No correlation is apparent between inhaled therapy  and myocardial involvement. These results seem to confirm that a more in-depth cardiovascular evaluation in patients with chronic respiratory disease allows the identification of unrecognized cardiovascular involvement. A transthoracic echocardiogram performed in asthmatic patients without clinically overt signs or symptoms of cardiovascular impairment has identified some features indicative of an early subclinical cardiac impairment not found in the control group. These findings, considering also the higher frequency of hypertension in the asthma group, deserve further validation in the future.The “Blood pressure levels, clinical features and markers of subclinical cardiovascular Damage of Asthma patients” (BADA) study is aimed at defining the cardiovascular risk profile and the markers of subclinical and clinical vascular and cardiac damage in asthmatic patients. Very few studies have assessed asthmatic patients without concomitant heart disease through a transthoracic echocardiogram. The goal of the present study is to investigate the prevalence of morphology and/or function changes in the cardiac chambers of a sample of 86 patients with chronic asthma, referred to the dedicated outpatient unit of the Division of Respiratory Diseases of the AOUP “P. Giaccone” of the University of Palermo, and the results obtained were compared with those of a control group without respiratory or cardiovascular diseases. Patients with asthma showed a marked and widespread involvement of the four cardiac chambers compared with the controls: enlargement of the two atria, greater left ventricular remodeling with interventricular septal thickening, increased indexed left ventricular mass with a significantly greater percentage of patients with overt left ventricular hypertrophy, worse left ventricular diastolic function proven by the significant difference in the E/A ratio, and worse right ventricular systolic function with global right ventricular dysfunction estimated by the Myocardial Performance Index (Tei Index). Multivariate regression analysis, after adjustment for essential hypertension, hypertension severity, diabetes, Body Mass Index, and creatinine clearance, seems to indicate that the indexed left ventricular mass, right atrial volume, and right ventricular Tei index (but not left ventricular hypertrophy) correlate significantly with asthma, severe asthma, and FEV Our previous results  suggesteIn view of the scarcity of available data, the aim of the current study is to ascertain the prevalence of alterations in the morphology and/or function of the cardiac chambers in a sample of asthmatic patients, comparing the results obtained with those of a control group without respiratory or cardiovascular diseases.The data reported in this study were collected on 86 patients with chronic asthma, referred to the dedicated outpatient unit of the Division of Respiratory Diseases of the AOUP “P. Giaccone” of the University of Palermo  in the period between 1 January 2018 and 1 June 2020. All subjects enrolled were Caucasian, were previously informed about the characteristics and the object of the study, and a written informed consent was obtained. The BADA study was approved by the local ethical committee (ref n. 018/2017).-Coexistence of Chronic Obstructive Pulmonary Disease (COPD);-Coexistence of Obstructive Sleep Apnea Syndrome (OSAS);-Active smoking status;-History of chronic ischemic heart disease, valve disease, or other structural heart disease with or without secondary impairment of left ventricular ejection fraction;-History, in the six months preceding the study, of any acute myocardial, endocardial, or pericardial pathology capable of transiently or permanently compromising cardiac structure and/or function.A control group of 100 subjects was created; patients were enrolled among those referring to the Division of Internal Medicine with Stroke Care of the University of Palermo for an outpatient visit due to different reasons, not affected by acute or chronic respiratory or cardiovascular disease. The subjects enrolled in this group, in particular, denied having a clinical history of bronchial asthma or active use of steroid therapy for any reason and did not presented spirometry evidence of respiratory flow limitations.The initial study procedure included, for all subjects, a comprehensive recording of medical history with specific attention to the cardiovascular risk profile, pharmacological anamnesis, complete physical examination, assessment of Body Mass Index (BMI), calculated as the individual’s body weight divided by the square of his or her height, and the following blood biochemical examinations: total cholesterol, High Density Lipoprotein (HDL) cholesterol, triglyceride, creatinine, fibrinogen, complete blood count, fasting glucose, and C-reactive protein. Subjects were defined as type 2 diabetics, if they had known diabetes treated by diet, oral hypoglycemic drugs, or insulin. Previous cerebrovascular disease: Transient Ischemic Attack (TIA) or ischemic stroke was assessed by history, specific neurological examination performed by specialists, and hospital or radiological (brain computed tomography or brain magnetic resonance) records of definite previous stroke. Previous coronary heart disease was detected by history, clinical examination, electrocardiogram, and echocardiogram. All subjects enrolled were self-reported as being sedentary.1 (forced expiratory volume in 1 s) expressed in liters and in percent predicted value (FEV1%), FVC  expressed in liters and in percent predicted value (FVC%), and the FEV1/FVC ratio, expressed as absolute values. Reversibility of bronchial obstruction was assessed.The enrolled asthmatic patients met the diagnosis of the disease based on GINA criteria , consideSevere asthma was defined as asthma that requires treatment with high-dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) or that remains uncontrolled despite this therapy . The sevThe quantification of the daily intake of ICS, in relation to patient age (in mcg/day), was obtained according to the clinical comparability table indicated by the GINA document .A transthoracic echocardiogram was performed in all enrolled patients. For all the subjects enrolled, the same GE-Vivid 7 echocardiographic device was used by the same experienced echocardiographer. The patient was placed in the supine position and in left lateral decubitus; data were stored digitally for offline evaluation using a specific program, to be subsequently interpreted by the same echocardiographer who performed the exam. All measurements and echocardiographic data were collected and analyzed in accordance with the latest guidelines of the American Society of Echocardiography , where PWTd is the posterior wall thickness of the LV and LVIDd is the telediastolic inner diameter of the LV.-2 was considered normal in both genders.Left atrium volume indexed for body surface (LAVI). The volume obtained by measuring atrial areas and diameters was indexed for body surface area, and a left atrial volume of up to 34 mL/m-2 for men and between 43 and 95 g/m2 for women.Left ventricular mass indexed for body surface (LVMI). We considered a normal LVMI in the case of values between 49 and 115 g/m-2 in men and 95 g/m2 in women.Left ventricular hypertrophy (LVH). We defined a subject having LVH when LVMI values exceed 115 g/m-Left ventricular ejection fraction (LVEF). We considered normal a LVEF > of 52% for men and >54% for women.-E/A ratio: Pulsed Doppler images at the mitral cusp level were used to measure transmitral flow velocities; these were measured (in m/s) during the passive early diastolic filling peak  and during the late diastolic flow peak provided by atrial contraction (A-wave). The E/A ratio was then calculated, which describes the blood flow from the atria to the ventricles during ventricular diastole and provides information on the atrial contribution to ventricular filling. The value of the E/A ratio in a subject with normal diastolic function is between 0.8 and 2. Three abnormal patterns were defined:-Impaired relaxation pattern or grade 1 diastolic dysfunction is the mildest degree of diastolic dysfunction (E/A < 1).-Pseudonormal mitral inflow pattern or grade 2 diastolic dysfunction has a falsely normal E/A ratio (between 0.8 and 1.5).-Restrictive pattern or grade 3 diastolic dysfunction, in which an E/A ratio >2 indicates a particularly severe impairment of ventricular compliance.-E/e’ Ratio. A Pulsed Tissue Doppler of the mitral annulus was used to measure the early protodiastolic peak (e’) velocities of the septal and lateral mitral annulus as well as the velocities of the lateral tricuspidal annulus; all velocities are expressed in cm/sec. The E/e’ ratio was then calculated using the mean value of e’ of the septal versant lateral side of the mitral valve. In accordance with the American Society of Echocardiography Recommendations for the Evaluation of LV Diastolic Function ,9, the f-2 in men and 15 to 27 mL/m2 in women was considered normal.Right atrium volume indexed for body surface (RAVi). The size of the RA was assessed using the apical 4-chamber projection. From this window, the area of the right atrium was measured by planimetry. The area of the right atrium was plotted in ventricular systole  excluding the area between the tricuspid flaps and the annulus, following the atrial endocardium. Volume was calculated from the data collected, and a right atrial volume of 18 to 32 mL/m-Tricuspid annular plane systolic excursion (TAPSE). It is measured in M-Mode using the apical 4-chamber projection. TAPSE quantifies the systolic excursion of the tricuspid annulus along the longitudinal plane, thus representing an index of the efficiency of right ventricular systolic function. The greater the excursion, the better the performance of the right ventricle. Although this index essentially describes RV longitudinal function, it has shown a good correlation with other parameters that estimate global RV systolic function, such as myocardial scintigraphy and 2D estimation of RV ejection fraction. A value >17 mm was considered normal in both sexes.-Right ventricular ejection fraction (RVEF). As with LVEF, it was calculated as a percentage of the volume difference. Although it is most appropriately conducted, it is a parameter that suffers from great variability in relation to possible acute/chronic RV overload, paradoxical left/right septal motion, or poor acoustic window. A right ventricular systolic function >45% was considered normal in both sexes.-Myocardial Performance Index (Tei Index). It was calculated for both ventricles by tissue Doppler, using the formula IVCT + IVRT/ET, where IVCT is the isovolumetric contraction time, IVRT is the isovolumetric release time, and ET is the ejection time. It is an index that incorporates both systolic and diastolic time intervals and is therefore capable of globally expressing both diastolic and systolic function. Systolic dysfunction prolongs projection  and reduces ejection time (ET). Both systolic and diastolic dysfunction result in abnormal myocardial release, prolonging the release period . A value >0.55 was considered normal for the RV, while a value of 0.39 ± 0.05 was considered normal for the LV ,9.t-test was used to compare the continuous variables between the two groups examined. The comparison of the proportions was performed using the chi-squared test or the exact Fischer’s test (used when the expected frequency of the event was lower than five times).The statistical analysis of quantitative and qualitative data, including descriptive statistics, was performed for all items. Continuous data are expressed as mean ± 1 standard deviation; unless otherwise specified, categorical variables are expressed as percentage. A Student’s 1%, average daily dosage of inhaled corticosteroids, and average daily dosage of short-acting beta-agonists) with the main four echocardiographic alterations that we showed to be associated with asthma and that we judged to be emblematic for the evaluation of the association between asthma and myocardial involvement . All the results of the multivariate analysis were adjusted for the following confounding factors: essential hypertension, diabetes, Body Mass Index, and creatinine clearance.A multivariate regression analysis was performed to evaluate the presence and strength of correlation between asthma and some of the main factors related to it , version 4.1.2.All p: 0.01) as well as mean Systolic Blood Pressure levels . The two groups did not differ in relation to the main comorbidities/risk factors associated with hypertension, except for a higher prevalence of type 2 diabetes mellitus (DM) in the asthma group (8 patients vs. 0) (p: 0.001), despite a concordance of fasting blood glucose values in asthmatics vs. controls (90. 