Objective: This study aimed to observe the effect of dapagliflozin on left ventricular ejection function (LVEF) and left ventricular end-diastolic volume (LVEDV) in patients with acute anesthesia ST segment elevation myocardial infarction (ASTEMI) and explore the effect of prophylactic treatment on ventricular remodeling (VR). Methods. A retrospective cohort design was employed to collect 188 patients with anterior wall STEMI who received emergency percutaneous coronary intervention (PCI). The patients were divided into dapagliflozin group and control group. The baseline data, the results of echocardiography at 6 months and on admission, and the proportion of VR were compared between the two groups. Echocardiography followed up for the two groups for 6 months after PCI and VR (LVEDV increased ≥20%) were considered the main clinical outcomes. Single-factor and multifactor logistic regression was conducted to explore the preventive effect of dapagliflozin on VR in patients with anterior wall STEMI. Results. There were significant differences in gender, history of diabetes, glycosylated hemoglobin (Hb1AC), admission LVEF, Killip grade of heart failure, and brain natriuretic peptide (BNP) between the dapagliflozin group and the control group regarding the baseline data. Compared with the results of echocardiography at admission and 6 months, the decrease in LVEDV and the increase of LVEF at 6 months in the dapagliflozin group were significantly higher than those in the control group. During the follow-up of 6 months, the VR rate in the dapagliflozin group was significantly lower than that in the control group. Multifactor logistic regression analysis suggested that the risk of VR was reduced by taking dapagliflozin after the adjustment of the confounding factors. Additionally, the combined use of dapagliflozin, ACEI/ARB, and β-block can further reduce the risk. Conclusion. Regular taking of dapagliflozin has a positive effect on the improvement of middle and LVEF and left ventricular volume enlargement in patients with anterior wall STEMI, as well as the prevention of the occurrence of VR. Nevertheless, the clinical effect is not satisfactory. The statistics suggest that the incidence of ventricular remodeling in STEMI patients under combined therapy is still 25% and 30%. Dapagliflozin is an inhibitor of sodium-glucose cotransporter 2 (SGLT2i). Basic studies have demonstrated that SGLT2i can reduce left ventricular volume load, improve interstitial fibrosis, lower myocardial inflammation, promote cardiomyocyte energy metabolism, and weaken cardiomyocyte apoptosis. This is the theoretical basis for preventing ventricular remodeling after STEMI. The 2021 ESC Heart failure guidelines revealed that dapagliflozin can reduce the risk of hospitalization and cardiovascular death in patients with heart failure of reduced ejection fraction (HFrEF) w/o diabetes [Acute ST segment elevation myocardial infarction (STEMI) is a cardiovascular disease severely influencing the national survival time and quality . The estInclusion criteria: (1) The diagnosis is in accordance with the fourth version of the STEMI global definition, and coronary angiography confirms that the left anterior descending is the anterior wall myocardial infarction of the target vessel; (2) the relevant clinical data is available from the chest pain center database and hospital medical record system; (3) if the time window of onset is less than 24 hours, the direct PCI treatment is performed with the time of D2W less than 90 min; (4) age: 45 to 75 years old. Exclusion criteria: (1) combined with severe hepatic and renal function injury or other organ injuries; (2) complicated with malignant tumor; (3) combined with rheumatic immune disease; (4) they have valvular heart disease, Cor pulmonale, hypertensive heart disease, and cardiomyopathy at the same time; (5) the blood flow of the left anterior descending still did not reach Thrombolysis in myocardial infarction 3 (TIMI3) grade at the end of the operation; (6) there is a serious lack of medical records; (7) follow-up cannot be completed through coordination; (8) patients who have taken dapagliflozin to treat related diseases. This study was a single-center, retrospective cohort study. Patients with STEMI in the anterior wall of the Chest Pain Center of the Second Hospital of Anhui Medical University from May 2020 to May 2021 were collected. This study was approved by the Ethics Committee of the Second Hospital of Anhui Medical University (PJ-YX2020-014 (F1)).199 patients were enrolled through the inquiry of medical records and the inclusion and exclusion criteria. The patients were divided into two groups according to whether they took dapagliflozin or not after the PCI operation. In the dapagliflozin group, 13 cases were eliminated , and 82 cases remained. In the control group, 8 cases were eliminated (5 cases were lost to follow-up and 3 cases took dapagliflozin midway), and 96 cases remained.The demographic data and clinical data  of 2 groups during admission were collected based on the case data.β-block is taken, admission Killip grade, complicated with atrial fibrillation, complicated with ventricular arrhythmia; (3) Echocardiography data (three indicators): left ventricular ejection function (LVEF) on admission, left ventricular end-diastolic volume (LVEDV) at admission, maximum velocity of the mitral valve at early diastole on admission; (4) Coronary angiography indicators (three indicators): SYNTAX score, number of diseased coronary vessels, grade of collateral circulation; (5) Blood test indicators (eleven indicators): uric acid, glycosylated hemoglobin, low-density lipoprotein, high-density lipoprotein, brain natriuretic peptide (BNP), troponin I (CnTI), creatinine, glutamic pyruvic transaminase, fibrinogen (FDP), neutrophil/lymphocyte (NLR), platelet count.(1) Demographic data (three indicators): gender, age, body mass index (BMI); (2) disease-related data (ten indicators): history of smoking, history of hypertension, history of diabetes, time of onset, time from entrance to smooth passage of occluded blood vessel with a guidewire (D2W), whether ACEI/ARB (angiotensin-converting enzyme inhibitors/Angiotensin II receptor blockers) is taken, whether The results of echocardiography 6 months after PCI operation in 2 groups were followed up. The increase in LVEDV of echocardiography ≥20% after 6 months compared to the period of admission was regarded as the standard of ventricular remodeling [t-test and analysis of variance were performed for the measurement data that accorded with the normal distribution and meet the homogeneity of variance. Meanwhile, a t-test was adopted for those that did not satisfy the homogeneity of variance. Besides, χ2 test and Fisher's accurate test were conducted for the measurement data comparison. The difference between the prerepeated measurement data and the postrepeated measurement data was calculated. The differences between the two groups were compared using the Mann–Whiney U rank-sum test. Logistics analysis was performed to analyze the clinical outcome of patients. The Enter method was used first, followed by the Forward: LR method . P < 0.05 was considered statistically significant.The data was analyzed by SPSS 24.0 statistical software. The measurement data is expressed as mean ± standard deviation (SD). The counting data are statistically described by frequency and constituent ratio. The independent sample β-block taking, atrial fibrillation, malignant ventricular arrhythmia, number of diseased coronary vessels, SYNTAX score, collateral circulation, uric acid, low-density lipoprotein, high-density lipoprotein, creatinine, glutamic pyruvic transaminase, FDP, CnTI, and NLR between the two groups. The difference was not statistically significant (P > 0.05). The gender, history of diabetes, and the proportion of Killip grade were not completely the same between the two groups, with a statistically significant difference (P < 0.05). Additionally, the LVEF of admission in the control group was higher than that in the dapagliflozin group, and the Hb1AC and BNP in the dapagliflozin group were higher than those in the control group.The results in P < 0.01). The results demonstrated that the use of dapagliflozin for 6 months could significantly reduce the LVEDV; the increase in LVEF 6 months after admission in the dapagliflozin group was higher than that in the control group, with a statistically significant difference (P < 0.01). It suggested that the use of dapagliflozin for 6 months can significantly increase LVEF. The changing trend of LVEDV and LVEF in the two groups is illustrated in Figures P < 0.05). The results revealed that the probability of ventricular remodeling decreased after 6 months of use of dapagliflozin.In β-block, LVEDV, LVEF, BNP, NLR, Hb1AC, history of diabetes, uric acid, and CnTI on admission on the prognosis. The Enter method was used. The results in β-block taking, and admission LVEF were prognostic protective factors, and the difference is statistically significant (P < 0.05); CnTI, BNP, and NLR were prognostic risk factors of patients, and the difference is statistically significant (P < 0.05); left ventricular end-diastolic diameter, uric acid, diabetic history, and Hb1AC did not influence the prognosis of patients, and the difference was not statistically significant (P > 0.05).The clinical outcome (ventricular remodeling) of the patients was analyzed through logistics regression to explore the effects of taking dapagliflozin, taking ACEI/ARB, taking The prognosis of patients (ventricular remodeling) was analyzed by logistics regression, as well as the effect of taking dapagliflozin on the prognosis of patients. Before and after the adjustment of the confounding factors, the use of dapagliflozin was the protective factor of ventricular remodeling. The results in β receptor blocker on the prognosis of the patients. Before and after the adjustment of the confounding factors, the use of the three drugs was a protective factor for ventricular remodeling. The results in β receptor blockers can reduce the risk of ventricular remodeling after myocardial infarction under the combined action of various clinical factors affecting ventricular remodeling. Moreover, the preventive effect is better than that of taking dapagliflozin alone.The clinical outcome (ventricular remodeling) of the patients was analyzed through logistics regression to reveal the effect of taking dapagliflozin + ACEL/ARB+ β/Smad pathway, and STAT3 pathway. In addition to ischemic and hypoxic necrosis of cardiomyocytes [Ventricular remodeling is a major change in the rational structure of heart disease that leads to high mortality in patients with STEMI in the middle and later stages . The lefmyocytes , there imyocytes , extensimyocytes . The abomyocytes . Clinicaβ pathway and reduce the degree of myocardial interstitial fibrosis. Gager et al. [2+ homeostasis in the animal model of heart failure. Myocardial interstitial fibrosis, cardiomyocyte inflammation, and cardiomyocyte apoptosis constitute the main pathological basis of ventricular remodeling after STEMI. Therefore, there is a theoretical foundation for dapagliflozin to prevent ventricular remodeling after STEMI.Dapagliflozin is a renal tubular sodium-glucose symporter inhibitor (SGLT2i). It is mainly used to reduce the reabsorption of urine glucose and then lower blood glucose by inhibiting renal tubular sodium-glucose symporter. Meanwhile, the osmotic diuretic effect is enhanced due to the decrease of glucose reabsorption in urine, contributing to reducing the cardiac volume load to a certain extent . As a rer et al.  proposedr et al.  discoverAt present, dapagliflozin can reduce the incidence of Major Adverse Cardiovascular Events (MACE) and mortality in patients with HFrEF and can be used as a first-line drug for the treatment of heart failure in patients with diabetes or nondiabetes, according to the 2021 ESC Heart failure guidelines . Regardiβ-block are effective drugs to prevent ventricular remodeling. In this study, there is no difference in whether the two groups took these drugs, indicating that the interference of the above drugs on the outcome observation is excluded. Additionally, there was no difference in onset time and D2W time between the two groups. This reflected that the ischemic time and revascularization time were similar between the two groups, and there was no difference in the effect of ischemic injury between the two groups. Furthermore, the distribution of the two groups of baseline data is balanced and comparable. The different factors of baseline data are mainly