Cardiac auscultation is one of the most cost-effective techniques used to detect and identify many heart conditions. Computer-assisted decision systems based on auscultation can support physicians in their decisions. Unfortunately, the application of such systems in clinical trials is still minimal since most of them only aim to detect the presence of extra or abnormal waves in the phonocardiogram signal, i.e., only a binary ground truth variable  is provided. This is mainly due to the lack of large publicly available datasets, where a more detailed description of such abnormal waves  exists. To pave the way to more effective research on healthcare recommendation systems based on auscultation, our team has prepared the currently largest pediatric heart sound dataset. A total of 5282 recordings have been collected from the four main auscultation locations of 1568 patients, in the process, 215780 heart sounds have been manually annotated. Furthermore, and for the first time, each cardiac murmur has been manually annotated by an expert annotator according to its timing, shape, pitch, grading, and quality. In addition, the auscultation locations where the murmur is present were identified as well as the auscultation location where the murmur is detected more intensively. Such detailed description for a relatively large number of heart sounds may pave the way for new machine learning algorithms with a real-world application for the detection and analysis of murmur waves for diagnostic purposes. I.CARDIOVASCULAR disease (CVD) is an umbrella term used to define a heterogeneous group of disorders of the heart and vessels, such as coronary artery disease (CAD), valvular heart disease (VHD), or congenital heart disease (CHD) . As a whThe majority of the populations in under-developed and developing countries do not have access to an integrated primary healthcare system, as a result diagnosis and treatment of CVD can be delayed, thus potentially leading to early deaths. Furthermore and according to , CVD conCurrently available annotated public PCG datasets have limited scope such that they either provide limited information regarding a general evaluation of the heart sound  , or the The hereby presented dataset aims to address these limitations, thus providing the necessary means to develop novel computer-assisted decision systems, which are able to offer a rich characterization of heart sound anomalies. This is accomplished by collecting a large set of sounds and characterizing them using the same scales and parameters commonly used in clinical practice. The presented dataset was collected during two independent cardiac screening campaigns in the Pernambuco state, Brazil. These campaigns were organized to screen a large pediatric population in Northeast Brazil and to provide the basis for the further development of a telemedicine network , 17]..17].The gathered dataset includes the characterization of each murmur in the recorded heart sounds from different perspectives, including timing, pitch, grading, shape and quality. Moreover, multi-auscultation location recordings are provided for each patient, alongside with the corresponding annotations, which are helpful for inferring the specific source of each murmur .The remainder of this paper is organized as follows. In II.A.Aortic valve (1): second intercostal space, right sternal border;Pulmonary valve (2): second intercostal space, left sternal border;Tricuspid valve (3): left lower sternal border;Mitral valve (4): fifth intercostal space, midclavicular line (cardiac apex).Normal heart sounds are primarily generated from the vibrations of cardiac valves as they open and close during each cardiac cycle and the turbulence of the blood into the arteries. The anatomical position of heart valves relative to the chest wall defines the optimal auscultation position; as such, a stethoscope should be placed at the following positions , for ausBlood flowing through these structures creates audible sounds, which are more significant when the flow is more turbulent . The firB.Apart from S1 and S2, additional heart sounds resulting from a turbulent blood flow and rapid movements  of cardiac structures, and are often associated with murmurs, “clicks” and “snaps” . Most ca1)Aortic stenosis is a narrowing of the aortic valve and often as a result of valve calcification. Furthermore, aging, chronic RHD or a congenital bicuspid aortic valve are some risk factors. During auscultation, Aortic stenosis generates a harsh crescendo-decrescendo systolic murmur heard best at the right upper sternal border (RUSB), with murmur radiating to the carotid arteries .2)Aortic regurgitation results from an inefficient Aortic valve closure, allowing the blood to flow back into the right ventricle in a turbulent manner, usually due to aortic root dilation, bicuspid aortic valve, and calcified leaflets. During auscultation, Aortic regurgitation generates a decrescendo-blowing diastolic murmur, heard best at the left lower sternal border (LLSB) .3)Mitral stenosis is a narrowing of the mitral valve, making blood passing from the left atrium to the left ventricle more difficult. It is often due to chronic RHD and infective endocarditis. During auscultation, Mitral stenosis generates a diastolic murmur, best heard at the apex .4)Mitral regurgitation allows the blood to flow back to the left atrium. This is mainly due to defective closure of the leaflets or rupture of the chordae tendineae in patients with infective endocarditis, chronic RHD disease, degenerative valve disease, or myocardial infarction. In auscultation, Mitral regurgitation results in a systolic murmur, best heard at the apex, with radiation to the left axilla .5)Mitral valve prolapse is characterized by a bulge of the leaflets into the left atrium, stopping the valve to close evenly. It can be explained by idiopathic myxomatous valve degeneration, RHD, endocarditis, and Ebstein’s anomaly. In auscultation, Mitral valve prolapse causes an early systolic click heard best at the apex, it is often followed by a late systolic murmur .6)Pulmonary stenosis is a narrowing in the pulmonary valve. It is often present in patients with Tetralogy of Fallot, although it may also be present in patients with chronic RHD, congenital rubella syndrome, or Noonan syndrome. Its auscultation is described as a crescendo-decrescendo systolic ejection murmur, heard loudest at the upper left sternal border (LUSB) .7)The tricuspid stenosis is a narrowing in the Triscupid valve. It is often due to intravenous drugs used in infective endocarditis and in carcinoid syndrome treatments. In auscultation, Tricuspid stenosis results in a diastolic murmur, best heard at the LLSB .8)Tricuspid regurgitation is usually caused by vegetative growth under the leaflets, causing it to degenerate and rendering them incompetent, allowing blood to flow back to the right atrium. It is often explained by infective endocarditis and carcinoid syndrome. Its auscultation, Tricuspid regurgitation is described as a systolic murmur best heard at the LLSB .9)Septal defects are congenital in nature and are defined as “ruptures” or “discontinuities” in the interatrial septum  or in the interventricular septum , allowing the blood to freely flow between them and mix. The auscultation of the atrial septal usually presents as a loud and a wide S1, fixed split S2 heart sound, loudest at the LUSB. Ventricular septal defects often generates a holosystolic murmur, best heard at the apex. Smaller defects are louder and have a harsher quality while large ones are quieter but more symptomatic. Therefore, atrial and ventricular septal defects in children can produce progressively louder murmurs as they close .10)Hypertrophic obstructive cardiomyopathy is an inherited myocardial disease in which the myocardium undergoes hypertrophic changes. During auscultation, hypertrophic obstructive cardiomyopathy presents a systolic ejection murmur, heard best between the apex and the left sternal border (LSB) and becoming louder with Valsalva or abrupt standing maneuvers .11)In patent ductus arteriosus, a channel fails to close after birth, establishing a shunt that allows oxygenated blood from the aorta to flow back to the lungs via the pulmonary artery. Its auscultation is described as a continuous “machine-like” murmur, loudest at the LUSB .III.In this section, we briefly present heart sound datasets that are open to the scientific community. We consider datasets that satisfy the following criteria: a) full availability of data for scrutiny; b) online accessibility; c) relevance to the current study; d) include relevant information regarding the study population ; and e) include relevant information regarding the audio recordings . With these criteria, we selected six datasets that will form the basis of our analysis. A summary of the selected datasets are presented in A.This database comprises of two datasets. Dataset A was collected from an unreported size population, through a smartphone application. Dataset B was gathered using a digital stethoscope system deployed in the Maternal and Fetal Cardiology Unit at Real Hospital Português (RHP) in Recife, Brazil. It contains a total of 656 heart sound recordings from an unknown number of patients. The duration of the PCG signals range from 1 to 30 seconds and were collected at a sampling rate of 4000 Hz. The sounds were obtained from the apex point of volunteer subjects in the Dataset A. In the Dataset B, sounds were collected from four cardiac auscultation locations on healthy and unhealthy children. Up to our knowledge, no additional data regarding the auscultation location is provided. The sounds were recorded in clinical and non-clinical environments, and divided into normal, murmur, extra heart sound, and artifact classes in Dataset A. In Dataset B, the sounds were divided into normal, murmur, and extra systole classes. Furthermore, in Dataset B, the positions of fundamental heart sounds were manually annotated by clinicians.B.This database merges nine independent databases: the Massachusetts Institute of Technology heart sounds database (MITHSDB), the Aalborg University heart sounds database (AADHSDB), the Aristotle University of Thessaloniki heart sounds database (AUTHHSDB), the Khajeh Nasir Toosi University of Technology heart sounds database (TUTHSDB), the University of Haute Alsace heart sounds database (UHAHSDB), the Dalian University of Technology heart sounds database (DLUTHSDB), the Shiraz University adult heart sounds database (SUAHSDB), the Skejby Sygehus Hospital heart sounds database (SSHHSDB), and the Shiraz University fetal heart sounds database (SUFHSDB).1 The sounds were obtained from four different auscultation locations  on both healthy  and pathological  subjects, with a variety of diseases including heart valve diseases and coronary artery diseases. The training and test sets are unbalanced, with the number of normal records being greater than abnormal records. The sounds were recorded at clinical and non-clinical environments, and divided into normal, abnormal and unsure classes. With the exception of the unsure class, annotations of the positions of fundamental heart sounds were provided for all records. Such annotations were provided by applying an automatic segmentation algorithm  an an30] anIf the expert disagreed with all recommended