Exponential family measurement error models for single-cell CRISPR screens.

CRISPR genome engineering and single-cell RNA sequencing have accelerated biological discovery. Single-cell CRISPR screens unite these two technologies, linking genetic perturbations in individual cells to changes in gene expression and illuminating regulatory networks underlying diseases. Despite their promise, single-cell CRISPR screens present considerable statistical challenges. We demonstrate through theoretical and real data analyses that a standard method for estimation and inference in single-cell CRISPR screens-"thresholded regression"-exhibits attenuation bias and a bias-variance tradeoff as a function of an intrinsic, challenging-to-select tuning parameter. To overcome these difficulties, we introduce GLM-EIV ("GLM-based errors-in-variables"), a new method for single-cell CRISPR screen analysis. GLM-EIV extends the classical errors-in-variables model to responses and noisy predictors that are exponential family-distributed and potentially impacted by the same set of confounding variables. We develop a computational infrastructure to deploy GLM-EIV across hundreds of processors on clouds (e.g. Microsoft Azure) and high-performance clusters. Leveraging this infrastructure, we apply GLM-EIV to analyze two recent, large-scale, single-cell CRISPR screen datasets, yielding several new insights.

Rechallenge With Switching Immune Checkpoint Inhibitors Following Autoimmune Myocarditis in a Patient With Lynch Syndrome.

Immune checkpoint inhibitors (ICIs) induce profound benefits in cancer patients with mismatch repair gene mutations or high levels of microsatellite instability. Herein, we present a case of a patient with history of Muir-Torre/Lynch syndrome and metastatic gastric adenocarcinoma in the presence of an MSH2 gene mutation. The patient was initially treated with a PD-1 inhibitor, pembrolizumab, but developed grade 4 myocarditis requiring treatment with infliximab and a prolonged steroid taper. Following discontinuation of pembrolizumab, surveillance testing showed no radiographic or endoscopic evidence of progression for 7 months, until biopsy results from a repeat upper endoscopy indicated local disease recurrence. The patient was subsequently rechallenged with another PD-1 inhibitor, nivolumab, at a 50% dose reduction without recurrent adverse events and eventually achieved a complete response after 13 cycles. This case highlights the relative importance of considering careful rechallenge with ICI therapy in patients with microsatellite instability-high malignancies and a high risk of severe adverse events.

Surgical versus catheter ablation in atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high stroke and mortality rate. The video-assisted thoracoscopic radiofrequency pulmonary vein ablation is a treatment option for patients who fail catheter ablation. Randomized data comparing surgical versus catheter ablation are limited. We performed a meta-analysis of randomized control trials to explore the outcome efficacy between surgical and catheter radiofrequency pulmonary vein ablation in patients with AF. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to December 2020. Included studies were published randomized control trials that compared video-assisted thoracoscopic and catheter radiofrequency pulmonary vein ablation. Data from each study were combined using the fixed-effects, generic inverse variance method of DerSimonian, and Laird to calculate odds ratios and 95% confidence intervals. RESULTS: Six studies from November 2013 to 2020 were included in this meta-analysis involving 511 AF patients (79% paroxysmal) with 263 catheter ablation (mean age 56 ± 3 years) and 248 surgical ablations (mean age 52 ± 4 years). Catheter ablation was associated with increased atrial arrhythmias recurrence when compared to surgical ablation (pooled relative risk = 1.85, 95% confidence interval: 1.44-2.39, p < .001, I2 = 0.0%) but associated with less total major adverse events (pooled relative risk = 0.29, 95% confidence interval: 0.16-0.53, p < .001, I2 = 0.0%). In subgroup analysis, catheter ablation was associated with increased AF recurrence in refractory paroxysmal AF when compared to surgical ablation (pooled relative risk = 2.47, 95% confidence interval: 1.31-4.65, p = .005, I2 = 0.0%) but not in persistent AF (relative risk = 1.09, 95% confidence interval: 0.60-2.0, p = .773). CONCLUSION: Catheter ablation was associated with higher atrial arrhythmia recurrence when compared with surgical ablation. However, our study suggests that the benefit of surgical ablation in patients with persistent AF is unclear. More studies and alternative ablation strategies investigation in persistent AF are warranted.

Echocardiography in Cardiac Assist Devices.

