Thyroid storm (TS) is a rare and fatal endocrine emergency that occurs due to undiagnosed and inadequately treated hyperthyroidism after stressful conditions in patients with thyroid disorders. The objective of this systematic scoping review was to better understand the pathophysiology of TS and its complications, in terms of myocardial affection, tachyarrhythmia, and cardiogenic shock. In addition, we explored the pharmacological, mechanical, and surgical treatments for TS. We also evaluated the outcomes of TS according to sex and cardiac involvement. Additionally, analytical analysis was performed on the selected data. A literature review of peer-reviewed journals was carried out thoroughly using medical terms, MeSH on PubMed, Google Scholar, and combinations such as thyrotoxicosis-induced cardiomyopathy, thyroid storm, cardiogenic shock, myocardial infarction, endocrine emergency, Burch–Wartofsky score, extracorporeal circulatory support, and thyroidectomy. A total of 231 papers were eligible  with a total of 256 TS patients with cardiac involvement between April 2003 and August 2023. All age groups, sexes, patients with TS-induced cardiomyopathy, non-atherosclerotic myocardial infarction, tachyarrhythmia, heart failure, shock, and different forms of treatment were discussed. Non-English language articles, cases without cardiac involvement, and cases in which treatment modalities were not specified were excluded. Female sex was predominant, with 154 female and 102 male patients. Approximately 82% of patients received beta-blockers (BBs), 16.3% were placed on extracorporeal membrane oxygenation (ECMO) support, 16.3% received therapeutic plasma exchange (TPE), and 13.8% underwent continuous renal replacement therapy (CRRT), continuous venovenous hemofiltration (CVVHD), or dialysis. Overall, 18 females and 16 males died. BB-induced circulatory collapse, acute renal failure, CRRT, and ventricular fibrillation were significantly associated with mortality. Awareness of TS and not only thyrotoxicosis is vital for timely and appropriate treatment. The early diagnosis and management of TS in cardiac settings, including pharmacological, mechanical, and surgical modalities, can save high-risk patients. Sex matters in the presentation, treatment, and mortality of this population. However, further large-scale, and well-designed studies are required. Thyroid storm (TS) is a rare, serious endocrine emergency that occurs as a consequence of undiagnosed or inadequately treated hyperthyroidism . It is aThe presence of thyrotoxicosis is made according to the elevation of free Triiodothyronine (free T3) to >8.3 mU/L and free thyroxine (free T4) to >19.4 mU/L and a low or undetectable thyroid-stimulating hormone (TSH) level of < 0.05 mU/L . NotablyDiagnosis of TS and its criteria: The diagnosis of TS is based on various factors . In mostThe most striking symptom of TS is fever >102 °F, and when combined with other thyrotoxic symptoms, immediate care should be provided . MoreoveObjectives: The first objective of this review aimed to explore the occurrence, pathophysiology, and pattern of myocardial affection due to TS in males and females. Second, we evaluated the pharmacological, mechanical, and surgical treatments of TS in these populations. Finally, the clinical outcomes of TS, cardiac complications, and patient management were evaluated.Protocol: this review followed the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) checklist (http://www.prisma-statement.org/documents/PRISMA-ScR-Fillable-Checklist) (accessed on 31 July 2023) (ly 2023) . Figure Data collection: A systematic scoping review of peer-reviewed articles published between April 2003 and August 2023 was conducted. Additionally, analytical analysis was performed on the selected data. A thorough search was performed using medical terms and combinations of thyrotoxicosis crisis, thyrotoxicosis-induced cardiomyopathy, thyrotoxic cardiomyopathy, Takotsubo cardiomyopathy (TCM), thyroid storm, endocrine emergency, heart failure, BWS, CS, circulatory collapse, tachyarrhythmias, non-atherosclerotic myocardial infarction, heart failure, organ failure, ejection fraction (EF%), extracorporeal membrane oxygenation (ECMO), extracorporeal mechanical support, intra-aortic balloon pump (IABP), Impella device, left ventricular assist device (LVAD), therapeutic plasma exchange (TPE), continuous renal replacement therapy (CRRT), thyroidectomy, and radioiodine ablation (RAI) in electronic databases, such as PubMed, Google Scholar, and MeSH on PubMed search engines.Eligibility criteria: To allocate eligible studies, a comprehensive search strategy using keywords and text words highlighting variable treatments and interventions was used. Data included prospective and retrospective studies, case reports, and case series. Abstract: Fully pertinent details have been included such as age groups, sex, cardiac involvement, and different forms of pharmacological, mechanical, and surgical treatment. Exclusion criteria were articles in languages other than English unless the abstract entailed all the required information, cases of TS without cardiac involvement, and cases where treatment modalities were not specified. Abstracts, systematic reviews, and meta-analyses in which relevant individual cases were not identified or missing data were excluded. Moreover, any cases of thyroid disorders without a clear statement of “thyroid storm” or BWS  were excluded , number of cases per article, sex, mean age, history of thyroid disease, presentation and BWS, electrocardiogram (ECG), initial and follow-up ejection fraction (EF%), CS and cardiac arrest timing, type of beta-blocker (BB) used, use of cardiac devices, extracorporeal circulatory support or surgery including intra-aortic balloon pump (IABP), Impella device, left ventricular assist device (LVAD), therapeutic plasma exchange (TPE), extracorporeal membrane oxygenation and duration (ECMO) and CRRT, thyroidectomy, radioactive iodine ablation, presence of organ failure, and patient outcomes.Risk of bias assessment in individual and across studies: The risk of bias assessment was not applicable, as all cases were collected from case reports, case series, and retrospective studies published in peer-reviewed journals; moreover, there were no other types of studies on this topic. However, this value was generally low. Bias across studies is at the level of the provider who executes management. This is based on their knowledge of the subject matter and preferred methods. No structured, large-scale studies have addressed the topic of this review.Definitions: The presence of thyrotoxicosis and TS will be discussed in detail later. Cardiac manifestations were identified based on the patient’s clinical findings, laboratory values of troponin and B-type natriuretic peptides, ECG, chest radiographs, echocardiogram, electrocardiogram, coronary angiogram (if available), and serial transthoracic echocardiogram (echo) for heart failure findings. Myocardial affection included myocardial injury, ST- or non-ST-segment elevation myocardial infarction, acute heart failure, tachyarrhythmia, cardiomyopathy, and particularly dilated cardiomyopathy (DCM). Echocardiographic findings of cardiomyopathy include atrial and ventricular dilation, global hypokinesis, and biventricular dysfunction with low ejection fraction (EF). Shock is defined as low blood pressure and insufficient end-organ hypoperfusion. Cardiogenic shock (CS) has a low cardiac index, elevated ventricular filling pressure, and decreased mixed venous oxygen saturation. However, most published TS cases do not define CS and sometimes mention circulatory collapse or cardiopulmonary arrest.Synthesis of results: Data are presented as proportions, medians, and interquartile ranges (IQR). Comparisons between the two groups  were made using Student’s t-test for continuous variables and the chi-square test (or Fisher’s exact test) for categorical variables. Mann–Whitney U and Kruskal–Wallis tests were used to compare variables with non-normal distributions (non-parametric tests). A two-tailed p value ≤ 0.05 was considered statistically significant. Statistical Package for the Social Sciences (SPSS) for Windows  was used for data analysis.Summary Measures: Principal summary was based on sex, management modalities, and outcome (death).Overall findings: A total of 256 patients who presented with TS-induced cardiac manifestations were retrieved from 231 studies. Of these, 5 articles were case series, 224 were case reports, and 2 were retrospective studies. Several articles did not specify a BWS score; however, the necessary criteria were mentioned throughout the articles. Hence, we manually calculated the BWS scores according to the presented criteria. Notably, 41 articles did not report BWS and had insufficient criteria for manual calculations. However, these articles were included because their authors defined cases as ‘thyroid storm’ or ‘thyrotoxic crisis. Three-quarters of the patients reported thyroid disorders. The most common diseases were Graves’ disease (28%), 11.4% hyperthyroidism/thyrotoxicosis (11.4%), drug-induced (11%), and nonspecific autoimmune thyroid disease (1%). Chronic thyroiditis or viral infection were observed in 4% of patients, whereas 7% of patients had no history of thyroid disease, and 26% had a specific thyroid disease.The most common symptoms were dyspnea and palpitations. Other symptoms included nausea, vomiting, diarrhea, weight loss, sweating, cough, and chest pain. Based on echocardiogram results, the median initial EF was 25, with an IQR of (19–40). The latest EF reading during the follow-up was 50%, with an IQR of (36–58). However, the follow-up EF was not reported for 68 patients; 16 did not report on this because the patients died early, and the authors simply defined the patients’ EF as normalized or recovered.The most common arrhythmias detected on electrocardiography (ECG) were atrial fibrillation (AF) (49%) and sinus tachycardia (28%), which are commonly detected in patients with cardiomyopathy. Approximately 15 patients showed no ECG findings. Other ECG findings included atrial flutter, ventricular fibrillation, ventricular tachycardia, multifocal atrial tachycardia (MAT), supraventricular tachycardia, pulseless electrical arrest, and asystole. A total of 14 patients presented with cardiac arrest on admission.Of the total number of cases, 48% presented with multiple organ failure, of which the most common were heart failure (any degree of severity) 70%, hepatic failure (41.5%), and renal failure (20.7%). It is worth noting that most patients survived following admission and treatment; however, their death was either due to complications or treatment failure.Gender and storm: There are no studies that have examined the impact of sex on the incidence of TS, its complications, treatment, and outcomes. Akamisu et al.  reportedManagement and Outcome: The treatment of TS involves targeting several mechanisms in terms of