CoDE-ACS models combine cardiac troponin as a continuous measure with age, sex, time from symptom onset, the presence of chest pain, known ischemic heart disease, hyperlipidemia, heart rate, systolic blood pressure, Killip class, myocardial ischemia on the electrocardiogram, renal function and hemoglobin  and sensitivity of 90.2 84.7–95.0). In those with myocardial injury, a CoDE-ACS score of 61 or more met our prespecified diagnostic performance criteria with a positive predictive value of 80.1 (78.5–81.6) and specificity of 83.4 (82.1–84.7). These scores identifying patients at low and high probability of myocardial infarction performed consistently across subgroups  and sensitivity of 95.5 (92.0–98.5) in those without myocardial injury at presentation and a positive predictive value of 82.5 (81.1–83.9) and specificity of 80.1 (78.4–81.6) in those with myocardial injury  with possible myocardial infarction pooled from seven prospective cohort studies enrolling patients across six countries . The negative predictive value and sensitivity were 99.7  and 98.3 , respectively. When the sex-specific 99th percentile diagnostic thresholds were applied at presentation, the proportion ruled in was 16% , with a positive predictive value and specificity of 63.6  and 93.4 , respectively. The remaining 57%  of patients had intermediate cardiac troponin concentrations or required serial testing as they presented early or had an abnormal electrocardiogram.In 10,286 patients from the external validation cohort, there was a total of 1,299 (13%) with a final diagnosis of myocardial infarction. When a threshold of less than 5 ng lA CoDE-ACS score of less than three identified 61%  of patients in the external validation cohort as low probability at presentation, with a negative predictive value of 99.6  and a sensitivity of 97.9  Fig.  and 4. AThere were 2,969 (29%) patients in the validation cohort with a CoDE-ACS score of 3–60 at presentation in whom serial testing would be recommended. When the first serial measure of cardiac troponin at any time point was incorporated, a CoDE-ACS score of less than 3 and 61 or greater identified a further 1,172 (11%) and 490 (5%) patients as low and high probability, respectively. Overall, this resulted in 72%  of patients being identified as low probability with a negative predictive value of 99.6  and sensitivity of 97.5  and 15%  of patients being identified as high probability with a positive predictive of 71.3  and specificity of 95.1 , respectively  had a diagnosis of myocardial infarction, the pathway identified 49%  of patients as low probability at presentation with a similar negative predictive value of 99.9  and a sensitivity of 98.4  and 2%  of patients as high probability with a lower positive predictive value of 61.5  but a similar specificity of 99.0  compared with the external validation cohort  having a final diagnosis of myocardial infarction , Age, Risk Factors, and Troponin (HEART) pathways, with 360 (16%) having a final diagnosis of myocardial infarction  for a higher negative predictive value  versus 99.6 ) and sensitivity  versus 97.9 ) (Supplementary Table P < 0.001)  deaths from a cardiac cause and 317 (3.1%) deaths of any cause in the external validation cohort. Compared with patients identified by CoDE-ACS at presentation as intermediate or high probability, those who were low probability of myocardial infarction had a lower rate of cardiac death and all-cause death at 30 days  and at 1 year  uses gradient boosting to compute a probability of myocardial infarction but has several limitations. First, while CoDE-ACS ruled in or ruled out myocardial infarction in 71% of patients with a single cardiac troponin test, MI3 requires two measurements in all patients to estimate probability. In practice, this would significantly limit the effectiveness of MI3 given that accelerated diagnostic pathways in use today enable decisions based on a single cardiac troponin measurement and have been shown to be safe and to prevent unnecessary admissions40. Second, the MI3 score was calculated using only age, sex and cardiac troponin concentrations. Although the use of a limited number of variables is laudable for its simplicity, by not including other important features that influence cardiac troponin, the positive predictive value and specificity were lower in patients with comorbidities43. Finally, MI3 was developed in a small cohort of selected patients, and when we performed a validation in unselected consecutive patients, we observed that calibration was poor, particularly for those at intermediate probability43. CoDE-ACS overcomes these limitations by estimating probability using a single cardiac troponin measurement, including other features that influence cardiac troponin concentrations and pretest probability, and by training the model in a large unselected patient population.The CoDE-ACS clinical decision support system was influenced by pioneering early studieshttps://decision-support.shinyapps.io/code-acs/). In the future, it may be possible to integrate CoDE-ACS with other machine learning approaches using the 12-lead electrocardiogram to further refine performance and reduce the proportion of patients requiring observation44. Likewise, the inclusion of findings from other investigations could help our models learn to differentiate between type 1 and type 2 myocardial infarction.The advantage of using machine learning models within a clinical decision support system over fixed cardiac troponin thresholds to generate a probability of myocardial infarction and the diagnostic metrics associated with this probability is that health care systems can apply a decision support system more flexibly. For example, in a health care setting that is more conservative, a lower CoDE-ACS score to identify patients as being at very low probability of myocardial infarction with a negative predictive value of 99.8 and false-negative rate of 1 in 500 could be applied to guide discharge in 50% of patients with a single test. Alternatively, in health care settings where capacity in the emergency department is limited, a lower CoDE-ACS score to identify those as high probability could be applied to reduce the proportion of patients considered of intermediate probability who require observation and serial testing within the department. Our clinical decision support system provides users with the option to select the diagnostic parameters and therefore, the CoDE-ACS score to define low and high probability in order to create a pathway that is optimal for patient flow according to local clinical priorities .The High-STEACS trial population was used for the derivation of the CoDE-ACS models. As previously described, High-STEACS was a stepped-wedged cluster-randomized, controlled trial to evaluate the implementation of a high-sensitivity cardiac troponin I assay in consecutive patients with suspected acute coronary syndrome presenting to 10 secondary and tertiary hospitals in Scotland between 10 June 2013 and 3 March 2016 (ref. STAT high-sensitivity cardiac troponin I assay (Abbott Laboratories) and (4) availability of electrocardiographic and physiological data for diagnostic adjudication. Patients with a diagnosis of ST-segment elevation myocardial infarction were excluded given they undergo coronary revascularization directly without troponin testing in the emergency department  in the context of a presentation with possible myocardial infarction due to either symptoms or signs of myocardial ischemia on the electrocardiogram. Patients with symptoms or signs of myocardial ischemia due to increased oxygen demand or decreased supply  secondary to an alternative condition or a coronary mechanism other than atherothrombosis and myocardial necrosis were defined as having type 2 myocardial infarction. Types 4b and 4c myocardial infarction were defined where myocardial ischemia and myocardial necrosis were associated with stent thrombosis or restenosis, respectively, on coronary angiography. Regional and national registries were used to follow patients for 1 year. The cause of death was adjudicated by investigators masked to troponin concentrations during the index presentation.The model was trained to identify patients with an adjudicated diagnosis of type 1, type 4b or type 4c myocardial infarction during the index hospital admission. The ground truth was adjudicated according to the Fourth Universal Definition of Myocardial Infarction by two clinicians independently, with a third reviewer providing consensus if there was disagreement−1) and rule in (99th percentile of 16 ng l−1 (women) and 34 ng l−1 (men)) myocardial infarction21. These were evaluated in the overall population and in prespecified subgroups by age, sex, time from symptom onset to troponin measurement, renal impairment, prior ischemic heart disease, diabetes mellitus, cerebrovascular disease and ischemia on the electrocardiogram.We evaluated the diagnostic performance and proportion of patients identified by guideline-recommended cardiac troponin thresholds to rule out 54. XGBoost is a supervised machine learning technique initially proposed by Chen and Guestrin52. In brief, gradient boosting employs an ensemble technique to iteratively improve model accuracy for regression and classification problems. This ensemble-based algorithm is achieved by creating sequential models using decision trees as learners, where subsequent models attempt to correct errors of the preceding models54. In the boosting method, individuals who were misclassified by the previous model are assigned a higher