In patients with medically refractory heart failure or cardiogenic shock, both temporary and durable mechanical circulatory support devices can be used to support cardiac circulation. Both transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are widely available, relatively noninvasive, and avoid radiation exposure. Thus, echocardiography is an invaluable tool that provides vital information aiding in preprocedure evaluation, placement, management, and weaning of cardiac assist devices. The purpose of this article is to review the utility of both TTE and TEE in managing patients with cardiac assist devices.

What are the significant turning demands of match play of an English Premier League soccer team?

This study aimed to compare the significant turning demands of English Premier League soccer match play relative to playing position using LiDAR technology. Turning data were collected from an English Premier League soccer team (2020-2021 season; 18 fixtures) using a Sportlight® LiDAR tracking system. Turns were tracked during match play, sub-categorised by entry speed (<3.0, 3.0-5.5, 5.5-7.0 and >7.0 m/s) and turning angle (Low: 20-59°; Medium: 60-119°; High: 120-180°). Turning metric frequencies were compared between playing positions (centre backs, full-backs, central midfielders, wide midfielders, and central forwards). On average, per match, central midfielders performed more total turns (~38 vs ~18-27), turns with entry speeds <3.0 (~15 vs ~7-10) and 3.0-5.5 m/s (~21 vs ~8-15) and low (~4 vs ~1-2), medium (~10 vs ~3-6) and high angled turns (~24 vs ~12-18) compared to all other playing positions (p ≤ 0.001, d = 0.96-2.74). Approximately, 90% of turns during matches were performed with entry speeds <5.5 m/s and ~63-70% were high angled turns. This study provides unique insights into the turning demands of English Premier League soccer matches , which can be used to inform position-specific physical preparation strategies, turning testing battery selection, agility drill construction, and rehabilitation and return to play standards.

Centromere tethering confines chromosome domains.

The organization of chromosomes into territories plays an important role in a wide range of cellular processes, including gene expression, transcription, and DNA repair. Current understanding has largely excluded the spatiotemporal dynamic fluctuations of the chromatin polymer. We combine in vivo chromatin motion analysis with mathematical modeling to elucidate the physical properties that underlie the formation and fluctuations of territories. Chromosome motion varies in predicted ways along the length of the chromosome, dependent on tethering at the centromere. Detachment of a tether upon inactivation of the centromere results in increased spatial mobility. A confined bead-spring chain tethered at both ends provides a mechanism to generate observed variations in local mobility as a function of distance from the tether. These predictions are realized in experimentally determined higher effective spring constants closer to the centromere. The dynamic fluctuations and territorial organization of chromosomes are, in part, dictated by tethering at the centromere.

Robust differential expression testing for single-cell CRISPR screens at low multiplicity of infection.

Single-cell CRISPR screens (perturb-seq) link genetic perturbations to phenotypic changes in individual cells. The most fundamental task in perturb-seq analysis is to test for association between a perturbation and a count outcome, such as gene expression. We conduct the first-ever comprehensive benchmarking study of association testing methods for low multiplicity-of-infection (MOI) perturb-seq data, finding that existing methods produce excess false positives. We conduct an extensive empirical investigation of the data, identifying three core analysis challenges: sparsity, confounding, and model misspecification. Finally, we develop an association testing method - SCEPTRE low-MOI - that resolves these analysis challenges and demonstrates improved calibration and power.

Robust differential expression testing for single-cell CRISPR screens at low multiplicity of infection.

Single-cell CRISPR screens (perturb-seq) link genetic perturbations to phenotypic changes in individual cells. The most fundamental task in perturb-seq analysis is to test for association between a perturbation and a count outcome, such as gene expression. We conduct the first-ever comprehensive benchmarking study of association testing methods for low multiplicity-of-infection (MOI) perturb-seq data, finding that existing methods produce excess false positives. We conduct an extensive empirical investigation of the data, identifying three core analysis challenges: sparsity, confounding, and model misspecification. Finally, we develop an association testing method - SCEPTRE low-MOI - that resolves these analysis challenges and demonstrates improved calibration and power.

Rapidly Progressive Apical Hypertrophic Cardiomyopathy: Not Everything is What It Seems.

Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM. A 43-year-old female with a past medical history significant for hypertension and kidney transplantation presented with recurrent syncopal episodes and dyspnea on exertion. Electrocardiogram showed characteristic diffuse giant T-waves inversion, and cardiac magnetic resonance showed HCM with circumferential apical thickening. This case highlights the rapid development of apical HCM and its challenging diagnostic characteristics.

Artificial intelligence-enabled electrocardiogram (AI-ECG) does not predict atrial fibrillation following patent foramen ovale closure.