inhibiting new thyroid hormone synthesis, inhibiting thyroid hormone release, inhibiting the peripheral effect of thyroid hormone (20% of T3 is secreted from the gland and 80% is produced by conversion of T4 to T3), inhibiting enterohepatic circulation of thyroid hormones, inhibiting deiodinases D1 and D2, blunting the adrenergic surge, and supportive, resuscitative, and circulatory support measures, plasma exchange, and surgical treatment [It was concluded that 91% of patients with cardiac involvement secondary to TS were administered anti-thyroid drugs (ATD). Additionally, 43% were administered inorganic iodide, such as potassium iodide one hour after ATD administration. As an additional treatment, 13% were administered cholestyramine and 70% were administered corticosteroids such as hydrocortisone or dexamethasone.Regarding cardiac medications, 82% were given BBs as non-selective  or cardioselective  BBs, in addition to short-acting cardioselective with short half-life . Calcium channel blockers were reported in 12.6% of cases. Moreover, 10.4% of patients were administered digoxin, and 33.6% of patients received inotropic medications and vasopressors. In addition, the patients received amiodarone.Mechanical treatment, mainly supportive of pharmacological therapy or bridge to definitive surgery; 16.3% were placed on ECMO. The other commonly used modality was TPE in 16.3% of the patients. Moreover, 13.8% of patients underwent CRRT. Five patients had an Impella device installed, and 9.3% had an intra-aortic balloon pump. Chaaya et al., Ahmad et al., and Korte et al. reported the use of a left ventricular assist device ,73,237. The overall mortality rate was 13.5% . This is a unique systematic scoping review exploring the pathophysiology and management of TSs complicated by cardiac involvement between 2003 and 2023. In addition, data analysis was performed for 256 patients with TS and cardiac involvement. TS is a thyrotoxicosis caused by an uncontrollable rise in endogenous thyroid hormones, leading to an exaggeration of wide clinical systematic presentations. The cardiovascular system is one of the organs that is most affected by TS. It has been noted that the cardiovascular events  that developed in TS were significantly associated with increased patient age ; howeverPrecipitating factors: TS can be triggered by various factors; some may spark underlying thyroid dysfunction, and others exacerbate existing thyroid diseases, particularly Graves’ disease . These pChen et al.  presenteNoncompliance with medications: The most common precipitating factor was noncompliance with medications in our analysis (32%). Galindo et al.  reportedDrug-induced TS: We found a few cases of amiodarone-induced TS that led to cardiomyopathy and CS ,43,173. Moreover, AlShehri et al. reported a case of alemtuzumab (ALZ)-induced TS further complicated by patient noncompliance with ATDs for Graves’ disease due to multiple factors . Mathew Kinoshita et al.  reportedThree cases reported the occurrence of TS following administration of iodine-based contrast ,99,146. Acute illness and infection: The presence of infection can aggravate thyrotoxicosis in patients with TS, especially if unresolved or missed. Acute illnesses such as myocardial infarction, stroke, diabetic ketoacidosis (DKA), or hypoglycemia can lead to TS ,165,169.White et al. reported a possible undescribed thyrotoxic crisis in which the patient’s initial presentation was pulseless electrical activity lasting for 15 min. There was significant LV dysfunction with an EF of 10% . The myoCardiac manifestations of TS: Thyroid hormone receptors are distributed in the myocardium and vascular tissue and can cause endothelial dysfunction and myocardial systolic and diastolic dysfunction [2+ ATPase and beta1-adrenergic receptors [function . The heafunction . T3 exereceptors . Hemodyneceptors . Moreoveeceptors .Tachyarrhythmia: Arrhythmias are frequently observed [observed . Sinus tobserved ,246. Heaobserved . A heartobserved ,248. Thiobserved . Thyroidobserved .In TS, AF is the most prevalent arrhythmia by 30–40% . In a JaTS-induced ventricular fibrillation (VF)/sudden cardiac death (SCD): A few cases of TS-induced SCD have been described in the literature ,182,224.J-point elevation on ECG in TS: Although early repolarization ) in at least two electrocardiographic leads is a common benign finding, it can be an arrhythmogenic substrate leading to VF . J-pointTroponin release, Myocardial Injury, and Infarction (AMI): The actual incidence of AMI in patients with TS is not well known or is under-defined. Myocardial injury with or without ECG changes has been reported in most cases of TS and is defined as a cardiac troponin T concentration of 0.03 ng/mL or more or high-sensitivity troponin T concentration of 10 ng/L or more for women or 15 ng/L or more for men. AMI of either type I or II may occur in patients with thyrotoxicosis, with or without atherosclerosis, and most articles did not define the significance of elevated troponin levels in TS, especially when coronary angiography was not performed. Most patients with AMI are treated conservatively without thrombolytics or intervention because the majority has non-obstructive or non-atherosclerotic causes. In addition, multiorgan dysfunction and hemodynamic instability are limiting factors for aggressive treatment of AMI. Moreover, a slight increase in troponin levels in TS may be due to tachycardia, coronary artery spasm, or Takotsubo cardiomyopathy [n = 5), TS was initially misdiagnosed as AMI and CHF, which delayed on-time treatment of the storm [myopathy . In a smhe storm .TS-induced coronary spasm: Non-atherosclerotic causes of myocardial injury include an imbalance (mismatch) between oxygen supply and demand, which can occur with epicardial coronary artery spasm, tachyarrhythmias, or thyrotoxicosis. These factors can lead to type 2 acute MI [acute MI . Excess acute MI ,253. Omaacute MI  describeacute MI ,255.Zheng et al.  reportedAcute Heart failure and cardiomyopathy: Heart failure may be the initial presentation of TS and the main cause of mortality [ortality . High-ouortality ,162,177.ortality . Most paortality .2+ ATPase, which is involved in excitation-contraction coupling and calcium-induced calcium release [Dilated Cardiomyopathy (DCM): Dilated cardiomyopathy is characterized by progressive heart muscle disease and is the most common cardiomyopathy phenotype. Dilated thyrotoxic cardiomyopathy, an unusual TS phenotype, initially manifests in 6% of patients; however, severe LV dysfunction is observed in <1% of patients . The pre release . Calcium release .Free T3 and T4 increase the expression of the more rapid contractile isoforms of the alpha-myosin heavy chain. In addition, these hormones stimulate erythropoietin secretion, contributing to increased blood volume, leading to high-output CHF. T3 leads to an increase in stroke volume and pulse rate and promotes peripheral vasodilation, causing a decrease in systemic vascular resistance, which in turn activates the renin–angiotensin system, leading to fluid and salt retention . NotablyAccording to our review, 11 cases of TCMP have been previously reported. Takotsubo cardiomyopathy is seen in 17.7% of thyroid diseases, of which 5.9% are attributed to hyperthyroidism . TCMP isn = 4), and one of them had IABP, ECMO, and CRRT. The LVEFs ranged between 14 and 20%, and the BWS scores ranged from 80 to 90, and all survived after a long hospital stay.Brain natriuretic peptide (BNB) in TS: Dyspneic patients with BNP > 100 pg/mL or NT-proBNP > 400 pg/mL are more likely to have CHF . In thisPericardial effusion: There were seven cases of pericardial effusion and TS [n and TS ,193,205.n and TS .Circulatory collapse and Cardiogenic shock: CS is an infrequent complication of TS, with a high fatality rate [ity rate . In patiity rate . A Japanity rate . Howeverity rate . Risk faity rate . Additioity rate . In addiity rate . Iwańczuity rate  reportedPulmonary Embolism (PE): Around 10–40% of hyperthyroidism cases are found to have arterial embolism [embolism . Notablyembolism ,230. A vembolism .Modalities of treatment of TS with myocardial involvementA multidisciplinary approach must be applied to patients with TS, because multiple organs are affected. It is crucial to adequately evaluate and avoid misdiagnosis of TS as early management plays a crucial role in the outcome. Generally, the Japanese guidelines for treatment include treatment of thyrotoxicosis (reduction in thyroid hormone secretion and production), management of systemic manifestations , organ-specific manifestations , triggers, and definitive therapy .(A)Pharmacological treatment modalitiesInitial Management: According to our findings, 90% of patients were administered ATDs once diagnosed with TS. This classic regimen includes thioamides such as carbimazole (CBZ), methimazole (MMI) and propylthiouracil (PTU). They act by inhibiting thyroid peroxidase (TPO), thereby blocking the synthesis of T3 and T4 from thyroglobulin . MMI andSteroid: Corticosteroids should be administered as prophylaxis for relative adrenal insufficiency caused by the hypermetabolic state in TS. Large doses of steroids have been shown to inhibit thyroid hormone synthesis and peripheral conversion of T4 to T3 . CorticoBeta-Blockers: BBs are essential components of the standard treatment of TS. BBs counteract the indirect effects of thyroid hormones by decreasing systemic vascular resistance, increasing cardiac output by 300%, and allowing peripheral vasodilatation . The docBeta-blocker associated with circulatory collapse: BBs therapy has been described as a double-edged sword in TS . PatientCalcium channel blockers (CCBs): Few authors have reported the use of CCB for the treatment of TS. However, Saakan et al. attributed diltiazem to the reversible CS in the setting of TS, as CCBs are atrioventricular blocker agents, leading to worsening of cardiac output and hemodynamic instability in a few cases .f) of the sinoatrial node and do not affect contractility. Frenkel et al. described a 37-year-old patient with thyrotoxicosis and CHF [Ivabradine: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers, such as Ivabradine, act by selectively and specifically inhibiting the cardiac pacemaker current , nitrate , and/or carperitide (intravenous α-human A-type natriuretic peptide); noninvasive positive pressure ventilation (NIPPV); vasoconstrictor agents; and cardiotonic agents ,262.Inotropes and vasopressors: In cardiogenic or refractory shock, dopamine should be administered intravenously at a dose of 5–20 μg/kg/min when systolic blood pressure is between 70 and 90 mmHg. Dobutamine at a dose of ~10 μg/kg/min should be considered when the patient is in CS and systolic blood pressure is ≤70 mmHg. Norepinephrine at a dose of 0.03– 0.3 μg/kg/min is also used when the patient’s hemodynamic condition does not improve with these agents, or systolic blood pressure is ≤70 mmHg . Mechani(B)Non-pharmacological therapyMechanical treatment of TS: The three main extracorporeal support systems  can be useful as bridges for stability and definitive surgery in TS. Both ECMO and TPE were used concurrently in multiple cases, and only a few cases utilized all three. Evidence for the use of these systems arises from case reports or a few case series, as there are no prospective clinical trials. The use of these systems is costly and does not have side effects. Therefore, they require an expert team and appropriate patient selection and timing.