weight to increase their chance of being selected in subsequent models. Each model is subsequently fitted in a stepwise fashion to minimize loss function, such as absolute error or squared error . XGBoost refers to the reengineering of gradient boosting to significantly improve the speed of the algorithm by pushing the limits of computational resources. The output of the XGBoost model is a probability that is computed by performing an inverse logit transformation of the sum of the weights of the terminal nodes of the trained model.We first developed and evaluated models using four statistical methods—logistic regression, naïve Bayes, random forest and extreme gradient boosting (XGBoost)f is a function that maps each variable vector xi  to the outcome yi, K is the number of Classification and Regression Trees  and F is the space of function containing all Classification and Regression Trees55.The mathematical formula for the gradient boosting model can be described asl, which evaluates how well the model fits the data by measuring the difference between the prediction ŷi and the outcome yi. The second term, the regularization term, is used by XGBoost to avoid overfitting by penalizing the complexity of the model. Furthermore, to improve and fully leverage the advantages of XGBoost, we tuned the hyperparameters of the algorithm defined below through a grid search strategy using 10-fold crossvalidation (Supplementary Table XGBoost optimizes an objective function of the form−1 in women and 34 ng l−1 in men) on the first measurement21. Furthermore, given that practice guidelines recommend diagnostic pathways that use a single measure of cardiac troponin to rule in or rule out myocardial infarction, we also trained these models separately using the first cardiac troponin measurement alone and then, incorporating the second serial measurement at a flexible time point, resulting in four separate models for each method. For all models in the derivation cohort, we multiply imputed 10 datasets to account for missing data56 and performed 10 iterations of 10-fold crossvalidation to compute a score (0–100) that corresponded to an individual patient’s probability of having myocardial infarction.Given that the features that inform diagnosis differ for ruling in and ruling out myocardial infarction, we developed separate models for those with and without myocardial injury at presentation. Here, myocardial injury was defined as a cardiac troponin I concentration above the sex-specific 99th percentile upper reference limit  myocardial infarction in those with myocardial injury and to rule out  myocardial infarction in those without myocardial injury. These criteria were based on prior analysis and an international survey of acceptable risk by physicianshttps://decision-support.shinyapps.io/code-acs/).The model with the best discrimination in those without myocardial injury at presentation that identified the largest proportion of patients as low probability according to our prespecified performance criteria was selected and integrated into our CoDE-ACS clinical decision support system , the Improved Assessment of Chest Pain Trial (IMPACT), the 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker (ADAPT), the Emergency Department Assessment of Chest Pain Score (EDACS), the Signal Peptide in Acute Coronary Events (SPACE) and the Use of Abbott High Sensitivity Troponin I Assay in Acute Coronary Syndromes (UTROPIA) cohorts from Switzerland, Spain, Poland, Czech Republic, Australia, New Zealand and the USNCT00470587). From the 8,267 adult patients (≥18 years) presenting to the emergency department with symptoms suggestive of myocardial infarction, 5,995 were included in the external validation dataset. Cardiac troponin samples from enrollment and on serial testing at 1, 2 or 3 h depending on availability were used for validation of the CoDE-ACS models. While enrollment was independent of renal function, we excluded patients with terminal kidney failure on chronic dialysis. The study was carried out according to the principles of the Declaration of Helsinki and approved by the local ethics committees. Written informed consent was obtained from all patients. For this analysis, patients with an ST-segment elevation myocardial infarction, patients with missing high-sensitivity cardiac troponin I concentrations at presentation and patients in whom the diagnosis remained unknown even after final adjudication with at least one elevated cardiac troponin concentration, thereby possibly indicating myocardial infarction, were excluded.APACE was a prospective international multicenter study with 12 centers in five countries aiming to advance the early diagnosis of myocardial infarction  and type 2 59. All other patients were classified as unstable angina, noncardiac chest pain, cardiac but noncoronary disease  or symptoms of unknown origin with normal concentrations of cardiac troponin.Myocardial infarction was defined and cardiac troponin concentrations were interpreted as recommended in current guidelines−1 in women, 34 ng l−1 in men) were used to define myocardial injury. Absolute changes in cardiac troponin were used to determine clinically significant changes66. Based on studies of the biological variation of cardiac troponin68 as well as on data from previous chest pain cohort studies69, a clinically significant absolute change was defined as a rise or fall of at least 10 ng l−1 within 6 h or in an assumption of linearity, as an absolute change of 6 ng l−1 within 3 h. Patients were contacted 3 and 12 months after discharge by telephone calls or in written form. Information regarding death during follow-up was furthermore obtained from the patient’s hospital notes, the family physician’s records and the national registry on mortality.The adjudication of final diagnoses was performed centrally in the core laboratory  for all patients using the Abbott ARCHITECT high-sensitivity cardiac troponin I assay (Abbott Laboratories). More specifically, two independent cardiologists not directly involved in patient care reviewed all available medical records , radiological tests, electrocardiography, echocardiography, cardiac exercise test, lesion severity and morphology in coronary angiography, and the discharge summary) pertaining to the patient from the time of emergency department presentation to 90-day follow-up. In situations of diagnostic disagreement, cases were reviewed and adjudicated in conjunction with a third cardiologist. Sex-specific 99th percentile upper reference limits of the high-sensitivity cardiac troponin I assay . Informed written consent was obtained from all participants. Recruitment occurred between 0800 and 1700 and included patients aged ≥18 years with at least 5 min of symptoms suggestive of and planned testing for acute coronary syndrome. Research staff identified eligible patients. Patients were excluded if they had a clear nonacute coronary syndrome cause for their symptoms, they were unwilling or unable to provide informed consent , staff considered that recruitment was inappropriate , they were transferred from another hospital, they were pregnant, they were recruited to the study within the previous 30 days or they were unable or unwilling to be contacted after discharge.IMPACT was an intervention trial on adult patients in the emergency department with potential acute coronary syndrome (ACTRN12611000206921)−1 and a 10% coefficient of variation of 0.06 μg l−1. Values of >0.04 μg l−1 were considered elevated. Blood samples were taken on presentation and 2 h later for low- and intermediate-risk patients and at 0 and 6 h for high-risk patients. All available troponin results were used for clinical decision-making.Risk stratification occurred per the IMPACT protocol. Initial troponin and electrocardiographic testing was performed on presentation. High-risk patients were treated according to the 2006 National Heart Foundation/Cardiac Society of Australia and New Zealand guidelines. Low- and intermediate-risk patients were assessed using an accelerated investigation strategy, with repeat troponin testing 2 h after the first test. Routine inpatient stress testing was recommended only for intermediate-risk patients. Low-risk patients were discharged after normal 0- and 2-h biomarkers, with correspondence to their general practitioner stating that additional objective testing was not indicated. Cardiac troponin was measured by the Beckman Coulter second-generation AccuTnI assay (Beckman Coulter) to guide clinical practice and in stored material using the Abbott ARCHITECT high-sensitivity cardiac troponin I assay (Abbott Laboratories). This clinical assay is a sensitive troponin assay with a coefficient of variation of 14% at the 99th percentile value of 0.04 μg lTelephone follow-up occurred 30 days after presentation by research nurses. All information was verified through medical record databases and cardiac investigation results. Outcomes were adjudicated independently by local cardiologists using predefined standardized reporting definitions, with access to the clinical record, electrocardiogram, cardiac troponin measurements and all subsequent investigations from standard care. A second cardiologist conducted a blind review of all acute coronary syndromes and 10% of nonacute coronary syndrome cases. In cases of disagreement between the two adjudicators, end points were agreed on by consensus. Myocardial infarction was defined according to international guidelines and based on evidence of myocardial necrosis and ischemia. Patients with acute myocardial infarction were