annotations, then he/she proceeded to manually segment at least five heartbeat cycles. The new audio file and its corresponding annotation file were then saved.Labels were retains for sections of the data for which the cardiac physiologists indicated were high quality representative segments. The remainder of the signal may include both low and high quality data. In this way, the user is free to use (or not) the suggested time window, where the quality of signal was manually inspected and the automated labels were validated.This methodology was applied to both the 2014 and 2015 screening campaigns, resulting in two independent folders , as present on the project repository on PhysioNet .The audio and the corresponding segmentation annotation file names are in ABCDE_XY.wav format, where ABCDE is a numeric patient identifier and XY is one of the following codes, corresponding to the auscultation location where the PCG was collected on the body surface: PV corresponds to the Pulmonary point; TV corresponds to the Tricuspid point; AV corresponds to the Aortic point, MV corresponds to the Mitral point, and finally PhC for any other auscultation location. If more than one recording exists per auscultation location, an integer index proceeds the auscultation location code in the file name, i.e, ABCDE_nXY.wav, where n is an integer. Furthermore, each audio file has its own corresponding annotation segmentation file. The segmentation annotation file is composed by three distinct columns: the first column corresponds to the time instance, where the wave was detected for the first time; the second column correspond to the time instance, where the wave was detected for the last time; the third column correspond to an identifier, that uniquely identifies the detected wave.All the collected heart sound records were also screened for presence of murmurs at each auscultation location. Each murmur was classified , while 32.5% were discharged. Seven patients (0.8%) had a severe pathology with, requiring surgery or intervention. Further details are provided in The high number of pathologies encountered within the screened population also translated into a significant number of patients presenting murmurs in their auscultations. Most of the murmurs were observed in the systolic period (96.8%), and only a few cases were reported in the diastolic period (3.2%), see Regarding the murmur timing analysis, the most common murmur is Holosystolic, which is a murmur that lasts over the full systolic period, see The majority of the detected murmurs have a Plateau shape, i.e., their intensities are approximately constant over time. Murmurs with such shapes can be associated to ventricular septal defect, a very common pathology in our database . Murmur Some innocent murmurs are “musical” in quality  . A “harsThe variable “grade” refers to intensity, i.e., the loudness of the murmur. The location of the lesion and the distance to the stethoscope affects the listener’s perception. Usually, louder murmurs (grade ≥ 3) are more likely to represent cardiac defects than silent ones . Regardidigital equalizers that compensate for the gain losses and amplitude/phase distortions of the analog front-end. Equalizers can also be applied to make the auscultations sound more similar to their analog counterparts, which are more familiar for expert annotators. The theory and practice of sound equalization have been extensively studied in the context of audio signal processing . L. LdigitaThe location where the systolic, diastolic or systolic-diastolic murmurs were detected with the highest intensity is also an important feature to analyze. A damaged valve usually generates a murmur louder in its corresponding auscultation area. This is mainly due to the proximity and vicinity between the auscultation point and the damaged valve. For example, a murmur caused by aortic stenosis is often best heard at the upper sternal border, and usually on the right side . In thisThe observed murmurs do radiate and spread homogeneously through the thorax cf. . Thus eaAs a final remark, the CirCor DigiScope dataset is by far the largest publicly available heart sound dataset (5282 recordings), including recordings collected from multiple auscultation locations on the body. Moreover, the majority of the heart sounds  were manually segmented and their quality was assessed by two independent cardiac physiologists. Furthermore, the study resulted in a very detailed murmur characterization and classification database , which can be used in future research.VII.The CirCor DigiScope dataset represents a unique cohort from a pediatric population, and a pregnant population, with significant congenital and acquired cardiac diseases. The age distribution is also homogeneously distributed in our dataset, thus potentially paving the way to the design of robust decision support systems for different target populations, from neonates to adults.Given the rich annotations and characterizations provided with CirCor DigiScope dataset, the current work can be leveraged in various ways, including the design of multi-channel systems for multi-site PCG analysis, detection and classification of heart murmurs; and the automatic generation of murmur reports. For future work, we intend to make a comparative study, concerning the segmentation and classification of heart sound signals, in the CirCor DigiScope dataset. In future screening campaigns a broader population from different age groups shall be screened for CHD. Furthermore, new data collection protocols and technologies are going to be proposed and developed, aiming to collect data from the four auscultation spot in a synchronous or asynchronous manner.


Non-compaction cardiomyopathy (NCCM) is associated with neuromuscular disorders; however, there has been little investigation on its association with other neurological diseases, such as multiple sclerosis. We present the case of a 46-year-old woman with a history of multiple sclerosis who developed heart failure and was diagnosed with non-compaction cardiomyopathy. Non-compaction cardiomyopathy (NCCM) is characterized by a bilayer myocardial structure, a thin compacted epicardial layer, and a thicker spongy endocardial layer with prominent trabeculations and deep intertrabecular recesses . There iWhen NCCM is systematically investigated, neuromuscular disorders are found in 80% of cases, and associated mutated genes have also been described ; unlike A 46-year-old woman was admitted to our hospital for pelvic inflammatory disease complicated by pelvic peritonitis; she underwent exploratory laparotomy with right salpingectomy, and double antibiotic therapy was started. In the postoperative period, she presented with stage 2 acute kidney injury  and new-onset dyspnea. Her past medical history revealed a history of relapsing-remitting MS  diagnose3/ul; at the beginning 19.60 103/ul), and the acute kidney injury had resolved .The Pro-B-type natriuretic peptide plasma level was elevated . High-sensitivity troponin T and dimer D concentrations were within the normal range. The complete blood count showed a decrease in white blood cell count  secondary to cardiomyopathy. The history of MS raised the suspicion of an undetected underlying structural heart disease. On the other hand, other differential diagnoses were considered, such as atelectasis that was ruled out in the chest X-ray, vascular causes like pulmonary embolism since the D-dimer was in the normal range, and systemic causes like sepsis of abdominal origin, because of the absence of fever and a marked decrease in infectious markers with double antibiotic therapy.Transthoracic echocardiogram (TTE) demonstrated a left ventricular ejection fraction (LVEF) of 30%, mildly dilated, diffusely hypokinetic, prominent trabeculations of LV, and a non-compacted to compacted (NC/C) myocardium ratio of 2.75 in end-systole at inferolateral mid-ventricular level , so the The clinical status was stabilized with diuretic therapy, enalapril 5 mg bid, spironolactone 25 mg OD, and bisoprolol 5 mg OD for heart failure, with reduced ejection fraction (HFrEF) were progressively initiated. During hospitalization, she was evaluated by neurology to regulate her treatment for MS and avoid any relapse crisis, which did not appear. The evolution of the patient was favorable, and she was discharged on the 14th day of hospitalization.Cardiovascular magnetic resonance (CMR) imaging was performed 1 month after discharge to confirm the diagnosis and demonstrated positive diagnostic criteria for NCCM; additionally, the study did not show late gadolinium enhancement (LGE) . CurrentNon-compaction cardiomyopathy (NCCM) is classified as primary genetic cardiomyopathy by the American Heart Association (AHA) and unclassified cardiomyopathy by the European Society of Cardiology (ESC), with an adult prevalence of 0.014% . NCCM isMomčilović et al. , in an eThe NCCM can be grouped into seven phenotypical subtypes , among wThe TTE fulfills a fundamental value in the initial diagnostic approach, being Jenni's criteria the most widely used, and evaluates a two-layer ventricular myocardium with thick non-compacted and thinner compacted myocardium, generating an NC/C ratio >2 in end-systole on short-axis parasternal view . These aThe ECG findings are non-specific and include left ventricular hypertrophy, inverted T waves, and different types of bundle branch blocks , 12. CurAnticoagulation is mandatory in all patients with NCCM with atrial fibrillation, previous thromboembolic events, or LV thrombus , whereas in those with NCCM and only LV dysfunction, it may be considered  , 15. PatThe prognosis depends on the development of HF or the need for heart transplantation; likewise, there is a variety of predictors associated with poor outcomes that include the presence of advanced age, inpatient's NCCM diagnosis, NYHA functional class III–IV, and LVEF <31% , 16. VaiIt was suggested that first-degree relatives undergo echocardiographic screening; however, because of health insurance issues and living in another locality in Peru, this has not yet been possible. When we were evaluating the family history, the patient mentioned that one of her sisters also had a diagnosis of MS and was being evaluated in a private clinic.This case serves to propose a possible pathway of association between NCCM and MS, through Tenascin C. In addition, it highlights the importance of performing a cardiovascular evaluation that includes echocardiographic screening in all patients with MS to timely identify NCCM, and particularly the dilated LV phenotype with reduced LVEF, to initiate OMT and prevent HF progression.Because of the lack of advanced genetic studies, it was not possible to perform genetic screening on our patient. Tenascin C was not measured in our patient because of the lack of resources in our reality. It is necessary to carry out studies on large population groups to confirm this possible association between the pathologies described.The NCCM is possibly associated with MS; however, the exact pathophysiological mechanisms that explain the association are not clear, and with the present case, we would like to encourage the research for evidence through studies with large population groups on Tenascin C.Patients with NCCM with a phenotype of dilated LV with reduced LVEF must be diagnosed promptly to initiate OMT and avoid the progression of HF.