Ventricular arrhythmias (VA) are a major cause of sudden cardiac death (SCD). Echocardiography is the first widely available imaging tool which guides VA management strategies. Along with other invasive and noninvasive imaging techniques, it provides essential information for identification of VA substrate such as differentiation between ischemic and non-ischemic etiology and identification of structural heart disease. Both classic as well as novel echocardiographic techniques such as left ventricular strain measurement and mechanical dispersion assessment provide prognostic information and assist in risk stratification. Furthermore, intracardiac echocardiography may have an adjunctive role for the VA ablation by providing real-time visualization of cardiac structures, continuous monitoring of catheter location and early recognition of procedural complications. This review gathers all relevant information that echocardiography may offer prior to VA ablation procedures. Ventricular arrhythmias (VA) consist of a large spectrum of ventricular rhythm disturbances ranging from premature ventricular complexes to ventricular tachycardia and fibrillation. VA are a major cause of sudden cardiac death (SCD) and a significant burden on the patient’s quality of life. In the majority of cases, VA are associated with structural heart disease.Cardiac imaging plays an essential role in revealing the underlying etiology of VA and for SCD risk stratification. Echocardiography is the first readily available, inexpensive and accurate imaging tool used to identify the structural changes associated with VA. It is usually followed by multimodality imaging techniques such as cardiac magnetic resonance (CMR), cardiac computed tomography (CT) and nuclear imaging which bring additional information about the VA substrate. Basic echocardiography measurements such as left ventricle ejection fraction (LVEF) have long been used to assess the risk of SCD and current guidelines still rely on it for the indication of a implantable cardiac defibrillator (ICD) .Substrate ablation is an efficient interventional treatment for VA. For a safe and successful ablation there is a need to understand anatomical VA substrate along with the electric substrate defined by the electroanatomic mapping (EAM). This review will focus on the necessary information provided by the echocardiography prior to the VA ablation procedure.Echocardiography is useful in the diagnosis of structural heart disease . TransthFor the evaluation of LV systolic function, LVEF is the main parameter used in VA management. The ESC guidelines recommend performing echocardiography in all patients with suspected or known VA for assessment of LV function and identification of structural substrate . In patiTransthoracic and transesophageal echocardiography are the routine tools for the diagnosis and severity assessment of underlying valvular heart disease which may contribute to VA occurrence.Echocardiography plays a significant role in the diagnosis and in management of patients with congenital heart disease and VA. Several studies have shown that right ventricle (RV) and LV dysfunction are risk factors for VA in congenital heart disease patients . It is mA multicenter study performed by Koyak et al. showed that moderate to severe systemic or subpulmonary ventricular dysfunction were associated with a high risk of SCD, especially in adults with transposition of great arteries, Eisenmenger physiology and surgically repaired tetralogy of Fallot .Finally, echocardiography may diagnose cardiomyopathy as the substrate for VA .The established echocardiographic criteria for diagnosis of the different cardiomyopathies are summarized in Almost 50% of SCD events occur in patients without structural heart disease . Table 2Other studies show an overlap between different VA etiology as for BrS and arrhythmogenic cardiomyopathy . The prePrior to VA ablation, echocardiographic data can be completed with cardiac magnetic resonance (CMR). CMR may be later combined with EAM information. Several studies have confirmed that low endocardial voltage corresponds to the presence of scar tissue as defined by the late gadolinium enhanced CMR . Pre-proEchocardiography plays an important role in SCD risk stratification. Reduced LVEF is associated with a high risk of VA and mortality, but the ability to predict VA is limited . Some ofOther echocardiographic markers, which are additive to LVEF, are associated with high risk of VA: low global and/or regional strain, low relative wall thickness, worsening mechanical dyssynchrony, high peak strain dispersion  18]..18].Global wall motion score index (GWMSI) is a prognostic echocardiographic parameter that evaluate wall motion abnormalities and helps to differentiate between ischemic and nonischemic etiology . MahenthThe evaluation of exercise- or dobutamine-induced wall motion abnormalities could provide additional value to LVEF for risk stratification for VA in patients with coronary artery disease. Also, Elhendy et al. showed that ischemia during stress echocardiography is an independent predictor of death and ICD therapy in patients with coronary heart disease at high risk of arrhythmic death .Relative wall thickness (RWT) is defined as twice the posterior wall thickness divided by the LV diastolic diameter. A study which included patients enrolled in the MADIT-CRT trial demonstrated a powerful predictive value of low RWT for estimating the risk of VA and VA risk or death in either ischemic or nonischemic cardiomyopathy, heart failure and left bundle branch block (LBBB) ,11.The reduction of LV global longitudinal strain (GLS) and regional longitudinal myocardial deformation, especially low inferior strain, was associated with the occurrence of VA, irrespective of etiology of cardiomyopathy ,25,26. AMechanical dispersion is a measure of myocardial deformation heterogeneity and it is regarded as a novel risk parameter of VA, independently of LVEF . It is dIn patients with ischemic cardiomyopathy, Mahenthiran et al. showed that GWMSI and right coronary region infero-posterior akinesia identified those at increased risk of events . ErsbollIn hypertrophic cardiomyopathy (HCM), the most frequent fatal arrhythmia is spontaneous fast monomorphic ventricular tachycardia (VT), whereas non-sustained ventricular tachycardia (NSVT) is often found on ECG monitoring . HCM risEchocardiography plays a central role in diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), showing regional RV akinesia, dyskinesia or aneurysm . In patiIn non-compaction cardiomyopathy (NCM) echocardiography is the first-line imaging modality but cannot provide tissue characterization or accurate evaluation of RV function . CMR proPatients with dilated cardiomyopathy (DCM) are at high risk of SCD and the annual event rate of sustained VA is 4.5% . LVEF < Furthermore, Perry et al. demonstrated that in patients with moderate and severe decreased LVEF, mechanical dispersion ≥ 75 ms is related to VA, with a 9-fold increase in risk of VA events . In a prEchocardiography may also offer specific relevant information prior to the ablation procedure. It is important to diagnose pericardial fluid prior to or during catheter ablation procedure. The presence of a cardiac thrombus should also be diagnosed before VA ablation. Traditionally, TTE was the main imaging tool to diagnose thrombosis, however recently CMR and cardiac CT are frequently used . The guiEchocardiography has little contribuition in deciding the access route before catheter ablation. When femoral access is required, ultrasound-guided femoral arterial and venous access has been widely implemented in electrophysiological procedures in an effort to reduce vascular complications . Sharma Intracardiac echocardiography (ICE) generates 3-dimensional ventricular reconstruction that can be integrated in real-time with electroanatomic mapping. ICE provides real-time imaging of ventricular anatomy, catheter contact, and facilitates catheter manipulation during ablation .In patients with scar-related VT, ICE may identify the thinned, akinetic myocardium and therefore it may localize the scar. There are studies which found a good correlation between scar area identified by ICE and that defined by EAM . FurtherLV access for endocardial mapping and VA ablation can be achieved either by retrograde transaortic or by antegrade transseptal approach. ICE has an important role in gaining safe left atrial access during transseptal puncture since it enables real-time visualization of the sheath-needle assembly, the fossa tenting and the puncturing the interatrial septum . The tecICE also provides early recognition of procedural complications, such as pericardial effusion or thrombus formation on sheaths and catheters. The presence of clots in the LV apex, especially in the setting of anteroapical aneurysms, can be evaluated with ICE to avoid catheter manipulation and prevent embolism . AdditioFuthermore, ICE facilitates significant reduction of radiation exposure during catheter ablation . Zero flConventional echocardiography has an established role in the management of patients suffering from ventricular arrhythmias, while novel echocardiographic techniques such as LV strain measurement and mechanical dispersion assessment upgrade the diagnostic and prognostic role of the technique. Additionally, intracardiac echocardiography may have an integrative role in real-time assessment of LV anatomy during VA ablation and early recognition of procedural complications.


Ventricular arrhythmias (Vas) are a life-threatening condition and preventable cause of sudden cardiac death (SCD). With the increased utilization of implantable cardiac defibrillators (ICD), the focus of VA management has shifted toward reduction of morbidity from VAs and ICD therapies. Anti-arrhythmic drugs (AADs) can be an important adjunct therapy in the treatment of recurrent VAs. In the treatment of VAs secondary to structural heart disease, amiodarone remains the most well studied and current guideline-directed pharmacologic therapy. Beta blockers also serve as an important adjunct and are a largely underutilized medication with strong evidentiary support. In patients with defined syndromes in structurally normal hearts, AADs can offer tailored therapies in prevention of SCD and improvement in quality of life. Further clinical trials are warranted to investigate the role of newer therapeutic options and for the direct comparison of established AADs. Ventricular arrhythmias (VAs) including ventricular tachycardia (VT) and ventricular fibrillation (VF) can be life-threatening and can adversely affect patient quality of life ,2. The gThe majority of patient data and discussion will focus on VAs in patients with abnormal heart structure, but this review also includes discussions on defined syndromes of sustained VAs including Brugada Syndrome, Long QT Syndrome, and Catecholaminergic Polymorphic VT.The Vaughan–Williams (VW) classification system is the most commonly used system to classify AADs. It has the advantages that AADs are clustered by channel, effect on the action potential, and effect on parameters within an EP study . All of the Class I Medications affect the cardiac electrical system via the blockade of sodium channels. Despite this, the blockade of different sodium channels can have a wide variety of effects, and therefore, this overall class is split into three subgroups: Class IA, Class IB, and Class IC. All Class I medications bind in a “use-dependent” fashion. This use-dependent behavior causes increased drug binding and consequently increased sodium channel blockade at faster stimulation rates  . PharmacThe Class 1A AADs exhibit similar electrophysiologic effects via blockade of the rapid inward sodium depolarization current in a use-dependent fashion and prolongation of repolarization via blockade of the delayed rectifier potassium channel in a reverse use-dependence fashion ,13. FurtThere have been multiple studies showing the efficacy of procainamide as an adjunct medication in patients with ongoing Vas, despite more commonly used AADs (Amiodarone or Lidocaine) in acute VA ,16,17. TIn contrast, the use of oral procainamide for outpatient prevention of secondary VA has limited evidentiary support. While the 1993 ESVEM trial data largely supported the use of Sotalol, it also found the procainamide was an effective agent at controlling VAs and limiting the inducibility of VAs in subsequent EP studies . SimilarGiven the efficacy of procainamide, quinidine, which is more readily available in oral formulations, has been used as a salvage therapy for patients with structural heart disease for recurrent VA despite prior AAD treatment. It has also shown to have efficacy in both idiopathic and post-infarct ectopy-triggered polymorphic VT (PMVT) syndromes ,24. A stQuinidine’s use as a primary agent in VA that may have a component of ectopy-triggered sustained arrhythmias, namely Brugada Syndrome, has been well studied. While the underlying pathophysiology of Brugada remains poorly understood, ventricular ectopy can lead to sustained and life-threatening VA in these patients . In multWith further data on procainamide and quinidine, the use of disopyramide has largely fallen out of clinical practice as an AAD. Its known effect of negative inotropy and proarrhythmic qualities at high dosages have been strong factors discouraging its use. However, older studies utilizing this medication are still informative for clinical decision-making in areas where disopyramide is readily available. Its disuse has also been driven by studies showing decreased efficacy when compared to alternative AADs ,34,35,36Due to its negative inotropic effects, disopyramide is frequently used in patients with hypertrophic cardiomyopathy (HCM) and LV outflow tract obstruction. Some observational evidence may suggest a decreased mortality secondary to SCD or VAs in patients appropriately considered for disopyramide therapy . HoweverThe Class IB AADs, lidocaine and mexiletine, exhibit a use-dependent blockade of the inward sodium depolarization current, thereby decreasing maximal velocity of depolarization, shortening of action potential and ERP duration, and decreasing automaticity of phase 4 depolarization .Lidocaine is only available in intravenous form and remains one of the most heavily used agents in the acute inpatient treatment of VAs . Despitep = 0.001) and ICD therapies  [The foundation for the frequent use for mexiletine therapy was established through efficacy demonstrated in multiple small studies in the 1980s and early 1990s ,48,49,50= 0.003) . Again, = 0.003) .An area with relatively strong support for mexiletine is in patients with Congenital Long QT Syndrome Type 3 (LQT3). The genetic gain-of-function mutation effects sodium channel NaV1.5. The result is a prolongation of QT through delayed sodium channel current which Mexiletine effectively blocks. The largest trial by Mazzanti et al. showed that 34 LQT3 patients treated with Mexiletine saw a reduction in not only QT intervals, but also an 87% relative reduction in patients with VAs (22 to 3%) and a 93% reduction in arrhythmia event rate .In regard to the effect on their target channel, Class IC AAD are the most potent among the inward sodium blocking agents. The strength of this binding thereby markedly reduces the action potential conduction velocity in atrial, ventricular, and specialized conduction tissues in a use-dependent fashion with minimal effect on overall action potential duration or ERP .Given the limited efficacy and use of these medications in chronic VAs, especially in the setting of the relative contra-indications in patients with structural heart disease, we will discuss both flecainide and propafenone in this section. Both the CAST trial and the CASH trial showed a significantly elevated mortality in patients with structural heart disease treated with these agents ,59. The Lastly, similar to procainamide, while flecainide should not be used to prevent VA in patients with Brugada syndrome, it has been shown to have a useful role in helping to establish a diagnosis .Beta blockers exhibit their antiarrhythmic properties via blunting sympathetic activity on cardiac tissue, most notably through decreasing phase 4 depolarization and thereby decreasing automaticity and conduction velocity . Beta blConversely, studies on the impact of beta blocker therapy on the morbidity of VAs and ICD therapies show improvement. The OPTIC trial showed that patients on beta blocker therapy with ICD devices had a reduction in ICD therapies . Even moThis improvement in combination is also seen with class I agents. Patients in the CAST trial showed a VA reduction in patients treated with both beta-blockers and class IC agents ; this imDespite its limitations in the general treatment of recurrent arrhythmias, there is clear evidence for the use of beta blockers in specialized circumstances. In acute ES, beta blocker therapy remains a cornerstone of dampening adrenergic stimulation . MultiplLastly, beta blockers have been shown to have a role in Long QT syndrome as well. The strongest evidence has been seen in types LQT1/LQT2, as beta blockers have been seen to historically reduce syncopal events and SCD while more modernly showing shorten QT intervals at faster rates ,88. HoweAmiodarone functions primarily through blockade of the delayed rectifier potassium channel, effectively prolonging repolarization and increasing the ERP to decrease the likelihood of reentry . Unlike Amiodarone is the most studied and most commonly used medication in the treatment of secondary VAs. It remains the only guideline-directed medication in patients with either ischemic or non-ischemic cardiomyopathy . Prior tWhile amiodarone has the strongest evidence base for its routine use in clinical practice, it is often avoided due to the frequency of its long-term side effects. The high iodine content within its formulation can lead to thyroid toxicity, and both thyrotoxicosis and hypothyroidism can occur . AmiodarDronedarone is non-iodinated benzofurane derivative structurally related to amiodarone . Due to Dofetilide is a class III antiarrhythmic that selectively blocks the delayed outward rectifying potassium current, thereby increasing the effective refractory period (ERP) without delaying intracardiac conduction . Importap = 0.008) [Sotalol is a racemic mixture of d- and l-sotalol with unique pharmacologic effects exhibiting class II (nonselective ß-blocker) properties in addition to class III inhibition of delayed potassium rectifier channel, resulting in an increase in action potential duration and effective refractory period . In cont= 0.008) . Due to = 0.008) . Althoug= 0.008) .The non-dihydropyridine calcium channel antagonists, verapamil and diltiazem, exhibit antiarrhythmic effects predominately at the AV-node via blocking of slow inward Ca current, thereby prolonging the effective refractory period (ERP) with minimal effects on atrial/ventricular myocytes or the His–Purkinje system . With isp = 0.03) [While most well known as a novel antianginal therapy, ranolazine exhibits features most similar to amiodarone, blocking inward depolarizing and outward repolarizing currents affecting sodium, potassium, and calcium channels. The net effect is a concentration-dependent prolongation of action potential duration and an early decrease after depolarizations . Initial = 0.03) . The MER = 0.03) . Further = 0.03) .Given its effect on inward sodium current and the subsequent increase in ventricular relaxation and perfusion, ranolazine has emerged as a therapeutic option in the treatment of HCM. The RESTYLE-HCM study showed that there was greater than 50% reduction in PVC burden with treatment versus placebo over five months . While tAdenosine is an endogenous nucleoside that acts on adenosine receptors primarily located on the specialized conduction tissues of the SA and AV nodes, resulting in activation of potassium channels and hyperpolarization and decreased automaticity of these tissues. With a half-life of only 10 s, this classically results in a transient AV nodal block to terminate SVT. However, in some forms of repetitive monomorphic ventricular tachycardia (RMVT), specifically in right ventricular outflow tract (RVOT) VT, adenosine is such an effective treatment that these arrhythmias are also known by the name “Adenosine-Sensitive VT” ,134,135.+/K+ ATPase with a resultant rise in intracellular calcium and increased contractility and the latter through enhancing vagal tone predominately at the AV node, resulting in decreased conduction velocity and increased ERP. Digoxin use has been largely relegated to advanced heart failure and refractory atrial fibrillation, as initial trials showed a trend toward increased mortality in these populations [Digoxin exhibits both mechanical and electrophysiologic effects on the cardiovascular system: the former through inhibition of Naulations . Furtherulations ,139. Altulations . In 2015ulations . PatientCA-L channels. Given the small patient population of this diagnosis, studies are largely case series but do show strong efficacy in the use of Isoproterenol [Isoproterenol is a beta-1 and beta-2 adrenergic receptor agonist that activates cardiac pacemaker cells . Given toterenol ,144.Ivabradine functions in a use-dependent fashion at the SA node, inhibiting the mixed sodium-potassium current (If) and thereby slowing depolarization of the pacemaker potential and lowering heart rate without affecting inotropy or vascular resistance . InitialAmiodarone remains the most evidence-based treatment of recurrent VAs. Beta blocker therapy is likely undervalued given the strength of evidence behind it and should be considered a cornerstone of VA pharmacologic therapy. There is limited but relatively strong data to support the use of specific antiarrhythmics in specialized circumstances . The medication choices in each of these specialized circumstances is listed in


Heart rate variability (HRV) is the physiological variation in the intervals between consecutive heartbeats that reflects the activity of the autonomic nervous system. This parameter is traditionally evaluated based on electrocardiograms . Seismocardiography (SCG) and/or gyrocardiography (GCG) are used to monitor cardiac mechanical activity; therefore, they may be used in HRV analysis and the evaluation of valvular heart diseases (VHDs) simultaneously. The purpose of this study was to compare the time domain, frequency domain and nonlinear HRV indices obtained from electrocardiograms, seismocardiograms  and gyrocardiograms  in healthy volunteers and patients with valvular heart diseases. An analysis of the time domain, frequency domain and nonlinear heart rate variability was conducted on electrocardiograms and gyrocardiograms registered from 29 healthy male volunteers and 30 patients with valvular heart diseases admitted to the Columbia University Medical Center . The results of the HRV analysis show a strong linear correlation with the HRV indices calculated from the ECG, SCG and GCG signals and prove the feasibility and reliability of HRV analysis despite the influence of VHDs on the SCG and GCG waveforms. Cardiovascular diseases remain the most common cause of death in the world and constitute a significant concern for public health due to the economic burden (expected to reach 47 trillion USD by 2030) and the overload on medical personnel (17.9 million deaths worldwide in 2016) despite progress in prevention, diagnosis and therapy . Due to Valvular heart disease is any cardiovascular disease that affects any heart valve  ,8. The mVHDs are usually diagnosed by echocardiography, computed tomography or magnetic resonance imaging , which aSeismocardiography (SCG) and gyrocardiography (GCG) are two complementary techniques ,17,18; sSeismocardiographic (SCG) and gyrocardiographic (GCG) signals are non-stationary signals with distinct quasiperiodic features known as waves, e.g., the mitral valve opening wave (MO), the mitral valve closure wave (MC), the isovolumetric contraction wave, the rapid ejection wave, the aortic valve opening wave (AO), the aortic valve closure (AC) wave and the cardiac filling wave ,26,27,28SCG and GCG have found applications in the diagnosis of several cardiovascular diseases, such as aortic stenosis ,31,32, aOne of the most prominent applications of seismocardiography and gyrocardiography is heart rate variability (HRV) analysis ,53,54,55HRV analysis has traditionally been performed on interbeat intervals obtained from electrocardiograms  ,55,56,59The advantages of using seismocardiography and/or gyrocardiography over electrocardiography for cardiac diagnosis are the simpler measurement setup (using only one sensor) and the availability of information on cardiac intervals, contractility and the state of heart valves at the same time ,56,59,63The purpose of this study is to evaluate the differences between the time domain, frequency domain and nonlinear HRV indices derived from electrocardiograms, seismocardiograms and gyrocardiograms in healthy volunteers and patients with valvular heart diseases. This study is an extended version of  and is bThis study was carried out on two publicly available datasets with concurrent electrocardiograms, seismocardiograms and gyrocardiograms. The first dataset if “Mechanocardiograms with ECG reference” published by M. Kaisti et al. ,66 contaThe first dataset consists of 29 recordings of concurrent ECG, SCG and GCG signals acquired from 29 healthy male volunteers that were registered with sensors attached to the chest wall over the sternum with a double-sided tape and with a sampling frequency of 800 Hz. The subjects were lying either in the supine position or on their left or right side ,65,66.Electrocardiograms were acquired with an ADS1293 , seismocardiograms were recorded with a triaxial capacitive digital accelerometer  and gyrocardiograms were acquired using a 3-axial MAX21000 gyroscope  ,65.The rotation and translation axes in seismocardiography and gyrocardiography were defined for both datasets as follows: the x axis was oriented laterally from left to right, the y axis was oriented from head to foot and the z axis was oriented from back to chest .The second dataset consists of 100 simultaneous recordings of raw ECG, SCG and GCG signals with annotated heartbeats acquired from 100 patients with valvular diseases admitted to two different clinical sites: 30 patients were admitted to Columbia University Medical Center  and 70 patients were admitted to the First Affiliated Hospital of Nanjing Medical University . ECG, SCG and GCG signals were recorded before any treatment in both populations of patients .To balance the number of healthy volunteers and patients with valvular heart disease in this comparison study, we took only 30 patients  who were admitted to the Columbia University Medical Center . A total of thirty patients had aortic stenosis, nine patients had tricupsid valve regurgitation (TR), five had mitral valve stenosis (MS), four had mitral valve regurgitation (MR) and no patients had aortic valve regurgitation. During registration, each subject was asked to be awake and stay in the supine position, breathing normally.The ECG, SCG and GCG signals were recorded with Shimmer 3 ECG module  with a sampling frequency of 256 Hz (recordings UP-01 to UP-21) and 512 Hz (recordings UP-22 to UP-30) ,67. The The basic characteristics of both datasets are shown in Signal processing started with importing the data into MATLAB R2022b ; data from  were dirHeartbeat detection in SCG signals and GCG signals for both datasets was based on the approach presented in ,53,54,69Local maxima that occur within 100 ms of the R wave in concurrent ECG signals are associated with the aortic valve opening waves that are single sharp peaks on the z-axis of the SCG signal and the y-axis of the GCG signal ,20,45,71HRV analysis was carried out according to the recommendations published in ,59 and cj-th sample and j-th sample [The frequency bands of the HRV spectrum were defined as follows: the very low-frequency band was defined as 0.0033–0.04 Hz, the low frequency band was defined as 0.04–0.15 Hz and the high-frequency band was defined as 0.15–0.4 Hz ,72. The h sample ,75.