further subdivided into acute myocardial infarction type 1 (primary coronary events) and acute myocardial infarction type 2 . Myocardial necrosis was defined as a 20% increase or decrease in cardiac troponin concentration with at least one value above the 99th percentile of the normal reference range. Evidence of myocardial ischemia included the electrocardiogram or cardiac imaging.48. From November 2008 to February 2011, a total of 978 unselected patients presenting to the emergency department of the Royal Brisbane and Women’s Hospital with symptoms of possible acute myocardial infarction were recruited, while 797 patients were included in the validation dataset. Cardiac troponin samples from enrollment and 2 h were used for validation of the CoDE-ACS models. Criteria for enrollment included age ≥18 years of age with at least 5 min of symptoms where the attending physician planned to perform serial cardiac troponin tests. Patients were excluded for any of the following: a clear cause other than acute coronary syndrome for the symptoms , inability to provide informed consent, staff considered recruitment to be inappropriate , transfer from another hospital, pregnancy, previous enrollment or inability to be contacted after discharge. Perceived high risk was not used as an exclusion criterion. Written informed consent was obtained from all patients. Patients were managed according to local hospital protocols, including clinical history, physical examination, 12-lead ECG, continuous ECG monitoring, pulse oximetry, standard blood tests and chest radiography. Clinical blood draws for local cardiac troponin measurement were performed at presentation and then, 6–12 h afterward. Management of patients was at the discretion of the attending physician.The ADAPT-BSN trial was a prospective observational validation study designed to assess a predefined accelerated diagnostic pathway that consisted of the TIMI  score risk assessment, electrocardiogram (ECG), and 0- and 2-h central laboratory contemporary cardiac troponin I as the only biomarker. The original study population was from both Brisbane, Australia and Christchurch, New ZealandFinal diagnoses were adjudicated by independent cardiologists not directly involved in patient care. Adjudication was based on all available medical records , radiological testing, electrocardiography, echocardiography, cardiac exercise test, lesion severity and morphology in coronary angiography, and the discharge summary) pertaining to the patient from the time of emergency department presentation to 30-day follow-up. Myocardial infarction was diagnosed when there was evidence of myocardial necrosis with a clinically significant rise and/or fall in a clinical setting consistent with myocardial ischemia. Patients with acute myocardial infarction were further subdivided into type 1 myocardial infarction (primary coronary events) and type 2 myocardial infarction (ischemia due to increased demand or decreased supply). After discharge, patients were contacted after 6 weeks and 12 months (Brisbane) by telephone calls or in written form. Information regarding death was furthermore obtained from the patients’ hospital notes, the family physician’s records and the national registry on mortality.The ADAPT-CH study was prospectively performed in accordance with the ADAPT-BSN study (see above). From the 1,125 patients recruited between February 2011 and March 2014, 1,000 were included in the validation dataset. Cardiac troponin samples from enrollment and 2 h were used for validation of CoDE-ACS models. It aimed to compare the effectiveness of a rapid diagnostic pathway with a standard care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. Patients in the emergency department, where the attending physician was investigating for possible acute coronary syndrome, were included.Two senior clinicians adjudicated for the presence independently for any major adverse cardiac event. A third senior clinician adjudicated any disagreements with the first two clinicians.The ADAPT-RCT was a single-center randomized parallel-group trial with blinded outcome assessments conducted in an academic general and tertiary hospital . Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing in the Emergency Department at Christchurch Hospital, Christchurch, New Zealand. Patient recruitment occurred from 11 October 2010 to 4 July 2012, with a 30-day follow-up. From the 635 patients recruited, 540 were included in the validation dataset.Adjudication and follow-up were as described for ADAPT-CH.EDACS was a pragmatic randomized, controlled trial  of adults with suspected acute myocardial infarction. The primary outcome was the proportion of patients discharged to outpatient care within 6 h of attendance without a subsequent major adverse cardiac event within 30 days. There were 558 patients recruited, 279 in each arm. From 558 patients presenting to a single center , 529 were included in the validation cohort.Adjudication and follow-up were as described for ADAPT-CH.http://www.anzctr.org.au, number 12609000057280). Patients with the primary complaint of acute chest, epigastric, neck, jaw or arm pain suspicious of acute coronary syndrome without obvious noncardiac origin lasting ≥20 min were enrolled in accordance with guideline definitions. More general/atypical symptoms  were not used as inclusion criteria, and those on dialysis or with terminal kidney failure were excluded. From the 346, a total of 339 patients were included in the external validation dataset. Blood samples for measurement of high-sensitivity cardiac troponin I (Abbott Laboratories) were taken at 0, 1, 2 and 12–24 h after presentation. Cardiac troponin concentrations from time 0 and 2 h were used for validation of CoDE-ACS models.For SPACE, patients presenting to Christchurch Hospital with the primary complaint of chest pain of less than 4 h in duration were offered recruitment into our prospective, observational study (−1) and a rise or fall of 50% of the reference limit (0.015 μg l−1) within 12 h of presentation. At 45 and 365 days following discharge, enrolled patients were contacted by telephone or in writing to complete a follow-up interview/questionnaire. Reported clinical events were identified from the patients themselves (or their primary physician) and confirmed by clinical adjudication, centralized New Zealand Ministry of Health database registry entries on mortality and events, and records of the treating institution.The adjudicated diagnosis of myocardial infarction was made in accordance with the 2012 European Society of Cardiology (ESC)/ American College of Cardiology Foundation (ACCF), American Heart Association (AHA)/ World Heart Federation (WHF) task force guidelines by two independent cardiologists with access to all clinical data from standard care. The biochemical component of the diagnosis of myocardial infarction was made using a late-generation cardiac troponin I assay with one value in the ≥99th percentile upper reference limit (0.03 μg lNCT02060760) to rule in or rule out acute myocardial infarction. The study protocol was approved by the institutional review committee. For inclusion, patients needed a baseline cardiac troponin I measurement at presentation, at least one additional cardiac troponin I measurement within 24 h of presentation before discharge and at least one 12-lead ECG performed. Exclusion criteria were younger than 18 years old, ST-segment elevation myocardial infarction, pregnancy, trauma, declined to participate, did not present through the emergency department, or the patient was transferred from an outside hospital. For patients with more than one presentation during the study period, only the first presentation was included.UTROPIA was a prospective cohort study enrolling consecutive, unselected patients who presented from 4 February 2014 through 9 May 2014 to the emergency department, in whom serial cardiac troponin I measurements  were ordered on clinical indication at Hennepin County Medical Center .We compared CoDE-ACS with the HEART pathway and the 0/1-h pathway recommended by the European Society of Cardiology. The HEART  pathway identifies low- and high-probability patients with a HEAR  score of less than or equal to three and negative cardiac troponin concentrations at 0 and 3 h and a HEAR score greater than or equal to four or positive cardiac troponin concentrations at 0 or 3 h, respectivelyNCT01852123) and approved by the Scotland A Research Ethics Committee, by the Public Benefit and Privacy Panel for Health and Social Care, and by each National Health Service Health Board25. This analysis was prespecified in the trial protocol and was performed according to a separate statistical analysis plan. As the trial intervention was implemented at the hospital level, consent was not sought from individual patients. All data were collected prospectively from the electronic patient record, deidentified and linked to regional and national registries in a data repository within a Secure Data Environment (DataLoch). All cohort studies contributing to the external validation were approved by their respective local research ethics committee or institutional review board with written informed consent from participants.The High-STEACS trial was registered (ClinicalTrials.gov registry number Further information on research design is available in the Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41591-023-02325-4.Supplementary InformationSupplementary Figs. 1–10 and Tables 1–11.Reporting SummarySupplementary Note 1Checklist for the supervised clinical ML study.