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Hospital Nacional Edgardo Rebagliati Martins. The patients/participants provided their written informed consent to participate in this study.JM contributed to conception and design of the article. JM and CH wrote the first draft of the manuscript. JM, CH, and CL wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Heart failure through the spectrum of reduced (HFrEF), mid-range (or mildly reduced or HFmEF), and preserved ejection fraction (HFpEF), continues to plague patients' quality of life through recurrent admissions and high mortality rates. Despite tremendous innovation in medical therapy, patients continue to experience refractory congestive symptoms due to adverse left ventricular remodeling, significant functional mitral regurgitation (FMR), and right-sided failure symptoms due to significant functional tricuspid regurgitation (FTR). As most of these patients are surgically challenging for open cardiac surgery, the past decade has seen the development and evolution of different percutaneous structural interventions targeted at improving FMR and FTR. There is renewed interest in the sphere of left ventricular restorative devices to effect reverse remodeling and thereby improve effective stroke volume and patient outcomes. For patients suffering from HFpEF, there is still a paucity of disease-modifying effective medical therapies, and these patients continue to have recurrent heart failure exacerbations due to impaired left ventricular relaxation and high filling pressures. Structural therapies involving the implantation of inter-atrial shunt devices to decrease left atrial pressure and the development of implantable devices in the pulmonary artery for real-time hemodynamic monitoring would help redefine treatment and outcomes for patients with HFpEF. Lastly, there is pre-clinical data supportive of soft robotic cardiac sleeves that serve to improve cardiac function, can assist contraction as well as relaxation of the heart, and have the potential to be customized for each patient. In this review, we focus on the role of structural interventions in heart failure as it stands in current clinical practice, evaluate the evidence amassed so far, and review promising structural therapies that may transform the future of heart failure management. Despite tremendous advances in medical therapy and revascularization techniques, heart failure continues to be a growing global epidemic– the prevalence of global heart failure doubled from 33.5 million in 1990 to 64.3 million in 2017 . In thisModerate or severe functional or secondary MR accompanies heart failure in about one-third of the patients and is mediated by mal-coaptation of the valve leaflets due to left ventricular remodeling and dysfunction secondary to ischemic and/or non-ischemic etiologies or due to annular dilatation in patients with long-standing atrial fibrillation or “atrial FMR” , 6. MechNot all mitral valve anatomies are ideal for performing a TEER and hence alternative mitral valve repair strategies are needed. One such device is a self-expandable nitinol ring that can be implanted in the coronary sinus through the right jugular vein– the Carillon™ Mitral Contour System– this device relies on the close relationship between the coronary sinus and the mitral valve annulus to effect an indirect annuloplasty . AdvantaAnother device that targets annular dilatation is a minimally invasive, catheter-delivered direct annuloplasty ring– the Cardioband™ valve reconstruction system (Edwards Lifesciences) . This imWhile these Transcatheter Mitral Valve Repair (TMVr) techniques offer promising results for patients with FMR, some patients have unfavorable mitral valve anatomy  for percutaneous repair and may experience complications or failure with significant residual or recurrent MR despite TMVr . TranscaIn 2005, ~1,600,000 patients were identified to have moderate-severe TR, however, only <8,000 of these patients underwent tricuspid repair or replacement . PrimaryTreatment strategies for Transcatheter Tricuspid Repair (TTVr) include TEER using the Triclip™ (Abbott) and PASCAL™ (Edwards Lifesciences) systems, direct annuloplasty with Cardioband™ (Edwards Lifesciences), Tricinch™ (4Tech Cardio Ltd.), Trialign™  and the Mistral™  device which effects a reduction in TR through grasping and inward pulling of the chordae tendineae . Among tIn patients with large coaptation gaps (>6–8 mm), massive/torrential TR, device-related TR, or prior failed repair with single leaflet detachment, TTVr may not be feasible and this has created the niche for Caval Valve Implantation (CAVI) and Transcatheter Tricuspid Valve Replacement (TTVR). CAVI involves placement of a heterotopic valve in the Inferior Vena Cava and possibly the Superior Vena Cava (SVC) to protect the hepatic and renal circulation by redirecting the TR jet and this modality also improves the forward stroke volume ejected through the right ventricle. CAVI is technically easier than other transcatheter tricuspid therapeutic options and can be easily combined with other modalities as the valve or sub-valvular apparatus are intact. While the initial experience with non-dedicated valves showed a high rate of complications related to device thrombosis and dislocation, the novel dedicated bicaval valves are currently undergoing early feasibility studies  66). Fo. Fo66). In patients with severe Aortic Stenosis (AS) and left ventricular dysfunction or in patients with Continuous-Flow Left Ventricular-Assist Devices (CF-LVAD) who develop moderate or higher degrees of Aortic Insufficiency (AI), the role of transcatheter aortic valve interventions has been growing. In the TOPAS-TAVI registry, 293 patients with low-flow, low-gradient aortic stenosis and depressed ejection fraction were included and patients with severely depressed EF (<30%) had greater improvements in LVEF at 1-year follow-up after Transcatheter Aortic Valve Replacement (TAVR) compared to patients with moderately reduced EF (<40%), irrespective of the presence of contractile reserve with dobutamine stress . Aortic de-novo AI following LVAD implantation– noted in ~15–52% of patients at 1-year post-implant , or replacement with a bio-prosthetic valve. Complete valve closure can be fatal in cases of device malfunction and the potential for myocardial recovery should also be weighed in. Surgical Aortic Valve Replacement (SAVR) at the time of VAD surgery would increase the bypass and aortic cross-clamping times and is associated with worse clinical outcomes in patients with INTERMACS 1 and 2 level heart failure . There i-implant . Moderat-implant . In a ca-implant .® Atrial Shunt) vs. a sham control and significant reduction in pulmonary wedge pressure with exercise was noted in patients treated with device therapy at 1-month follow-up  vs. a sham control in a similar heart failure population failed to show any improvement in heart failure events or heart failure symptoms at 12–24 months follow-up  – these devices are implanted through the femoral veins and trans-septal access and aim to lower the left-atrial pressure with activity thereby improving symptoms and outcomes in patients with HFpEF and HFmEF. REDUCE-LAP HF I was a phase-II randomized trial in patients with symptomatic refractory heart failure (wedge pressure ≥25 mm Hg during exercise) with LVEF>40% and a gradient of ≥5 mm Hg between the left and right atria– patients were randomized to treatment with IASD (Corviaollow-up . Furtherollow-up . Howeverollow-up . Patientollow-up . While C-months) . A modifHF trial . AnotherHF trial .Recently, there has been active research in the development of implant-free Inter-Atrial Shunts– the Alleviant System is one such strategy that creates a shunt using radiofrequency energy-based septectomy that has shown safety and clinical efficacy with patency through 12-months follow-up in the first-in-human clinical study (ALLEVIATE HF-1) . The impImplantable micro-electromechanical-based sensors in the Pulmonary Artery (PA) have been developed to assist in real-time monitoring of cardiac filling pressures to tailor medical therapy and pre-empt a heart failure exacerbation. This is particularly important for patients with HFpEF, where patients are threading a narrow line between hypervolemia and heart failure and hypovolemia and underfilling of the ventricle resulting in hypotension. CHAMPION was a single-blinded randomized controlled trial that showed a clinically meaningful and significant reduction in HF admissions in patients with moderately symptomatic heart failure (New York Heart Association (NYHA) class III HF with a recent admission in the past 12 months) with the use of the wireless PA pressure monitoring using the CardioMEMS™ HF system (Abbott) compared to medical therapy alone. HF admissions were consistently reduced in patients with HFpEF and HFrEF with a significant change in diuretic dosing across the two arms; this effect was apparent after about 3 months of diuretic titration in the treatment arm and persisted up to 17 months of follow-up (50% relative reduction for HFpEF and 26% for HFrEF) . CardioM® (Cardiokinetix) is a catheter-based, self-expanding, umbrella-shaped, partitioning device, that was intended to separate the aneurysmal portion of the LV and create a new apex in patients with ischemic cardiomyopathy. While the first-in-human study (PARACHUTE) in patients with HFrEF (EF 15–40% and an akinetic of dyskinetic apex) showed safety and feasibility, at 3-year follow-up, a reduction in stroke volume and LVEF were noted. This device was subsequently tested in a randomized, controlled trial (PARACHUTE IV) that enrolled 331 subjects with NYHA class III-IV ischemic cardiomyopathy and wall motion abnormalities (EF 15–35%) with suitable anatomy for the device, however, the trial was terminated prematurely in 2017 and this device is not in use currently (® (Ancora Heart Inc.) Ventricular Restoration System– a nitinol anchor-based cinching cable positioned in the LV cavity below the mitral valve through a retrograde transventricular approach. This is still being tested in early feasibility trials in patients with HFrEF or moderate or higher degree of FMR with NYHA class III-IV symptoms despite optimal medical therapy (CorCinch)  . BioVentorCinch) . Based oorCinch) .Cardiac sleeves envisage the use of biomimetic implantable robotic devices for ventricular support in heart failure patients. The sleeves have certain benefits compared to current VAD in clinical practice– they can provide bi-ventricular support, no contact with blood reduces the risk for thrombosis, they can be activated to provide support to the heart during systole as well as diastole, and finally, level of support can be weaned as the native function recovers . These rIn summary, in the last decade, there has been tremendous growth in the development of transcatheter interventions to improve heart failure outcomes. Given the multitude of structural therapies available and the clinical complexity involved in decision-making, the role of team-approach with involvement of the advanced heart failure team, multi-modality cardiac imagers, different medical sub-specialties  and the structural heart team cannot be overstated. Finally, early consideration of structural therapies is paramount to ensure good outcomes before end-organ damage has ensued. The ongoing trials for cardiac robotic sleeves, ventricular restorative devices, implant-free inter-atrial shunts, novel transcatheter mitral and tricuspid valve devices would help shape the future of heart failure management.DK and MM were involved in the planning, execution, writing, and critical appraisal of this manuscript. All authors contributed to the article and approved the submitted version.MM: primary investigatory at University of Miami for Clinical Evaluation of the AccuCinch ventricular restoration system in patients who present with symptomatic heart failure with reduced ejection fraction (HFrEF): the CORCINCH-HF study. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Abrupt change in the caliber of the main pancreatic duct (MPD) with distal pancreatic atrophy (PA) was considered as one of worrisome features in the International Association of Pancreatology guideline and American College of Gastroenterology guideline for the management of intraductal papillary mucinous neoplasms (IPMNs). However, this feature was not included in other guidelines. Moreover, the association between PA alone and malignancy in IPMNs has not been fully evaluated. In the present study, we investigated the role of image-based PA in identifying malignant IPMNs or invasive carcinoma.A total of 186 patients with IPMNs were included for analysis. The tumor size, location, MPD diameter, presence of a mural nodule (MN), and PA were evaluated using magnetic resonance imaging. Demographic information and serum carbohydrate antigen 19-9 and carcinoembryonic antigen (CEA) levels were also collected. IPMNs with high-grade dysplasia and associated invasive carcinoma were regarded as malignant IPMNs.PA was observed in 34 cases (18.3%). The occurrence of malignant IPMNs or invasive carcinoma in patients with PA were significantly higher than in those without PA . Multivariate logistic regression analysis showed that PA was an independently associated factor for malignant IPMNs  or invasive carcinoma  after modified with confounders. Subgroup analysis in MPD-involved IPMNs also indicated that PA was an independently associated factor for invasive carcinoma . PA had a similar performance with MPD plus MN [the area under the curve (AUC) was both 0.71] in identifying malignancy. PA had a higher performance in identifying invasive carcinoma in MPD-involved IPMNs than MN .Our data showed that imaging-based PA was associated with malignancy or invasive carcinoma regardless of abrupt change in the caliber of MPD in IPMNs. PA had an acceptable performance in identifying malignant IPMNs. Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a cystic tumor with papillary growth and mucin secretion in the duct. IPMNs have a great potential of malignant transformation. The management of IPMNs remains a challenge in clinical practice  because Pancreatic atrophy (PA) is usually occurred in pancreatic ductal adenocarcinoma. Excessive mucin secretion from IPMNs can obstruct the main pancreatic duct (MPD), leading to PA and fibrosis . CurrentInterestingly, some studies have found that pathological PA was also related to invasive carcinoma or malignant IPMNs –11. SaitThe retrospective study was approved by the Ethnic Committee of Affiliated Hospital of Nanjing University of Chinese Medicine. A total of 214 patients with pathologically proved IPMNs were found in our institutions during January 2016 to May 2021. Among these patients, 29 patients were excluded for the following reasons: the absence of magnetic resonance imaging (MRI) or MRI examinations at an outside hospital (n = 16); absence of contrast-enhanced examinations (n = 5); and other pancreatic tumors (n = 8). Because MRI or MR cholangiopancreatography (MRCP) has an advantage in identifying BD-IPMNs, we only included patients with MRI examinations. The clinical information, including demographic data ; tumor biomarkers [CA19-9 and carcinoembryonic antigen (CEA)]; and medical history of diabetes mellitus (DM), pancreatitis, and jaundice, were recorded from the medical system. DM was considered if plasma glucose levels were higher than 7.1 mmol/L or if there is a history of DM.MR scans were performed by using a 3.0-T or 1.5-T unit . Conventional axial, sagittal, and coronal T1-weighted turbo spin-echo imaging sequence (without and with gadolinium), fast spin-echo T2-weighted fat-suppressed sequence . MRCP was performed using heavily T2-weighted fast acquisition spin echo sequence . Contrast enhanced imaging was also performed after the intravenous injection of 0.1 mmol/kg gadolinium (2.5 ml/s).The following imaging parameters were collected: tumor location (head–neck or body–tail), tumor size, MPD diameter, and the presence of enhanced MN with a size ≥5 mm. The MPD diameter was measured at the point of the maximally dilated pancreatic duct . EnhanceIPMN was divided into three subtypes based on the degree of involvement of the pancreatic ductal system: main duct (MD), BD, and mixed type (MT). The pathological grade of IPMN was classified as low-intermediate dysplasia, high-grade dysplasia, and invasive adenocarcinoma according to the World Health Organization guideline. Those IPMNs with high-grade dysplasia and associated invasive carcinoma were regarded as malignant IPMNs.<3.0 cm; and ≥1.0 and <1.0 cm. Two-tailed independent t tests or the Mann–Whitney U-test were adopted to compare the variables between patients with and without PA. A chi-square test or Fisher exact test was used to compare categorical variables. Univariate and multivariate logistic regression analyses were used to investigate the association between the presence of PA and malignant IPMNs or invasive carcinoma. Receiver operating characteristic (ROC) curves were conducted to show the performance of PA alone or combination with other markers in identifying malignant IPMNs or invasive carcinoma. Two-tailed P-values < 0.05 were considered as a statistical significance.Data management and statistical analysis were all performed by using SPSS 16.0 . CA19-9, CEA, the tumor size, and MPD diameter were divided into two groups: <37.0 and ≥37.0 U/ml; <5.0 and ≥5.0 ng/ml; ≥3.0 and A total of 186 patients met the selection criteria and were included in the analysis. The characteristics of subjects with PA and without PA are shown in The occurrences of malignancy and invasive carcinoma in patients with PA were all higher than those without PA  (both P < 0.01). Subsequently, we assessed the correlation between the prevalence of PA and grade of IPMNs Figure 1Next, we observed the association between PA and malignancy or invasive carcinoma in IPMNs 3. Both We examined whether the correlation between PA and malignancy or invasive carcinoma was present in MD-involved IPMN patients Table 4.The ROC curves in identifying malignancy or invasive carcinoma are presented in PA also had acceptable performance in identifying invasive carcinoma in MD-involved IPMNs (AUC = 0.71), which was higher than that of MN (AUC = 0.65) (P = 0.02). Moreover, the AUC of MN plus PA (AUC = 0.76) was higher than that of MN (AUC = 0.65) or PA (AUC = 0.71) alone in MD-involved IPMNs.An abrupt change in the caliber of MPD with distal PA has been regarded as a risk factor for malignant IPMNs or feature for surgical resection in IAP and ACG guidelines , 7. HoweThe occurrence of PA in IPMNs is not uncommon. Two recent radiological studies showed that 23% of IPMN patients had PA in computed tomography (CT) images , 17, whiSeveral guidelines have showed malignant features or surgical indications for IPMNs , such asA single biomarker in isolation was also used to identify malignancy in IPMNs. Sugimoto et al. showed that the diagnostic performance of an MPD diameter cut-off of 7.2 mm for malignant neoplasms was acceptable . Kim et al.  demonstrCT, MRI, and endoscopic ultrasonography (EUS) are all useful for IPMN diagnosis or malignancy identification. A recent meta-analysis showed that contrast-enhanced EUS had good performance  in identifying a mural nodule . EUS alsOur study has several limitations. First, only the patients who underwent surgery and MRI examinations were included, which may cause selection bias. The generalization of our results should be confirmed by other studies, even though pathological studies have shown that PA was related to invasive carcinoma or malignant IPMNs , 11. SecIn conclusion, the occurrence of PA in IPMNs was common. PA was associated with malignant IPMNs and invasive carcinoma. PA alone or combined with MPD and MN had an acceptable performance in predicting malignancy in IPMNs. Our data support that PA could be regarded as one of the associated factors or worrisome features in the guidelines.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.The retrospective study was approved by the Ethic Committee of Affiliated Hospital of Nanjing University of Chinese Medicine. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.CW and XiaoC participated in the design of the study. TL, XinC and XiaoC wrote the manuscript. TL, XinC, JL, YC, and WC collected and analyzed the data. TL, XinC, CW and ZW contributed to interpretation of data and preparation of the manuscript. All authors read and approved the final manuscript.Peak academic talent training fund of Jiangsu Province Hospital of Chinese Medicine(y2018rc04); Science and Technology Development Plan fund of Chinese Medicine of Jiangsu Province (ZD201907) and National Natural Science Foundation of China (No. 81773460).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Ongoing concerns with single-ventricle palliation morbidity and poor outcomes from primary biventricular strategies for neonates with borderline left heart structures have led some centers to attempt alternative strategies to obviate the need for ultimate Fontan palliation and limit the risk to the child during the vulnerable neonatal period. In certain patients who are traditionally palliated toward single-ventricle circulation, biventricular circulation is possible. This review aims to delineate the current knowledge regarding converting certain patients with borderline left heart structures from single-ventricle palliation toward biventricular circulation. Ongoing concerns with single-ventricle palliation morbidity and poor outcomes from primary biventricular strategies for neonates with borderline left heart structures have led some centers to attempt alternative strategies to obviate the need for ultimate Fontan palliation. The objective of this manuscript is to review the current literature on gaining successful biventricular circulation in patients with borderline left heart structures with patency of the aortic and mitral valves.A satisfactory definition of what constitutes “borderline left heart structures” is complicated by the fact that it is a diagnosis of exclusion. There is universal agreement about some amalgamations of morphologies that are biventricular, i.e., bicuspid aortic valve without stenosis and coarctation, or univentricular, i.e., HLHS with aortic and mitral atresia. Large portions of the diagnoses along the continuum between these two morphologies are managed very differently amongst centers. Part of the issue is that the definition of biventricular is a matter of the success of the postoperative functional status of repair, depending on