9 vs. 86.9 mg/dL) (p: 0.07). In asthmatics, we found a worse renal function  (66.83 vs. 88.12 mL/min) (p: 0.01). Body Mass Index was higher in cases than in the controls (28.11 vs. 24.22) (p: 0.05). Spirometry indexes of asthmatic patients were within the normal range, although FEV1 and FEV1/FVC ratio were mildly but significantly reduced compared with the healthy controls .p: 0.01); IVS thickness: 11.33 ± 1.55 vs. 7.57 ± 0.87 mm (p: 0.01); LVMi: 99.48 ± 33.11 vs. 89.22 ± 26.19 g/m2 (p: 0.01); LV RWT: 0.37 ± 0.21 vs. 0.31 ± 0.12 (p: 0.045); LAVi: 40.23 ± 4.47 vs. 32.34 ± 5.51 mL/m2 (p: 0.001); the percentage of subjects who exceeded the threshold for the definition of LVH ; LV diastolic function estimated by the mitral E/A ratio ; RAVi: ; RV systolic function measured by the ejection fraction ; and global right ventricular function assessed by the Tei index .Our results show that asthma affects the structure and function of all four cardiac chambers. We observed statistically significant differences for: LV-EDV: 50.14 ± 3.38 vs. 66.51 ± 2.66 mL (1% (and to a lesser extent asthma duration) correlated significantly with indexed left ventricular mass, right atrial volume, and right ventricular Tei index (but not with the presence of left ventricular hypertrophy). No correlation was instead shown between inhalation therapy  and myocardial involvement.The main findings of our study, one of the few to have performed a transthoracic echocardiographic evaluation in a cohort of asthmatic subjects without respiratory and cardiovascular comorbidities, comparing them with a control group comparable in sex and age, are the following. Patients with asthma have marked and widespread involvement of the four cardiac chambers compared with the controls: enlargement of the two atria, greater left ventricular remodeling with interventricular septal thickening, increased indexed left ventricular mass, and a significantly greater percentage of patients with overt left ventricular hypertrophy; worse diastolic function shown by the significant difference in the E/A ratio; and right ventricular systolic dysfunction with less valid global right ventricular function estimated by the Tei index. Multivariate regression analysis, after adjustment essential hypertension, hypertension severity, diabetes, Body Mass Index, and creatinine clearance, confirmed that asthma, severe asthma, and FEVp: 0.013), diabetes mellitus (9.1% vs. 0% p: 0.005), higher BMI , and lower creatinine clearance (66.8 vs. 97.6 mL/min p: 0.04). The special association existing between chronic respiratory disease  with hypertension [1, FVC, and FEV1/FVC ratio, may contribute more than other determinants to the development of mild cardiac dysfunction. Despite this, it should be pointed out that hypertension is a disease more closely associated with asthma than suspected to date [Our data on LV structure and function in asthmatics highlight a significant increase in LV thickness, LV mass, and a four-fold prevalence of LV hypertrophy compared with the non-asthmatic controls. In our study, increased LV mass appears to be one of the pivotal elements of the cardiac remodeling in asthmatic patients. LV remodeling and thickening is commonly the result of chronic volume and/or pressure overload, with an estimated prevalence in the general population of 14.9% in men and 9.1% in women, respectively, and an acme of 36 to 41% in subjects with high blood pressure . LVMi isrtension  particulHigher BMI is associated with the development of LV hypertrophy  as well Our finding of a worse systolic and diastolic performance of the right ventricle in asthmatic subjects, although novel, has rather solid pathophysiological assumptions. Pulmonary artery wall tension, or pulmonary arterial stiffness (PAS), is a relatively recent noninvasive echocardiographic index aimed at assessing the structural and functional characteristics of the pulmonary vascular bed . PrimaryThe possible role of inhaled therapy taken daily by patients with asthma for many years in the genesis of cardiovascular complications is much debated. Several authors ,20 have A strength of our study is the choice of the sample: asthmatic adults without concomitant cardiovascular or respiratory disease. Many of the studies that have assessed, through echocardiography, the impact of asthma on cardiac function are conducted in children, adolescents, or teenagers ,19. AlthIn conclusion, in this second phase of the BADA study, we confirm that a more in-depth cardiovascular evaluation in patients with chronic respiratory disease, particularly in asthmatic patients, allows the identification of a significant subclinical level of cardiac involvement. A transthoracic echocardiogram performed in asthmatic patients without clinically overt signs or symptoms of cardiovascular impairment identified some features indicative of an early subclinical cardiac impairment not found in the control group. These findings, considering also the higher frequency of hypertension in the asthma group, deserves further validation in the future.Our results, along with others currently being evaluated in the upcoming phases of the BADA study, could contribute to a more comprehensive framing of asthmatic patients, allowing the clinical-therapeutic approach to be optimized as well.


Validated acute heart failure (AHF) clinical decision instruments (CDI) insufficiently identify low‐risk patients meriting consideration of outpatient treatment. While pilot data show that tricuspid annulus plane systolic excursion (TAPSE) is associated with adverse events, no AHF CDI currently incorporates point‐of‐care echocardiography (POCecho). We evaluated whether TAPSE adds incremental risk stratification value to an existing CDI.cont), ΔSensitivity (NRIevents), and ΔSpecificity (NRInonevents). Random forest assessed variable importance. To benchmark risk prediction to standard of care, ΔSensitivity and ΔSpecificity were evaluated at risk thresholds more conservative/lower than the actual outcome rate in discharged patients.Prospectively enrolled patients at two urban‐academic EDs had POCechos obtained before or <1 h after first intravenous diuresis, positive pressure ventilation, and/or nitroglycerin. STEMI and cardiogenic shock were excluded. AHF diagnosis was adjudicated by double‐blind expert review. TAPSE, with an a priori cutoff of ≥17 mm, was our primary measure. Secondary measures included eight additional right heart and six left heart POCecho parameters. STRATIFY is a validated CDI predicting 30‐day death/cardiopulmonary resuscitation, mechanical cardiac support, intubation, new/emergent dialysis, and acute myocardial infarction or coronary revascularization in ED AHF patients. Full (STRATIFY + POCecho variable) and reduced  logistic regression models were fit to calculate adjusted odds ratios (aOR), category‐free net reclassification index (NRIp = 0.009). Five right heart  and no left heart measures improved prediction (p < 0.05) adjusted for STRATIFY. Right heart measures also had higher variable importance. TAPSE ≥ 17 mm plus STRATIFY improved prediction versus STRATIFY alone , and specificity improved by 6%–32% (p < 0.05) at risk thresholds more conservative than the standard‐of‐care benchmark without missing any additional events.A total of 84/120 enrolled patients met inclusion and diagnostic adjudication criteria. Nineteen percent experiencing the primary outcome had higher STRATIFY scores compared to those event free (233 vs. 212, TAPSE increased detection of low‐risk AHF patients, after use of a validated CDI, at risk thresholds more conservative than standard of care. Acute heart failure (AHF) accounts for 1 million emergency department (ED) visits annuallyIn a previous pilot study we identified that tricuspid annulus plane systolic excursion (TAPSE) on EP‐performed point‐of‐care echocardiography (POCecho) is associated with short‐term adverse AHF events.The Right ventricular Echocardiography in ED AHF (REED‐AHF) study was a two‐center prospective cohortThe primary methods, protocol, design, and patient cohort of REED‐AHF have been described previously.REED‐AHF was a prospective multicenter cohort study at two urban EDs with 80,000–100,000 annual visits each. Detroit Receiving Hospital is an urban‐academic referral hospital and Level I trauma center; Sinai‐Grace Hospital is an urban‐community Level II trauma center. Both sites host 3‐year emergency medicine (EM) residencies.Patients were enrolled from September 2019 to February 2020 and November 2020 through March 2021. Enrollment was paused during the intervening 8 months per institutional policies regarding clinical research during the early phase of the COVID‐19 pandemic. Patients were screened 7 days per week by trained research staff and study personnel; however, enrollment was limited to times when a study sonographer was available.Full inclusion, exclusion, and diagnostic adjudication criteria have been described previously.The POCecho protocol, performed using a Vivid q ultrasound system, has been described previously.Demographic and clinical variables were collected prospectively at enrollment, throughout hospitalization, and through 90‐day follow‐up as previously described.STRATIFY was chosen as the primary clinical risk measure for a few reasons. First, as cited above, it is one of three CDIs endorsed by ACEP to be helpful in risk stratification.The primary clinical outcome was the 30‐day composite of serious adverse AHF events which STRATIFY was derivedOutcomes were adjudicated by telephone follow‐up, supplemented by multiple blinded abstractors reviewing electronic medical record data and health information exchange data for the state of Michigan as previously described.All statistical analyses were performed in the R language (R Studio 2021.09.1). Patient characteristics were stratified by those with versus without the primary outcome, and echocardiography parameters by outcome and ED disposition, to calculate descriptive statistics using the Wilcoxon rank‐sum test for continuous variables and Fisher's exact test for categorical variables (α = 0.05).Based on our pilot study which showed association between adverse events and TAPSE < 17mmAdditional right heart measures included fwRVLS, RV‐LV ratio, pulmonary artery systolic pressure (PASP) by tricuspid regurgitant jet velocity , RV fractional area change (FAC), pulmonary vascular resistance, and RVOT acceleration time. Left heart measures included left ventricular ejection fraction (LVEF), mitral E/A ratio, septal E', lateral E', E/E' ratio, and LV global longitudinal strain (LVGLS) by speckle tracking.Exploratory analyses were conducted with two goals. First, we explored the possibility that measures besides TAPSE may have incremental value in risk stratification, since few descriptions of any POCecho measure exist in ED‐based AHF risk stratification literature. Second, the other measures served as indirect comparators to TAPSE in evaluating our primary hypothesis. We approached comparison in two ways: (1) evaluating relative variable importance of all POCecho measures with STRATIFY in a random forest model and (2) modeling each POCecho variable in the same way as TAPSE in full (POCecho measure plus STRATIFY) and reduced (STRATIFY only) logistic regression models for measures of incremental improvement in prediction . Secondary POCecho measures were also analyzed as continuous variables and using a priori binary cutoffs corresponding to the American Society of Echocardiography guidelinesThe random forest model for assessing variable importance was run under the following specifications: (1) all 15 echo variables including TAPSE and the STRATIFY score were able to be incorporated into classification trees; (2) no more than two total variables  were allowed to be sampled in a single classification tree ; and (3) 10,000 trees were grown for prediction of the clinical primary outcome using the randomForest package in R, with importance (mean decrease in Gini) calculated and plotted. Random forest utilized in this way aids in selection of independent variables (features) in the context of high dimensionality by calculating the importance of each variable in predicting the outcome of interest, of which mean decrease in Gini is a common importance measure.cont). NRI measures the degree by which addition of a single variable to an existing prediction model improves the classification of that model, focused on the observations which are reclassified to a different prediction category by the added predictor, and specifically whether or not those reclassifications resulted in fewer or greater correct classifications overall .cont assesses classification across all risk thresholds, while the categorical NRI assesses reclassification at specific risk cutoffs.events) and nonevents (NRInonevents) by methods previously describednonevents = ΔSpecificity and NRIevents = ΔSensitivity—i.e., the improvement or worsening in sensitivity and specificity in the standard risk stratification  after adding a novel risk marker Reduced  and full (POCecho measure plus STRATIFY) logistic regression models were fitevents/ΔSensitivity and NRInonevents/ΔSpecificity) were calculated at thresholds that would ensure that the model's “miss rate” was more conservative than the standard‐of‐care miss rate. The rationale of this approach was that even if the exact value of an “acceptable miss rate” is debated, most EPs would likely agree that a model which misses fewer events than the standard of care is potentially useful, particularly if it can also increase identification of low risk  without adding missed events .There is no currently agreed upon “acceptable” miss rate for serious adverse events at which patients should be considered for outpatient treatment of AHF after ED treatment. To account for this, we benchmarked categorical risk prediction and reclassification to standard‐of‐care risk stratification. Model predicted risk thresholds  were chosen to be below the true/observed rate of the primary outcome among patients actually discharged from the ED by standard EP decision making. Thus, measures of categorical reclassification , PH, ED systolic blood pressure (SBP), pre‐ED adherence to guideline‐directed medical therapy, and sex were chosen a priori as patient‐level factors that could be associated with both TAPSE and outcomes while not being incorporated in STRATIFY. Several treatment‐level variables were chosen based on being possible therapeutic indications why a patient would not be a candidate for outpatient treatment , including total ED IV furosemide dose, ED NIPPV, ED IV nitroglycerin, and any new or increased oxygen requirement during the ED visit compared to baseline. Finally, EP disposition decisions of discharge versus admission and ICU versus another level of care were included to assess actual clinical decision‐making compared to the POCecho variables. EPs were blinded to all POCecho data during the study, including when selecting disposition.cont when added to STRATIFY by similar methods as described above for the echocardiography variables in sensitivity analyses. The hypothesis of these sensitivity analyses was that significant improvement in classification by any of these variables compared to STRATIFY alone would diminish the importance of any risk stratification benefit observed for a POCecho variable, since these clinical variables are more easily obtained through history and medical record review than a POCecho, are commonly found in current AHF risk stratification literature and ED‐based CDIs, and/or inherently reflect the standard‐of‐care in EP decision‐making.Each of the variables here was tested for NRI2 initiation, and +102 min (+47 to +177) after ED arrival. A CONSORT diagram with enrollment details has been previously published.n = 11), failure to obtain consent from the patient or a representative within 24 hours of the POCecho (n = 20), and expert‐adjudicated diagnoses of not‐AHF (n = 5), 84 patients remained for analysis.A total of 120 patients met initial inclusion criteria, with POCechos obtained at a median of −75 min (interquartile range [IQR] −131 to +13) before first IV loop diuretic, +33 min (+6 to +59) after initiation of PPV, −21 min (−49 to +23) before first IV/SL nitroglycerin, +33 min (−234 to +162) after first supplemental On = 50), 18% received NIPPV (n = 15), 3.6% (n = 3) were admitted to the ICU, 14% (n = 12) placed in outpatient observation, and 9.5% (n = 8) discharged from the ED.Description for selected clinical and POCecho measures are presented in Tables n = 16) had one or more serious adverse AHF events in the composite primary outcome at 30 days, including three (3.6%) deaths. Experiencing the primary outcome was associated with (Table Nineteen percent of patients n = 6 had onep = 0.011), TAPSE/PASP (p = 0.035), TAPSE/RVDD (p = 0.011), and fwRVLS (p = 0.034). There was no difference in TAPSE between admitted versus discharged patients , as did TAPSE/RVDD (+0.67 [+0.18 to +1.16]) and fwRVLS (+0.49 [+0.01 to +0.98]). Significant reclassification by NRIcont was not observed for other POCecho variables or any of the clinical variables of interest including past history of COPD, history of PH, new or increasing supplemental O2 requirement, ED IV loop diuretic dose, ED NIPPV or intubation, ED IV nitroglycerin, or disposition decisions of ICU or discharge home  and ΔSpecificity (NRInonevents) obtained when TAPSE at the a priori cutoff of ≥17 mm was added to STRATIFY. At every risk threshold less  than the 8.3% benchmark (standard‐of‐care event rate among discharged patients), TAPSE ≥ 17 mm significantly increased specificity without changing sensitivity. At the 8% cutoff, a peak 32% (95% CI 20%–44%) of event‐free patients at 30 days would have been appropriately reclassified from high risk  to low risk (by STRATIFY and TAPSE ≥ 17 mm). At an even more conservative 4% predicted risk cutoff, 15% (6%–24%) of patients incorrectly classified as high risk by STRATIFY alone would have been appropriately reclassified to low risk. Figure ED treatments and disposition decisions were similar between events and nonevents Table . Figure Figure Figure Four additional right heart variables were associated with the outcome after adjusting for STRATIFY: TAPSE/RVDD ratio (aOR 0.35 [0.13–0.94]), TAPSE/PASP ratio (0.38 [0.15–0.96]), RV‐FAC (0.41 [0.17–0.94]), and fwRVLS (0.31 [0.11–0.9]). RV‐LV ratio < 1 (but not as a continuous variable) was also associated with the primary outcome after adjustment (0.24 [0.06–0.78]). No left heart measures were associated with the primary outcome.cont, aOR, and the ability to identify low‐risk AHF patients  without increasing “missed” high‐risk patients . Second, TAPSE and other right‐heart measures showed greater importance .events] and ΔSpecificity [NRInonevents]) to risk thresholds more conservative than the actual outcome rates experienced by patients whom POCecho‐blinded EPs chose to discharge. This was done to acknowledge the status quo: conservative disposition practices resulting in admission for 80%–90% of patients and < 50% of patients receiving an intervention requiring hospital admission . At the outcome rates observed, we would have required more than eight times the number of patients enrolled to have enough events to prevent overfitting on logistic regression fitting an entirely new CDI with as many variablesThird, we had slightly less than 10 events per variable when considering both the STRATIFY score and a POCecho variable . Our sample size was slightly abridged due to the COVID‐19 pandemic as discussed, and prior research has shown that as low as five events per variable is usually sufficient to prevent overfitting.Fourth, we did not directly test learning curves for TAPSE in EP hands , although ICC to experts was high and feasibility of EP‐performed TAPSE for risk stratification has been demonstrated in prior studies of PE.Fifth, the study was not designed to compare POCecho variables head to head, and the abridged enrollment likely decreased this power even further. Given this, we cannot say that other echocardiography variables such as LVEF and mitral inflow parameters are of low utility, but rather only that we had low power to detect a difference among various echocardiography parameters. Nevertheless, other measures all had lower variable importance Figure  and aOR Sixth, our population is medically underserved, predominantly non‐White, coming from only two hospitals  and two institutions (Wayne State and Michigan State University College of Osteopathic Medicine). Generalizability to different populations is therefore uncertain.Tricuspid annulus plane systolic excursion (TAPSE) significantly improved risk stratification compared to the validated STRATIFY clinical decision instrument. Most critically, TAPSE appears to improve detection of low‐risk acute heart failure, even among patients misclassified as high risk. TAPSE, the TAPSE/PASP ratio, the TAPSE/RVDD ratio, and fwRVLS may all help increase the identification of low‐risk acute heart failure patients in the ED who could be considered for outpatient treatment rather than hospital admission. Our hypothesis‐generating results support a need to further define and evaluate point‐of‐care echocardiography's role in acute heart failure risk stratification. Future studies should investigate the incorporation of point‐of‐care echocardiography variables, and particularly right‐heart measures, into acute heart failure clinical decision instruments given their demonstrated potential here, the face validity for acute heart failure risk‐stratification, and the status of echocardiography as one of the few accessible clinical parameters not already used to risk‐stratify acute heart failure in the emergency department.Study concept and design: Nicholas E. Harrison, Robert Ehrman, Mark J. Favot, Phillip Levy, Aiden Abidov. Acquisition of the data: Nicholas E. Harrison, Laura Gowland, Jacob Lenning, Sarah Henry, Sushane Gupta, Robert Ehrman, Mark J. Favot. Analysis and Interpretation of the data: Nicholas E. Harrison, Jacob Lenning, Laura Gowland, Robert Ehrman, Mark J. Favot. Drafting of the manuscript: Nicholas E. Harrison. Critical revision of the manuscript for important intellectual content: all authors. Statistical expertise: Nicholas E. Harrison, Robert Ehrman. Acquisition of funding: Nicholas E. Harrison, Robert Ehrman, Mark J. Favot.Funded by the Blue Cross Blue Shield of Michigan Foundation (BCBSMF) Investigator‐Initiated Grant Program. This publication was made possible with support from Grant Numbers, KL2TR002530 , and UL1TR002529  from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award.JL, SH, SG, and LG report no conflicts of interest. NH's first institution, Wayne State University, has received