Some of them block β-adrenergic receptors selectively while the others work non-selectively. Consequently, they reduce the influence of the sympathetic nervous system on the heart, acting negatively inotropic, chronotropic, bathmotropic and dromotropic. Although they have been present in medicine since the beginning of the 1960s, they still play a crucial role in the treatment of cardiac arrhythmias. They are also first-line group of drugs used to control the ventricular rate in patients with the most common arrhythmia–atrial fibrillation. Previous reports indicate that infection with SARS-CoV-2 virus may constitute an additional risk factor for arrhythmia. Due to the aging of the population in developed countries and the increase in the number of patients with cardiac burden, the number of people suffering from cardiac arrhythmias will increase in the upcoming years. As a result the role of above-mentioned beta-blockers will remain significant. Particularly noteworthy is propranolol–the oldest beta adrenergic antagonist, which in recent years has found additional applications due to its unique properties. In this article, we reviewed the accessible literature and summarized the current guidelines on the use of beta-blockers in the treatment of cardiac arrhythmias. Beta-blockers are well-established in the treatment of arrhythmias. Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It is estimated to affect 1%–4% of the population . The incCurrently, the role of the SARS CoV-2 virus and its impact on the work of the heart cannot be overlooked. Among patients hospitalized due to COVID-19, an arrhythmia incident was reported in case of 7.9% of patients in New York hospitals and 16.7% of patients in Wuhan hospitals . In contBased on the American Heart Association/American College of Cardiology (AHA/ACC) and European Society of Cardiology (ESC) guidelines and taking into account changes in the electrocardiographic record, we can distinguish supraventricular and ventricular arrhythmias. The division according to clinical symptoms is also important–cardiac arrhythmias may be asymptomatic, symptomatic or may only manifest themselves in the form of complications, including sudden cardiac death (SCD). The selection of the optimal treatment depends on many factors, such as the type of disorders, their etiology and the clinical picture. It is important that beta-blockers are effective not only in the treatment of cardiac arrhythmias, but also in heart failure, being well-established alongside drugs such as ACEI, aldosterone antagonists, alongside with the new, and more promising drug called levosimedan . It shouNormal heart function depends on the presence of two separate types of cells–the cells forming the heart’s conduction system and the cardiomyocytes that perform a mechanical function. Both types of cells are dependent on each other and only the correct operation of both types of cells determines the proper functioning of the heart muscle. The synchronous interaction between these two properties is complex, precise and relatively permanent, and among other things, its disturbance may result in the occurrence of cardiac arrhythmias. The main center of the cardiac conduction system is the sinoatrial node, which imposes the rhythm on other centers in the heart. There are at least several mechanisms responsible for the development of cardiac arrhythmias. Among the basic ones, several mechanisms may be distinguished: impulse formation disorders, impulse conduction disorders and the phenomenon of circulating excitation (reentry). Behind the occurrence of tachycardia disorders is excessive stimulation of the sympathetic nervous system. The sympathetic nervous system acts on the heart through the α and β receptors. The effect of stimulation of these receptors is the intracellular influx of Ca2 + ions through voltage-dependent membrane channels. There are mainly β1 receptors in the heart, the stimulation of which increases the rhythm frequency, the speed of atrioventricular conduction and increases the contractility of the atria and ventricles .β-blockers belong to the second group of antiarrhythmic drugs in the Williams classification. They work by blocking β receptors, either selectively or non-selectively. The effect of the cardiovascular system on the blockade of β-adrenergic receptors depends on the level of sympathetic tone. Their antiarrhythmic effect is the result of a decrease in the activity and speed of conduction of the stimulatory tissue and contractility of the heart muscle by inhibiting the effect of catecholamines on beta adrenergic receptors, which reduces the concentration of Ca2 + ions in the cytoplasm. The main features of β-blockers are due to the reduced stimulation of the sympathetic nervous system: reduced automatism, reduced myocardial contractility, and reduced secretion of renin from the glomerular apparatus in the renal cortex. It can be briefly stated that β-blockers have an inotropic, chronotropic, bathmotropic and negative dromotropic effect on the heart .An additional feature characterizing some of the β-blockers is intrinsic sympathomimetic activity (ISA). It is the ability to partially stimulate the β-adrenergic receptor despite its blocking. As a result, a negative inotropic effect is exerted with a much weaker negative chronotropic effect, which is of particular importance for heart failure . In thisResearch indicates the presence of intracellular β1-adrenoceptors in myocytes, which, by generating a local signal, may be involved in accelerating Ca2 + uptake . Beta-blBeta-blockers may also have an additional effect–on the basis of studies analyzing the use of beta-blockers in ischemic heart disease or liver diseases, it was found that they lower the concentration of inflammatory markers such as C-reactive protein or procalcitonin .Recently, the subject of interest of scientists and clinicians is the relationship of beta-blockers with the release of nitric oxide (NO) from vascular endothelial cells and the consequences associated therewith. NO is an endogenous gas messenger stimulating guanylate cyclase through intraepithelial nitric oxide synthase (NOS-3), which increases the production of cGMP and, as a result, vasodilation. Nitric oxide synthase is an enzyme that catalyzes the synthesis of NO in two different steps–the first is the oxidation of L-arginine to Nω-hydroxy-L-arginine; then the substrate under the influence of NOS and oxygen is broken down into L-citrulline, which is accompanied by the release of NO from the vascular endothelial cells . The relOne of the most important parameters differentiating individual β-adrenolytics are the pharmacokinetic properties. Pharmacokinetics is the science of describing, under the acronym LADME, the processes of liberation, absorption, distribution, metabolism, and excretion of a drug. The use of pharmacokinetics in pharmacotherapy allows the correct dose levels and length of the dose intervals to be determined. The absorption process is influenced, among others, by: the degree of ionization, solubility in the lipid layer of the biological membrane [characterized by the logarithm of the n-octanol/water partition coefficient (logP)], the size of the drug molecule and technological factors such as the drug formulation method or the auxiliary substances that were used .More ionized substances are absorbed slower and to a lesser extent. The way and intensity with which a substance passes through the membrane is a function of the dissociation constant (pKa), characteristic of a given chemical compound, and the pH of the environment in which the compound is presently located. The pKa value corresponds to the pH value at which the number of ionized molecules of a given compound is equal to the number of non-ionized molecules . ChangesMany drugs achieve their biological effect by inhibiting enzymes. To understand the mechanism of action of these drugs as enzyme inhibitors, the relationship between drug concentration and the rate of reaction performed by an isolated enzyme is studied. To describe the degree of inhibition of the enzymatic reaction, various parameters are used, including the inhibition constant–pKi, which is the dissociation constant of the enzyme-inhibitor complex reaction and the inverse of the affinity of the inhibitor to the enzyme  Graph 1.A measure of the hydrophobic-hydrophilic properties of a given compound is lipophilicity, represented by the partition coefficient P or its logP logarithm. It is a physicochemical parameter that determines transport to the site of action of the substance. The more polar a given component is, the higher the logP value and the lower the ability to penetrate lipid membranes . HoweverBack in the early 1960s, James Black developed the first β-blocker drug, propranolol, which has been shown to have a “sedative” effect on the heart. In 1988 he was awarded the Nobel Prize in Physiology and Medicine . Thus, hWhen choosing the right treatment, it is also important to pay attention to interaction - not only with drugs but also with food. A flagship example of drug and drug interactions with food are drugs from the VKA group (vitamin K antagonist). In recent studies it has been shown that the effectiveness of therapy with drugs from the group DOAC/NOAC  also depends on the type of food consumed . In the The classification of cardiac arrhythmias usually distinguishes two groups of arrhythmias: supraventricular and ventricular arrhythmias.Traditionally, the term supraventricular tachycardia (SVT) refers to a tachycardia that originates in the His bundle or upstream structures. The traditional classification of arrhythmias classifies all types of tachycardia as SVT, excluding atrial fibrillation and ventricular tachycardia. The conventional classification of supraventricular tachycardia includes: atrial tachycardia, AV junctional tachycardia, and atrioventricular recurrent tachycardia (AVRT)  Table 2Table 2.According to the literature on the subject, the division into narrow-complex tachycardia (QRS complexes ≤120 ms) and wide-complex tachycardia (QRS complexes lasting> 120 ms) is used. However, in clinical practice, supraventricular tachycardia may be manifested as narrow or wide QRS complex tachycardias, mostly occurring as regular rhythms.The traditional classification of atrial fibrillation distinguishes five forms of AF based on duration, clinical presentation, and spontaneous ending of AF episodes . In the Under normal conditions, excitation begins in the sinus node, which is located in the right atrium. In contrast, in ventricular arrhythmias, depolarization is generated by the medium located in the right or left ventricle. The most common causes of ventricular arrhythmias include: coronary heart disease and myocardial infarction, heart defects , cardiomyopathies, genetic and congenital diseases. The basic classification of ventricular arrhythmias is based on electrocardiographic changes. On this basis one may distinguish: non-sustained ventricular tachycardia (nsVT), sustained ventricular tachycardia (sVT), polymorphic ventricular torsade de pointes, ventricular flutter (VFl), ventricular fibrillation (VF). Another classification of ventricular arrhythmias applicable in clinical practice is the classification by clinical symptoms. On the basis of the clinical picture, there are haemodynamically stable disorders, haemodynamic unstable disorders, sudden cardiac arrest and sudden cardiac death . VentricIn hemodynamically stable patients with a regular narrow–QRS complex tachycardias, when vagal maneuvers or adenosine are ineffective, the administration of intravenous β-blockers (ex. esmolol or metoprolol) may be beneficial . These dβ-blockers may be considered in symptomatic patients with inappropriate sinus tachycardia unresponsive to lifestyle modifying strategies . HoweverA β-blocker (propranolol) in combination with diltiazem should be taken into account in acute management of atrioventricular nodal reentry tachycardia (AVNRT). The research have proven, that it may lead to termination of arrhythmia and conversion to sinus rhythm in majority of patients . NeverthIn acute management of patients with AVRT, β-blockers can be a therapeutic option, in case vagal manoeuvres and adenosine fail. In long-term treatment β-blockers should be taken into consideration, if there is no signs of preexcitation in resting ECG and when the ablation is either not desirable or feasible . β-blockβ-blockers remain one of the main rate-control agents in patients with AF and in majority of patients they are the first-line therapy . In contCombining β-blockers and verapamil or diltiazem is associated with a risk of bradycardia and therefore requires careful heart rate monitoring, preferably by 24-h ECG. In acute management of AF for heart rate control three of the β-blockers can be administered intravenously. The following are: metoprolol tartrate, esmolol and–newly mentioned in the recommendations–landiolol. The results of the J-Land study, conducted on 200 patients, have shown, that landiolol was more efficient in controlling HR in