Cardiac ventricular outpouchings and invaginations are rare structural abnormalities and usually incidental findings during cardiac imaging. A definitive diagnosis is possible through the use of multimodality imaging. A systematic review of the literature was carried out in November 2022 to identify studies regarding ventricular outpouchings and invaginations. The main aim of the review is to summarize knowledge regarding epidemiology, etiology, diagnosis and prognosis of patients with ventricular outpouchings (aneurisms or diverticula) and invaginations (crypts and recesses). Overall, 26 studies published between 2000 and 2020 were included in the review. Diverticula and congenital aneurysms incidence ranges between 0.6 and 4.1%. Myocardial recesses and crypts range between 9% in the general population and up to 25% in patients with hypertrophic cardiomyopathy. The combined use of echocardiography, cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) is useful to establish tissue contractility, fibrosis, extension and relationship with adjacent structures for differential diagnosis of both invaginations and outpouchings. In conclusion, both outpouchings and invaginations are rare entities: a definitive diagnosis may be aided by the use of combining multiple imaging techniques, and the treatment depends both on the lesion-specific risk of complications and on the potential association of some lesions with cardiomyopathy. Cardiac ventricular outpouchings and invaginations are rare structural abnormalities (SA). They are often incidentally diagnosed during cardiac imaging ,2. The dThe effective prognosis after diagnosis of these features is uncertain, especially because of the lack of systematic studies on large samples of individuals.Although it is known, for example, that myocardial crypts are associated with hypertrophic cardiomyopathy and recesses with the presence of left ventricular non-compaction, these SA are also frequent in the general population in the absence of any cardiac disease ,5.The diagnosis of both outpouchings and invaginations, especially if they are of small dimensions, can be complex and not sufficiently accurate using echocardiography alone, even though this is still the first diagnostic method used. Multimodality imaging with the addition of cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) to the echocardiographic study alone is the cornerstone to reach a definitive diagnosis . TherefoWe performed a systematic review of literature following the Preferred Reporting Items for Systematic reviews and Meta-Analyses PRISMA,  statemenThe quality of the included studies was tested using pre-specified electronic forms of MINORS criteria .Overall, 683 studies were selected. After an evaluation of records, 17 studies published between 2000 and 2020 were included in the review ,20,21,22Overall, 1998 patients were included in studies regarding ventricular outpouchings and 13,013 in studies regarding ventricular invaginations, of whom 1180 were with confirmed invaginations and 156 with outpouchings, respectively .Data regarding diagnosis of ventricular outpouchings with echocardiography are poor. Epidemiology data are mainly referred to in studies with CCT or CMR made for other reasons. In particular, the prevalence of diverticula range between 0.6% and 4.1% as detected by CCT ,11,12 anThe prevalence of crypts/recesses reported in the literature varies according to criteria and methods used to identify them (some authors used a cut-off of 50% of penetration in the myocardium and others 30%)  [5]. No For both ventricular outpouchings and invaginations, a wide discussion on the main findings of the literature review have been summarized in terms of definitions, epidemiology, etiology, diagnosis, prognosis and treatment in the following paragraph.The most frequent ventricular outpouchings are VD and VA. VA are frequently acquired and associated with coronary artery disease and myocardial infarction and rarely are a part of congenital heart disease . The definitions of VD and VA are not unique in literature : some auThe epidemiology of these ventricular lesions is debated  and in pIn previous series of echocardiographic, autoptic, surgical or cardiac catheterization studies on the prevalence of cardiac outpouchings were very few (0.04–0.26%) . Some auDe Bruecker et al. analyzed 482 CCTs  and founNakazono et al.  analyzedSrichai et al.  screenedAnother study used CMR to define the prevalence of VD: Aquaro et al.  reviewedIn addition, a small case series  describeOhlow et al. reviewed 809 cases of left VD and VA and found that VA were larger and more frequently in the sub-mitral location; VD, instead, were localized in the left ventricular apex and were more frequently associated with cardiac or extracardiac anomalies .The etiology of VD and VA is controversial; the most accepted hypothesis  is that The etiology of non-apical VD and VA  has beenIn right VD, the etiology  of apicaFor the diagnosis of left ventricular outpouchings, echocardiography should be the initial diagnostic tool because it is inexpensive, reproducible and demonstrates localization, relation to adjacent structures and eventual associated congenital heart abnormalities  Figure . HoweverWhen an alteration of the myocardial wall is seen with echocardiography, cardiac computer tomography (CCT) or cardiac magnetic resonance (CMR) should be used to differentiate between invaginations or outpouchings. When the abnormal structure involves the outer profile of the myocardial wall, it is defined ventricular outpouching, otherwise ventricular invagination. When a ventricular outpouching is diagnosed, if the structure is akinetic or dyskinetic with a fibrotic wall and a large neck, it is called an aneurysm, and coronary artery anatomy must be investigated and a CMR performed. If the outpouching has synchronous movements with the ventricular wall, with a narrow neck, and the wall of the lesion contains all myocardial layers, it is is called diverticulum and CCT or CMR must be performed to investigate eventual associated congenital cardiac abnormalities or compression of adjacent structures. When a ventricular invagination is diagnosed, if it involves more than 50% of myocardial wall thickness, it is named a crypt and CMR must be performed to investigate the hypertrophic cardiomyopathy phenotype. Otherwise, if the invagination involves less than 50% of the myocardial wall thickness, it is named recess and CMR must be performed to investigate the left ventricular non-compaction phenotype.CMR is another diagnostic method very accurate in diagnosis, follow-up and differential diagnosis of VD and VA, with the identification of a fibrous wall of VA with late gadolinium enhancement (LGE) . In CMR,2, p = 0.02) and more frequently associated with late enhancement. VA volume, but not location, correlated with left ventricular size (p < 0.0001) and ejection fraction (p < 0.0001).McMahon et al.  analyzedIn clinical practice, most VD are asymptomatic and with good long-term prognosis , but somLeft VA more frequently presents with ventricular arrhythmias than VD  and outpp < 0.00001) .,19.18,19ECG-gated CCT has high spatial and temporal resolution and permits the evaluation of the myocardial wall . The stuProminent trabeculations on the luminal surface and recesses that extend into the myocardial wall may be representative of a pathology defined as left ventricular non compaction (LVNC), a genetic cardiomyopathy transmitted as an autosomal dominant trait. The pathogenesis is like that of crypt formation, and it is related to a defect of embryonic myocardial morphogenesis. There have been two forms described: the isolated LVNC, which occurs in absence of other conditions, and the non-isolated one, when it is associated with other congenital heart diseases ,4.Contrary to crypt identification, the first suspect of LVNC originates from echocardiographic images and the diagnosis is based on the following criteria: presences of numerous trabeculations especially in the mid-ventricular and apical segments; two-layer myocardium with a non-compacted (N) and compacted (C) ratio (N/C) > 2 in the adults and >1.4 in children; and perfusion of intertrabecular spaces demonstrated by color Doppler ,4.CMR has stricter criteria than echocardiography and requires a NC/C ratio > 2.3 in the end-diastolic phase to make a LVNC diagnosis. Furthermore, the presence of increased signal intensity related to the blood flow between the myocardial trabeculae is attributable to LVNC. Subendocardial LGE can be also detected .Like other techniques described, CT is also able to analyze accurately the two layers (compacted and non-compacted) of the LVNC. Melendez-Ramirez et al. proposed a NC/C ratio > 2.2 in at least two segments to diagnose LVNC accurately. CT has the disadvantage of using iodinated contrast medium and is characterized with low sensitivity for the fibrous tissue but can be a good choice for patients with an implanted device or those requiring a coronary artery evaluation ,31.The LVNC has always been considered a rare entity with an adult prevalence < 0.3%; however, studies have demonstrated that echocardiographic criteria can overestimate the LVNC diagnosis, especially in in black individuals and patients with LV dysfunction . ContrasThe prognostic role of crypts was investigated in two major studies and neither recorded an increased risk of major adverse cardiovascular events (MACE) in the affected population compared to the general one ,22. FurtThe high prevalence of crypts in patients with a family history of HCM may represent a marker of sarcomeric mutations—carrier status—before a manifested hypertrophy, and it could be used to select patients that deserve a genetic test or a closer echocardiographic follow-up. In other clinical scenarios, crypt identification does not have clinical significance and does not require additional investigations .Finally, the clinical history of patient with crypts and LVNC varies radically because the first ones have a preserved LV ejection fraction and are generally asymptomatic; the other ones develop a progressive reduction in cardiac function, heart failure (HF) symptoms, arrhythmias and thromboembolic events that might require HF treatments, anticoagulation and ICD implantation .Outpouchings and invaginations are a more frequent incidental finding than previously thought due to the increasing use of CCT and CMR . Diverti