(2)t1, SD2 and SD1/SD2.The non-linear analysis of heart rate variability was based on three indices derived from the geometrical features of Poincaré maps: SD1 is a measure of the short-term heart rate variability that is defined as the width of an ellipse fitted to scatter points of a Poincaré map and may be expressed as the standard deviation of the distances from the identity line SDion (SD) ,79,80,812 is the length of an ellipse fitted to the scatter points of a Poincaré map that reflects the long-term heart rate variability and is calculated as the standard deviation of the distance of points from the SD1/SD2 is calculated as the ratio between SD1 and SD2 and reflects the unpredictability of the heart rate [SDart rate .1, SD2 and SD1/SD2.The results of HRV analyses on electrocardiograms, seismocardiograms and gyrocardiograms obtained from healthy volunteers and patients with VHDs were expressed as the mean and standard deviation (SD) values and are shown in t-test for the significance level of 0.05. The results of the t-test are shown in The mean and standard deviation values of most HRV indices for patients with VHD are significantly different from those of healthy volunteers, except for AVNN and VLF. These differences were further evaluated by applying the Student’s 2. This proves a significant influence of ventricular heart diseases on the results of heart rate variability in time domain, frequency domain and nonlinear analyses. These results confirm the findings related to The differences between the HRV indices in healthy volunteers and in patients with VHD shown in The findings reported in ,22,45,51datasets .p-value under 0.001, except for SD1/SD2 between ECG and SCG signals from VHD patients. The correlation between the analyzed HRV indices obtained from ECG and GCG signals .The results presented in We have performed HRV analysis on electrocardiograms, seismocardiograms and gyrocardiograms from healthy volunteers and patients with VHD based on publicly available datasets.The mean and standard deviation values of HRV indices obtained from healthy subjects are similar to those reported by Siecinski et al. in ,50,52,532. This observation was confirmed by a Student’s t-test. Despite the fact that RMSSD and SD1 should be identical [The mean and standard deviation values of most HRV indices for patients with VHD are significantly different from those of healthy volunteers, except for AVNN, LF and SDdentical , there w2, which was in line with [We have shown the significant influence of valvular heart disease on HRV indices, except for AVNN, SDNN (ECG and SCG), pNN50 (ECG), VLF (GCG), LF, HF (ECG) and SDine with ,85. The ine with  prove thine with ,53,54,622. Obtained values of Despite the significant influence of VHDs on HRV indices, the correlation between the HRV indices obtained from ECG and SCG signals is strong, except for SDt al. in  and Chart al. in . Howevert al. in ,43,45,52Such results are influenced by age , comorbidities, signal quality and the use of different accelerometers and gyroscopes operating with different sampling frequency and accuracy, according to the available datasheets ,87,88.1 values did not result in significantly different The differences between RMSSD and SDr ageing ,54.The limitations of the study include the use of only one type of heartbeat detector for seismocardiograms and gyrocardiograms that depends on a concurrent electrocardiogram, the influence of specific cardiovascular conditions or medication on the calculated HRV indices was not considered and the morphological changes in SCG and GCG signals due to valvular heart disease was not evaluated.In future studies, we will consider evaluating the influence of various cardiovascular conditions on HRV indices derived from ECG, SCG and GCG signals; indices derived from larger and more diverse groups, including the analysis of SCG and GCG signal morphology; and indices derived from other detectors of SCG and GCG signals. In this study, we proved that a heart rate variability analysis based on cardiac mechanical signals ,31,89 ma1 and SD1/SD2. The linear correlation between the HRV indices obtained from the ECG and the mechanocardiograms is strong both in healthy volunteers and in patients with VHD, except for SD2.The results of the heart rate variability analysis based on mechanocardiograms  in both a healthy population and patients with VHD remain valid as long as heartbeats are correctly detected. Valvular heart disease significantly affects RMSSD, pNN50 , VLF , HF , LF/HF, SDFuture studies should include an evaluation of other cardiovascular conditions, larger and more diverse groups and other heartbeat detection methods for mechanocardiograms, and an analysis of the morphology of cardiac mechanical signals. We showed that mechanocardiogram-based heart rate variability analyses can be used in the diagnosis and monitoring of cardiovascular disease, which could be more cost-effective and convenient for patients.


Background: The correlation between myocardial strain and infraction size by cardiac magnetic resonance imaging in ST-segment elevation myocardial infarction (STEMI) with preserved left ventricular ejection fraction (LVEF) is not clear.Objective: To investigate the correlation between myocardial strain and myocardial infarction size in patients of acute STEMI with preserved LVEF.Materials and Methods: A retrospective study was conducted to assess 31 patients with acute ST-segment elevation myocardial infarction (STEMI)after primary percutaneous coronary intervention (PCI) who received cardiac magnetic resonance (CMR) imaging during hospitalization at the Central Hospital of Shandong First Medical University from 2019 to 2022 and whose echocardiography indicated preserved LVEF (LVEF≥50%). The control group consisted of 21 healthy adults who underwent CMR during the same period. We compared the CMR characteristics, global and segmental strain between the two groups. Furthermore, the correlation between the global strain and the segmental strain of the left ventricle and late gadolinium enhancement (LGE) were evaluated.Results: Compared with healthy controls, the left ventricular ejection fraction (LVEF) of STEMI patients with preserved LVEF was significantly decreased (p < 0.05). Moreover, the global radial strain (GRS) , global circumferential strain (GCS) , and global longitudinal strains (GLS)  were damaged in patients. Furthermore, GCS and GLS were associated with LGE size (%left ventricle) . In the multivariate model, we found that LGE size was significantly associated with GCS  but was not associated with GLS  and LVEF . The receiver operating characteristic (ROC) results showed that GCS emerged as the strongest LGE size (LGE >25%) prognosticator among strain parameters  and was significantly better (p = 0.001) than GLS  and LVEF .Conclusion: Among STEMI patients with preserved LVEF after PCI, CMR-FT-derived GCS had superior diagnostic accuracy than GLS and LVEF in predicting myocardial infarction size. In the last decade, advances in reperfusion and preventive therapies have reduced ST-segment elevation myocardial infarction (STEMI)-related mortality in hospitalized patients . Early rin vivo reference standard for measuring infarct size in STEMI patients (The left ventricular ejection fraction (LVEF) shown by echocardiography can reflect only global systolic function, whereas regional functional abnormalities or diastolic dysfunction cannot be accurately portrayed . With LVpatients . It is rpatients . Howeverpatients . The preTherefore, we aimed to explore whether CMR myocardial strain could be more sensitive and accurate than LVEF in detecting the degree of cardiac dysfunction and predicting myocardial infarction size in STEMI patients with preserved LVEF. In addition, we aimed to find parameters related to the infarction size so we may better stratify patient risk in clinical practice and formulate treatment plans based on reference data.The cases for this retrospective study originated from the Affiliated Central Hospital of Shandong First Medical University, which owns the first national chest pain emergency center in Jinan City. Our study selected patients who underwent emergency PCI and were hospitalized for acute ST-segment elevation myocardial infarction in the Central Hospital of Shandong First Medical University from 2019 to 2022. Thirty-one patients who underwent cardiac MRI over 14 days after PCI and whose echocardiography results showed LVEF ≥50% were selected for the study . Among tBased on the clinical baseline characteristics of the patients and the control group, the following information was obtained: age, gender, height, weight, body mass index (BMI), body surface area (BSA), smoking status, and history of hypertension, history of diabetes and of hyperlipidemia. The following are the diagnostic criteria for ST-segment elevation (measured at the J-point) in myocardial infarction: 1) Signs and symptoms consistent with myocardial ischemia , 2) Electrocardiogram findings (ST-segment elevation measured at the J-point) suggestive of ongoing coronary artery acute occlusion, as in the following cases: at least two contiguous leads with ST-segment elevation of 2.5 mm in men <40 years, 2 mm in men 40 years, or 1.5 mm in women in leads V2—V3 or 1 mm in the other leads [in the absence of left ventricular (LV) hypertrophy or left bundle branch block (LBBB)] or new left bundle-branch block on the 18-lead electrocardiogram and elevated troponin I level . The excCardiac MRI was performed on 3.0 T MRI systems  using a 32-channel phased-array abdomen coil. The protocol consisted of cine imaging and LGE imaging for analysis. First, standard cine images were acquired with end-expiratory breath hold steady-state free precession sequences (SSFP). Then, phase-sensitive inversion recovery (PSIR) was applied to late gadolinium enhancement (LGE) imaging. Infarct size was determined from the LGE images. The acquisitions of SSFP cine and PSIR were conducted in 2-chamber, 3-chamber, and 4-chamber