To perform this task, we compared two groups of patients with acquired valvular heart disease: patients who had undergone surgical AF ablation and patients with sinus rhythm. The decrease in norepinephrine (NE) level in the coronary sinus had a direct association with the heart-to-mediastinum ratio (p = 0.02) and a negative correlation with 123I-MIBG uptake defects (p = 0.01). The NE level decreased significantly after the main surgery, both in patients with AF (p = 0.0098) and sinus rhythm (p = 0.0039). Furthermore, the intraoperative difference between the norepinephrine levels in the ascending aorta and coronary sinus (ΔNE) of –400 pg/mL was determined as a cut-off value to evaluate RFA efficacy, as denervation failed in all patients with ΔNE < –400 pg/mL. Hence, ΔNE can be utilized to predict the efficacy of the “MAZE-IV” procedure and to assess the risk of AF recurrence after RFA.Although the autonomic nervous system has an evident impact on cardiac electrophysiology and radiofrequency ablation (RFA) is the conventional technique for treating persistent atrial fibrillation, the specific effects of RFA have been insufficiently studied to date. Here, we investigated whether RFA affects neurohumoral transmitter levels and myocardial  As has been established over the years, the autonomic nervous system (ANS) plays a significant role in modulating the cardiac electrophysiology and arrhythmogenesis through its effect on cardiac physiology . CardiovA significant discovery was made with regard to neurohumoral markers that were found to be reflective of autonomic activity in the heart. Unfortunately, there is no versatile method for studying the ANS, and current techniques in this field impose certain requirements that are not always possible to meet. By identifying specific ANS markers and triggers, the study of autonomic cardiac activity can become more efficient than many other invasive methods. Patients with long-term persistent atrial fibrillation (AF) might benefit most from this.AF represents a typical and common complication of cardiac surgery in 30% of cases of coronary artery bypass surgery, 40% of patients after valvular heart surgery and 50% of cases if these interventions are combined ,3. The cNormal cardiac electrophysiology is, to a significant extent, governed by the ANS. Pre- and postganglionic sympathetic and parasympathetic fibers form a complex network and synapses on extrinsic and intrinsic cardiac ganglia. Both sympathetic and parasympathetic fibers directly innervate the cardiac myocytes. One clinically significant implication is that the evaluation of the ANS modulation of the myocardium following RFA can be useful in predicting the recurrence of AF, and other adverse cardiac events as well ,18,19. AThe role of sympathovagal imbalance in the pathogenesis of arrhythmias is still a serious and unresolved problem for practitioners and researchers. The development of this direction has been propelled by Pappone and colleagues who showed a relationship between the impact on the paraganglionic nerve plexi of the heart and AF recurrence after catheter ablation . Their dIt is therefore reasonable to speculate that denervation may be a common mechanism underlying many of the therapeutic effects associated with various procedures for treating AF. However, the effects of denervation on the long-term efficiency of AF surgical treatment require further studies. As research on the relationships between autonomic tone and cardiac dysrhythmias continues to evolve, there is increasing evidence that autonomic ganglia play an essential role in the pathogenesis of AF.To obtain information about the state of the autonomic innervation of the heart, the determination of heart rate variability and measurements of epinephrine and norepinephrine (NE) concentrations in blood plasma are widely used ,24. Howe123I-metaiodobenzylguanidine (123I-MIBG) has acquired the greatest popularity in assessing the sympathetic activity of the myocardium today [To date, the best way of carrying out the visual and quantitative assessment of sympathetic innervation of the myocardium is the use of nuclear medicine methods such as positron emission tomography (PET) of the heart with labeled catecholamines ,28. Howeum today ,31,32,33123I-MIBG was compared with the results of the quantitative measurements of metanephrine, normetanephrine, and NE in plasma obtained intraoperatively from the coronary sinus and ascending aorta.Given the lack of a “gold standard” assessment of the sympathetic innervation of the heart in vivo, in the present study, myocardial scintigraphy with 123I-MIBG uptake in patients with long-standing persistent AF.The aim of this study was to evaluate the consequences of RFA on neurohumoral transmitter levels and n = 53) and those with sinus rhythm . The study protocol was approved by the Local Ethical Committee of the Research Institute for Complex Issues of Cardiovascular Diseases  and Cardiology Research Institute within Tomsk National Research Medical Centre . Written informed consent was provided by all study participants after receiving a full explanation of the study’s purposes. Comorbid conditions  were diagnosed and treated according to the corresponding guidelines of the respective research societies. Clinicopathological information was collected at the time of hospital admission. In total, we enrolled 68 patients with mitral valve disease recommended for surgical correction: those suffering from long-standing persistent AF (The criterion of inclusion was the preserved function of the sinus node (SN) determined by intraoperative electrophysiological examination . Among tn = 15).The patients were given 7 days prior to surgery to discontinue medications that affect the rhythm and heart conduction. During the intraoperative electrophysiological examination, we measured sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), and Wenckebach point. Patients with preserved SN function were enrolled and randomized into two groups using envelopes. In the first group of patients, RFA was administered in combination with postganglionic plexus ablation based on the Doll (2008) scheme, while in the second group, lesions were performed according to the MAZE-IV scheme without the addition of postganglionic plexus ablation. In the case of normal SN function, the procedure was performed using the MAZE-IV technique (penetrating technique) to seal atrial appendages and additional postganglionic plexi ablation. Patients with SR who underwent surgery only due to valvular lesions comprised the control group (123I-metaiodbenzylguanidine (123I-MIBG) was performed before and after the surgery. 123I-MIBG is an analogue of guanethidine adrenergic blocker which allows the visualization of sympathetic innervation of the heart and assessment of myocardial adrenergic nerve activity [Each patient underwent a standard set of clinical and laboratory tests, including complete blood count , biochemical profiling using an automated biochemical analyzer , urinalysis, X-ray examination , echocardiography , color duplex screening , spirometry , and coronary angiography  in accordance with the guidelines . Planar activity . During Patients with persistent AF (group I) differed from patients with SR (group II) with regard to left atrial (LA) diameter and results of 6 min walking test. Chronic rheumatic heart disease was diagnosed in 50% of patients with persistent AF and in 44.4% of patients with SR. Connective tissue dysplasia was found in 28 and 44.4% of cases, respectively. Some patients from both groups required coronary artery bypass grafting (1–2 grafts).Surgical treatment was performed in accordance with the recommendations for the management of patients with valvular heart diseases . The frequency of mitral valve (MV) repair with annuloplasty rings in the groups was 50 and 55.5%, respectively, and MV prosthetic valve replacement was performed in one-third of cases in both groups. Several patients required multi-valvular interventions , and 4 patients underwent simultaneous intervention on the aortic valve. In the case of paroxysmal AF, an antiarrhythmic therapy was prescribed in group I.Blood samples were collected intraoperatively from the ascending aorta and coronary sinus prior to cardiopulmonary bypass and 10 min after removal of the clamp from the aorta. The study was performed in the absence of any medications that could affect the catecholamine levels in the samples. In the case of any catecholamine injections, patients were excluded from the study. NE level in blood was assessed both before and after RFA. For the quantitative determination of plasma NE level, we applied Noradrenalin enzyme-linked immunosorbent assay kit  according to the manufacturer’s protocol. Colorimetric analysis was conducted using Multiskan Sky microplate spectrophotometer . In order to avoid any external influence on the sympathetic tone of the heart during surgery, sympathomimetic drugs were withdrawn before the main phase of the operation, during and after the main stage before the sampling of blood from the ascending aorta and the coronary sinus. All patients underwent 24 h Holter ECG monitoring before the surgery and after removal of sutures before hospital discharge. A re-examination was performed 6 months after the operation.t-test or Mann–Whitney U test. To assess the significance of intragroup differences (measurements before and after the exposure within one group), Wilcoxon matched pairs signed rank test was used. p-values ≤ 0.05 were regarded as statistically significant. Discriminant analysis was used to build a model for the assessment of the RFA efficacy based on neurohumoral factors.Statistical analysis was performed using STATISTICA 13 software . For descriptive statistics, data were presented as median (Me), upper and lower quartiles . Depending on the data distribution, two independent groups were compared using Student’s p = 0.1). The