patients with AF and LV disfunction, compared to digoxin . FurtherThe effective management of underlying diseases and co-morbidities is fundamental for the successful treatment of ventricular arrhythmias and prevention of sudden cardiac death. By the selection of an appropriate therapy for the VA and for prevention of SCD the following factors should be taken into account: type of arrhythmia, the accompanying diseases, the risk posed by arrhythmia and the potential adverse events of such therapy. Even though β-blockers remain a relatively safe drug group, a recent study, in which a group of 34,661 patients with STEMI or NSTEMI was examined, showed that in patients with two or more risk factors for shock , systolic blood pressure <120 mm Hg), the risk of death or shock was significantly higher in patients treated with β-blockers in acute management . NeverthIn OPTIC trial the researchers wanted to determine, whether the use of beta-blockers alone, sotalol alone or beta-blockers with amiodarone prevents the ICD shocks . The comThe use of a β-blocker is recommended in management of patients with acute coronary syndrome without VA, in order to prevent ventricular fibrillation (VF) . In caseBeta-blockers are recommended in management of patients with dilated cardiomyopathy (DCM) to decrease the risk of SCD and attenuate the progress of HF, as well as in case of recurrent VA . In patiβ-blockers are also the first-line treatment in some of cardiac channelopathies. Patients with congenital long QT syndrome (LQTS) are recommended for β-blockers treatment . Beta-blAlso, the latest, recently published guidelines from 2022 emphasize the importance of beta-blockers in the treatment of ventricular arrhythmias. For instance, they are recommended in LQTS patients to reduce risk of arrhythmic events and in all patients with a clinical diagnosis of CPVT. In patients presenting with a hemodynamically tolerated idiopathic VT, treatment with intravenous beta-blocker is also recommended. The latest guidelines invariably emphasize the use of beta-blockers in ventricular arrhythmias, cardiomyopathies and channelopathies .Beta-blockers are considered a relatively safe group of drugs during pregnancy. However, they may cause, among others, bradycardia or fetal hypoglycemia. In order to minimize the risk of possible complications for the fetus, the selection of the appropriate drug should be aimed at the lowest effective dose of the drug. It has been observed that the use of β-blockers by a woman in the first trimester of pregnancy is not associated with a large increase in the risk of any malformation in the fetus. Intravenous preparations are used both in patients with SVT and in AF attacks . SelectiThe current research have shown, that the SARS-CoV-2 infection is associated with a greater risk of arrhythmias . In a stA retrospective observational study conducted by Beta-blockers also present with various other, less known, nevertheless very promising qualities, especially in the midst of the COVID-19 pandemic. They have an anti-inflammatory effect by inhibiting the release of IL-6 and TNF-α, allowing the mitigation of the cytokines storm in the COVID-19. Moreover, beta-blocking agents decrease the release of catecholamines caused by SARS CoV-2 infection and also attenuate the development of the sympathetic storm. Furthermore, metoprolol reduces the oxidative stress as it blocks the activity of myeloperoxidase (MPO)—an enzyme, which is one of many common steps linking the development of the cytokines and sympathetic storms. Those two processes interacting together lead to lethal complications in patients with severe COVID-19 .The results of a study conducted by in vitro, for example in the capillary endothelial cells , which is responsible for the regulation of VEGF–the main proangiogenic factor. As a result, the tumor-related angiogenic process is impaired. In addition, various studies have shown that blockade of β1-and β2-adrenergic receptors by propranolol can induce apoptosis in some types of cells and tumors al cells . Howeveral cells .All these mechanisms contributed to the successful use of propranolol in the treatment of infantile hemangiomas (IH) . It has Taking into consideration the wide and nuanced application of beta-blockers over the years, it is impossible not to mention their use in the treatment of situational anxiety, such as stage fright, fear of public speaking or performance anxiety on various fields. In a double blind placebo controlled study conducted by In recent years, a number of studies have been conducted on the possible use of propranolol in oncology. As it turned out, it can be useful in many areas. Propranolol in high doses inhibits the undesirable effects of cisplatin, including on histological symptoms as well as BUN and creatinine levels, which may prove that it reduces the nephrotoxicity of cisplatin . AdditioThe effect of beta-blockers on breast, ovarian, colorectal and pancreatic cancer has been investigated in observational studies . In studLast studies have shown that propranolol may also have beneficial effects in other diseases. In post-traumatic stress disorder (PTSD), propranolol did not show a beneficial effect on PTSD symptoms, but significantly reduced the heart rate after traumatic memory recall as compared to placebo . ResearcPropranolol has undoubtedly become an object of interest in many areas of medicine–and for good reason. Propranolol is an example of an extremely valuable drug, showing numerous therapeutic properties in many areas, not only in treatment of cardiovascular diseases.β-blockers are one of the main groups of drugs used in management of arrhythmias. Their specific qualities and efficacy however, does not simply result from the blockade of beta-receptors, but also from many additional acting mechanisms, as each of these agents is pharmacologically diverse. Beta-blockers are widely used and have been known for decades now. Even though, 60 years has passed since the invention of propranolol, new beta-blocking agents, such as intravenously administered landiolol, are still being discovered. The pharmacochemical diversity of this group of drugs indicates a necessity for further research on therapeutic qualities and potential adverse effects of newly invented beta-blockers. The most important factors, that should be considered, while choosing the most suitable β-blocker are the type of the arrhythmia, the patient’s profile and the accompanying diseases along with appropriate guidelines. Nowadays, the COVID-19 pandemic already caused and most likely will still cause an increased number of new-onset arrhythmias. Also in this group of patients beta-blockers are widely used. Moreover, in one study the hypotensive therapy with beta-blockers in patients with COVID-19 and preexisting hypertension was associated with lower mortality. In conclusion, regardless of the type of the arrhythmia beta-blockers remain one of the most essential agents used in management of heart rhythm disorders.


MI substantially affected the systolic shape of the MV, and the range of stretch experienced by the MV leaflet at peak systole was substantially reduced when referred to the current time-point. Interestingly, when we referred the leaflet strains to the pre-MI configuration, the systolic strains remained very similar throughout the post-MI period. Overall, we observed that post-MI ventricular remodeling induced permanent changes in the MV leaflet shape. This predominantly affected the MV’s diastolic configuration, leading in turn to a significant decrease in the range of stretch experienced by the leaflet when referenced to the current diastolic configuration. These findings are consistent with our previous work that demonstrated increased plastic (i.e. non-recoverable) leaflet deformations post-MI, that was completely accounted for by the associated changes in collagen fiber structure. Moreover, we demonstrated through noninvasive methods that the state of the MV leaflet can elucidate the progression and extent of MV adaptation following MI and is thus highly relevant to the design of current and novel patient specific minimally invasive surgical repair strategies.Each year, more than 40,000 people undergo mitral valve (MV) repair surgery domestically to treat regurgitation caused by myocardial infarction (MI). Although continual MV tissue remodelling following repair is believed to be a major contributor to regurgitation recurrence, the effects of the post-MI state on MV remodelling remain poorly understood. This lack of understanding limits our ability to predict the remodelling of the MV both post-MI and post-surgery to facilitate surgical planning. As a necessary first step, the present study was undertaken to noninvasively quantify the effects of MI on MV remodelling in terms of leaflet geometry and deformation. MI was induced in eight adult Dorset sheep, and real-time three-dimensional echocardiographic (rt-3DE) scans were collected pre-MI as well as at 0, 4, and 8 weeks post-MI. A previously validated image-based morphing pipeline was used to register corresponding open- and closed-state scans and extract local in-plane strains throughout the leaflet surface at systole. We determined that MI induced  More broadly, the societal burden of MI-induced IMR is expected to continue to increase, given existing trends in the growth of the elderly population2.The mitral heart valve (MV) valve regulates blood flow between the left atrium and left ventricle (LV). Due to its intimate anatomical integration with the LV via the annulus, chordae tendineae (MVCT), and papillary muscles (PMs), the MV is considered part of the LV functional unit. Ischaemic MV regurgitation (IMR) often follows a myocardial infarction (MI), whose aftereffects distort the MV geometry through annular dilation and MVCT tethering, and the severity of IMR coincident with LV dysfunction has been directly associated with premature death3, in which the annular orifice area is forcibly decreased, this approach remains problematic, with about a third of repairs failing over the longer term (i.e. leading to a recurrence of IMR)4. It has been hypothesised that the failure rate of URA-based repairs is at least partially attributable to the substantial changes in MV geometry and closing behaviour that this procedure induces, including constriction and flattening of the annulus6. Moreover, the repair does not halt continued LV remodelling post-MI, which over time alters the MV’s “boundary conditions” sufficiently to cause recurrent IMR9. The mechanisms of MV repair failure have been partly elucidated through analysis of real-time three-dimensional echocardiography (rt-3DE) images collected pre- and post-surgery. Recently, Bouma et al. showed that the pre-surgical tethering angle of the posterior leaflet could be used as a predictor of recurrent IMR 6 months after URA10. Our current knowledge of MV function and IMR-induced remodelling thus suggests that despite high rates of short-term repair success, in some cases URA may actually exacerbate posterior leaflet tethering by displacing the posterior annulus anteriorly, which increases the probability of recurrent IMR over the long term11.While IMR has most successfully been addressed through a surgical MV repair procedure known as undersized ring annuloplasty (URA)14. In addition, post-MI and post-URA MV growth and remodelling undoubtedly play a critical role in determining repair outcomes15. In addition to changes in tissue-level properties, there is evidence of MV interstitial cell activation and matrix turnover in the MV leaflets following MI17. Due to the established causal link between tissue stretch and cell-driven remodelling mechanisms, a detailed account of tissue-level deformation patterns in the post-MI MV can provide substantial insight into the current biosynthetic state of the MV19. Consequently, it is likely that quantitative estimates of MV leaflet tissue deformation, and changes therein following MI, can serve as valuable independent predictors of long-term remodelling phenomena that affect MV function and thus repair outcomes. Yet, our understanding of MV tissue remodelling remains profoundly limited in both the unmodified pathological and post-surgical scenarios.Accurate prediction of MV repair success or failure, for the purposes of patient stratification and/or personalised treatment, will depend on developing a fuller understanding of the interrelationships between the MV’s geometry, mechanics, and capacity for biologically mediated remodelling. The accumulated body of previous studies relating particular preoperative MV characteristics  to the success or failure of URA underscores the possibility and an urgent clinical need for noninvasive, patient-specific methods to optimise MV repair procedures based on pre-surgical information alone20 to noninvasively quantify how the in vivo diastolic and systolic MV deformation patterns change after MI, in an effort to more fully understand how and to what extent the MV remodels post-MI. Such an understanding is critical and must be established