both ventricles providing adequate cardiac output with low left atrial pressures, for which we have limited preoperative predictors. Because of the potential dire consequences of choosing a biventricular strategy and failing , reasonaThis difficulty in the inter-center prediction of biventricular success is evident in the poor external validity of scoring systems, such as the Rhodes score  and the p = 0.048), left ventricular end-diastolic dimension z-score , aortic valve annular dimension z-score , and ascending aortic diameter z-score . A mitral valve z-score ≥−1.9 or a tricuspid: mitral valve ratio ≤1.5 suggests a high probability of biventricular repair; whereas, a right: left ventricular end-diastolic dimension ratio ≥2.1 confers a likelihood of single-ventricle palliation.The Rhodes and CHSS scores were specifically validated for patients with critical aortic stenosis. Other anatomic substrates of hypoplastic left heart variants, such as unbalanced atrioventricular septal defects (uAVSD), posterior mal-aligned ventricular septal defects, etc., may not be appropriate to utilize these scores. Since the early 2000s, there have been multiple studies utilizing echocardiography to predict the postnatal surgical outcome. In a retrospective study of fetal echocardiographic images by Jantzen et al. , researcIn a study to identify preoperative parameters that predict intervention-free survival with biventricular circulation after primary aortic arch repair , infantsMart et al.  created 2 as potentially adequate ventricles to maintain biventricular circulation [Differentiating borderline left heart structures is still an imprecise science. Advanced imaging modalities have the potential to add additional data to help with decision making. Computed tomography (CT) can add to the precision of the assessment of ventricular columns and morphometric parameters . Severalculation ,10,11.Other anatomies, such as uAVSD, may have straightforward preoperative features to guide the surgical pathway. A multi-institutional study from the CHSS used an echocardiogram to define the limits of uAVSD . An atriUnfortunately, despite the advances in echocardiographic imaging, these modalities frequently have inadequate sensitivity. We have found that before committing a child to single-ventricle palliation, it is frequently prudent to perform intracardiac exploration. We and other groups have found that, frequently, preoperative imaging may underestimate the actual size of structures, especially when the subvalvar mitral apparatus is normal .There is a concern that patients with borderline left heart structures, who are forced into biventricular circulation before they are ready, may have left atrial hypertension and poor cardiac output that can lead to death or to poor future candidacy for univentricular conversion or heart transplant . For thep = 0.07), and they were more likely to have had a balloon aortic valvuloplasty at some point, preoperatively. Twelve of the nineteen patients (63%) with significant ASD restriction would receive catheter-based balloon dilation or stenting for significant left atrial hypertension. As a recurring theme that will be observed consistently in all of these series of left ventricular recruitment and biventricular conversions, there was a need for more reinterventions with left ventricular recruitment and a longer length of hospital stay. The median cumulative duration of all hospitalizations from stage 1 single-ventricle palliation to the most recent follow-up was 94 days (range 37 to 518 days) in the left ventricular recruitment group, and 54.5 days (range 8 to 348 days) in the single-ventricle palliation group (p = 0.006). The wide range underscores how these patients can differ among themselves, and stresses, once more, the need for individualized, personalized care.This was an asymmetric cohort study with a mix of historical and contemporary controls, leading to the possibility of some selection bias. In fact, the staged LV recruitment cohort had a trend toward a larger left ventricular end-diastolic volume (LVEDV) z-score . There was improved freedom from death or transplant with the left ventricular recruitment strategy over single-ventricle palliation . Thirteen patients (38%) achieved biventricular circulation after left ventricular recruitment. At catheterization, before biventricular conversion, the mean left atrial pressure, with balloon occlusion of the atrial septal defect, was 14 ± 4.7 mmHg. At a median follow-up of 2.9 years (range 1 to 6 years), all of these patients were alive. As a proof of concept, this manuscript demonstrated significant success. The LVEDV and left ventricular long-axis z-scores were not significantly different between groups before stage 1 palliation, but there were significant increases in size in the left ventricular recruitment group before bidirectional Glenn (p < 0.005) and before Fontan or biventricular repair (p < 0.01). Of note, restriction of the atrial septum was the only predictor of an increase in LVEDV (p < 0.001). It is possible to increase the left heart dimensions by using a left ventricular recruitment strategy, by “force volume loading” the left heart in a stepwise manner.Luckily, there is an overall increase in the ejection fraction between the postnatal echocardiogram and the echocardiogram before biventricular conversion  and median indexed systolic volume . Biventricular conversion was performed in 14 patients (67%), with 2 deaths (14%).p = 0.04) and mitral valve z-scores  increased after the hybrid Norwood procedure. They did not report LV length z-scores, but there was no change in the LV/RV ratio. Of interest, in looking toward facilitating LV growth in these patients, they maintained a restrictive interatrial communication. Left atrial pressure up to 15 mmHg and a gradient across the ASD between 5 and 10 mmHg seemed to be tolerable. The patients in this study were included if they underwent a hybrid Norwood and biventricular repair. No comparison could be made with patients who had the anatomy for potential biventricular repair, but who were unable to achieve adequate left-sided growth to attempt biventricular repair. Furthermore, other centers have shown the potential for left heart growth after the hybrid Norwood procedure [p < 0.05)  .The valvar and left ventricular outflow tract operative techniques are similar to other strategies performed on pediatric patients. As observed above, restriction of the atrial septal defect is consistently the most significant maneuver to help grow the left-sided cardiac structures. A patch with a fenestration in it or a partial primary closure can be used. The residual shunt has been anywhere between 2 and 6 mm, depending on the perceived sizes of the mitral valve, aortic valve, and left ventricle. Our center and other centers use judicious balloon septostomy as needed, to keep the left atrial pressure ≤15 mmHg. To further strengthen the argument, inter-atrial communication that is left open at the time of aortic arch augmentation in neonates with biventricular physiology is predictive of a need for reintervention on the left ventricular outflow tract .The other key surgical piece of left ventricular recruitment is the augmentation of pulmonary blood flow. A Sano or modified Blalock-Taussig shunt are employed in a standard fashion. If there is a bidirectional Glenn (BDG) present, then we may choose to place a pulmonary artery band between the shunt and BDG to prevent the reversal of flow in the superior vena cava. It is not at all evident that augmentation adds to left heart growth. It makes intuitive sense, but, in fact, Qp and Qp: Qs were not found to be statistically significant predictors in the development of left heart growth . The neeSix-to-twelve months after left ventricular recruitment, when the left heart structures look adequate echocardiographically, we then test the patients’ readiness for biventricular conversion. We obtain an MRI to assess ventricular volumes, valvar morphology, and, if present, ventricular septal defect orientation to the systemic semilunar valve. To assess hemodynamic tolerance, we also obtain cardiac catheterization to assess Qp: Qs and to balloon occlude the atrial septal defect, to check what the left atrial pressures would be after septation with a Qp: Qs near one. If all of this is adequate, then the patient will be recommended for biventricular conversion, after multidisciplinary discussions with pediatric cardiology, pediatric radiology, and pediatric cardiac surgery. Biventricular conversion includes the takedown of aortopulmonary amalgamation; the takedown of a cavopulmonary connection; ventricular septation, if necessary; and separation of the left and right ventricular outflow tracts by direct re-anastomosis, conduit reconstruction, or pulmonary autograft translocation.2 (56.6 to 251.5 mL/m2) from 58.1 mL/m2 (26.6 to 97.5 mL/m2) in the HLHS group, and to 58.5 mL/m2 (45.7 to 69 mL/m2) from 28.1 mL/m2 (16 to 86.2 mL/m2) in the uCAVSD group; p < 0.05 in both groups. The left ventricular end-diastolic pressure (LVEDP) increased to 17 mm Hg (9 to 29 mm Hg) from 12 mm Hg (6 to 20 mm Hg) in the HLHS group; p < 0.05. The LVEDP non-significantly increased to 11 mm Hg (8 to 24 mm Hg) from 8 mm Hg (7 to 10 mm Hg) in the uCAVSD group; p = 0.079.Kalish BT et al.  describep = 0.037) and postoperative right ventricular pressure > ¾ of the systemic pressure  were significantly associated with the primary composite endpoint of death, heart transplant, or biventricular repair takedown. Of 51 patients, 11 (22%) experienced the primary endpoint. Patients with HLHS were more likely to experience this endpoint compared to those with uCAVSD . A total of 25 (49%) patients required surgical re-intervention after biventricular conversion. There was a transplant-free survival of 80% at 3 years. The survival rate was 85% for the group with LVEDP < 13 mm Hg and 60% for the group with LVEDP ≥ 13 mm Hg (p = 0.037). This survival rate does not include any patients who were censored before they were deemed adequate biventricular conversion candidates. Considering the survival and reoperation rates, the question arises as to whether a focus on patient selection for those patients with risk factors for single-ventricle palliation, or outright single-ventricle palliation failure, should trump strict anatomic and functional criteria [Further investigation of preoperative parameters and postoperative outcomes in patients with HLHS or uCAVSD, undergoing biventricular conversion, was performed . Multivacriteria .p = 0.005).To help address the concerns with this question, Boston looked specifically at patients with uAVSD . These pAs for patient selection, in 23 patients who underwent biventricular conversion for Fontan failure, the 2-year survival rate was 72.7%  . This isIn certain patients who are traditionally palliated toward single-ventricle circulation, biventricular circulation is possible. The short- and medium-term results are satisfactory. This circulation offers the prospect to prevent the well-known Fontan morbidities at the consequence of greater re-interventions, left atrial hypertension, and unknown long-term outcomes. Further studies and follow-ups are needed to assist in refining optimal patient selection, improved surgical techniques, and proper postoperative management.