divided into two categories: heart failure indicators  and diabetes indicators . Among them, LVEF in the dapagliflozin group was significantly lower than that in the control group on admission, while the Killip grade and BNP in the heart failure group were higher than those in the control group. In other words, many patients with acute heart failure after anterior wall STEMI were treated with dapagliflozin in this study. This is consistent with the recommended medication strategy of the latest ESC guidelines for heart failure. Meanwhile, there are more patients with a history of diabetes and higher glycosylated hemoglobin value in the dapagliflozin group, revealing that STEMI patients with diabetes were more likely to use dapagliflozin in this study owing to the hypoglycemic effect of dapagliflozin.In this study, the baseline data included a total of 30 indicators, except for gender, and only 6 factors had statistical differences. Among them, ACEI/ARB and In this study, echocardiography suggested that the increase of LVEF in patients with anterior wall STEMI 6 months later was higher than that in the control group at the time of admission. Therefore, the left ventricular blood pumping function induced by STEMI was improved to some extent in patients with anterior wall STEMI who received standard treatment for 6 months, consistent with the clinical findings of Packer et al. . YuristaThis study is not aimed at patients with STEMI, though Gamaza-Chulián et al.  confirmeβ-block, admission LVEF, BNP, NLR, and CnTI were confounding factors. Then, the multifactor logistic regression analysis was conducted. It was revealed that taking dapagliflozin was the protective factor of ventricular remodeling before and after the adjustment of the confounding factors. Thus, taking dapagliflozin could still benefit patients with anterior wall STEMI and reduce the risk of ventricular remodeling in the middle and later stage in practical clinical application under the combined action of various factors affecting ventricular remodeling. According to the specific analysis of the related confounding factors, ACEI/ARB, β-block, and admission LVEF were protective factors, while BNP, NLR, and CnTI were risk factors. The lower the admission LVEF, and the higher the BNP, the more severe the acute heart failure, and the greater the risk of ventricular remodeling in the middle and later stage. NLR, as an evaluation indicator of inflammation, can reflect the degree of myocardial inflammation caused by acute ischemia. The higher the value, the higher the probability of remodeling of heart failure. Seropian et al. [β-block drugs, which are classic antiventricular remodeling drugs, acting by inhibiting the RASS system and sympathetic nervous system, respectively [β-block in action targets. No relationship between dapagliflozin and the RASS system or sympathetic nervous system has been discovered in related studies.Subsequently, further statistical analysis was performed in this study based on simple correlation analysis. Exposure factors (taking dapagliflozin) were included as the main observation factors; baseline difference factors and clinically confirmed factors affecting ventricular remodeling were selectively included as potential confounding factors. Ventricular remodeling was taken as the clinical outcome. The single-factor logistic regression analysis suggested that ACEI/ARB, n et al.  revealedn et al.  demonstrectively , 25. Conβ-block on ventricular remodeling in patients. After the interference of confounding factors was excluded, the combination of three drugs can further reduce the risk of ventricular remodeling in the middle and later stages of STEMI. According to the analysis of the reasons, the mechanism of action of dapagliflozin is different from that of ACEI/ARB and β-block. Besides, the analysis of the mechanism of action of dapagliflozin revealed that dapagliflozin can improve the state of acute heart failure, reduce myocardial inflammation, and weaken cardiomyocyte injury in patients with STEMI through non-RASS and nonsympathetic pathways, so as to produce the clinical effect of preventing ventricular remodeling. This is a powerful supplement to the existing clinical strategies for the prevention of ventricular remodeling after STEMI. Lee et al. [in vitro experiment, demonstrating that the AMPK/mTOR pathway is one of the key targets for SGLT2i to improve cardiomyocyte apoptosis. Tian et al. [β pathway. Therefore, in clinical application, dapagliflozin in combination with ACEI/ARB and β-block can coordinate in many ways to improve the clinical prevention effect.Finally, logistic regression was conducted to analyze the effect of the combined use of SGLT2+ACEL/ARB+ e et al.  suggestee et al.  conducten et al.  validateThere are some limitations to this study as follows: (1) inadequate source of cases in the single-center study and lack of a good representative sample; (2) this study is an observational study, and the conclusions still need to be further validated by large-scale randomized controlled studies; (3) cardiac magnetic resonance is more accurate than cardiac ultrasound in measuring left ventricular diastolic volume (determining whether ventricular remodeling is present).To sum up, dapagliflozin is a new first-line drug for the treatment of heart failure, and there is a theoretical foundation for it to prevent ventricular remodeling after STEMI. This study demonstrated that dapagliflozin can effectively improve left ventricular ejection function and left ventricular volume and prevent the occurrence of ventricular remodeling in the middle and later stages of STEMI. However, this study is a single-center observational study, with a small sample size and limited sample sources. The research conclusions still need to be further verified by multicenter prospective randomized controlled trials.


In addition, the mask method produced a significant decrease in LV-EDV and LV-ESV. LVEF was significantly increased with the mask method . MOPTM was positively correlated with BMI, septal wall thickness, LVM, LV-EDV, and LV-ESV. LVEF was inversely correlated with MOPTM. In addition, MOPTM correlated positively with NT-proBNP  and CK-MB . In conclusion, inclusion of PTMs in the myocardium has a substantial impact on quantification of the LVM, LV-EDV, LV-ESV, and LVEF in patients with HOCM. The effects of the PTMs in women was greater than that in men. Furthermore, the MOPTM was positively associated with NT-proBNP and CK-MB. The PTMs might be included in the myocardium when measuring the LV volumes and mass of patients with HOCM. At present, the clinical and prognostic meaning and relevance of the PTMs is not clear and should be further studied.Patients with obstructive hypertrophic cardiomyopathy (HOCM) have large papillary and trabecular muscles (PTMs), which are myocardial tissue. PTMs are usually excluded from the myocardium and included in the left ventricular (LV) cavity when determining LV mass (LVM) and volumes using cardiac magnetic resonance (CMR). This conventional method may result in large distortion of LVM and other indices. We investigated 74 patients with HOCM undergoing CMR imaging. LV short-axis cine images were obtained. LV contours were drawn using two different methods: (1) the conventional method, where PTMs were included in the LV cavity; and (2) the mask method, which includes the TPMs in the LV myocardium. The LV end-diastolic volume (LV-EDV), LV end-systolic volume (LV-ESV), LV ejection fraction (LVEF), and the LVM were then calculated. Fasting NT-proBNP and CK-MB levels were measured with ELISA. In patients with HOCM, mass of PTMs (MOPTM) was 47.9 ± 18.7 g, which represented 26.9% of total LVM. Inclusion of PTMs with the mask method resulted in significantly greater LVM and LVM index (both  Affecting possibly 1/200 of the general population, hypertrophic cardiomyopathy (HCM) is a primary inherited myocardial disorder characterized by unexplained left ventricular (LV) hypertrophy . Owning The papillary and trabecular muscles (PTMs) are myocardial tissue, and thus should be included in the myocardium when determining the LV volumes and mass . HoweverWe enrolled patients with HOCM who were evaluated in Fuwai Hospital  from October 2015 to September 2016. The diagnosis of HCM was based on a maximum left ventricular (LV) wall thickness ≥ 15 mm , as measured by echocardiography or cardiac magnetic resonance imaging (CMRI), in the absence of other cardiac or systemic diseases capable of producing comparable magnitude of hypertrophy . Evaluat2, repetition time/echo time = 30.9/1.2 ms, slice thickness 6 mm, inter-slice gap 2 mm, image matrix 192 × 162, and flip angle 70°. Patients were asked to hold their breath while images were being acquired.The CMRI was performed using a 1.5-T speed clinical scanner  or a 3.0-T scanner . The imaging protocol has been described previously ,13. FirsAll the CMRI analysis was performed using a commercial software  by an experienced radiologist who was blinded to patients’ clinical data. End-diastole and end-systole were identified on the basis of the respective image frames showing the largest and smallest cavity size.LV contours were drawn using two different methods . (1) TheThe LV end-diastolic volume (LV-EDV), LV end-systolic volume (LV-ESV), LVEF, stroke volume, cardiac output (CO), and LV mass (LVM) were then calculated in a standard fashion . The LVMVenous blood samples of fasting patients with HOCM were collected within 2 days of echocardiography and 1 week of CMR examination. Plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured with an electrochemiluminescent immunoassay  on a Cobas 6000 analyzer (Roche Diagnostics), with a lower detection limit of 0.6 pmol/L. The inter-assay coefficient of variation was <4.6% and the intra-assay coefficient of variation was <4.2%. Serum CK-MB was determined by an immunoinhibition assay  on an Olympus AU-5400 analyzer (Olympus Diagnostics), with a lower detection limit of 3 IU/L. The inter-assay and intra-assay coefficients of variation were <6%.t-test. Pearson’s correlation test was used to examine correlations between two continuous variables. Logarithmic transformations were performed for NT-proBNP to obtain normal distribution. Bland–Altman analysis was used for intra-observer and inter-observer reproducibility. A 2-tailed p value < 0.05 was considered as statistically significant. Statistical analysis was performed with SPSS version 19.0 software .Continuous variables are expressed as mean ± SD or median (interquartile range (IQR)), according to their normality. Categorical variables are shown as frequencies (percentages). Comparisons of continuous variables between two groups were assessed with a paired Student’s The clinical characteristics of the 74 patients with HOCM are presented in p < 0.0001; p < 0.0001). The LVEF was significantly increased with the mask method , septal wall thickness , LVM , LV-EDV , and LV-ESV . The LVEF was inversely correlated with MOPTM . In addition, the MOPTM correlated with Ln (NT-proBNP)  and CK-MB . In addition, the MOPTM index was also positively correlated with NT-proBNP  and CK-MB  (= 0.001) .The intra-observer and inter-observer reproducibility and variability for the conventional method and the mask method are summarized in In the present study of 74 patients with HOCM undergoing CMRI, we demonstrated that inclusion of the PTMs in the myocardium using the mask method resulted in greater LVM and LVEF. In addition, the mass of PTMs (MOPTM) correlated positively with the LVM, whereas inversely with the LVEF. Furthermore, the MOPTM index correlated positively with NT-proBNP and CK-MB levels, which reflect severity of heart failure and myocardial damage, respectively.2), which is close to our data [A few studies have demonstrated that inclusion of the PTMs in the myocardium will lead to greater LVM. A study in a community-based adult cohort performed by Michael L. Chuang et al. showed that the LVM increased by 28% if the PTMs were regarded as myocardium rather than part of the LV cavity . In addiour data . The minour data . Taken tour data , the PTMDecreased LVEF is an important prognostic marker of mortality in patients with chronic HF . AlthougIn the current study, our data revealed that the LVMI was increased by 30.2% in women and 25.7% in men when the mask method was used. Similar to our findings, Jeanette Schulz-Menger et al. studied 64 HCM patients (33 with HOCM) who were assessed with CMR, and found that the increase in the LVMI from non-obstructive HCM to HOCM was more pronounced in females compared to males . TherefoPrevious studies have