prior to any endeavour to optimise MV repair approaches on a patient-specific basis.The objective of the present investigation was thus to gain insight into the post-MI MV remodelling behaviour by directly quantifying the effects of MI on MV in vivo leaflet tissue deformation. To this end, we utilised a recently developed image-based computational modelling pipeline21. Moreover, both leaflets were severely tethered post-MI. Paired Initial analysis of rt-3DE images from eight ovine subjects collected pre-MI as well as 0, 4, and 8 weeks post-MI indicated that the MV annulus became substantially dilated post-MI, consistent with previous findings Fig. 21. Moreopermanent leaflet deformations in the diastolic (fully opened) state. These deformations were permanent in the sense that they appeared in the diastolic (opened) configuration, which is under minimal loading. Moreover, such permanent changes in the MV leaflet have been observed in previous studies on post-MI excised leaflets using the same animal model22. As such, they are not associated with other mechanisms and represent intrinsic changes to the MV leaflet dimensions. We thus quantified these permanent changes as a form of plastic deformation, represented as stretches in the circumferential and radial directions referenced to the initial pre-MI configuration , and do not appear to be due to any other pathophysiological processes.However, enabling such models requires a detailed understanding of MV remodelling, of which there remains a paucity of information. In the present study, we have taken a step towards addressing this issue utilising our noninvasive image-based computational method to quantify MV leaflet deformations. We divided our analysis into two functional parts: (1) Changes in the open (diastolic) configuration, which are driven by plastic (i.e. non-recoverable) deformations induced by changes in the post-MI LV, such as annular dilation and leaflet tethering, and (2) changes in the closed (systolic) deformations which are induced by LV pressure. We examined how these quantities evolved during an 8-week post-MI period in the absence of treatment. As such, this study represents an essential “baseline” investigation of MV remodelling post-MI. It offers a detailed picture of the extent to which the MV is 39, who previously performed a detailed fiducial marker-based analysis of acute and chronic MV leaflet enlargement using the same ovine model of posterior MI. Although the two studies partitioned the leaflet differently for regional analysis, the results are generally in very close agreement. Specifically, both studies found that (1) immediately post-MI, diastolic stretches were not significant in either the circumferential or radial directions; (2) chronically, circumferential stretches were close to 5% on average, with significant increases detected near the anterolateral commissure (segment A1) but no differences detected near the posteromedial commissure (segment A3); (3) chronically, circumferential stretches near the free edge tended to be smaller than in the central belly, while those near the annulus tended to be larger than in the central belly; and (4) chronically, radial stretches were significant and close to 10% in the central belly region (segment A2). The agreement of these key findings serves as a notable additional validation of our novel noninvasive method for image-based stretch estimation.In regard to related studies, it is possible to compare our findings to those of Rausch et al.41. The collagen fibres are crimped when unloaded but rapidly straighten and thus stiffen the tissue in systole . Regardless of the exact time course of these processes, our results clearly indicate that the post-MI MV leaflet tissues are no longer normal, which in turn may be another source of repair failures.The above findings can be best understood mechanistically in relation to the underlying mitral valve fibre architecture. As in all heart valve tissues, MV leaflet directional extensibility is directly determined by the underlying network of collagen fibresle Figs. , 10. The42, in which only passive MV adaptation was observed in early pregnancy, followed by active remodelling of the tissue’s collagen and elastin networks throughout middle and late pregnancy. Together, these studies indicate that MV adaptations to alterations in loading do not occur at the same rate—nor via the same mechanisms—over time, highlighting the complexity of the MV as a biologically responsive tissue. To further elucidate the MV remodelling process, we are currently performing detailed in vitro studies to examine how collagen fibre architecture, tissue composition, and biosynthetic activity in the MV change following MI, which will allow us to draw connections between tissue-level deformations and cellular behaviour in vivo15.From a broader perspective, the results of the present study have several important clinical implications with respect to the treatment of IMR. While IMR is not inherently a valvular disease, but rather a consequence of maladaptive LV remodelling post-MI, the present study is one of the few to elucidate the large extent to which the MV can adapt, either positively or negatively, to substantial changes in its ventricular and haemodynamic environment. The timeline of MV remodelling we have observed in the case of post-MI adaptation is consistent with a previous investigation of MV remodelling in the non-pathological case of pregnancy43 and chord-based (e.g. Neochord)44 repair devices, which induce more local stress concentrations, remain largely unknown. The design and refinement of such devices, as well as their proper selection for treating a heterogeneous patient population, would thus greatly benefit from a deeper understanding of the MV remodelling process. Future extensions of this work may also jointly account for the synergy between the MV and LV, since they more precisely behave as a single unit. Insights from the present study can be exploited to improve outcomes of post-MI therapies that primarily target the LV wall affected by MI (e.g. hydrogel injections), for example46. Moreover, our results hint at the possibility of exploiting patient-specific post-MI MV remodelling assessments to steer not just the design of MV repair techniques themselves, but also the timing of repair surgery. We speculate, for example, that IMR treatment plans accounting for both the current functional state of the MV—which is far from “normal” (i.e. pre-MI)—as well as a rational, evidence-based prediction of how MV remodelling will progress until and after surgery would yield lower rates of IMR recurrence following repair.The modelling and analysis pipeline we have utilised is not specific to post-MI MV assessment and can be applied to the evaluation of repair-induced MV remodelling as well. The long-term adaptive effects from annuloplasty, which alters MV geometry globally, as well as recently developed leaflet clipping (e.g. MitraClip)47. We note too that the rt-3DE images were collected only over an 8-week period post-MI. Even though our results suggest that at least some of the changes experienced by the MV have already stabilised by 4 weeks, longer term follow-ups will be required to confirm whether the trends observed over this time remain steady, accelerate, or even reverse as a consequence of complex remodelling mechanisms. More comprehensive studies are also necessary to examine the effects of different MI locations as well as repair surgery on the geometry, deformation, and remodelling of regurgitant MVs on a patient-specific basis. Furthermore, the effects of spatial heterogeneity in the MV leaflet tissue’s microstructure, including fibre orientation and alignment as well as constituent volume fractions in different regions of the leaflet, must also be examined more closely, since these aspects of the leaflet’s biomechanics may themselves change post-MI52.While comprehensive, the scope of the present study was limited in several respects. First, our computational method uses image-derived diastolic and systolic geometries of the leaflets only and not the MVCT (which are mostly invisible in rt-3DE). Thus, our ability to predict the post-MI state using only the pre-MI geometry, or similarly to predict the post-repair state using only the pre-repair geometry, is limited. In our ongoing work, however, we are combining this leaflet-based approach with a novel methodology for creating functionally equivalent models of the MVCT, which will enable such predictions given only knowledge of the requisite boundary conditionsAn additional consideration is the potential confounding effects of age-related growth on the results. While there was no control group explicitly used, we felt it was unnecessary as the current animal model is very well established for the studies of left ventricular infarction and ischemic mitral valve regurgitation, and has been used extensively by our group for almost three decades. Moreover, as stated in the "47. We note too that the present study also has implications for minimally invasive MV repair technologies, such as clips, which induce focal stress concentrations. Such focal effects may lead to long-term remodelling that may limit the durability of such devices, so that patient-specific methodologies may be required to determine optimal design and usage.The results of our present study shed significant light on the post-MI remodelling behaviour of the MV. These findings are highly relevant to the design of MV repair devices and the optimisation of surgical strategies, as they directly elucidate the the pre-surgical state of the MV. While current repair endeavours largely seek to return the MV to its pre-MI state, our results suggest that this approach may not be favourable, or even possible, especially given the substantial changes in stretch exhibited by the valve. Instead, an effort to place the MV in an alternative state, as close as possible to its homeostatic state, may lead to decreased maladaptive long-term remodelling and thus superior repair outcomes. In our ongoing work, we are building upon the present study to investigate how fibre architecture, tissue composition, and biosynthetic activity in the MV change following MI, which will allow us to draw connections between tissue-level deformations and cellular behaviour in vivoAll animal protocols used in this study were approved by the University of Pennsylvania’s Institutional Animal Care and Use Committee and complied with the National Institute of Health’s guidelines for the care and use of laboratory animals . The University of Pennsylvania, with the Supervision of the School of Veterinary Medicine, maintains a full-service vivarium facility operated by the University Laboratory Animal Research (ULAR) organisation. The vivarium is directly adjacent to the laboratory’s operating room suite.55. Briefly, subjects were anaesthetised with sodium thiopental (10–15 mg/kg intravenously), intubated, and ventilated with isoflurane (1.5–2%) and oxygen. Surface electrocardiogram, arterial blood pressure, and other vital signs were continuously monitored throughout the procedure55. Under sterile conditions, subjects underwent a thoracotomy to allow ligation of the second and third obtuse marginal branches of the circumflex coronary artery. Permanent occlusion of these arteries reliably results in a transmural posterior MI that involves approximately 20% of the LV mass, includes the entire posterior PM, and causes a gradual onset of severe IMR within 8 weeks55. After haemodynamic and electrophysiological stabilisation, the incisions were closed and subjects were allowed to recover for subsequent follow-up imaging.A posterior MI was induced in eight non-diseased adult Dorset sheep, following established procedures that have been previously described in detail57, electrocardiographically gated full-volume images were acquired over four consecutive cardiac cycles, with an imaging depth of 12–16 cm. From each subject’s data series, representative rt-3DE images of the MV in the end-diastolic and end-systolic states were selected for analysis and exported in Cartesian format with an approximate isotropic resolution of 0.6–0.8 mm. Each specimen was imaged pre-MI, immediately post-MI , the same stretch estimation method was applied, only without atrioventricular pressurisation. To allow for both biomechanical and clinical interpretations, all systolic stretch fields were then expressed with respect to both pre-MI and current diastolic states.64. The use of a conformal map was crucial to our approach, as it preserved orthogonality between the circumferential and radial directions. The stretch fields of each subject were then defined in the parametric space, which registered the stretch values from each original 3D valve geometry to a 2D domain with orthogonal coordinates that were correspondent across all specimens  map, which was obtained by solving the Laplace equation on each triangulated mesh with Dirichlet boundary conditions on the annulus and free edgeens Fig. . The abiSupplementary Information.


Time‐resolved three‐directional velocity‐encoded (4D flow) magnetic resonance imaging (MRI) enables the quantification of left ventricular (LV) intracavitary fluid dynamics and energetics, providing mechanistic insight into LV dysfunctions. Before becoming a support to diagnosis and patient stratification, this analysis should prove capable of discriminating between clearly different LV derangements.To investigate the potential of 4D flow in identifying fluid dynamic and energetics derangements in ischemic and restrictive LV cardiomyopathies.Prospective observational study.Ten patients with post‐ischemic cardiomyopathy (ICM), 10 patients with cardiac light‐chain cardiac amyloidosis (AL‐CA), and 10 healthy controls were included.4D flow sequences.1.5 T/balanced steady‐state free precession cine and V] and viscous energy loss [ELV]), and pressure‐derived hemodynamic force (HDF) were compared between the three groups.Flow was divided into four components: direct flow (DF), retained inflow, delayed ejection flow, and residual volume (RV). Demographics, LV morphology, flow components, global and regional energetics ; differences in energetic variables and peak HDF were tested by two‐way ANOVA. A V, mostly in the basal region, in systole (−44%) and in diastole (−37%); altered flow components, with reduced DF (−33%) and increased RV (+26%); and reduced basal–apical HDF component on average by 63% at peak systole. AL‐CA patients exhibited the following alterations vs. controls: significantly reduced KEV at the E‐wave peak in the basal segment (−34%); albeit nonstatistically significant, increased peaks and altered time‐course of the HDF basal–apical component in diastole and slightly reduced HDF components in systole.ICM patients exhibited the following statistically significant alterations vs. controls: reduced KEThe analysis of multiple 4D flow‐derived parameters highlighted fluid dynamic alterations associated with systolic and diastolic dysfunctions in ICM and AL‐CA patients, respectively.23 Cardiac magnetic resonance imaging (MRI) is the reference standard imaging technique for morphofunctional assessment and noninvasive tissue characterization of cardiac diseases.4D flow is increasingly employed in clinical practice and researchAccording to the etiology of LV cardiomyopathy, the pattern of chamber remodeling may differ. For instance, ischemic cardiomyopathy (ICM), secondary to coronary artery disease and myocardial infarction, is the most common type of dilated cardiomyopathy and is characterized by myocardial scarring, progressive chamber dilation, and impaired systolic function.Given the expected interplay between LV wall function and intracavitary flow, we hypothesized that different LV pathological conditions, such as ICM and AL‐CA, may exhibit a different pattern of intracavitary flow derangements.et al. showed that post‐ischemic patients have reduced global LV kinetic energy (KE),et al.et al.Previous studies have already employed 4D flow to assess hemodynamic derangements associated with pathological LV conditions. Garg However, although previous studies demonstrated the relevance of specific 4D flow parameters, no study has investigated LV flow components,Hence, the aims of this study were to: 1) investigate the potential of 4D flow to identify derangements in fluid dynamic features specifically associated with ICM and AL‐CA as examples of depressed LV systolic function and altered LV diastolic compliance, respectively, and 2) evaluate if the combined analysis of multiple fluid dynamic features provides extra insight into the underlying pathophysiological mechanisms.The study conformed to the Ethical Guidelines of the Declaration of Helsinki; all subjects provided written informed consent.Ten ICM patients, 10 AL‐CA patients, and 10 controls with no history of cardiac disease and no cardiovascular risk factors were included in the study.ICM was defined based on the history of previous anterior myocardial infarction, LV dilation, and systolic dysfunction  assessed by 2D echocardiography and MRI; severe aortic or mitral valvulopathies were excluded.Cardiac involvement in AL‐CA patients was defined according to the established consensus criteria.Blood samples for hematocrit were obtained at the time of MRI.All subjects underwent MRI at 1.5 T using a MAGNETOM Aera  scanner. A balanced steady‐state free precession (b‐SSFP) cine sequence with retrospective ECG gating was used to acquire short‐axis (SAx) and long‐axis  LV views with the following parameters: TE (Echo Time) = 1.1–1.8 msec, TR (Repetition Time) = 2.0–5.9 msec (segments = 14–16), slice thickness = 8 mm (no gap), pixel spacing = 1.25–1.65 mm, and reconstructed temporal resolution = 22–46 msec (reconstructed phases = 30). ICM and AL‐CA patients were administered with a bolus of gadobutrol . No contrast agent was used in controls.3, reconstructed temporal resolution = 22–65 msec, and reconstructed phases = 20 (9 subjects) or 30 (21 subjects). 4D flow data were corrected for eddy currents and aliasing. All patients were in sinus rhythm during MR acquisition.In the same session, 4D flow images were acquired using a prototype time‐resolved 3D gradient echo sequence with three‐directional velocity encoding a parasagittal‐oriented field of view covering the entire LV. 4D flow was performed during free‐breathing with retrospective ECG‐triggering and adaptive respiratory gating. The following scan parameters were implemented: velocity encoding = 80–150 cm/sec to limit aliasing, flip angle = 7°(without contrast) to 15°(with contrast), TE = 2.3–2.8 msec, TR = 4.8–5.2 msec (segments = 2), voxel size = (2.0 × 2.0 × 2.0) to (2.8 × 2.8 × 2.8) mmLV volumes, mass, and EF were calculated from b‐SSFP cine images using a thresholding method in Medis  by an expert cardiologist . Also, an expert operator  employed b‐SSFP images to reconstruct dynamic LV masks as in a previous workFor each condition, LV flow subdivision, LV energetics in terms of KE and viscous energy loss (EL), and LV HDF were quantified Table ; A.R. ov42  according to Eriksson et al.The intraventricular blood flow was automatically divided into four components using cvi12mv2 for each voxel, where m is the mass of blood in one voxel and v is the velocity magnitude in each voxel.KE and EL  were computed for each LV region and for the whole chamber.b) was computed from the Navier–Stokes equation.b over the entire LV volume and was then projected onto three mutually orthogonal directions , perpendicular to the atrioventricular plane and defined from apex and mitral landmarks on the HLA view; 2) septal–lateral , parallel to the LVOT view; and 3) inferior–anterior (HDFinferior–anterior), perpendicular to the septal–lateral and basal–apical directions.septal–lateral, HDFinferior–anterior, and HDFbasal–apical were computed over the cardiac cycle. The three values were combined to derive the ratio between the RMS of the transversal and basal–apical components of the HDF (RRMS)The pressure gradient b was co3 and viscosity μ dependent on patient‐specific hematocrit and shear rate, i.e., the velocity gradient between adjacent layers of bloodFor all calculations, blood was assumed to be a non‐Newtonian fluid with density equal to 1025 kg/mAt each time‐point, KE, EL, and HDF were normalized to the current LV volume to account for the potentially confounding effect of heart size.V and HDF, computed based on the different binary masks, were statistically compared. Further details are reported in Our analyses are characterized by two manual steps of the processing pipeline: 1) the manual initialization of the semiautomatic segmentation of the LV endocardium on cine MR images, and, when needed, 2) the manual corrections of the LV endocardial contour yielded by the automated tracking algorithm. These steps can impact the binary masks defined in the 4D flow data to identify the LV chamber. We assessed their combined impact via interobserver variability analysis of the binary masks obtained upon segmentation by two independent and double‐blinded operators  of the data of 15 randomly selected subjects. Also, peak values of KEDemographic and standard MRI measures are reported as mean ± SD. Normality of the distribution of continuous data was assessed through the Shapiro–Wilk test. One‐way analysis of variance (ANOVA) with Tukey's post hoc test was used to compare the three groups in terms of flow components. Changes in energetic variables and in HDF peak values were assessed using two‐way ANOVA.In the interoperator analysis, the Dice Score Coefficient (DSC) was computed to compare the LV binary masks obtained by the two independent operators; also, linear regression was adopted for KE and HDF components computed based on different LV masks.P‐value of <0.05 was considered significant.Statistical analyses were performed with GraphPad Prism 8 ; a P = 0.055; 95% CI: 54–63 in controls, 59–70 in ICM and 61–72 in AL‐CA). ICM patients had significantly greater LV volumes and lower EF with respect to both controls and AL‐CA patients; AL‐CA patients had significantly lower stroke volume (SV) compared to control subjects.Characteristics of the three groups are detailed in Table Compared to controls, the overall partition in flow components in AL‐CA patients was preserved, while ICM subjects showed significantly reduced DF and DE and significantly increased RI and RV compared to both AL‐CA subjects and controls , and a subsequent small but clearly separated peak, corresponding to atrial contraction (A‐wave)  Fig. . In ICM ve) Fig. . AL‐CA pV  in KEV was noticed in the basal region for E‐wave peak , KEV associated with the basal region was significantly reduced in ICM vs. controls.In diastole Fig. , there wV was comparable between systole and diastole (Pphase = 0.074). Yet, in both phases, significant intergroup differences were observed . In diastole, instead, a statistically significant reduction vs. controls was observed only in E‐wave peak of HDFbasal–apical; the reduction in the A‐wave peak of HDFbasal–apical was not statistically significant (P = 0.06). No statistically significant alteration in HDFseptal–lateral nor in HDFinferior–anterior was observed at the E‐wave and at the A‐wave peaks. As a result, in systole, the HDF vector remained aligned with LVOT despite the depressed magnitude; in diastole, it was not aligned with the LV long‐axis  or at the E‐wave  and A‐wave  diastolic peaks , with the strongest level of agreement (r2 = 0.99) in diastole .V vs. healthy controls and consistently with previous studies.V regional analysis showed a significant reduction in the systolic KEV peaks in the mid and basal regions vs. controls. The former was more severely affected, consistently with the location of the original ischemic injury, but the latter was still notably reduced, highlighting the impact of post‐infarct injury on the remote, although not scarred, myocardium.V was paired by a proportional reduction in ELV, suggesting that the systolic intracavitary blood flow is characterized by lower velocities, but with no evident changes in the velocity field pattern  that would lead to increased viscous dissipation. Of note, the reliability of regional data was allowed for by our patient‐specific subdivision of the LV chamber, which proved effective in correctly distinguishing the apical, mid‐cavity, and basal LV regions, despite the heterogeneous LV remodeling patterns affecting our ICM patients.Our ICM patients suffered from anterior myocardial infarction; as such, they were characterized by an extended scar region.et al.'s cohortMoreover, the SV composition was different compared to healthy controls due to the derangement of flow component redistribution: there was a reduction in the DF component, which was recently found by Stoll et al to be comparable between ICM and apparently compensated dilated cardiomyopathy patients.basal–apical was almost absent and reduced on average by approximately one half vs. controls. This likely reflects a severely reduced “piston‐like” motion of the valvular plane toward the apex and thus the inability to effectively move blood from the sub‐mitral region toward the apex at the onset of systole, and from the more apical regions toward the outflow tract at peak systole.inferior–anterior was barely present, reflecting the reduction in anterior wall contractility, and there was a milder reduction of HDFseptal–lateral leading to abnormally high RRMS,systole values.Analysis of HDF can yield the link between derangements in intracavitary systolic blood flow and the depressed LV function in ICM patients.Altogether, the different fluid dynamic parameters stress that ICM is a systolic dysfunction, yet derangements in the diastolic phase are also present.V peak in the mid‐cavity region associated with the E‐wave was delayed with respect to the corresponding peak in the basal region, whereas no significant delay was observed in controls. This is consistent with the increased duration of the E‐wave peak that was observed in the flow rate time‐course compared to controls. Also, it is consistent with the observations by Garg et al.,basal–apical that were synchronous to the E‐wave and the A‐wave in healthy controls. As a result, the value of RRMS,diastole was almost doubled compared to healthy controls. This lack of transfer of momentum in the basal–apical direction is consistent with the presence of blood RV that remains confined in the dilated and akinetic mid‐apical regions.At diastole, LV energetics showed that the KEV. Also, while in healthy controls, a valley clearly separated the E‐wave and A‐wave peaks in KEV time‐course, in AL‐CA patients this valley almost disappeared, suggesting the preservation of the time‐averaged value of KEV over the diastolic phase. This is consistent with the computed time‐course of the diastolic flow rate, which in AL‐CA was characterized by a markedly reduced E‐wave peak and absence of a clear distinction between the E‐wave and A‐wave peaks. This behavior is consistent with the reduced volume entering the LV in diastole and hence significantly reduced SV in AL‐CA patients.In our AL‐CA cohort, compared to healthy controls, we observed derangements in LV diastolic fluid dynamics. Specifically, the energetics analysis showed a significant reduction in the E‐wave peak of global and basal KEbasal–apical over the end of systole and the onset of diastole. In controls, we obtained two negative peaks separated by a short notch at the transition between systole and diastole; the earlier peak was characterized by a higher amplitude and was concomitant to the closure of the aortic valve, and the later peak had a smaller amplitude and anticipated the onset of the E‐wave. This pattern is consistent with the observations by Arvidsson et al in healthy volunteers and elite athletes.The derangements in diastolic LV energetics were not paralleled by anomalies in flow subdivision, thus suggesting that flow organization might not be a suitable marker to highlight AL‐CA‐related fluid dynamic derangements. On the contrary, a more subtle feature was noticed during LV relaxation in HDFbasal–apical alterations at the onset of diastole in AL‐CA patients, as proposed by Arvidsson et al.,basal–apical to early diastolic chamber filling by integrating the time‐course of this HDF component from aortic valve closure, identified as the time‐point with zero flow rate at end‐systole, to the time‐point with zero HDFbasal–apical . This early diastolic filling impulse, normalized to LV chamber volume, proved to be nearly two thirds higher in AL‐CA patients than in controls with values equal to 4.58 × 10−2 and 2.77 × 10−2 Ns/L, respectively. This mismatch, given the statistically negligible differences of intracavitary volume between controls and AL‐CA patients, may reflect the reduced diastolic LV compliance during early filling in AL‐CA patients. If this outcome was confirmed by the analysis of larger cohorts of subjects, this index may be considered attractive as it is quantitative and synthetic, and it can be computed in a simple and repeatable way. The observed diastolic derangements in both KEV and HDFs may be signs of deteriorating diastolic function in AL‐CA,To pinpoint HDFV, although localized in the basal region, was found with respect to healthy controls. This reduction should not be interpreted as an energetically more efficient filling in AL‐CA patients; in fact, this parameter reflects the phenomena occurring in the bulk of the blood flow and does not account for the dissipative phenomena occurring in the boundary layer at the endocardial level, largely contributing to the actual amount of dissipated energy.V may be due to the absence or reduction of physiological vortical structures in the bulk flow during diastolic filling, potentially due to the reduced compliance of the LV. Of note, the decrease in ELV was mainly localized in the basal region, possibly because of an absent or mitigated toroidal vortical structure that characterizes the sub‐mitral region of healthy subjects during LV filling.Moreover, a significant reduction in diastolic ELV remained comparable to controls, but with an anomalous regional repartition: KEV median value was reduced in the basal region and increased in the mid region. Concomitantly, RRMS significantly increased. This result may suggest that:RRMS is due to a decrease in the RMS of HDFbasal–apical, which is consistent with the reduced GLS observed by Buss et al.In AL‐CA patients, the LV wall has a slightly impaired capability of transferring momentum to the intracavitary blood rapidly, which is reflected in a reduced net motion of blood toward the LVOT even if the overall amount of KE is preserved or even increased. This interpretation is consistent with the reduced flow rate recorded in these patients, and with the depressed SV reportedThe impairment may be mostly associated with the basal region, and the LV wall tries to compensate for it by an extra pumping action of its mid portion. This speculation may be consistent with previous MRI findings in cardiac amyloidosisEven if AL‐CA is mostly associated with diastolic dysfunction, slight fluid dynamic derangements were also detected in systole. Global KEKE and EL provide volume‐averaged global (over the LV chamber) or regional  information on the LV systolic function and on the presence of velocity patterns with relevant gradients, such as vortical structures.HDF, which is a 3D vector providing information on the direction of the transfer of momentum from LV wall to cavity,Flow component analysis allows for exploring the interplay between consecutive cardiac cycles.The selected fluid dynamic parameters have complementary features and can elucidate different aspects of LV function:V together provided an exhaustive understanding of the post‐ischemic scenario; HDF highlighted the anterior location of the infarcted region, which could not be done by the analysis of KEV, while the regional analysis of KEV allowed to assess the impact on scarred myocardium as well as on remote myocardium, which could not be done based on HDF quantification. Likewise, for our AL‐CA patients, only the joined analysis of the peaks in regional KEV and of RRMS allowed us for a reasonable interpretation of the mechanism underlying the impairment of systolic LV function in a pathology typically used as an example of diastolic dysfunction.The analysis of only one of these parameters could be insufficient to highlight LV function derangements: for instance, based on flow component analysis only, LV function in AL‐CA patients would not be detected as significantly altered. Even when not insufficient, it still is not as powerful as the combined analysis of multiple parameters: in our ICM patients, the analysis of HDF components and of KEet al.,Future work is required to explore if the proposed indexes could be useful to monitor disease progression, as well as the effects of therapy during follow‐up. It also remains to be tested whether their alteration could allow for an earlier detection of changes in LV function compared to standard functional indexes, at least in the two pathological scenarios herein considered. The seminal study by Pedrizzetti The study population was relatively small; therefore, our results are preliminary. Also, both groups of patients were heterogeneous: ICM patients, although all affected by the anterior infarction of comparable severity, were heterogeneous in terms of LV characteristics and remodeling severity, and AL‐CA patients had different levels of cardiac involvement. However, despite the limited sample size, this study shows the potential of 4D flow in providing a noninvasive, time‐efficient and multifaceted quantification of specific hemodynamic parameters, whose alterations can be associated with different LV remodeling patterns. Despite their intragroup variability, our ICM and AL‐CA cohorts represent not only two clinically relevant scenarios, but also two opposite LV remodeling mechanisms.In addition, the limited spatial and temporal resolution of 4D flow acquisitions may impact the granularity of the computed parameters. This may inevitably affect the velocity derivatives computation, and thus the accuracy of computed ELIn a preliminary cohort of patients, 4D flow‐based quantification of LV fluid dynamics characterized intracavitary flow derangements associated with ICM and AL‐CA, selected as representative of systolic and diastolic dysfunction, respectively.V and HDF provided consistent and complementary information on the interplay between intracardiac blood fluid dynamics and LV wall function.In particular, the analysis of alterations in KEAppendix S1 Supplementary methods.Table S1 LV peak kinetic energy normalized to LV volume for the study population, evaluated for the global LV, basal LV, and mid LV.Table S2 LV peak hemodynamic forces, for the basal–apical, septal–lateral, and inferior–anterior component, normalized to LV volume for the study population.Table S3RRMS ratio for the study population.Table S4 Reproducibility analysis.Fig. S1 Exemplification of long‐axis CMR views tracing of papillary muscles (tip and base), mitral and aortic valves, and apex for the left ventricle at end diastole.Fig. S2 Schematic of the four flow components of the left ventricular blood flow.Fig. S3 Definition of hemodynamic force directions.Fig. S4 Peak systolic and peak diastolic values of KEV and HDFV components (c–h) extracted from the segmentation performed by two operators.Fig. S5 Quantification of the early diastolic filling impulse for IBA.Fig. S6 Parameters required to compute the roto‐translation matrix M.Click here for additional data file.Video S1 Left ventricular flow component visualization for one healthy control, one ischemic cardiomyopathy patient, and one cardiac amyloidosis patient. Direct flow is indicated in green, retained inflow in yellow, delayed ejection flow in blue, and residual volume in red.Click here for additional data file.