(a)Extracorporeal Membrane Oxygenation (VA-ECMO): In 2021, Lim et al.  reportedECMO is mainly indicated in cases of acute severe cardiac or pulmonary failure unresponsive to conventional therapy (ELSO guidelines) . In addiDespite the recent incorporation of ECMO in the management of endocrine emergencies, the overall survival rate could be unreliable because of possible publication bias, patient selection bias, and small sample size . The cau(b)Therapeutic plasma exchange (TPE): it is a class II indication of TS. TPE is one of the most effective methods for eliminating excess thyroid hormones circulating in patients with TS . It uses(c)Continuous Renal Replacement therapy (CRRT) and continuous venovenous hemofiltration (CVVH): CRRT includes the use of large volumes of room-temperature fluids , which can cause hypothermia. In addition, intravenous infusion of albumin and plasma in CRRT increases the ability of proteins to bind free thyroid hormones . CRRT is(d)CVVH is one of the modes of CRRT, which was described in six of this review cases. Our data showed that CRRT was significantly associated with a high mortality rate, particularly in patients with acute renal failure. CVVH uses convective clearance to remove toxins and solutes from the patient’s circulation, whereas CVVHD relies on diffusive clearance to remove the same toxins and solutes . CVVH he(e)Intra-aortic balloon pump (IABP): This device is used in cases of acute heart failure with shock after ineffective inotropic or vasopressor administration. The IABP works by inflating the balloon during diastole and aortic valve closure and rapidly deflating before systole . This re(f)Impella: The Impella device pumps blood from the left ventricle into the ascending aorta and helps maintain systemic circulation at an upper rate between 2.5 and 5.0 L/min. The use of the Impella over ECMO is based on the concept of ventricular unloading to allow ventricular time to recover. It is a very small catheter-based device used as ventricular support in patients with CHF and CS . ImpellaHypothermia resuscitation: Fu et al. described an in-hospital TS-induced cardiac arrest in a 24-year-old woman. After resuscitation, the patient was hyperthermic (39 °C) and comatose [comatose . Targetecomatose .Radioactive iodine ablation (RAI): RAI is considered a safe and effective option for destroying thyroid tissue in many thyroid disorders such as cancer and hyperthyroidism. In our review, RAI was used in four cases. All patients presented with Graves’ disease and secondary heart failure that were successfully managed. RAI was performed after successful management to minimize the risk of relapse. All the patients developed hypothyroidism after RAI [fter RAI .Surgical treatment: Thyroidectomy entails removal of the thyroid gland to eliminate the primary source of excess secretion of thyroid hormones [hormones . Althoughormones . Our anahormones .Outcome and Prognosis: TS represented 16% of hospitalized patients with thyrotoxicosis and had 12 times the mortality rate compared with thyrotoxicosis without a storm [ a storm . In the  a storm . Two pat a storm ,121. One a storm . Chao et a storm . Another a storm . CRRT is a storm . The com a storm . Moreove a storm . HoweverBased on this systematic scoping review, we proposed an algorithm for the management of TS with cardiac involvement .LIMITATIONS: This systematic scoping review has some limitations, including papers published in languages other than English and gray literature. Moreover, articles that presented cases without specified treatment modalities, abstracts, or abstract posters (unless the required information was available) were not included. We did not use diagnostic criteria other than BWS, such as the Japanese criteria [criteria , which mcriteria .The exact mechanism underlying the development of TS in uncomplicated thyrotoxicosis is not yet well defined; however, most manifestations of the latter occur in an exaggerated and wider manner during the storm. This could be due to the abrupt increase and availability of free thyroid hormones in the circulation, in addition to the enhanced response of the tissue receptors (which increase in number) to the hormone and catecholamine surge. Therefore, early and appropriate treatment of severe thyrotoxicosis is crucial to prevent the progression to TS and its higher fatalities. Frontline physicians should be aware of “TS” and not only “thyrotoxicosis” and the on-time appropriate treatment. The index of suspicion should be high, especially in the absence of a prior history of hyperthyroidism or clear triggers, as it may be missed in 30% of cases. Management should be guided by the affected end organ, indication versus contraindication (safety) of certain therapies, and the prevention of recurrence. The early diagnosis and management of TS in cardiac settings, including pharmacological, mechanical, and surgical modalities, may save high-risk patients. Mechanical support is required to bridge the gap between stability and definitive treatment. Sex matters in the presentation, treatment, and mortality of these populations, to a certain extent. However, further large-scale and well-designed studies are required.


To describe the efficacy and safety of sodium-glucose cotransporter 2 inhibitors as a specific treatment for anthracycline-related cardiac dysfunction in a small real-world population.Seven patients with anthracycline-related cardiac dysfunction were clinically and echocardiographically evaluated before and after the introduction of sodium-glucose cotransporter 2 inhibitors.p < 0.010). A noteworthy left ventricular reserve remodeling  was also observed. Sodium-glucose cotransporter 2 inhibitors therapy was well tolerated by every patients; no cases of discontinuation or relevant side effects were observed.After a median period of 24 weeks with uninterrupted sodium-glucose cotransporter 2 inhibitors treatment, a significant clinical improvement was observed with at least one New York Heart Association Functional Class (NHYA FC) improvement in all patients (median NYHA FC: I vs. III, Sodium-glucose cotransporter 2 inhibitors induce a significant clinical improvement and left ventricular reserve remodeling in patients affected by anthracycline-related cardiac dysfunction. While advancements in oncological treatment have led to improved survival rates, they have also resulted in an increase in cardiac side effects. Anthracyclines are effective and widely used oncological treatments, although they are associated with the risk of severe myocardial damage which can often necessitate the discontinuation of chemotherapy. The European Society of Cardiology (ESC) has recently published the first edition of guidelines on cardio-oncology, defining anthracycline-related cardiac dysfunction (ARCD) as a form of heart failure (HF) characterized by left ventricle (LV) remodeling and mild-to-severe impairment of ejection fraction . CurrentWe collected seven cases of patients with ARCD and symptomatic HF with reduced ejection fraction (HFrEF). They had all been exposed to a high dose of anthracycline for treating different types of cancer. No other cause of HF was found, and coronary angiography was negative in all cases. All the patients had clinical and echocardiographic assessments in three different time periods: before chemotherapy (T0), after chemotherapy when ARCD was diagnosed (T1), and after SGLT2-i therapy (T2). New York Heart Association functional class (NYHA FC), two-dimension LV ejection fraction (LVEF), LV end-diastolic and volume indexed (LVEDVi), were considered to describe the clinical status and LV remodeling. We compared T0 vs. T1, T1 vs. T2, and T2 vs. T0.α) was considered at a two-tailed probability level of significance of 95% (p < 0.05). The Chi2 test through Person's analysis was used to test NYHA functional class changes. The statistical analysis was carried out using SPSS version 28.0.1.0.The non-parametric statistical Wilcoxon Signed Rank Test was adopted. The significance level . All the patients had a NYHA FC I before completing the chemotherapy cycles, and none had previous cardiovascular disease or diabetes. All patients had normal echocardiographic morpho-functional parameters before chemotherapy, and none had more than mild valvular disease.The demographic, clinical, and echocardiographic characteristics are reported in 2, p = 0.018), significant reduction in LVEF , and a relevant degradation of symptoms . At T1, all patients had been treated with at least two HF drugs for at least 6 months, the most common combination being a beta-blocker and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor-neprilysin inhibitor (ARNI). Symptomatic hypotension was the main limitation to the simultaneous administration of GDMT for HFrEF. If indicated, cardiac resynchronization therapy (CRT) was implanted, and SGLT2-i initiation occurred at least 6 months after the implantation.Since ARCD was diagnosed, all parameters showed a significant statistical difference from T0 to T1: patients presented with remarkable LV remodeling (median LVEDVi 46.8 vs. 82.5 ml/mp < 0.010). We also observed noteworthy LV reserve remodeling .Of the seven patients, six were given dapagliflozin 10 mg and one empagliflozin 10 mg daily. After a median period of 24 weeks with uninterrupted SGLT2-i treatment, significant clinical improvement was observed at T2 compared to T1 with at least one NYHA FC improvement in all patients   .SGLT2-i therapy was well tolerated by every patients; no cases of discontinuation or relevant side effects were observed.We report below the two most significant cases:2. The echocardiographic follow-up showed normal LV volume and preserved LVEF, and the patient remained asymptomatic for 10 years following the end of chemotherapy. However, the patient showed severe dyspnea and LV systolic dysfunction. Cardiac magnetic resonance (CMR) revealed an initial dilatation of the LV (LVEDVi 106 ml/m2), a significant reduction in LVEF (34%), and a small LGE stria in the interventricular septum. Coronary angiography yielded negative results. Due to persistent symptoms and severe reduction in LVEF under GDMT, a CRT-D was implanted. One year after the implantation, clinical picture was unchanged. At this point, SGLT2-i was added to previous therapy . After 6 months, LVEDVi and LVEF normalized (respectively 46.6 ml/m2 and 50%) and NYHA FC improved to I.Patient 1 was diagnosed with follicular lymphoma and treated with a