The relative importance of left atrial reservoir strain (LASr) regarding the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology (HFA-PEFF) score, a diagnostic tool for patients with heart failure with preserved ejection fraction (HFpEF), remains unclear. We aimed to identify the relative importance of LASr compared with variables associated with HFpEF and HFA-PEFF scores.Between August 2021 and July 2022, we obtained retrospective data from the participants visiting a single cardiovascular center with subjective symptoms of heart failure, such as dyspnea or chest discomfort. In total, 2,712 participants with sinus rhythm and ejection fraction of more than 50% were enrolled. Multivariable logistic regression analysis, random forest analysis, and supervised machine learning algorithms were performed to identify the relative importance of LASr to the HFA-PEFF score.p < 0.001). Impaired LASr < 25.2% was an independent variable affecting a high HFA-PEFF score with traditional diastolic function parameters and components of the HFA-PEFF diagnostic algorithm. The odds ratio (OR)  for LASr was higher compared to that of left ventricular global longitudinal strain , septal E/e’ , and relative wall thickness . LASr was also a relatively more important variable in estimating a high HFA-PEFF score than TR-Vmax, septal E/e’, septal e’, left ventricular mass index, and relative wall thickness, the major echocardiographic components of the HFA-PEFF score.The average HFA-PEFF score was 2.4 ± 1.6 points. Two hundred and thirty-eight participants had 5 or 6 points. LASr showed a moderate correlation with the HFA-PEFF score (r = −0.50, LASr is an important factor with components of the HFA-PEFF score and is a useful tool to assess patients with HFpEF.https://clinicaltrials.org. Unique identifiers: NCT05638230.URL:  The cauLeft atrial (LA) longitudinal strain, which measures the systolic and diastolic function of the left atrium during the entire cardiac cycle via speckle-tracking echocardiography, has less angle and load dependence and reflects the physiological characteristics according to the cardiac cycle of the left atrium more than conventional echocardiography parameters . LA stra2.2.1.https://clinicaltrials.org. Unique identifiers: NCT05638230). Patients were excluded based on the following parameters: supraventricular arrhythmia such as atrial fibrillation/flutter or atrial tachycardia (n = 177); left ventricular ejection fraction < 50% (n = 212); permanent pacemaker or implantable cardioverter defibrillator procedure (n = 12); and unable to complete strain analysis because of poor imaging (n = 70). In total, 2,712 participants were enrolled  and had an International Classification of Disease-10 code of 150 (heart failure)  through speckle-tracking and semiautomatic analysis methods per the guidelines . An expe2.4.The endpoint was the relative importance of the LAS in predicting a high Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology (HFA-PEFF) diagnostic algorithm score of 5 or 6 compared to components of the 2016 guideline for diastolic function and the HFA-PEFF diagnostic algorithm.2.5.t-test, while the categorical variables were compared using the chi-squared test. Missing data were evaluated using the MssForest algorithm .The values of each variable were presented as mean ± standard deviation or median (interquartile range) based on the fulfillment of normality for continuous variables and as numbers and percentages for categorical variables. The continuous variables were compared using Student's lgorithm . The beslgorithm . We used3.3.1.2), half of them had a history of hypertension, and 28.0% had a history of diabetes mellitus, which are risk factors for HFpEF   . The mea3.2.p < 0.001). In the receiver operating characteristic curve analysis, LASr had good diagnostic performance to estimate the HFA-PEFF score . The area under the curve of LASr was similar to or higher than that of traditional diastolic function parameters   had a high HFA-PEFF score. LASr, previously identified as a useful LAS parameter, was moderately correlated with the HFA-PEFF score ] .p’s < 0.001] and LVGLS . LASr was found to be mildly correlated with the peak velocity of tricuspid regurgitation  and relative wall thickness  and had a very weak correlation with NT-proBNP (r = −0.12. p < 0.001). In addition, LASr was found to be was moderately correlated with the number of abnormal diastolic function parameters from the ASE/EACVI 2016 diastolic function guideline .Among diagnostic function parameters, there were moderate correlations between LASr and three of four major diastolic function parameters . The OR of LARs < 25.2% was higher than that of septal E/e’ , which is a useful parameter to estimate LV filling pressure in real clinical practice. In model 2 , impaired LASr < 25.2% also had a significant role in predicting a high HFA-PEFF score with covariates   . LASr < We conducted random forest analysis to analyze the relative importance of LAS  in predicting a high HFA-PEFF score in relation to 33 other demographic, clinical, laboratory, and echocardiographic covariates. The best-predicting model generated from the training cohort was built on a model of 1,500 tree with an area under the curve of 0.91 (95% CI 0.89–0.92), as evaluated on the validation cohort. Along with LAVI, NT-proBNP, age, LVGLS, hemoglobin, and glomerular filtration rate, LASr had a higher importance in predicting a high HFA-PEFF score than traditional diastolic parameters such as E/e’, TR-Vmax, LV mass index (LVMI), RWT, and septal e’ . Presumi3.4.p < 0.001, NRI 0.910 (95% CI 0.784–1.035), IDI ] ] .4.The present study showed that LAS, especially LASr, was independently associated with a high HFA-PEFF score and good performance to diagnose HFpEF and was similar or a more important parameter than traditional diastolic function parameters such as septal E/e’. In contrast to previous studies that focused on LASr as an independent or incremental predictor for prognosis in patients with heart failure, this study aimed to examine the relative importance of LAS compared to existing parameters for assessing diastolic function. Although LAS is not yet used in the diagnosis algorithm or guidelines for HFpEF, demonstrating the usefulness of LAS could serve as evidence for its potential utilization in the diagnosis of HFpEF.LAS is a useful indicator to predict a poor cardiovascular prognosis, including readmission, in patients with heart failure (HF) , 20. A pThe HFA-PEFF diagnostic algorithm was developed to diagnose HFpEF more accurately, which was previously difficult and challenging . The algThe E/e’ is a long-standing predictor of LV filling pressure and is an important indicator for evaluating diastolic function. However, conditions such as annular calcification, mitral regurgitation, and pericardial disease may not accurately reflect LV filling pressure . Among tAF patients, who were excluded from our study, show a significant decrease in LASr compared to that in patients in sinus rhythm, a phenomenon that can be explained mechanistically by the absence of booster pump action and the atrioventricular dyssynchrony. In previous studies, LASr in patients with AF was lower than those in the healthy population, with LASr values averaging approximately 10%–15% , 32. AnoOur study had some limitations. First, the study was designed retrospectively; thus, the power of the evidence may be weaker than that of a prospective or randomized control study. However, we tried to overcome any shortcomings of a retrospective study by measuring LAS across a large cohort. Furthermore, various models and statistical methods were used to demonstrate the concordant significance of LAS. Second, the primary endpoint of our study was not an indicator measured through invasive measurement or a hard endpoint, such as cardiovascular mortality. However, the HFA-PEFF score is an excellent and validated diagnostic algorithm. In addition, for scores of five or higher, the sensitivity and positive predictive value for diagnosing HFpEF were very high, at 93% and 98%, respectively . Third, 5.LASr is a relatively important factor with components of the HFA-PEFF score, a useful tool to assess patients with HFpEF. Ultimately, additional efforts are needed to incorporate LAS into the diagnostic process for HFpEF.