Background: Atrial fibrillation (AF) is a known complication following patent foramen ovale (PFO) closure. AI-enabled ECG (AI-ECG) acquired during normal sinus rhythm has been shown to identify individuals with AF by noting high-risk ECG features invisible to the human eye. We sought to characterize the value of AI-ECG in predicting AF development following PFO closure and investigate key clinical and procedural characteristics possibly associated with post-procedural AF. Methods: We performed a retrospective analysis of patients who underwent PFO closure at our hospital from January 2011 to December 2022. We recorded the probability (%) of AF using the Mayo Clinic AI-ECG dashboard from pre- and post-procedure ECGs. The cut-off point of ≥ 11 %, which was found to optimally balance sensitivity and specificity in the original derivation paper (the Youden index) was used to label an AI-ECG "positive" for AF. Pre-procedural transesophageal echocardiography (TEE) and pre- and post-procedure transcranial doppler (TCD) data was also recorded. Results: Out of 93 patients, 49 (53 %) were male, mean age was 55 ± 15 years with mean post-procedure follow up of 29 ± 3 months. Indication for PFO closure in 69 (74 %) patients was for secondary prevention of transient ischemic attack (TIA) and/or stroke. Twenty patients (22 %) developed paroxysmal AF post-procedure, with the majority within the first month post-procedure (15 patients, 75 %). Patients who developed AF were not significantly more likely to have a positive post-procedure AI-ECG than those who did not develop AF (30 % AF vs 27 % no AF, p = 0.8).Based on the PFO-Associated Stroke Causal Likelihood (PASCAL) classification, patients who had PFO closure for secondary prevention of TIA and/or stroke in the "possible" group were significantly more likely to develop AF than patients in "probable" and "unlikely" groups (p = 0.034). AF-developing patients were more likely to have post-procedure implantable loop recorder (ILR) (55 % vs 9.6 %, p < 0.001), and longer duration of ILR monitoring (121 vs 92.5 weeks, p = 0.035). There were no significant differences in TCD and TEE characteristics, device type, or device size between those who developed AF vs those who did not. Conclusions: In this small, retrospective study, AI-ECG did not accurately distinguish patients who developed AF post-PFO closure from those who did not. Although AI-ECG has emerged as a valuable tool for risk prediction of AF, extrapolation of its performance to procedural settings such as PFO closure requires further investigation.

"Unkinking" the "Kink" Normalizes the Doppler Pattern.

Coarctation of the aorta (CoA) comprises 5-7% of congenital heart disease and can present as an isolated narrowing in the aortic arch just distal to the left subclavian artery or can be associated with cardiac abnormalities such as a bicuspid aortic valve, aortopathy, or ventricular septal defects. With the advances in the medical field, intervention on CoA can either be via surgical repair or endovascular stenting. Echocardiography is the mainstay in diagnosing CoA, with tomographic imaging such as magnetic resonance imaging (MRI) or computed tomography providing supplementary assessment of the aorta, valves, and collateral vessels. We present a case of a young hypertensive male who was noted to have a continuous cardiac murmur with diagnostic Doppler pattern of CoA on echocardiography that normalized soon after percutaneous stenting.

Role of lipoprotein(a) concentrations in bioprosthetic aortic valve degeneration.

OBJECTIVES: Lipoprotein(a) (Lp(a)) is associated with an increased incidence of native aortic stenosis, which shares similar pathological mechanisms with bioprosthetic aortic valve (bAV) degeneration. However, evidence regarding the role of Lp(a) concentrations in bAV degeneration is lacking. This study aims to evaluate the association between Lp(a) concentrations and bAV degeneration. METHODS: In this retrospective multicentre study, patients who underwent a bAV replacement between 1 January 2010 and 31 December 2020 and had a Lp(a) measurement were included. Echocardiography follow-up was performed to determine the presence of bioprosthetic valve degeneration, which was defined as an increase >10 mm Hg in mean gradient from baseline with concomitant decrease in effective orifice area and Doppler Velocity Index, or new moderate/severe prosthetic regurgitation. Levels of Lp(a) were compared between patients with and without degeneration and Cox regression analysis was performed to investigate the association between Lp(a) levels and bioprosthetic valve degeneration. RESULTS: In total, 210 cases were included (mean age 74.1±9.4 years, 72.4% males). Median time between baseline and follow-up echocardiography was 4.4 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.7%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in patients affected by degeneration versus non-affected cases: 50.0 (IQR 72.0) vs 15.6 (IQR 48.6) mg/dL, p=0.002. In the regression analysis, high Lp(a) levels (≥30 mg/dL) were associated with degeneration both in a univariable analysis (HR 3.6, 95% CI 1.7 to 7.6, p=0.001) and multivariable analysis adjusted by other risk factors for bioprostheses degeneration (HR 4.4, 95% CI 1.9 to 10.4, p=0.001). CONCLUSIONS: High serum Lp(a) is associated with bAV degeneration. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) levels could slow bioprostheses degradation.