Myocardial infarction is a very dangerous cardiovascular disease with a high mortality rate under the modern developed medical technology. miRNA is a small molecule regulatory RNA discovered in recent years, which can play an important role in many cancers and other diseases. Medical data, machine learning and medical care strategies supporting the Internet of Things (IoMT) have certain applications in the treatment of myocardial infarction. However, the specific pathogenesis of myocardial infarction is still unclear. Therefore, this paper aimed to explore the expression of microRNA-320 and microRNA-204 in myocardial infarction and used the expression of microRNA-320 and microRNA-204 to predict the prognosis of patients with myocardial infarction. In order to discuss the expression of microRNA-320 and microRNA-204 in myocardial infarction in more detail. In this paper, 40 patients in the trial period were selected for clinical research, and 10 patients with normal cardiac function were selected in NHF group as control group. 10 patients with heart failure were selected as AMHF group. 10 patients with acute myocardial infarction were selected as AMNHF group. 10 patients with heart failure after old myocardial infarction were selected as OMHF group. AMHF group, AMNHF group and OMHF group were taken as the case group. This paper analyzed the difference of miR between different groups and determined that there were significant differences in the expression of miR-320 and miR-204 between different groups. Finally, the expression and prognosis of miR-320 and miR-204 in myocardial infarction were analyzed. The analysis results showed that the expression of microRNA-320 and microRNA-204 can inhibit the activity of myocardial cells. On the fifth day, the corresponding expression of microRNA-320 and microRNA-204 reduced the optical density of myocardial cells to 1.75 and 1.76, which was significantly lower than that on the first day. Moreover, excessive miR-320 expression and excessive miR-204 expression can increase the apoptosis rate of myocardial cells. The above results indicated that the high expression of microRNA-320 and microRNA-204 can be a bad prognostic factor in patients with myocardial infarction, showing that medical data, machine learning and medical care strategies supporting IoMT can play a role in the treatment of myocardial infarction. Therefore, it is urgent to understand the pathogenesis of heart failure after myocardial infarction and find new treatment schemes to improve the positive prognosis. In developed countries, heart failure after myocardial infarction is an important cause of hospitalization and death. With the development of medical technology, the survival rate of patients has also been improved and the life cycle of patients with heart failure has also been extended. However, the aging population in China has led to an increasing incidence of heart failure year by year. Heart failure is a major public health problem facing China in the 21st century. In the past 10 years, although the treatment strategy of heart failure has changed from simply short-term hemodynamics to the goal of inhibiting and delaying the development of cardiac remodeling, its 5-year mortality is still close to that of malignant tumors. Therefore, to seek new therapeutic targets and reduce the mortality of patients are the most important for heart failure after myocardial infarction.Myocardial infarction is still one of the diseases with the highest mortality rate, and there are many researches on the treatment of myocardial infarction. Fan Xiaoming studied the role of interleukin-10 in reducing renal injury after myocardial infarction in diabetes. The experimental results suggested that interleukin-10 is expected to become a detection index of myocardial infarction in diabetes . Reed GrFor the specific pathogenesis of myocardial infarction, many scholars have discussed the expression level of related factors. Dai Wangde showed the specific mechanism of myocardial ischemia in rats through the rat model of myocardial infarction, and he found that some factors had obvious relationship with the area of myocardial infarction and cardiac blood return in rats . GoncalvThis paper analyzed the expression of microRNA-320 and microRNA-204 in myocardial infarction, which was rarely studied by predecessors. In addition, microRNA-320 and microRNA-204 are frequently thought to have a stronger connection to cancer and have a role in the development of cancer. The expression of microRNA-320 and microRNA-204 in myocardial infarction, however, has not received much attention. Therefore, the research in this paper is of great significance for the treatment of future myocardial infarction and the subsequent research on miRNA.β Oxidase and the expression of miRNA are also decreased. In the myocardial biopsy, the blood glucose intake and metabolism of patients with dilated cardiomyopathy have been significantly improved. In addition, some studies have shown that improving the utilization of fatty acids and sugars is an effective means to treat heart failure after myocardial infarction. In recent years, scholars from China and other countries have discussed the changes of small molecule metabolite content, aiming to explore the pathogenesis of heart failure and find new therapeutic targets  . MEE detThe left atrial end systolic stress is a non-invasive measurement method. In addition, the multispectral imaging technology can analyze the blood flow through the aorta and accurately measure the stroke volume and ejection time. Therefore, circumferential end-systolic wall stress (cESS) can be used to replace the left ventricular systolic tension, so that patients with myocardial infarction can be evaluated non-invasive. In addition, studies have proved that the left ventricular external work is in direct proportion to the average cardiac pressure and cardiac output .The patient should lie on the left side to be examined by PHILIP 7500 color Doppler ultrasound. At the same time, ECG signals should be recorded. The standard profile recommended by the American Ultrasonic Association is adopted, and the S3 ultrasonic probe is adopted, with the probe frequency of 2.5 MHz. The main parameters required for the experiment are shown in LVEF:LVFS:Among them, LVM represents the mass of left ventricle and BSA represents the body surface area.cESS:SBP is the systolic pressure measured by Mercury cuff sphygmomanometer.MEE:LVSV is left ventricular stroke volume.The patients with myocardial infarction hospitalized in a hospital from October 2020 to October 2021 were selected as the research objects, and 40 patients were randomly selected as the observation objects in this experiment. According to the myocardial infarction’s progression, they were split into four groups. One group is the NHF group, which stands for the control group with normal myocardial function. Patients with heart failure, those with acute myocardial infarction, and those with heart failure following an older myocardial infarction make up the other three case groups. These groups are designated as AMHF group, AMNHF group, and OMHF group, respectively. All participants are aware of the experimental content and signed the informed consent form to agree and cooperate with the experiment.Patients with myocardial infarction who meet the diagnostic criteria of coronary heart disease: there are typical chest tightness, chest pain and elevation of S and T segments of ECG (electrocardiogram), and coronary angiography result shows acute coronary artery occlusion. Acute myocardial infarction is evaluated according to the killip grade. The killip score of patients in the AMHF group is more than II, and the killip score of patients with AMNHF is I .Patients who have had an old myocardial infarction and are experiencing heart failure must fulfill two criteria. First, they should have a history of coronary heart disease and coronary intervention. Second, they should have a cardiac function score of Grade 3 or above as determined by the New York Heart Association .The enrolled patients should keep stomach empty in the morning of the next day after entering the group. They were collected 3 mL of peripheral venous blood through an ethylene diamine tetraacetic acid anticoagulant catheter, and plasma was separated 2 h later. The collected plasma was transferred to a 1 mL standard non RNA enzyme centrifuge tube. In different centrifuge tubes, the plasma of five patients is 100 ul each, a total of 500 ul, which should be put in the refrigerator at - 80°C.The flow chart of miRNA labeling is shown in t-test is used to screen miRNAs. The Volcano Plot is obtained by taking Fold Change as the abscissa and the negative logarithm of P-log10  as the ordinate. When the variation is more than 1.5 times, and p < .05, the gene expression difference between the two samples can be directly obtained.The scanned image is extracted by GenePixPro6.0 software, and the average value is obtained by repeating 10 times. The miRNAs with a gene expression intensity of 50 or higher in all samples are medially normalized. The independent t-test is used. S When multiple groups of measurement data conform to the positive and the square difference, the analysis of variance method is used; otherwise, the Welch test is used. PSS13.0 statistical software is used to analyze the data.All measurement data are expressed in terms of average standard deviation. When two measurement data conform to normal and variance, two independent t-tests are used respectively. If they do not conform, a modified p-value is 1.232. There is no difference. In the basic situation, such as age, height and sex, the p-value is greater than .05, indicating that there is no difference in the physical condition of each group of patients, and subsequent experiments can be carried out.The general clinical data of different groups are shown in p-value, which can clearly reflect the relationship between different magnification (variation measurement) and statistical significance (taking into account the variation degree and variation degree). According to different data, they can be isolated from a group of special genes. In order to reveal miRNAs with