Since its first introduction, the role of three-dimensional (3D) echocardiography in diagnosing structural and congenital cardiac defects has been identified. However, its adaptation for congenital and structural defects has been slow. This is primarily driven by a lack, until recently, of dedicated pediatric 3D transesophageal echocardiography (TEE) probes, the relatively small size of the primary target population with these defects, no learning curriculum, limitations of “on-the-cart” software, and the length of time needed to process more complex lesions. With advancement in probe technology and software quality, there has been a renewed interest in using 3D echocardiography in real time during procedures in patients with structural and congenital heart diseases. It has been found to provide invaluable information during interventional procedures that helps with decision-making.In this report we describe a case of an iatrogenic left ventricle– (LV) to–right atrium (RA) shunt (Gerbode defect) where the real-time 3D (4D) echocardiogram provided additional information that was not available through two-dimensional (2D) echocardiography and that impacted management decisions.A 43-year-old man with a known diagnosis of Noonan's spectrum disorder/RASopathy, secondary to pathogenic variant in SOS1 , was initially referred to our tertiary-care center for care of their complex multisystem disease. A cardiac evaluation was ordered as part of the workup and was concerning for a right atrial mass. Cardiovascular magnetic resonance (CMR) imaging was performed to further delineate the mass and for tissue characterization. The CMR showed a pedunculated mass attached to the atrial septum in the RA with characteristics consistent with myxoma. The patient was also noted to have an additional small atrial septal defect (ASD). They subsequently underwent ASD repair and RA mass excision. After an uneventful postoperative course, they were discharged. However, during follow-up they were noted to have developed an LV-to-RA shunt at the site of the surgical excision of the mass. The patient complained of increasing fatigue but otherwise was stable with normal blood pressure; examination was remarkable for a soft systolic murmur at the right upper sternal border, mild bilateral lower extremity edema, and elevated jugular venous distension to right mandible with prominent ventricular systolic wave. No other signs of heart failure were identified.The patient was discussed with the pediatric interventional and cardiovascular surgical team, and a decision was made to attempt to close the defect with a percutaneous device if suitable. With this goal in mind, the patient was brought to the pediatric cardiac catheterization suite. A TEE was ordered to further delineate the anatomy prior to closure. The 2D images showed the LV-RA shunt , Video 1Echocardiography starting with the initial use of M mode and progressing through advances to the current use of 2D, 3D, and 4D imaging of cardiac structures has led to dramatic improvements in cardiovascular medicine and is now the most widely used diagnostic cardiac test after electrocardiography.Most of the advances have been targeted at assessment of acquired valvular diseases, which predominantly impact adult patients, but these modalities are now being introduced to investigate diseases in pediatric patients and in patients with more complex lesions as well as structural cardiac defects.et al.,,,12Along with the development of the applications, the hardware has also seen significant upgrade over the decades, with the introduction of newer more powerful probes of different sizes, which has led to an exponential growth of echocardiography over the last few decades. Its use has widened to support interventional techniques for percutaneous treatment of structural heart diseaseOur case is an attempt to increase the experience in this direction by highlighting the usefulness of the 4D echo to provide additional clinically important information that cannot be gleaned by 2D imaging for structural heart defects. We recommend that 3D echocardiography be fully incorporated in the evaluation of structural cardiac defects. Fortunately, the development in echocardiography is complemented by the development in cardiac computed tomography imaging, CMR imaging, and fluoroscopy . A future direction entails the integration of multiple modalities. Some platforms already allow such integration,Since its inception, echocardiography has come a long way and has now become the mainstay and workhorse of any cardiac evaluation. The introduction of 3D and 4D imaging has further boosted the utility of this imaging modality. However, weaknesses of 3D imaging remain and have slowed its adoption in congenital and structural heart defects, especially in scenarios where an immediate answer is desired . Our case highlights that this is achievable and that in select cases it can provide invaluable additional information that can impact management. Hence, its use should be considered in any scenario where 2D imaging is not enough to provide the desired information.The authors declare that the work described has been carried out in accordance with the following guidelines: This is a case report with no patient identifiers.The authors declare that informed patient consent was not provided for the following reason: this was a non-interventional, retrospective case report utilizing de-identified data, informed consent was not required from the patient as per institutional IRB.The authors declare that this report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.The authors reported no actual or potential conflicts of interest relative to this document.


Breast cancer is the most commonly diagnosed cancer in women worldwide, and with the increased survival of patients by novel treatments, the frequency of complications of cancer treatments rises. Radiotherapy, especially on the chest wall, can damage different cardiac structures. Radiotherapy-induced cardiomyopathy mainly occurs over 10 years after breast cancer treatment; however, there is a gap in the literature on acute myocarditis following radiotherapy. Here, we present a 54-year-old woman who developed acute myocarditis shortly after 25 sessions of radiotherapy with 50 Gy of radiation, successfully diagnosed with the use of speckle tracking echocardiography (STE) and cardiac magnetic resonance (CMR), and responded to the medical treatment with relative clinical improvement until the final follow-up. This case suggests the necessity of detailed examination of patients after radiotherapy, not only for chronic occurrence of cardiomyopathy but also for acute myocarditis. Although STE and CMR resulted in accurate diagnosis, in this case, further studies are required to determine the diagnostic accuracy of these two imaging methods compared with other imaging modalities in such patients and investigate the best diagnostic tool and therapeutic approach for these patients. Cardiovascular diseases (CVDs) and cancers are the top causes of death worldwide, and female breast cancer is the most diagnosed cancer with an increasing trend . With thCardiomyopathy, induced by RT, is mainly silent  with minor electrocardiography (ECG) changes, and the diagnosis is usually made by the abnormal findings of transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) . Further2, her blood pressure was 105/64 mmHg, heart rate was 110 bpm, and respiratory rate was 28/min. She had no family history of cardiomyopathy. She had been on daily oral long-acting nitrate (nitrocontin 2.6 mg twice a day), 6.25 mg carvedilol thrice a day, 80 mg aspirin once a day, and 20 mg rosuvastatin once a day. Six months before her referral, left breast cancer was diagnosed for the patient , and she underwent a left-sided mastectomy (R0 resection) and conventional RT, which included 25 courses of 50-Gy external beam RT with a compact machine , delivered within 5 weeks. Computed tomography (CT) simulation was done before planning. The clinical target volume was 185.7 and the planned target volume was 548.3; we did not have gross tumor volume (GTV) because the patient underwent surgery, and the gross tumor was resected surgically. Organs at risk (OAR) included the heart, the left and right lung, and the cord. For sparing OARs, the patient was initially immobilized in the treatment position, with immobilization devices (supine breast boards); and posterior jaw was set at zero to half-beam block/beam split to minimize dose of lung and heart. Gantry angle, collimator angle, and table angle were adjusted to optimize coverage of desired targets, while minimizing normal tissue inclusion within the field. Three-dimensional (3D) treatment planning was done for delineation of the breast, heart, lungs, and the cord. All of these organs received radiotherapy less than their tolerant dose. In this plan, mean dose of the heart was 541.7 cGy. The dose–volume histogram is provided in the A 54-year-old woman, with known case of diabetes mellitus  and ischemic heart disease (left main and advanced three-vessel disease), presented to our center with complaints of dyspnea on exertion and orthopnea, with neither feverishness, sputum production, nor chest pain. She was a nonsmoker, had a body mass index of 23 kg/mIn the history, the patient was under cardiac follow-up because of the right ventricular outflow tract tachycardia (RVOT VT) with the impression of idiopathic type, left ventricular (LV) ejection fraction (EF) of 49%, and negative single-photon emission computed tomography (SPECT) for more than 2 years. Also, 24-h ECG Holter recordings showed sinus tachycardia, in addition to nonspecific ST-T changes in the precordial leads with premature ventricular complexes (PVC) of 24%, for which medical treatment with 40 mg verapamil thrice a day was prescribed 2 years ago. Four months later, with 14.7% PVC count and a drop in LV EF to 31%, the patient was scheduled for PVC ablation. However, because of the demonstration of calcified coronaries in fluoroscopy, she underwent diagnostic angiography, which determined left main and three-vessel disease, according to which the treatment strategy shifted to coronary artery bypass grafting (CABG). After the surgery, LV EF improved to 48%, and PVC count reached <1% in serial ECG Holter follow-up.Before mastectomy, TTE evaluation  showed an LV EF of 42% and a global longitudinal strain (GLS) of −18.2% , 2A withThe results of serum tests showed a high sensitivity troponin I level six times above the normal limit (up to 14 ng/L), evaluated using high sensitivity (hs) troponin I assay technique, high level of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate aminotransferase (AST), estimated sedimentation ratio (ESR), C-reactive protein (CRP), and mild elevated total white blood cell (WBC) count , as well as elevated N-terminal pro-B-type brain natriuretic peptide (NT pro-BNP) . Serum lipids were within normal limits . The viral antibody markers were negative, which include Coxsackie virus group B, human immunodeficiency virus (HIV), cytomegalovirus, Epstein–Barr virus, hepatitis virus family, and influenza virus.The patient did not accept to undergo endomyocardial biopsy. CMR was performed using a Siemens Skyra 3 T MRI scanner with the application of real-time cine images of LV, short inversion time inversion-recovery (STIR) T2-weighted image (T2WI), T2 mapping, native and postcontrast T1 mapping, and delayed postcontrast images. The results of CMR showed diffuse myocardial inflammation in T1 mapping and extracellular volume (ECV) map of LV, mid-wall late gadolinium enhancement (LGE) in basal segments of the interventricular septum (IVS), and subepicardial delayed enhancement in the basal inferolateral segments of LV without an ischemic pattern of myocardial injury . The regThe prescribed medications included: carvedilol (12.5 mg twice a day), spironolactone (25 mg once a day), furosemide (40 mg twice a day), rosuvastatin (20 mg once a day), and prednisolone (10 mg once a day). Prednisolone and other medications were prescribed for improving cardiac function based on the available evidence , 9. StatThe timeline of the signs, symptoms, and diagnostic and therapeutic procedures are shown in Our case developed acute myocarditis after completing RT sessions. Pre-radiotherapy cardiac examinations, including ECG, echocardiography, and SPECT nuclear scan, were negative; therefore, the patient did not have any diagnosed coronary as well bypass graft failure in blood supply to the heart before radiation. Matching the postradiation clinical signs and results of cardiac examinations  with the European guideline of diagnosis of myocarditis guided the physician toward RIHD ; diagnosAlthough the cardiotoxic effects of RT is a known quantity, the frequency and severity of myocardial damage are not parallel in all patients and depend on several factors, including the site of action, radiation dose, the method of administration, and patients’ characteristics, such as underlying CVDs or their risk factors, and the current or previous use of other antineoplastic therapies . BecausePatients with an underlying CVD and/or other diseases, including hypertension and DM, have also a higher vulnerability to the RT-induced endothelial damage and are thus at a higher risk of RIHD , 16; ourConsidering the high prevalence of breast cancer and the risk of damage to the adjacent organs, a high incidence has been reported for RIHD within 2 years of RT . AccordiPericardial fibrosis is caused by collagen deposition in the interstitium and parietal region of the thickened pericardium. Collagen deposition in the cardiac tissue results in RT-induced myocardial fibrosis that replaces cardiomyocytes . The oxiAbnormalities observed on ECG, such as arrhythmia, ST segment depression, and conduction block, can help diagnosis, but are not always present, and multimodality imaging techniques are suggested to be used for accurate diagnosis . Our patAlthough ECG and TTE are suggested as the preferred tools used for the assessment of the cardiovascular damage induced by RT, they may not be sensitive for the detection of myocardial fibrosis . AccordiThe general therapeutic strategies suggested for RT-induced myocardial injury include antioxidants and anti-inflammatory agents, statins, and angiotensin-converting enzyme inhibitors; however, the treatment strategy is mainly selected individually based on the identified myocardial pathology and underlying diseases . In our The case presented here suggested the necessity of detailed examination of patients after radiotherapy, not only for chronic occurrence of cardiomyopathy but also for the early occurrence of acute myocarditis. The three layers of the endocardium, myocardium, and epicardium can be affected by the RT, both at early and late phases. It has to be kept in mind that RIHD can also occur in the early phase, resulting in acute diseases, which can be of great significance. Therefore, it is suggested to pay greater attention to the risk factors of RIHD that can help the physician in the identification of patients with a higher risk. Also, the literature suggests that the available screening methods, such as serum tests, ECG, and TTE, can help with the diagnosis in some cases. However, the screening methods cannot result in a definite diagnosis. Here, we showed that STE and CMR could accurately diagnose LV dysfunction and myocarditis in a patient. However, further studies are required to determine the diagnostic accuracy of these two imaging methods compared with other imaging modalities in such patients in order to determine the best diagnostic tool for these patients. Also, the follow-up examination of the patient showed the appropriateness of the treatment strategy used for this patient, while there are no specific guidelines for the most appropriate treatment approach for such patients, and more studies are required in this regard.