Multi-Modality Imaging in Vasculitis.

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.

Association between echocardiographic velocity time integral ratio of mitral valve and left ventricular outflow tract and clinical outcomes post transcatheter edge-to-edge mitral valve repair.

Background: Residual mitral regurgitation (MR) is frequent after transcatheter edge-to-edge repair (TEER). There is controversy regarding the clinical impact of residual MR and its quantitative assessment by transthoracic echocardiography (TTE), which is often challenging with multiple eccentric jets and artifact from the clip. The utility of the velocity time integral (VTI) ratio between the mitral valve (MV) and left ventricular outflow tract (LVOT), (VTIMV/LVOT), a simple Doppler measurement that increases with MR, has not been assessed post TEER. Methods: Baseline characteristics, clinical outcomes, and TTE data from patients who underwent TEER between 2014 and 2021 across three academic centers were retrospectively analyzed. Post-procedure TTEs were evaluated for VTIMV/LVOT in the first three months after TEER. One-year outcomes including all-cause and cardiac mortality, major adverse cardiac events, and MV reintervention were compared between patients with high VTIMV/LVOT (≥2.5) and low (<2.5). Results: In total, 372 patients were included (mean age 78.7 ± 8.8 years, 68 % male, mean pre-TEER ejection fraction of 50.5 ± 14.7 %). Follow up TTEs were performed at a median of 37.5 (IQR 30-48) days post-procedure. Patients with high VTIMV/LVOT had significantly higher all-cause mortality (HR 2.10, p = 0.003), cardiac mortality (HR 3.03, p = 0.004) and heart failure admissions (HR 2.28, p < 0.001) at one-year post-procedure. There was no association between raised VTIMV/LVOT and subsequent MV reintervention. Conclusion: High VTIMV/LVOT has clinically significant prognostic value at one year post TEER. This tool could be used to select patients for consideration of repeat intervention.

Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. It follows an autosomal dominant inheritance pattern in most cases, with incomplete penetrance and heterogeneity. It is familial in 60% of cases and most of these are caused by pathogenic variants in the core sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1). Genetic testing using targeted disease-specific panels that utilize next-generation sequencing (NGS) and include sarcomeric genes with the strongest evidence of association and syndrome-associated genes is highly recommended for every HCM patient to confirm the diagnosis, identify the molecular etiology, and guide screening and management. The yield of genetic testing for a disease-causing variant is 30% in sporadic cases and up to 60% in familial cases and in younger patients with typical asymmetrical septal hypertrophy. Genetic testing remains challenging in the interpretation of results and classification of variants. Therefore, in 2015 the American College of Medical Genetics and Genomics (ACMG) established guidelines to classify and interpret the variants with an emphasis on the necessity of periodic reassessment of variant classification as genetic knowledge rapidly expands. The current guidelines recommend focused cascade genetic testing regardless of age in phenotype-negative first-degree relatives if a variant with decisive evidence of pathogenicity has been identified in the proband. Genetic test results in family members guide longitudinal clinical surveillance. At present, there is emerging evidence for genetic test application in risk stratification and management but its implementation into clinical practice needs further study. Promising fields such as gene therapy and implementation of artificial intelligence in the diagnosis of HCM are emerging and paving the way for more effective screening and management, but many challenges and obstacles need to be overcome before establishing the practical implications of these new methods.

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.

Identifying the Causes of Unexplained Dyspnea at High Altitude Using Normobaric Hypoxia with Echocardiography.