significant differences in gene expression, volcanic maps of different groups were selected. The results are as shown in Volcanic images are an effective means to intuitively display the differences between various samples. The index includes expression variation multiple and MiRNA microarray analysis is a method to detect the difference of miRNA expression between patients with heart failure and normal control group by using peripheral venous blood plasma detection technology, so as to screen out differential miRNAs. The successful detection of differential miRNAs can find new heart failure markers, thus laying the foundation for new therapeutic goals.As shown in As shown in As shown in By comparing the difference miRNAs between the control group and different case groups, it can be found that there are significant differences in miR-320 and miR-204 between patients with normal myocardial function and patients with myocardial infarction, and this difference occurs in each course of disease. Therefore, it is meaningful to make targeted diagnosis and treatment of myocardial infarction through miR-320 and miR-204.The selected gene information was miR-204-3p and miR-320C. The carrier information is GV254. The sequence of elements is Ubi-EGFP-MCS-IRES-Puromycin, and the cloning site is Nhe I.The acquisition of target gene fragments is shown in The target gene is extracted from the plasmid containing the target gene by PCR technology, and the target vector is digested. After electrophoretic extraction, it is exchanged, and the final result is bacterial competent cells. The isolated clone is detected by PCR technology, and then the positive clone detected by PCR method is compared with it. If there is no error, the target gene can be obtained.The cells were separated from liquid nitrogen and quickly poured into 37°C water for rapid dissolution. It was then transferred to a centrifuge containing medium and centrifuged at room temperature for 5 min. The speed is 1,000 rpm. After centrifugation, the supernatant was removed and blown with fresh medium and then transferred to the culture bottle for culture in the incubator. 10% bovine serum protein and 1% penicillin streptomycin double antibody solution were used to culture in the medium at 37°C and saturated humidity. Cells with logarithmic growth cycles were used in the experiment.In the case of high density, cell passage must be carried out. The suspension cells were discarded at a ratio of 1:2-1:4 and then cultured in a new complete medium. During passage, the old medium was discarded and washed with normal saline, and then .25% trypsin was added into the culture dish. When the cell volume increased, the complete culture medium was added. The cells were dried and then sent to a centrifuge, and then the supernatant was poured out, resuspended, and divided into a new medium at a ratio of 1:2-1:4.The cells were centrifuged at normal temperature for 5 min and then resuspended and transferred to a labeled refrigerated container. The container should be placed in a freezer at minus 80°C to transfer to liquid nitrogen the next day for long-term freezing.Myocardial cells in logarithmic growth cycle were counted after suspension from body weight. Cells in the 24 well plate were seeded into the 24 well plate according to the density of 105 cells per well. Myocardial infarction differential miRNA and different concentrations of myocardial infarction drugs were added. At the same time, the blank culture medium and blank control group were set  and placed in the culture dish for 48 h. The cells in the 24 well plate were transferred to the 96 well plate, 200 ul for each well, and four well plates in each group were incubated at 37°C for 3 h. The microplate reader was used to measure the optical density (OD) absorption value at the wavelength of 490 nm. Under stable transfection conditions, 200ul × 104 cells were placed on 96 well plates, and 20 ul nutrient solutions were added at different culture times. The OD value was determined after incubation at 37°C for 3 h.The cells of the three same treatment groups in the 6-well plate were gathered together for centrifugation and washed through the pre cooled PBS  to absorb the supernatant as much as possible. Next, the inhibitor of 1% phosphatase and protease was added, and the cells were subjected to ultrasonic wave for 5 s on the ultrasonic cell grinder after repeated blowing.18 ul PBS and two ul protein supernatant were added to the 96 well plate hole, and 200 ul premixed water-soluble compound working solution was added to fully mix and put in the 37°C incubator for 30 min. The protein concentration of each sample is calculated according to the standard curve formula and then multiplied by the corresponding dilution multiple to obtain the protein concentration.The bottom of 10% of the preform was torn to get a white adhesive strip, and then the rubber was added to the electrophoresis buffer in the electrophoresis tank. The liquid wass injected beyond the conductor. The comb was pulled out, and the comb hole was cleaned with electrophoresis buffer to remove foam and adhesive. According to the preset sampling sequence and feeding amount, the protein sample shall be placed in the comb hole marked with protein. At the beginning of electrophoresis, the constant voltage should be 80 V. When the protein is gradually separated, the voltage should be increased to 140 V until the electrophoresis is completed.After electrophoresis, the glue, polyvinylidene fluoride membrane, filter paper and sponge pad were cleaned in the membrane rotation buffer solution to ensure that no bubbles are generated between each component. Next, the electrophoresis plate was placed in the groove of the rotary film buffer, ensuring that the adhesive faces black (cathode), and the polyvinylidene fluoride film faces white (anode), with a constant current of 350 mA. The membrane transfer time is usually 90–180 min, depending on the molecular weight of the target protein.The myocardial cells were reverse transcribed into RNA and complex DNA. The PCR reaction system is shown in Demethylated drugs can play a certain role in the treatment of patients with myocardial infarction. It can be seen from the above text that compared with patients with normal myocardium, the expression levels of microRNA-320 and microRNA-204 in patients with myocardial infarction are significantly reduced. Therefore, .5 umol and two umol of demethylated drugs were used to treat myocardial cells, and the expression levels of microRNA-320 and microRNA-204 genes were studied. The results are as shown in The results are shown in In order to analyze the specific effects of miRNA on cardiomyocytes, overexpression of miRNA was used to culture cardiomyocytes. The experiment was divided into 5 days, and the expression levels of microRNA-320 and microRNA-204 were gradually increased to observe the cell activity. The change of OD value for five consecutive days is shown in In order to analyze the impact of overexpression of miR-320 and miR-204 on patients in different groups, the apoptosis rate of myocardial cells in the case of overexpression of miR-320 and miR-204 was tested respectively. The results are shown in At present, the function of miRNA in human heart disease has been studied from patients with heart failure. Heart failure is due to the pump failure of the heart, which can not provide sufficient blood supply for the heart and usually can lead to pathological cardiac hypertrophy and death.Cardiac hypertrophy is an important manifestation of myocardial cells in various aspects such as blood pressure overload, endocrine disorder, myocardial injury, myocardial tissue and contractile protein gene mutation. Heart failure and sudden cardiac death are related to pathological myocardial hypertrophy . TherefoThe relationship between the expression level of target genes and the prognosis of patients with myocardial infarction.In this paper, Kaplan-Meier method was used to compare the expression level of target genes in 30 patients with myocardial infarction. The results showed that the total survival period (OS) of the group with high expression of target genes is lower, as shown in By analyzing the treatment response of patients with myocardial infarction in the high expression group and the low expression group of target gene, it can be found that the total survival period of patients with myocardial infarction in the high expression group is shorter. This shows that the role of high-level target genes in myocardial infarction is an important factor to affect the prognosis of myocardial infarction.etc. In this paper, experiments have proved that miR-320 and miR-204 have differential expression in patients with myocardial infarction. Compared with people with normal myocardial cells, the expression levels of microRNA-320 and microRNA-204 in patients with myocardial infarction are significantly down regulated. The level of target gene expression corresponding to miR-320 and miR-204 has an important impact on the prognosis of myocardial infarction, and the expression of target gene transcripts is a negative factor for the prognosis of myocardial infarction. In this paper, there are still some deficiencies in the experiment, so in the follow-up research, more about medical data, machine learning and healthcare strategies supporting IoMT should be learned, hoping to better understand the pathogenesis of myocardial infarction.The human genome has more than 1,000 miRNAs, which regulate 1/3 of the human genes. MiR-1 and miR-133 are less expressed in genes, but MiR-126-3p, miR-125a, miR-125a, MiR-143, miR-320 and miR-204 are mainly expressed in tissue cell types. In other words, miRNA expression is different in different diseases. Therefore, the differential expression of miRNAs can be used to predict and diagnose diseases. In recent years, the abnormal expression of gene mRNA is closely related to cardiovascular diseases such as tumor, diabetes, heart failure,