long-axis planes, as well as a stack of contiguous short-axis slices, which encompassed the left ventricle from the atrioventricular ring to the apex.2 × 300 mm2, voxel = 2 mm × 2 mm × 6 mm, flip angle = 45°, and 6–8 mm slice thickness. LGE images were acquired 10–15 min after intravenous injection of 0.2 mmol/kg of gadolinium-based contrast agent  using a phase-sensitive inversion recovery (PSIR) sequence. The scanning parameters were as follows: TR/TE = 4.4/2.1 ms, FOV = 300 mm2 × 300 mm2, voxel = 1.5 mm × 1.5 mm × 10.0 mm, flip angle = 5°, and 10 mm slice thickness.Cine images were obtained using a steady-state free precession (SSFP) sequence with a breath-hold and ECG trigger for cardiac morphologic and functional analyses. The scanning parameters were as follows: repetition time (TR)/echo time (TE) = 2.8–3.0/1.4–1.5 ms, field of view (FOV) = 300 mmAll the analyses were conducted by two investigators with more than 5 years of experience each using the commercial software CVI42 . Endocardial and epicardial contours of the myocardium were applied, followed by subsequent software-driven automatic tracking . A qualiU test was applied to compare the continuous variables. Categorical variables were presented as exact numbers with percentages, and the x2 test or Fisher exact test was conducted for comparison. Correlation between variables was performed using Spearman’s rank or Pearson correlation test. A multiple linear regression model was constructed to assess correlates of GCS, GLS, LVEF, and LGE size. The optimal cut-off values to identify the LGE size of STEMI patients, whether higher than 25% or not, were derived from receiver operating characteristics (ROC) analysis by the Youden Index. AUCs were compared using validated methods described by DeLong et al. .Continuous variables were presented as mean ± standard deviation (SD) or median values with interquartile range (IQR), depending on the normality variables. Student’s t-test or Mann–Whitney g et al. . All tesA total of 31 STEMI patients with preserved LVEF who met the selection criteria were retrospectively identified in this study ; 21 healthy controls  were also included. No differences were observed between STEMI patients and healthy controls regarding age, gender, height, weight, body mass index (BMI), and body surface area (BSA) . In addip < 0.05). However, we did not detect any impairments of the CMR parameters of the right ventricular in the STEMI group .CMR examinations were conducted between the STEMI patients with preserved LVEF and healthy subjects. An overview of assessed CMR parameters is presented in p < 0.001; GCS: 14.66% [IQR: 17.91–11.56] vs. −19.26% [IQR: 21.03–17.73], p < 0.001; GLS: 8.88 ± 2.25% vs. −13.46 ± 2.63%, p < 0.001). Furthermore, we divided the left ventricle into apical, middle, and basal parts, according to the American Heart Association model (p < 0.05) except basal radial strain (p = 0.173). In addition, the left atrial total ejection fraction of the STEMI patients was worse than in healthy controls (p < 0.05)  .p < 0.05; GLS: r = 0.37, p < 0.05). However, we found that LV GRS was not associated with LGE . Also, an inverse correlation was found between LVEF and LGE .As p = 0.02) but not associated with GLS  and LVEF   .p = 0.001; GLS: 0.761 , p = 0.009, and for LVEF: 0.673 , p = 0.061 (p < 0.05) but no statistical significance with GLS (p > 0.05).The area under the curve (AUC) for the ability of each cardiac function parameter to correctly identify the LGE size of the STEMI patients with preserved LVEF (whether higher than 25% or not) were as follows: GCS: 0.836 ,  = 0.061 . The cutpre-a. Additionally, LVSVi and total LA EF tended to decline in patients. However, we did not find any significant differences in RVEF, RVEDV, RVEDVi, RVESV, RVESVi, or RVSVi between the two groups. GCS, GLS, and LVEF were associated with LGE size. Furthermore, GCS had superior diagnostic accuracy to GLS and LVEF in identifying myocardial infarction size in the STEMI patients with preserved LVEF. This work demonstrates that it may be possible to detect infarction size when GCS is impaired.In the present study, we investigated the characteristics of conventional CMR parameters and the correlation between the strain and LGE assessment by CMR-FT in STEMI patients with preserved LVEF. Our research has found that STEMI patients with preserved LVEF have impaired segmental strain, GLS, GCS, and GRS. Compared with healthy controls, STEMI patients had enlarged LVEDV, LVEDVi, LVESV, LVESVi, and LAVAlthough an integrated myocardial infarction emergency system allows more patients to receive timely revascularization treatment and is more likely to minimize the size of the infarcted myocardium, it is essential to note that the adult heart does not possess any regenerative capacity. Therefore, a scar is formed when the infarcted myocardium heals. As part of the healing process, alarmins released by dying cells trigger a cascade of inflammatory reactions. When fibroblasts are activated by the renin-angiotensin-aldosterone system and released by transforming growth factor-β , they bep < 0.05). Several different processes may cause expansion of the infarcted segment. First, this may reduce the number of layers across the ventricular wall due to the rearrangement of bundles of cardiomyocytes, accompanied by the elongation of these cardiomyocytes. Second, through activation of matrix metalloproteinases (MMPs), the interstitial matrix may be degradable, leading to increased dilation of the chambers , perhaps due to the patient’s left ventricular systolic function being preserved due to ventricular interdependence, resulting in little effect on the right ventricle. RV dysfunction is associated with worse in-hospital outcomes regardless of the localization of AMI and a lower 1-year survival rate  CMR parameters in patients . A more extensive analysis by Ledwoch and others, including 684 STEMI patients, measured LA function only by ejection fraction and found an independent association between LAEF and adverse clinical events. However, the prognostic value of LAEF was not incremental to LVEF  parameters were also measured, and we found that LAEF was significantly decreased compared to the control group ( to LVEF . Therefop < 0.05). Nevertheless, LVEF is still critical, making it difficult for cardiologists to judge the infarction size accurately, predict outcomes, and give appropriate treatment guidance based on the parameter.Different researchers have demonstrated that LVEF for predicting challenging clinical events post-STEMI is independent and incremental to established outcome factors such as echocardiography-based LVEF . AdditioAn analysis of myocardial strain evaluates deformations of the myocardium throughout the cardiac cycle, providing information on global and regional LV function . MyocardSeveral investigations have shown that cine-derived strain analyses can be performed with high accuracy and reproducibility after STEMI . The gloThe results of this study are consistent with those of a previous study. Notably, our population did not define the site of myocardial infarction, indicating that global and segmental strain has decreased regardless of the location of the myocardial infarction in patients. However, the global strain had better reproducibility than the segmental strain in CMR feature-tracking . Global IS by LGE has been recommended as a primary CMR endpoint measure in experimental and clinical trials . For thep < 0.05) and a weak correlation between GLS and LGE , but we found no correlation between GRS and LGE (p > 0.05). In the multivariate model, we found that the LGE size was significantly associated with GCS  but was not associated with GLS  or LVEF .Unlike our study, previous ones did not delineate study populations based on LVEF, whereas we included patients with preserved LVEF. In addition, our patients underwent CMR up to 14 days after PCI, and the site of myocardial infarction included the anterior and inferior-posterior walls. Our results showed that there was a moderate correlation between GCS and LGE  , taggingThis study had several limitations. First, the sample size was relatively small. Second, this study was a single-center, retrospective study based on the preferred time point for assessing late gadolinium enhancement imaging. CMR scans were performed up to 14 days after MI, but it is not sure that this time point was optimal for the CMR measurements. Third, because the study focused on STEMI patients with preserved LVEF, extrapolating the findings to STEMI patients who had decreased LVEF or non-STEMI patients was limited. Moreover, we included patients with preserved LVEF based on echocardiographic findings, which were likely to be affected by equipment and operator factors. Furthermore, we could not perform predictive analysis on the relationship between strain, LGE, and prognosis due to a lack of follow-up for many patients. There may be a need for a more comprehensive prospective study with a more significant number of participants.In conclusion, global and segmental strain were impaired in STEMI patients with preserved LVEF treated by contemporary primary percutaneous coronary intervention. GCS and LGE were correlated, and GCS, as determined by CMR, emerged as a strong and independent predictor of infarction size. Moreover, GCS had superior diagnostic accuracy to GLS and LVEF for predicting myocardial infarction size. Consequently, multiparametric CMR imaging (including the strain) has an emerging role in infarction size prediction in post-STEMI patients that warrants further research.