revealed that hypertrophic papillary muscles may cause or exacerbate heart failure in patients with HOCM . Our priIt was believed that inclusion of the PTMs in the myocardium was very time-consuming when measuring CMR images . In prevRegarding the intra-observer and inter-observer reproducibility and variability for the conventional method and the mask method, the Bland–Altman plots in this study indicated that the mask method was comparable to the conventional method; additionally, a Pearson’s correlation test showed that reproducibility of LVM and LV-EDV was better than that of LV-ESV and LVEF for both the mask method and the conventional method. As mentioned above, the LV cavity is smaller in HOCM patients compared with healthy subjects . When thThis study has some limitations that warrant discussion. First, we were not able to address accuracy because the true LV mass and volumes were unavailable. Second, because most of patients enrolled in the present study underwent septal myectomy or alcohol septal ablation after comprehensive assessment, and these invasive therapies may be predominant influence factors of long-term prognosis, we did not assess the influence of the PTMs on prognosis of HOCM. In future investigation, it will be interesting to explore the effects of the PTMs on clinical outcomes in HOCM patients who receive drug therapy, alcohol septal ablation, or septal myectomy.Inclusion of PTMs in the myocardium has substantial impact on quantification of the LVM, LV-EDV, LV-ESV, and LVEF in patients with HOCM. The effects of the PTMs in women were greater than that in men. Furthermore, the MOPTM was positively associated with NT-proBNP and CK-MB. The PTMs might be included in the myocardium when measuring the LV volumes and mass of patients with HOCM. At present, the clinical and prognostic meaning and relevance of the PTMs is not clear and should be further studied.


Myocardial fibrosis, measured using magnetic resonance extracellular volume (ECV), associates with adverse outcome in heart failure with preserved ejection fraction (HFpEF). In the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial, the novel anti-fibrotic agent pirfenidone reduced myocardial fibrosis. We sought to identify baseline characteristics that associate with myocardial fibrotic burden, the change in myocardial fibrosis over a year, and predict response to pirfenidone in patients with HFpEF. Amongst patients enrolled in the PIROUETTE trial (n = 107), linear regression models were used to assess the relationship between baseline variables and baseline myocardial ECV, with change in myocardial ECV adjusting for treatment allocation, and to identify variables that modified the pirfenidone treatment effect. Body mass index, left atrial reservoir strain, haemoglobin and aortic distensibility were associated with baseline ECV in stepwise modelling, and systolic blood pressure, and log N-terminal pro B-type natriuretic peptide were associated with baseline ECV in clinically-guided modelling. QRS duration, left ventricular mass and presence of an infarct at baseline were associated with an increase in ECV from baseline to week 52. Whilst QRS duration, presence of an infarct, global longitudinal strain and left atrial strain modified the treatment effect of pirfenidone when considered individually, no variable modified treatment effect on multivariable modelling. Baseline characteristics were identified that associate with myocardial fibrosis and predict change in myocardial fibrosis. No variables that independently modify the treatment effect of pirfenidone were identified .The online version contains supplementary material available at 10.1007/s10554-022-02544-9. Myocardial fibrosis, measured using cardiovascular magnetic resonance (CMR) extracellular matrix volume (ECV), is associated with adverse outcome in patients with heart failure with preserved ejection fraction (HFpEF), including hospitalisation for heart failure (HF) and death –5.The Pirfenidone in patients with heart failure and preserved left ventricular ejection fraction (PIROUETTE) study was a phase II, double-blind, placebo-controlled, randomised trial designed to evaluate the efficacy and mechanism of the novel anti-fibrotic agent, pirfenidone, in patients with HFpEF and myocardial fibrosis . PirfeniIdentification of characteristics that are associated with myocardial fibrosis at baseline, and which predict change in myocardial fibrosis over time and response to pirfenidone, would improve risk stratification of patients with HFpEF, guide patient management, and guide future trial recruitment.This analysis of data from the PIROUETTE trial aimed to identify baseline characteristics that associate with baseline myocardial fibrotic burden, predict change in myocardial fibrosis over one year, and predict response pirfenidone, in patients with HFpEF.Between March 7, 2017, to December 19, 2018, the PIROUETTE trial  randomised 94 patients with HFpEF and myocardial fibrosis to pirfenidone or placebo for 52-weeks. The trial design and results have previously been published  / [ΔR1bloodpool], where ΔR1 is the difference in relaxation rates (1/T1) between pre- and post-contrast [Myocardial ECV was calculated from basal and mid left ventricular (LV) short axis T1 maps (MOdified Look-Locker Inversion recovery [MOLLI]), acquired before and 15 min following gadolinium contrast (0.15 mmol/kg of gadoterate meglumine), as: ECV = (1–haematocrit) x [ΔR1contrast . Haematocontrast .The trial was analysed and reported according to the ‘Consolidated Standard of Reporting Trials’ (CONSORT) and the International Conference on Harmonisation E9 guidelines. Analysis was conducted on an intention to treat basis, including all randomised patients retained in their randomised treatment groups. Continuous data are presented as mean ± standard deviation (SD) or as median (interquartile range (IQR)), as appropriate. Categorical data are presented as counts and percentages.Univariable and multivariable linear regression models were used to assess the relationship between baseline variables and baseline myocardial ECV. Variablesfor which p-values were < 0.3 in the univariable analyses were included in forward stepwise selection models, with p-value thresholds of 0.05 for entry and 0.1 for removal. The chosen variables were then included in multivariable regression models, where the outcome variable was baseline myocardial ECV. Collinearity was investigated by assessing correlation between variables and by assessing the variance impact factor for each model, which confirmed that collinearity correction measures were not required. Additional models using absolute myocardial ECM volume and absolute myocardial cell volume as outcome variables were constructed to assess ECV component associations. ‘Clinically-guided’ multivariable models were also constructed that included variables that, based on the published literature and clinical judgment, were hypothesised to be associated with myocardial ECV. The variables included in the ‘clinically-guided’ models were limited to 10 variables: age, sex, body mass index, diabetes, atrial fibrillation, log-N-terminal pro B-type natriuretic peptide (NT-proBNP), left atrial strain, systolic blood pressure, right ventricular end diastolic volume index and global longitudinal strain.Analysis of variance (ANOVA) models were used to assess the relationship between baseline variables and change in myocardial ECV , adjusting for treatment allocation. Variables for which p-values were < 0.3 in the ANOVA models were included in forward stepwise selection models, with p-value thresholds of 0.05 for entry and 0.1 for removal. Treatment allocation was forced into the selection model. The chosen variables were then included in a multivariable regression model, where the outcome variable was change in myocardial ECV . Additional models using absolute myocardial ECM volume and absolute myocardial cell volume as outcome variables were constructed to assess ECV component associations. ‘Clinically-guided’ multivariable models, as described above, were also constructed, limited to eight variables: age, sex, diabetes, log NT-proBNP, left atrial strain (reservoir), systolic blood pressure, right ventricular end diastolic volume index and global longitudinal strain.In order to provide an indication of which baseline variables predicted a response to pirfenidone, linear regression was used to model week 52 myocardial ECV with each baseline variable in turn, including an interaction between treatment allocation and each baseline variable, adjusting for baseline myocardial ECV, in order to identify baseline variables that modified treatment effect. Variables identified as being treatment effect modifiers were subsequently included in a multivariable ordinary least squares regression model, where the outcome was week 52 myocardial ECV. All analyses were performed in SAS .107 patients were enrolled, including 94 who had evidence of myocardial fibrosis (ECV ≥ 27%) who were randomised, and 13 patients without evidence of myocardial fibrosis (ECV < 27%) who were not randomised , haemoglobin and higher aortic distensibility were associated with higher ECV at baseline Table . There wMultivariable models for extracellular and cellular myocardial components revealed that the associations between log NT-proBNP and impaired left atrial strain (reservoir), and baseline ECV, were predominantly driven by associations with baseline myocardial ECM volume (Supplementary Tables S2-3). The inverse associations between body mass index, systolic blood pressure, global longitudinal strain, and baseline ECV, were predominantly driven by positive associations with baseline myocardial cell volume (Supplementary Tables S4-5).In stepwise multivariable analysis, shorter baseline QRS duration, higher baseline LV mass and presence of an infarct at baseline were associated with an increase in change in ECV from baseline to week 52. In the ‘clinically-guided’ multivariable model, only impaired baseline global longitudinal strain was associated with an increase in change in ECV Table .Table 3AMultivariable models for cellular and extracellular myocardial components revealed that a diagnosis of diabetes at baseline was associated with an increase in change in myocardial ECM volume from baseline to week 52, and lower baseline renal function and diastolic blood pressure were associated with an increase in change in myocardial cellular volume from baseline to week 52 (Supplementary Tables S7-10).Shorter QRS duration, the presence of an infarct, impaired global longitudinal strain and impaired left atrial strain (conduit) were each associated with a greater treatment effect of pirfenidone on 52 week ECV when considered individually. However, when these variables were entered into the same model, no baseline variable independently modified the treatment effect of pirfenidone .This analysis of data from the PIROUETTE trial identified several baseline characteristics that associated with myocardial fibrotic burden. Metrics reflecting important processes in the pathophysiology of HFpEF that associated with myocardial fibrosis included abnormal atrial mechanical remodelling and adaptation to elevated left ventricular filling pressures via natriuretic peptide release. Characteristics that predicted change in myocardial fibrosis over one year included those reflecting a more advanced stage of abnormal LV remodelling at baseline . Baseline QRS duration, presence of an infarct, global longitudinal strain and left atrial strain modified the treatment effect of pirfenidone when considered individually, but no baseline variable modified treatment effect on multivariable modelling.Parametric mapping techniques  are now standard sequences utilised in clinical CMR that provide non-invasive assessment of myocardial tissue composition and characterisation. ECV measurement not only identifies extracellular matrix infiltration and expansion, as seen in cardiac amyloidosis and myocardial fibrosis, but can reliably quantify myocardial fibrotic burden with high reproducibility, thereby allowing serial tracking and assessment of response to anti-fibrotic therapy.The baseline characteristics found to associate with baseline myocardial fibrosis in HFpEF in the current study are in keeping with the study by Kanagala et al. , which sAn association was identified between aortic distensibility and myocardial fibrosis. Aortic distensibility measures the change in the cross-sectional area of the ascending aorta (measured at the level of the main pulmonary artery) corrected for pulse pressure and therefore reflects aortic compliance. As compliance and stiffness are reciprocals it is commonly used as an inverse metric of aortic stiffness i.e., distensibility reduces as stiffness increases. Increased central arterial stiffness and magnitude of arterial wave reflections are well recognised in subgroups of patients with HFpEF –14, howeThe current study is the first to investigate characteristics that predict change in myocardial fibrosis over time in HFpEF. Given the association between myocardial fibrosis and adverse outcome in HFpEF, identification of factors that predict an increase in myocardial fibrotic burden may help to risk stratify patients. Remote myocardial fibrosis is well recognised post-myocardial infarction and, in studies using ECV, remote myocardial fibrosis is predictive of adverse remodelling post-infarction, although these studies have focused on the early period (first 3–6 months) post-infarction , 19. It 2 = 0.04). Given the multiple statistical testing employed, the findings of the current study require confirmation in larger natural history studies.Regarding the identified association between baseline global longitudinal strain and change in ECV, as discussed earlier, the relationship between myocardial ECV and myocardial mechanics is not straightforward, and, whilst some cross sectional data have shown associations between ECV and global longitudinal strain, in the largest cohort to date , cross-sectional myocardial ECV correlated minimally with global longitudinal strain Below is the link to the electronic supplementary material.