Exposure to high altitude results in hypobaric hypoxia, leading to physiological changes in the cardiovascular system that may result in limiting symptoms, including dyspnea, fatigue, and exercise intolerance. However, it is still unclear why some patients are more susceptible to high-altitude symptoms than others. Hypoxic simulation testing (HST) simulates changes in physiology that occur at a specific altitude by asking the patients to breathe a mixture of gases with decreased oxygen content. This study aimed to determine whether the use of transthoracic echocardiography (TTE) during HST can detect the rise in right-sided pressures and the impact of hypoxia on right ventricle (RV) hemodynamics and right to left shunts, thus revealing the underlying causes of high-altitude signs and symptoms. A retrospective study was performed including consecutive patients with unexplained dyspnea at high altitude. HSTs were performed by administrating reduced FiO2 to simulate altitude levels specific to patients' history. Echocardiography images were obtained at baseline and during hypoxia. The study included 27 patients, with a mean age of 65 years, 14 patients (51.9%) were female. RV systolic pressure increased at peak hypoxia, while RV systolic function declined as shown by a significant decrease in the tricuspid annular plane systolic excursion (TAPSE), the maximum velocity achieved by the lateral tricuspid annulus during systole (S' wave), and the RV free wall longitudinal strain. Additionally, right-to-left shunt was present in 19 (70.4%) patients as identified by bubble contrast injections. Among these, the severity of the shunt increased at peak hypoxia in eight cases (42.1%), and the shunt was only evident during hypoxia in seven patients (36.8%). In conclusion, the use of TTE during HST provides valuable information by revealing the presence of symptomatic, sustained shunts and confirming the decline in RV hemodynamics, thus potentially explaining dyspnea at high altitude. Further studies are needed to establish the optimal clinical role of this physiologic method.

The effect of acute taurine ingestion on 3-km running performance in trained middle-distance runners.

Limited research examining the effect of taurine (TA) ingestion on human exercise performance exists. The aim of this study was to investigate the effect of acute ingestion of 1,000 mg of TA on maximal 3-km time trial (3KTT) performance in trained middle-distance runners (MDR). Eight male MDR (mean ± SD: age 19.9 ± 1.2 years, body mass 69.4 ± 6.6 kg, height 180.5 ± 7.5 cm, 800 m personal best time 121.0 ± 5.3 s) completed TA and placebo (PL) trials 1 week apart in a double-blind, randomised, crossover designed study. Participants consumed TA or PL in capsule form on arrival at the laboratory followed by a 2-h ingestion period. At the end of the ingestion period, participants commenced a maximal simulated 3KTT on a treadmill. Capillary blood lactate was measured pre- and post-3KTT. Expired gas, heart rate (HR), ratings of perceived exertion (RPE), and split times were measured at 500-m intervals during the 3KTT. Ingestion of TA significantly improved 3KTT performance (TA 646.6 ± 52.8 s and PL 658.5 ± 58.2 s) (p = 0.013) equating to a 1.7 % improvement (range 0.34-4.24 %). Relative oxygen uptake, HR, RPE and blood lactate did not differ between conditions (p = 0.803, 0.364, 0.760 and 0.302, respectively). Magnitude-based inference results assessing the likeliness of a beneficial influence of TA were 99.3 %. However, the mechanism responsible for this improved performance is unclear. TA's potential influence on exercise metabolism may involve interaction with the muscle membrane, the coordination or the force production capability of involved muscles. Further research employing more invasive techniques may elucidate TA's role in improving maximal endurance performance.

Case series: cardiac sarcoma.

Background: Cardiac masses encompass a wide differential including primary and secondary malignancies and can present with a variety of symptoms, many of which are non-specific. Early identification and classification are important, particularly for cardiac malignancies such as sarcomas as these are aggressive tumours with exceptionally poor prognoses when metastases are present at diagnosis. Case summary: We report two cases of patients who presented with dyspnoea and were diagnosed with cardiac sarcomas; the former a primary sarcoma (undifferentiated pleomorphic subtype) and the latter a secondary sarcoma (round cell myxoid liposarcoma) that serve as comparisons for presentation and management of different types of this disease. Computed Tomography (CT) and echocardiography imaging findings are demonstrated showing the typical location and morphology of each subtype. Discussion: Cardiac sarcomas are the most common primary cardiac malignancy, of which undifferentiated pleomorphic sarcoma is a common subtype. Undifferentiated pleomorphic sarcomas are aggressive, have a tendency to arise in the left atrium, and can appear similar to benign cardiac masses. Round cell myxoid liposarcomas by contrast are rare causes of secondary cardiac malignancies, metastasizing to the heart from soft tissues. Both diagnoses carry poor prognoses and although rare, are important to recognize as timely intervention with surgery, radiotherapy, and consideration of chemotherapy is key to maximizing survival.

Three-Dimensional Transesophageal Echocardiography in Percutaneous Catheter-Based Cardiac Interventions.

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.