Transthyretin (ATTR) cardiac amyloidosis has recently received increased attention; however, the diagnosis is often delayed. We present a case of ATTR cardiac amyloidosis in which a comprehensive history-taking and focused physical examination played an important role in establishing the diagnosis. A 75-year-old man was referred to the cardiology department for left ventricular hypertrophy on electrocardiography. No fourth sound was audible despite concentric biventricular hypertrophy and diastolic dysfunction on echocardiography. Additional history-taking revealed that he had undergone bilateral carpal tunnel syndrome surgery almost 35 years earlier and had a biceps tendon rupture about 15 years earlier; bunching of the arm on flexion, or Popeye's sign, was noted. Technetium-99m-pyrophosphate showed diffuse uptake not only in both ventricles but also in both atria. The findings were consistent with the absence of the fourth sound. The present case highlights the importance of a focused physical examination as well as history-taking as a clue to ATTR cardiac amyloidosis in patients with unexplained left ventricular hypertrophy. Transthyretin (ATTR) cardiac amyloidosis has more recently gained increasing attention because of the establishment of a non-invasive diagnostic technique and fundamental treatment ,2. HowevAn asymptomatic 75-year-old man was referred to the cardiology department for left ventricular hypertrophy on electrocardiography. His medical history was notable for transurethral resection for bladder cancer, catheter ablation for atrial fibrillation, well-controlled hypertension, and hyperuricemia. His medications included rivaroxaban 15 mg daily, amlodipine 5 mg daily, and febuxostat 20 mg daily. He drank three cans of beer daily, had quit smoking two years earlier with a 20-pack-year smoking history, did not use illicit drugs, and had no known allergies. There was no family history of heart disease.On examination, his blood pressure was 122/96 mmHg, his heart rate was 79 beats per minute, his respiratory rate was 18 breaths per minute, and his oxygen saturation was 98% while he was breathing ambient air. The jugular venous pressure was not elevated, and neither a heart murmur nor an additional heart sound, including the fourth heart sound, was audible , and the brain natriuretic peptide level was 204 pg/mL .Electrocardiography showed left ventricular hypertrophy with an R height in lead V2 . Tissue Doppler imaging showed the ratio of the mitral valve E to the A wave of 2.66 and the deceleration time of the E wave of 209 ms. The ratio of mitral E to early diastolic mitral annular tissue velocity (E/e') was 32.0. There were no findings suggestive of significant valvular heart disease, ventricular outflow tract obstruction, or shunt disease. A diagnosis of diastolic dysfunction along with concentric hypertrophy was made. Two-dimensional speckle-tracking echocardiography showed a global longitudinal strain of -12.4% with an apical sparing pattern.Echocardiography showed a left ventricular ejection fraction of 55% with diffuse hypertrophy in both the left and right ventricles . The left ventricular mass index was 111.9 g/msAdditional history-taking showed that the patients had received bilateral surgery for carpal tunnel syndrome almost 35 years earlier. In addition, approximately 15 years earlier, a biceps tendon rupture developed while attempting to carry a 20-kg barrel. A bunching of the biceps when the patient flexed his arm, known as Popeye's sign, was noted  but also a focused physical examination  as a clue to ATTR cardiac amyloidosis in patients with unexplained left ventricular hypertrophy.


Venography demonstrated total occlusion of the left brachiocephalic vein  through the right subclavian vein and tunneled it subcutaneously to the left pocket of the previous pacemaker under general anesthesia . Phase standard deviation and bandwidth histogram became narrow with an increase in LV ejection fraction and a decrease in LV volumes after CRT implantation  PET/CT after 20 hours fasting with low-carbohydrate diet preparation for screening of inflammatory heart disease, in which no 18F-FDG uptake was seen in the myocardium  ejection fraction of 31%. Coronary angiography revealed no coronary abnormalities, whereas endomyocardial biopsy showed myocardial fibrosis Supplementary file1 Video 2. Placing the left ventricular lead through the subcutaneous tunnel. (MP4 867 kb)Supplementary file2 Video 3. Gated SPECT before cardiac resynchronization therapy. (MP4 715 kb)Supplementary file3 Video 4. Gated SPECT after cardiac resynchronization therapy. (MP4 682 kb)Supplementary file4 Below is the link to the electronic supplementary material.


Hypoplastic left heart syndrome is a spectrum of complex congenital cardiac defects. Although in borderline cases, biventricular repair is a viable option, in the majority of cases, univentricular palliation is the treatment of choice. Hybrid palliation can be a valid alternative to classic Norwood operation in the neonatal period, especially in selected cases such as high-risk patients or borderline left ventricles. Echocardiography is the main diagnostic modality in this pediatric population, from the fetal diagnosis to the subsequent surgical steps of palliative treatment. Hybrid palliation is performed after birth and is characterized by surgical banding of the pulmonary arteries along with transcatheter stenting of the ductus arteriosus. There are some peculiar aspects of cardiac imaging that characterize this type of palliation, and that should be considered in the different phases before and after the procedure. We aimed to review the current literature about the role of echocardiography in the management of patients with hypoplastic left heart undergoing hybrid palliation. Hypoplastic left heart syndrome (HLHS) is a spectrum of complex congenital cardiac defects in which the anatomy and physiology of the heart are profoundly altered. Diagnosis of HLHS is based exclusively on ultrasound imaging modalities, whose versatility offers high accuracy and widespread availability. Prenatal diagnosis is of paramount importance since it allows to program the most appropriate management of the newborn with HLHS in a tertiary care center. Then, echocardiography provides important information for planning the subsequently staged palliation, and it is essential to watchfully care for the patient afterward.Although the classic surgical approach in the first stage is the Norwood operation, the hybrid strategy has become a valid alternative in the last 20 years ,2. HybriClinical and surgical management of patients with HLHS is based largely on cardiac imaging, mainly echocardiography, aimed to evaluate different targets in every different phase, from fetal life to various surgical steps . In the Our aim was to review the current knowledge about the role of echocardiography in the management of hybrid palliation for HLHS .There is great interest in prenatal diagnosis of HLHS, and the argument has been accurately discussed ,22,23. AThen, a careful, thorough study is required for the evaluation of the hallmarks of HLHS: mitral atresia or stenosis, aortic atresia or stenosis, and hypoplastic aortic arch. The three major anatomic variants include (1) mitral atresia and aortic atresia, (2) mitral stenosis and aortic atresia, (3) mitral stenosis and aortic stenosis. For instance, the grade of development of the LV cavity and ascending aorta is proportional to the severity of mitral and aortic stenosis, respectively, depending on the amount of forward blood flow. Due to the inability of the left ventricle to provide adequate cardiac output, systemic circulation is dependent on the right ventricle through the ductus arteriosus, while the pulmonary venous return is redirected to the right chambers through the foramen ovale. In addition to a segmental and sequential anatomic definition of the fetal heart, special consideration is needed for the foramen ovale and for the ductus arteriosus since systemic circulation in this setting is provided exclusively through these fetal communications.A small amount of fetal cardiac output is directed to the lungs; even though small, it is crucial for the proper development of the pulmonary vasculature . ConsequCareful evaluation of the width and flow pattern across the ductus arteriosus is crucial, being the ductus is the only pathway for systemic output. For this reason, ductal constriction is never observed in viable fetuses with HLHS, and ductal size is rather wide . The augRight ventricular (RV) function is another key point of fetal evaluation. Since RV is the only pumping chamber, any cause of RV dysfunction or overload may not be hemodynamically tolerated and should be carefully investigated . HoweverCoronary artery origin and course are usually normal in HLHS. However, ventriculo-arterial connections, also called sinusoids, are relatively common in the MS/AA variant, though they are not necessarily associated with the worst outcome .Finally, fetal echocardiography has a major role when a transcatheter intervention is planned during fetal life, as it is performed in a limited number of institutions. In this setting, prenatal echocardiography is essential to identify those patients who may ultimately benefit from such intervention, and for instance, these challenging procedures, like aortic balloon dilatation or atrial septostomy, are entirely guided by ultrasounds .Once the newborn is stabilized and prostaglandin infusion has been initiated to maintain ductal patency, echocardiography is expected to define anatomic details and early adaptation from fetal to postnatal physiology. Diagnostic cardiac catheterization at birth is not mandatory; therefore, echocardiography is requested to provide hemodynamic information along with an anatomic assessment.In the last decades, the hybrid palliation of HLHS has gained favor as an alternative to the classical Norwood operation ,2. TargeFor instance, the ductal-dependent nature of this disease makes the evaluation of the ductus arteriosus a key point immediately after birth. Parasternal short axis, suprasternal, and the in-between off-axis views allow clear visualization of ductal width, morphology, and flow pattern .Although the exact measurement of ductal width and length is better obtained by angiography, later in the hybrid suite, a proper echocardiographic assessment of these critical measures can be useful in planning the procedure. In fact, a very short and wide duct may not be suitable for stenting or may carry a high risk of stent migration .Then, at birth, patency of the foramen ovale is critical for neonatal survival, and five different morphologies of the atrial septal defect (ASD) have been described in HLHS . The mosThis particular variant of malaligned ASD is characterized by leftward attachment of the posterosuperior aspect of the septum primum, far to the left from the normal central attachment of the septum secundum, therefore creating potential flow obstruction. When this morphology of the ASD with restrictive physiology is observed, and ASD stenting is required, the interventional cardiologist should be alerted of the risk of stent migration due to the irregular, unfavorable shape of the defect. Partial anomalous drainage