In modern society, dairy products have become increasingly important in our diet because of changes in consumption patterns due to urbanization. However, Chinese residents’ dairy consumption remains at a relatively low level, with great potential for growth. Exploring the main determinants of dairy consumption and their effect mechanisms not only helps to improve the health status of residents, but also has important policy implications for the development of China’s dairy industry. Based on the data of China Health and Nutrition Survey (CHNS) from 1989 to 2011, this study empirically analyzes the impact of urbanization on residents’ dairy consumption. The results indicate that urbanization could significantly promote residents’ consumption of dairy products and the effect is higher in areas with low urbanization levels and in midwestern regions than in areas with high urbanization levels and in midwestern regions. From the perspective of effect mechanism, income growth, employment structure transition and the rise of modern markets are three important mediating paths. Additionally, the results imply that in areas with low urbanization levels, income growth and the rise of modern markets are the main significant mediators; while in areas with high urbanization levels, employment structure transition is a significant mediator. Moreover, in midwestern regions, income growth is a significant mediator, and employment structure transition is a significant mediator in all regions. These findings have practical implications for understanding the relationship between urbanization and residents’ food consumption and for further promoting residents’ dairy consumption and the development of China’s dairy industry. Since the reform and opening up, China’s urbanization rate has continued to increase, from the 17.92% in 1978 to 51.27% in 2011 and more than 64% in 2021. In the process of urbanization, residents’ food consumption patterns have undergone significant changes, which are mainly reflected in the gradual decline in the consumption of cereal grains and continuous increase in the consumption of animal products [As animal-derived foods are rich in nutrients, dairy products have become an important part of residents’ food consumption. However, the dairy consumption of Chinese residents remains at a relatively low level. Residents’ dairy consumption expenditure accounts for only a small percentage of the total food expenditure, and the per capita consumption of dairy products is only one-third of the world average, which indicates great potential for further growth. Therefore, exploring the main determinants of dairy consumption and their effect mechanisms not only helps to improve the health status of residents, but also has important policy implications for the development of China’s dairy industry.Existing empirical research on residents’ dairy consumption mainly focuses on residents’ consumption characteristics and preferences for dairy products –7, the fMain aim of this study is to analyze the relationship between urbanization and residents’ consumption of dairy products in China using the data collected from 1989–2011 CHNS surveys. We first calculate residents’ average daily dairy consumption amount, urbanization rate, and the main key variables in each community. Subsequently, we take both urban and rural residents as research samples to explore the impact of urbanization on residents’ dairy consumption. Next, we use a parallel multiple mediator model to analyze the impact paths and mechanisms of urbanization on residents’ dairy consumption, and find that income growth, employment structure transition and the rise of modern markets are three significant mediators. Additionally, we divide the samples into community groups with different urbanization levels and groups from different regions to explore the heterogeneity. Last, we use the percentile bootstrap method to check the robustness of the models and instrumental variable method to avoid potential endogeneity problems.The remaining contexts are organized as follows: Section 2 reviews relevant literature and introduces the study area and proposes the research hypotheses. Section 3 introduces the data and models used in this study. Section 4 conducts the empirical analysis, including the regression of the baseline models, heterogeneity analysis, robustness test and potential endogeneity solving. Section 5 provides the conclusions, discussions and directions for future works.According to extant literature, urbanization mainly affects residents’ dairy consumption through three paths: income growth, employment structure transition, and the rise of modern markets.In most of the studies on dairy consumption, income is found to be an important factor ,10–15,18Keynes’s consumption theory believes that people’s consumption is a function of income level. The increase in income will directly enhance residents’ food consumption capacity  and reduAccordingly, the improvement of urbanization promotes residents’ income levels, and income growth further promotes residents’ consumption of dairy products. Therefore, we consider income growth as an important mediation effect.In the process of urbanization and economic development, populations transfer at both spatial and industrial levels. In addition to the increase in urban population, residents’ employment structure gradually shifts from agricultural sectors See , which mAccordingly, the increase of urbanization level reduces the participation rate in agricultural sectors, and the reduction of manual labors in agriculture sectors, in turn, boosts residents’ demand for dairy products. Therefore, we consider employment structure transition as an important mediation effect.The process of population gathering in cities also promotes the continuous concentration of retail terminals in cities. Convenient consumption channels will promote the purchase and consumption of dairy products in cities with high urbanization and development level.In 2011, the total number of chain retail stores in China was 195.8 thousand, approximately tenfold that of the late 1990s, and the 1990s and beginning of the 21st century were periods of rapid urbanization in China See . Areas wAccordingly, the process of urbanization promotes the rise of modern markets, and the development of retail network system further helps promote residents’ dairy consumption. Therefore, we consider employment structure transition as an important mediation effect.Based on the above analysis, this study proposes the following hypotheses:H1: Income growth plays a mediating role in the impact of urbanization on residents’ dairy consumption. Specifically, the improvement of urbanization promotes residents’ income levels, and income growth further promotes residents’ consumption of dairy products.H2: Employment structure transition plays a mediating role in the impact of urbanization on residents’ dairy consumption. Specifically, the improvement of urbanization reduces the participation rate in agricultural sectors, and the transition of employment structure boosts residents’ demand for dairy products.H3: The rise of modern markets plays a mediating role in the impact of urbanization on residents’ dairy consumption. Specifically, the improvement of urbanization promotes the rise of modern markets, and the rise of modern markets further promotes residents’ dairy consumption.The relationships and influence paths between the variables in the hypotheses are depicted in The data used in this study are obtained from the China Health and Nutrition Survey (CHNS). The samples in the CHNS comprise populations from provinces in the east, northeast, central and west regions of China, which vary substantially in geography, economic development, public resources, and health indicators; thus, it is nationally representative. For the sample, we select the full period data of 1989, 1991, 1993, 1997, 2000, 2004, 2006, 2009 and 2011. The year 2015 is omitted because the data from the diet survey, which is the important source for our dependent variable, has not been released to the public. All variables in this study are obtained from community-level data or have been aggregated to the community level.The dependent variable is the residents’ average daily consumption of dairy products. The CHNS nutrition surveys include the household food survey and the individual diet survey. Both surveys are conducted on three randomly chosen consecutive days of a week at the same time. The household food survey adopts the food inventory method, that is, it records the daily purchasing amount and discarding amount of each food item and the number of people dining in the household in detail. The daily consumption of each food item per person is calculated from the changes in food inventory. Differently, the individual diet survey adopts the 24-hour Dietary Recall. This method requires the respondent to recall the food type, quantity, eating time, dining place, and preparation method within the last 24 hours. Compared with the individual diet survey, the household food survey might be biased if there are guests eating at respondent’s home during the survey period; furthermore, the household food survey does not consider the cases of dining out. However, with the development of the economy and the increase of residents’ income, dining out has become increasingly frequent for Chinese residents. Therefore, to obtain more precise consumption data, we finally choose the dataset from the individual diet survey based on the 24-hour Dietary Recall.China Food Composition. The data of 1989, 1991 and 1993 refers to the edition published in 1989; the data of 1997 and 2000 refers to the edition published in 1993; the data of 2004, 2006, 2009 and 2011 refers to the edition published in 2004. We calculate the average consumption amount of each person per day during the three survey days, and then aggregate to the community-level. The units from different years are unified to grams (g).To identify the dairy products in the CHNS individual diet survey, we refer to the book hukou i in the total community population. The individuals who have been abroad, moved out to other cities or lived in the local community for less than six months each year are not considered in the calculation.The key independent variable in this study is the urbanization level. For the purposes of this study, it is calculated as the proportion of permanent residents with urban Based on the literature review, this study selects three mediating variables to explore the ways in which urbanization affects residents’ dairy consumption: income level, employment structure and the rise of modern markets. In this study, Income level is the per capita annual net income at the community level in logarithmic form. Employment structure is defined as the proportion of people engaged in the agriculture sector among the total labor force. We employ the market component scores provided by the CHNS, which considers the types of markets available, distance to the markets in or near the local community, and number of days these markets are open, to evaluate the local development of modern markets in each community . The higThis study selects the purchasing power, production value of cow products, proportion of the elderly and children among the total population, education level, and 2008 milk scandal as the control variables.Purchasing power significantly affects residents’ consumption expectations for food . The decIt is difficult to obtain the dairy output data for each community from the CHNS survey. Instead, we consider the total value of the products produced from the third livestock type .The increase in the number of elderly people and young children might enhance the demand for dairy products. In this study, the proportion of the elderly and children is calculated by measuring the proportion of residents in community who are older than 65 years and younger than 6 years.The improvement of education level will improve residents’ cognition and consumption preferences for dairy products. In this study, we calculate the residents’ average years of education for each community.Food safety incidents, such as the melamine incident that occurred in 2008, have a direct inhibitory effect on the consumption of dairy products. Therefore, a dummy variable “milk scandal” is added to the control, for which the years before and after 2008 are coded as 0 and 1, respectively.Qit is the average amount of dairy products consumed per person per day in community i in year t, URit is the proportion of permanent residents with urban hukou in the total population of community i in year t, Contrkit are k controlled variables, Yeart is the time effect, and εit is the random disturbance term.First, we construct the following model:Mit are m mediating variables , and Contrkit are the same controlled variables as in Model 1.Additionally, the following models on mediators are used to construct the whole mediating effect model:α1 is significant, there is a mediating effect; otherwise, there is a suppressing effect because different mediators may have opposite effects. Second, the key independent variable, urbanization level, is regressed on three mediating variables: income level, employment structure and the rise of modern markets (Model 2). Third, the three mediating variables, key independent variable and control variables are added to the whole regression (Model 3). If the coefficients of both βm1 and γm2 are significant, the indirect effect is significant, and the analysis proceeds to step 5; if at least one of the coefficients is not significant, the analysis proceeds to Step 4. Fourth, the bootstrap method needs to be used to test whether the interaction term (βm1γm2) is significant. If the interaction term is significant, the indirect effect is significant, and the analysis proceeds to step 5; whereas if it is not significant, the analysis is terminated at this step. Fifth, the coefficient of urbanization level γm1 in Model 3 is tested. If γm1 is significant, the direct effect is significant, and the analysis proceeds to the final step. If γm1 is not significant, then no direct effect exists, indicating that there is only a mediating effect. Lastly, the signs of the interaction term βm1γm2 and coefficient γm1 are compared: if the signs are the same, there is a complementary mediating effect; if the signs are different, there is a competitive effect. This procedure is proposed by Zhao et al. (2010), which is improved on the basis of Baron-Kenny procedure and considers the bootstrap test as a supplement reference.The procedure for testing the mediating effect is as follows ,32: Firsα1), is positive but insignificant. From the literature discussion above, the increase in income level and transition in employment structure may have opposite effects on dairy consumption, so the insignificance of the coefficient is reasonable. This indicates that the increase in urbanization rate is related to an increase in residents’ dairy consumption, but the specific impact mechanism needs to be further explored.The empirical analysis is mainly using the statistical software Stata version 14.0. First, we start from the Model 1. This model is used to examine the direct effect of urbanization level on residents’ dairy consumption. In addition to the time fixed effect, we include the province as a fixed effect to control the provincial effect. The empirical results of Model 1 are presented in Column 1 of β11, β21, β31) are significant. This indicates that the increase in urbanization rate is related to a significant increase in residents’ income level, decrease in agricultural engagement, and improvement in the local development of modern markets.Then, we further regress urbanization level on the three mediating variables: income level, employment structure and the rise of modern markets see . It can β11 and γ12, are both significantly positive, indicating that the development of urbanization enhances residents’ income levels, and the increase in income further promotes the consumption of dairy products. This implies that the “urbanization level–income level–residents’ dairy consumption” path is a significant effect path, and the mediating effect equals 3.83 (20.499×0.187). Similarly, the coefficients of the rise of modern markets, β31 and γ32, are both significantly positive, indicating that the “urbanization level–the rise of modern markets–residents’ dairy consumption” path is a significant effect path, and the mediating effect equals 4.39 (1.341×3.272). On the contrary, the coefficients of the employment structure, β21 and γ22, are both significantly negative, indicating that the increase of urbanization level reduces the participation rate in agricultural sectors, and the reduction of manual labors in agriculture sectors, in turn, boosts residents’ demand for dairy products. This implies that the “urbanization level–employment structure–residents’ dairy consumption” effect path is also significant, and the mediating effect equals 22.37 ((-30.726)×(-0.728)).Next, the mediating variables are added to the regression on residents’ dairy consumption. Columns 2–4 in γm1 in Model 3. γm1 decrease after the mediating variables are added to the model. Specifically, the coefficient γ21 decreases to a significant negative value with an opposite sign to β11γ12, indicating a competitive mediating effect for the “urbanization level–employment structure–residents’ dairy consumption” path. The coefficients γ11 and γ31 become insignificant, indicating an indirect-only mediation for the “urbanization level–income level–residents’ dairy consumption” path and the “urbanization level–the rise of modern markets–residents’ dairy consumption” paths.We proceed to check the coefficient Accordingly, the empirical analysis supports all the hypothesis put forward when considering the full-size sample.The impact of urbanization on residents’ dairy consumption and its effect mechanisms may differ between areas with different urbanization levels and between different geographic regions of China. To further explore the potential heterogeneity, we divide the samples into high-urbanization-level and low-urbanization-level community groups based on the average urbanization level, as well as community groups from eastern and midwestern regions, and then repeat the above process.th and 97.5th percentiles of sequence C are adopted to estimate the 95% confidence interval of the mediating effect. If the confidence interval does not contain the value 0, the mediating effect is significant; otherwise, it is not significant. We use the statistical software SPSS version 18.0 with the Process plug-in version 3.2 written by Andrew F. Hayes to complete the test.For the insignificant mediation path in regression, the bootstrap test is used to verify its mediation effect. The steps of the percentile bootstrap test are as follows ,34: FirsAs for the total indirect effect . To check the robustness of the models, we also add the three mediating variables simultaneously to the model in Model 3. The results show that the coefficients of income level and employment structure are still significant, but the coefficient of the rise of modern markets becomes insignificant  to further investigate the effect of urbanization on residents’ dairy consumption. We employ the housing condition score and the sanitation score for each community provided by CHNS as the instrumental variables. The housing condition score considers the electricity availability, the possession of indoor tap water and flush toilets, and natural gas usage. The sanitation score considers the proportion of households with treated water and prevalence of households without excreta present outside the home in the community. The two indexes are important indicators of urbanization level, but they are irrelevant with the dairy consumption. Therefore, the two indexes can be the instrumental variables for urbanization level.α1 of both instrumental variables is significantly positive, indicating that the increase in urbanization rate is related to a significant increase in residents’ dairy consumption. Moreover, the significance and signs of other model coefficients are basically consistent with the baseline models. Therefore, the core conclusions of this study still hold.This study uses income growth, employment structure transition, and the rise of modern markets as mediating variables, and data from the 1989–2011 CHNS to analyze the impact of urbanization on residents’ dairy consumption in China. The results indicate that urbanization has a significant effect on the promotion of residents’ dairy consumption. Primarily, income growth, employment structure transition and the rise of modern markets mediate the effects of urbanization on residents’ dairy consumption, and all these mediating variables play a positive role. However, the significance of the rise of modern markets is not robust, which can be explained by Chinese consumers’ consumption structure of dairy products. Further, this study explores the heterogeneity in areas with different urbanization levels and in different geographic regions. The results imply that the impact of urbanization on residents’ dairy consumption is larger in areas with high urbanization levels and in eastern regions than areas with low urbanization levels and in midwestern regions. Moreover, income growth is the main significant mediator in areas with low urbanization levels and in midwestern regions, employment structure transition is a significant mediator in areas with high urbanization levels and in all regions, and the rise of modern markets is also a significant mediator in areas with low urbanization levels.The findings of this study have practical implications for understanding the relationship between urbanization and residents’ food consumption and for further promoting residents’ dairy consumption and the development of China’s dairy industry. First, this study proves that the process of urbanization has a positive impact on residents’ dairy consumption, which indirectly verifies that urbanization will change residents’ food consumption patterns and even their health status. Therefore, to increase residents’ consumption of dairy products and improve their health, the Chinese government needs to promote the urbanization process. Second, from the perspective of the impact path and effect mechanism of urbanization on residents’ dairy consumption, we recommend focusing on improving residents’ income level, employment structure, and the development of modern markets to further increase the consumption level of dairy products. Third, in areas with low urbanization levels, more emphasis should be placed on increasing residents’ disposable income and the development of the retail network, to increase residents’ consumption capacity and accessibility to various dairy products. In areas with high urbanization levels, the government should focus more on improving employment structure to change residents’ consumption habits; this will help better promote residents’ consumption of dairy products. Last, encouraging the transfer of agricultural manual laborers to change their consumption habits is an effective way to increase residents’ dairy consumption in all regions.In this study, the historical consumption data of dairy products is not continuous, only updated to 2011, and the distribution of consumption data is uneven, which may affect the accuracy of the model establishment. In future work, we will consider using datasets with longer continuous time spans and wider geographical distribution to obtain accurate and precise results.S1 File(RAR)Click here for additional data file.