washout rate did not show statistically significant differences either  % and 24.3  %, respectively, p = 0.15). The 123I-MIBG uptake defect before surgery was comparable between the groups  % and 19.0  %, respectively, p = 0.59). At the pre-operative stage, the parameters of the sympathetic nervous system tonus were similar across the groups. Four weeks after the surgery, patients underwent a postoperative examination  and 2.06 , respectively, mination .123I-MIBG scintigraphy with the concurrent measurement of metanephrine, normetanephrine, and NE in the blood withdrawn from the ascending aorta and coronary sinus. In patients with atrial RF fragmentation (group I), the heart-to-mediastinum ratio after intervention in the late phase of the study was significantly lower compared to the patients with SR:  and 1.8 , respectively, p = 0.02), whilst the uptake defect was significantly higher  % and 15.0  %, respectively, p = 0.01). A statistically significant (p = 0.01) decrease in the NE level in patients with RFA was found in the blood collected from the coronary sinus after the main stage of the surgery as compared to the preoperative level. In contrast, no significant difference (p = 0.2) in the NE level was found in the control group.The efficacy of AF RFA was evaluated using postoperative p = 0.004) in the postoperative NE level  but the p-value did not reach 0.05 . Wilks’ lambda was 0.56, with p = 0.0037, indicating the adequacy of the created model . The significance of the intraoperative difference between the levels of NE, metanephrine, and normetanephrine in the ascending aorta and in the coronary sinus  was measured by the F-value. If the F-value exceeded the critical value (1.23), the variable was kept in the model. In the case of ΔNE, the F-value was 13.20 and was retained in the model as its ed model .ΔNE was therefore considered as a statistically significant factor. The calculation of ΔNE for each patient was performed as follows:As the percentage of correct assignments  was 88.9%, we concluded the model had high discriminative power in terms of its sensitivity/specificity .Upon the calculation of the coefficients for the canonical linear discriminant function and plotting of ΔNE values across the RFA outcomes, we found that all patients with ΔNE < −400 pg/mL suffered from AF paroxysms in the early postoperative period (indicative of the perfect sensitivity of this cut-off) whereas, at higher ΔNE values, only one case of AF paroxysm was detected . Hence, we propose a ΔNE of –0.400 pg/mL as a cut-off reflecting RFA efficacy .123I-MIBG in all patients who underwent RFA of postganglionic nerve plexi, and these parameters were associated with the effectiveness of the AF surgical treatment.As described above, we detected a reduced NE level and the accumulation of AF is a frequent heart rhythm disorder, the etiology of which is still not fully understood ,38,39,40+/Ca++ pump activity, which is responsible for the generation of early afterdepolarization and trigger activity [The effect of the ANS sympathetic component on cardiac electrophysiology is complex and depends on myocardial function. The predominance of sympathetic activity in the intact heart leads to a shortening of the cardiac action potential duration and to a decrease in the repolarization dispersion. In the injured myocardium, sympathetic activity leads to an increase in the repolarization dispersion and to the early afterdepolarization generation ,46 proviactivity ,47.The cardiac ANS comprises the extrinsic and intrinsic innervation of the heart. The postganglionic neurons of the heart may still function normally despite active central regulatory mechanisms. Studies by Choi and colleagues demonstrated a connection between the external and internal mechanisms of sympathetic heart tonus activation. Though activation of extracardiac ANS contributed to the onset of most AF paroxysms, in some cases  the internal nervous activity of the heart preceded the external one and led to the development of AF paroxysms . In addi123I-MIBG scintigraphy, yet they still lack clear diagnostic criteria [123I-MIBG is that its current use is limited to specialized clinics and research centers due to the specificity of this isotope. Other methods are not sufficiently specific to identify cardiac autonomous activity, or they take an excessive amount of time, which restricts their application. Thus, there is no versatile method to measure the ANS activity of the heart [Among the most common approaches for studying ANS is the analysis of heart rate variability, although it has several limitations. First, this method reflects only the sympathovagal balance between the ANS components but not their activity. Second, this analysis requires an intact SN that mediates an adequate cardiac response to ANS activity, whereas a notable proportion of patients with persistent AF and heart failure have comorbid SN dysfunction. This imposes restrictions on using heart rate variability for studying the ANS tonus and this is not suitable for some patient categories . An objecriteria . AnotherThis study shows that neurohumoral markers, such as NE, detectable by cheap and broadly employed enzyme-linked immunosorbent assay, can serve as a quantitative measure of the effectiveness of RFA in long-term persistent AF. Importantly, low concentrations of NE and its short decay period permit its measurement only in the absence of its entry into the blood from other sources.The difference in the NE level in the blood collected from the aorta and the coronary sinus after the main stage of the surgery (ΔNE) is an informative factor in assessing the effectiveness of autonomic denervation of the heart, as ΔNE < −400 pg/mL can be considered as a reliable marker of unsuccessful denervation. As the effectiveness of AF surgical treatment was confirmed by 24 h Holter ECG monitoring, we then developed a mathematical model to evaluate the quality of atrial RF denervation based on the Wilks’ lambda, which makes possible the prediction of AF recurrence in the postoperative period. These data correlated with the scintigraphic and clinical data, allowing us to state that the completeness of heart autonomic denervation directly correlates with the effectiveness of the MAZE-IV RF procedure.Considering a number of factors influencing the recurrence of postoperative AF, a decrease in the neurohumoral activity of the ANS enables the SR to be maintained and reduces the risk of postoperative complications, such as a reduction in left ventricular ejection fraction and systemic thromboembolism. The development of a tool to predict arrhythmia-associated complications has been the cornerstone of this study. An important result is the comparison of scintigraphic and laboratory methods for studying the autonomic activity of the heart, which will enable further research for new criteria and technologies.The limitations of this study include the relatively small number of patients, the need to cancel the medications affecting ANS activity, the ability to take blood samples only in an “open” heart, and the limited options for administering sympathomimetics during the surgery. Although the results of the study showed the importance of determining the NE level in the assessment of autonomic atrial denervation, further studies are necessary to obtain more data.Neurohumoral markers of the ANS in the postoperative period may indicate the efficiency of the RFA and MAZE-IV RF procedure, as the intraoperative gradient between the levels of NE in the ascending aorta and coronary sinus (ΔNE) of −400 pg/mL discriminates well between a successful and an unsuccessful RFA. Hence, we propose ΔNE as a promising tool for assessing the atrial denervation quality, although replication studies are clearly needed.


Recent studies have shown that the right ventricular (RV) quantitative analysis in myocardial perfusion imaging (MPI) SPECT can be beneficial in the diagnosis of many cardiopulmonary diseases. This study proposes a new algorithm for right ventricular 3D segmentation and quantification.The proposed Quantitative Cardiac analysis in Nuclear Medicine imaging (QCard-NM) algorithm provides RV myocardial surface estimation and creates myocardial contour using an iterative 3D model fitting method. The founded contour is then used for quantitative RV analysis. The proposed method was assessed using various patient datasets and digital phantoms. First, the physician’s manually drawn contours were compared to the QCard-NM RV segmentation using the Dice similarity coefficient (DSC). Second, using repeated MPI scans, the QCard-NM’s repeatability was evaluated and compared with the QPS (quantitative perfusion SPECT) algorithm. Third, the bias of the calculated RV cavity volume was analyzed using 31 digital phantoms using the QCard-NM and QPS algorithms. Fourth, the ability of QCard-NM analysis to diagnose coronary artery diseases was assessed in 60 patients referred for both MPI and coronary angiography.The average DSC value was 0.83 in the first dataset. In the second dataset, the coefficient of repeatability of the calculated RV volume between two repeated scans was 13.57 and 43.41 ml for the QCard-NM and QPS, respectively. In the phantom study, the mean absolute percentage errors for the calculated cavity volume were 22.6% and 42.2% for the QCard-NM and QPS, respectively. RV quantitative analysis using QCard-NM in detecting patients with severe left coronary system stenosis and/or three-vessel diseases achieved a fair performance with the area under the ROC curve of 0.77.A novel model-based iterative method for RV segmentation task in non-gated MPI SPECT is proposed. The precision, accuracy, and consistency of the proposed method are demonstrated by various validation techniques. We believe this preliminary study could lead to developing a framework for improving the diagnosis of cardiopulmonary diseases using RV quantitative