of the right pulmonary veins has been reported in association with this type of malaligned ASD, even in the setting of normal connection; in fact, right pulmonary veins may still be connected to the leftward aspect of the septum secundum, even draining into the right atrium due to the malaligned septum primum. Furthermore, despite normal anatomic connection, total anomalous pulmonary venous drainage through a persistent vertical vein is described and should be investigated in the presence of a nearly intact ASD .With an underdeveloped LV, the RV is responsible for the total cardiac output, and therefore it is subjected to significantly higher pressure and volume load regimens compared to normal. Furthermore, until stage II with cavo-pulmonary connection is established, the single ventricle is forced to manage more than one stroke volume at the same time, depending on the Qp/Qs. Indeed, RV function is a central issue in the global assessment of a newborn with HLHS, being closely related to long-term outcomes . HoweverHowever, two-dimensional (2D) derived RV volumes result systematically in an underestimated value when compared to those obtained by magnetic resonance imaging (MRI), which represents the gold standard for cardiac volume quantification. Nonetheless, three-dimensional echocardiography has been shown to almost reach MRI accuracy for the assessment of volumes, mass, and ejection fraction, even in the setting of a functional single ventricle ,29. HoweA semi-quantitative method for RV evaluation has been proposed to overcome geometric-derived limitations, and it is based on CW-Doppler tricuspid flow. The systolic to diastolic duration ratio (S/D) is a simple measure of the TR jet duration, which represent the RV systolic interval divided by the interval free from the TR jet, which is occupied by diastolic RV inflow . When S/Experiences with tissue Doppler velocity and myocardial deformation in HLHS patients have been reported ,13,14,15Under the same denomination of HLHS encompassed a spectrum of anatomical variants of left-sided obstructive lesions that share the common feature of an underdeveloped LV, which is unable to support systemic circulation  31]..31].In the original description by Lev , only th2. Moreover, ventriculo-arterial discordance with hypoplastic systemic ventricles or univentricular hearts with aortic outflow obstruction are not accepted in the usual classification of HLHS, but still, they share with HLHS a similar pathophysiology.Beyond the aforementioned HLHS and HLHC variants, there are several situations in which the systemic ventricle is functionally unable to support circulation, like an unbalanced atrio-ventricular septal defect or total anomalous pulmonary venous return, mainly due to RV pressure and/or volume overload resulting in LV compression. However, in case of total anomalous pulmonary venous return or isolated aortic coarctation, the LV is usually adequate to manage systemic circulation after repair, even with preoperative volume as low as 8 mL/mWith the advent of the hybrid palliation for standard HLHS, followed by single ventricle staged reconstruction, it appeared soon that such a palliative strategy could also be extended to “HLHS-like” situations and even used as a bridge to biventricular repair in all those borderline cases in which the LV would have shown a sufficient growth at the end of the interstage period .A small LV can be referred to as “borderline” when its actual size appears inadequate to sustain systemic output, but it is not excessively undersized to show potential growth after the optimal hemodynamic status has been restored. Furthermore, it has been observed that the timing of the decision plays a crucial role in the fate of the hypoplastic borderline LV because the longer the ventricle is allowed to grow, the higher the probability of achieving functional independence. Hence, the goal of hybrid stage I would be to postpone the decision until LV fully expresses its growth potential; then, many more biventricular repairs might be reached than at the time of the first evaluation.In this setting, the most accurate assessment of LV size and aortic and mitral valve annular diameter acquires great importance in order to choose the best surgical option. Serial measurements of LV diameters, volumes, and mass, along with mitral and aortic valve annular diameters, LV long axis to heart long axis ratio, and aortic arch diameters, should be carefully reported and expressed as a z score. A standardized assessment, based on currently accepted guidelines for chamber quantification , is crucUnfortunately, there is no consensus regarding the criteria of the appropriateness of biventricular repair for borderline HLHS instead of what is available for critical aortic stenosis ,35. The While echocardiographic features of HLHS after Norwood stage I operation have been widely described, few data are available in the literature about the role of echocardiography in the interstage period after hybrid palliation. The interstage period should last 4 to 6 months, between the hybrid procedure and the subsequent “comprehensive stage II operation”, which consists of stent removal, aortic arch reconstruction and anastomosis with main pulmonary artery, debanding and augmentation of pulmonary artery branches with superior cavo-pulmonary anastomosis, and atrioseptectomy. The interstage period has been recognized to be a very frail phase in which the hemodynamic balance is highly labile and needs close surveillance. In this setting, echocardiography, along with clinical evaluation, plays a key role in the tight follow-up that these particular patients require.For instance, ductal stents must be carefully evaluated from suprasternal and parasternal views to ensure that there is no obstruction to forward flow through the stent .Different types of stents have been reported for ductal stenting , but all share the same potential complications in terms of lumen obstruction, which can occur in a central position or at the proximal or distal edge ,36. ColoA serious complication that can occur in up to 29% of cases during interstage is a retrograde aortic arch obstruction  18]. Si. Si18]. In the ideal system with aortic atresia and negligible pulmonary regurgitation, the total cardiac output can be calculated from the antegrade velocity-time integral (VTI) on the CW–Doppler curve through the ductal stent . HoweverIn hybrid stage I palliation, pulmonary blood flow is provided by the native pulmonary arteries which are selectively narrowed with Goretex bands to avoid pulmonary overload. This might appear as a technically easy procedure, but the subtle equilibrium between excessive and insufficient narrowing that may inadvertently lead to pulmonary hypoperfusion or over-circulation makes this surgical gesture actually challenging . MoreoveThough anatomical distortion of the banded pulmonary arteries can cause difficult visualization from the usual views, CW–Doppler through the narrowed site usually provides a reliable measure of the amount of flow that is distributed to the lungs. For this purpose, a certain number of Doppler parameters have been studied that can help with noninvasive hemodynamic assessment during interstage. Systolic and diastolic peak velocities should be noted and related to each other to express the pulsatility index. Moreover, velocity-time integral, systolic slope, and pressure half-time of the waveform is useful to better characterize pulmonary flow pattern. When high systolic peak velocity is observed along with low diastolic velocity, the pulsatility index increases, and this can be translated into elevated pulmonary pressure. A steeper slope with reduced pressure half-time indicates rapid equalization of pressures across the bands, and this phenomenon has been observed in association with ASD restriction, which is responsible for increased diastolic pulmonary pressure, counteracting flow access through the bands. This concept has been documented by the “normalization” of the pulmonary flow Doppler waveform after relief of ASD restriction; in fact, with reduced diastolic pressure in the pulmonary vascular bed, the pulsatility index and pressure half-time increased, along with a less-steep slope of the waveform .Because the natural tendency of ASD is towards spontaneous restriction, it is important to ensure that pulmonary venous return to the right atrium is kept unrestrained. Even more, in the presence of a stented ASD, tight surveillance is required. Along with direct signs of turbulent flow through the ASD, usually well seen with color and CW-Doppler, it can be useful to look for indirect signs of high left atrial end-diastolic pressure, as reported about modification of the pulmonary flow waveform across the bands .It should be underlined that all these measurements do not assume absolute value, but they should rather be considered as dynamic values, expected to change over time. Several reasons can be mentioned to explain these changes. First of all, during the interstage, the patient is expected to grow up as much as possible, even reaching twice or more his/her initial weight. Likewise, the heart and vessels grow up, but non-native tissues do not, like ductal stents and pulmonary bands. Then, pulmonary vascular resistances tend to decrease over time, making the initially adequate banding inappropriate. Finally, the interaction of native tissues with the ductal stent leads to cellular proliferation, so progressive lumen obstruction is not a rare complication. Particularly, the takeoff of the retrograde aortic arch is a matter of concern because whatever cause of impaired flow  can translate into life-threatening central hypoperfusion. For these reasons, all hemodynamic parameters that can be assessed by echocardiography should be carefully reported during interstage evaluations and compared with previous recordings. Peak flow velocities through the ductal stent, retrograde aortic arch, pulmonary bands, and ASD are all expected to increase over time, so the actual challenge is to detect how much change is too much. So far, the answer cannot be achieved by echocardiography alone, but a high-grade suspicion in the setting of a thorough clinical evaluation is needed.The term “comprehensive” has been coined to define the incorporation of surgical aspects pertaining to the classical Norwood stage I and II. The optimal timing of this second-stage palliation after the hybrid approach is not known since it may not necessarily be the same as for classic Norwood, for which the best long-term outcome has been identified in patients who received the second-stage operation between 3 and 6 months . Aortic The surgically reconstructed neo-aorta must be carefully investigated to rule out any obstruction, particularly at the distal site of anastomosis .In addition to a Doppler peak gradient higher than 30 mmHg through the distal arch, a useful parameter has been proposed to detect distal obstruction after Norwood stage I, that is, the “coarctation index”. It is defined as the ratio of the narrowest to the widest descending aortic diameter, and a value below 0.7 has been correlated with coarctation . Since aA critical evaluation of the atrial septum is warranted whenever clinical observation of cyanosis would raise the suspicion of inadequate atrial septal resection. However, increased velocities might also be due to augmented pulmonary venous return as it occurs in the case of pulmonary overcirculation.Perhaps the reconstruction of the pulmonary artery branches represents Achille’s heel of the whole hybrid palliation strategy. Comparing the hybrid palliation to the classic Norwood strategy for HLHS, a substantial equivalence in terms of survival has been observed, but it has been underlined that the hybrid approach carries a higher rate of pulmonary artery branches stenosis, requiring repeat reintervention  40,41].,41.40,41RV function should be carefully evaluated with serial monitoring, along with surveillance of tricuspid regurgitation and neo-aortic regurgitation.In the last two decades, a hybrid approach has been adopted by many institutions as a possible palliative strategy for patients with HLHS. Echocardiography plays a crucial role throughout the whole management of hybrid palliation and should be evaluated by highly skilled operators. First, ultrasound techniques are a prerequisite for the diagnosis and evaluation of candidacy for hybrid procedures. Second, during interstage echocardiographic surveillance of life-threatening complications is warranted. Finally, after comprehensive stage II, close monitoring by imaging is still required to ensure a favorable outcome for such complex and frail patients.