Gestational diabetes mellitus (GDM) may increase the risk of cardiovascular disease and accompany asymptomatic deterioration of the myocardial function. This study aims to identify the subclinical impact of GDM on maternal left ventricular function by two-dimensional speckle tracking echocardiography (2D-STE).We prospectively recruited 47 women with GDM and 62 healthy pregnant women who underwent transthoracic echocardiography (TTE) at 24 to 28 weeks of pregnancy. GDM diagnosis agreed with the IADPSG criteria. TTE was performed according to the criteria of the American Society of Echocardiography. Conventional echocardiographic data and 2D-STE parameters were compared between the two groups.vs. 22.36 ± 6.33, p < 0.001), and 31 patients (66%) in our study had an absolute LV-GLS less than 20%. The LA reservoir and conduit strain in patients with GDM were also significantly reduced . However, there was no significant difference in LA contractile function between the two groups. In multiple regression analysis, LV-GLS and LA conduit strain independently associated with GDM.Age, gestational weeks, heart rate, and conventional echocardiographic parameters had no difference between the two groups. The average LV global longitudinal strain (LV-GLS) of GDM patients was lower than controls (18.14 ± 2.53 2D-STE could detect the subclinical myocardial dysfunction more sensitively than conventional echocardiography, with LV-GLS and LA conduit strain as independent indicators of the GDM impact on maternal cardiac function during pregnancy. Diabetes mellitus (DM) is a systemic metabolic disease that may lead to multiple organ dysfunction, among which cardiovascular impairment is relatively prominent , 2. The Patients with DM may be asymptomatic, with decreased myocardial diastolic function but preserved left ventricular ejection fraction (LVEF) , 8. Two-The study was approved by the Ethics Committee of Harbin Medical University. From October 2020 to January 2021, we recruited 124 consecutive Chinese women with a singleton pregnancy who underwent comprehensive transthoracic echocardiography (TTE) assessment. All the patients have signed the informed consent before examination. Fifteen patients were excluded due to their poor acoustic window, and finally 47 GDM patients and 62 healthy pregnant women were included in the study.The International Association of Diabetes and Pregnancy Study Groups (IADPSG) defined GDM as any degree of low glucose tolerance first diagnosed during pregnancy . The diaThe age, body mass index (BMI), blood pressure (BP), heart rate (HR), gestational weeks, and blood glucose level of the study population were queried at their enrollment. BP was measured three times and averaged after at least ten minutes of rest. BP was measured in a silent room 5 to 10 min before echocardiography with an aneroid sphygmomanometer twice in a seated position, with the right arm at the level of the heart, after 5 min of rest.Echocardiography was performed by two senior sonographers (Ziyao Li and Wei Li) on GE Vivid E9 and E95  with an M5S probe (2.5 ~ 4.0 MHz). All data were averaged from three consecutive cardiac cycles. Patients with poor image quality were excluded before recruitment. Images were recorded and studied according to the recommendations of the American Society of Echocardiography .3–LVEDd3]} + 0.6g. Relative wall thickness (RWT) was calculated using the formula RWT = 2 × (PWT/LVEDd). LVEF and LA volume (LAV) were measured using the biplane Simpson method. LVM, LAV, and stroke volume (SV) were indexed for body surface area (BSA) to get LV mass index (LVMI), LA volume index (LAVI), and stroke volume index (SVI), respectively. In the apical four-chamber view, pulse Doppler and tissue Doppler were performed to measure early diastolic mitral inflow velocity (E), and early diastolic annular velocity (e′). And mean e′ was the averaged velocity of the septal and lateral mitral annulus [In the parasternal long-axis view, LV end-diastolic diameter (LVEDd), interventricular septum (IVS) thickness, posterior wall thickness (PWT), and LV end-systolic diameter (LVESd) were measured by M-mode echocardiography. LV mass (LVM) was calculated by using the Devereux formula : LVM = 0 annulus .LV global longitudinal strain (LV-GLS) and LA phasic strain were analyzed offline using EchoPAC software . Allow the patient to hold their breath to get ultimate images of three consecutive cardiac cycles at a frame rate ≥ 60 frames per second. The 2D-STE measurements were performed by two physicians in a double-blinded manner for intraclass correlation coefficients (ICC) testing.To measure LV-GLS, 2D-STE was performed by tracing the LV endocardial boundary in the apical three-chamber, four-chamber, and two-chamber views . We use The biplane (4-chamber and 2-chamber) views were accepted for LA strain evaluation, according to the consensus from the European Association of Cardiovascular Imaging (EACVI)/American Society of Echocardiography (ASE)/Industry Task Force . When trt-test. We firstly performed the univariate logistic regression to assess the crude correlations between clinical/echocardiographic characteristics and GDM. Variables with a p-value less than 0.05 in univariate regression entered the multivariate models, and a forward “likelihood ratio” selection approach was applied to identify parameters that were independently associated with GDM. The current study conducted two multivariate models which separately included either LV-GLS or LA phasic strain, to better identify their associations with GDM. ICC was examined by the Bland–Altman plot. We used SPSS version 25.0  statistical software. A p-value less than 0.05 was considered statistically significant.Continuous variables were expressed as mean ± standard deviation (SD) and compared by the student p > 0.05). Compared with the control group, GDM had increased BMI , higher SBP  and DBP . Based on the GDM level, only diet treatment was recommended clinically, no oral hypoglycemic drugs or insulin therapy were initiated.Table p < 0.001). LVEF was preserved in GDM and had no statistical difference with control. The mean e' velocity of mitral annulus was lower in GDM than control . However, there was no difference regarding the peak mitral inflow velocities (E and A), E/A ratio, or mean E/e'.Table vs. 22.36 ± 6.33, p < 0.001) . However, LA-Sct had no difference between the two groups (p > 0.05)  was independently associated with GDM. In another model that mainly involved LA phasic strain, LA-Scd showed a good independent association with GDM  , and the increase of oxidative stress and inflammation. They may trigger extracellular matrix accumulation, cardiomyocyte apoptosis, and myocardial fibrosis. Eventually, the left ventricle will develop centripetal hypertrophy and diastolic dysfunction [Owing to the hemodynamic changes during normal pregnancy , 21, phyfunction –26. As efunction , we founfunction , we alsoOn the other hand, LV diastolic function may also deteriorate in GDM patients. Among all the conventional echocardiography biomarkers of LV diastolic function, only the mean e' was independent associated with GDM. Although LA remodeling is considered a signal of LV diastolic functional changes , LAVI diThe current study reveals the ability of 2D-STE to distinguish the difference in myocardial function between newly diagnosed GDM and healthy pregnant women with preserved LVEF. However, there are intrinsic limitations of the current study. Firstly, the sample size of the study was small and from a single center. Secondly, we are lacking the information regarding the normal threshold of LV GLS and LA strains in pregnant women. Thirdly, we currently do not have either short-term or long-term follow-up information of GDM patients regarding the subclinical myocardial deformation impact on future CVD events, further observations are still needed regarding the cardiovascular outcomes in patients with GDM.This is a preliminary study on the performance of 2D-STE in GDM, and due to the limited number of patients and lack of follow-up information, the results need to be confirmed by larger studies. However, we have elucidated that 2D-STE may serve as a powerful indicator of transient myocardial deterioration in GDM.


We present a case of a 66‐year‐old male with a history of two previous diagnoses of myocardial infarction, followed by drug‐eluting stent implantation. During the check‐up, he complained of dyspnea, fatigue, and dizziness. Echocardiography revealed a massive left ventricular pseudoaneurysm (LVP). According to the patient's clinical manifestations and radiologic data, urgent surgical intervention was performed. Postoperatively, several complications appeared, which were managed successfully. The patient was discharged in stable condition. This is an interesting case of massive LVP without hemodynamic instability. Left ventricular pseudoaneurysm can lead to serious morbidity or mortality. The reported incidence is 10%–35% and has declined, primarily after coronary angioplasty. Several treatment methods are currently available. These all need to be taken individually when surgery or medical treatment is appropriate. The reported incidence of LVA after MI is 10%–35% and has declined, primarily due to treatment with coronary angioplasty performed in the acute phase of the event.2A 66‐year‐old male presented to our hospital for an outpatient visit with a history of past MI, arterial hypertension, and heart failure (NYHA III). According to the medical history, he was admitted twice to the ER for an inferior wall MI, followed by PCI . During his last hospitalization, he experienced atrial fibrillation. Transesophageal echocardiography (TEE) revealed reduced ventricular function EF‐43%), left atrial dilatation of 4.2 cm without any presence of thrombus, and moderate mitral valve regurgitation. The sinus rhythm was restored after electric cardioversion. Without any significant symptoms, he was discharged from the hospital with triple anticoagulation therapy, anti‐hypertensive medications, and heart failure medications. One month after the last event, during an outpatient visit, he complained of dyspnea, fatigue, and dizziness. The ECG demonstrated sinus rhythm, and echocardiography revealed a massive left ventricular false aneurysm located in the inferolateral wall, with reduced ventricular function (EF of 32%), LVED of 175 ml, and moderate mitral regurgitation .3A left ventricular pseudoaneurysm is a rare but very serious complication of acute MI that may lead to fatal rupture. The main pathophysiological factors are increased intracavitary pressure and structural weakness of the necrosed myocardium. The clinical presentation of LVP lacks specific characteristics. The symptoms of heart failure and associated mitral regurgitation are the most frequent presenting features.In addition, a large study by Yeo and colleagues demonstrated that patients treated conservatively had higher mortality than those managed surgically.Eventually, the LV pseudoaneurysmectomy with cardiac bypass and mitral valve annuloplasty with adequate postoperative drug treatment can effectively limit ventricular dilatation, improve left ventricular function, improve clinical symptoms, improve quality of life, and prolong survival.4As noted above, the long‐term outcome of patients with post‐MI left ventricular pseudoaneurysm depends on the severity of clinical symptoms, left ventricular function, and concomitant diseases. These all need to be taken into consideration when surgery or medical treatment is appropriate.In order to get a successful outcome in LVP management, every case should be approached individually.Zviad Bakhutashvili: Supervision; validation. Lia Janelidze: Project administration; writing – review and editing. Kakhaber Beria: Resources; writing – review and editing. Nana Bakashvili: Conceptualization; data curation; visualization; writing – original draft; writing – review and editing. Nika Kuridze: Conceptualization; data curation; visualization; writing – original draft; writing – review and editing.This work did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.No conflict of interest.Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.The manuscript has been approved by the institutional review board.No material from other sources has been reproduced.The work is not a clinical trial.


Heart block is the most common and concerning complication associated with transcatheter device closure of perimembranous ventricular septal defect (pmVSD) and its occurrence remains a great challenge for device closure.Between June 2002 and June 2020, 1076 pediatric patients with pmVSD, who successfully underwent transcatheter device closure in our center, were enrolled in this cohort study, with a median follow-up of 64 months (range: 1 to 19 years).P = 0.041), and oversized devices  were independently associated with occurrence of postprocedural heart block. Moreover, heart block was less likely to occur when the left disk of occluder was placed within the aneurysmal tissue .Of 1076 patients, 234 (21.8%) developed postprocedural heart block, with right bundle branch block being the most common (74.8%), followed by left bundle branch block (16.2%), and atrioventricular block (5.6%). Complete atrioventricular block occurred in 5 cases, including 3 cases with permanent pacemaker implantation, 1 case with recovery to normal sinus rhythm, and 1 case with sudden cardiac death. Most patients (97.9%) developed heart block within 1 week of procedure. Finally, 138 cases returned to normal cardiac conduction. Multivariate logistic regression revealed that thin-waist occluders (odds ratio [OR]: 1.759; 95% confidence interval [CI]: 1.023 to 3.022; The outcome of postprocedural heart block is favorable in most cases. Oversized devices and thin-waist occluders should be avoided. Placement of the left disk of the device should into the aneurysmal tissue is highly recommended. Ventricular septal defect (VSD) is one of the common types of congenital heart diseases (CHD), with perimembranous ventricular septal defect (pmVSD) subtype being the most frequent (70% of cases) . With reThe data underlying this article will be shared on reasonable request to the corresponding author.From June 2002 to June 2020, 1131 consecutive pediatric patients with pmVSD underwent successful transcatheter closure procedure with a single device in our center. Due to incomplete follow-up data for 55 patients, a total of 1076 patients were finally included in the analysis. All patients’ guardians provided written informed consent before participation. The local Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong First Medical University approved the study protocol. This study complied with the ethical standards of the Declaration of Helsinki.The inclusion criteria were as follows: ages ≥ 2 years or body weight ≥ 10 kg, diagnosed with hemodynamically significant pmVSD , defects identified at 9- to 12-o’clock positions in the short-axis parasternal view by transthoracic echocardiography (TTE), and pulmonary artery systolic pressure < 70 mmHg on TTE.The major devices used in this study were the Amplatzer eccentric VSD occluder , modified double-disk VSD occluders , and Amplatzer Duct Occluder II (ADO II) device . There were 3 subtypes of modified double-disk VSD occluders, namely symmetric, eccentric, and thin-waist. Methods of device selection and their descriptions have been reported elsewhere . HoweverAll patients underwent conventional electrocardiography (ECG), chest X-ray, TTE, and 24 h Holter monitoring before the catheterization procedure. The procedure for occluder implantation has been described in detail previously  was prescribed daily for the following 6 months in all patients.de novo onset of heart block or progression of a pre-existing heart block. If patients developed any of the AVB, CLBBB, or complete right BBB (CRBBB) symptoms, intravenous dexamethasone was administered at a dosage of 0.5−1.0 mg/kg  daily for 3 to 5 days and then gradually tapered the dose  over 2 weeks.In this study, the diagnostic criteria for postprocedural heart block  were either The follow-up ECG, chest X-ray, and TTE tests were scheduled for 1, 3, 6, and 12 months after the pmVSD closure and yearly thereafter. Additionally, 24 h Holter monitoring was carried out for each patient who suffered from AVB, CLBBB, or CRBBB at each outpatient visit. The follow-up data were available until December 2021. Patients with at least 1 year of follow-up were enrolled in the study. We characterized the postprocedural heart block as an early-onset (developing within 1 week of procedure), and late-onset (initiating after 1 week of procedure) adverse event. The postprocedural heart block patients who could restore their normal heart conduction by the last follow-up visit were included in the recovery group, and those who failed were allocated to the persistence group.Independent variables used in the analysis included gender, age, body weight, duration of hospital stay, defect diameter on TTE and ANG (inlet and outlet), subaortic rim , membranous aneurysms (yes and no), aneurysmal tissue involving the tricuspid valve (yes and no), the left disk placement within the aneurysmal tissue (yes and no), device type , device size, device diameter/defective outlet diameter (measured on ANG) ratio, device diameter/patient’s body weight ratio, procedure time, fluoroscopic time, and radiation dose.2) test, Fisher’s exact test, Student’s t-test, and analysis of variance (ANOVA). Multiple logistic regression analysis was conducted to examine risk factors for the occurrence and persistence of postprocedural heart block. Results with a value of P < 0.05 were considered statistically significant. Independent variables with statistical significance in the univariate analysis entered the multivariate model.Statistical analysis was performed using the SPSS software v25.0 . Data are expressed as counts and/or percentages for categorical variables and mean ± standard deviation (SD) or median with range for continuous variables. Univariate analysis was performed by chi-square . The general characteristics of patients are summarized in Postprocedural heart block was recorded in 234 patients (21.8%) , and theOf 13 AVB patients, 5 individuals (0.46%) had cAVB. Their clinical characteristics and follow-up results are shown in Among the 25 CLBBB patients, 23 patients developed early-onset symptoms, and the other two cases were late-onset, occurring 6 months post-procedure. Eventually, 21 subjects restored normal sinus rhythm, while 4 subjects continued to have persistent CLBBB. Of the recovered cases, 4 cases showed restoration of normal cardiac conduction after the defect repair and removal of the surgical device on 6, 6, 13, and 40 days post-procedure, respectively. In 4 cases of persistent CLBBB, 3 cases had normal LV end-diastolic diameter (LVEDD) and LV ejection fraction (LVEF) with no clinical symptoms. One case received cardiac resynchronization therapy due to reduced exercise capacity, increased LVEDD, and decreased LVEF (40%) 58 months after the disease onset. Then, both LVEDD and LVEF were returned to the normal in 4 months. All 13 cases of left anterior hemiblock (LAH) were early-onset. The normal conduction was restored in 10 cases, 2 cases had persistent LAH, and 1 case progressed to CRBBB after recovery.Except for 1 case of CRBBB, 42 cases of CRBBB, and 8 cases of CRBBB with LAH exhibited early-onset symptoms. In the group of 42 CRBBB patients, 18 subjects were able to return to normal heart conduction. While in the group of 8 CRBBB plus LAH patients, only 2 individuals recovered completely, 4 were reverted to CRBBB only, and 1 person temporarily restored the normal conduction but reported recurrent CRBBB events during follow-up, and 1 subject did not recover at all. Furthermore, among 132 IRBBB cases, 77 cases were included in the recovery group, and recurring BBB events were recorded in 1 case.P = 0.010), use of eccentric or thin-waist occluder (P = 0.002), oversized devices (P < 0.001), the left disk placed at the inlet (P = 0.003), and longer procedural and fluoroscopic times (P < 0.001) were significant etiological factors in inducing heart block. Moreover, patients with heart block required a longer hospital stay (P = 0.001). Furthermore, comparisons of baseline variables between patients with and without heart block were performed using four main types of devices (P < 0.001), the left disk placed at the inlet (P = 0.021), longer procedural and fluoroscopic times  were significantly associated with the occurrence of heart block. In patients with eccentric occluder, younger age (P = 0.007), lower body weight (P = 0.034), larger defect inlet diameter (P = 0.029), bigger occluder size (P = 0.035), and an increase in the ratio of device diameter to patient’s body weight (P < 0.001) were critical determinants of heart block. In patients using a thin-waist occluder, the left disk placed at the inlet (P = 0.028), an increase in the ratio of device diameter to patient’s body weight (P = 0.005), and longer procedural and fluoroscopic times  were closely correlated to heart block. There were no significant differences between these variables in patients with ADO II devices.As shown in  devices –9. In paP = 0.041) and oversized device  were independent risk factors for the occurrence of postprocedural heart block. Besides, heart block was less likely to develop when the left disk of the occluder was placed within the aneurysmal tissue . Likewise, in patients with symmetric occluders, the oversized occluder  was confirmed as an independent risk factor for inducing heart block, and the placement of the left disk in the aneurysmal tissue  was less susceptible to cause heart block. In patients using eccentric occluders, increasing the ratio of device diameter to patient’s body weight  was significantly associated with the onset of heart block. Logistic regression analysis showed no variable was significantly associated with the occurrence of heart block in patients using either a thin-waist occluder or ADO II device.After adjustment of the confounding factors, multivariate logistic regression analysis revealed that the thin-waist occluder , larger defect inlet diameter by TTE (P = 0.019), larger defect diameter on ANG (P = 0.049), bigger occluder size (P = 0.030), late time of occurrence (P = 0.011), and longer procedural and fluoroscopic times . In multivariate analysis, there was no significant parameter to predict the recovery of heart block  developed early-onset heart block after the defect closure. Although the exact mechanism of heart block remains undefined, various mechanisms might be considered causative. Since the distribution of the cardiac conduction system is adjacent to the pmVSD boundary, the conduction bundle has a high probability of getting injured by the pressure of the catheter or device. Therefore, the most likely mechanism of postprocedural heart block could be the mechanical compression and associated inflammatory edema of the conduction system. In our experience, inhibition of local inflammation and related edema and/or relief of compression was highly beneficial in most 60.3%) of the early-onset heart block patients facilitating the restoration of normal cardiac conduction after the procedure. However, 8 subjects developed recurring heart blocks, even after their initial symptom reversal using corticosteroids. It should be noted that heart block may also occur later after the occluder closure. The present finding revealed that 5 patients developed such late-onset heart block, including 1 case of CRBBB in a 1-month post-procedure, 2 cases of CLBBB in 6 months post-procedure, and 2 cases of cAVB - one in 2 years and another in 4 years after the procedure, respectively. Postprocedural recurrence and late-onset of cAVB and CLBBB have already been reported, showing the cAVB onset as late as 9 years after the closure procedure . Due to the progressive damage induced by the hyper-activated inflammatory responses as well as continuous friction of the device disk on the septal myocardium, the formation of fibrosis or scar around the implantation area may be another reasonable explanation for the