cumulative doxorubicin equivalent dose >250 mg/m2. The echocardiography at baseline showed normal LV volumes and LVEF >60%. However, 1 year after the end of chemotherapy, the LV was mildly dilated (LVEDVi 82 ml/m2), and LVEF had decreased to 45%. The patient was started on treatment with bisoprolol and ramipril. Three months later, a further decrease in LVEF to 40% was observed through echocardiography. Therefore, CMR was performed, which revealed LV dilatation (105 ml/m2), diffuse hypokinesis, and a significant reduction in LVEF (37%). The patient also reported dyspnea during moderate physical activity (NYHA FC II). Coronary angiography was negative. At this time, SGLT2-i was added. At the follow-up 6 months later, the patient was asymptomatic (NYHA class I), and a recovery in LV volumes and contractility was observed (LVEDVi 46 ml/m2 and LVEF 50% at echocardiography).Patient 2 was diagnosed with Hodgkin's lymphoma and underwent chemotherapy with a cumulative doxorubicin equivalent dose >250 mg/mTo our knowledge, this is the first case series that demonstrates the benefits of SGLT2-i in ARCD. All patients showed a significant improvement in symptoms and echocardiography assessment after adding SGLT2-i to their HF GDMT. Additionally, we observed that SGLT2-i was well-tolerated and safe, with no cases of discontinuation or recorded side effects.Despite none of our patients having a diabetes diagnosis, our findings are consistent with a recent retrospective study by Gongora et al. In their study, SGLT2-i were found to be effective in preserving LV function and reducing the incidence of cardiac events among patients with diabetes who were treated with anthracyclines. It is worth noting that no cases of ARCD were observed in the group treated with SGLT2-i . Our datIndeed, our research group recently reviewed basic science data supporting the potential role of SGLT2-i in preventing ARCD. Through a meta-analysis of 8 studies conducted on mouse models we showed that LVEF after chemotherapy with anthracyclines was significantly higher in rats preventively treated with SGLT2i , 6. Take+/Hydrogen exchanger 1, consequently reducing cytoplasmatic sodium and calcium concentrations, and increasing mitochondrial calcium concentration. This effect on calcium homeostasis is likely to improve myocardial contractility and reduce oxidative stress. Finally, SGLT2-i reduce inflammation, which plays a crucial role in the pathogenesis of ARCD. This effect is mediated by an increased activation of 5' adenosine monophosphate-activated protein kinase and a reduction in pro-inflammatory cytokines , which is investigating the efficacy of SGLT2-i in preventing ARCD.At present, the ESC guidelines on cardio-oncology recommend treating patients with symptomatic ARCD and asymptomatic moderate or severe ARCD as indicated by HF guidelines. Therefore, the concomitant use and up-titration at the maximal tolerated dose of a beta-blocker, an ACE-I/angiotensin II receptor blocker (ARB) or ARNI, a MRA and a SGLT2-I is suggested . However


It was estimated that about 1.3 billion people were diagnosed to be hypertensive in 2015. All countries consistently show this high prevalence. Ischemic heart disease stands as the most common cause of systolic blood pressure-related deaths per year. Left ventricular hypertrophy determined by echocardiography can predict cardiovascular morbidity and mortality. The question of whether the LV geometric pattern has an additional prognostic value is still not clearly answered. Currently, coronary computed tomography is widely used in clinical practice with a great capability of simultaneous evaluation of the LV mass and the coronary arterial tree. Our study aims to examine the relationship between LV mass and geometry and coronary artery disease using an ECG-gated 320-detector- row CT scanner.2 respectively. One-fifth of the patient had CAD luminal stenosis ≥ 50%. Normal LV geometric pattern was observed in about 37% of the study population. About one-third of the patients showed concentric remodeling. Patients with increased LV mass index represented one-third of the study population with a greater percentage of the concentric hypertrophy pattern than the eccentric hypertrophy pattern. Patients with high CAD-RADS showed statistically significant higher LV mass, LV mass index, and septal wall thickness. Patients with high CAD-RADS showed a greater percentage of concentric and eccentric hypertrophy. The LV geometric pattern was the only independent predictor of the high CAD-RADS. The LV geometric patterns associated with high RADS ordered from the highest to the lowest, were concentric LVH, Eccentric LV, and concentric remodeling.Two hundred ninety-eight hypertensive Egyptian individuals were enrolled in our study, the mean age was 57.5 ± 10.5, and males comprised 76.5% of the study population. The mean LV mass and LV mass index were 193 ± 60 gm and 95.2 ± 27.5 g/mLV geometric pattern is the only independent predictor of high CAD-RADS after adjustment for LV mass index and septal wall thickness. Among abnormal LV geometric patterns, concentric hypertrophy stands as the most important predictor of high CAD-RADS. It was estimated that about 1.3 billion people were diagnosed to be hypertensive based on office blood pressure in 2015. All countries consistently show this high prevalence irrespective of their economic status [The disability-adjusted life years owing to hypertension have increased by 40% since 1990. Ischemic heart disease stands as the most common cause of systolic blood pressure-related deaths per year .Chest X-ray and ECG are insensitive techniques for the detection of left ventricular hypertrophy. On the other hand, LVH determined by echocardiography has a well-established prognostic value in predicting cardiovascular morbidity and mortality –11.The geometric pattern of hypertrophy of the left ventricle associated with arterial hypertension is identified by calculating the LV mass and the relative wall thickness. The question of whether the LV geometric pattern has an additional prognostic value is still not clearly answered , 12–14.Coronary computed tomography is widely used in clinical practice for the non-invasive evaluation of the coronary arterial tree. The three-dimensional capability of the ECG-gated CT study allowed for the simultaneous, accurate evaluation of the LV volumes and mass. Its accuracy has been validated against cardiac magnetic resonance imaging –the gold standard for LV volume and structure assessment– in previous studies –19.Our study aims to examine the relationship between LV mass and geometry and coronary artery disease using an ECG-gated 320-detector- row CT scanner that can simultaneously evaluate the coronary arterial tree and the LV chamber size and mass.This is a prospective, non-randomized, cross-sectional, observational study that enrolled 298 hypertensive patients scheduled for MSCT coronary angiography for suspected coronary artery disease.All patients gave written informed consent to publish the data contained within this study.Hypertensive Individuals aged over 30 years who were scheduled for MSCT coronary angiography. Hypertension is defined as office BP measurements of SBP ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg .Diabetes mellitus (DM), dyslipidemia, or smoking.Valvular heart disease.Cardiomyopathy.Previous coronary artery bypass (CABG) or percutaneous coronary intervention (PCI).Individuals who refuse to participate in this study.Clinical assessment: All individuals were subjected to focused medical history and clinical examination with emphasis on the following:Demographic characteristics and anthropometric measurements:Age and genderb-Cardiovascular risk factors: DM, dyslipidemia, and smoking.Height measurement using the standing height scaleb-Cardiovascular risk factors: DM, dyslipidemia, and smoking.2). Adults were classified according to BMI (table adapted from WHO Consultation on Obesity): Underweight < 18.5 Normal range 18.5–24.9 Overweight 25–29.9 Obese class I 30–34.9 Obese class II 35–39.9 Obese class III ≥ 40 [Body weight and body mass index (BMI). The latter was calculated using the following formula: BMI = body weight in kg / height in mIII ≥ 40 .b-Cardio0.425 × height in cm0.725.b-Cardiovascular risk factors: DM, dyslipidemia, and smoking.Body surface area (BSA): This was calculated using Du Bois formula: BSA = 0.007184 × weight in kgMulti-slice CT Angiogram (MSCT) Study Protocol:A retrospective, ECG-gated multi-slice CT coronary angiography was done using a 320-slice, Toshiba Aquilion one machine . After acquiring the non-contrast enhanced sequence, a high flow rate injection of ''A patient-weight tailored contrast dose ''average of 75 ml of non-ionic contrast (5.3 ml/sec.) via an anti-cubital vein was done, followed by the acquisition of ultra-thin cardiac sections to evaluate the coronary arteries. The study was evaluated at the systolic and diastolic phases . Selective reconstruction of the poorly visualized segments of the coronary arteries at different phases of the cardiac cycle was done. Coronary artery disease reporting and data system (CAD- RADS) was used to standardize our reports .Additional images to evaluate the LV diameters, LV wall thickness, and LV volume was reconstructed during diastole with increments of 5% from 75 to 90% of the RR interval. Data were transferred to a workstation with commercial software  for analysis. Multi-planar reformation (MPR) images of the LV cardiac chamber  were automatically generated.2). The cutoffs of 115 g/m2 for men and 95 g/m2 for women were used to define the presence of LVH [The LV volumes were calculated by automatic detection of the LV epicardial and endocardial borders by the software without the inclusion of the papillary muscles Fig. . Both boe of LVH , 24.Fig.The LV end-diastolic inner dimension  on the 4-chamber multi-planar reformatted images (MPR), LV wall thickness; both the septum  and the posterior wall  on the short-axis MPR at the chorda level were measured Fig. . The relThe patients were classified into four groups of geometric patterns based on the values of LV mass index and RWT: normal , concentric remodeling , eccentric LVH , and concentric LVH (increased LV mass and RWT) . To asseP-value < 0.05 was considered significant.After data collection, analysis was done using Statistical Package of Social Science (SPSS) version 19. Categorical data were displayed as numbers and percentages and continuous data were displayed as means ± SD  or median and range . Comparison analysis was conducted using student’s t-test  or a Mann–Whitney test  and a Pearson Chi-square test . Multiple linear regression analysis was used to predict significant CAD. A two-tailed CT data (CT coronary angiography and LV measurements) of the first twenty patients were repeated by the same operator one week later to test for intra-observer variability, and the intra-observer correlation coefficient ranged from 0.88 to 0.98. The CT data of the same twenty patients was measured by another operator to test for inter-observer variability and the intra-observer correlation coefficient ranged from 0.89 to 0.97.This non-randomized, observational, cross-sectional study was conducted in Cairo, Egypt from November 2019 to November 2021. This study enrolled 298 Egyptian patients who underwent CT coronary angiography for suspected CAD.2/kg and the mean BSA was 20 ± 0.2 m2. About two-thirds of the study population were overweight or mildly obese. These data are presented in tables Two hundred and ninety-eight Egyptian individuals were enrolled in our study. The mean age was 57.5 ± 10.5, males comprised 76.5% of the study population, the mean weight and height were 87.6 ± 15.7 kg and 171.1 ± 8.0cm respectively, the mean BMI was 29.6 ± 5.1 cm2 respectively. The CAD RADS score shows a median of 2. Only 20% of the patient had CAD luminal stenosis ≥ 50%. Normal LV geometric pattern was observed in about 37% of the study population. About one-third of the patients showed concentric remodeling. Patients with increased LV mass index represented one-third of the study population with a greater percentage of the concentric hypertrophy pattern than the eccentric hypertrophy pattern  and a group with 50% or more luminal diameter stenosis . A comparison between both groups was conducted   Fig. .Table 8LConducting multiple linear regression analysis Table  had showThis is the first study to investigate the relationship between CAD using CAD-RADS and both LV mass and its geometric patterns in hypertensive patients using a 320-detector-row CT scanner.Hypertension consistently shows high prevalence in all countries irrespective of their socio-economic status. The disability-adjusted life years due to hypertension has increased by 40% since 1990. Ischemic heart disease stands as the most common cause of systolic blood pressure-related deaths per year .Coronary computed tomography angiography (CCTA) is a widely available, clinically validated, noninvasive imaging tool that is used to evaluate the coronary arterial tree. CAD-RADS is a standardized system for reporting the CCTA results. It has the advantages of improving communication with the referring physicians and facilitating research work, resulting in better patient care and outcomes . CCTA usLeft ventricular hypertrophy determined by echocardiography is an independent risk factor for increased cardiovascular morbidity and mortality. This well-established relationship is continuous and graded , 28, 29.Koren et al. and Muiesan et al. conducted two prospective studies including relatively healthy adults with essential hypertension, following them up for ten years. Levy et al. also conducted a prospective study that included Framingham study participants without prevalent cardiovascular disease with four years of follow-up. The three studies showed an adverse prognostic value of LVH determined by echocardiography using different cardiovascular disease endpoints, but all included MI , 10, 30.Tang et al. conducted a non-randomized study on the members of the National Heart, Lung, and Blood Institute Family Heart Study and the Hypertension Genetic Epidemiologic Network study. They found a significant association between coronary artery calcium score (CAC) and LV mass index. This relationship was stronger in African Americans than whites .Altunkan et al. conducted a study on two hundred forty-nine asymptomatic hypertensive patients. They found a direct relationship between LVH and coronary artery calcium where patients who were CAC positive showed significantly greater LVM than those who were CAC negative .Mintu et al. conducted an observational study on one thousand and sixteen patients with coronary heart disease and a follow up period of three and half years. They found that LV mass index adjusted for clinical and other echocardiographic parameters was significantly associated with both all-cause mortality and sudden or arrhythmic death. This association maintained its significance even in patients with normal LV systolic function (defined as more than 55%) .In agreement with the previously mentioned studies, our study using a 320-detector-row CT scanner showed that LV mass, LV mass index, and septal wall thickness were significantly higher in patients with significant coronary artery disease (CAD-RAD ≥ 3) than in those with non-obstructive CAD (CAD-RADS < 3). This finding confirms the significant relationship between LVH and CAD with the use of a wide detector CT scanner.Despite representing different hemodynamic loads with different pathophysiologic mechanisms, the body of evidence that supports the prognostic value of the LV geometric pattern beyond LV mass is small, less clear, and sometimes contradictory , 34, 35.Koren et al. first reported the prognostic value of the LV geometric pattern in patients with uncomplicated essential hypertension. The mortality rate over a follow-up period of 10 years was highest in patients with concentric LVH, followed by patients with eccentric hypertrophy and concentric remodeling  [Verdecchia et al. confirmed the adverse prognosis of concentric remodeling in 694 hypertensive patients, even after adjustment for several covariates  . One yeaIn the Framingham Heart Study, three thousand two hundred and sixteen Caucasian population sample had been investigated and followed up for 8 years. The outcome events were incident cardiovascular disease and death. The event rates were greatest in the concentric LVH group and lowest in the group with normal geometric pattern in both genders. However, this association eroded after adjustment for the LV mass .The LIFE echo sub-study investigated nine hundred and sixty-three patients with a mean age of 66 years. One hundred and forty-nine patients had CAD and eight hundred and fourteen did not. The definition of CAD in this study was clinical, history of angina pectoris, myocardial infarction, or electrocardiographic evidence of myocardial infarction. This definition may underestimate the true prevalence of CAD. This study found that the prevalence of eccentric hypertrophy was significantly higher in patients with CAD .Ghali et al. investigated nine hundred and eighty-eight predominantly African American hypertensive patients. The definition of CAD was the presence of at least one vessel with seventy percent diameter narrowing or more by conventional coronary angiography in multiple projections. They were followed up for a mean of nine years. They found that all-cause mortality increased progressively with different LV geometric patterns . Cardiac deaths increased progressively from eccentric to concentric hypertrophy. The adjusted relative risk and 95% confidence of interval of cardiac death were significantly increased in patients with concentric hypertrophy (RR 2.21 to 297 for patients with and without CAD respectively). Patients with eccentric hypertrophy showed a moderate increase in cardiac death (RR 1.3 to 2.87 for patients with and without CAD respectively). Of note, concentric remodeling was not associated with an increase in the relative risk of cardiac death  .Altunkan et al. found that significantly more patients with LV concentric hypertrophy had a positive CAC (57% of the patients in this group) compared to other LV geometric patterns. There was no significant difference in the number of CAC-positive patients among the other groups . In addition, the patient in the concentric hypertrophy group shows an average coronary calcium score (315 ± 761) that is significantly higher than other groups .P-value of less than 0.05. Patients with eccentric hypertrophy show significantly higher SS than patients with concentric remodeling and normal geometry. Patients with concentric remodeling and normal geometry showed similar SS. Of note, concentric LV hypertrophy was the most important independent predictor of SS by regression analysis [Uçar et al. studied two hundred and fifty hypertensive patients who underwent invasive coronary angiography. Coronary angiography was performed to investigate suspected ischemic heart disease based on clinical indications. The cumulative SYNTAX score (SS) was calculated to show the complexity and extent of CAD. They found that patients with concentric hypertrophy show the highest SS compared to other groups with a analysis .The previously mentioned studies investigated different types of populations with different study designs. The outcomes were all-cause mortality, cardiovascular mortality, or coronary artery disease. The extent of CAD was used as a surrogate for increased cardiovascular mortality. In the previous studies, multiple methods were used for CAD assessment; clinical, non-invasive , or invasive coronary angiography. There were also limitations regarding the methodology, the small number of patients in each LV geometric pattern, and the low? number of outcome events.In our study, patients with high CAD-RADS showed a significantly higher percentage of abnormal LV geometric patterns (concentric and eccentric hypertrophy represent 65% of this group) while patients with low CAD-RADS showed a higher percentage of normal and concentric remodeling patterns (about 60% of this group). Patients with normal LV geometry is the predominant pattern in patients with low CAD-RADS (about one-third) and is the least predominant pattern (about 15%) in those with high CAD-RADS.P = 0.002). LV concentric hypertrophy is the most important predictor of high CAD-RADS  followed by eccentric hypertrophy  and lastly concentric remodeling . There was no significant difference in the LV mass index between the LV concentric hypertrophy group and the LV eccentric hypertrophy group which confirms the independent role of LV concentric hypertrophy in predicting high CAD-RADS. The weak correlation between LV mass index and relative wall thickness emphasizes the independent adverse prognostic value of concentric remodeling in patients with lower LV mass index .Among septal wall thickness, LV mass index, and LV geometry, LV geometric pattern was the only independent predictor of the high CAD-RADS  cannot be used for routine assessment of the LV mass due to the risk of radiation, cost, and availabilityThe effect of patient gender could not be addressed in our study.Dividing the patients into four LV geometric patterns and separating them based on CAD-RADS led to a small number in each group. Therefore, a larger number of patients in each group is needed to strengthen our results.Abnormal LV geometric pattern (concentric and eccentric hypertrophy) is associated with high CAD-RADS. Among septal wall thickness, LV mass index, and LV geometry, the LV geometric pattern is the only independent predictor of high CAD-RADS. LV concentric hypertrophy is the most important predictor of high CAD-RADS, followed by eccentric hypertrophy then concentric remodeling. Therefore, assessment of the LV geometric pattern with the use of a wide scanner CT can improve the risk stratification of patients with hypertension.


Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies.MVP patients with indication for surgery due to severe mitral regurgitation (n=19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE). CMR T1 mapping was performed on 21 healthy volunteers as controls. LV inferobasal myocardial biopsies were obtained in MVP patients and compared to CMR findings.MVP patients  had a dark-appearance of the PM with higher native T1 and extracellular volume (ECV) values compared with healthy volunteers . Seventeen MVP patients (89.5%) had fibrosis by biopsy. BB-LGE+ in LV and PM was identified in 5 (26.3%) patients, while DB-LGE+ was observed in LV in 9 (47.4%) and in PM in 15 (78.9%) patients. DB-LGE+ in PM was the only technique that showed no difference with detection of LV fibrosis by biopsy. Posteromedial PM was more frequently affected than the anterolateral  and correlated with biopsy-proven LV fibrosis .CMR imaging in MVP patients referred for surgery shows a dark-appearance of the PM with higher T1 and ECV values compared with healthy volunteers. The presence of a positive DB-LGE at the posteromedial PM by CMR may serve as a better predictor of biopsy-proven LV inferobasal fibrosis than conventional CMR techniques. Mitral valve prolapse (MVP) is the most common valvular heart disease in high-income countries with a prevalence of 2–3% . MVP mayIn MVP patients, regional myocardial fibrosis, mainly in the basal inferolateral LV wall  and at the level of the papillary muscles (PM), has been demonstrated –6. This While conventional “bright-blood” LGE (BB-LGE) has been commonly used to detect PM fibrosis in MVP patients , 12–14, Hence, the aims of this prospective study involving MVP patients referred for MV surgery due to severe MR are: 1) to perform a comprehensive tissue characterization of the PM on CMR using healthy individuals as reference group for CMR T1 mapping-derived measurements; 2) to evaluate the diagnostic accuracy of conventional and DB-LGE compared to the results of intraoperative LV myocardial biopsy; and 3) to analyze the association between histological quantification of LV fibrosis and the comprehensive tissue characterization of the PM on CMR. We hypothesize that CMR tissue characterization of PM increases the identification of myocardial fibrosis in MVP patients as determined by myocardial biopsy.Patients were prospectively enrolled in the study between March 2020 and February 2022. The study was conducted in accordance with the Declaration of Helsinki, and was approved by the local research ethics committee (450–18-ek). All subjects gave written informed consent prior to study initiation. Patients with MVP referred for MV surgery were included in the analysis. Screening and assessment of MVP and MR severity were performed using echocardiography according to standard guidelines  was performed using standard commercially available ultrasound machines equipped with 2.25–4.25 MHz transducers. Evaluation of MVP was carried out by one cardiologist, expert in echocardiography and valvular heart diseases, blinded to the results of CMR exams. TTE was acquired using standard views, and Doppler measurements were evaluated as the average of three cycles. Color Doppler interrogation of the MR jet was performed in multiple views. A multimodal approach was used to determine MR severity, in concordance with recent guidelines , 21.All CMR examinations were performed on a dedicated 1.5 Tesla magnetic resonance scanner  using a 28-element array coil. Image data acquisition  adhered to current recommendations . In briePapillary muscles signal (dark-appearance). For the measurement of PM signal, a mid-ventricular short-axis cine SSFP image in end-systolic phase was selected as it allowed for a better visualization of both PM. The PM signal was visually categorized as “dark- appearance” or “normal PM” when compared with LV myocardium, and quantified using the signal intensity ratio as previously described  in the same three long-axis and short-axis views used for cine imaging . All LGE images were acquired during breath-holding, and dark-blood was acquired as the last sequence of each CMR study.Images were evaluated offi ine for the presence (LGE+) or absence (LGE-) of LGE in LV and both PM, LV pattern , and regional distribution of LGE areas using a standardized myocardial 17-segment model.T1 and extracellular volume measurements. An ECG-gated modified Look-Locker inversion (MOLLI) sequence with SSFP image readout was acquired at a basal, mid, and apical LV short-axis geometry pre- and 15 min post-contrast, making efforts to obtain the maximal myocardial mass of PM. Native T1 and ECV values were determined for the 16 LV segments of the short axis and separately also for both PM: anterolateral  and posteromedial (PMpm).Post-processing was carried out offi ine  with all readers fully blinded to clinical and echocardiographic data. T1-mapping, BB-LGE and DB-LGE sequences were analyzed by a cardiologist (RS) with over 7 years of experience in CMR imaging, separated and in random order at least 4 weeks apart from initial acquisitions, and blinded to the general imaging and histological data. In case of uncertainty, consensus was provided by a second level III observer (CJ).LV biopsies were obtained from each patient from the inferobasal LV wall using a surgical rongeur under thoracoscopic guidance. The biopsies were fixed in 4% formaldehyde/phosphate-buffered saline and embedded in paraffi n before cutting 3 μm sections. Histopathology and immunohistochemistry methods are described in the Appendix . Briefly, Masson-Goldner’s trichrome staining kit  was used to stain connective tissue and collagen I was stained by immunohistochemistry using the mouse anti-collagen I antibody .Documentation and quantification of connective tissue and collagen were performed using AxioPlan 2 microscope, Axio Cam camera system, AxioVision Release 4.8.2 SP3 software , and Adobe Photoshop CS2 software . Fibrosis burden was quantified as connective tissue volume fraction (CVF) and a normal upper limit of 10.9%, as previously reported, was used to dichotomize into normal/abnormal .th to 75th percentile) for non-normally distributed continuous variables, or frequency and percentages for categorical variables. Statistical differences between groups were assessed using Student’s t-test for continuous variables or Fisher’s exact test for categorical variables. Differences in the detection of fibrosis between histology, conventional bright-blood and dark-blood modalities were evaluated using McNemar’s test. Spearman or Pearson (for linear relationships) coeffi cient was used to assess correlations between variables. Two-tailed p-values <0.05 were considered statistically significant. Analyses were performed using SPSS software .Normal distribution was assessed with Q-Q plots and Shapiro-Wilk test. Data are presented as mean and standard deviations for normally distributed continuous variables, median and interquartile range  were enrolled in the study and underwent CMR imaging preoperatively and myocardial biopsy during MV surgery. A group of 21 healthy volunteers  also underwent a 1.5T CMR scan including T1 mapping of the PM for comparison. CMR T1 mapping analysis was successfully performed in all PM of MVP patients and in 90.5 % of the PM in the control group .Demographic and baseline patient characteristics are presented in In the CMR derived SAX cine, MVP patients had a significant lower PM/LV signal ratio compared with healthy volunteers  showing LV myocardial LGE was present in 5 of 19 MVP subjects by BB-LGE and in 9 subjects by DB-LGE . By BB-LGE intra-myocardial pattern was present in 2 cases and a sub-endocardial pattern in 3 cases, with location in basal inferior (n = 3), basal inferolateral (n = 3), basal anterolateral (n = 1), mid inferoseptal (n = 1), mid inferior (n = 2), or mid inferolateral (n = 3) LV segments. By DB-LGE intra-myocardial pattern was present in 2 cases and a sub-endocardial pattern in 7 cases, located in the basal inferoseptal (n = 1), basal inferior (n = 3), basal inferolateral (n = 4), basal anterolateral (n = 1), mid inferoseptal (n = 2), mid inferior (n = 5), mid inferolateral (n = 4), apical inferior (n = 1), or apical lateral (n = 1) LV segments. There was insuffi cient evidence to support differences in the numbers of LV segments detected by each LGE methods.LGE was detected in the PM in 5 subjects by BB-LGE and in 15 subjects by DB-LGE . All cases with BB-LGE+ at the level of the PM were confirmed on DB-LGE. Overall, fibrosis was found more frequently in the PMpm than the PMal .In all MVP patients, a myocardial biopsy was obtained from the inferobasal LV region. The extent of histological fibrosis was quantifed by CVF with a mean value of 25.1 ±16% and a collagen I fraction of 13.7 ±11%. In the entire cohort, a total of 17 MVP patients (89.5 %) had an abnormal histological finding (CVF >10.9 %). There were no sex-related differences in fibrosis .Compared with histologic findings, only PM DB-LGE+ showed no statistical differences in detection of fibrosis  only MVP patients showed a dark-appearance of the PM on CMR cine compared with healthy volunteers, with higher native T1 and ECV values at the level of the LV myocardium and even more pronounced at the level of the PM; 2) with the use of a DB-LGE technique there was only a tendency to detect a higher prevalence of LGE within LV myocardium, but a significantly higher rate of LGE detection at the level of the PM when compared with BB-LGE; 3) compared with histology, only PM DB-LGE showed no statistical differences in detection of fibrosis; 4) the presence of DB-LGE + at the PMpm correlated with biopsy-proven fibrosis of the inferobasal LV wall, while other CMR sequences did not; and 5) there was an inverse correlation between extent of fibrosis and CMR derived LV volumes and MR severity.Scatteia and coworkers have previously described a dark-appearance of the PM on standard short axis cine CMR images as a typical feature of MVP, which was not linked to myocardial fibrosis by LGE or to the occurrence of malignant arrhythmias . In accoWhile altered T1 mapping parameters at the level of the LV in MVP patients , 19 and With BB-LGE, we detected LV myocardial late contrast uptake in 5/19 patients 26%) with MVP and severe MR, similar to previous studies demonstrating  LV myocardial LGE in around 25 to 37% of MVP patients % with MV, 26, 27,We could not find a significant difference between BB-LGE and DB-LGE in detecting LV myocardial surrogate of fibrosis . However, we observed a higher prevalence of LGE + at the level of the PM with DB-LGE compared with BB-LGE . Previous studies using conventional BB-LGE technique reported PM LGE in around 7 to 36% , 15, 26.Interestingly, we found that the PMpm was affected more frequently than the PMal and we describe for the first time a significant correlation between DB-LGE + at the PMpm and fibrosis by biopsy of the inferobasal LV wall. Previous studies demonstrated less contraction or higher stretch of the PM in MVP patients. In a CMWe did not find a correlation between LV LGE and inferobasal LV myocardial biopsy. This is in line with findings by Liu and colleagues , and migFinally, we found an inverse correlation between CVF by biopsy and CMR LV volumes and MR severity . AlthougRegionalized inferobasal LV and PM fibrosis have been identified as an arrhythmogenic substrate and plausible explanation for SCD even in asymptomatic patients with hemodynamically uncomplicated MVP , 34, 35.The present study has some limitations. First, the study was not powered or designed to assess the relationship of the results with MVP subtypes or with clinical characteristics like ventricular arrhythmias. Second, the results should be interpreted with caution since a small sample size could lead to type II errors and correlations could not be adjusted for type I errors. Finally, histological findings might be limited by sampling error. Thus, further studies utilizing a longitudinal design are required to better evaluate the influence of MVP subtypes and disease progression on unfavorable myocardial structural changes and cardiac arrhythmias.CMR derived tissue characterization of the PM in MVP patients referred for MV surgery due to severe MR, demonstrates a characteristic CMR pattern of the PM with dark-appearance and higher T1 and ECV values compared with healthy volunteers and a possible better prediction of biopsy-proven LV inferobasal fibrosis when a positive DB-LGE at the posteromedial PM (PMpm) is present.