analysis in MPI SPECT.The online version contains supplementary material available at 10.1186/s40658-023-00539-6. Myocardial perfusion imaging (MPI) is a powerful diagnostic and prognostic method in patients with known or suspected coronary artery disease and ventricular function . MPI hasThe following four clinical factors may result in an elevated stress RV-to-LV (RV/LV) uptake ratio: increased myocardial blood flow within RV, a global reduction in LV tracer uptake, RV hypertrophy, and RV dilation –6. HowevSome works have demonstrated that assessing RV perfusion, function, and metabolism in patients with cardiovascular diseases can offer valuable diagnostic and prognostic information –11. AddiHowever, RV abnormality detection is still a challenging issue. For instance, a change in the sensitivity and resolution of the gamma camera may alter the count statistic of the RV region. Additionally, the RV measured counts may be impacted by attenuation correction, resolution modeling, and image acquisition and reconstruction techniques . FurtherSeveral commercial and non-commercial packages have been developed for LV myocardial quantitative analysis in MPI. Some researchers used geometrical models to segment the LV in perfusion images –29. For Although the RV segmentation and analysis was developed and advanced in cardiac blood pool SPECT –37, RV aAs accurate segmentation of the RV is an essential step for MPI quantitative analysis, a novel technique for RV segmentation, named QCard-NM , is proposed in this study. In the proposed method, the LV is segmented first using an improved technique based on the Cedars-Sinai approach . An initIn our proposed approach, we named it QCard-NM, the LV is segmented first, and RV segmentation starts based on the position of the LV. Based on the RV shape in the MPI scan, an appropriate model is generated for RV segmentation, as discussed later in this section. Epicardial and endocardial surfaces are then determined via an iterative process based on the fitted model. The segmented RV volume is then used for quantification.The transversal reconstructed image is rotated based on the predefined constant angle to estimate the short-axis view. To calculate the predefined rotating angle, a group of images was automatically rotated into short-axis slices by the method described in . Then, tP” is denoted as the sphere center. The distance between P and the apex is called “f” which is equal to Eq.  originating from the sphere center are extracted from the image volume. The local maxima of each profile are found. The local maximum that satisfies the following conditions is chosen: 1—Its distance to the sphere surface is less than or equal to a pixel size (6.4 mm), and 2—the voxel count value is more than one-quarter of the maximum LV count value. The corresponding voxel count value called d by Eq. .5\documeThe final sphere model delineates the epicardial and endocardial surface points. Radial profiles  originating from the sphere center are extracted from the image volume. Epicardial, endocardial, and mid-myocardial surface points are delineated as described previously. A new sphere is fitted to the mid-myocardial points. Each selected epicardial and endocardial surface point which does not meet the local maxima criterion is replaced with a point from the spherical model.X-axis in the horizontal long-axis view. Voxels enclosed by the endocardial surface and the valve plane are used to determine RV cavity volume. The intersection of the RV and LV valve planes is placed on the LV epicardial surface. A fifth-degree polynomial equation (with boundary condition) is used to construct the mid-myocardial surface. Polynomial is fitted to the surface points by the Levenberg–Marquardt method  with an average of 0.83 ± 0.14. The physician could delineate or modify the contours with the help of fused SPECT/CT images. The LV region in the fused SPECT/CT was masked in order to improve RV visibility. Figure In this section, the QCard-NM and QPS algorithms were applied to the supine/prone dataset, and by using the segmented images, the LV and RV cavity volumes were measured. Results for each individual are presented in Additional file Y-axis and X-axis in the Bland–Altman graph indicate the percentage difference between the measured cavity volumes of successive scans and the average of the measured cavity volume, respectively. The mean of the difference (blue lines), upper and lower bound of LoA (orange lines), and the corresponding 95% CI (dashed lines) were determined for the QCard-NM  are presented in Table see Fig. A and QPSsee Fig. B algoritMoreover, the RV cavity volumes obtained by the QCard-NM and QPS algorithms are compared in Fig. Thirty-one XCAT phantoms with different RV sizes and uptakes were fed into the SIMIND software, which simulated the non-gated SPECT. The reconstructed images were segmented by using the QCard-NM and QPS algorithms. The difference between the measured RV cavity volumes and the actual simulated values was reported by MAPE metric. The MAPEs 95% CI) were 22.6% (15.3–29.9) and 42.2% (30.0–54.4) for the QCard-NM and QPS algorithms, respectively. An example of a segmented phantom with QCard-NM and QPS algorithms, as well as the simulated phantom, is illustrated in Fig. 5% CI werP value were calculated . Therefore, it can be concluded that the quantitative RV/LV uptake ratio in a stress MPI scan appears to be statistically associated with RV visual assessment.The stress maximal RV/LV uptake ratio  in the SPECT/Angio and normalcy datasets was compared by the physician’s visual assessment. The maximal RV/LV was lower in individuals with imperceptible stress RV uptake (median (IQR): 28 (23–32.5)) than in patients with visible stress RV (median (IQR): 36.5 (31.5–41.5)). This difference was statistically significant  and CAD. The results are visualized in box-and-whisker plots see Fig. . The medMoreover, a ROC curve was plotted to evaluate the performance of the stress maximal RV/LV uptake ratio for binary classification of patients belonging to 3VD and LAD, LCX > RCA subgroups from three others subgroups see Fig. . The AUCFigure On the other side, there are two main causes of failure in appropriate RV segmentation by QCard-NM. As Fig. As a summary, based on the results and our viewpoint, in Table From the spatial similarity assessment section, we determined that the proposed approach is sufficiently compatible with the physician’s opinion. Due to partial volume effect in SPECT imaging, only a small portion of the RV wall exhibits significant intensity compared to the background which can be delineated with thresholding. As a result, a proper model-based approach must be used to estimate the portions of the RV wall with low signal intensity. Based on the spatial similarity result, the spherical model which is proposed in QCard-NM appears to be reasonable. However, a more complicated model, such as the one presented in , may proIn the repeatability assessment section, the patients were scanned in both prone and supine positions. Prone imaging results in an apparent reduction in extracardiac activity in the adjacent myocardial segment . ConsequP value < 0.001). In this part, the QPS algorithms performed poorly .Additional file 1. Flowchart S.1: LV segmentation algorithm. Flowchart S.2: RV segmentation algorithm. Table S.1: Individual results of repeated scans of the supine/prone dataset.


It is a well-known fact that COVID-19 affects the cardiovascular system by exacerbating heart failure in patients with preexisting conditions. However, there is a poor insight into the cardiovascular involvement and sequelae in patients without preexisting conditions. The aim of the study is to analyse the influence of COVID-19 on cardiac performance in patients without prior history of structural heart disease. The study is part of the CRACoV project, which includes a prospective design and a 12-month follow-up period.The study included 229 patients hospitalised with a diagnosis of COVID-19 . A standard clinical assessment and laboratory tests were performed in all participants. An extended echocardiographic image acquisition was performed at baseline and at a 3-, 6-, and 12-month follow-up. All analyses were performed off-line. A series of echocardiographic parameters was compared using repeated measures or Friedman analysis of variance.p = 0.08), while a significant improvement of the parameters in the biventricular strain was observed . In addition, a decrease in the LV wall thickness was also observed .In all subjects, the left ventricular (LV) ejection fraction at baseline was preserved . Elevated levels of high-sensitivity cardiac troponin T were detected in 21.3% of the patients, and elevated NT-proBNP levels were detected in 55.8%. At the 1-year follow-up, no significant changes were observed in the LV diameter and volume (LV 48.0 ± 5.2 vs. 47.8 ± 4.8 mm, In an acute phase of COVID-19, the elevation of cardiac biomarkers in patients with normal left ventricular ejection fraction is a frequent occurrence; however, it does not translate into clinically significant cardiac dysfunction after 1 year. The serial echocardiographic evaluations conducted in patients without preexisting structural heart disease demonstrate an overall trend towards an improved cardiac function and a reduced myocardial thickening at 1-year follow-up. This suggests that the acute cardiac consequences of COVID-19 are associated with systemic inflammation and haemodynamic stress in patients without preexisting conditions. For the first time in the modern history, we witnessed, observed, and examined a highly infectious disease causing respiratory inflammation with multiorgan involvement for a large girth of the global population but also presented numerous possibilities for the application of innovative technology to describe the disease and its epidemiology, transmission, onset and pathogenesis, and prognostic