Fetal ductal constriction (DC) is associated with excessive polyphenol-rich food (PRF) consumption during pregnancy. However, the effect of this hemodynamic change on fetal cardiac function still needs to be elucidated. Therefore, this study aimed to evaluate the cardiac function of fetuses with PRF-related DC and to describe serial observations of cardiac function changes.We compared the traditional echocardiographic indices, including morphological, hemodynamic, and functional parameters, between study fetuses and controls. For global and segmental deformation analysis of the left and right ventricles, fetalHQ with the speckle-tracking technique was used to calculate sphericity index (SI), global longitudinal strain (GLS), fractional shortening (FS), fractional area change (FAC), etc. In addition, follow-up data were compared with the generalized linear model.p < 0.001), RVFAC , left ventricular GLS (LVGLS) (−19.52 ± 3.24 vs. −23.81 ± 2.01 p < 0.001), and LVFAC . For 24-segment FS analysis, DC fetuses showed lower FS in left ventricular (LV) segments 18–24, with no difference in LV segments 1–17. Right ventricular (RV) FS in segments 4–23 was also reduced in the DC group. The 24-segment SI analysis indicated significantly lower SI in DC than those in controls for LV segments 1–14 and RV segments 19–24. We found that the pulsatility index (PI) of ductus arteriosus (DA) was an independent variable for RVGLS . In 20 DC fetuses with follow-up echocardiograms, no obvious difference in myocardial deformation was found between the initial examination and follow-up data.A total of 60 DC fetuses and 60 gestational-matched controls were enrolled in our study, with 20 DC fetuses undertaking a follow-up echocardiogram after 2–3 weeks. Compared with controls, there was a distinct decrease in right ventricular GLS (RVGLS) (−13.39 ± 3.77 vs. −21.59 ± 2.51, Left and right ventricular performances were both impaired in DC fetuses, along with a series of morphological and hemodynamic changes. Although the state of DA constriction improved on second examinations, cardiac function was not completely restored. Previous studies have indicated that blood flow across the DA accounts for approximately 78% of the right cardiac output and 46% of the combined cardiac output (Ductus arteriosus (DA) patency is essential for normal hemodynamics c output . Prematuc output . Ductal c output –6. DC caAlthough traditional echocardiographic parameters, such as ejection fraction (EF), fractional area change (FAC), and myocardial performance index (Tei index), are used to evaluate fetal cardiac function in drug-induced DC, it is impossible to specify changes in cardiac function because measurement of these parameters is affected by beam angle, fetal position, and other objective conditions . Based oTherefore, this study aimed to evaluate the cardiac function of fetuses with polyphenol-induced DC and to make serial observations of the ventricular performance.We retrospectively reviewed 60 fetuses with 24–34 gestational weeks diagnosed as DC by echocardiography from January 2016 to April 2022 in the Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. After the diagnosis of DA constriction, we advised pregnant women to suspend polyphenols and expected them to come back for a follow-up in 2–3 weeks. Follow-up records were collected for 20 fetuses. Sixty normal fetuses with matching gestational age were selected as the control group. The prenatal diagnosis of DC was based on the following ultrasonic signs: (1) DA peak systolic velocity (PSV) ≥ 140 cm/s; (2) DA maximum diastolic velocity ≥ 30 cm/s; and (3) DA pulsatility index (PI) ≤ 2.2. All the three criteria are necessary for DC diagnosis  Figure . The excz-score, aortic valve (AV) z-score, main pulmonary artery (MPA) z-score, pulmonary valve (PV) z-score, left pulmonary artery (LPA) z-score, right pulmonary artery (RPA) z-score, and DA z-score were measured. The global sphericity index (GSI) was calculated by 4-chamber view length/4-chamber view width. The fetal heart blood flow, heart rate, and rhythm were observed and evaluated by M-mode echocardiography and color Doppler flow imaging. The spectrum of the aorta, the pulmonary artery, and the ductus arteriosus was obtained by spectral Doppler. The peak systolic velocity of arteriovenous (AV) and PV flow and the peak systolic and diastolic velocity of DA were measured at three vessels and the trachea (3VT) view. The spectrum of DA for PI was manually traced. The acceleration time/ejection time (AT/ET) was calculated from fetal pulmonary artery flow (FPAF) velocity waveforms. The above data were measured repeatedly three times and the results were averaged. The results of fetal echocardiography were blinded to the experimenter.A detailed fetal echocardiogram was performed by two experienced fetal echocardiography physicians using Voluson E10 and E8 ultrasound machines with eM6C and C2-9 transducers (2–9 MHz) . Conventional views and two-dimensional four-chamber dynamic images were obtained according to a sonographic screening examination of the fetal heart . BiventrA cardiac cycle was selected from the two-dimensional (2D) 4-chamber images for extracting the parameters of cardiac shape and function. As described in the previous investigation , fetalHQ1 Continuous variables were expressed as mean ± SD or median (interquartile range). The Shapiro–Wilk test was used to evaluate the data normality. For normally distributed continuous variables, the Student’s t-test for independent samples was used for comparisons between the groups. For those non-normally distributed data, the Mann–Whitney U-test was applied. Categorical variables were analyzed by the chi-squared test or Fisher’s exact test when appropriate. The univariate regression analysis was used to identify the risk factors affecting cardiac performance in fetal DC. Follow-up data were compared with the generalized linear model. Left ventricular GLS (LVGLS), LVFAC, right ventricular GLS (RVGLS), and RVFAC of 30 randomly selected fetuses for interobserver and intraobserver reproducibility were calculated by intraclass correlation coefficients (ICCs) with a 95% CI. A p-value < 0.05 was considered statistically significant.Statistical analysis was performed by SPSS version 23.0  and GraphPad Prism version 9.0.0 (121) for Windows .The baseline characteristics of the study population are shown in p = 0.006] was enlarged. No obvious disproportion in great arteries (similar MPA/AO diameter ratio) was detected. The aortic and pulmonary dimensions did not differ between the groups, except for the slightly lower diameter of the pulmonary valve annulus in DC . DA z-score  was lower in the DC group. Blood flow across the aortic and pulmonary valves was not accelerated or decelerated when compared with controls. Fetuses with DC showed a decrease in pulmonary AT/ET ratio . Tricuspid regurgitation occurred in 70% of fetuses, including mild, moderate, and severe regurgitation in 28 (46.67%), 8 (13.33%), and 6 (10.00%) fetuses.Fetal cardiac morphometric and hemodynamic measurements are given in p < 0.001), RVFAC , LVGLS , and LVFAC . The stroke volume (SV), cardiac output (CO), and CO by EFW were similar between the two groups.Fetal cardiac functional measurements of the study population are given in The results of the 24-segment FS analysis of LV and RV are shown in The results of the 24-segment SI analysis of LV and RV are shown in P = 0.04)  in DC fetuses were examined using the univariate regression analysis , which r = 0.04) .Twenty  fetuses in the DC group underwent an echocardiogram two times, first at diagnosis and second after 2–3 weeks of observation. Follow-up data were reviewed with the generalized linear model tests. As expected, during the DC reversal in the follow-up examination, DA peak diastolic velocity (PDV) was significantly decreased and DA PI increased . MyocardThe intraobserver and interobserver intraclass correlation data for LVGLS, LVFAC, RVGLS, and RVFAC indicated excellent results .z-score of the diameter of the pulmonary valve annulus. If it deteriorates, the result might be pulmonary valve annular enlargement and pulmonary valve regurgitation (Our study found that fetal hearts with DA constriction showed ventricular remodeling and cardiac dysfunction through conventional ultrasound parameters and fetalHQ technology. In normal fetuses, the DA flows in a tubular shape from the distal pulmonary artery branches into the descending aorta, slightly wider than the pulmonary artery; the middle layer of the DA is composed of a large number of smooth muscle cells; it provides an anatomical basis for DA contraction and relaxation . DA z-scgitation , 3.Although the difference was statistically significant from segment 19, RV 24-segment SI values were lower than those of normal fetuses. It was also indicated that the right ventricle of fetuses with DA constriction was more globular. Reduced RVGLS, RVFAC, and 24-segment FS values suggest decreased right ventricular compliance and systolic dysfunction. Similar to our results, a preliminary study found that DA constriction led to decreased RVFAC and an increased TEI index , 21. TheWe collected the prenatal results of the electrocardiogram of 20 fetuses, during which premature ductal contraction was diagnosed. By comparing the ultrasound parameters of the fetuses in the two