The ferumoxytol-enhanced 4D MR angiography with MUSIC (Multiphase Steady State Imaging with Contrast) technique provides a single data set that captures dynamic cardiovascular anatomy and ventricular function at the same time. Homogeneous opacification of all cardiovascular structures within the imaging volume allows full sequential segmental approach to the congenital heart diseases without any blind spots. The complex systemic and pulmonary venous anatomy is particularly well captured in the MUSIC. Cinematographic display of multiplanar sectional and 3D volume images is helpful in the morphological identification of the cardiac chambers, the assessment of the dynamic nature of the ventricular outflow tracts, and the assessment of the coronary arterial origins and courses. It iThe contrast-enhanced magnetic resonance (MR) technique known as 4D MUSIC (Multiphase Steady State Imaging with Contrast) acquires data continuously over several minutes during uninterrupted positive pressure ventilation, offering near-perfect respiratory gating . When usOwing to its high T1 relaxivity and long intra-vascular half-life (approximately 15 h), ferumoxytol supports homogeneous opacification of all cardiac chambers and vascular structures for a prolonged period of 3D MR data acquisition that is typically performed with electrocardiographic (ECG) gating and respiration navigation. MUSIC images are acquired with isotropic spatial resolution for accurate 2D and 3D reformation. Maximum intensity projection (MIP) and volume rendering (VR) can be used to view images in an infinite number of imaging planes or views for both anatomical and functional assessment, without restrictions on orientation or view angle. While 4D MUSIC with ferumoxytol allows high quality dynamic 3D visualization of the beating heart, it also allows 2D cine planar reformation that is analogous to prescription of conventional 2D cine imaging planes. This property shifts the time and labor from the acquisition phase in a scan room to the post-processing phase in a reading room. Therefore, it results in shortened examination times relative to traditional approaches but with higher resolution and without repeated breath holding. Furthermore, the acquisition protocol is independent of anatomic and structural complexity, and the same protocol applies to all patients. Therefore, the total examination time for 4D MUSIC MR is potentially much shorter than the time required for conventional MR approaches that rely on sequential 2D breath-held cine and single-phase contrast-enhanced MR angiography.Rotating Cartesian k-space (ROCK) MUSIC is a further development of the MUSIC technique that does not require external signals for respiratory and cardiac gating . Another4D MUSIC MR is well suited for sequential segmental approach to complex congenital heart diseases because of its wide field of view without any blind spots, homogeneous opacification of all cardiovascular structures, and dynamic demonstration of the cardiovascular anatomy as well as function. This imaging essay illustrates the utility and major advantages of 4D MUSIC MR for the sequential segmental approach to CHD using select case examples with 2.2.1.Situs refers to the pattern of arrangement of the solid organs relative to the midline or sagittal plane of the body , 18. To Abdominal and bronchopulmonary situs is easy to determine by observing the liver, stomach, spleen, airways and pulmonary arterial branches at cross-sectional imaging , Case 1.2.2.Juxtaposition of the atrial appendages on either side of the arterial trunks is uncommon and usually occurs as part and parcel of complex malformation , 22. Jux2.3.Clear definition of the venous connections to the atria is particularly important in patients with heterotaxy as rerouting of the systemic and pulmonary venous circulation is required not only for biventricular but also for univentricular repair. From the imaging perspective, 3D imaging with a wide field of view is helpful for the assessment of the venous abnormalities. MR angiography is certainly advantageous over CT angiography as proper contrast enhancement of both systemic and pulmonary venous structures is a difficult task at CT angiography.The most common is bilateral superior venae cavae with or without a bridging vein , Case 4.Heterotaxy with left isomerism is often associated with extrahepatic portosystemic shunt , 30. As 2.4.With rare exceptions, the ventricular mass consists of two ventricles, one morphologically right and the other morphologically left. When the two ventricles are well developed, the ventricular morphology can easily be identified by using the criteria including the overall shape of the ventricle, the trabeculation pattern, the presence or absence of the moderator band and the level of attachment of the atrioventricular valve to the septum , 31, 32.The relationship between the two ventricles is classified into D-loop (the right ventricle on the right side of the left ventricle) and L-loop (the right ventricle on the left side of the left ventricle) ventricular relationships. In the majority of cases, the right-left relationship is described by referencing the right-left coordinates of the body . DespiteOnce the atrial and ventricular relationship are determined, the atrioventricular connection is assessed. The most helpful for assessment of the atrioventricular connections is cine display of the thin MIP and VR images. In the vast majority of cases, the two atrioventricular connection axes are parallel and the type of atrioventricular connection is predictive of the relationship of the underlying ventricles. Therefore, the atrioventricular connections are usually readily appreciated in 4-chamber plane regardless of whether there are biventricular or univentricular atrioventricular connections , Case 6.2.5.The great arterial relationship is determined by describing the position of the aortic root and valve in relation to the pulmonary arterial trunk and valve. The ventriculoarterial connection is unequivocally definable when the ventricular septum is intact. When there is a ventricular septal defect underneath one or both arterial valves, the type of ventriculoarterial connection can be controversial as the ventricular septum is not uniformly oriented in relation to the arterial valves . Althoug2.6.The ventricular outflow tract obstruction can be a fixed lesion but, more commonly, a dynamic lesion. The dynamic ventricular outflow tract obstruction cannot be accurately assessed using static imaging technique. It is also difficult to clearly demonstrate the exact severity of dynamic narrowing at 2D cine imaging as the region of the interest moves in and out of the imaging plane during the cardiac cycle. 4D VR imaging is particularly helpful as the dynamic nature of the obstruction can be observed throughout the cardiac cycle  minutes. Homogeneous opacification of all cardiovascular structures within the imaging volume allows full sequential segmental approach to the congenital heart diseases without any blind spots. The complex systemic and pulmonary venous anatomy is particularly well captured in 4D MUSIC imaging when compared to other conventional techniques. Cinematographic display of multiplanar sectional and 3D volume images is helpful in the morphological identification of the cardiac chambers, the assessment of the dynamic nature of the ventricular outflow tracts, and the assessment of the coronary arterial origins and courses. Because acquisition takes several minutes, the image quality relies heavily on successful mitigation of cardiac and respiratory motion artifact. To date, limited access to ferumoxytol for off-label diagnostic use, as well as its high cost, have posed obstacles to the more widespread utilization of the 4D MUSIC technique. However, the hope is that these limitations will subside as generic versions become available within and beyond the U.S.


Stronger relationships were observed with NYHA class, 6MWT, and BNP . There were moderately strong correlations with LVEF and other whole-heart myocardial mechanics or morphometrics. Moreover, LVEF with global regurgitation volume (GRV) and right ventricle free wall longitudinal strain (RVFWLS) were the most usually detected parameters in multivariate analysis to be associated with changes in HF prognostic factors. Conclusions: in NIDCM patients, the main prognostic factors of HF are correlated with whole-heart myocardial mechanics and morphometrics. However, LVEF, GRV, and RVFWLS are the most usually found 2D echocardiographic factors associated with changes in HF prognostic factors.Background: there are many prognostic factors of heart failure (HF) based on their evaluation from imaging, to laboratory tests. In clinical practice, it is crucial to use widely available, cheap, and easy-to-use prognostic factors, such as left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, 6 min walk test (6MWT), B-type natriuretic peptide (BNP), etc. We sought to evaluate the relationships between whole-heart myocardial mechanics and cardiac morphometrics with the main commonly used prognostic factors of HF in patients with non-ischemic dilated cardiomyopathy (NIDCM). Methods and results: two-dimensional (2D) echocardiography for myocardial mechanics  and cardiac morphometric (diameters and volumes of both atria and ventricles) parameters were performed, and the HF main traditional prognostic factors were identified. We assessed 109 patients  with newly diagnosed NIDCM. Myocardial mechanics and morphometrics were weakly correlated with the patient’s age, gender, and smoking (R = 0.2,  Dilated cardiomyopathy (DCM) is a myocardial disease that causes cardiac dysfunction and HF. Patients with NIDCM have dilatation and systolic dysfunction of left or both ventricles, without coronary artery disease and abnormal loading conditions ,2,3,4. DTwo-dimensional echocardiography is the first-line imaging test in the assessment of patients with DCM. The evaluation of myocardial mechanics by speckle-tracking echocardiography (STE) in NIDCM plays an important role in HF, and may add additional value to improve risk stratification with other clinical markers or biomarkers . MyocardMore data are needed to evaluate which whole-heart myocardial mechanics and cardiac morphometric parameters are associated with the main prognostic factors of HF. In this context, our study objective was to evaluate the potential relationships between myocardial mechanics and morphometric parameters of both ventricles and atria with the main prognostic factors of HF, in a prospective cohort of NIDCM patients.2), tachycardia-induced HF , peripartum cardiomyopathy, with the implantation of an intra-cardiac defibrillator or cardiac resynchronization therapy, in the case of alcohol or drug abuse, and under the age of 18, were excluded from the study.The patients were studied at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics. DCM definition was established according to the current criteria as left ventricle (LV) or both ventricle dilatation and systolic dysfunction (LVEF ≤ 50%), without coronary artery disease (CAD) . CAD wasThe initial examination of the patients was based on a detailed medical history , physical examination, laboratory tests, 12-lead baseline electrocardiogram, 2D transthoracic echocardiography, and Holter monitoring .The study received institutional ethical approval and all patients provided written informed consent.Global regurgitation volumeTwo-dimensional echocardiography was performed using Philips “EPIQ 7 ultrasound system by one experienced echocardiographer, and stored images were analyzed offline . Echocardiography was performed during the first contact with the patient within 24 h of the start of hospitalization, or if it was an outpatient, during the first visit.Left ventricleThe GRV was expressed as the sum of mitral and tricuspid regurgitant volumes, using the proximal flow convergence method. Three consecutive beats were average in the sinus rhythm and five consecutive beats in atrial fibrillation  Figure .Left veThe LV end-systolic and end-diastolic diameters were obtained from parasternal LV long-axis view, and measured below the level of the mitral valve leaflet tips. LV volumes were obtained from the apical four- and two-chamber views. The volumes were calculated by the biplane method of disk summation. LVEF was calculated by the Simpson’s biplane method .Right ventricleFor the evaluation of LV global longitudinal strain (LVGLS), apical four-chamber, two-chamber, and long-axis views were obtained. LV global circumferential strain (LVGCS) and global radial strain (LVGRS) were calculated by endocardial tracing in the basal, middle, and apical levels of LV short-axis views .Right vThe right and left atriaThe right ventricular (RV) dimensions were estimated from an RV-focused apical four-chamber view . Global The left atrial (LA) size was measured at the end of the LV systole (when the LA chamber is at its greatest diameter), and the LA volume was assessed in apical four-and two-chamber views, using the disk summation algorithm. The right atrial (RA) volume was measured using a single-view area-length technique . The sin2 was calculated. Multivariate regression analysis was used to determine which myocardial strain and morphometric parameter were most associated with prognostic factors of HF. First, for the selection of myocardial deformation and morphometric values, univariate analysis was performed. Univariate analysis was followed by stepwise multivariate linear regression and standardized coefficients (ß), and 95% confidence intervals (CI) were obtained. The data were analyzed using SPSS version 22 . A p-value < 0.05 was considered significant.Patients’ characteristics were provided by n (%), or the means± standard deviations (SD). The Kolmogorov-Smirnov test was used to evaluate the normality distribution of the data. Pearson’s correlation coefficient was used to evaluate correlations between prognostic factors of HF with myocardial mechanics and morphometrics. If one variable was categorical and one was continuous, the point-biserial coefficient of correlation RTwenty-five patients were randomly selected to evaluate the intra-observer variability , which showed good agreement, with the small bias of 0.7 ± 2.7%.The patients with NIDCM had dilated LV and both atria. It was evaluated by measurement of the diameters and volumes of all chambers. A significant reduction of LVEF was detected (27.7 ± 8.7). Moreover, all myocardial mechanical parameters of both ventricles and atria were reduced. There were no cut-off limits for GRV severity; however, our study revealed that the mean GRV was increased (49.5 ± 32.8) .p < 0.05). There were weak–moderate correlations between systolic blood pressure and the volumes of LV and GRV. AF was related to changes in LA mechanics and LA volume index (p < 0.001). Stronger relationships were observed between myocardial mechanics and morphometrics with NYHA class, 6MWT, and BNP . There were moderate–strong correlations with LVEF and other whole-heart myocardial mechanics or morphometrics.p = 0.013). NYHA class was associated with changes in GRV (p = 0.018), LASr (p = 0.006), LVEF (p < 0.001), and RVFWLS (p = 0.049). A similar tendency was noticed in correlation with 6MWT. BNP concentration was most associated with LVEF. The systolic LV function correlated well with all mechanical and morphometric parameters; however, the strongest correlations were with LVGLS, LVGRS, GRV, and LASr.The systolic blood pressure, NYHA class, 6MWT, BNP, and LVEF were included in multivariate regression analysis . The resOur study encourages simple non-invasive clinical tools to evaluate the relationships between the main prognostic factors of HF and whole-heart myocardial mechanics and morphometrics. The diagnosis of NIDCM includes various diagnostic methods, but echocardiography remains the cornerstone. This study focused on the whole-heart myocardial mechanistic and geometric insights of NIDCM for a better understanding of pathophysiology relationships with prognostic factors of HF, with the purpose of showing some possible new imaging markers through echocardiography.The findings of this study can be summarized as follows: (1) in patients with NIDCM, the prognostic factors of HF are correlated with the whole-heart myocardial mechanics and cardiac morphometric parameters; (2) LVEF, GRV, and RVFWLS are the most usually found 2D echocardiographic factors associated with changes of HF prognostic factors.Prognostic factors of HF should be evaluated early ,16. It iMany studies analyzed the independent predictors of HF severity and outcomes ,19. ProgDespite age being one of the strongest parameters affecting mortality risk in HF ,32,33, tFocusing on either valve separately, it does not reflect on the global hemodynamic burden arising from concomitant functional regurgitation of the mitral and tricuspid valves . Bartko RV dysfunction has a known crucial role in functional capacity and prognosis in HF, regardless of the degree of LV dysfunction. The issue of which factors contribute to RV dysfunction in HF is still unclear. In our study, patients with NIDCM had decreased mechanical strain parameters of RV. It was found that RVFWLS is well correlated with NYHA class and 6MWT .The patient’s functional status , instrumental and laboratory tests were important in daily clinical practice to follow the dynamics of the patient’s disease, the effectiveness of the treatment and to determine the indications for the implantable devices. This monitoring is important for a timely referral to specialized HF centers. Echocardiography is the most important non-invasive instrumental tool in the care of HF patients. The results of this study showed that the main prognostic factors of HF correlate with whole-heart myocardial mechanics and morphometric parameters. Regardless of LVEF, GRV and RVFWLS were the other most usually found 2D echocardiographic factors associated with changes in HF prognostic factors. Based on this, this might aid additional values in the clinicians’ decision-making, and the reclassification of patients suitable for interventional treatment or assessing the effectiveness of medical treatment.There are several limitations to our study. This is a single-center experience and is related to the small sample size. Additionally, our study group may not represent all patients with NIDCM. We evaluated only the main and most common prognostic factors of HF in clinical practice. Our study revealed weak–moderate correlations between prognostic factors of HF and myocardial mechanics or morphometrics of both ventricles and atria. However, these correlations were statistically significant. Further research is needed to confirm our findings. The quantitative assessment of the whole-heart structure and function, especially the assessment of RV and right atrium, is challenging. However, the limited access to the technology in daily practice and common contraindications in the presence of implanted devices make other technologies, especially cardiac magnetic resonance imaging, less suitable than 2D echocardiography for studies involving large cohorts of patients. Based on this, we presented only 2D echocardiography for the assessment of myocardial mechanics and morphometrics.In NIDCM patients, the main prognostic factors of HF are related to the whole-heart myocardial mechanics and morphometrics. Combined with LVEF, GRV and RVFWLS may add additional clinical value to patients selected for advanced treatment or assessing the effectiveness of medical treatment.


Right ventricular (RV) aneurysm is a very rare ventricular lesion. An aneurysm is formed mainly as a complication of myocardial infarction (MI). As an RV aneurysm is a potentially life-threatening occurrence, its appropriate diagnosis is of great significance. However, right-sided heart diseases, especially RV aneurysms, have been neglected for years. Recent studies in the literature have elucidated the role of the right side of the heart in patients’ prognosis and response to treatment. However, RV aneurysm has been scarcely investigated, and most of the attention has been given to the left ventricular aneurysm in patients with ischemic heart diseases (IHD). Herein, we investigated a total of 625 patients with IHD referred for two-dimensional transthoracic echocardiography (2D TTE), among whom 18 were diagnosed with RV aneurysms through precise examination of several TTE views. The characteristics of these cases, including demographics, medical history, and results of cardiac tests (which the patients underwent previously), were recorded and presented. This study emphasized the importance of performing a meticulous 2D TTE evaluation and a thorough examination of different views by an expert echocardiographer, with special attention to the presence of an RV aneurysm in a patient suffering from IHD who presented either with acute coronary syndrome, including MI, or chronic IHD. The scarcity of information, especially in terms of complications and the most appropriate diagnostic methods, calls for further studies in this regard. Cardiovascular diseases (CVDs), which include ischemic heart disease (IHD), heart failure (HF), stroke, and peripheral arterial disease, are the leading causes of global mortality, responsible for 17.8 million deaths and 35.6 million disabilities worldwide in 2017 .Ventricular aneurysms are diastolic as well as systolic outpouchings of the ventricle containing endocardium, epicardium, and thin-wall non-contractile scarred myocardium, which mainly develop in the setting of a full-thickness infarct, replaced by fibrous tissue because of MI. They occur most frequently in the left ventricle (LV) apical, anterior, and anteroseptal walls, and rarely in inferior-posterior or lateral walls . Other cOther causes of right ventricle (RV) aneurysms, such as congenital, traumatic, and right arrhythmogenic ventricular cardiomyopathy (ARVC), have also been reported ,9,10 andAlthough electrocardiography (ECG) changes in favor of old infarction or ischemia usually remain for long periods and would be helpful when detecting the presence of LV aneurysms with high probable diagnostic accuracy , the chaFrom June 2020 to August 2021, a total of 625 patients with IHD were referred to the echocardiography department at our center for 2D TTE by a European accredited cardiologist echocardiographer. The echocardiographer examined several views, namely parasternal long axis, parasternal short axis (LV papillary muscle level and AV level), RV inflow, apical four and five chambers, RV focus and modified, and subcostal views. The diagnoses were confirmed by another expert cardiologist echocardiographer, who reviewed all recorded movies. The performance of 2D TTE, with special attention to RV, identified a total of 18 cases of RV aneurysms during this period.The characteristics of the cases, including demographics, medical history, and results of cardiac tests that the patients had undergone previously were recorded and are presented in n = 12) underwent coronary artery bypass graft (CABG) in the past, and another was indicated but refused to undergo CABG; 11 patients underwent percutaneous coronary intervention (PCI); three patients underwent the PCI procedure twice.The patients had a wide range of underlying diseases, including coronary artery disease , chronic kidney disease , hyperlipidemia (8 patients), hypertension (10 patients), and type II diabetes mellitus ; however, only 2 patients reported no underlying diseases. Most patients  and one patient had single-vessel disease (case #12). Right coronary artery (RCA) cut proximal to first acute marginal branch was observed in all except three patients . LV systolic dysfunction was observed in all patients: nine severe dysfunctions (LVEF < 30%), five moderate (LVEF: 30–39%), and four mild (LVEF: 40–49%). Ten patients had LV aneurysms, four with clots. Thirteen patients had severe RV systolic dysfunction, while four had moderate RV systolic dysfunction. Three patients had RV aneurysms with a clot, while the rest had no clots. As the patients were referred to our center for 2D TTE, we could not follow them up and had no information on the patients’ conditions after TTE. The important imaging findings, including 2D TTE in cases 1, 3, 12, 13, 16, and 17 are presented in n = 12) had undergone CABG, the procedure was performed years prior (CABG was performed a week prior in only one case) and traumatic origin is not presumed in these patients.Identification of 18 cases of RV aneurysms using 2D TTE among 625 patients with a positive history of IHD in the present study suggests that RV aneurysms are not very uncommon in this group of patients, although the present study was not an epidemiological study and cannot be used to make a conclusion on the frequency or rate of the disease. A series published in 1991 reported diagnoses of 12 cases of RV aneurysm among 137 patients with acute MI (8.75%) who were diagnosed using radionuclide angiocardiography . This frOther etiologies have also been associated with RV aneurysms, and there are frequent reports of RV aneurysms in different settings, including cardiomyopathy , traumatGenerally speaking, when MI is discussed in the clinical setting, LV is the focus of attention during clinical and paraclinical cardiac examinations, including ECG and TTE, which results in a lower diagnosis of RV pathologies. Nevertheless, as recent evidence has emphasized, RV MI is present in more than half of patients with LV MI, resulting in poorer patient prognosis and more major cardiac events . PresumaBecause of the scant evidence on MI-related RV aneurysms, the complications and adverse events associated with this condition are not clearly defined but may be similar to those associated with LV aneurysms, during which the thin-walled ventricle cannot contract appropriately during systole (against the pulmonary artery) and herniates outward (out pouch). The paradox contractility and dyskinesia caused by the aneurysm result in malignant arrhythmia, HF, and sudden cardiac death . ThrombuAll in all, right ventricular aneurysm is potentially a very rare complication of MI, and the few case reports available in the literature have not determined the exact complications and prognosis, nor the most appropriate diagnostic modalities and treatment strategies. As ventricular aneurysms can be fatal, appropriate diagnosis and treatment are necessary. It is important to keep in mind that RV aneurysm is not a very rare condition and should not be neglected in the echo labs, as well as in the current literature. We believe that diagnosis of RV aneurysm is possible using the currently available and cost-effective cardiac imaging performed routinely in patients with a history of IHD. Therefore, cardiologists should pay greater attention to the hallmarks suggestive of RV aneurysm and train echocardiograph fellows and technicians on this regard as well. Furthermore, prospective research studies are required to accurately determine the incidence rate of RV aneurysm and the most accurate diagnostic method and to suggest the most appropriate treatment strategy.