grant money to conduct investigator‐initiated research conceived and written by NH from BCBSMF. NH and their second institution, Indiana University, have received grant money to conduct investigator‐initiated research conceived and written by NH from the Doris Duke Foundation and the National Institutes of Health (5KL2TR002530‐05). NH's second institution, Indiana University, has received grant money for industry‐initiated research from Abbott Laboratories and Roche Diagnostics. NH has received funding from Vave Health Inc. for consulting. RE has received grant money to conduct investigator‐initiated research from the National Institutes of Health conceived and written by Dr. Peter Pang at Indiana University (1R34HL136986‐01) and investigator‐initiated research conceived and written by NH from BCBSMF. RE has received funding from UltraSight for consulting. MF has received grant money to conduct investigator‐initiated research conceived and written by NH from BCBSMF. MF serves on the medical advisory board for Echonous Inc. and has received stock options from Echonous Inc. AA has received grant money to conduct investigator‐initiated research conceived and written by NH from BCBSMF. PL has received funding for consulting from Apex Innovations, AstraZeneca, BMS, Mespere, Novartis, Cardionomics, Baim Institute, Ortho Clinical Diagnostics, Roche Diagnostics, Siemens, Hospital Quality Foundation. PL and their institution have received investigator‐initiated research support from American Heart Association, Beckman Coulter, Agency for Healthcare Research and Quality (AHRQ), BCBSMF, Emergency Medicine Foundation, Edwards Lifesciences, CardioSounds, Michigan Department of Health and Human Services, Michigan Health Endowment Fund, Patient Centered Outcome Research Institute, and the National Institutes of Health NIH. PL is a member of the ACC's National Cardiovascular Data Registry Oversight Committee.Figure S1Figure S2Click here for additional data file.


The term chronic coronary syndromes encompasses a variety of clinical presentations of coronary artery disease (CAD), ranging from stable angina due to epicardial coronary artery disease to microvascular coronary dysfunction. Cardiac magnetic resonance (CMR) imaging has an established role in the diagnosis, prognostication and treatment planning of patients with CAD. Recent advances in parametric mapping CMR techniques have added value in the assessment of patients with chronic coronary syndromes, even without the need for gadolinium contrast administration. Furthermore, quantitative perfusion CMR techniques have enabled the non-invasive assessment of myocardial blood flow and myocardial perfusion reserve and can reliably identify multivessel coronary artery disease and microvascular dysfunction. This review summarizes the clinical applications and the prognostic value of the novel CMR parametric mapping techniques in the setting of chronic coronary syndromes and discusses their strengths, pitfalls and future directions. Chronic coronary syndromes is a term which encompasses various clinical presentations of coronary artery disease (CAD), including patients with established or suspected CAD and stable anginal symptoms, patients with angina due to microvascular dysfunction or coronary vasospasm, asymptomatic patients after initial diagnosis and treatment and patients with left ventricular systolic dysfunction . AccordiStress CMR can detect differences in myocardial perfusion with a high degree of precision by utilizing first-pass imaging of gadolinium-based contrast agents during pharmacological stress ,5,6,7. MTaking into consideration the recent advances in parametric mapping and quantitative perfusion CMR techniques, the aim of the current review is to summarize their clinical applications in the detection of chronic coronary syndromes, highlighting their strengths and pitfalls, and to explore their potential future role as the imaging modality of choice for the assessment of stress-induced myocardial ischemia.T1 allows measurement of the longitudinal or spin-lattice relaxation time, which reflects the mobility of protons and the time required to recover to their thermal equilibrium after being excited by magnetization . With thMyocardial T1 values are affected by technical parameters, including partial volume effects and magnetic field strength, as well as physiologic parameters such as age, gender and heart rate ,22. T1 m2a-specific receptor agonist which is increasingly used due to its safety profile and ease of administration [Stress CMR is usually performed using three vasodilatory agents: adenosine, dipyridamole, and regadenoson. Adenosine, a non-selective adenosine receptor agonist with a quick onset of action, is administered as a continuous infusion at doses ranging from 140 mcg/kg/min to 210 mcg/kg/min in order to achieve the desired hemodynamic response . Adenosistration . It is astration . Howeverstration . The abostration . Withdrastration .Native stress T1 mapping has emerged as a useful diagnostic tool for the detection of CAD. Myocardial blood volume (MBV) represents myocardial water content both in macro- and microcirculation. It constitutes approximately 10% of the total myocardial volume at rest and may increase two-fold during coronary vasodilatory stress . CompareBohnen et al. conducted a study on the performance of non-contrast stress T1 mapping in detecting myocardial ischemia in 100 patients with suspected or known CAD. Myocardium with inducible ischemia demonstrated no significant T1 reactivity, suggesting that MBV is maximally increased at rest in areas where there is severe coronary artery stenosis. Focal regions from areas of interest were more sensitive in depicting ischemia compared to the American Heart Association segmental model . Van AssPre- and post-contrast T1 mapping have been shown to have clinical utility in chronic myocardial infarction. For example, Messroghli et al. demonstrated that pre-contrast T1 values of infarcted myocardium were higher than the ones of remote areas but not as high as in the setting of acute myocardial infarction. Post-contrast T1 mapping also showed high sensitivity and specificity in discriminating infarcted segments as the hyperenhanced areas demonstrated shorter T1 times compared to remote areas after administration of gadolinium contrast agent and allowed for accurate measurement of the infract size . AdditioThe prognostic role of T1 mapping in CAD remains unclear. Puntmann et al. demonstrated that native T1 of non-infarcted myocardium was significantly elevated in patients with CAD and was the sole independent predictor of all-cause mortality, superior to commonly used biomarkers, including myocardial volumes, left ventricular ejection fraction and clinical scores .The impoThe main advantage of T1 mapping is that it eliminates the need for gadolinium contrast, which is contraindicated in people with known allergy to gadolinium and should be avoided in certain patient groups, such as those with severe renal impairment or pregnant/breast-feeding women. Rest and stress T1 mapping offer the unique potential to assess myocardial ischemia, the coronary vasodilatory reserve, and the health of the coronary microcirculation with a single, non-invasive test and without exposure to ionizing radiation.Limitations of T1 mapping arise from the several factors that affect the accuracy of T1 measurements. Protocol parameters, sequence design, field strength and scanner adjustments, fit model, tissue characteristics and patient characteristics may lead to variations in normal values and influence reproducibility . MOLLI aQualitative stress perfusion CMR has demonstrated a high diagnostic accuracy in the detection of significant CAD ,50, withSeveral studies have shown that quantitative stress perfusion CMR can reliably identify significant CAD with a similar diagnostic accuracy to conventional methods. Lockie et al. compared MPR calculated by quantitative analysis of perfusion CMR data performed at 3T with invasively measured fractional flow reserve and demonstrated that an MPR of 1.58 provided a sensitivity of 0.80 and specificity of 0.89 in discriminating functionally significant from non-significant CAD . Morton On the contrary, two sub-studies of the CE-MARC trial in a small number of patients showed that while quantitative perfusion CMR indeed has a high diagnostic accuracy for CAD, its diagnostic value may not necessarily outweigh qualitative visual analysis ,64.Three-vessel CAD is characterized by balanced ischemia which can be difficult to detect with functional imaging, especially with SPECT myocardial perfusion imaging . Recent Microvascular dysfunction is characterized by impaired autoregulation of arterial microcirculation resulting in insufficient increase of MBF from rest to stress. Noninvasive diagnosis of microvascular dysfunction can be achieved by measurement of MPR and MBF on several imaging modalities, with PET having the most clinical and prognostic data thus far. CMR perfusion has been validated against invasive and non-invasive techniques, such as coronary angiography with FFR and PET for the assessment of microvascular dysfunction, and has shown robust accuracy . Zorach Data regarding the prognostic benefit of quantitative perfusion mapping CMR are limited. However, a few recent studies have investigated the prognostic value of quantitative perfusion CMR analysis in patients with CAD. Sammut et al. demonstrated that ≥10% ischemic burden based on MPR was superior to visual assessment and provided incremental prognostic value over conventional risk factors, including age, sex, and LGE for the prediction of the composite endpoint of cardiovascular death, nonfatal myocardial infarction, aborted sudden cardiac death and revascularization after 90 days . Knott eAutomated quantitative perfusion CMR mapping has many advantages. Firstly, apart from its ability to identify the extent of ischemia in patients with multivessel CAD and differentiate from microvascular dysfunction, quantitative perfusion analysis can improve the differentiation of dark rim artifacts from true perfusion defects. Furthermore, the assessment of perfusion gradients , provides further physiological insights for the evaluation of myocardial ischemia. Moreover, newer techniques allow for free breathing acquisition with motion correction, as well as pixel-wise quantification of MBF in a quick and accurate way. The software used for image reconstruction (Gadgetron framework) is widely available and may be used by all scan manufacturers, thus facilitating its clinical adoption.On the other hand, significant variability in heart rate and breathing patterns may negatively affect the image quality. Furthermore, as with other mapping techniques, there is need for the establishment of normal ranges before routine clinical use. Lastly, the implementation of quantitative perfusion CMR has been limited so far to expert CMR centers, and it remains to be seen whether the technique can be incorporated into routine clinical practice.T1 mapping and quantitative CMR using artificial intelligence and deep learning models have shown promise in the reliable non-invasive assessment of patients with chronic coronary syndromes. More specifically, deep learning techniques which allow preprocessing for quantitative CMR have already been developed and incorporated in pipeline processes, resulting in faster and accurate image acquisition and post-processing . MeasureQuantitative stress CMR and T1 mapping are evolving non-invasive imaging techniques which hold promise for the assessment and management of clinical decisions in patients with CAD. Artificial intelligence, machine learning and automation in image acquisition and analysis are expected to increase the availability and clinical application of these techniques in daily clinical practice and to improve patient care.


ACE inhibitors, beta-blockers, and spironolactone are the most widely prescribed drugs for the chronic condition of CHF. This study shows the current status of medical therapy for critical as well as persistent pediatric HF.Congestive heart failure (CHF) is a complex, heterogeneous medically ill condition that can occur due to diverse primary  and secondary causes  and leads to significant morbidity and mortality. The approach toward managing the patient of CHF in the pediatric age group is more complex than in the adult population. Currently, in the adult group of the population of CHF, there are well-established guidelines for managing these patients, but in the case of children, there are no well-established guidelines; therefore, this systematic review gives more ideas for managing the pediatric population undergoing CHF. Treatment of the underlying cause, rectification of any advancing event, and management of pulmonary or systemic obstruction are the principles for management. The most widely used drugs are diuretics and angiotensin-converting enzyme (ACE) inhibitors, whereas beta-blockers are less commonly used in children than in adults. ACE inhibitors such as captopril, enalapril, and cilazapril are widely used in the pediatric age group. ACE inhibitors act on the renin-angiotensin-aldosterone system (RAAS) similar to those in the adult population. In children with heart failure (HF), ACE inhibitors reduce the pressure in the aorta, resistance in the systemic blood vessels, and upper left and right chamber pressures but do not appreciably influence pulmonary vascular resistance. We use a patient's initial perfusion and volume status assessment to decide further action for the supervision of acute HF. This paradigm was adopted from adult studies that showed higher rates of morbidity and mortality in patients with HF whose hemodynamic or volume status assessment results were stable with a pulmonary capillary wedge pressure >18 mmHg and a combined index (CI) of 2.2 L/minute/m Heart failure (HF) is a complex clinical condition that results from any structural and functional cardiac disease that leads to an inability to fill the heart chamber or propel the blood forward . CongeniDepending on the systolic function, there are two main types of HF:· HF with reduced ejection fraction (HFrEF) or left ventricular ejection fraction (LVEF) <40%· HF with preserved ejection fraction (HFpEF) or LVEF >= 50%HF results in a decrease in cardiomyocyte contractility, regardless of the etiology. A reduction in cardiac output caused by the original injury is then compensated by two main compensatory mechanisms. The first mechanism is the activation of the sympathetic nervous system, which causes a rise in norepinephrine discharge and diminished norepinephrine uptake as well as peripheral vasoconstriction to preserve the mean pressure of arteries and perfusion of organs (by raising systemic vascular resistance). However, elevated catecholamine levels trigger further cardiomyocyte damage, abnormal signaling in the cell, and eventually cardiomyocyte death. The activation of the renin-angiotensin-aldosterone system (RAAS), which involves elevated levels of renin, angiotensin II, and aldosterone in the blood is the second significant compensatory mechanism. Angiotensinogen is broken down by renin into angiotensin I, which is then transformed by the angiotensin-converting enzyme (ACE) into angiotensin II. A powerful vasoconstrictor angiotensin II maintains end-organ perfusion. The effects of aldosterone on salt and water maintenance include amplified preload and cardiac output . ModifieDyspnea (shortness of breath), fatigue, and common clinical manifestations such as pulmonary rales, peripheral edema, or distended jugular veins are all indicators of HF . The 201Given that, almost all medications that have been shown to improve prognosis have an impact on these factors as well as renal function, blood pressure, and ionic balance. It is intriguing to think about how the delivery of this treatment might be optimized in light of the unique characteristics of each patient. Furthermore, given that there is no convincing cause to begin lifesaving medications in a step-by-step manner, it is reasonable to begin medications with a demonstrated prognostic benefit simultaneously to administer the various agents by their pharmacodynamic effects and patient characteristics. With this strategy, HF medications could be escalated more quickly to provide the patient with the greatest possible benefits . ClinicaMethodologyWe undertook a systematic search through PubMed Central in November 2020 using keywords such as HF, beta-blockers, diuretics, ACE inhibitors, aldosterone antagonists, G-protein-coupled receptor antagonists, digoxin, wet and cold patients, catecholamines, phosphodiesterase inhibitors, calcium sensitizers, action cardiac therapy improving outcome network (ACTION). We additionally searched for key references from bibliographies of the relevant studies. The search was updated in February 2022. One reviewer independently monitored the retrieved studies against inclusion criteria, in the beginning, based on the title and abstract and then on full texts. Another reviewer also reviewed approximately 20% of these studies to validate the inclusion of studies.Mechanism of actionThe purpose of clinical therapy for CHF in a child is to promote recovery, preserve steadiness, limit disease progression, and create a conducive environment for somatic growth and the best possible development of the child into an adolescent. ACE inhibitors, beta-blockers, diuretics, and aldosterone antagonists are typically used in combination .ACE Inhibitors and Aldosterone AntagonistsCHF disease with diminished systolic function is characterized by activation of the RAAS pathway, which is a physiological response to reduce renal perfusion. Renin promotes the process by which hepatic angiotensinogen is transformed into angiotensin I, which is then processed by the ACE, primarily in the lungs, to create angiotensin II, a powerful constrictor of the blood vessels that has long-term detrimental consequences on HF. The mechanism of action of ACE inhibitors is shown in Figure The synthetic steroid spironolactone, a commonly used mineralocorticoid antagonist in pediatrics, reduces aldosterone's capacity to bind to its receptor in the distal renal tubule in a competitive manner, causing sodium to be excreted while potassium is preserved. Spironolactone has a very modest diuretic impact, but because of its potassium-saving properties, it is very effective in treating acute HF patients .Beta-BlockersBeta-blockers are the mainstay treatment in the management of CHF with reduced ejection fraction. Different drugs have varying selectiveness for beta 1 or 2 receptors: some only partially activate the receptors (inherent sympathomimetic action), some have supplementary belongings on adrenoceptors, or they may stimulate the production of nitric oxide . The majDiureticsSLC12A2 (solute carrier family 12 members 2), a second sodium-potassium chloride symporter isoform that is highly expressed in every part of the body and also in the ear, is another feature of loop diuretics that contributes to its ototoxicity [The prototypical diuretics are furosemide, bumetanide, and torsemide bind to the outside of the cell surface of the sodium-potassium chloride symporter, directly inhibiting ion transport . These dtoxicity . Loop ditoxicity . Cells otoxicity . In conttoxicity .Sodium-Glucose Cotransporter 2 InhibitorsEmpagliflozin, dapagliflozin, and canagliflozin are widely available SGLT2 Inhibitors that act by their osmotic diuresis and natriuretic effect, contributing to the decrease in plasma volume and drop in systolic pressure and diastolic pressure by 4 to 6 and 1 to 2 mmHg, respectively . AlthougG-Protein-Coupled ReceptorThe most common class of surface receptors that are the target of many medications is the G-protein-coupled receptor (GPCR), which plays a crucial role in the control of heart functioning in both healthy and sick people. Adrenergic and angiotensin II receptors are examples of the many GPCR antagonists that are now accepted as standard therapy for a variety of disorders, such as hypertension, coronary artery disease, and cardiac failure. Guanine nucleotide-binding proteins (G proteins) allow GPCR to transmit signals. G proteins are so termed because they can bind the nucleosides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). When G proteins are attached to GTP, they are activated, and when bound to GDP, they get inactive. They serve as a molecular switch in the transmission of signaling into the cell . CurrentThe second messenger, cyclic adenosine monophosphate (cAMP), is produced by the effector enzyme adenylyl cyclase in response to the G stimulatory. PKA is then stimulated, and a variety of intracellular proteins regulate cellular response . Gi, on DigoxinDigoxin, a glycoside for the heart, served as the mainstay of HF management for many years before a hypothesis shift in HF pathophysiology resulted in a switch from inotropic therapy to neurohormonal control. Digoxin prevents sodium from being removed from the myocytes during the potassium exchange by binding to the sarcolemma sodium-potassium ATPase pump. In turn, the sodium-calcium exchanger can accept more sodium intracellularly, allowing for an influx of calcium. A more powerful mechanical contraction is aided by the transport of calcium into the sarcoplasmic reticulum. Additionally, some studies indicate that digoxin binds to ryanodine receptor 2 . The DigWet and cold patients Wet PatientsUnder the most recent ISHLT guidelines, there is a Class I indication for the initiation of diuretics in patients presenting with fluid retention coupled with ventricular dysfunction for the management of pediatric HF. The use of diuretics should continue until euvolemia is reached.Cold PatientsWhen pediatric patients present in cardiogenic shock, there is a Class I indication for temporary use of intravenous inotropic support .Drugs for acute HFCatecholaminesAdrenergic receptors play a dose-dependent and mediating role in catecholamines' hemodynamic effects. Adrenergic receptors are closely linked to membrane-bound G proteins, which are also linked to GDP and GTP. The key mechanism underlying these medicines' beneficial inotropic and chronotropic effects is their activation of GTP, which can work in either a stimulatory or an inhibitory manner . AdrenerPhosphodiesterase InhibitorsFor immediate therapy to decrease cardiac output, milrinone is the only phosphodiesterase inhibitor currently available. cAMP metabolism is carried out by the enzyme phosphodiesterase III, which is inhibited by this substance. Milrinone is mild inotropic and vasodilatory effects causing it to lower the ventricle fill-up demands while enhancing cardiac output .Nitric Oxide Donors: Nitroprusside and NitroglycerinNitric oxide and cyanide anions are linked to sodium salt, which is then converted into nitroprusside. After interacting with red blood cells and some proteins, nitric oxide is released, inducing the production of cyclic guanosine monophosphate by guanyl cyclase and inhibiting the contraction of smooth muscle. On venous capacitance and arterial resistance vessels, nitroprusside has a dose-dependent vasodilatory effect . The greCalcium SensitizersNowadays, the most commonly used drug is levosimendan due to its various mechanisms of action, that is, by inhibiting phosphodiesterase III, increasing the calcium sensitivity of cardiac troponin C, and stimulating the opening of potassium adenosine triphosphate channel, which leads to its vasodilatory effect . It is aACTIONACTION is the first pediatric ventricular assist device (VAD) that is widely used nowadays to improve the quality of life (QoL). There are still few treatments available for people with end-stage HF, despite the rising prevalence of acute and chronic HF in children. Before the development of VADs, the mortality rate was very high, especially in younger patients . Now, reInternational Society of Heart and Lung transplantation The 2019 International Society for Heart and Lung Transplantation (ISHLT) study states that today, a VAD is used to bridge more than one-third of patients having transplants. The use of VADs as a transitional measure before transplant is a growing trend. The primary goal of VAD therapy is to stabilize the hemodynamics of a failing circulation that is not responding to conventional treatment. The VAD should be placed before the development of severe end-organ dysfunction to maximize therapeutic effects. The objective is to enhance the QoL, enhance tissue and organ perfusion, and enhance patient survival. The need for a consensus statement on the selection and treatment of children and adults with CHD receiving VAD implantation has been acknowledged by ISHLT .ISHLT has stated guidelines for patient selection, which include the timing of the VAD, indication for VAD, intent of VAD, pre-implant planning, device selection, operative management, postoperative hemodynamic goals, and adverse events following VAD implantation. The various indications for VAD include failure in medical management, postcardiotomy failure to wean from cardiopulmonary bypass (CPB), and arrhythmias. The important steps in pre-implant planning include end-organ assessment, right heart assessment, support-type assessment, psychosocial assessment, and device fit. The devices used for short-term VAD in children are Rotaflow , Pedimag , Centrimag (Abbott Laboratories), Tandem Heart , Tandem Life ProtekDuo (LivaNova), and Impella RP . For long-term VAD, Berlin Heart EXCOR  and Heartmate 3 (Abbott Laboratories) system devices are used .This research contains all the latest information about drugs used in CHF and their mechanisms of action. A completely different spectrum of diseases, including CHD rather than cardiomyopathy, are responsible for pediatric HF. HF can be prevented from developing by early identification of risk factors and the initiation of proper therapy. Initially, an adaptive response occurring to ventricular dysfunction sets off a cascade of modifications that result in compensatory hypertrophy, which over time, if unchecked, leads to fibrosis and ventricular failure. Pediatric HF therapy includes surgical palliation and repair, as postoperative cardiac lesions that are left untreated might result in persistent HF. Although neurohumoral stimulation is similar in children to that in adults with HF, there are significant physiological variations between children and adults, notably regarding alterations in development that are most noticeable in newborns. A significant number of cardiovascular medications that have a solid database for lowering the hazards of unfavorable cardiac outcomes are selective beta 1 adrenoceptor inhibitors. Implementation of medical therapy in individuals with HF with reduced ejection fraction is difficult as these patients' physiological factors and comorbidities restrict the up-titration of lifesaving drugs. Lifestyle factors like poor diet, lack of physical exercise, obesity, and increased mental and emotional stress also contribute to developing HF. The availability, cost, and prescription policies of medications may also restrict patient access to them, with particular concerns arising in different areas over the globe.


Physical activity (PA) and resting heart rate (RHR) are connected with all-cause mortality. Moreover, there was an inverse correlation between PA and RHR. However, the causal relationship between PA, RHR, and long-term mortality has been rarely evaluated and quantified, particularly the mediation effect of RHR in the association between PA and all-cause mortality.via cardiac implantable electronic devices (CIED) and further explore the mediation effect of PA on all-cause mortality through RHR.To describe the relationship between PA and RHR when consistently measured Patients who underwent CIED implantation and received remote home monitoring services were included. During the first 30–60 days after CIED implantation, daily PA and RHR were continuously measured and automatically transmitted by CIED. The primary endpoint was all-cause mortality. The multiple linear regression model was used to confirm the relationship between PA and RHR. The predictive values of both PA and RHR for all-cause mortality were assessed by multivariable Cox proportional hazards models. The causal mediation model was further established to verify and quantify the mediation effect of RHR in the association between PA and all-cause mortality.p < 0.001). Multivariable Cox proportional hazards analysis showed that both lower levels of PA  and higher RHR  were independent risk factors of all-cause mortality. Causal mediation analysis further confirmed and quantified the mediation function of RHR in the process of PA improving all-cause mortality .A total of 730 patients with CIED were included. The mean daily PA and RHR were 10.7 ± 5.7% and 61.3 ± 9.1 bpm, respectively. During a mean follow-up period of 55.8 months, 187 (26.5%) death was observed. A negative linear relationship between PA and RHR was demonstrated in the multiple regression model (β = −0.260; 95% CI: −0.377 to −0.143, The effects of the higher level of PA on improving life prognosis may be partially mediated through RHR among patients with CIED. It indicates that changes in the autonomic nervous function during postoperative rehabilitation exercises should get more attention. Physical activity (PA) is defined as any bodily movement produced by the skeletal muscles that need to consume energy . Thus, ivia cardiac implantable electronic devices (CIED) and further explore the mediation function of RHR in how PA improves prognosis.Heart rate, especially resting heart rate (RHR), is an easily accessible indicator in the assessment of sympathetic and parasympathetic activity; thus, it can reflect physical and general fitness , 14. TheThe Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device-implanted Patients (SUMMIT) registry is an observational, prospective, and multi-center trial. We retrospectively analyzed archived home monitoring transmission data from the SUMMIT registry. The present study was approved by the ethics committee of Fuwai Hospital (ID: 2010-296) and all other participating organizations. All patients provided written informed consent before entering this study, which complied with the Declaration of Helsinki.n = 182), PA group 2 , PA group 3 , and PA group 4 .From May 2010 to April 2014, patients who underwent CIED implantation, including implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D), were included upon meeting two inclusion criteria: (i) CIED with a remote home monitoring system and the system is continuously working during the follow-up, and (ii) data including RHR and PA are available during the target window. The exclusion criteria were as follows: (i) during the target window for RHR measurement, the percentage of daily ventricular pacing in a single-chamber device was more than 10%, or the percentage of average daily atrial and ventricular pacing percentage in a dual-chamber device was more than 10%; (ii) age at CIED implantation was younger than 18 years; (iii) the postoperative survival period was less than 3 months; or (iv) received heart transplantation. Patients were divided into four groups on average based on the baseline level of daily PA. PA group 1 , clinical complications , and medication intake  were collected before discharge from medical history.2 was recognized as activity. The value of daily PA was shown as the percentage in the remote monitoring system. For example, 1% means 0.24 h of daily PA and 10% means 2.4 h. Previous studies have proved that the acceleration sensors were highly sensitive in detecting PA . PA was measured using the acceleration sensors of CIED, and any acceleration above 0.473 m/scting PA –24. In oDaily PA and RHR were measured and automatically transmitted to the service center after CIED implantation. If data transmission is interrupted during the follow-up, clinical specialists will contact the patient and family members to confirm the monitoring function of the device and the condition of the patient. Also, routine telephone and outpatient follow-ups were conducted to collect clinical information about outcomes. The primary endpoint was all-cause mortality and the date of death was confirmed by medical records or death certificate.P value of < 0.05 in the univariable models and other potential confounders were entered into the multivariable analysis .Categorical variables, which were presented as numbers with relative percentages, were compared using the chi-square test, whereas continuous variables, which were expressed as mean standard deviation, were compared between the groups using one-way analyses of variance. Box plots and Scatter plots were used to describe the distribution of RHR among different PA groups and assess the relationship between PA and RHR, respectively. Then, simple and multiple linear regression models were used to further confirm the trend. The independent predictive values of both PA and RHR for long-term all-cause mortality were assessed by univariable and multivariable Cox proportional hazards models. Variables with a According to Baron and Kenny’s  procedurP value < 0.05, and all tests were two-sided.All statistical analyses were performed using IBM SPSS Statistics for Windows, version 23  and R version 4.0.3 . Statistical significance was set at a n = 229); the average atrial pacing percentage > 10% or average ventricular pacing percentage in a dual-chamber device > 10% (n = 50), age at CIED implantation is younger than 18 years old (n = 3), and the postoperative survival is less than 3°months (n = 3). The flow chart is shown in Of the 1,015 patients who underwent CIED implantation with home-monitor function, 285 patients were excluded because of the following reasons: home monitoring data including PA or RHR were unavailable (n = 182), PA group 2 , PA group 3 , and PA group 4 . The mean age of the participants at CIED implantation was 60.4 ± 13.9 years, 74.8% were men, 26.4% of patients received CRT-D implantation, 31.2% had hypertension, and 33.8% were ICM. The means of body mass index (BMI) and LVEF were 23.6 ± 3.0 kg/m2, and 42.8 ± 14.9%, respectively. Significant differences in the RHR (p < 0.001), age at CIED implantation (p < 0.001), LVEF (p = 0.03), history of diabetes (p = 0.002), stroke (p < 0.001), ICM (p < 0.001), diuretics usage (p = 0.008), and aldosterone antagonist usage (p = 0.005) were observed among different groups. During a mean follow-up period of 55.8 ± 22.7 months, 187 (26.5%) death was observed in the total cohort. With the daily PA increased, the rate of all-cause mortality in each group was gradually decreased .A total of 730 patients were included in the analyses and Baseline characteristics are shown in p < 0.001). After adjustment for potential confounders  in the multiple linear regression analysis, the β of RHR was −0.260  which means that RHR was decreased by 0.26 bpm for each additional 1% increase of daily PA.p < 0.001) after adjustment of possible variables . In multivariable Cox regression model 2, adjusting for all confounders included in model 1 and additional RHR, daily PA was still a protective factor of all-cause mortality , illustrates that each additional 1% increase of daily PA can reduce the risk of all-cause mortality by 8.9%.Estimated survival by the Kaplan-Meier method for the entire cohort stratified by quartile of daily PA  and RHR P = 0.003) after adjustment for the confounders in model 1 . After adjustment for the confounders mentioned in model 1 and additional PA (multivariable model 2), RHR as a continuous variable remained an independent predictor of all-cause mortality , indicating that each 1 bpm increase in RHR can account for a 1.6% increase in the risks of all-cause mortality. However, the association was weak in different RHR quantile groups.Also, the univariable multivariable Cox regression analyses were established to further assess the predictive value of RHR on the risk of all-cause mortality . ElevateP = 0.036; total effect = 11.25; 95% CI: 8.05–15.09, P < 0.001), and the mediation proportion was 3.9% , indicating 3.9% effect of PA on the risks of all-cause mortality was mediated through RHR.As mentioned above, all three principles for causal mediation analysis have been met . In PathThis retrospective analysis aimed to explore the relationship between RHR and PA which are continuously measured by CIED, and their value in predicting long-term all-cause mortality. The causal mediation analysis was established to verify the possible mediation effect of RHR on how PA improves all-cause mortality. The main findings were: (1) RHR was negatively related to PA, and both PA and RHR were independent predictors for long-term all-cause mortality; and (2) the mediation function of RHR was firstly confirmed and quantified in the process of PA improving all-cause mortality using causal mediation analysis for the first time, which may be critical to elucidate the potential mechanisms of the association between PA and all-cause mortality.Clear evidence for the health benefits of PA began to emerge in the 1950s –4. AlthoAlso, our findings support that elevated RHR is independently associated with increased all-cause mortality, since every additional 1 bpm increase in RHR could lead to a 1.6% increase in the risks of all-cause mortality. Previous research has focused on the relationship between RHR and prognosis, RHR was measured by palpating the radial pulse or during blood pressure monitoring and assessed at a single point after several minutes of rest , 20, 24.Given the methodological limitations of self-reported PA, as an indicator of physical fitness and general health, RHR might be an alternative measure of the level of daily PA , 12, 15.P = 0.036) of the mediation effect of PA on the risks of all-cause mortality was mediated through RHR. This is the first study that verified and quantified the mediating effect of RHR on the progress of high PA improving long-term prognosis. The mechanism by which a high level of PA improves prognosis may partly be because of the low RHR induced by high PA. Specifically, the improvement in the autonomic nervous functions may be one of the reasons why regular PA decreased all-cause mortality. Therefore, RHR may be essential in providing insights into understanding the benefits of high levels of PA. Furthermore, changes in the autonomic nervous function during postoperative rehabilitation exercise should be considered among patients with CIED. Finally, when direct measures of PA levels are lacking, RHR may be used as an alternative to assess the relationship between PA and prognosis.As discussed above, both PA and RHR have independent predictive values for all-cause mortality among patients with CIED, and they also have a linear relationship. Thus, causal mediation analysis was performed following Baron and Kenny’s  procedurThis study has some potential limitations that should be recognized. First, The mediation effect in this analysis is significant but relative low. It may indicate that the mechanism by which enhanced exercise improves prognosis is very complex, and the improvement of autonomic nervous function is only part of it. Data like PA and RHR were retrospectively collected and analyzed in this study. Prospective studies are needed to further quantify the mediation function of RHR. Second, the relationship between RHR and outcomes was weak in different RHR quartile groups. Although it does not affect the main results, a large sample and more detailed grouping methods were also needed to further explore differences in RHR subgroups. Third, although the accelerometer was highly sensitive in detecting whether a person is active or not, the intensity of PA measured was limited by the preset threshold. More accurate algorithms are needed to further distinguish the levels of PA. In addition, all selected patients were those with ICD or CRT-D and underwent a high risk of sudden cardiac death, which may cause potential effects on daily PA and RHR. Thus, generalizing the findings to other populations requires more caution.The findings of this study show that both PA and RHR, continuously measured by CIEDs, were independent predictors for long-term all-cause mortality. Moreover, causal mediation analysis further verified that the partial mediation effects of PA on improving life prognosis were mediated through RHR. It indicates that the changes in autonomic nervous function may be an important step in the process of improving the prognosis by regular PA. Changes in the autonomic nervous function during postoperative rehabilitation exercise should get more attention among patients with ICD/CRT-D.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. The patients/participants provided their written informed consent to participate in this study.CC and XS had the idea for the study. CC wrote the draft report. SZ and XS revised the manuscript. All authors contributed to the study design, data interpretation, read, and approved the final manuscript.