We aimed to determine the Echocardiographic and clinical parameters predicting AF in patients with a dual-chamber (DDD) pacemaker. This retrospective study included 208 patients with permanent pacemaker, classified according to development of AF during follow up into 2 groups: AF  and non AF , baseline: clinical, ECG(P-wave dispersion) and echo {diastolic wall strain (DWS),left arial volume index (LAVI), left ventricular stiffness index(LVSI)} data were assessed. AF group were older with more P wave dispersion, lesser DWS, greater LVSI& LAVI, LVSI at a cut off > 0.13 and DWS at a cut off < 0.34 were predictors of AF in patients with DDD pacemakers. LVSI and DWS could be used as simple good predictors for AF in patients with DDD pacemakers, for timely initiation of anticoagulants according to CHA Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia that increases with aging, associated with increased risk of morbidity and mortality. It may be associated with all types of cardiovascular disorders; no single mechanism is concerned with the development of AF. Its pathophysiology may involve a complex interplay of electrophysiologic factors and structural changes. Clinical entities, such as hypertension, heart failure, and coronary disease, through mechanisms such as myocardial stretch, fibrosis, disruption in cell-to-cell coupling, and autonomic dysfunction all may promote development of AF . Up to aPatients on implanted permanent pacemakers frequently develop atrial high-rate events (AHREs); defined as events with an atrial frequency of ≥ 180 bpm and a duration of ≥ 5 min (6 min exclude most episodes of over sensing), which is considered as clinically relevant according to current guidelines , ischemiAtrial-based pacing is as close as possible to a physiological pacing method; ventricular pacing is more non-physiological and causes cardiac mechanical dysynchrony. Higher atrial pacing rate by virtue of pacing alone may maintain uniform atrial rate and suppress premature atrial contractions, prevent short-long-short sequences and may prevent bradycardia-induced dispersion of atrial repolarization. Therefore it is conceivable to prevent AF virtually by pacing atria at high rates , 12.The present study aimed to determine the echocardiographic and clinical parameters predicting the occurrence of AF in patients with a dual-chamber (DDD) pacemaker, without previously documented AF and to detect the high risk groups vulnerable for AF.This retrospective study (obtained from data base from 2016 to 2021 in the electrophysiology unit) was performed in Cardiology department, Faculty of Medicine, Zagazig University Hospitals, included 208 consecutive patients who had dual-chamber (DDD) pacemaker for sinus node dysfunction (SND) or atrioventricular block (AVB), according to the indication guidelines. Patients were excluded from the study if they had: < 18 years old, no follow-up data/Echocardiographic findings, undergone cardiac surgery, prior clinical atrial tachyarrhythmia , significant valvular disease, decompensate renal or liver diseases, uncontrolled thyroid disorders, COPD or pulmonary diseases. the study has been approved by the local ethics committee.Group (A): patients who developed AF episodes on follow up .Group (B): patients without AF .They were classified according to development of AF during follow up into 2 groups:All patients subjected (at base line before pacemaker implantation) to the following:Complete history taking: concerning the basic demographic information including age, gender and risk factors to assess the CHA2DS2VASc score.Physical examination: Full general and local examination.Serum creatinine, creatinine clearance, HbA1C and Hb level., [12-lead electrocardiography (ECG) analysis for; heart rate, PR interval, P wave dispersion  for; left atrial volume (LAV) indexed to the BSA for the LAVI, left ventricular ejection fraction (LV EF) and LV mass index  by 2D- echo. The LV diameters were assessed using M-mode in the long axis left parasternal view. Mitral E and A wave velocities and E wave deceleration time were measured using pulsed wave Doppler. Tissue Doppler study for mitral (e') wave velocities  and E/e' ratio was calculated.LV stroke volume (SV) was measured; (LV end diastolic volume-LV end systolic volume) and indexed to BSA for SV index (SVI).Diastolic wall strain (DWS) estimated from the following equation: DWS = (PWs-PWd)/PWs; reported as a non-invasive direct measure of the LV compliance .LV stiffness index was measured using the following equation:This parameter provides an estimate of the pressure to volume relationship .The main demographic data of the study groups are in Table 2DS2VASc score among the studied cases was 1.59, AF group had higher score but not reach statistical significance (p = 0.09).Anticoagulants, BBs and diuretics were more used in AF group, the mean CHAP wave dispersion was higher in AF group compared to non AF , Table 2), E/é (12.19 ± 0.83 vs. 6.3 ± 0.98) and LVSI (0.14 ± 0.01vs. 0.06 ± 0.01 ml−1), p < 0.001, and a highly significant decrease in posterior wall thickness in systole (PWs); (12 ± 1.7 vs. 13.6 ± 1.2 mm), DWS (0.28 ± 0.08 vs. 0.38 ± 0.10), EDV(128.64 ± 5.59 vs. 154.81 ± 11.99 ml), SVI (43.43 ± 3.88 vs. 59.61 ± 9.12 ml/m2) and EF (57.78 ± 3.39 vs. 65.56 ± 6.1%), p < 0.001, Table AF group compared to non AF group; had a highly significant increase in LAVI , LAVI  and P wave dispersion and had significant − ve correlation with end diastolic volume (EDV), r = − 0.937, p < 0.001), SVI , EF  and DWS  among AF cases.DWS had significant –ve correlation with LAVI , P wave dispersion, and LVSI  and significant + ve correlation with age , EDV, SVI  and EF among AF group.Univariate analysis indicated that reduced DWS, EDV and SVI, older age, larger LAVI, higher P wave dispersion and increased LVSI were significant variables. On multivariable analysis, only the LVSI  and DWS  were independent predictors of AF occurrence in patients with dual chamber (DDD) pacemakers, Table ROC analysis showed that: DWS at a cut off value < 0.34 had a sensitivity of 80.5%, a specificity of 75.6%, NPV of 86.8%, PPV of 66% and an accuracy of 77.4%  in prediction of AF among the studied cases, Fig. In an aging patient population, it is frequently necessary to implant a permanent pacemaker. Current dual-chamber permanent pacemakers (PPMs) that incorporate atrial leads are able to detect and store occurrence of arrhythmia as AF , most ofThe link between echocardiographic parameters, clinical data of patients on permanent pacemakers and occurrence of AF need more extensive studies.LV diastolic wall strain (DWS) can identify a subgroup of subtle LV diastolic dysfunction, as low DWS indicates increased LV stiffness . LV stifIn this study we found an increase in the LV stiffness assessed by lower DWS and higher LV stiffness index in AF group, in agreement with many studies , 19–22; −1) had a higher risk to develop AF.We found that EDV and SVI had –ve correlation with LV stiffness index and + ve correlation with DWS, in agreement with Ngiam et al.  who stat2DS2-VASc score, in agreement with these findings, we found that patients in AF group had higher CHA2DS2-VASc score but not reached significance.Rovaris et al.  indicateOther parameters of LV diastolic dysfunction as E/é ratio was higher in the AF group in our study in agreement with H. Kishima et al. .2DS2-VASc score are essential for management of this group of patients.Asymptomatic AF delays clinical diagnosis, which can result in ischemic stroke or other embolic complications, so early detection of asymptomatic AF and timely initiation of anticoagulants according to the CHA2DS2-VASc score, for patients who develop asymptomatic AF to prevent thromboembolic events and decrease ischemic stroke burden.High LV stiffness index at a cut off value > 0.13 and Low DWS at a cut off value < 0.34 could be used as simple good predictors for development of AF in patients with dual chamber (DDD) pacemaker implantations, for timely initiation of anticoagulant therapy according to CHAThis is a retrospective study only from the same geographic area and from a single medical center  with a small number of patient subgroups, cases of cardiac resynchronization therapy (CRT) or ICD implantation were excluded and, thus, the AF detection rate may be underestimated, with lake of information about the incidence of stroke, systemic embolism, heart failure, acute myocardial infarction, and other cardiovascular and cerebrovascular events within the period of pacemaker implantation, in many of our cases the echo report/measurements obtained from the data base.2DS2-VASc score need oral anticoagulation to prevent thromboembolic events and decrease burden of ischemic stroke as the incidence of subclinical AF is high in this patient population. On follow up of pacemaker, once AHRE occurs, 24-h Holter should be carried out for early AF detection and treatment. Time lapse between pacemaker implantation and development of AF, body mass index and presence of coronary artery disease or if any of AV block events that may be driven by underlying CAD/ACS can improve the results and so the novel markers such as LV/LA strain.LV stiffness index and DWS are simple useful predictors of AF in patients with DDD pacemaker. Our findings may provide additional diagnostic information for the other diagnostic parameters. In our opinions patients with pacemakers detected AHREs, low DWS, high LV stiffness index and high CHA


Takotsubo cardiomyopathy (TCM) is regarded as an acute and often reversible cardiac syndrome characterised by apical ballooning of the left ventricle that occurs in the absence of coronary artery obstruction and myocarditis. The underlying pathophysiology remains largely unknown, but the most widely accepted theory is catecholamine toxicity.More recently, atypical variants of TCM have been described, and are characterised by the regional wall motion abnormalities that are observed. Mid-ventricular Takotsubo cardiomyopathy (MVTCM) is characterised by hypokinesia/akinesia of the mid left ventricular wall segments with hyperdynamic basal and apical function. This report describes the first documented case of a patient who developed MVTCM after receiving a dose of intravenous adrenaline. This case provides further evidence to support the notion that catecholamine toxicity is implicated in the pathogenesis of TCM. Classically, Takotsubo cardiomyopathy (TCM) is regarded as an acute and often reversible cardiac syndrome characterised by apical ballooning of the left ventricle. It often occurs as a result of intense emotional or physical stress, and hence is commonly referred to as stress cardiomyopathy or ‘broken heart syndrome’. The underlying pathophysiology remains largely unknown, but various theories have been proposed such as coronary artery spasm and coronary microvascular disease; but the most widely accepted theory is catecholamine toxicity . A diagnA young lady who was 39 weeks pregnant developed post-partum haemorrhage following a vaginal delivery. She was immediately transfused with 4 units of cross-matched blood. During this period, a venous blood gas demonstrated a low serum calcium. The anaesthetist attempted to replace this with intravenous calcium gluconate but accidentally drew up and administered a bolus of intravenous adrenaline. Immediately following this, the patient had a cardiac arrest. The initial rhythm was ventricular fibrillation, and following a single direct current cardioversion shock converted to pulseless electrical activity. Return of spontaneous circulation was achieved after 4 cycles of cardiopulmonary resuscitation. The patient was then transferred to intensive care where endotracheal ventilation continued and the patient received haemodynamic support with noradrenaline and dobutamine.Initial blood tests demonstrated a troponin-T 6261 ng/L, which then decreased to 3784 ng/L 24 h later. All remaining routine biochemistry and haematological blood results were unremarkable. A resting 12-lead electrocardiogram showed a sinus tachycardia with no ischaemic changes and a normal QTc. A bedside transthoracic echocardiogram demonstrated a dilated left ventricular cavity with moderately impaired systolic function . The mid-left ventricular segments were akinetic, while the basal and apical segments were hyperdynamic . There were elevated native-T1 and T2 mapping signals seen in the mid left ventricular segments, consistent with myocardial oedema, but there was no late gadolinium enhancement to indicate infarction, scar or fibrosis Fig. . The patA follow-up cardiac magnetic resonance imaging scan 3 months later demonstrated complete recovery of her left ventricular systolic function. There were no regional wall motion abnormalities, and on tissue characterisation native-T1 and T2 values returned to within normal limits, and there was no late gadolinium enhancement.The clinical history of accidental adrenaline administration, troponin rise, transient moderate left ventricular systolic impairment and myocardial oedema in the mid segments is consistent with a diagnosis of MVTCM.TCM accounts for 1–2% of patients who present to hospital with an acute coronary syndrome; and hence the initial diagnosis and subsequent treatment of these patients can be challenging. MVTCM is the second most common form of TCM, and accounts for roughly 15% of cases; compared to the far more common conventional apical TCM, which accounts for 82% of cases. The majority of patients present with chest pain, while the second most common presenting complaint is shortness of breath. MVTCM is far more common in women, the majority of whom are postmenopausal. Initial investigations usually reveal raised cardiac enzymes, and the resting electrocardiogram may demonstrate ST-changes, while the QTc can be markedly prolonged .The underlying triggers for MVTCM are reported to be similar to those for conventional apical TCM, with many patients presenting after significant emotional or physical stress. However, in over one quarter of patients, a trigger is often not identified . The aboIn order to exclude acute coronary syndrome and confirm a diagnosis of TCM, patients previously required an invasive coronary angiogram as part of their work up; however, the more recent emergence of advanced cardiac imaging techniques has resulted in clinicians combining the clinical history with cardiac imaging to establish a diagnosis, rather than proceeding straight to an invasive angiogram. Cardiac magnetic resonance imaging has emerged as a first line diagnostic tool in suspected cases of TCM, and was utilised in the case described. The use of steady state-free precession cine imaging is used to identify regional wall motion abnormalities, while black-blood T2-weighted triple inversion recovery can be used to identify myocardial oedema, and 2D inversion-recovery gradient echo 5 − 10 min after gadolinium contrast administration is utilised to identify areas of myocardial necrosis. Typically, T2-weighted imaging reveals circumferential transmural myocardial oedema matching the regional wall motion abnormalities .Early cardiac magnetic resonance imaging studies suggested that the lack of late gadolinium enhancement was necessary to diagnose TCM, as its presence would suggest irreversible myocardial necrosis caused by an alternative underlying disease process. It was previously thought that the presence of late gadolinium enhancement could help differentiate acute myocardial infarction and myocarditis from TCM . HoweverOften, a diagnosis can be established following a multiparametric approach that utilises either cardiac magnetic resonance imaging or a combination of transthoracic echocardiography and an invasive coronary angiogram. Rarely, there are cases where there is diagnostic uncertainty following the above investigations, and once ischaemia has been excluded through coronary angiography, an endomyocardial biopsy may be required to differentiate between TCM and myocarditis. Endomyocardial biopsy is likely to demonstrate features consistent with a myopathic process such as myocyte hypertrophy with enlarged nuclei and nucleoli . In ordeManagement of TCM is predominantly supportive. There is ongoing debate amongst cardiologists regarding the use of conventional heart failure medications such as beta-blocker and angiotensin converter enzyme inhibitors in this cohort of patients, but at present there is no concrete evidence to suggest that their use is beneficial . In a laAlthough TCM and its variants are regarded as reversible cardiomyopathies, patients are still at a significant risk of morbidity and mortality. Complications include left ventricular thrombus formation, ischaemic stroke, ventricular tachycardia and cardiogenic shock, such as in the case outlined above , 11. ThiIn summary, this case describes a patient who developed MVTCM following an intravenous adrenaline bolus. This is the first case of iatrogenic MVTCM, and provides further evidence to support the notion that catecholamine toxicity is implicated in the pathogenesis of TCM. The combination of a clear precipitant and characteristic cardiac magnetic resonance imaging findings meant that a diagnosis could be established without the need for an invasive coronary angiogram; and serial imaging confirmed complete recovery of the left ventricular systolic function. Lastly, although patients with MVTCM often have a good prognosis, clinicians must be mindful that complications can occur, and cardiogenic shock should be treated with prompt initiation of inotropes.