examinations and the fetalHQ parameters, we found that the flow rate in the diastolic phase decreased and the PI value increased, but there was no significant change in the systolic flow rate, which might be due to diet control that eased premature contraction , 26. RVGIn this study, fetal cardiac function was evaluated by the fetalHQ technology for the first time in the setting of DC. Fetal cardiac function contraction mode was described by a 24-segment analysis. Both the left and right ventricles of the fetus with DC were abnormal. In addition to the GLS, the transverse contractility also changed. However, the causes of fetal cardiac function changes are different. The principal cause of right ventricular dysfunction is the increase of ventricular afterload, while left ventricular dysfunction is the result of the secondary increase of ventricular preload. Although premature contraction eased on the second ultrasound examination, cardiac function was not completely restored. Therefore, DA constriction induced by polyphenols requires a close monitoring of changes in fetal cardiac function.There are some limitations to our study. First, it was a retrospective investigation and single-center design; follow-up data could not be collected for all the fetuses. Second, it was difficult to perform fetal echocardiography in the late trimester of pregnancy; the duration of the effect of premature ductus arteriosus constriction on fetal cardiac function requires further clarification. Finally, we did not measure changes in the flow of the foramen ovale in the state of DA constriction to find out the mechanism responsible for changes in the left cardiac preload.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.JM performed the experiments and wrote the manuscript. HC performed the data analyses and manuscript preparation. LH and JL helped perform the analysis with constructive discussions. XS and JS contributed to the conception of the study. YZ and LC helped collect follow-up data. LZ and MX provided conception and final approval of the article. All authors contributed to the article 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.


C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3–9 d after onset of STEMI symptoms and quantified by myocardial infarct size , left ventricular ejection fraction , circumferential strain (CS) and longitudinal strain (LS). Compared with the control group (n = 34), cardiac damage was significantly lower in the apheresis group (n = 32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65–177) d whether the effect of CRP apheresis is clinically maintained. After this time period, wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of <0.6 mg/L/h in the hours after STEMI (9 of 32 patients in the CRP apheresis group) did not significantly benefit from CRP apheresis in CMR2, patients with high CRP production and a CRP gradient cut off of >0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS , a better LVEF , and an improved CS . No significant improvement, however, was observed for LS . These data suggest a sustained positive effect of CRP apheresis on heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue.In the multicenter, non-randomized, exploratory  In case of acute, aseptic tissue damage such as STEMI, CRP concentration in the blood, within few hours, can increase up to 100–200 times over the initial value . ObviousTwo issues are highly relevant for patient prognosis after STEMI: First, a timely revascularization within 2 h after the onset of STEMI symptoms. The latter will result in almost complete preservation of cardiac function with a very good long-term prognosis. Secondly, and mainly in case of delayed intervention, the healing process during the weeks after STEMI. This healing process of injured myocardial tissue is supported by medical therapeutic management in the ICU.Up to the present day, a “healing process” has been discussed for the myocardium after STEMI . The conCRP apheresis is obviously important for STEMI patients with delayed revascularization. CRP apheresis achieves the local absence of CRP in the myocardium. It thereby provides more time to the cells to switch back from anaerobic to aerobic metabolism in order to be able to revert the apoptotic appearance of their outer cell membranes to prevent disposal by phagocytes.Whereas CMR1 2–9 d after STEMI was subject matter of the original CAMI-1 publication, we have now taken a closer look at the data of the second CMR (CMR2) and whether the improvement of cardiac function observed in CMR1 is sustained for an average of 88 (65–177) d after the STEMI event. This report thus investigates the long-term sustainability of the initial beneficial effect of CRP apheresis after STEMI with respect to the CMR outcome parameters IS, LVEF, LS and CS.grad) within the first 32 h after onset of symptoms was used as the basis for analysis. Myocardial parameters were measured using CMR. The main cardiac parameters were % IS, % LVEF, % LS and % CS. CMR1 was assessed 2–9 d after onset of STEMI symptoms, and CMR2 was assessed 88 (65–177) d after STEMI. The baseline characteristics of both groups are comparable .The CAMI-1 trial demonstrated the benefit of CRP-apheresis in acute inflammation but has some limitations. The number of patients should be enlarged and a follow-up study should only include patients with CRPCRP apheresis is the first innovative therapeutic method to avoid the expansion of the cardiac infarction area and to sustainably improve cardiac performance.


Cardiac auscultation is a traditional method that is most frequently used for identifying congenital heart disease (CHD). Failure to diagnose CHD may occur in patients with faint murmurs or obesity. We aimed to develop an intelligent diagnostic method of detecting heart murmurs in patients with ventricular septal defects (VSDs) and atrial septal defects (ASDs).Digital recordings of heart sounds and phonocardiograms of 184 participants were obtained. All participants underwent echocardiography by pediatric cardiologists to determine the type of CHD. The phonocardiogram data were classified as normal, ASD, or VSD. Then, the phonocardiogram signal was used to extract features to construct diagnostic models for disease classification using an advanced optical coherence tomography network (AOCT-NET). Cardiologists were asked to distinguish normal heart sounds from ASD/VSD murmurs after listening to the electronic sound recordings. Comparisons of the cardiologists’ assessment and AOCT-NET performance were performed.Echocardiography results revealed 88 healthy participants, 50 with ASDs, and 46 with VSDs. The AOCT-NET had no advantage in detecting VSD compared with cardiologist assessment. However, AOCT-NET performance was better than that of cardiologists in detecting ASD .The proposed method has the potential to improve the ASD detection rate and could be an important screening tool for patients without symptoms. Congenital heart disease (CHD) is one of the major causes of morbidity and death in children. Although CHDs may be associated with chromosomal or genetic anomalies , most arDelayed diagnosis of a non-critical CHD is not uncommon. Pfammatter and Stocker reported that of 323 patients, 32 had a delayed diagnosis of heart defects . The mosSeptal defects may be detected by physical examination, electrocardiography, and/or chest radiography. Cardiac auscultation of heart sounds is the most common, simple, and effective method of detecting heart diseases with heart murmurs, and auscultation can be enhanced using an electronic stethoscope . However2 for men and > 74 mL/m2 for women. Left ventricular dilation was defined by a left ventricular end-diastolic volume  normalized by body surface area > 74 mL/m2 for men and > 61 mL/m2 for women  was measured using echocardiography . For paror women .This study included 216 participants. After excluding poor recordings (loud breathing sounds or faint heart sounds), 184 participants were analyzed, including 46 with VSDs, 50 with ASDs, and 88 with a normal heart structure. The median age was 8.58 years. The participants enrolled in the study were divided into the training dataset group and validation dataset group; there were 92 participants in each group and 552 recordings per group.Electronic heart-sound recordings were obtained by well-trained technicians using an electronic stethoscope . Electronic heart sounds were recorded at the left upper sternal border (LUSB), left midsternal border (LMSB), and left lower sternal border (LLSB) . Heart sRecordings of heart sounds from each participant in the training dataset group were used to construct the deep learning model. Heart sounds recordings from the participants in the validation dataset group were used to validate the accuracy, sensitivity, and specificity of the model. The electronic recordings of normal heart sounds (270 recordings) and ASD heart sounds (144 recordings) in the validation dataset were selected and allocated to the developed deep learning model and two pediatric cardiologists who independently listened to the heart sound recordings. Cardiologists were asked to distinguish normal heart sounds from ASD murmurs after listening to the electronic sound recordings. The cardiologists did not review the electrocardiograms or perform cardiac auscultation directly on patients. The