Cardiac structural and valve interventions have remained surgical procedures for several decades. The ability to directly visualize the region of interest during surgery made imaging of these structures pre- and postsurgery a secondary tool to compliment surgical visualization. The last two decades, however, have seen rapid advances in catheter-based percutaneous structural heart interventions (SHIs). Due to the “blind” nature of these interventions, imaging plays a crucial role in the success of these procedures. Fluoroscopy is used universally in all percutaneous cardiac SHIs and helps primarily in the visualization of catheters and devices. However, success of these procedures requires visualization of intracardiac soft tissue structures. Due to its portable nature and rapid ability to show cardiac structures online, transesophageal echocardiography (TEE) has become an integral tool for guidance for all percutaneous SHI. Transcatheter aortic valve replacement—one of the earliest catheter-based procedures—while initially dependent on TEE, has largely been replaced by preprocedural cardiac CT for accurate assessment of valve sizing. Developments in echocardiography now allow live three-dimensional (3D) visualization of cardiac structures mimicking surgical anatomy during TEE. Besides showing actual 3D intracardiac structures, 3D-TEE allows visualization of the interaction of intracardiac catheters and devices with soft tissue cardiac structures, thereby becoming a “second pair of eyes” for the operator. Real-time 3D-TEE now plays an important role complementing multiplane two dimensional and biplane TEE during such interventions. In this review, we discuss the incremental role of 3D-TEE during various SHIs performed today. There has been enormous progress in catheter-based structural heart interventions (SHIs), with widespread use in the cardiology community. This has been made possible as a result of the development of new devices with improved performance as well as significant advances in the cardiovascular imaging field . FluorosThis 3D approach may improve the interventional cardiologist’s ability to interact with the TEE images during SHI. Among many advantages, 3D-TEE images can reconstruct a more realistic anatomic display of cardiac chambers and valves in real time and provide critical intraprocedural information . TherefoThe aim of this review is to analyze the current role of 3D-TEE imaging for SHI, focusing on the more common procedures that are FDA approved in the United States in which this rapidly evolving imaging technique can better assist the heart team in ensuring the best outcomes for patients. Non FDA approved devices currently undergoing phase three clinical trials including mitral and tricuspid valve replacement are also covered. Trans-septal puncture is a common procedure for SHI involving left-side cardiovascular structures. Some general rules need to be followed during this procedure; however, the majority of SHIs require a site-specific puncture for interventional success. Although trans-septal puncture is usually performed using only fluoroscopy, intraprocedural 3D-TEE could provide guidance for a more accurate targeted puncture and can be complementary to fluoroscopy and 2D-TEE imaging. Intracardiac ultrasound (ICE) may also be used to guide trans-septal puncture but requires the use of an additional catheter and offers limited 3D capability.The 3D technique could also help to avoid iatrogenic trauma, to ensure alignment of devices and catheters, and to secure adequate space to maneuver within the left atrium . AlthougRecommended 3D-TEE imaging reconstructions to display the interatrial septum correspond to fluoroscopy projections: in the anteroposterior projection, the septum is displayed in an oblique perspective corresponding to the 3D-TEE oblique perspective from the right atrium; the right anterior oblique projection corresponds to the 3D-TEE en face view from the right atrium—by using this view, interventional cardiologists can follow the catheter tip from the superior vena cava to the fossa ovalis; in the left anterior oblique projection, the side-on profile of the septum corresponds to the 3D-TEE lateral perspective .When the catheter is facing the interatrial septum, the puncture site is traditionally recognized by the tenting . This apRecently, there has been an expanding increase in the availability and utilization of transcatheter aortic valve replacement (TAVR) . The majThe aortic annulus is an ovoid shape that is less accurately sized by 2D-TEE imaging planes alone. A contemporary meta-analysis explored the precision of 3D-TEE in measuring aortic annular area, perimeter, diameter, and left ventricular outflow tract pre-TAVR . The corDuring the procedure, precise positioning of the bioprosthetic aortic valve is critical. Although fluoroscopy plays the main role, the use of 3D-TEE can help with confirming the correct placement during valve deployment and minimizing the need for contrast injection. The differentiation between the valve and the underlying balloon relies on the detection of an echo-dense, sharp-edged structure . In compAfter deployment, it is important to examine if complications have occurred, particularly prosthetic aortic regurgitation (AR). If 2D methods fail to accurately determine the severity of post-TAVR AR, color Doppler 3D volumes can help estimate the effective regurgitant orifice area (EROA) and the 3D color Doppler planimetry of the vena contracta area . This reFollowing valve deployment, it is also important to explore mitral valve (MV) morphology and function. A low deployment in the left ventricular outflow tract (LVOT) can cause impingement of the anterior mitral annulus and the anterior leaflet deriving in pseudo-stenosis or mitral regurgitation (MR), which can also be assessed with 3D-TEE if conventional parameters are inconclusive. However, there may be an improvement in pre-existing secondary MR following TAVR, predominantly related to changes in left ventricular hemodynamics and mitral leaflet tethering . A studyPost-TAVR complications involving the aorta or left ventricle are rare but could be potentially catastrophic . Real-tiThe complexity of the MV apparatus and the proximity of the transcatheter devices with other cardiac structures could lead to difficulties during MV catheter-based interventions . While cReal-time 3D-TEE imaging has fundamentally revolutionized the MV transcatheter edge-to-edge repair (TEER) procedure using MitraClip devices by facilitating the procedure, shortening the procedural time, and improving results. First, as already mentioned, successful trans-septal puncture requires a 3D understanding of the interatrial anatomy and its relationship to the surrounding structures. Obtaining an accurate view of the puncture site could be challenging using only 2D images, especially when the site is very posterior . Thus, 3The maneuvering of the delivery system into the left atrium and its advancement toward the MV could be monitored by using 3D-TEE images from an oblique perspective of the interatrial septum. This view displays the relation between catheters, the atrial wall, and the interatrial septum, thus allowing the operator to maneuver the catheters without injuring cardiac structures [The correct orientation of the clips in a perpendicular manner to the coaptation line is critical for the intervention success and adequate leaflet grasp. This requires visualization of the MV on the short-axis plane. Two-dimensional TEE can only show this view in the transgastric plane and oftentimes may not be able to show this view in the correct anatomical plane or only show the view limited by gastric air. Real-time 3D imaging of the MV with the probe at the mid esophageal level provides a superb view of the entire MV from the atrial perspective, including anterior and posterior leaflet scallops, anterior and posterior commissures, and mitral annulus. This 3D-TEE view enables imaging of the clips’ arms and the MV coaptation line; therefore, it should be used to ensure that clips are perpendicular to the coaptation line [Only a limited number of 3D-TEE views are normally required for the intraprocedural guidance; meanwhile, for 2D-TEE, various views are usually needed to establish the adequate position of the clip(s). Additionally, 2D-TEE can be inaccurate in locating the tip of the catheters and its spatial relationship with the coaptation line while, with 3D-TEE, the spatial location of catheters in relation to surrounding structures is easier to comprehend . TherefoIn a series of 26 patients, Altiok et al. demonstrated that 3D-TEE provided critical additional information compared with 2D-TEE in various central steps of the TEER intervention. Those steps included the guidance and maneuvering of the catheters, the accurate positioning and alignment of the first clip, the confirmation of correct grasping location, and the proper positioning of any additional clips, if required . Real-tiPercutaneous annuloplasty or leaflet repair techniques may not be sufficient to eliminate MR in some scenarios depending on native valve characteristics . TranscaHowever, TMVR procedures are highly challenging due to several factors. These include the complex geometry of the mitral apparatus, the large size of the mitral annulus, the relative lack of calcification (which is a landmark used for fluoroscopic guidance), and the need to protect neighboring structures such as the coronary sinus, coronary arteries, and the LVOT . In ordeFor preprocedural planning, 3D-TEE datasets centered on the MV can be reconstructed using different planes to perform thorough quantifications of the mitral annulus. One study confirmed the clinical feasibility and accuracy of the assessment of the MV geometry with 3D-TEE when compared to CT measurements . In addiRegarding the use of intraprocedural TEE, 2D- and 3D-TEE guidance could be important for successful valve deployment. The mid-esophageal short-axis and bicaval views allow us to display the interatrial septum and maneuver the catheters; the mid-esophageal commissural view can help achieve correct medial–lateral positioning of the device; the mid-esophageal long-axis view is useful to estimate the anterior–posterior positioning of the device; lastly, a transgastric short-axis view can evaluate coaptation of leaflets .Postdeployment, 3D-TEE can be useful to verify the proper position and function of the device, to identify and quantify the severity of residual MR, and to detect procedural complications.Perivalvular dehiscence is an undesired complication that may happen after a prosthetic valve replacement procedure, more frequently affecting patients with mechanical mitral replacements. Transcatheter leak closure has emerged as a viable alternative to surgical redo procedures, especially in high-risk patients. However, these percutaneous procedures are usually complex and detailed imaging guidance is required ,33.The 3D multiplane reconstruction can be particularly useful to confirm the location and extent of periprosthetic regurgitation. Intraprocedural 3D-TEE guidance may provide critical information to the interventional cardiologist when crossing the dehiscence, as imaging can confirm the guidewire position across the perivalvular defect. In particular, the use of multiplane 3D images can be important in cases with severe calcification, sinuous dehiscences, or complex locations . The en Traditional 2D-TEE has several limitations in the assessment of dehiscences, including the interference of prosthetic material, sutures, or calcifications. However, the most challenging one is its inability to delineate the complete extent of periprosthetic dehiscences, which can be multiple and frequently anatomically complex . In thisFusion between TEE and fluoroscopy imaging may simplify the closure procedure, particularly in cases of radiolucent prosthetic valves . By compOne study investigated the clinical value of 3D-TEE for the catheter-based closure of paravalvular leaks in mitral prosthesis. This study showed no significant disagreement between 2D- and 3D-TEE color flow Doppler for the location of each leak, the vena contracta width, and the reduction in the paravalvular leak vena contracta width. However, only 3D-TEE had the ability to detect the decrease in the effective orifice circumferential length of the leak, suggesting that this technology could provide unique and additive information in this scenario .A study of ten patients with persistent mitral leak following transcatheter closure demonstrated that 3D-TEE was able to confirm the location and number of the residual leaks, along with their morphological characteristics . Additionally, 3D-TEE imaging also helped identify the exact location of the devices, allowing improved comprehension of the causes underlying the intervention’s failure .In a study of 166 patients with either mitral or aortic paravalvular leaks, TTE, TEE, and 3D printing were utilized for the preoperative evaluation of the defects. Among the included cases, 68 used preoperative TEE and 3D printing and showed advantages when compared with traditional TEE guidance, with a decrease in interventional and fluoroscopic times .Catheter-based treatments of tricuspid regurgitation (TR) are becoming a viable option for patients who are at high risk of surgical procedures. Therefore, different devices with diverse mechanisms of action have been developed . SpecifiThe 3D multiplane imaging could be crucial during these complex cases. The 3D multiplane mode is usually most useful from the mid-esophageal commissural views at the site of the TR jet to display the four-chamber view, as well as from the transgastric short-axis tricuspid valve (TV) view. These views display the leaflet grasping view, which is critical to evaluate feasibility and to decide the final transcatheter device placement. These views also provide information to determine the TR mechanism, orifice size, septal leaflet length, and septal leaflet curling . In addiLastly, 3D-TEE multiplane reconstructions can help with the final evaluation of the position of the device following placement and 3D color Doppler should assess the presence and magnitude of potential residual jets. For some particular devices, transgastric views with 3D reconstruction of the right ventricle anchor path and landing zone may be important .With the FDA approval of left atrial appendage (LAA) catheter-based occlusion devices, the use of cardiovascular imaging for real-time assessment of the LAA orifice area has become critical for accurate sizing and placement of devices . PreviouDuring transcatheter occlusion procedures, the 3D-TEE technique is usually used to ensure the proper position of the catheter by using an en face view of the LAA orifice [Pulmonary vein stenosis is considered an uncommon disease with a challenging diagnosis and potential undesired consequences if left untreated. Currently, injury from radiofrequency ablation for atrial fibrillation has become the main cause of this condition, and transcatheter intervention is the most common therapeutic approach. When this diagnosis is suspected, multimodality imaging methods are usually required for confirmation .Angiography is traditionally utilized to locate pulmonary veins stenosis. Using only this technique, it could be difficult to easily identify occluded pulmonary veins; however, 3D-TEE could help locate them. The use of 3D-TEE during pulmonary vein interventions provides a real-time assessment of pulmonary veins anatomy along with a better understanding of the spatial relationships between cardiac structures . These aAnother scenario for the potential use of 3D-TEE is to complement other imaging methods during anatomy-driven catheter-based radiofrequency pulmonary veins ablation . A 3D-TEThe use of intraprocedural 3D-TEE has been also proposed in patients with Scimitar syndrome, characterized by an anomalous venous return from the right lung directly into the inferior vena cava. Full-volume 3D-TEE imaging can illustrate the abnormal pulmonary vein entrance into the inferior vena cava and can help identify the orientation of the scimitar vein with respect to the hepatic veins and the inferior vena cava . This caFluoroscopy has been the traditional method for intraprocedural guidance in SHI and has its own strengths. Wires, devices, and catheters for SHI have been designed and developed to be radiopaque to maximize fluoroscopic guidance, while these medical tools usually create undesired artifacts in echocardiography imaging. Moreover, in contrast to echocardiography, fluoroscopy displays a larger field of view that allows interventional cardiologists to follow and visualize long segments of catheters. The temporal resolution of fluoroscopy is also appropriate to maneuver the catheters and devices, while a major limitation of 3D imaging is its poor temporal resolution, which is related to the increased use of data points to generate 3D images . TherefoAs outlined in this review, multiplane 3D-TEE imaging can offer an interesting number of advantages when utilized in a complementary manner to fluoroscopy during SHI. Soft tissues of critical cardiac structures are transparent to radiography; so, echocardiography is of paramount importance for an accurate anatomical assessment of the targeted structures. When comparing the more novel 3D approach with traditional 2D techniques, real-time multiplanar 3D-TEE imaging, and particularly en face views, supply additive and more appropriate guidance of catheter manipulation by providing improved imaging and comprehensive information about the spatial positioning of wires and devices and their relationships with surrounding cardiac structures. The multiplanar perspective of 3D-TEE allows the use of several imaging planes specific to each procedure with no need for several changes in probe position. This may lead not only to more accurate technical outcomes but can also help in reducing complications and suboptimal deployments during SHI. Additionally, 3D-TEE techniques can help shorten the duration of procedures, thus reducing the volume of contrast and radiation exposure both for the patients and the heart team.New technologies are continually being developed in the field of cardiovascular imaging. ICE has been proposed as an alternative for TEE guidance for SHI. However, this method is not without disadvantages, including costly single-use catheters, the potential interference between the catheter and temporary/permanent pacemaker leads, limited 3D evaluation , and smaller field of view, making it challenging to appropriately display structures far away from the right atrium . AdditioAs the use of 3D-TEE is becoming more frequent for cardiac SHI, the applications of this technique are now expanding to other percutaneous interventions. It has been proposed that 3D-TEE techniques could also have a role in planning or guiding percutaneous aortic procedures , as the However, potential barriers exist for the general implementation of 3D-TEE imaging in the catheterization laboratory. First, interventional cardiologists are more familiar with fluoroscopy guidance than with echocardiography imaging for SHI. As 3D-TEE is becoming a useful complementary tool during SHI, training programs for interventional cardiologists could better include the use of this novel technique. Moreover, images obtained from fluoroscopy and echocardiography are usually displayed on separate screens, thus limiting the understanding of the spatial relationships between cardiac devices and cardiovascular structures. In this sense, further advances to refine the management of digital images would allow researchers to improve the creation of fusion images from both fluoroscopy and TEE. This fusion between two imaging modalities in one 3D space and time will create sophisticated images that can be shown on a single screen and better utilized by the cardiologists. Another frequent limitation with 3D images is related to the artifacts that may occur when the ultrasound beam intersects catheters and devices. Additional limitations include the lack of a standardized core curriculum for SHI imagers and the lack of unified guidelines for the use of 3D-TEE during SHI; however, efforts are being made to establish a current state-of-the-art regarding the use of imaging techniques during SHI, including the use of new imaging technologies . Lastly,The use of 3D-TEE imaging during SHI has several benefits, including an easier localization of the anatomical structures of interest and devices, an easier navigation inside the heart chambers, and a more precise localization of the landing zone of devices. As the use of this technology is expected to extensively increase during transcatheter interventions, appropriate and consistent recommendations for intraprocedural guidance are critical. Future large-scale prospective studies are still needed to demonstrate that the use of 3D-TEE in this scenario generates practical advantages such as shortening of the procedural time, increased procedural success, reduction in procedural complications, and reduced radiation and contrast exposure.


The clinical features of mitochondrial cardiomyopathy (MCM) are diverse. It can present as hypertrophic cardiomyopathy or dilated cardiomyopathy. The diagnosis of MCM is challenging and usually based on biopsy.The 30-year-old man was admitted to hospital due to dyspnea for 1 month and edema of both lower extremities for 1 week. Echocardiography suggested a whole heart enlargement, a whole heart diminished function. Renal impairment and diabetes were observed. Coronary angiography showed single-vessel disease . Left ventricular endomyocardial biopsy was performed.Myocardial histopathology demonstrated a large number of abnormal mitochondrial accumulation, so the diagnosis was considered as mitochondrial cardiomyopathy. Mitochondrial disease is a group of specific diseases caused by dysfunction of the mitochondrial energy synthesis system , 2. AbnoA 30-year-old man presented with a history of dyspnea for 2 months and edema of both lower extremities for 1 week without precipitating factors such as infection or alcohol abuse. The patient did not show improvement in the above symptoms after receiving standard-dose furosemide diuretic therapy. There was no history of seizure, previous use of medication, diabetes mellitus, hypertension, smoking or cardiac disease. He had no family history of a similar complaint.Physical examination upon admission: temperature(T) 37.1 °C, pulse(P) 100 beats/min, respiration(R) 18 beats/min, blood pressure (BP) 145/95 mmHg, no wet rales in lungs, neat heart rate, 100 beats/min, A2 > P2, no murmur in the auscultation area of the valve. There were no apparently positive signs in abdomen. Mild edema of both lower extremities was found.9/L; blood biochemistry: GLU 7.5 mmol/L, CRE 103 μmol/L, UREA 5.94 mmol/L, normal liver function and electrolytes; no obvious abnormality in coagulation function; myocardial injury marker: cTnI 0.06 ng/mL, Myo 25.0 ng/mL, CK-MB 2.6 ng/mL; BNP: 957.94 pg/mL. His NT-pro-BNP was marked elevated at 4075 pg/mL. urine routine: protein 0.5 g/L; 24 h urine protein quantitation 0.15 g/24 h, 24 h urine sodium 304 mmol/24 h, protein quantitative determination of 189.3 mg/L, N-acetyl-β-D glycosaminidase 13U/L. Fasting venous blood glucose was 7.5 mmol/L, and glycated hemoglobin was 7.6%.Laboratory examination: blood routine: WBC 12.60*10Electrocardiogram suggested sinus rhythm, left ventricular hypertrophy, and changed non-specific T wave. Doppler echocardiography showed left ventricular end-diastolic anteroposterior diameter: 48 mm, left ventricular end-diastolic diameter: 64 mm, right atrial diameter: 47 mm, right ventricular end-diastolic anteroposterior diameter: 32 mm, septal thickness: 9 mm, left ventricular posterior wall thickness: 9 mm. Mild mitral regurgitation and tricuspid regurgitation with left ventricular systolic dysfunction was observed .Admission diagnosis was heart failure with possible dilated cardiomyopathy. Magnetic resonance imaging (MRI) was terminated, because the patient was pale and sweaty during the examination. Transradial coronary angiography (CAG) illustrated no abnormalities in LM, LAD, or LCX, 25% stenosis in the middle of RCA, 90% stenosis in the sharp margin, and superior coronary in the right coronary, thus diagnosing coronary atherosclerosis heart disease, single-vessel disease, right-handed dominant type. Left ventricular angiography revealed that the left ventricular total systolic function was reduced, and no abnormal wall motion was observed, LVEDP 20-25 mmHg, LVEF 28.5%.Left ventricular endocardial myocardial biopsy through the same radial artery suggested that degenerative changes occurred in the cardiomyocytes, and extensively "worm-like" changes could be observed. . The enlargement and nuclear atypia could be observed in cardiomyocytes  versus 71.4% (n = 1711) in RV tissue (p < 0.001). In these two trials, although statistical significance was not achieved, the safety profile of left ventricular endomyocardial biopsy appears to have greater potential. This could be further validated through trials with an expanded sample size. In terms of efficacy, left ventricular endomyocardial biopsy provides more comprehensive pathological diagnostic clues, resulting in a higher net value [The patient, a young man who was physically healthy, was admitted to the hospital with whole heart failure. Echocardiography suggested a whole heart enlargement and the ejection fraction was only 25%. According to coronary angiography, we diagnosed coronary atherosclerotic heart disease, a single-vessel disease, but the coronary lesions couldn’t explain the patient's whole heart enlargement and severe cardiac insufficiency. It was also accompanied by kidney damage and diabetes. Left ventricular endocardial myocardial biopsy revealed that the cardiomyocytes were extensively "worm-like" changes, which manifested a large number of abnormal mitochondrial accumulation areas under the electron microscope. According to the diagnostic criteria proposed by Lev, in the myocardial ultrastructure of the cardiomyopathy patients, there was a large amount of abnormal mitochondrial accumulation, and MCM should be considered. According to the diagnostic criteria proposed by Meyers, the patient had multiple systemic involvements such as myocardial, renal damage and diabetes. Abnormal mitochondrial accumulation could be seen under electron microscope, which matched one major criterion and one secondary standard, and might be MCM. At this point, the patient's diagnosis was clear, but unfortunately, the patient refused to conduct any further examinations in enzymology, functional science, or molecular science, so we couldn’t obtain more clinical data. Myocardial biopsy is an important breakthrough in the diagnosis of MCM. In other words, obtaining myocardial histopathology and electron microscopy results plays a decisive role in the diagnosis of MCM. A study involving 755 myocardial biopsies and 6371 myocardial biopsy specimens demonstrated that the incidence of severe complications was similar between left ventricular biopsy and right ventricular biopsy (0.64% vs. 0.82%). The incidence of minor complications was lower in the left ventricular biopsy group (0.64–2.89% vs. 2.24–5.10%). The left ventricular biopsy had a higher rate of histopathological diagnostic yield (64.5–74.8% vs. 55.8–57.1%) . Anotheret value .This case report manifests that if a young patient, admitted with whole heart failure, has multiple organs dysfunction and clinical features of cardiopathy, mitochondrial cardiomyopathy should be considered. A myocardial biopsy can be performed to determine the type of cardiomyopathy. A Left ventricular endocardial myocardial biopsy helps to improve the diagnostic rate of MCM and is safer. The transradial approach used in these patients also facilitates myocardial biopsy.