biomarkers. The first observations of patients with COVID-19 indicated that the factors of unfavourable prognosis are age and the coexistence of cardiovascular diseases, including hypertension, diabetes, and chronic kidney disease . ConsideNevertheless, early observations with regard to cardiac involvement in COVID-19 raised the question about its long-term consequences on the circulatory system. Special concern was related to the possible development of heart failure resulting from systolic dysfunction of the left or right ventricle and pulmonary hypertension as a complication of lung fibrosis secondary to the infection.There is a poor insight into the cardiovascular involvement and sequelae in those with no preexisting conditions. We performed a systematic and comprehensive serial echocardiographic evaluation of patients hospitalised with COVID-19. The aim of the study was to analyse cardiac performance in subjects without prior history of structural heart disease in relation to inflammatory markers and clinical outcomes at baseline and during the 12 months of follow-up.2.Our study is a part of the CRACoV-HHS project that aims at integrating basic and clinical research to better understand the pathomechanism, the course of infection, and the prognosis, including early and long-term physical and mental health complications associated with COVID-19, with details published elsewhere . The stu2 at admission, (5) active cancer, and (6) chronic inflammatory disease.Of the 498 patients with COVID-19 included in the CRACoV study, 229 patients were qualified to be included in the echocardiographic sub-study. The primary inclusion criteria consisted of the following: (1) informed consent to participate in the study, (2) confirmed COVID-19 infection (positive RT-PCR or antigen test), and (3) age of ≥18 and <75 years. The patients were recruited between 8 January 2021 and 30 April 2021. Patients without prior history of structural heart disease were eligible for the study. The exclusion criteria were the following: (1) a prior diagnosis of left ventricular systolic dysfunction with an ejection fraction (EF) of <40%, (2) a prior diagnosis of severe valvular heart disease, (3) a history of an atherosclerotic cardiovascular event within 6 months prior to inclusion in the study , (4) chronic kidney disease with eGFR of <30 ml/min/1.73 mIn all patients included in the study, a comprehensive medical history was taken according to a standardised questionnaire, and a physical examination was performed. The severity of the disease on the admission was categorised into asymptomatic, mild, moderate, severe, and critical according to the COVID-19 Treatment Guidelines provided by the National Institutes of Health .2.1.Blood samples were collected on the first (H1) and seventh day of hospitalisation (H7), and cardiac and inflammatory markers were assessed .2.2.n = 44) had their first echocardiographic examination performed at the first check-up, which was 4 weeks after discharge from the hospital.After the inclusion criteria were met, a bedside echocardiography was performed within the first 72 h after admission in 185 patients hospitalised in the New University Hospital. The bedside echocardiography was performed using the Vivid IQ device . Patients hospitalised in the Temporary COVID Ward . The study analyses were performed off-line using an EchoPack v204 workstation integrated with the ViewPoint system. All follow-up examinations were performed using the GE Vivid E95 device . All patients underwent a follow-up examination after 3, 6, and 12 months. Trained investigators performed the off-line image analysis of the echocardiographic examinations, and they were blinded to all clinical information including the order of the study for each patient. However, they were not blinded to the specific date of the examination. All conventional measurements of the chamber size and volumes were performed following the recommendations of the guidelines , 13.The left ventricle (LV) EF was calculated with the use of the Simpson's biplane method. Left ventricular mass (LVM) was calculated according to the Devereux cube formulaAs an estimate of the global right ventricular (RV) systolic function, the fractional area change (FAC) was measured. In the images optimised on maximising the right ventricle, the border of the endocardium was traced in the end-systole and end-diastole, and the difference in the end-diastolic area and end-systolic area divided by the end-diastolic area was calculated. The function of RV longitudinal fibres was measured by calculating the tricuspid annular plane systolic excursion (TAPSE) in M-mode of the apical four-chamber projection, as well as by the systolic velocity of the tricuspid annulus (S’) assessed by pulsed tissue Doppler.The right atrial area and volume (RAV) was calculated according to the single disk summation technique. Left atrial volume (LAV) was measured based on the biplane disk summation technique and further indexed to body surface area (LAVi).Using the continuity equation with measurement of the left ventricular outflow tract diameter (LVOT) and pulsed-wave Doppler velocity time integral, the left ventricular stroke volume (SV) and cardiac output (CO) were calculated.The maximal velocity of tricuspid regurgitation (TR Vmax) was measured by the continuous wave Doppler across the tricuspid valve, and by following the guidelines, the echocardiographic probability of pulmonary hypertension was calculated, integrating data from other measurements obtained .S’), early diastole (E’), and late diastole (A’) were measured. The final value represented the average of two sites. The ratio of early mitral inflow and mitral annulus velocities (E/E’) was calculated.Mitral inflow velocities were recorded with pulsed-wave Doppler sonography to assess the left ventricular diastolic function. Three consecutive cardiac cycles were averaged to measure the peak velocities reached in early diastole (E-wave) and after atrial contraction (A-wave), and calculate the E/A ratio. Colour-coded tissue Doppler images were acquired for lateral and septal segments of the mitral annulus. The sample volume was placed at the junction of the LV wall with the mitral annulus of the septal and lateral myocardial segments from the four-chamber view. The peak velocities during systole  assessment was based on four parameters: E′, E/E′ ratio, LAVI, and TR V max . Their cA two-dimensional speckle tracking technique and dedicated semi-automated software were employed to calculate left and right ventricular and left atrial strain (LAS). Projections with the highest available frame rate were used. The measurement of the left ventricular global longitudinal strain (GLS) was performed in the three apical long-axis views. The region of interest (ROI) was manually traced. From each projection, six regions were included into a global model of the LV. GLS was calculated as the average of all segments included by an automated software function.The right ventricular longitudinal strain (RVLS) was measured in an apical four-chamber projection optimised for a view of the RV. The RV free wall was divided into three segments. The peak systolic strain was calculated separately for the RV free wall and RV including septal deformation.LAS was calculated from the apical four- and two-chamber projections. The ROI was defined with landmarks at the endocardial border on both sides of the mitral annulus and one landmark at the atrial roof. The region of interest provided by the system was manually edited as required. Then, the system automatically tracked speckles inside the ROI and provided strain measurements with zero strain defined at the left ventricular end-diastole (R-wave of the electrocardiogram). Based on the cardiac cycle, three components of LAS were defined: reservoir strain (LAS-r), conduit phase strain (LAS-cd), and contractile strain (LAS-ct).2.3.Individual characteristics are presented as numbers and percentages for categorical variables, and depending on the variable distribution, normally or non-normally distributed variables are presented as means with standard deviations (SD) or medians with 25th–75th percentiles, respectively.t-test or the Mann–Whitney U test for non-normally distributed continuous variables. The categorical variables were compared between independent groups based on chi-square testing or Fisher's exact test.The Shapiro–Wilk test was used to verify the normality. The differences between independent groups, such as baseline severity of the disease or in-hospital outcome, were compared with Student’s t-test for continuous variables with normal distribution and Wilcoxon rank-sum test for variables with non-normal distribution were used to analyse the changes between repeated measurements taken in consecutive follow-up time points compared with baseline points. A series of echocardiographic parameters was compared using repeated measures or Friedman analysis of variance (ANOVA) depending on whether parametric assumptions are met. Wilcoxon rank-sum test for pairwise comparisons was used following Friedman's analysis of variance. Correlation coefficients between two variables were calculated using Spearman's correlation test.Paired A multiple logistic regression was used to evaluate the risk factors associated with unfavourable COVID-19 prognosis defined as composite end-point consisting of in-hospital death, intensive care unit admission, or respiratory failure requiring high-flow oxygen therapy. To evaluate the discriminative performance of the logistic model, the area under the receiver operating characteristic (ROC) curve was calculated, comparing the actual outcome to the outcome predicted by the model.p < 0.05 was set as the level of significance.Intra- and interobserver variability were calculated using the weighted Cohen's Kappa and the intraclass correlation coefficient (ICC). All analyses were performed using STATISTICA version 