Body auscultation is a frequent clinical diagnostic procedure used to diagnose heart problems. The key advantage of this clinical method is that it provides a cheap and effective solution that enables medical professionals to interpret heart sounds for the diagnosis of cardiac diseases. Signal processing can quantify the distribution of amplitude and frequency content for diagnostic purposes. In this experiment, the use of signal processing and wavelet analysis in screening cardiac disorders provided enough evidence to distinguish between the heart sounds of a healthy and unhealthy heart. Real-time data was collected using an IoT device, and the noise was reduced using the REES52 sensor. It was found that mean frequency is sufficiently discriminatory to distinguish between a healthy and unhealthy heart, according to features derived from signal amplitude distribution in the time and frequency domain analysis. The results of the present study indicate the adequate discrimination between the characteristics of heart sounds for automatic detection of cardiac problems by signal processing from normal and abnormal heart sounds. Heart auscultation is a technique used to evaluate the sound wave generated by the heart's mechanical motion . This isThe heart sounds can have indicators of the current disorders or warnings about any forthcoming disorder. The indicators can be present randomly throughout the signal if they may be occurring all the time. This type of nonlinearity of heart sounds can be presented using a discrete wavelet transform (DWT). The digital recording of the heart sound that is generated with an electronic stethoscope is called PCG . The tecOne of the leading causes of death across the world is cardiac disease . It has The significant contribution of this paper is finding out a way to differentiate between normal and abnormal hearts for automated screening of cardiac disorders. Various domains were studied in order to comprehend and analyze the variations in heart sound. This work is aimed at isolating cardiac and pulmonary sounds. Modulation filters are added to the time-frequency representation of the initial signal reported in the chest. Then, an iterative wavelet decomposition and reconstruction filter algorithm are applied. The lung signals are taken as noise, and all signals are segregated. Then, the signal-to-noise ratio is determined.The people from rural areas who have no immediate access to any medical care can be benefited from this study. Body auscultation is the basic diagnostic process held by an expert. But in rural areas, there is a scarcity of expert doctors. In that case, this study titled “Wavelet and Spectral Analysis of Normal and Abnormal Heart Sound for Diagnosing Cardiac Disorders” came into action. We can follow the working overview of the proposed system given in The paper is organized as follows: Introduction is described in Previous literature provides us with some insights into the research areas associated with the early detection of heart failures. Automatic heart sound categorization is a potential study area that is now being explored using signal analysis and artificial intelligence techniques. Auscultation of the heartbeat is still inadequate for diagnosing some cardiac diseases . It doesThe PCG audio recordings of patients were used to expert chronic heart failure (CHF) by Gjoreski et al. . The resBased on wavelet analysis as well as random forest identifier, Qiao et al.  introducSome of the key challenges in the classification of heart sound are the segmentation of sounds, creating the distinction between heart and lung sound, and the time shift changes of wavelet transformation. The heart sound segmentation algorithm was used usually, but Das et al.  proposedLi et al.  proposedThe heart is one of the most vital organs, and sustaining life is dependent on its ability to beat in a rhythm. Mondal et al.  proposedThe available algorithms and the experimental data are in a positive direction. Therefore, there is more scope for development in the direction of creating effective models for heart sound-based automated cardiac illness detection. Several methodologies and techniques used by authors prove that there are significant methods that can be employed to find the heart sound across various age groups. This results in early detection and regular monitoring. Some of the techniques included machine learning, deep learning, wavelet analysis, and analysis of PCG signals. However, the limitation that is existent in almost all papers included the challenger of differentiation between heart and lung sound. The differentiation between a healthy heart and an unhealthy heart is done through some parameters. This suggests that there is a gap in the previous literature in examining and differentiating between heart and lung sounds.In this section, the required steps are described to construct the device to collect real-time data. The main component of the circuit stethoscope has been used in this work, and it is essential to collect generated data from the heart. The stethoscope has chest parts in the form of rods that are used shown in  to listeThe total phenomenon has been shown in the block diagram given in After successfully assembling and constructing the circuit, it is programmed to operate and collect data from the heart. The auscultation that is done with an electronic stethoscope is a cost-effective method. The characteristics of the heart sounds on various domains can be explored using this device to identify more differences between healthy hearts and cardiac patients. This paper proved an analysis of heart sounds using various parameter analyses for the automated detection and screening of cardiac disorders. We collected real heart sound data from both medically fit and unfit people. By doing some spectral analysis, we come to a conclusion that there are several differences in feature between healthy and unhealthy sounds.(1)24-year-old man, no symptoms, Autism Spectrum Disorder (ASD). Upon examination, the pulses are normal, and the heart's activity is maximum and maybe slightly elevated towards the left sternal border. Observed the left top sternal margin23-year-old man, asymptomatic, Patent Ductus Arteriosus (PDA). The examination results in noticeably elevated radial and femoral pulses as well as a significantly elevated heart rate. The heart activity was also slightly raised. Observed the left top sternal marginAortic stenosis, regurgitation, and an elevated heart rate and irregular pulses in a 20-years-old patient. He seems worn out and ill. No prior symptoms, normal historical development in terms of growthAbnormal sounds(2)23-year-old girl, no symptoms, and in good condition, regular medical examination and regular heartbeat and pulse. Used the stethoscope's diaphragm to listen at the left upper sternal border20-year-old male. No symptoms, standard physical examination, regular bodily habits, normal heartbeat and pulse, and attended to all four regions. Due to microphone noise on the skin, there are a few crackles; listened to the recurrent noisesBoy, 19, without symptoms. Routine medical examination of cardiac impulse and pulse that are normal. Listened to the upper left sternal boundaryNormal soundsThere are accurate live audio recordings of normal and abnormal heart sounds for finding out the relation of healthy and unhealthy heart sounds to make common cardiac diagnoses. Unhealthiness means abnormal heart rhythms (arrhythmia), heart muscle disorders (cardiomyopathy), congenital defects (problems with the formation of the heart and blood vessels that are present from birth), atrial fibrillation, sick sinus syndrome, sinus tachycardia, heart block, heart failure, etc. If any of these problems happens, then the patient's heart sound becomes weak which leads to a decrease in amplitude than a person who is totally free of those diseases. Description of some of the healthy and unhealthy patients from whom we took our heart sound signals is as follows:The comparison of healthy and unhealthy person's heart sound is shown in Result and Discussion. There are clear findings that a healthy person's heart sound is always greater in amplitude, variance, and energy than that of an unhealthy person. It is understandable that if amplitude is greater, then a healthy man's mean value will also be greater. And these mean, variance, and energy are differentiating criteria between healthy and unhealthy people.Figures Soft thresholding is used here so that our information does not get cut out unexpectedly. Only the noise signal will be cut out from the original heart sound. Different level of thresholding explains throughout the steps of noise removal from the signal. It is the second phase of noise removal as the first phase of noise removal was done by REES52.Signal: two different signals are found from healthy and unhealthy subjects. They differ in amplitude and frequency. Healthy signals show much higher amplitude than unhealthy heart signalsSpectrogram: healthy heart sound shows higher magnitude with constant variation in magnitude as time progresses. On the other hand, unhealthy subjects are more consistent with magnitude and small in valueNormal distribution: according to the normal distribution, data that are close to the mean happen more commonly than data that are far from the mean. Symmetric with respect to the meanDetailed coefficient (cD): denoising of collected heart signals is done so that analysis of heart sound is accurate and efficient. Symlet wavelet levels 1 to 4 are being used here. Healthy and unhealthy heart sounds showed a difference in character and were easy to differentiate between themApproximation coefficient (cA): noise-free signal wavelet levels are much more accurate than noisy signal symlet levels. Healthy and unhealthy signals present different characteristics even after being denoised. So, we can count the approximation coefficient of heart sound also as a differentiating factor between healthy and unhealthy peopleSo, we came to the conclusion that healthy and unhealthy sound signals show different characteristics and there are enough parameters to differentiate between them. It encourages us to analyze further to extract many more differences between them. We found some factors to differentiate between them as follows:The threshold level is found about 0.07-0.09 to differentiate between them. If a signal poses a higher mean value of 0.09, then it is healthy; if it is less than 0.07, the person is unhealthy.If the variance of a heart sound is above 0.015, it is healthy. On the other hand, if the variance value is less than 0.01, it will be tagged as unhealthy.i=1n(x)2/n. Here, n = no.of heart sample. x = signal amplitude. We found the threshold value of 2e − 08 to 0.5e − 05 for differentiating between them. Unhealthy samples' energy is much lower than the energy of healthy samples. So, this energy is being counted as a differentiating factor between healthy and unhealthy samples of the heart sound. If a signal has more than 0.5e − 05 value, then the person is healthy, and if it is less than 2e − 08, the person is unhealthy.The energy of discrete wavelet transform coefficient is derived by the simple equation of energy, energy = ∑The wavelet domain was studied to understand and interpret the variations in heart sound. The characteristics of the heart vibrations are analyzed using the signal and discrete wavelet transform analysis. In this section, real-time data collected by the proposed device will be presented with appropriate figures. Real data was found through a stethoscope with some electronic devices. Body auscultation is one of the most important clinical testing methods for the examination of cardiac disorders. This medicinal approach is inexpensive and efficient and allows trained physicians to recognize and analyze the sound of the heart for diagnosis. But in the rural areas of Bangladesh, there is a scarcity of medical experts who can give a proper interpretation of heart sounds. To overcome this obstacle, the stethoscope heart sound was converted into an electrical signal via a condenser microphone and then PLX-DAQ tools. PLX-DAQ converted serial monitor data of Arduino into Excel data file. Matlab interpreted the sound to signal. The denoised signal was then plotted, and a comparison of the normal heart sound with abnormal heart sound was conducted. Using the visual comparison, the decision on whether a person is healthy or unhealthy was taken by simply collecting his heart sound.Quadratic time-frequency analysis methods produce spectrograms, which are 2D matrices. Figures The probability distribution of heart sounds recorded from a healthy and unhealthy subject with normal distribution predicts the probability of subjects being healthy or unhealthy. Figures The detailed coefficient for healthy and unhealthy subjects: Figures 11Wavelet family Sym4 is used here. Approximation coefficient of a healthy and unhealthy subject: Figures 17Additionally, the variations in levels before and after denoising are visible. Compared to noisy signal symlet levels, noise-free signal wavelet levels are substantially more accurate.After being denoised, good and sick signals exhibit different features. The heart sounds are converted from the spatial domain here to the wavelet domain in the suggested wavelet analysis to obtain more noticeable characteristics. The wavelet initial level decomposition of the heart sound was performed using the symlet filter. The heart sound signal is separated into approximate and precise coefficients using a wavelet. A single number has been computed as a characteristic feature because the range of the amplitude dispersion of the signal in the time and wavelet domain exhibits discriminating behavior for screening of heart diseases. The value of energy of wavelet coefficients can be able to distinguish between healthy and unhealthy heart sounds because the range of amplitude is varied.Therefore, the mean, variance, and energy value of the heart sound signal's wavelet coefficients are taken into account when determining a person's level of health.i=1n(x)2/n. Here, n = no.of heart sample. x = signal amplitude. We plot the energy for each healthy and unhealthy sample in Figures e − 08 to 0.5e − 05 for differentiating between them. Threshold values of variance, absolute mean, and energy of DWT for differentiating normal and abnormal signals have been shown in Figures Body auscultation is now a key and useful human health assessment clinical diagnostic procedure. For automated detection of cardiac diseases, this study introduced heart sound analysis for differentiation of heart sounds collected from normal and abnormal subjects using an IoT device. Features derived from signal amplitude distribution in the time domain and frequency domain analysis reveal that mean frequency is discriminatory enough to distinguish normal and abnormal hearts. The experiment's findings indicate adequate heart sound characteristic differentiation for automated cardiac issue screening employing signal processing from healthy/unhealthy heart sounds. The mean threshold level is found about 0.06-0.09. Above the threshold value is the healthy subject, and below the threshold value is the unhealthy subject. To derive discriminatory features from wavelet heart sound coefficients, the heart sound signal was converted into the wavelet domain.An advanced IoT-based system can be improved so that the data collected from far areas can easily be transferred to the server to do the analysis. Then, update information about the health condition could be supplied to a person. If we find any abnormality, we can check it earlier before it gets worse. Many transform techniques can be used for further extraction of different features in the biomedical field. Artificial intelligence can be used in this sector for better output and discriminatory features. Machine learning can also be used for the accurate diagnosis of cardiac diseases from heart sounds.