Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: The AGENT IDE Randomized Clinical Trial.

Importance: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States. Objective: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention. Design, Setting, and Participants: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023. Interventions: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon. Main Outcomes and Measures: The primary end point of 1-year target lesion failure-defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death-was tested for superiority. Results: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P = .003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P = .001) and target vessel-related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P = .02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P = .38) in the coated vs uncoated balloon groups, respectively. Conclusions and Relevance: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04647253.

Echocardiography for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) provides advanced cardiopulmonary life support for patients in cardiac and/or respiratory failure. Echocardiography provides essential diagnostic and anatomic information prior to ECMO initiation, allows for safe and efficient ECMO cannula positioning, guides optimization of flow, provides a modality for rapid troubleshooting and patient evaluation, and facilitates decision-making for eventual weaning of ECMO support. Currently, guidelines for echocardiographic assessment in this clinical context are lacking. In this review, we provide an overview of echocardiographic considerations for advanced imagers involved in the care of these complex patients. We focus predominately on new cannulas and complex cannulation techniques, including a special focus on double lumen cannulas and a section discussing indirect left ventricular venting. Echocardiography is tremendously valuable in providing optimal care in these challenging clinical situations. It is imperative for imaging physicians to understand the pertinent anatomic considerations, the often complicated physiological and hemodynamic context, and the limitations of the imaging modality.

Bivalirudin as a Systemic Anticoagulant and Flush Solution Additive for Sequential Mitral and Tricuspid Valve Percutaneous Edge-to-Edge Repair in a Patient With Heparin-Induced Thrombocytopenia.

Herein the case of a patient with a prior history of heparin-induced thrombocytopenia who underwent percutaneous mitral valve edge-to-edge repair that was followed by a tricuspid edge-to-edge repair two months later is presented. Recommendations exist for systemic anticoagulant alternatives for percutaneous mitral valve edge-to-edge repair with the MitraClip device (Abbott, Chicago, IL), but minimal guidance and experience are present regarding alternative systemic anticoagulation during the performance of right-sided interventions, including tricuspid edge-to-edge repair (TriClip; Abbott). Notably, there is no clear consensus regarding the use of an alternative anticoagulant in the catheter flush solution for the delivery systems used during these procedures, particularly for right-sided interventions.

Incremental value of three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of a partially detached MitraClip.

We describe an elderly male patient with two MitraClip devices, one fixed and the other detached, in whom live/real-time three-dimensional echocardiography (3DTEE) provided incremental value and additional information compared to two-dimensional transesophageal echocardiography (2DTEE). 3DTEE offered the ability to comprehensively assess the mitral valve (MV) utilizing full volume and multiplanar reconstruction (MPR) modes. 3DTEE proved useful in assessing the position of the properly attached and the partially detached MitraClip, including assessment of orifice size and degree of mitral regurgitation (MR). In addition, trapping of MV chordae by both clips was noted in the 3DTEE image dataset and confirmed at the time of surgery. Chordal trapping was not detected by 2DTEE. 3DTEE proved useful in more accurately estimating the severity of residual MR with the MitraClips in place since the regurgitant jet vena contracta (VC) could be viewed en face and VC area measured by planimetry in the correct imaging plane as compared to limited linear images from 2DTEE.

Utility of transesophageal echocardiography to assess real time left atrial pressure changes and dynamic mitral regurgitation following placement of transseptal multistage venous cannula for systemic venous drainage and indirect left ventricular venting in venoarterial extracorporeal membrane oxygenation.

A patient with heart failure due to nonischemic cardiomyopathy presented as a transfer to our institution following peripheral (femoral) venoarterial (VA) extracorporeal membrane oxygenation (ECMO) placement. With peripheral VA ECMO cannulation, the patient continued to have unstable ventricular tachyarrhythmias. Echocardiography demonstrated left ventricular (LV) dilation and severe mitral regurgitation (MR) with clinical and chest X-ray evidence of pulmonary edema. To provide venous drainage and simultaneous decompression of the left atrium (LA) and thereby indirect LV venting, a single multistage venous cannula was placed across the inter-atrial septum (IAS) using the previously described left atrial venoarterial (LA-VA) ECMO cannulation technique. Two- and three-dimensional (3D) transesophageal echocardiography (TEE) demonstrated utility in guiding cannula placement into the appropriate position and providing real time assessment of ventricular decompression and MR severity. There was subsequent improvement in pulmonary edema. This case is thought to be the first demonstration of real time resolution of pulmonary venous flow reversal in a patient undergoing LA-VA ECMO cannulation. This demonstration offers important mechanistic insight into some of the potential benefits of such an approach.

Contemporary suprasternal transcatheter aortic valve replacement: A multicenter experience using a simple, reliable alternative access approach.

OBJECTIVES: To describe outcomes after suprasternal (SS) transcatheter aortic valve replacement (TAVR) as a new alternative access approach. BACKGROUND: There still remains a cohort of the TAVR population who are not suitable for a transfemoral (TF) approach. SS-TAVR is a safe and effective alternative to TF-TAVR and has now become our preferred alternative access route. METHODS: We retrospectively reviewed all patients from New York Presbyterian Hospital, Columbia University Medical Center and Princeton Baptist Medical Center who underwent SS-TAVR from 2015 to July 2018. A total of 84 patients were included in the study. RESULTS: Technical success was achieved in all cases. Thirty-day survival was 98.8% (n = 83). There were minimal complications. Most notably, there were no transient ischemic attacks or strokes (0%, n = 0). Reexploration for bleeding was 3.6% (n = 3), and major bleeding was 1.7% (n = 1). We also achieved satisfactory results with a mean aortic valve gradient of 6.07 ± 3.79 mmHg and an aortic valve area of 2.21 ± 0.51 cm2 . No patients had anything more than mild paravalvular leak. The mean length of stay (LOS) in the intensive care unit was 1.42 ± 1.23 days, and hospital LOS was 4.20 ± 3.29 days. CONCLUSIONS: SS access for TAVR is an extremely important technique to have in any valve team's alternative access armamentarium. This technique can be safely and reliably reproduced with any standard hybrid operating room setup and no additional equipment, and it can be used with any commercially available valve system. In the current experience, minimal complications and excellent early term results were obtained.

Utility of three-dimensional transesophageal echocardiography to guide transseptal positioning of a single multistage venous cannula to provide both venous drainage and indirect left ventricular venting in veno-arterial extracorporeal membrane oxygenation.

A patient with heart failure due to dilated ischemic cardiomyopathy presented in cardiogenic shock for institution of veno-arterial extracorporeal membrane oxygenation as a bridge to cardiac transplantation. To provide adequate venous drainage and simultaneous decompression of the left atrium (indirect left ventricular venting), a single venous cannula was placed across the interatrial septum so that the distal orifice and side ports were located within the left atrium and the proximal set of side ports were positioned at the cavoatrial junction. Three-dimensional transesophageal echocardiography demonstrated utility in guiding cannula placement and appropriate positioning within the left atrium.

Femoral venoarterial extracorporeal membrane oxygenation using a novel biatrial cannula for venous drainage and left ventricular venting.

Extracorporeal life support (ECLS) is an expanding technology for patients in cardiogenic shock. The majority of patients requiring ECLS can be managed with percutaneous venoarterial (VA) femoral cannulation. Despite sufficient extracorporeal circulatory support, a unclear number of patients develop left ventricular distension which can result in increased wall tension and stress as well as worsening pulmonary edema. Indications to vent the left ventricle can be controversial. When venting is indicated, a number of additional procedures may be considered including inotropic support, intra-aortic balloon pump, impella, balloon atrial septostomy, or placement of a transseptal cannula. We present a unique case of a femoral VA extracorporeal membrane oxygenation as a bridge to transplant with left-sided venting using a Bio-Medicus NextGen cannula (Medtronic) with a transseptal approach.

Usefulness of two- and three-dimensional transesophageal echocardiography in combined mitral valve-in-valve implantation and paraprosthetic leak closure.

We demonstrate the usefulness of two- and live/real time three-dimensional transesophageal echocardiography in a procedure, which combined transcatheter mitral valve-in-valve deployment and paraprosthetic leak closure in the same setting using the less invasive transfemoral approach in an adult patient with bioprosthetic mitral valve degeneration. We also highlight the additive value of three-dimensional echocardiography over the two-dimensional technique.

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic atherosclerotic thrombi and ulcers.

We present two cases in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided incremental value in the assessment of atherosclerotic disease in the aorta. In one patient, it identified additional atherosclerotic ulcers as well as thrombi within them which were missed by two-dimensional (2D) TEE. In both cases, the size of the large mobile atherosclerotic plaque was underestimated by 2DTEE as compared with 3DTEE. Furthermore, 3DTEE provided volume quantification of the thrombi and ulcers which is not possible by 2DTEE. The echocardiographic findings of atherosclerotic plaques were confirmed by computed tomography in one patient and by surgery in the other.

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload.

Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine to measure mitochondrial membrane potential. Transmission electron microscopy and immunohistochemistry were used for cardiomyocyte structural assessment. In vitro cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial ROS production and decreased mitochondrial membrane potential, which were significantly improved by MitoQ. ACF had extensive loss of desmin and ß2-tubulin that was paralleled by mitochondrial disorganization, loss of cristae, swelling, and clustering identified by mitochondria complex IV staining and transmission electron microscopy. MitoQ improved mitochondrial structural damage and attenuated desmin loss/degradation evidenced by immunohistochemistry and protein expression. However, LV dilatation and fractional shortening were unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not affect LV dilatation or function in ACF, these experiments suggest a connection of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption and mitochondrial damage in the VO of ACF.

Usefulness of three-dimensional transesophageal echocardiography in retrieval of a dislodged vascular plug used to close paraprosthetic mitral regurgitation.

In this report, we describe a case of periprocedural dislodgement of an Amplatzer Vascular Plug II device during percutaneous closure of severe paraprosthetic mitral regurgitation. The free plug in the left atrium was successfully retrieved percutaneously using a snare inserted through a sheath under live/real time three-dimensional transesophageal echocardiographic guidance. This proved crucial not only in guiding device deployment but also in detecting and helping management of complications.

Incremental Value of Three-Dimensional Transesophageal Echocardiography over the Two-Dimensional Technique in the Assessment of a Thrombus in Transit through a Patent Foramen Ovale.

We report a case of a right atrial thrombus traversing a patent foramen ovale into the left atrium, where three-dimensional transesophageal echocardiography provided considerable incremental value over two-dimensional transesophageal echocardiography in its assessment. As well as allowing us to better spatially characterize the thrombus, three-dimensional transesophageal echocardiography provided a more quantitative assessment through estimation of total thrombus burden.

Incremental value of three-dimensional transesophageal echocardiography over the two-dimensional technique in percutaneous closure of aortic paraprosthetic regurgitation.

We describe 2 patients with significant aortic paraprosthetic regurgitation who underwent percutaneous closure where live/real time three-dimensional transesophageal echocardiography provided incremental value over two-dimensional transesophageal echocardiography.

Utility of live/real time three-dimensional transesophageal echocardiography in the assessment and percutaneous intervention of bioprosthetic pulmonary valve stenosis.

Accurate echocardiographic evaluation of the pulmonary valve is technically difficult because of its close proximity to the left lung, which often limits decision making. Pulmonary valvotomy is the intervention of choice for symptomatic pulmonary valve stenosis, but fluoroscopy lacks appropriate real time anatomic detail. In this report, we present a case where direct imaging of the pulmonary valve with live/real time three-dimensional transesophageal echocardiography (3DTEE) aided in accurate evaluation and was then used to help guide and monitor successful valvuloplasty of a stenotic pulmonary valve bioprosthesis. We demonstrate that even in cases where two-dimensional (2D) evaluation of the pulmonary valve is difficult, the use of live/real time 3DTEE allows for accurate evaluation of bioprosthetic pulmonary valve structure and function, and enhances the precision and monitoring of percutaneous valvuloplasty.

Incremental value of three-dimensional echocardiography over the two-dimensional technique in the assessment of combined sinus of valsalva rupture into the right ventricle and adjacent perimembranous ventricular septal defect.

We describe the incremental value of live/real time three-dimensional (3D) echocardiography over the 2D technique in the assessment of ruptured right sinus of Valsalva into the right ventricle associated with an adjacent perimembranous ventricular septal defect in an elderly patient.

Live/real time three-dimensional transesophageal echocardiographic assessment of the spinal cord.

We present an adult patient in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided incremental value in the assessment of the spinal cord as compared to two-dimensional transesophageal echocardiographic (2DTEE) findings published in the literature. It improved accurate identification and assessment of the anterior radiculomedullary spinal arteries which may have an important clinical application in monitoring for spinal cord ischemia during thoracic aortic surgery. Because the spinal cord and spinal canal could be examined using not only transverse but also coronal (frontal), sagittal, and oblique planes, 3DTEE further allowed for three-dimensional measurements of the dimensions and volumetric analysis of the visualized spinal cord and spinal canal. These may have implications in the assessment of spinal cord edema due to trauma and other conditions which result in increase in the size and volume of the spinal cord.

Gene expression and ultra-structural evidence for metabolic derangement in the primary mitral regurgitation heart.

Aims: Chronic neurohormonal activation and haemodynamic load cause derangement in the utilization of the myocardial substrate. In this study, we test the hypothesis that the primary mitral regurgitation (PMR) heart shows an altered metabolic gene profile and cardiac ultra-structure consistent with decreased fatty acid and glucose metabolism despite a left ventricular ejection fraction (LVEF) > 60%. Methods and results: Metabolic gene expression in right atrial (RA), left atrial (LA), and left ventricular (LV) biopsies from donor hearts (n = 10) and from patients with moderate-to-severe PMR (n = 11) at surgery showed decreased mRNA glucose transporter type 4 (GLUT4), GLUT1, and insulin receptor substrate 2 and increased mRNA hexokinase 2, O-linked N-acetylglucosamine transferase, and O-linked N-acetylglucosaminyl transferase, rate-limiting steps in the hexosamine biosynthetic pathway. Pericardial fluid levels of neuropeptide Y were four-fold higher than simultaneous plasma, indicative of increased sympathetic drive. Quantitative transmission electron microscopy showed glycogen accumulation, glycophagy, increased lipid droplets (LDs), and mitochondrial cristae lysis. These findings are associated with increased mRNA for glycogen synthase kinase 3ß, decreased carnitine palmitoyl transferase 2, and fatty acid synthase in PMR vs. normals. Cardiac magnetic resonance and positron emission tomography for 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake showed decreased LV [18F]FDG uptake and increased plasma haemoglobin A1C, free fatty acids, and mitochondrial damage-associated molecular patterns in a separate cohort of patients with stable moderate PMR with an LVEF > 60% (n = 8) vs. normal controls (n = 8). