Background and Objectives: Similar to diabetes, the presence of left ventricular (LV) diastolic function (DD) has been reported in various studies which were conducted with people with a diagnosis of an impaired fasting blood glucose (FBG). This study aimed to examine the effects of the fasting blood glucose (FBG) levels on the left atrial strain (LAS) estimated by two-dimensional echocardiography speckle tracking analyses in patients without known diabetes. Material and Methods: The study included 148 participants  without a history of diabetes mellitus or chronic disease. The patients were divided into two groups as follows: individuals with an FBG < 100 mg/dL and those with an FBG between 100 and 125 mg/dL after at least 8 h of overnight fasting. According to these FBG levels, speckle tracking echocardiography (STE) measures were compared. Results: There was a significant decrease in the LA reservoir  and conduit strain  in the impaired FBG group. When the STE findings of both ventricles were compared, no significant difference was observed between the groups in right and left ventricular strain imaging. Conclusions: In the earliest stage of LVDD, changes in atrial functional parameters become particularly evident. Echocardiographic analyses of these parameters can help to diagnose and determine the degree of LVDD while the morphological parameters are still normal. The addition of LAS imaging to routine transthoracic echocardiography (TTE) studies in patients with an impaired FBG but without a DM diagnosis may be helpful in demonstrating subclinical LVDD or identifying patients at risk for LVDD in this patient group. Diabetes mellitus (DM) significantly increases the risk of developing cardiovascular disease (CVD) . While tOne of the cardiovascular diseases caused by an impaired FBG is heart failure (HF) . The relThe left atrial strain (LAS) is a new parameter that is used in the evaluation of the LV filling pressure and the LV diastolic function ,7. The LAlthough diastolic function studies in patients with an impaired FBG are generally conducted with LV diastolic function parameters, we planned to investigate whether there is a difference in LAS findings between individuals with a normal FBG and an impaired FBG without known diabetes in our study.This was a single-centre, retrospective study of echocardiographic measures of LV diastolic function and LAS. A total of 148 individuals without any known chronic disease who were admitted to our cardiology outpatient clinic between January 2021 and January 2022 were included in the study. The enrolment of patients with an absence of chronic disease and verified absence of any chronic medication history was corroborated through patient anamnesis and a national database. The patients were divided into two groups: those with an FBG between 70 and 100 mg/dL and those with an FBG between 100 and 125 mg/dL after at least 8 h of overnight fasting. The criterion for an impaired FBG was determined according to the criteria of the ADA [The physical examination findings, electrocardiography and transthoracic echocardiography (TTE) data, and laboratory values of the patients included in the study were obtained from the hospital database. Those with an FBG < 70 mg/dL or >125 mg/dL and those whose echocardiographic images were insufficient for speckle tracking analyses were excluded from the study. Patients with valvular disease, pulmonary hypertension, left or right ventricular dysfunction on echocardiography, symptoms or signs of cardiovascular disease, arterial hypertension, heart failure, previous myocardial infarction, moderate or severe valvular disease, arrhythmias, congenital heart diseases, asthma, chronic obstructive lung disease, neoplastic disease, morbid obesity, cirrhosis, or renal failure were excluded from the study.TTE examinations were performed by an experienced cardiologist with a Philips Epiq 7C ultrasound machine according to the recommendations of the American Society of Echocardiography . All echLVEF was calculated by using the standard Simpson method. The transmitral Doppler inflow and tissue pulsed Doppler velocities were obtained in the apical 4-chamber view. Pulsed Doppler measurements included the transmitral early and late diastolic peak flow velocities (Em and Am) and their ratio (E/Am). The average of the peak early diastolic relaxation velocities (e′) of the septal and lateral mitral annulus was calculated.Patients with suboptimal image quality for strain analysis were excluded from the study. The echocardiographic images were analysed by a cardiologist who is particularly interested and trained in cardiovascular imaging and strain echocardiography. The strain values, including the right ventricle GLS (RVGLS) and right ventricle free wall strain (RV-FWSL), the LVGLS, and components of the LAS , conduit (LAS-cd), and contractile (LAS-ct) function), were examined from the stored echocardiographic images using a commercially available workstation (QLAB version 13) and by following the recommendations of the EACVI [Speckle tracking echocardiography (STE) was performed using four consecutive cardiac cycles of two-dimensional LV images from the three standard apical LV, LA, and RV focused apical 4-chamber views, according to the latest guidelines . For strAll participants were interviewed at each annual examination using standard questionnaires that collect data on demographic characteristics and medical history. Blood samples were then taken after a 12 h fast and analysed immediately. The IFG was defined according to current guidelines [2) test. The patient population was divided into two groups according to blood glucose levels. A univariate linear regression analysis and a multivariate linear regression model were tested for determining LAS-r by entering conventional clinical variables  and contributors with a significant correlation. Results for which the p value was <0.05 were considered statistically significant.All statistical analyses were performed using SPSS v25.0. Continuous variables are presented as the mean and standard deviation, and categorical data are presented as percentages or frequencies. A Kolmogorov–Smirnov test was used to determine the normality of the distribution of continuous variables. Parametric and nonparametric variables were compared by using paired t tests and Wilcoxon tests, respectively. Categorical variables were compared by using a chi-square . The demographic, clinical, and laboratory characteristics of the patients included are given in p = 0.001), and no significant difference was found in other demographic parameters , the LA volume was greater , the right atrium was larger , the IVRT was longer , the mitral E wave was shorter , and the septal e’ was lower  in the impaired FBG group.Considering all TTE parameters, the LA was larger  and conduit strain  in the impaired FBG group, no significant difference was observed in contractile strain . The findings from the LA speckle tracking imaging of the patients are shown in While there was a significant decrease in the LA reservoir  LA diameter or LA volume obtained by two-dimensional (2D) echocardiography are the simplest markers of LA remodelling . Due to In our study, the LA diameter and volume were found to be significantly higher in patients with an impaired FBG, in parallel with other studies. Diastolic dysfunction causes various changes in the functions of the LA apart from geometric changes in the LA. Echocardiographic evaluation of LA deformation is a relatively novel modality for the assessment of LA remodelling. There are two methods of assessment: tissue Doppler imaging and speckle tracking imaging. Tissue Doppler imaging is widely available and practical for routine echocardiography. The A′ velocity at the mitral annulus provides information about the regional atrial systolic motion. Early systolic (S′) and early diastolic (E′) velocities correspond to the LA reservoir and conduit function, respectively. However, these velocity measurements also bear some limitations related to angle dependency and tethering . LA defoStudies have shown that LAS imaging is a useful additional method for evaluating the LV diastolic function ,28. E/e′Similar to diabetes, prediabetes is also associated with HF and atrial fibrillation, which are determinants of cardiovascular mortality. In a prospective study involving 294,057 patients, high glucose levels, including in the impaired FBG range, were found to be associated with the development of atrial fibrillation and HF during an average of 19.1 years of follow-up of patients with known diabetes mellitus, newly diagnosed diabetes or an impaired fasting glucose . The devThe limitations of our study include the single-centre nature of the study and the small number of patients.In conclusion, the addition of LAS imaging to routine TTE studies in patients with an impaired FBG but without a DM diagnosis may be helpful in demonstrating subclinical LVDD or identifying patients at risk for LVDD in this patient group. We believe that further studies are needed on this subject.


Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients diagnosed with HF had IHD as the underlying cause. Furthermore, IHD predicts a worse outcome for patients with HF, leading to a substantial increase in late morbidity, mortality, and healthcare costs. In recent years, new pharmacological therapies have emerged for the treatment of HF, such as sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, selective cardiac myosin activators, and oral soluble guanylate cyclase stimulators, demonstrating clear or potential benefits in patients with HF with reduced ejection fraction. Interventional strategies such as cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy might provide additional therapeutic benefits by improving symptoms and promoting reverse remodeling. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of HF. By analyzing the existing data from the literature, this review aims to evaluate the impact of new HF therapies in patients with IHD in order to gain further insight into the best form of therapeutic management for this large proportion of HF patients.  Heart failure (HF) is a clinical syndrome described as the incapacity of the heart to maintain the necessary blood flow in order to satisfy the body’s requirements. It is caused by structural and functional anomalies of the myocardium which result in impaired ventricular filling or blood ejection ,2. AlthoThe process involved in HF progression is currently known as cardiac remodeling and it includes a series of molecular, cellular, and interstitial changes which result in alterations in left ventricular (LV) size, shape, and function ,5,6. In Novel therapies including revolutionary drugs such as angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose co-transporter-2 (SGLT2) inhibitors have demonstrated their effectiveness in improving outcomes and promoting reverse remodeling in HF with reduced EF (HFrEF). Although coronary revascularization therapy limits the progression to cardiac dysfunction and adverse LV remodeling, a significant percentage of patients with IHD continue to develop HFrEF ,11. In the first part of this narrative review, we have addressed the main pathophysiological mechanisms that promote ventricular remodeling in IHD, which could represent potential therapeutic targets to counteract cardiac maladaptive changes. In the second part, we have discussed the results of recent HFrEF clinical trials that have employed novel therapeutic pharmacological agents and devices, with the purpose of exploring existing knowledge on their potential role in IHD. In acute myocardial infarction (MI), the process of LV remodeling begins rapidly, within the first hours of ischemia, as myocyte loss will initiate a cascade of immuno-inflammatory pathways and cellular activities such as complement activation, the production of reactive oxygen species (ROS) and the activation of inflammasomes. The repair process begins with the action of inflammatory cells which will replace the necrotic myocardium with granulation tissue, while fibroblasts will form a new collagen matrix that contributes to the formation of the post-infarction scar in the infarcted area ,13,14. TSeveral mechanisms involved in the appearance and progression of cardiac remodeling are discussed below and summarized in Myocyte loss is a key factor in the development of ventricular remodeling in IHD. During ischemic conditions, cell death may be induced by activating an intrinsic pathway originating in the mitochondria and an extrinsic pathway mediated by several cell death receptors such as tumor necrosis factor (TNF) receptors . As a reDuring the initial phase of MI, the more predominant process is apoptosis, a form of programmed, non-lytic cell death, which consists of cell shrinkage, nuclear fragmentation, and chromatin condensation ,22,23. AFollowing acute MI, the inflammatory response plays a critical role in the healing process of the infarcted myocardium, as well as in the progression of adverse remodeling. Myocardial necrosis triggers both systemic and local inflammatory responses to clear the myocardial tissue from dead cells and matrix debris. The releasing of endogenous danger molecules called damage-associated molecular patterns (DAMPs) will activate the complement cascade and toll-like receptor (TLRs)/ interleukin-1 (IL-1) signaling, which will stimulate the synthesis of pro-inflammatory cytokines such as TNF-α, interleukin-1β (IL-1β), and interleukin-6 (IL-6) . DAMPs wStudies have shown that levels of pro-inflammatory cytokines are correlated with the development of LV remodeling after MI. In post-infarct mice, IL-1β secretion was stimulated after the onset of the ischemic event . Also, IAdaptive immunity influences the remodeling process following acute MI as well, with the role of T cells being the most extensively evaluated. After interacting with the antigen-presenting cells, T cells will differentiate into either cytotoxic T cells (CD8+ cells) or T-helper (Th) cells (CD4+ cells) and will infiltrate the injured myocardium ,54,55. TOxidative stress makes a major contribution to the remodeling process of the injured myocardium in ischemic disease. Normally, cells have an antioxidant defense mechanism. When the balance between oxidants and antioxidants is altered, the levels of reactive oxygen species (ROS) increase, and radicals such as superoxide anion are produced . The mecThe effects of ROS on the injured myocardium consist of the oxidation of nucleic acids, lipids, and proteins and alterations of cell membrane properties, leading to cellular dysfunction and death. Furthermore, oxidative stress stimulates matrix metalloproteinases (MMPs) expression and modulates collagen synthesis, leading to fibrosis . DespiteFibroblasts are generally known for producing and organizing the ECM. Fibroblasts act as regulators of myocardial remodeling after an ischemic event. Under pathological conditions, fibroblasts are activated into myofibroblasts with the capacity to remodel the ECM through activated integrins and cadherin receptor proteins. During the early phase of MI, cytokine secretion will contribute to the accumulation of fibroblasts in the injured area ,71. HoweNeurohormonal activity serves as a key regulatory mechanism in the progression of cardiac remodeling. The activation of the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone (RAAS) system occurs initially as a compensatory mechanism in the acute decompensated state to become later a maladaptive process. While in the acute phase the compensatory action of SNS aims to maintain an adequate stroke volume, prolonged sympathetic activity can sustain the ventricular remodeling by enhancing the apoptotic pathways, promoting the release of proinflammatory cytokines, and impairing the myocardial contractility. Also, chronic stimulation induces myocardial alterations by promoting RAAS activation ,78. ReniDetrimental ventricular remodeling following ischemic injury is a key contributor to HFrEF progression. Traditional HFrEF therapies, which include beta-blockers, ACE inhibitors (ACEI), angiotensin II receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA), have extensive data from clinical trials to support their beneficial effect in patients with IHD and HFrEF, translated into improvements in survival and ventricular remodeling and function ,83. MoreARNI is a dual regulator that inhibits the RAAS as well as the breakdown of physiologically active natriuretic peptides and several other vasoactive substances, including bradykinin. The rise in circulating natriuretic peptides caused by neprilysin inhibition leads to vasodilatation, natriuresis, and lowering of intracardiac pressures, while blocking the angiotensin receptors type 1 exerts antiproliferative, antihypertrophic, and antifibrotic effects, all of these mechanisms promoting favorable ventricular remodeling ,86,87. T2 to 28.2 mL/m2 vs. from 29.8 mL/m2 to 30.5 mL/m2), the LVEDVI (from 75.1 mL/m2 to 70.3 mL/m2 vs. from 79.1 mL/m2 to 75.6 mL/m2), and the LVESV index (LVESVI) (from 50.8 mL/m2 to 46.3 mL/m2 vs. from 54.1 to 50.6 mL/m2). These results suggest that sacubitril/valsartan is superior to ACEI in promoting LV reverse remodeling, regardless of the etiology of HF, being a valuable therapy to consider for counteracting the adverse remodeling process associated with chronic IHD [Several small studies demonstrated the positive effects of ARNI on cardiac remodeling, as suggested by improvements in LV EF and LV end-systolic and end-diastolic volumes and diameters after therapy with sacubitril/valsartan ,91. Subsonic IHD .Considering the tremendous benefits of ARNI in the management of HFrEF, including the ischemic etiology, several trials sought to investigate the potential role of sacubitril/valsartan in acute MI. The SAVE-STEMI trial evaluated the safety and efficacy of ARNI compared to ramipril in 200 patients with STEMI after undergoing primary percutaneous coronary intervention. The primary endpoint of major adverse cardiac events (MACE) representing a composite of cardiac death, MI, and HF hospitalizations was similar between groups at 30 days, while at 6 months, it was significantly reduced with sacubitril/valsartan, mainly driven by the reduction in HF hospitalizations. In addition, at 6 months, sacubitril/valsartan was associated with a significantly greater improvement in LV EF, LV end-diastolic diameter (LVEDD), and LV end-systolic diameter (LVESD) . p = 0.17), leading to the conclusion that sacubitril-valsartan was not superior to ramipril in reducing the incidence of cardiovascular death or incident HF in patients with acute MI [A subsequent trial that further evaluated the benefits of ARNI in MI was the PARADISE-MI trial, which included 5661 patients with acute MI with reduced LV EF of less than 40%, pulmonary congestion associated with the index acute MI, or both. The patients were randomly assigned to receive sacubitril/valsartan or ramipril. The primary outcome was cardiovascular death or an HF episode . During a mean observation period of 22 months, a primary-outcome event occurred in 11.9% of patients in the sacubitril-valsartan group and in 13.2% of patients in the ramipril group  to a greater proportion compared to the control group. In addition, sacubitril/ valsartan was associated with lower levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and with a greater increase in exercise capacity. Moreover, it further reduced the incidence of adverse cardiovascular events and the rate of HF rehospitalization compared to ACEI/ARB without significantly reducing the incidence of cardiac death or MI recurrence . SGLT2 inhibitors are therapeutic agents originally designed for the treatment of type 2 diabetes (T2D) which exert their hypoglycemic effect by inhibiting glucose reabsorption in the proximal convoluted tubule, subsequently promoting glycosuria and lowering plasmatic glucose levels ,99,100. The tremendous cardiac benefits of SGLT2 inhibitors emerged for the first time from the major cardiovascular safety trials of these drugs, such as DECLARE-TIMI 58 and EMPA-REG OUTCOME, which showed that SGLT2 inhibitors therapy was associated with remarkable improvements in cardiovascular outcomes, including a reduction in mortality and HF hospitalization ,105.Later, the effects of dapagliflozin in HF were studied in the DAPA-HF trial, which included patients with HF with a reduced EF of 40% or less, regardless of the presence of T2D. In this trial, dapagliflozin reduced the risk of HF hospitalization and cardiovascular death with similar efficacy in patients with or without diabetes . SimilarConsidering the categorical benefits of SGLT2 inhibitors in cardiovascular mortality and HF prognosis, several studies were designed to evaluate the impact of these drugs on cardiac function and remodeling. The SUGAR-DM-HF trial included patients with NYHA class II to IV HF, LV EF ≤ 40%, and T2D or prediabetes, that were randomly assigned to receive empagliflozin or placebo. After 36 weeks of treatment, empagliflozin significantly reduced the LVESVI and LVEDVI (assessed with cardiac magnetic resonance) compared to placebo, suggesting that SGLT2 inhibitors promote LV reverse remodeling, which might explain their benefits on cardiovascular mortality and HF hospitalizations . AnotherAs SGLT2 inhibitors appear to exert pleiotropic cardiovascular effects, their role in acute myocardial ischemia was evaluated in several trials. The EMMY trial included 476 patients with acute MI that were randomized to receive empagliflozin or placebo 3 days after interventional coronary revascularization. The primary outcome was represented by the change in NT-proBNP value after 26 weeks, while secondary outcomes included changes in echocardiographic parameters. The results showed a significantly greater reduction of NT-proBNP in the empagliflozin group. In addition, markers of ventricular remodeling such as LV EF, LVESV, LVEDV, and LV filling pressures improved with a greater magnitude in patients with empagliflozin therapy. These results suggest that the early initiation of the SGTL2 inhibitors in the treatment of acute MI could be beneficial for the prevention or attenuation of LV remodeling ,113. OthImpaired myocardial contractility is the central pathogenic process leading to HFrEF development, and therapeutic strategies which increase myocardial contraction should have a positive therapeutic impact. However, traditional inotropic drugs were not demonstrated to be beneficial for chronic administration in HFrEF, and they have been linked to an increased risk of morbidity and mortality due to increased myocardial oxygen consumption and myocyte toxicity as a consequence of intracellular calcium overload . OmecamtThe COSMIC-HF study was a phase 2 clinical trial that evaluated the pharmacokinetics and impact on the ventricular remodeling of orally administered omecamtiv mecarbil in patients with HFrEF. After 20 weeks of treatment, omecamtiv mecarbil compared to placebo was associated with increased systolic ejection time and stroke volume and improvements in LVESD and LVEDD, suggesting a beneficial effect of omecamtiv mecarbil on cardiac function and LV remodeling ,121. In The GALACTIC-HF phase 3 trial evaluated the cardiovascular outcomes of omecamtiv mecarbil compared to placebo in patients with symptomatic HF and an EF of less than 35%. The results showed that patients who received omecamtiv mecarbil had a lower incidence of a composite of HF events or cardiovascular death compared to placebo. In addition, NT-proBNP had lower values in the omecamtiv mecarbil group, and the clinical benefit was greater among patients with LVEF ≤ 28% and systolic blood pressure ≤ 100 mm Hg. Half of the included patients had ischemic HF. There were no considerable differences between groups regarding the occurrence of cardiac ischemic events and ventricular arrhythmias ,122,123.There is no data in the literature specifically analyzing the role of omecamtiv mecarbil in the management of acute or chronic IHD. Scarce evidence coming from experimental studies suggests that omecamtiv mecarbil could have cardioprotective properties against I/R injury . Soluble guanylate cyclase (sGC) stimulators emerge as a valuable treatment option in patients with impaired LV systolic function. HFrEF is associated with decreased cyclic guanosine monophosphate (cGMP) production, which promotes myocardial dysfunction and abnormal vasomotor regulation. cGMP deficiency is caused by altered nitric oxide (NO)-sGC-cGMP pathway signaling, due to decreased levels of NO in the context of the endothelial dysfunction state, which characterizes HFrEF . By direVericiguat is an oral sGC stimulator approved for the treatment of HFrEF, following the results of the VICTORIA trial. This phase III trial included patients with EF < 45% and a history of recent episodes of HF decompensation and showed that vericiguat added to standard therapy is associated with a lower incidence of the primary composite outcome of cardiovascular death or HF hospitalization compared to placebo added to standard therapy . A post The potential effect of vericiguat on ventricular remodeling was evaluated in the VICTORIA echocardiographic substudy, in which echocardiographic evaluation was performed at baseline and after 8 months of therapy in the two groups of patients with vericiguat and placebo therapy, respectively. The results failed to demonstrate a superior effect of vericiguat compared to placebo on ventricular function and dimensions. Although treatment with vericiguat significantly improved LV EF and LVESVI after 8 months, it did not show an additional significant effect on LV EF or LVESVI compared to placebo . HoweverCurrently, there are no trials evaluating the effects of sGC stimulators on cardiac remodeling and HF development in patients with acute MI. However, data coming from experimental studies suggest a potential beneficial effect of sGC stimulators on ventricular remodeling after acute MI. In this regard, a study showed that riociguat administration in mice after 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion therapy, resulted in a reduction of the infarct size and prevented the further development of HF. The beneficial effect was persistent, as the LV systolic function was preserved at 28 days after the ischemic event ,133. SimCardiac resynchronization therapy (CRT) is a valuable therapeutic resource in the management of patients with HFrEF and wide QRS complex that remain symptomatic despite guideline-directed medical therapy (GDMT). Biventricular pacing improves intraventricular and interventricular synchrony and increases diastolic filling time, which overall translates into improved cardiac performance and amelioration of symptoms . MultiplPatients with IHD represented over 50% of the patients included in every trial evaluating CRT, except for CARE-HF, in which IHD was the etiology of HF in 36% of the patients . The triThe CARE-HF trial included patients with symptomatic HF NYHA class III or IV, prolonged QRS, and a reduced LV EF < 35%, which were randomized to receive CRT plus optimal medical therapy, and standard HF therapy alone. The primary endpoint was a composite of death from any cause or an unplanned hospitalization for a major cardiovascular event. After a mean period of follow-up of 29.4 months, the primary endpoint was significantly lower in the CRT group compared to the group with medical therapy alone (39% vs. 55%). In addition, CRT was associated with clinical response, attributed to improved symptoms and quality of life, and with LV reverse remodeling, measured as a reduction in LVESVI, and in the area of the mitral regurgitant jet, or an increase in the LV EF .The MIRACLE trial was among the first to show the clinical benefits of CRT. It included patients with NYHA class III or IV, LV EF of 35% or less, and a QRS duration of 130 msec or more, that were randomized in a CRT group and a control group with the maintenance of conventional HF therapy in both groups. Patients with IHD represented 58% of the total number of included patients ,141. TheMADIT-CRT was another trial that included patients with ischemic HF (NYHA class I or II) and nonischemic HF (NYHA class II only), an LV EF of 30% or less, and a QRS duration of 130 msec or more. Patients with IHD represented 55% of the total included patients. They were randomized to receive CRT plus an implantable cardioverter-defibrillator (ICD) or an ICD alone. The primary endpoint was death from any cause or a nonfatal HF event. The results showed that CRT-ICD was superior to ICD alone, as it reduced the risk of death or HF events by 34%. In addition, CRT was demonstrated to favor LV reverse remodeling, as the LV volumes were reduced and the EF was increased to a greater amount in patients with a CRT-ICD compared with those with an ICD only . HoweverThe REVERSE trial included patients with mildly symptomatic HF (NYHA class I or II) and a LV EF ≤ 40% who received a CRT device and were randomly assigned to active CRT (CRT-ON) or control (CRT-OFF) for 12 months. The results showed that patients from the CRT-ON group had a lower risk of HF hospitalization, as the worsened HF clinical response was lower in this group compared to the CRT-OFF group. In addition, patients who had active CRT had greater improvement in the LVESVI and other markers of ventricular remodeling. Notably, the improvement in LVESVI in CRT-ON patients was 3 times greater in the nonischemic group than in patients with IHD .2 and left atrial volume < 40 mL/m2 [Sub-analysis of the trials presented above showed that indeed, CRT is associated with a greater LV reverse remodeling in nonischemic HF, compared to the ischemic etiology. Integrating data from the MADIT-CRT trial, seven factors were identified to predict echocardiographic response to CRT with defibrillation (CRT-D): female sex, nonischemic origin, left bundle-branch block (LBBB), QRS ≥ 150 msec, prior hospitalization for HF, LVEDVI ≥ 125 mL/m40 mL/m2 . However40 mL/m2 . Moreove40 mL/m2 ,147.Considering the compelling data from clinical trials, current European and American guidelines recommend CRT with a class I indication in patients with symptomatic HF despite optimal medical therapy, with reduced ejection fraction (LV EF < 35%), and a QRS with LBBB morphology and a duration ≥ 150 msec ,148. Sympathetic overactivation is a major contributor to the progression of HF and ventricular maladaptive remodeling. Baroreflex activation therapy (BAT) emerges as a novel therapeutic approach in HFrEF, consisting in carotid baroreceptor stimulation, which subsequently decreases the sympathetic hyperreactivity and augments the parasympathetic tone, rebalancing the cardiac autonomic modulation ,150. BATWhile IHD was the etiology of HF in 66% of the included patients, there is no specific data regarding the particular response to BAT of patients with ischemic cardiomyopathy. Furthermore, the LV EF and dimensions were not endpoints in the BeAT-HF trial, therefore there is no data regarding the possible LV remodeling in the BAT group . HoweverCardiac contractility modulation (CCM) is a device-based treatment that involves delivering relatively high-voltage precisely timed electric pulses to the right ventricle (RV) septal wall for 30–40 milliseconds after cardiomyocyte activation, during the absolute refractory period of the action potential. CCM is provided by the implantable OPTIMIZER system, composed of a generator that delivers electrical signals through the two right ventricular leads . The phyInitial research showing clinical benefit from CCM in patients with HFrEF led to the design of the largest clinical trial of CCM, the FIX-HF-5 study. This trial included patients with NYHA class III or IV HF, narrow QRS, and LV EF ≤ 35%, that were randomized to optimal medical therapy (OMT) plus CCM versus OMT alone. At 6 months, the primary endpoint of ventilatory anaerobic threshold (VAT) did not improve, while peak oxygen uptake (VO2) and quality of life scores significantly improved with CCM. Also, a sub-analysis identified a subgroup of patients with baseline EF ≥ 25% that derived a greater benefit from CCM . This fiWhile these studies included a significant proportion of patients with ischemic etiology of HF, there are no available data from these trials regarding the particular response to CCM in this subgroup of patients. Recently, the MAINTAINED observational retrospective study compared the long-term effects of CCM therapy in patients with IHD versus non-IHD. After 5 years of CCM, the entire cohort had improvements in LV EF and LVEDD, but non-IHD patients showed a significantly greater augmentation of LV EF and RV systolic function, although these parameters were similarly reduced at baseline in both groups. This finding might suggest that patients with non-IHD manifest a greater functional improvement in response to CCM therapy than IHD patients . The resDespite significant progress in the pharmaceutical and device therapy of HF and the strategies of coronary revascularization in acute or chronic myocardial ischemia, a substantial proportion of patients still develop adverse ventricular remodeling, which ultimately leads to ischemic HF. As the therapeutic resources for advanced HF are limited to ventricular assist devices and heart transplantation, the finding of new therapeutic strategies for these patients is of major importance. Stem cell regeneration medicine represents a novel potential HF therapy, currently still under research, that aims to promote myocardial regeneration and repair . SeveralClinical trials utilized different types of stem cell populations to evaluate their regenerative capacity. First-generation stem cells include bone marrow-derived mononuclear cells (BM-MNCs), which were the most extensively used in clinical trials, due to their relatively easy procedure of isolation and the associated low costs. BM-MNCs include hematopoietic stem cells, endothelial progenitor cells, and a small fraction of mesenchymal stem cells (MSCs) . MSCs arAs research on animal models suggested that cell therapy could limit infarct expansion and promote cardiac recovery in acute ischemia, several trials evaluated the potential role of cell therapy in acute MI. The most frequently explored stem cells in acute MI were BM-MNCs, followed by MSCs. Among the first trials in the field, the BOOST trial included 60 patients with acute ST-segment elevation myocardial infarction that had undergone interventional coronary revascularization and then were randomized to receive optimal medical treatment or intracoronary BM-MNCs. After 6 months, patients that received cell therapy had a greater improvement in LV EF compared to controls (6.7% vs. 0.7%), with ameliorated myocardial function in the periinfarct area . HoweverSubsequent studies explored the role of MSCs in acute MI, with expected better results, since these cells are a purer type of stem cellularity. Indeed, a meta-analysis that compared the effects of MSCs and BM-MNCs in acute MI and included a total of 36 trials demonstrated that MSCs are more effective in increasing LV EF . AnotherData evaluating the effect of stem cells isolated from cardiac tissue in patients after MI are scarce, due to the small number of clinical trials. CADUCEUS was the first trial of CDCs, a phase I trial that evaluated the safety of the intracoronary administration of autologous CDCs in the infarct-related artery in patients with MI and reduced LV EF. The results showed that CDCs infusion was safe, and it was associated with a reduction in scar size and an increase in the viable myocardium mass, suggesting that CDCs therapy could promote cardiac regeneration . These rIn summary, current evidence suggests that cell therapy delivered in patients with acute MI could exert cardioprotective effects, but further research is needed to determine to what extent these effects are translated into improved cardiac function and clinical outcomes.In the setting of HF of both ischemic and non-ischemic etiology, cell therapy demonstrated promising results. Similar to the MI trials, a robust body of work consisting of multiple phase I and II trials mainly using MSCs, revealed potential benefits of cell therapy in HF, such as improvements in NYHA class, quality of life or functional capacity, and to lesser extent in LV EF and LV volumes . CONCERT-HF was one of the landmark trials that provided strong evidence in this field. This trial was a rigorously conducted phase II, placebo-controlled, double-blind study that enrolled 125 patients with HF of ischemic etiology, with LF EF of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in NYHA class II or III, and randomized them in a 1:1:1:1 ratio to receive transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo. After 12 months, the MACE were significantly reduced by CPCs alone compared with placebo, driven mainly by hospitalization for HF, and the quality of life was significantly improved by MSCs alone and MSCs combined with CPCs compared with placebo. No significant differences were observed in LV EF, LV volumes, scar size, and functional capacity among groups. These results suggest that CPCs or MSCs therapy has predictable beneficial effects in patients with ischemic HF, such as a reduction in hospitalization for HF and an improvement in quality of life . DREAM-HF is the largest trial of cell therapy in HF up to the present, and its results were recently published in 2023. It was a phase III, randomized, double-blind, sham-controlled study that included 565 patients with ischemic (56% of the patients) or non-ischemic HF, randomized to receive a single transendocardial injection of MSCs or sham-control catheterization procedure. At baseline, the patients had a LV EF below 40% by 2-dimensional echocardiogram or below 35% by multigated acquisition scan. Although the primary endpoint was similar between groups, namely the time-to-recurrent events caused by decompensated HFrEF or ventricular arrhythmias, there were significant effects on other end-points. Compared to controls, MSCs therapy increased the LV EF in patients with baseline high-sensitivity C-reactive protein (hsCRP) ≥ 2 mg/L and improved the ventricular volumes independent of the baseline inflammatory status. In addition, MPCs decreased the risk of MI or stroke by 58% in the analysis population  and by 75%, respectively, in patients with baseline hsCRP ≥ 2 mg/L . It also reduced the risk of 3-point MACE by 28%  in the analysis population and by 38% , respectively, in patients with hsCRP ≥ 2 mg/L. These results are of tremendous importance in the development of cell therapy in HF, as they offer strong evidence of the capacity of cell therapy to reduce MACE in patients with HF. Moreover, as the beneficial effects were more pronounced in patients with baseline inflammation, this trial adds proof to the concept that MSCs reduce inflammation by paracrine stimulation, which is a major contributor to the progression of HF and adverse ventricular remodeling . Summarizing the above, there is more and more evidence that cell therapy can positively impact the evolution of patients with HF of both ischemic and non-ischemic etiology by improving clinical outcomes, without necessarily modifying the LV systolic function or volumes . Future As a substantial proportion of patients with acute or chronic ischemic events still develop adverse ventricular remodeling and HF despite coronary revascularization, further substantial efforts are still required to find the best therapeutic strategies to improve their cardiac performance and clinical outcomes. There are continuous advances in our current understanding of the pathophysiologic processes that lead to infarct expansion and progression of adverse remodeling in HF, and perhaps, the key to a better prognosis will be to specifically address each of these maladaptive mechanisms. While efficient counteracting therapy for certain deleterious processes, such as neurohormonal activation, is already well established, there are still unmet needs regarding other contributing mechanisms such as inflammation and increased oxidative stress. In addition, as the research field of cardiac regenerative therapies is continuously evolving, they might be part of HF therapeutic arsenal in the future. Apart from the first and second-generation cell therapies described above, next-generation cardiac regeneration strategies such as biomaterials, extracellular vesicles, endogenous generation of cardiomyocytes, and direct reprogramming of cardiac fibroblasts into cardiomyocytes emerge and are currently being tested in numerous preclinical trials, thus opening new perspectives in the treatment of HF. IHD represents the cause of chronic HFrEF in a significant proportion of patients, and improving their prognosis is a major therapeutic target. Novel HF pharmacotherapies such as ARNI and SGLT2 inhibitors were demonstrated to reduce cardiac mortality and HF hospitalizations and to promote cardiac reverse remodeling in HFrEF of both ischemic and non-ischemic etiology. When initiated early in acute MI, these drugs might play a role in promoting cardiac function recovery, limiting the progression to HF. Other novel HF therapies include omecamtiv mecarbil, a selective cardiac myosin activator, and vericiguat, a sGC stimulator, which demonstrated to improve cardiovascular outcomes and potentially ameliorate ventricular remodeling in HF of both ischemic and non-ischemic etiology. CRT reduces mortality rates and promotes ventricular reverse remodeling, and newer techniques regarding left ventricle lead positioning could augment the response rates in patients with ischemic HF. Other device therapies such as BAT and CCM can be therapeutic options for improving HF symptoms and exercise capacity, while their role in promoting reverse ventricular remodeling remains to be further explored in future studies. Cell therapy improves clinical outcomes in HF of both ischemic and non-ischemic etiology and might promote reverse ventricular remodeling.


Echocardiographic measurement of left ventricular function using a user-friendly automated three-dimensional algorithm is highly attractive as it promises quick and accurate diagnosis, circumventing limitations associated with visual estimation or manual biplane measurements. We sought to assess the feasibility and correlation of such automated analysis with clinically established methods.A total of 198 patients undergoing transthoracic echocardiography (TTE) with assessment of left ventricular parameters by automated software algorithm  which additionally had either left ventricular angiography (LVA) or cardiac magnetic resonance (CMR) within 24 h of the TTE examination were analyzed. Left ventricular parameters  were compared between 3D-HM, CMR and LVA.r = 0.824) than for LVA (EF r = 0.746). Unexperienced and expert clinicians yielded comparable good results. For CMR, highest correlation was detected in patients with BMI < 25 and excellent image quality. High agreement was seen between 3D-HM and CMR or LVA when stratifying patients according to heart failure categories.Correlation of left ventricular measurements was overall good to excellent and stronger for CMR (EF .Echocardiographic quantification of left ventricular parameters using a software-based algorithm correlated well with established invasive and non-invasive modalities in the clinical setting, even for unexperienced clinicians. Such automated approaches are promising as they allow a reliable, more observer-independent as well as reproducible assessment of left ventricular functionThe online version contains supplementary material available at 10.1007/s12574-022-00590-9. A.I., Philips Healthcare) against qualitative, visual grading using left ventricular angiography and quantitative assessment of LV-function using cardiovascular magnetic resonance imaging (CMR), which is currently accepted as the clinical gold standard in this matter [Evaluation of left ventricular function by transthoracic echocardiography (TTE) is at the corner of many diagnostic and therapeutic decisions in cardiovascular care and one of the most often performed examinations in clinical practice. Measurement of left ventricular ejection fraction (LVEF) is often done by visual estimation from experienced echocardiographers or manual biplane measurement according to the Simpson method , 2. Asses matter , 8.n = 2302). In this population, patients who underwent either cardiac magnetic resonance (CMR) or invasive left ventricular angiography (LVA) within 24 h of the TTE examination were included in our analysis. Retrospectively, echocardiographic image quality was graded with respect to the visual tracing of the endocardial borders of the left ventricle and scored as “poor” if no endocardial border was visible, “sufficient” if the endocardial border was partially visible and “excellent” if the entire endocardial border was visible. All examinations graded as “poor” or in which automated lumen contour detection by 3D-Heartmodel was insufficient were excluded from the analysis (n = 14). Representative examples for each image quality category are shown in Supplementary Figure 5. A total of 198 examinations were available for analysis. For baseline characteristics of patients, please see Table For study flow, please see Fig. ysis n = 4. RepresAll 198 patients underwent standard transthoracic echocardiography using the EPIQ systems . The examination involved an apical four-chamber view which was acquired for initializing the 3D-HeartModel, allowing automated measurement of left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) as well as left ventricular ejection fraction (LVEF). Manual correction of automated lumen contour detection by 3D-Heartmodel was done at the discretion of the echocardiographer. All measurements, images and loops were stored offline. Observer variability of the 3D-Heartmodel was measured by the same clinician within 24 h of the examination (intraobserver variability) and by two blinded clinicians within the same examination (interobserver variability). Clinicians performing the examination were classified based on the level of experience as “beginner” (< 6 months experience in performing standard TTE) or “expert” (>6 months experience).Cardiac magnetic resonance imaging was performed in conformity with the recommendations on standardized CMR imaging in 39 subjects and indicated for the assessment of ischemic and nonischemic cardiomyopathies. All subjects underwent a CMR examination in a 1,5-Tesla MRI scanner  using cardiac‐dedicated phased‐array coils. Continuous monitoring of vital signs throughout the entire CMR scan was performed with a 4-lead ECG. The CMR protocol comprised of functional imaging, T2 imaging, and assessment of relative and late gadolinium enhancement (LGE). Functional imaging was performed using steady‐state free‐precession cine sequences in short axis (SA), horizontal long axis (HLA), vertical long axis, and left ventricular outflow tract orientation. Fat‐suppressed T2‐weighted black‐blood turbo spin echo images in SA and HLA were obtained and allowed for visualization of myocardial edema. The following imaging parameters were used: field of view 340 × 340 mm; acquisition matrix 256 × 256; reconstruction matrix 512 × 512; slice thickness was 6–8 mm, with 2–4 mm interslice gaps; spatial resolution 0.65 × 0.65 × 0.65 mm, etc.CMR datasets were transferred to a dedicated workstation and functional analysis was performed on a commercially available software program . The end-diastolic and end-systolic phases were determined for each CMR dataset. For the detection of each phase, the largest and narrowest diameters of the ventricular cavity at the middle of the ventricle were used. The endocardial and epicardial borders were traced manually in short axis images in both phases. The basal segment of the left ventricle was defined as the most basal slice that was surrounded by at least 50% of the myocardium filled with blood and was included in the LV chamber volume. The apex was defined as the last slice with a visible lumen throughout the entire cardiac cycle. The ESV, EDV, SV, EF, and LV myocardial masses were determined according to the Simpson’s rule.® 350, Bracco Imaging Deutschland GmbH) and simultaneous X-ray image acquisition. Ejection fraction was graded visually by an expert clinician.Left ventricular angiography was performed in 159 patients during left heart catheterization according to current standard of care using commercially available contrast dye  experience of the echo-performing clinician (“beginner” versus “expert”), (2) echocardiographic imaging quality  and (3) body mass index .p value of < 0.05 was considered statistically significant.Data are presented as mean ± standard deviation. Correlation and agreement between measurement of LVEDV, LVESV and LVEFVF were assessed by two-sided Pearson’s correlations and Bland–Altman comparisons. Intra- and interobserver variability was measured using intraclass correlation coefficients (ICC). All statistical analyses were performed using commercially available software . A In total, transthoracic studies from 198 patients were suitable for analysis.n = 0 patients (0%), “good” in n = 75 patients (37.9%) and “excellent” in n = 123 patients (62.1%). Left ventricular parameters such as LVEF, LVEDV and LVESV as derived from CMR and 3D-heart model were 53.1% (± 11.5), 160.3 ml (± 51.4), 78.3 ml (± 46.9) and 53.9% (± 14.9), 167.1 ml (± 65.5) and 82.9 ml (± 60.5) respectively, showing no significant differences between the two aforementioned methods , LVEF, LVEDV and LVESV derived from 3D-Heartmodel were 55.1 % (± 9.5), 164.8 ml (± 76.0) and 78.0 ml (± 55.2), respectively. Comparison of left ventricular angiography and 3D-Heartmodel showed no significant difference with respect to left ventricular ejection fraction  patients received cardiac magnetic resonance imaging (CMR) and 159 (80.3%) left ventricular angiography within 24 h to the echocardiographic examination. Echocardiographic image quality was graded as “poor” in r = 0.824, p < 0.0001, while correlation of LVEDV and LVESV was r = 0.921 and r = 0.944, respectively.Correlation of left ventricular parameters was assessed using Pearson’s method. Correlation of LVEF for measurement by 3D-Heartmodel and cardiac magnetic resonance was overall good to excellent with r = 0.745, p < 0.0001. Similar, Bland–Altman plots demonstrated good agreement for both modalities with a bias of − 0.74 for CMR and − 0.89 for LVA.  and expert echocardiographers . Comparing 3D-HM and LVA yielded similar results, however with lower correlation with EF r = 0.605 and r = 0.765, respectively  EF < 40% (= heart failure with reduced EF or HFrEF), (2) EF 41-49% (= heart failure with mildly reduced EF or HFmrEF) or (3) EF > 50% (= heart failure with preserved EF or HFpEF). High agreement was seen between CMR and 3D-HM as well as LVA and 3D-HM regarding confirmation of heart failure class  and slightly lower for ESV  and EDV (r = 0.891 versus r = 0.940) but similar correlation for ESV  with clinically established quantification . The main findings of our work are given as follows:Measurement of left ventricular parameters with 3D-Heartmodel showed strong correlation with analysis regarded as gold standardCorrelation was stronger for biplane measurement using cardiac magnetic resonance than for visual estimation with left ventricular angiography.Clinical experience did not have an impact upon correlation, supporting the use of 3D-HM even for unexperienced clinicians.Using 3D-Heartmodel, approximately 90% of patients were correctly stratified into heart failure class Highest correlation of LVEF and LVEDV was seen in patients with normal BMI and excellent image quality.The aim of this study was to compare parameters of left ventricular function  derived by a novel, algorithm-based analysis (3D-Heartmodelr = 0.720).Evaluation of left ventricular function is extremely important in daily clinical care. Accurate and reliable evaluation of left ventricular ejection fraction in the clinical setting is essential, since it has a major impact on further diagnostic testing and clinical workflow and is most frequently performed by two-dimensional transthoracic echocardiography with Simpsons’ biplane measurements. This is especially true for heart failure patients where adequate monitoring of disease progression and pharmacological treatment is essential , 10. HowSemi-quantitative assessment of left ventricular dimensions using cardiac magnetic resonance is considered the gold standard for quantification of left ventricular dimensions  but locar = 0.824), which is in accordance with previous findings:Our results demonstrate a strong correlation of LVEF between 3D-Heartmodel and CMR (r = 0.79) [r = 0.84–0.95) [r = 0.93 [Recently, a comparison between 3D-Heartmodel and manual 3D echocardiography showed good correlation ( = 0.79) . Additio84–0.95) . Similarr = 0.93  which war = 0.93 . Finallyr = 0.93 . HoweverAdditionally, we demonstrate that the 3D-Heartmodel is able to stratify the overwhelming majority of patients into correct heart failure categories (approximately 90% for both CMR and LVA). Hence, even though the EF might be slightly under- or overestimated, 3D-HM could allow proper risk stratification of patients with heart failure, which is important for therapeutic decision such as intensified pharmacotherapy.To the best of our knowledge, no study has so far investigated the comparison of 3D-Heartmodel with visual estimation of left ventricular function by left ventricular angiography. While left ventricular angiography is no longer regarded as the clinical gold standard for quantification of left ventricular function and visual estimation of left ventricular function can be criticized for its possible inaccuracy, it is the authors’ experience that it is still widely used in daily clinical practice.In conclusion, an echocardiographic-based automated software algorithm to obtain left ventricular functional parameter showed excellent agreement with clinically established methods such as CMR or invasive angiography and can easily be used in the clinical setting. Our findings support the use and application in daily clinical practice. Larger, prospective studies are needed to validate our findings and to assess its impact of subsequent clinical work-up.Supplementary file1 (TIFF 831 kb) Representative echocardiography samples with different levels of image quality (A) Excellent image quality: Delineation of endocardial borders is fully possible (B) Good image quality: Delineation of endocardial borders is mostly possible excepts small segments (such as the apex). (C) Poor image quality: Delineation of endocardial borders is feasible in less than 50%Below is the link to the electronic supplementary material.


Background: Hemodynamic load and heart structural remodeling rise during pregnancy because these changes are physiologically necessary. Adaptations in the mother's circulatory system may either initiate or aggravate the development of cardiovascular disease in the offspring. If the body is unable to adjust to these changes, it may develop heart conditions like cardiomyopathy. There is a lack of third-trimester echocardiographic data on left ventricular (LV) volume and function in healthy Iraqi women. To understand the cardiac alterations that occur during normal pregnancy, a precise tool that evaluates cardiac function is needed. In that regard, the four-dimensional echocardiography (4DE) technique has markedly improved the quality and accuracy of assessing the size and function of the left ventricle.Aim: The present study aimed to assess LV volume and function in the third trimester of a healthy pregnancy using 4DE and to compare the results of LV assessment using 4DE with those of LV assessment using conventional two-dimensional (2D) echocardiography.Methods: The study was conducted on 75 healthy pregnant women (the case group) and 75 non-pregnant women (the control group). The participants attended Al-Fortat Teaching Hospital from April 1, 2022, to May 30, 2023, and had 2D and 4D echocardiographic studies performed on them.Results: The LV end-diastolic volume (EDV), end-systolic volume (ESV), and cardiac output (CO) were significantly increased in the case group compared to the control group . In contrast, the LV ejection fraction (LVEF) was significantly decreased in the pregnant group compared to the control group . Additionally, the study showed significant differences in EDV, ESV, ejection fraction (EF%), and CO (P<0.001) between 2D and 4D echocardiography, according to the Bland Altman test.Conclusion: In healthy pregnant women in their third trimester, there is an increase in the indicators of preload (ventricular volume and CO) and a decrease in EF%. The 4DE provides detailed images and information about cardiac volumes and function, allowing for the early detection of any potential problems that may arise during pregnancy and thus improving the health outcomes of both the mother and the developing fetus. In women, heart disease is the top killer. Mothers are expected to have some kind of cardiovascular disease in 1-4% of all pregnancies, making it the leading non-obstetric cause of maternal mortality . PregnanDuring pregnancy, the total blood volume increases by about 45% above the pre-pregnancy volume, and red blood cell production increases by up to 40% via erythropoiesis . The oveThere are several effects of these alterations on the mother's heart. Heart remodeling  occurs in tandem with the reduction in systemic vascular resistance, which reduces LV hemodynamic afterload. The rise in blood volume also raises venous preload . InducinBecause of its general availability and safety, echocardiography is the recommended diagnostic technique for the examination of structural, functional, and hemodynamic changes during pregnancy. Variations in ventricular loading circumstances occur during pregnancy, limiting the use of the standard indices of myocardial systolic function, such as ejection fraction (EF), shortening fraction, and tissue Doppler velocity, all of which are load-dependent . Four-di2) [The study samples were collected from the gynecological consultation unit of Al-Furat Teaching Hospital in Al-Najaf Governorate from the beginning of April 2022 to the end of March 2023. The study included 75 healthy pregnant women in their third trimester (18-40 years old) and 75 healthy non-pregnant young women of the same age group, which were used as the control group. All subjects had a complete medical history obtained and were examined physically to rule out illnesses including organic heart disease, kidney disease, thyroid disease, severe anemia, diabetes, hypertension, and chronic medication or smoking. The height (cm) and weight (kg) of the women were obtained using a measuring tape and a digital weight scale, respectively. The body mass index of each woman was calculated as weight (kg)/height (m2) . ECG andEchocardiographic analysisAll of the ladies had a full 2D and 4D ultrasound utilizing commercially accessible Vivid E9 ultrasound equipment  with a 2.5 MHz S5-1 transducer. As suggested by the American Society of Echocardiography, the ladies were assessed with the echocardiography leads placed across the chest while lying in the left lateral decubitus position, which brings the heart closer to the chest wall and laterally to the sternum .To acquire a parasternal long-axis view for the LV ejection fraction measurement, the transducer was positioned in the third intercostal space with the indicator pointing toward the right shoulder, as in 2D-guided M-mode echocardiography. Each and every purchase was handled by the same seasoned professional. We used a commercially available, previously validated semi-automated technique called 4D auto LV volume quantification  to analyze the data sets digitally after they had been collected and saved off-line .Automatically presented in quad-view  were the end-diastolic (ED) frames used for contour identification. First, the four-chamber plane had to be manually adjusted such that the correct intersecting line of all the planes passed through the exact middle of the LV cavity, spanning the LV apex and the mitral valve opening. When using the program, two points must be placed at the mitral annulus limits and one point must be placed at the apex in end diastolic (ED) frames and then in end systolic (ES) frames. The LV endocardial boundary is drawn in a 3D model automatically during the ED and ES phases. If the endocardial boundary was not properly drawn by the computer, the boundaries were changed by hand. Finally, the left ventricular (LV) systolic volume, end-diastolic volume, end-systolic volume in four dimensions, and EF were shown .Statistical analysisThe research was quantitative, and SPSS version 18 was used to analyze the data. Both the whole bunch I (n = 75) and a control group (n = 75) were used to analyze the data. The review groups were examined using a free T-test, and the mean, standard deviation, and standard blunder of the mean were calculated. The Boring Altman study was used to compare the accuracy of 2D and 4D echocardiography, and a significance level of 0.05 was deemed necessary.Four-dimensional LVEDVThis study showed that the mean 4D EDV in the pregnant women group was 90.87 ± 18.03 ml; this result was significantly higher (p<0.001) than that of the non-pregnant women group (62.64 ± 14.11 ml).Four-dimensional LVESVOur study revealed that the mean 4D ESV of the pregnant group was 35.59 ± 6.52 ml, which was significantly p<0.001) higher than that of the non-pregnant women's group (22.42 ± 5.82 ml)  compared with the non-pregnant women group (64.04 ± 4.99%); therefore, pregnancy was independently and significantly associated with a lower EF% (p<0.01).Four-dimensional cardiac output (4D CO)The mean 4D CO of the pregnant group 4.87 ± 1.27 L/m) was significantly higher (p<0.001) than that of the non-pregnant group (3.35 ± 0.87 L/m). The distribution of 2DE variables in the pregnant and non-pregnant groups showed a significant difference  levels were significantly higher in the pregnant group (p = 0.001). Different studies have shown either an increase, a decrease, or no change in CO during the third trimester, and this discrepancy has been attributed mainly to the mother's adaptations throughout pregnancy as well as the effects of anthropometric variables and body positioning . AlthougFurthermore, in the pregnant women's group, 2D EDV (117.73 ± 23.16) was significantly higher than 4D EDV (90.87 ± 18.03) and 2D ESV (40.96 ± 10.72), which in turn was significantly higher than 4D ESV (35.59 ± 6.52). The same is true for CO, which had significantly higher values on 2DE (6.7 ± 2.1) than on 4DE (4.87 ± 1.27); this is attributed to the fact that the ventricular volumes and CO (which are both indicators of preload) increased progressively during pregnancy . The venThe LVEF% is generally unchanged or slightly increased during pregnancy. Currently, the data are conflicting ,23, but Volumes of LVs are estimated in M-Mode; however, this method has several problems since it assumes the LV is a prolate ellipse and that volume can be determined by measuring a single axis dimension and cubing it. Errors grow exponentially with the number of measurements, leading M-Mode and 2DE to incorrectly assume the geometric properties of the left ventricle .In healthy pregnant women in the third trimester, there is an increase in the indicators of preload, ventricular volumes (ESV and EDV), and cardiac output and a decrease in EF%. Four-dimensional echocardiography provides detailed images and information about the cardiac volumes and function, allowing for the early detection of any potential problems that may arise during pregnancy and hence improving the health outcomes of both the mother and the developing fetus.


In addition, the liver 3T MRI liver T2* data of 55 TM patients were measured as the 3T group: the curve equation of 3T T2* value and LICF was constructed.1.5T MRI TF (0.6–43 mg/g dw) and the corresponding 1.5T T2* value, the equation was LICF = 37.3932 = 0.971; P < 0.001). There was no significant difference between LICe − 1.5T and LICF in each validation group . There was significant consistency  and high correlation  between the two methods. There was no significant difference between the clinical grading results of LICe − 1.5T and LICF in each validation group , and there was significant consistency between the clinical grading results . There was no statistical correlation between the LICF (≥14 mg/g dw) and the 3T T2* value of severe iron overload (P = 0.085). The LICF (2–14 mg/g dw) in mild and moderate iron overload was significantly correlated with the corresponding T2* value . The curve equation constructed from LICF and corresponding 3T T2* values in this range is LICF = 18.463T2*∧(−1.142) . There was no significant difference between LICF and LICe − 3T in the mild to moderate range , and there was a significant correlation  and significant consistency  between them. LICe − 3T had high diagnostic efficiency in the diagnosis of severe, moderate, and mild liver iron overload .Based on the test group LIC2* value of the liver and the specific LIC-T2* curve equation. 3T T2* technology can accurately quantify mild-to-moderate LIC, but it is not recommended to use 3T T2* technology to quantify higher iron concentrations.The liver iron concentration can be accurately quantified based on the 1.5T T F), based on the MRI T2/R2 (1000/T2) technique and reported by FerriScan , has been certified by the Food and Drug Administration (FDA) of the United States and has high reliability  imaging sequence of MRI has been established as a non-invasive standard for quantifying tissue iron levels  values, to indirectly obtain the estimated value of organ iron concentration  patients based on large sample size and multicenter data and also to investigate the feasibility, reliability, and accuracy of 1.5T and 3T MRI T2* techniques in quantifying LIC in TM patients.The aim of this study was to investigate the relationship between liver 1.5T, 3T T2* data of thalassemia patients from three medical centers from January 2014 to June 2022 were retrospectively analyzed: 273 patients from the First Affiliated Hospital of Guangxi Medical University (Center 1), 54 from the Guangxi Zhuang Autonomous Region Ethnic Hospital (Center 2), and 64 from the Guangxi Medical University Affiliated Tumor Hospital (Center 3). In total, 13 patients underwent 1.5T MRI T2* liver scans at three centers (within 24 h of the same patient being scanned at different centers). In addition, 3T liver MRI T2* data of 55 TM patients from center 1 were collected. The inclusion criteria were: (1) patients diagnosed with thalassemia by genetic diagnosis, with a history of regular or irregular blood transfusion; (2) age ≥ 9 years old; (3) MRI for thalassemia was performed with liver T2 (as required by FerriScan) and T2* sequences. Exclusion criteria were: (1) the image data artifacts were large and did not meet the measurement requirements; (2) patients were complicated with other chronic liver diseases or neoplastic diseases. This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (2022-E457-01).Liver 1.5T MRI T2, layer thickness = 5 mm, FOV = 400 mm × 400 mm. The scan time was 15 min. GRE scan sequence: the same level above the hepatic hilum was scanned with one breath hold at the end of exhalation. rotation angle = 20°, TR = 200.00 ms, TE = 1.29, 2.35, 3.43, 4.6, 5.68, 6.85, 7.93, 9.1, 10.18, 11.35, 12.43, 13.6 ms, matrix = 256 × 256 mm2, layer thickness = 10 mm, FOV = 400 mm × 400 mm.1.5T data: a Siemens 1.5T MRI scanner , a Philips 1.5T MRI scanner , and the body coil were used. The images reported by FerriScan use a free-breathing two-dimensional multilayer spin-echo pulse sequence: rollover angle = 90°, repeat time (TR) = 1,000 ms, echo time (TE) = 6.0, 9.0, 12.0, 15.0, 18.0 ms, matrix = 256 × 256 mm2, layer thickness = 10 mm, FOV = 200 mm × 400 mm.3T data: a Siemens 3T MRI scanner was used . TR = 200 ms, TE = 0.97, 2.38, 3.79, 5.20, 6.61, 8.02, 9.43, 10.84, 12.25, 13.66, 15.07, 16.48 ms; Rotation angle = 20°, matrix = 64 × 128 mmF used in the study was obtained from the final FerriScan report . Measurement procedure: T2* image data were exported from the PACS system and imported into a personal computer with CMRtools software installed. The “Thalassemia” function of CMRtools was used to draw a roughly similar ROI according to the range of liver levels measured by FerriScan, avoiding the visible intrahepatic vessels and bile ducts at the same liver level. The delineated ROIs and the fitted T2* values were then displayed in the post-processing software. The truncation method  ≥ 0.98 (All T) ≥ 0.98 .2* values measured by different MRI scanners.SPSS 26.0 statistical software package was used for statistical analysis. All test results were statistically analyzed according to the test significance α = 0.05. MedCalc 19.8.0 statistical software was used to analyze the consistency of TThe 1.5T data of 273 patients from center 1 were divided into 191 patients in the test group and 82 patients in the validation group 1 according to the ratio of 7:3 by random number method. The 1.5T data of 54 patients from Center 2 were used as validation group 2. The 1.5T data of 64 patients from Center 3 were used as validation group 3. The 3T data of 55 cases from Center 1 were taken as the 3T group .2* image data of 50 randomly selected patients from the test group (n = 35) and validation group 1 (n = 15) were measured to evaluate intra-observer and inter-observer agreement . The intra-observer ICC was calculated by comparing the T2* values measured by observer A twice. The inter-observer ICC was calculated by comparing the T2* values measured by observer B with the T2* values measured by observer A. The ICC between the different MRI scanners was calculated by comparing the 1.5T T2* values of 13 patients at three centers. “Two-way random” was selected for “model” and “absolutely consistent” was selected for “type.” When ICC > 0.75 and P < 0.05, the measured T2* values were considered to be highly consistent. The remaining T2* value measurements were performed by observer A. Bland–Altman plots were used to analyze the consistency of the 1.5T T2* values of 13 patients measured by different MRI scanners.The intraclass correlation coefficient (ICC) was used, according to the ratio of 7:3. The 1.5T TF, and the measured liver T2* values of each group did not follow the normal distribution by the normality test (P < 0.05). The interquartile range  and median (M) were used as statistical descriptors. By curve fitting, the calibration curve equation was constructed between the T2* value of the test group and the LICF of the 3T group. The T2* values in each validation group and the 3T group were converted into LICe − 1.5T and LICe − 3T by the constructed curve equation. Both LICe − 1.5T and LICe − 3T did not conform to the normal distribution (P < 0.05). The Wilcoxon signed-rank test was used to examine the difference, and P > 0.05 was considered as no significant difference. Kendall's W coefficient was used to examine consistency. If the consistency coefficient W > 0.75 and P < 0.05, it indicated a high degree of consistency. Spearman rank correlation analysis was used to examine the correlation; if the correlation coefficient of |rs| > 0.75 and P < 0.05, it indicated a high correlation.The age, LICe and LICF were graded according to the severity of clinical liver iron overload, which was divided into normal (< 1.8 mg/g dw), mild (1.8–7.0 mg/g dw), moderate (7.0–14.0 mg/g dw), and severe (>14.0 mg/g dw) liver iron overload  was used to examine the consistency of clinical grading results. If K > 0.75 and P < 0.05, the two were highly consistent. With the LICF grading results as the reference standard, the area under the curve (AUC), sensitivity, and specificity of the receiver operating characteristic curve (ROC) was used to evaluate the accuracy of the LICe − 1.5T and LICe − 3T clinical classification results in each validation group. The Youden index was used to evaluate the authenticity of the clinical classification results, and the cutoff values of different clinical classifications were recorded when the Youden index was maximum.LICoverload . The McN25% = 12.00, P75% = 27.00). In Center 2, there were 19 male subjects (35.19%) and 35 female subjects (64.81%), aged from 9 to 47 years . In Center 3, there were 42 male subjects (65.63%) and 22 female subjects (34.37%), aged from 10 to 63 years . In the 3T group, there were 33 males (60.00%) and 22 females (40.00%), aged from 9 to 25 years .In Center 1, there were 152 male subjects (55.68%) and 121 female subjects (44.32%), aged from 9 to 49 years , and P < 0.001. The ICC between different MRI scanners was 0.999 (95%CI = 0.998–1) and P < 0.001. The results showed that the T2* values obtained by different MRI scanners were highly consistent with intra-observer and inter-observer. The Bland–Altman plots also showed significant consistency in the T2* values measured by different MRI scanners  = 0.992–0.998) and scanners .F and T2* and LICF and LICe in each group are shown in 2* value of the test group and LICF, the curve equation constructed was LICF = 37.3932 = 0.971, P < 0.001)  of mild-to-moderate iron overload, the curve equation was LICF = 18.4632 = 0.889, P < 0.001)  . Accordi< 0.001) . The live − 1.5T and LICF in verification groups 1, 2, and 3 . There was significant consistency between them  and high correlation . There was no statistical difference between the clinical grading results of LICe − 1.5T and LICF in verification groups 1, 2, and 3 , and the grading results are shown in P < 0.001). The accuracy indexes and corresponding cutoff values of the clinical classification results of LICe − 1.5T for the test group and each validation group are shown in There was no significant difference between LICF in the mild-to-moderate range was significantly correlated with the corresponding T2* value . There was no statistically significant correlation between LICF and T2* values in the severe range (P = 0.085). Of the 36 patients with severe iron overload diagnosed by LICF, 1 (2.78%) was diagnosed with moderate iron overload by LICe − 3T. Of the eight patients with moderate iron overload diagnosed by LICF, two (25%) were diagnosed with mild iron overload by LICe − 3T. Of the 11 patients with mild iron overload diagnosed by LICF, one (9.10%) was diagnosed with moderate iron overload by LICe − 3T. There was no significant difference between LICF and LICe − 3T in the mild to moderate range . There was a significant correlation between them  and significant consistency . There was no significant difference between the clinical grading results of full range LICF  and LICe − 3T . There was significant consistency among the clinical grading results . The ROC curve of LICe − 3T clinical grading results is shown in In the 3T group, LIC2 technology can generate reports including liver iron concentration, but it cannot be widely applied due to a variety of limiting factors, especially for long-term and timely quantitative monitoring of LIC in patients  [95% CI = 0.013–0.024], intercept = 0.277 (mg/g) [95% CI = 0.328–2.49]. In an early study by Wood et al. , the R2 was 0.72, and the correlation coefficient was 0.98. In an early study by Christoforidis et al.  was compared. The final LIC-R2* regression model was R2* = 0.851(MR-LIC) – 2.137 (correlation coefficient = 0.851). In the study by Garbowski et al. (2* range = 28.7–54.4 s−1). The final regression models of LIC (biopsy) -T2* and LIC (biopsy)-R2* were constructed: (1) LIC = 31.94(T2*)−1.014, 95%CI of coefficient = 27.8–36.7 (87–115%), 95%CI of index = −1.118–0.91(110–90%). (2) LIC = 0.029(R2*)1.014, 95%CI of coefficient = 0.016–0.054 (55–186%), 95%CI of index = 0.910–1.118 (90–110%). Garbowski et al. (2* and LIC-T2*: (1) R2-LIC = 0.83T2* – LIC1.04, 95%CI of coefficient = 0.96 ~ 1.11, 95%CI of index = 0.55 ~ 1.29. (2) R2-LIC = 0.87R2* – LIC – 0.55, 95%CI of slope = 0.74–0.99, 95%CI of intercept = −0.01–1.19.In the first quantitative study of liver iron overload using Rr et al. , the rels et al. , TE = 1.s et al. , MRI wasi et al. , TE was i et al.  also conF = 37.3932*. For the 3T MRI quantification of liver iron overload, the relationship LICF = 18.4632* technique should be avoided for the quantification of LIC in patients with severe iron overload, and 1.5T or other methods should be used instead. This conclusion is similar to that of d'Assignies  The high iron concentration corresponds to a very low T2* value, thus it is necessary to set a very short minimum echo time for more accurate measurement. However, due to the differences in the technique and scanning sequence used by different research centers, the different minimum echo time set obviously limits the lowest T2* value, which is the maximum value of LIC measured by the center. Some studies have shown that LIC with severe iron overload in the liver should be measured in combination with the signal intensity ratio between the liver and the paravertebral muscles (SIR)  .2* image ROI was as close as possible to the T2 image ROI delineated by FerriScan, but the artificial delineation of ROI was susceptible to various subjective and objective factors, and measurement error was inevitable; (2) In this study, the proportion of patients with moderate or severe liver iron overload was relatively large, and the proportion of patients with mild iron concentration was relatively small, which had a certain bias. However, in general, this study was analyzed with large sample size and was validated in multiple centers, which makes the results reliable; (3) In this retrospective study, LICF was used as the reference standard, in other words, the T2*-LIC calibration equation was constructed under the assumption that FerriScan based on T2/R2 technique was very reliable. Therefore, the equations obtained should not be extended to other techniques or organs for calculating iron concentration; (4) The sample size of 3T data is small, and it is difficult to perform grouping verification; (5) Accurate quantification of severe liver iron load by 3T T2* technique still cannot be achieved due to the technical limitation of the 3T scanning sequence in this study.The shortcomings of this experiment are as follows: (1) the definition of the ROI. In this study, the delineated T2* value and LICF provided by FerriScan in patients with thalassemia, and the related curve equation was constructed. After measuring the liver 1.5T T2* value, the liver iron concentration could be accurately quantified, and liver iron concentration in patients with iron overload could be better monitored. An important reference for timely and better formulation of appropriate diagnosis and treatment plans can be made. 3T T2* can be used to quantify liver iron concentration in patients with mild-to-moderate liver iron overload, while 1.5T T2* or other methods are recommended for patients with severe liver iron overload.This study explored the relationship between liver TThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (2022-E457-01). Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.PP contributed to the study's conception and design. Materials preparation and data collection were performed by FX, YP, HX, GY, FZ, and YL. Data analysis was performed by FX, HX, and YP. The first draft of the manuscript was written by FX and BL and all authors commented on earlier drafts of the manuscript. All authors have read and approved its final version.


Ventricular hypertrophy is associated with diastolic dysfunction, resulting in increased left atrial (LA) pressure, enlargement, fibrosis, and decreased LA function. Hypertrophic cardiomyopathy (HCM) is characterized by myocyte disarray, myocardial fibrosis, and hypertrophy. Notably, a thickened and noncompliant LV results in the impairment of diastolic function. These conditions promote LA remodeling and enlargement, which contribute to developing and maintaining atrial fibrillation (AF). AF is an atrial arrhythmia that occurs frequently in HCM, and evaluating the morphology and physiology of the atrium and ventricle is important for treatment and prognosis determination in HCM patients with AF. In addition, it provides a clue that can predict the possibility of new AF, even in patients not previously diagnosed with AF. Cardiac magnetic resonance (CMR), which can overcome the limitations of transthoracic echocardiography (TTE), has been widely used traditionally and even enables tissue characterization; moreover, it has emerged as an essential imaging modality for patients with HCM. Here, we review the role of multimodal imaging in patients with HCM and AF. Hypertrophic cardiomyopathy (HCM) is an inherited cardiomyopathy caused by mutations in genes encoding sarcomere proteins, affecting approximately 1 in 500 patients in the general population , making This review aimed to focus on what should be evaluated using multimodal imaging, including echocardiography and cardiac magnetic resonance (CMR) in terms of AF prediction and disease prognostication in the HCM population on the basis of LA and LV assessment. AF is the most common arrhythmia in patients with HCM, occurring in approximately 20–30% of previous HCM cohorts ,5,6. A sLA remodeling is a major echocardiographic predictor for AF ,9. In HCLV remodeling and impaired LV function are associated with AF in patients with HCM. Although primary impairments of sarcomeres caused by sarcomere gene variants are associated with the progression of LV remodeling, increased oxidative stress can also contribute to secondary alterations of sarcomeres. Oxidative stress strengthens sarcomere mutation, and mutant sarcomere proteins become a source of reactive oxygen species, forming a cycle that worsens each other . OxidatiIn addition, left ventricular outflow tract (LVOT) obstruction, systolic anterior motion (SAM) of the mitral leaflet, and combined MR contribute to LA remodeling and the development of AF. LA enlargement is not only LA remodeling itself but also a surrogate that reflects the pathophysiology of LVs, such as increased wall thickness, diastolic dysfunction, LVOT obstruction, and MR. These conditions can be confirmed mainly by echocardiography. The atrium and ventricle should be carefully evaluated using imaging modalities in patients with HCM and AF. Accurate information on LA size and function is crucial for clinicians regarding the prognosis and treatment of AF ,19. FurtTTE is the first-choice modality for evaluating cardiac anatomy and function. Cardiac morphology, as well as cardiac chamber size, function, LVOT obstruction, SAM, and MR that cause or maintain AF in HCM, can also be evaluated using TTE. 2; hazard ratio, 2.68; p = 0.008) predicted new AF, but LA diameters  did not significantly predict it, although univariate analysis revealed that both LA volume and LA diameters predicted new AF [The accurate determination of LA size is important for patient risk stratification. LA size is a key predictor of future AF development and clinical outcomes, including stroke, in patients with AF ,21,22. Td new AF . In clinical practice, when measuring LA volume, maximum LV volume is typically assessed; however, the minimum LA volume (measured at the LV end-diastole) should also be evaluated because the minimum LA volume may better reflect LV end-diastolic pressure because the LA is constantly exposed and affected by LV pressure during diastole . A recenIn addition to LA size, LA function is also an important indicator of clinical progress in patients with AF ,31. ImpopreA) during AF. However, LA phasic function measured using the volumetric method in TTE is difficult to use in actual clinical practice because of the great variability between individuals. Currently, strain analysis is widely used to assess LA phasic function. Furthermore, LA function can be assessed using tissue Doppler imaging (TDI) or speckle-tracking (ST) measurements of LA strain and strain rate [2) even in patients with a preserved LA diameter (<45 mm) [LA function in sinus rhythm can be subdivided into three components: (1) reservoir, (2) conduit function, and (3) booster pump function. Both the passive (conduit) and active (booster pump function) phases are components of atrial emptying in sinus rhythm. However, there is only a passive phase during AF; therefore, the term “ejection fraction” was used instead of “emptying fraction” . The totain rate . Howeverain rate . If the ain rate ,35. Receain rate . In patiain rate . Furtherain rate . Debonna(<45 mm) . In addi(<45 mm) .In HCM, a thickened and noncompliant LV results in impaired diastolic function, which promotes LA remodeling and enlargement. Therefore, LV evaluation is important in patients with HCM. LV evaluation by TTE includes assessment of the location and extent of ventricular hypertrophy, LVOT obstruction, the presence and degree of MR, papillary muscle abnormalities, and the presence of aneurysms. Fundamentally, LV morphology, such as asymmetric septal hypertrophy, should be evaluated in patients with HCM using TTE. Therefore, it is important to evaluate the degree of ventricular hypertrophy and myocardial function, including diastolic and systolic functions. In HCM, accurate measurement of the wall thickness is important. In the parasternal long-axis view, the interventricular septum and posterior walls were measured at the end diastole. Notably, wall thickness is associated with sudden cardiac death and AF in patients with HCM and is a very important parameter in clinical decisions, such as implantable cardiac defibrillator implantation. A previous study has reported that LV wall thickness is associated with AF . However2), pulmonary vein atrial reversal velocity , and peak velocity of TR jet by CW Doppler (>2.8 m/s), which can be applied with or without the presence of LVOT obstruction [As mentioned earlier, LV diastolic dysfunction serves as a trigger for AF and promotes the formation of a structural substrate called atrial remodeling, contributing to the generation and maintenance of AF. For the assessment of LV diastolic function in HCM patients, current guidelines recommend a comprehensive approach including the E/e’ ratio (>14), LAVI . Currently, it is recommended that the biplane method is optimal for LVEF measurements. LV systolic dysfunction in HCM is defined as LV < 50%, and previous studies have reported that the proportion of LV systolic dysfunction in HCM is between 4% and 9% ,47,48. CTwo methods, TDI and ST, are used to evaluate LA. The TDI method is limited to measuring movement parallel to the ultrasound beam, whereas the ST method can assess movement independent of the angle. Vasquez et al. reported that LV GLS is impaired in HCM patients with paroxysmal AF compared to patients without AF (13.0 ± 3.3% vs. 15.6 ± 3.0%) . It has Notably, analyzing regional wall mechanics with strain is helpful. Segments with normal thickness but reduced strain values are occasionally observed, and such segments may progress with myocardial disarray and fibrosis even in the absence of an increase in thickness. Urtado et al. showed that the regional longitudinal segment strain value decreased in segments with significant fibrosis evaluated using CMR, even after adjusting the wall thickness . In addition, LVOT obstruction, systolic anterior motion of the mitral leaflet, and MR findings, which increase the risk of AF, must be evaluated using TTE. A large prospective observational trial reported that moderate or severe MR was one of the predictors of major AF events, defined as those requiring electrical cardioversion, catheter ablation, hospitalization for >24 h, or clinical decisions to accept permanent AF . Current guidelines recommend conducting CMR imaging when it is unclear whether to diagnose HCM using echocardiography or when it is required to differentiate it from other infectious diseases . CMR imaAlthough TTE is the most widely used modality for measuring LA size and LA phasic function, CMR is considered an emerging technology because of its high-quality images, acquisition at a high spatial resolution, wide field of view, high tracking quality, high reproducibility, and low inter- and intra-observer variability . Because2 increase , LAmin per 10 mL/m2 increase , LA total emptying fraction per 5% decrease , LA active emptying fraction per 5% decrease , LA reservoir strain per 5% decrease , LA active strain per 5% decrease , and LA strain rate per 1/s increase  [In a study that continuously monitored the occurrence of AF by inserting ILR into 203 stroke patients who were not diagnosed with AF, it was shown that both LA size and LA phasic function measured by CMR- and CMR-FT-derived LA strain values significantly predicted new AF: LAmax, per 10 mL/m= 0.002) . Further= 0.002) . Yang et= 0.002) . CMR-FT-= 0.002) . p = 0.014) in patients with non-paroxysmal AF (n = 72) [Despite CMR’s advantages of analyzing the degree of myocardial fibrosis owing to the possibility of tissue characterization, assessing atrial fibrosis using LGE is challenging because the LA wall is thin. A previous study that analyzed 65 patients with paroxysmal or persistent AF showed that LA LGE was inversely correlated with LA strain and strain rate, and the extent of LA LGE was greater in patients with persistent AF than in those with paroxysmal AF . A recen(n = 72) . A recen(n = 72) . In HCM, CMR plays various roles in LV assessment. TTE has several limitations, owing to its poor acoustic windows. CMR can accurately define and differentiate the myocardium. Compared to TTE, CMR enables more accurate measurement of LV wall thickness, LV mass, and systolic function. Because it is sometimes difficult to accurately exclude RV trabeculation or papillary muscle, TTE often overestimates the wall thickness. In addition to being able to accurately evaluate ventricular size and function by visualizing the endocardial border more clearly, CMR can measure strain using FT techniques . SimilarCMR imaging can provide information on myocardial tissue characterization. In particular, LGE is crucial for assessing myocardial fibrosis; after gadolinium administration, it is redistributed from the intravascular space to the extracellular space and accumulates in areas with an expansion of the extracellular space due to myocardial edema or fibrosis, resulting in increased signal intensity on T1-weighted imaging. T1 mapping may provide an advantage over LGE by enabling a more valid quantification of diffuse fibrosis. The native T1 value is a tissue-specific time constant measured without a contrast agent. The T1 relaxation time is measured for each pixel of the myocardium. Fibrotic tissues alter the water composition and T1 values . The extp < 0.001), burden of LV LGE , LGE-involved segments , and ECV  [Myocardial fibrosis is a hallmark of HCM that contributes to diastolic dysfunction, resulting in LA remodeling, which acts as a substrate for AF. Furthermore, ventricular fibrosis is associated with adverse outcomes, including ventricular arrhythmia, SCD, and death, in HCM . In HCM,= 0.001) . The rel= 0.001) . A facto= 0.001) . Notably= 0.001) ,70. Guo = 0.001) . Further= 0.001) . However= 0.001) . In addi= 0.001) . As previously discussed, factors related to atrium and ventricle size and function, as well as fibrotic burden, are associated with the occurrence of AF in patients with HCM. However, in addition to these factors, the unique characteristics of HCM as a genetic disease must be considered. Sarcomere gene mutations can lead to dysregulation of calcium handling, thereby increasing arrhythmogenicity . AlthougHCM is a disease with diverse pathophysiology and ventricular hypertrophy. TTE is a fundamental tool for assessing various hemodynamic phenomena and remains pivotal in imaging. However, TTE images have inherent limitations, whereas CMR offers a more precise assessment of cardiac morphology, chamber dimensions, and function. AF is a common arrhythmia in HCM, and its co-occurrence in HCM can significantly impact clinical outcomes. Therefore, early detection and management of AF are crucial in HCM patients. TTE or CMR can be utilized to assess the extent of atrial and ventricular remodeling as well as their function in HCM patients, serving as predictors for the development of new AF. Using such imaging modalities, it would be possible to detect AF early in HCM patients at risk of new AF through more intensive electrocardiography monitoring and surveillance. These measures can also be employed as indicators for prognostication in HCM patients with AF undergoing treatment. Furthermore, CMR assumes significance as it enables the evaluation of myocardial fibrosis, which is directly linked to adverse outcomes in HCM patients. Therefore, a comprehensive diagnosis and treatment approach for HCM entails evaluating myocardial function from multiple perspectives and measuring fibrotic burden using varied imaging techniques. Further research and data accumulation are necessary, particularly in domains such as LA fibrosis and strain assessment through FT-CMR.