interpretations of the two cardiologists were recorded as “normal” if there was agreement on normal. The interpretations were recorded as “ASD” if one of the cardiologists considered the heart sound as “ASD.” These results were used to calculate the detection sensitivity and specificity. The cardiologists also listened to 270 recordings of normal heart sounds and 138 recordings of VSD heart sounds in the validation dataset. Sounds were recorded as “VSD” or “normal,” and these recordings were also allocated to the deep learning model to identify them as normal or VSDs.The electronic signals of heart sounds were denoised before the heart sounds were segmented to reduce the noise generated during the collection process. Throughout this study, we used the adaptive wavelet threshold for noise reduction in addition to performing segmentation.The discrete wavelet transform comprises multi-resolution decomposition that separates information into different frequency bands . We decoK-means clustering is an unsupervised machine-learning algorithm that is frequently used to group similar data points together identifying underlying patterns. K-means + + is based on the K-means algorithm; however, it utilizes smart centroid initialization by randomly selecting random k-points during the first step of the process . This meTo extract features, we used the bispectrum to convert the segmentation signal into a two-dimensional image associated with heart sound intervals . Using tThese converted bispectrum signals were entered into the advanced optical coherence tomography network (AOCT-NET) and then subsequently used to train the AOCT-NET to construct the models for heart-sound classification  , 17. Onct-tests were used to compare the means of two independent datasets. The chi-square test was used to determine whether there were non-random associations between two categorical variables. Conversely, if the sample size was small (n < 5) in a 2 × 2 contingency table, the Fisher’s exact test was used to test the associations between two categorical variables. Sensitivity was defined as the number of defects detected by a screening method divided by the number of defects observed using echocardiography. Specificity was defined as the number of normal heart sounds determined using the screening method divided by the number of normal echocardiograms. The Kappa coefficient was used to test consistency between the screening method and echocardiography. P < 0.05 was considered to indicate statistical significance.Statistical analyses were performed using SPSS Statistics version 22 . Two-tailed Student’s Among the 50 patients with ASDs, right ventricular dilation was observed in 32 (64%) patients, and none of the patients had tricuspid regurgitation that was more than moderate. Fourteen patients had pulmonary hypertension with a tricuspid regurgitation velocity greater than 2.7 m/s. Among patients with ASDs, 16 had an estimated Qp/Qs ratio < 1.5, and 34 had an estimated Qp/Qs ratio ≥ 1.5. Of the 46 cases of VSD, 26 were peri-membranous type, 11 were muscular type, and 9 were outlet type. Thirty-seven (80%) patients with VSDs had left ventricular dilation on echocardiography. Of these, 20 patients had an estimated Qp/Qs ratio < 1.5, and 26 patients had an estimated Qp/Qs ratio ≥ 1.5. Patient characteristics of the training and validation groups were similar .When evaluating the electronic recordings of heart sounds of the validation group, cardiologists recognized 44 ASD murmurs, including fixed S2 splitting in 21 cases. Among the 44 ASD murmurs identified, all were detected in patients with Qp/Qs ≥ 1.5. Furthermore, cardiologists detected 117 VSD murmurs and, of these, 73 murmurs were detected in patients with Qp/Qs ≥ 1.5 and 44 in patients with Qp/Qs < 1.5.The AOCT-NET was capable of differentiating VSD murmurs from normal heart sounds as successfully as the assessment by cardiologists , 3. AddiAOCT-NET had greater screening sensitivity for detecting ASDs than cardiologist assessment , 3. MoreThis study developed a novel tool for detecting asymptomatic ASD patients that may be used in outpatient screening. This study determined that AOCT-NET had a higher sensitivity for detecting ASD murmurs than cardiologist assessment, although their screening sensitivities for detecting VSD murmurs were comparable.The use of advanced diagnostic modalities, particularly echocardiography, has resulted in inadequate emphasis on cardiac auscultation . HoweverAutomatic detection of valvular heart diseases based on higher-order spectral estimation and the bispectrum of phonocardiogram recordings is feasible. A 98% accuracy using this methodology has been reported for the diagnosis of heart valve diseases . BispectIn this study, the AOCT-NET model distinguished ASD murmurs from normal heart sounds more accurately than cardiologist assessment, although the two methods displayed similar accuracy in detecting VSD . This maA recent study performed by Wang et al. using a novel algorithm constructed to identify systolic murmurs demonstrated high sensitivity (96%) and specificity (96.7%) for distinguishing VSD murmurs from normal heart sounds . A furthWhen evaluating the sound recordings of patients with ASD in the validation group, cardiologists recognized a fixed S2 splitting in 21 sound recordings. Eighteen of the 21 electronic sound recordings were classified as ASDs by the AOCT-NET. Because the fixed S2 split also contributed to a sound signal, it also resulted in a change of the color mapping on the bispectrum. Although the color mapping change was subtle to human eyes, the AOCT-NET still recognized these sound recordings as ASDs. By combining the fixed S2 splitting and systolic murmurs reflected on the color mapping of the bispectrum, machine-learning has an advantage in detecting ASDs. In patients with ASD in the validation group with right ventricular dilation, 12 had mild or moderate tricuspid regurgitation, and 7 had pulmonary hypertension. The murmurs from tricuspid regurgitation and pulmonary hypertension increased the ability of both the AOCT-NET and the cardiologists to detect murmurs. AOCT-NET still had a higher sensitivity for patients with ASD with right ventricular dilatation than the cardiologist assessment (88.2 vs. 60.8%). The presence of right bundle branch block, defective T waves, and notch findings in the R wave of inferior derivations on electrocardiograms may also contribute to the detection of ASDs . AlthougDespite the capacity of the AOCT-NET to accurately identify VSDs and ASDs, technical difficulties were encountered as we developed the artificial intelligence-based heart murmur detection model. The original heart-sound recordings contained noises that had the potential to interfere with the characteristics of normal heart sounds and heart murmurs. To minimize the effect of these noises on our results, we utilized a Butterworth band-pass filter to produce the best output response. Automatic segmentation and classification of heart sounds were achieved with high accuracy and sensitivity using empirical wavelet transform-based phonocardiogram signal decomposition as previously described . Prior tThe cost of developing the AOCT-NET was low because only an electronic stethoscope and a computer to transform the sound signal into optical tomography data were required. Machine-learning cannot replace echocardiography to confirm the final diagnosis of CHDs. However, machine-learning is a tool that physicians can use to improve the detection rate of heart murmurs, allowing referral of patients for further cardiac evaluation.This study has some limitations. First, the sensitivity for detecting ASDs by AOCT-NET was limited because the tool could not recognize a cardiac lesion with no or slight heart murmurs, such as a patent foramen ovale or a small ASD. However, patients with minor heart diseases rarely need interventions. Moreover, screening with this method can reduce the number of undiagnosed cases of CHD, particularly for ASDs which are more difficult to recognize clinically. Further, patients with functional murmurs were excluded from this study, and cardiologist assessment was based on a dichotomous diagnosis, such as “normal or ASD” and “normal or VSD.” Nonetheless, the purpose of AOCT-NET was to enhance the screening sensitivity of non-critical CHDs. Furthermore, we achieved preliminary success in identifying heart murmurs. More studies are needed to differentiate functional murmurs from pathological murmurs. In the future, this model also has the potential to recognize other murmur types.The AOCT-NET can improve the detection of ASD murmurs and may be used as a screening tool for patients without symptoms and signs. This tool can be applied in clinical practice and contribute to the early detection and management of patients with ASDs.The original contributions presented in this 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 the institutional review board of the E-DA Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.P-KH, M-CY, Z-XW, W-CL, C-LP, and Y-JH performed the material preparation and data collection. P-KH, M-CY, Z-XW, and M-HG performed the analysis. P-KH wrote the first draft of the manuscript. All authors contributed to the study conception and design, commented on previous versions of the manuscript, and read and approved the final manuscript.