A total of six (n = 6) of athletes had eccentric hypertrophy, while others had normal heart geometry. LVEDd, LVEDs, LVEDd/BSA, and LVEDs/BSA were significantly higher in judokas (p < 0.05). LVEDd in athletes ranged from 48 to 62 mm. These values, combined with normal diastolic function, ejection fraction, and shortening fraction, indicate that the judokas’ cardiac adaptation was physiological rather than pathological.The long-term practice of judo can lead to various changes in the heart including increased dimensions of the left ventricle in diastole and thickening of the interventricular septum and the posterior wall of the left ventricle. This study aimed to assess left ventricular morphology and function in elite male judokas. A comparative cross-sectional study was conducted that included a total of 20 subjects, 10 judokas, and 10 healthy non-athletes aged 24 ± 2.85 years. Demographic and anthropometric data were analyzed. All subjects underwent a medical examination and a two-dimensional transthoracic echocardiogram. Different parameters of left ventricular morphology and function were measured and compared between athletes and non-athletes. Left ventricle mass and LV mass index were higher in judokas than in non-athletes ( A regular training program for elite athletes often causes morphological changes in the heart and blood vessels, increases the thickness of the left ventricular (LV) wall (hypertrophy) and ventricular mass, causes LV cavity enlargement (dilatation), and enhances resting parasympathetic tone . The chaDifferent types of activity create different forms of cardiac hypertrophy . DynamicTo be successful in any sport, athletes should achieve a high level of physical conditioning and physical fitness. Judokas show great anaerobic capacity and strength when exercises involve the upper body. Judo, as a high-intensity intermittent sport, relies mainly on anaerobic sources, although other sources also contribute significantly to performance. The aerobic component in judoka contributes to better and faster recovery during short breaks between efforts .Judo is a dynamic, high-intensity, intermittent sport . PracticAt the Serbian Institute for Sports and Sports Medicine and the Institute of Cardiovascular Diseases of Vojvodina, a comparative cross-sectional study was conducted that included a total of 20 subjects divided into 2 groups. The first group consisted of 10 male judokas. The second group consisted of 10 healthy non-athletes, all male subjects. All participants were Caucasians. The sample of judokas was purposive and included the best judokas from Serbia who participated in more than five international competitions that are scored for the Olympic norm. The athletes had 24 h of high-intensity training per week. All judokas had started with judo training at the age of seven. The second group was randomized from non-sporting groups. Demographic, anthropometric, and echocardiographic data were analyzed for all subjects. The average age of the judokas was 25.5 ± 3.17 years and the non-athletes’ group average was 22.5 ± 1.43 years. All participants underwent a medical examination and 2D transthoracic echocardiogram. Exclusion criteria were: a previous history of hypertension, heart diseases, hepatic, kidney, malignant and infections disorders, diabetes mellitus, and electrolyte imbalance.The analysis of anthropometric characteristics included the measurement of body height (BH), which was performed with an anthropometer according to Martin , with an accuracy of 0.1 cm, in a standing position with heels together, toes apart, and hands close to the body. The position of the head during the measurement of body height was horizontal, and the values are expressed in cm. Body mass (BM) was determined using an Omron weight scale BF511  with an accuracy of 0.1 kg. The body surface area (BSA) was calculated according to the appropriate formula:All subjects underwent two-dimensional transthoracic echocardiography using a low-frequency probe of 2.5 MHz on an ultrasound device, Vivid 9, produced by General Electric, Boston, MA, USA. For each acquisition, three cardiac cycles of uncompressed data were stored in a cine-loop format and estimated by one researcher who was blinded to the clinical characteristics of the subjects. The examination was performed in the supine position , and the measurements and calculations of morphological and functional indicators of the left ventricle were according to the standards of the American Association for Echocardiography and the European Association for Cardiovascular Imaging .2). Left ventricular ejection fraction (EF%) was calculated according to the modified Simpson disk method EF = ((EDVLV − ESVLV)/EDVLV) × 100%, and left ventricular shortening fraction (FS) was expressed in %.The following parameters were measured and calculated: The parasternal long-axis view was used to measure the thickness of the posterior wall of the left ventricle in diastole , the thickness of the interventricular septum in diastole , the left ventricular dimensions . The left ventricular myocardial hypertrophy level was calculated based on the formula LVHL = (IVSd + PWd)/2. The relative LV wall thickness (RWT) was calculated from the formula RWT = 2 × PWd/LVIDd. Left ventricular mass (LVM) was automatically calculated via area–length in the software according to measures obtained from the echosonographic parameters acquired from the parasternal cross-sectional view in which mid-ventricular diastolic and systolic epicardial and endocardial surfaces were observed without papillary muscles; diastolic and systolic mitral-to-apical distance in the apical 4C view was also acquired: LVM = 1.05 × (0.8 × A1 × (L + t)) − (0.8 × A2 × L). Specific muscle gravity is 1.05 g/mL; A1 is end-diastole epicardial area (cm); A2 is end-diastole endocardial area (cm); L is end-diastole ventricular length; and t is average wall thickness (cm). LV mass index was calculated by indexing with the patient’s body surface area  begins with the opening of the mitral valve, and atrial wave A (cm/sec) indicates the rate of late atrial filling of the left ventricle associated with atrial contraction. E/A ratio and the septal and lateral velocity of early movement of the mitral ring, “e’sep” and “e’lat,” were calculated; the ratio of early transmitral inflow and the mean early mitral ring velocity (E/e’mean) were also calculated.p < 0.05.The data obtained in this way were sorted in Microsoft Excel , while the statistical data processing used the software package Statistical Package for Social Sciences . Data processing included descriptive and inferential statistics. Numerical features are presented as means, measures of variability , and attributive features using frequencies and percentages. Depending on the nature of the data, the comparison of the values of numerical features between the two groups was performed using Student’s t-test, while the differences in the frequencies of attribute features were compared using the chi-square test. The results are presented in tables and graphs. The significance level was set at p > 0.05).The average age of the judokas was 25.5 ± 3.17 years, and the non-athletes’ average age was 22.5 ± 1.43 years. p <0.05). In the control group, seven (n = 7) subjects had normal heart geometry, while the others (n = 3) had concentric LV remodeling. A total of six (n = 6) athletes showed eccentric hypertrophy, while the others (n = 4) had normal heart geometry . There was a difference between groups in left ventricle mass in that the absolute values were higher in the judokas (233.44 ± 68.75 g). There was also a difference in LV mass indexed to the body surface area (geometry .p < 0.05). The average end-diastolic diameter of the left ventricle in the judokas was 55.2 ± 5 mm, ranging from 48 mm to 62 mm, while in the non-athletes, it was 47.00 ± 3.26 mm, ranging from 43 mm to 52 mm (p < 0.05). The end-systolic diameters were 35.2 ± 5.5 mm in the judokas and 30.90 ± 3.90 mm (p < 0.05) in the non-athletes. The average LVEDd/BSA in athletes was 27.22 mm/m2, while in the control group, it was significantly lower, 23.89 mm/m2 (p < 0.05). There was a significant difference between the groups concerning LVEDs/BSA (p < 0.05), and athletes showed higher average values (17.36 ± 1.5 mm/m2 vs. 15.65 ± 1.1 mm/m2). The thickness of the posterior wall in athletes was, on average, 9.78 mm, while in non-athletes, it was significantly lower, 8.95 mm (p < 0.05). There was no statistically significant difference in interventricular septal thickness.Comparing the echocardiographic characteristics of the examined groups , the absp < 0.05). However, there were no significant differences in the ascending aortic dimensions.The absolute aortic root dimensions and cusp separation values differ statistically significantly between the judokas and the control group  did not differ between athletes and non-athletes. There was a statistically significant difference in the late atrial filling (A), as well as in the E/A ratio. The judokas and the control group also differed significantly in e’sep. However, when we indexed E with e’sep and e’av, there was no statistically significant difference. E/e’av was within normal limits, ≤8 in both the athlete and non-athlete groups.n = 6) had eccentric left ventricle hypertrophy, while the others had normal heart geometry, which may be related to endurance training combined with strength training. Although there were differences in systolic and diastolic heart function between the athletes and non-athletes, these parameters were within normal limits in both groups.This study shows that in our small sample, highly trained judokas exhibited significant changes in heart morphology and function compared with non-athletes. The internal dimensions of the heart, LVEDd, and LVEDs were significantly higher in the judokas compared with the control group. The difference is retained when these values are indexed with the body surface area. The judokas also had significantly increased left ventricle posterior wall thickness and left ventricular mass. Most of them , so future research should involve more athletes so that we can draw more definite conclusions.Left ventricle hypertrophy level and relative wall thickness were similar between athletes and non-athletes. There was no significant difference. In the literature, we find that most athletes have normal heart geometry, but abnormal geometry is not rare and depends on the type of sport, race, and training time . Urhause115 g/m2 . The sizn = 2) of our judokas had LVED ≥ 60 mm, none of the athletes showed signs of global systolic dysfunction or abnormal diastolic filling, suggesting that ventricular enlargement was more likely due to intense sports training rather than a consequence of primary heart disease [Markedly increased dimensions of the heart cavity can be found in athletes in response to long-term intensive and systematic training, especially in those who engage in aerobic sports, which entail a physiological adaptation of the heart . Dilated disease .Elite athletes have a larger aortic root compared with control groups, especially in sinus Valsalva. The enlargement of the aortic root is greater in the Valsalva sinus than in the aortic valve annulus because it is fibrous and less extensible. Aortic root dimensions ranged from 30.2 to 33.1 mm .EF and FS did not differ between the judokas and the control group, and the values of these parameters were within normal limits. Previous research also shows that EF is preserved in athletes, indicating that resting contractility is not increased ,32.The early wave (E) was similar in judokas and non-athletes. However, the A-wave was significantly higher in the control group. Considering the difference in the A-wave velocity, there is also a difference in the E/A ratio, which was significantly higher among the judokas. Despite this difference, there is no abnormality in this ratio between LV filling and relaxation. For all participants, the E/A ratio was >1, which is similar to other studies ,34. CaseA common finding in athlete’s heart is an increased left ventricular mass associated with thickening of the walls and an enlarged inner diameter of the left ventricle . The norOur study also provides insight into the dimensions of the heart to define the upper limits of left ventricular dimensions associated with long-term and intense training of judokas, such as athlete’s heart. The recognition of the upper limits of left ventricular size in athletes has clinical significance and offers the opportunity to distinguish benign heart remodeling, seen with increased physical exertion, from pathological structural changes such as dilated and hypertrophic cardiomyopathy ,38,39. DThe study has several limitations. First, participants in our study were highly trained judokas, Caucasians, and <30 years old. For these reasons, the results may not be applicable to recreational athletes, athletes of different ethnic backgrounds, and ages. Second, due to the cross-sectional nature of the study, no follow-up was conducted, which limits the understanding of the nature of the remodeling process. Third, we used BSA to index cardiac dimensions, which is sometimes not the most acceptable method for estimating LV size in athletes. Other studies suggest using LV dimensions normalized per height, lean mass, and allometric scaling ,42 becauIn the present study, highly trained male judo players demonstrated significantly higher LV posterior wall thickness and increased left ventricular mass compared with sex-matched non-athletes. The internal dimensions of the left ventricle were also significantly increased in judokas. Although most athletes had eccentric left ventricular hypertrophy, RWT and LVmass index were within normal limits. These changes in left heart morphology, combined with normal diastolic function, ejection fraction, and shortening fraction, indicate that the judokas’ cardiac adaptation was physiological rather than pathological, showing the pattern of left ventricular remodeling commonly observed in strength and power training, with a limited endurance training contribution. This research provides insight into the upper limits of heart dimensions in judokas and can help clinicians distinguish between athlete’s heart and primary heart disease, especially HCM and DCM.Future research should be expanded to a larger number of subjects and should also include female judokas. Our study included the best judo players from Serbia, who participated in a large number of international competitions and achieved Olympic norm, which distinguishes our research from most published research.