13 software . Two-sided tests were used, and 3.3.1.The echocardiographic arm of the CRACoV-HHS project included 148 men (65%) and 81 women (35%) in the study, and the median age of the population under study was 59 years (48–67). The characteristics of the study population are presented in n = 127, 55.4%), obesity , and diabetes .Among the associated comorbidities, the most common were found to be arterial hypertension . The data are presented in the Majority of the clinical and biochemical parameters of the patients admitted to the New University Hospital did not differ significantly from the parameters of the patients admitted to the Temporary COVID Ward, except for higher baseline CRP values , the reasons were due to poor image quality, variable heart rate during acquisition, or incomplete acquisition of necessary views. An impaired LV GLS (defined as higher than −18%) was detected in 73 patients (36.1%). The free wall RV strain had decreased (cutoff point −20%) in 111 patients (58.7%). RV thrombus was detected in one patient. Pericardial effusion was present in 11 patients (4.8%). The baseline echocardiographic data are presented in The interobserver agreement between investigators analysing images was good or very good on overall echocardiographic results, with the highest values for 2D measurements [LVDD: ICC 0.954 (95% CI 0.814–0.995)] and the lowest values for deformation analyses [LAS: ICC 0.801 (95% CI 0.251–0.977)]. The intraobserver variability demonstrated high reproducibility of re-measured parameters [ICC for 24 measurements 0.995 (95% CI 0.986–0.998)].3.3.n = 115, 55.8%) at baseline had elevated NT-proBNP levels .Baseline high-sensitivity cardiac troponin (hs-cTnT) levels were observed in 188 patients, and baseline NT-proBNP levels were observed for 205 patients. Elevated levels of hs-cTnT, that is, values greater than 14 ng/L [>99th percentile upper reference limit (URL)], were observed in 40 (21.3%) patients on admission. More than half of the patients  and oxygen saturation (SpO2) , and parameters of inflammation: hs-CRP H1 , neutrophil count , and lymphocyte count  as well as hs-cTnT  and D-dimers H1 . Among echocardiographic parameters, only NT-proBNP was significantly correlated with LV GLS , RV FAC , TR V max , LA reservoir , and contractile strain .Baseline NT-proBNP level was significantly correlated with indices of the severity of COVID-19, including respiratory rate  and SpO2 , while correlation with hs-CRP H1 was of borderline significance . hs-cTnT was also correlated with the diameter of the right ventricle  and negatively correlated with FAC .Cardiac troponin H1, similar to NT-proBNP, was correlated with respiratory rate  and posterior wall thickness . Myocardial thickness was correlated with hs-cTnT H1  and SpO2 levels , but not with levels of inflammatory markers.Moreover, there was a significant correlation between troponin concentration and end-diastolic interventricular septum (3.4.n = 121) did not differ from patients with an asymptomatic, mild, or moderate disease . Despite the lack of differences in the parameters of left ventricular function, significantly higher levels of myocardial necrosis  and markers of heart failure  were observed in the group of severely ill patients. Patients with a severe course of the disease had lower of SpO2 levels , lower systolic blood pressure , and lower diastolic blood pressure . Among echocardiographic parameters, higher TAPSE values , larger right atrial area , and higher E/E’ as a parameter of left ventricular filling pressure  were observed in patients with a severe course of the disease.According to the NIH classification, the initial severe course of the disease was found in 120 patients, with one patient classified as being in a critical condition. In terms of age, patients with a severe/critical disease , hs-CRP H7, and D-dimers H7. In the logistic regression analysis, the significant predictors of death were the following: age (p = 0.002), hs-CRP H7 (p = 0.008), D-dimer H7 (p = 0.023), NT-proBNP H7 (p < 0.001), tricuspid annulus velocity (S’) (p = 0.002), TR Vmax (p = 0.024), RV FW GLS (p = 0.022), and left atrial reservoir strain (p = 0.001).Compared with the survivors, the non-survivors were older and had higher respiratory rate and lower SpOn = 9), intensive care unit admission (n = 8), or respiratory failure requiring high-flow oxygen therapy (n = 44). Patients with unfavourable outcomes were characterised by higher levels of hs-CRP, NT-proBNP, and hs-cTnT (both at baseline and at Day 7). There were no significant differences between the groups in the parameters of LV systolic and diastolic function, while greater left ventricular posterior wall thickness, larger left atrial dimension, and lower left atrial reservoir strain as well as higher TR Vmax and shorter pulmonary artery flow acceleration time were detected  and NT-proBNP H1 .An unfavourable outcome was defined as the composite of death  after 1 year, while a decrease of more than 10% was observed in 21 (9.1%) patients. However, in none of them did EF drop below 45% at the final exam. In the group with an EF decrease of more than 10% in the 1-year follow-up, the patients were characterised by higher left ventricular EF at baseline , higher levels of TR Vmax , and lower levels of SpO2 .In the echocardiographic evaluation, the average change in ejection fraction was −1.5% ± 6.7, p < 0.01). In the group of 14 patients (6.1%) with baseline ejection fraction of <55%, EF was observed to increase from 51.9 ± 2.1% to 57.3 ± 6.4% in the long-term follow-up (p < 0.01).Features of hyperkinetic circulation were observed in 18 patients from the study group (7.8%) during the first examination, with left ventricular EF of >70%. In the long-term follow-up, EF had decreased to the mean value of 62.7 ± 5.1% . This raises the question of whether COVID-19-related respiratory failure differs from other ARDS. While studies comparing ARDS with COVID-19 did not yield consistent results, COVID-19 patients with ARDS were found to have lower pulmonary vascular resistance and higher cardiac output compared with ARDS –39. The Enlargement of the right heart chambers, increased tricuspid regurgitation velocity, shortening of pulmonary artery acceleration time, and hypercontractility reflect the homeometric adaptation of the right heart to an increased afterload caused by various factors in respiratory failure and ARDS, such as direct pulmonary endothelial injury/inflammation, microthrombi, and hypoxaemia. Two states of cardiac injury have been described: the first with mild/moderate dilation and compensated function, and the other with RV/LV failure. The initial increase in RV/LV contractility maintains cardiac output, ensuring a sufficient forward flow to meet the oxygen demand. The temporal relationship between these two stages is not clear and may depend on various patient and disease-dependent factors.In the examined group during the acute phase of the disease, an enlargement of the right atrium was detected in almost half of the population (49.3%), but a decreased RV FAC was observed in only 12.7%. An impairment of RV function was found in over one-half of the patients and an impairment of LV function in one-third of the patients when using more sensitive parameters of ventricular contractility, such as strain.In our study, reduced RV strain, higher tricuspid valve regurgitation velocity, shorter acceleration time of pulmonary flow, lower LA strain, and increased myocardial thickness were among the factors associated with a worse prognosis.During the follow-up, changes in the size and function of the heart were observed, including a gradual decrease in heart rate and an increase in stroke volume, as well as improvements in deformation parameters of both ventricles. Furthermore, a reduction in the RV diameter, right atrial volume, and velocity of the regurgitation wave through the tricuspid valve and an increase in the pulmonary flow acceleration time were observed. These consistent changes reflect recovery from the acute phase of the disease and align with the described pathomechanism of alterations associated with acute inflammatory and haemodynamic stress resulting from COVID-19.In addition, our data demonstrate that assessing left atrial mechanics through strain measurement offers further understanding of cardiac involvement in COVID-19. An acute enlargement and impaired left atrial function may be attributed to increased left ventricular filling pressure and/or direct inflammation-induced atrial myopathy. Previously, reduced left atrial strain has been identified as a predictor of atrial fibrillation and cardiovascular events in the general population . In a reAlthough our study was an observation of the cohort of homogenous and consecutive patients hospitalised with COVID-19, it was limited by being a single-centre project and by strict inclusion criteria. Focusing on subjects without structural heart disease, as a strategy to avoid the influence of comorbidities on the cardiac performance, resulted in preselection of patients with better prognosis. In our study, the mortality rate was four times lower than in the whole cohort of patients hospitalised in the University Hospital during the pandemic , and ourIn conclusion, in patients hospitalised with COVID-19, an increase in cardiac biomarkers is common and affects in-hospital prognosis. Serial echocardiographic evaluations conducted in patients without preexisting structural heart disease demonstrate an overall trend towards an improved biventricular function and a reduced myocardial thickening during the 1-year follow-up. This suggests that in patients without preexisting conditions, the acute cardiac consequences of COVID-19 are associated with systemic inflammation and haemodynamic stress. However, even in patients with a severe course of the disease, no clinically significant cardiac dysfunction is observed after 1 year.