Low-dose steroids are known to increase arterial pressure during septic shock through restoration of vasopressor response to norepinephrine. However, their effects on cardiac performance and ventriculo-arterial coupling (VAC) have never been scrutinized during human septic shock. The aim of this study was to perform a comprehensive description of the cardiovascular effects of low-dose steroids using modern echocardiographic tools (including speckle tracking imaging).This prospective study was conducted in the intensive care unit (ICU) of a university hospital in France. Consecutive adult patients admitted for septic shock and requiring low-dose steroid therapy were prospectively enrolled within 24 h of septic shock onset. We recorded hemodynamic and echocardiographic data to explore left ventricle (LV) contractility, loading conditions and VAC just before the initiation of low-dose steroids  and 2–4 h after.Fifty patients  were enrolled. Arterial pressure, heart rate, almost all LV afterload parameters, and most cardiac contractility parameters significantly improved after steroids. VAC improved with steroid therapy and less patients had uncoupled VAC (> 1.36) after (24%) than before (44%) treatment.In this comprehensive echocardiographic study, we confirmed an improvement of LV afterload after initiation of low-dose steroids. We also observed an increase in LV contractility with improved cardiovascular efficiency (less uncoupling with decreased VAC). Relative adrenal insufficiency, also appraised as critical illness-related corticosteroid insufficiency is common during septic shock. It is the main pathophysiological rationale for the use of low-dose corticosteroid therapy in septic shock . The antIn addition to vasoplegia, septic shock is also characterized by myocardial dysfunction, with a major interaction between contractility and loading conditions . Animal We conducted a prospective observational monocenter study in the medical intensive care unit (ICU) of Henri Mondor University Hospital, Créteil, France, between August 8, 2018 and May 29, 2021. All consecutive patients admitted during this period for septic shock (as defined according to the American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM) Consensus Conference  and requThe study was approved on July 12, 2018 by the institutional ethics committee, Institutional Review Board (IRB) Mondor (reference number: 2201948) as a component of standard care, and patient consent was waived, as per French law. Written and oral information about the study was given to the families.Norepinephrine was the first-choice vasopressor therapy (used to target a MAP of 65 mmHg or more); dobutamine was added, based on physician decision, in the presence of decreased LVEF (<45%) with ongoing signs of hypoperfusion despite adequate MAP and correction of hypovolemia with absence of fluid responsiveness. Catecholamine dose and fluid management were kept constant between the two ultrasound assessments, unless significant hemodynamic instability; patients who required a change in norepinephrine dose and/or fluid loading during the study protocol were secondarily excluded. The steroid replacement therapy consisted of hydrocortisone 50 mg intravenously every 6 h plus enteral fludrocortisone (50 μg/day). The patients were followed up until ICU discharge.Transthoracic echocardiography (TTE) was performed in early phase of septic shock after hemodynamic stabilization by trained operators  . The TTEE/A and E/e’ ratios from pulsed-wave Doppler early (E) and late (A) and tissue Doppler early (e’) diastolic wave velocity at the lateral and septal mitral valve annulus] , to reflect the pulsatile component of peripheral load (Afterload was assessed using the following indices: (i) diastolic arterial pressure (DAP) which is often used as a surrogate of LV afterload in clinical practice ; (ii) syral load  = 0.9*smHg)) ; and (v)mL)1000 .es(sb)], as proposed by Chen et al. (LV systolic function was assessed using indices obtained from the following techniques: (i) two-dimensional echocardiography, with LVEF  is a major determinant of the LV systolic performance and the interaction between heart and vascular system. Ees corresponds to the slope of the end-systolic pressure-volume relation, which is classically invasively determined by catheter with LV pressures and volumes recorded under different cardiac loading conditions. Several alternatives have been proposed for estimating Ees without loading interventions, and these are generally referred to as single-beat methods [Ees(sb)]. The algorithm for Ees(sb) proposed by Chen et al. ] and at end systole [Ees(sb) = Pes/(Ves-V0)], their ratio [ENd = Ed/Ees(sb)], called the time and amplitude normalized time varying elastance, has been shown to be conserved during the isovolumic contraction period in humans ((a) If we consider LV elastances during isovolumic contraction /[SV × ENd] ((b) If we consider the onset of ejection (end of isovolumic contraction) for EV × ENd] .Nd, a regression model has been developed using systolic function (LVEF) and arterial load , along with pre-ejection and ejection times, as follows: non-invasive estimated normalized left ventricular elastance at the onset of ejection [ENd(est)] = 0.0275–0.165 × LVEF + 0.3656 × (Pd/Ps) + 0.515 × ENd(avg); where ENd(avg)  = Σai × tNdi; ai values are 0.35695, –7.2266, 74.249, –307.39, 684.54. –856.92, 571.95, and –159.1 for i = 0 to i = 7, respectively; the tNd value is determined by the ratio of pre-ejection time (R-wave to flow onset) to total ejection time (R-wave to end-flow), with the time at onset defined by the aortic Doppler waveform ((c) To estimate Ewaveform .EA) was assessed using a simple non-linear approach as recently proposed = We also assessed the heart-arterial interaction with the ventricular-arterial coupling (VAC) = s(sb) , as suggs(sb) ; a VAC >s(sb) , 33. LV .m-2)145 , 35. Laslastance .The following data were collected at inclusion: age, sex, body mass index, past medical history, standard treatments, Sequential Organ Failure Assessment (SOFA) score , SimplifWe defined septic cardiomyopathy as the appearance at echocardiography of hypokinesia  during the first day of septic shock with the absence of acute coronary syndrome or history of chronic heart failure in the medical charts. We assessed the change in MAP between baseline and 2–4 h after steroid administration. We defined steroid MAP responders (non-responders) as patients with a relative increase in MAP above (below) the median value of the cohort.T-test or Mann-Withney test for independent variables, and a paired T-test or paired Wilcoxon test for paired variables, with Benjamini-Hochberg correction for multiple comparisons. The reproducibility of some echocardiographic variables in our laboratory was assessed using the British Standards Institution coefficient (twice the standard deviation of the differences in repeated measurements)  and Graph-Pad Prism software . The primary endpoint of this study was the change in LV contractility after the first administration of low-dose steroid therapy. For the analysis of the primary endpoint, the LV-GLS was chosen for its robustness, reproducibility and sensitivity. We calculated that a sample size of at least 43 patients would have a 90% power to detect a 20% improvement in LV-GLS after low-dose steroid therapy initiation, considering a baseline LV-GLS of –14% with a standard deviation (SD) of 4%, based on previous echocardiographic studies in septic shock patients –41. TakiDuring the study period, 188 patients admitted for septic shock and receiving steroid therapy were screened for enrolment. Among these patients, 135 were eligible for the study and 85 were excluded for logistical reasons, poor echogenicity, hemodynamic instability, or withdrawing of life support; finally, 50 patients were included in the study . The logAt inclusion, all patients were receiving norepinephrine, at a median dose of 3.8 (2.3–5.5) mg/h, after a significant fluid resuscitation [median fluid balance of 3 (2–4) L since admission] . As compTo the exception of LV end-systolic wall stress, all afterload parameters significantly improved after low-dose steroid therapy  . Among pp < 0.01).To the exception of LVEF, all contractility parameters  significantly improved after low-dose steroid therapy . VAC sigOverall, the hemodynamic and echocardiographic changes induced by low-dose steroids were similar in patients with or without septic myocardial dysfunction . MAP resThe main findings of this echocardiographic study in septic shock patients were that in addition to their role in peripheral vascular tone (increased afterload), low-dose steroids increased the LV contractility and improved the cardiovascular efficiency.In this cohort of septic shock patients, the hemodynamic effects of low-dose steroids therapy were coherent with the literature. Indeed, all arterial pressures  increased in accordance with previous reports on this topic . Moreoveper se. Our finding of increased cardiac contractility with low-dose steroids is in accordance with previous reports suggesting inotropic properties  estimate; (ii) the formula of Ees(sb) uses the ratio of pre-ejection to total systolic time raised to multiple powers, such that small variations in the measurements of time intervals may lead to relatively large changes in the estimated Ees(sb) value.End-systolic elastance is a theoretical load independent variable of LV contractile function deduced from the pressure-volume loops, obtained by invasive ventricular catheterization. Herein, we assessed LV end-systolic elastance by the bedside single beat method proposed by Chen et al. , which io  is assumed to be null, like in the normal heart, but this is not the case in heart failure or during hemodynamic instability  Mondor (reference number: 2201948) as a component of standard care, and patient consent was waived. Written and oral information about the study was given to the families.FB had full access to all of the data in the study and took responsibility for the integrity of the data, and the accuracy of the data analysis. FB and AM designed the study and wrote the manuscript. FB, AC, PM, and KR performed echocardiographies. FB, AC, and PM collected the data. FB, AC, PM, NP, GC, KR, and AM contributed to interpretation of data, drafting of the submitted article, and critical revisions for intellectual content. All authors read and approved the final manuscript.