recurrent and late-onset heart blocks. We found that corticosteroid therapy-mediated transient recovery of normal conduction in one late-onset case and one recurrent case might support the notion of postprocedural short-term inflammation around the implantation area. Furthermore, displacement of the occluder or change of device shape may be another causal factor for damaging the conduction bundle. Therefore, during the follow-up, an X-ray examination may be required particularly for such patients. Finally, abnormal development of the conduction tissue may induce permanent cardiac malfunctions, leading to late-onset heart blocks.The larger ratio of device size to defect size was identified as an independent risk factor for the occurrence of postprocedural heart block in this study. In our cohort, in the cases of membranous aneurysms with multiple outlets, the larger outlet diameter was less than 4 mm in some cases, and different types of occluders were often available. In our experience, the principle of size selection varies for different types of devices in order to avoid oversized devices. The selected device size of symmetric and eccentric occluders was usually 2 to 4 mm larger than the defect diameter on angiography, and that of the ADO II device was usually 1 to 2 mm larger than the defect diameter, whereas the size of thin-waist occlude should generally be selected according to the inlet diameter of the membranous aneurysms. The larger the device used, the wider the scope of the device disk in contact with the interventricular septum, increasing the susceptibility of compression of the conduction bundle. Furthermore, a thin-waist occlude was proved to be an independent predictor of postprocedural heart block. While device waist diameters were the same for both subtypes, the left disk of the thin-waist occlude was relatively larger (4 mm) than that of the symmetric occlude. Hence, a thin-waist occlude might have interfered with the conduction bundle. We identified that another predictor, the placement of the left disk within the aneurysmal tissue, can significantly reduce the occurring events of heart block. Therefore, for VSD with membranous aneurysms, especially when the inlet diameter is larger, the placement of the left disk within the aneurysmal tissue would be more beneficial. It is further recommended that the left disk should be placed inside the aneurysmal tissue as much as possible, even if a larger aneurysmal pmVSD with multiple outlets is closed, using a thin-waist occlude. If the left disk cannot be completely placed into the aneurysmal tissue, partial placement of the left disk may be considered, which may reduce the compression effect of the left disk on the interventricular septum, at least to some extent. Additionally, in patients using eccentric occluders, increasing the ratio of the device diameter to the patient’s body weight was another independent predictor of heart block. For patients with relatively lower body weight who use a larger eccentric occlude, the ECG should be observed more closely after the procedure.Compared with the symmetric occlude, the use of the eccentric occlude imposed an increased potential risk for postprocedural heart block. Due to the asymmetric structure of the disk, the force point on the left ventricular septal by the eccentric occlude is closer to the region where the conduction bundle mainly passes through. ADO II appears to have a unique advantage in reducing arrhythmias. Several studies have confirmed these observations , 14. NonSome authors have confirmed that the onset time of postprocedureal heart block is an independent predictor of its persistence. Nevertheless, these similar observations indicated some obvious distinctions. Yang et al.  concludeComplete AVB is known to be the most serious type of heart block after VSD occlusion. In our study, the parents of one patient with postprocedural cAVB refused the surgical removal of the occlude. After active treatment, the patient temporarily restored the sinus rhythm. Unfortunately, the patient suffered from a recurrent cAVB after discharge, leading to an acute sudden cardiac death. It has already been confirmed that LBBB induces an abnormal LV contraction pattern resulting in LV dysfunction with a decrease in LVEF. Over time, it remains uncertain whether this abnormal contraction pattern could lead to cardiomyopathy. However, the clinical findings strongly support the presence of LBBB-induced cardiomyopathy . As the High-dose corticosteroids can alleviate acute inflammatory edema and have been shown in this study to achieve complete or partial relief of most early-onset heart blocks . Interestingly, in our cohort, it appeared that corticosteroid therapy was more effective against the first- and second-degree AVB and CLBBB, but less effective against cAVB and CRBBB. Studies have proved that steroid therapy has an encouraging effect on the recovery of early heart block after VSD closure .Zuo et al.  reportedThe majority of patients with persistent postprocedural cAVB require permanent pacemaker implantation. As described in a study involving 17 patients with post-VSD closure cAVB, all 8 cases that failed to restore the sinus rhythm were implanted with permanent pacemakers . CardiacThere are certain limitations to this study. First, it was a single-center experience with a retrospective study. Second, although our study identified risk factors for heart block after transcatheter device closure of pmVSD, the exact mechanism of its occurrence remains unclear. Furthermore, in multivariate logistic regression analysis, no definitive predictors of the continuance of postprocedural heart block were found. Therefore, a multi-center and prospective study with larger sample size is needed to validate these findings.With the largest sample size ever known, we report risk factors and long-term follow-up results for pediatric patients with heart block after transcatheter pmVSD closure. The overall incidence rate of heart block following the device closure of pmVSD in children is relatively high, and its outcomes are mostly favorable, as most of them are temporary. However, owing to the recurrence and late-onset heart block complications, more careful monitoring of sinus rhythm is essential during follow-up examinations.According to our results, thin-waist occluders and oversized devices should be avoided to prevent postprocedural heart block, and eccentric occluders should be carefully selected. The left disk of a device placed into the aneurysmal tissue is recommended.The original contributions presented in the study are included in the article/Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.DJ and BH designed the study. DJ, SZ, and YZ analyzed and interpreted the patient data of the cases. JL, YY, JW, YW, XY, JZ, and BH contributed to the intellectual content of this manuscript. DJ wrote the manuscript. BH and JZ supervised the study. All authors contributed to the article and approved the submitted version.


A double-chambered left ventricle (DCLV) is an extremely rare congenital malformation. The exact prevalence of DCLV is not known, although studies have reported prevalence of 0.04–0.42%. This abnormality is characterized by the sub-division of left ventricle into two chambers, the main left ventricular chamber (MLVC) and the accessory chamber (AC) by a septum or muscle band.We are reporting two cases of DCLV, one in an adult male and an infant, who were referred for undergoing cardiac magnetic resonance (CMR) imaging. The adult patient was asymptomatic, whereas the infant had the diagnosis of left ventricular aneurysm on fetal echocardiography. On CMR, we confirmed the diagnosis of DCLV in both patients, as well as moderate aortic insufficiency in the adult patient. Both patients were lost to follow-up.The double-chambered left ventricle (DCLV) is commonly detected in infancy or childhood. Although echocardiography can help detect double-chambered ventricles, MRI provides a better knowledge of this problem and can also be used to diagnose other related heart disorders. Double-chambered left ventricle (DCLV) is an extremely rare congenital heart disease. Only a few cases of DCLV with variable morphologies have been reported in local and international literature –3. It isThe pathogenesis or exact etiology of this rare anomaly remains elusive but DCLV is considered to result from hypoplasia of regional myocardial intra-trabecular sinusoids or from intra-myocardial aneurysm that develops during embryogenesis . AnotherLike other cardiac diseases i.e. hypertrophic cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction and Ebstein anomaly there must be genetic cause of this rare anomaly. Wang et al.  identifiLiterature review reveals that five overlapping / interchangeable and poorly defined terms are used in reporting this rare entity: LV aneurysm, LV diverticulum, Cysts, DCLV, and accessory left ventricle, which confounds the prevalence reported. The two most important differential diagnoses of DCLV are LV aneurysm and diverticulum. True LV aneurysm is a saccular protrusion of the LV wall due to mechanical weakness containing all the three cardiac tissue layers, with scarred/fibrotic wall having wide based neck with the LV and is either akinetic or dyskinetic . PseudoaThis condition can be diagnosed by Cardiac CT or echocardiography, even fetal echo can sometimes give a clue to the diagnosis of DCLV; however, it can be misdiagnosed as atrial or ventricular septal defect. CMR is a better modality to confirm the diagnosis because of its better spatial resolution and tissue characterization ability specially when differentiating normal myocardium from fibrosis . GeneralThere is no extensive data on treatment options and on outcomes, due to rarity of this condition. Nonetheless, few studies , 19 haveA 35-year-old man with history of cardiac surgery during childhood for which no record was available, was referred to our institute for cardiac magnetic resonance (CMR) imaging after the echocardiographic evaluation that was also done outside of our hospital and no images were available for the review.CMR was done on 1.5 Tesla, Siemens Avanto scanner. There were prominent muscle bundles in the left ventricle, dividing the left ventricle into two chambers (double-chambered left ventricle)  on fetal echocardiography that was done outside of our institute and no record of images were available except a written report with suspicion of DCLV versus true aneurysm, was referred to us for CMR.Postal natal echocardiography showed large out-pouching, most probably aneurysm versus diverticulum of left ventricular posterior wall with wide open connection with left ventricle and some dyskinetic contractility. The infant was electively intubated for CMR, which was done on 1.5 Tesla, Siemens Avanto scanner. CMR showed a large out-pouching of left ventricle from basal lateral wall, with a broad base and measuring up to 27 mm in the long axis along lateral wall and 14 mm in the short axis. It was giving the appearance of double-chambered left ventricle; with contracting but hypokinetic walls , a rare cardiac malformation is characterized by the sub-division of the left ventricle and is usually diagnosed in the neonatal or pediatric age but rarely it remains asymptomatic and undiagnosed till adulthood as in one of our cases. Even though echocardiography or fetal echocardiography, as in one of our cases, can aid in the detection of double-chambered ventricles, however, MRI allows a better delineation and understanding of this condition because of its higher spatial resolution and tissue characterization ability. CMR is also helpful in the assessment of other associated cardiac abnormalities including congenital, structural, or valvular heart diseases. Due to the rarity of this illness, there is little evidence on treatment approaches and the prognosis.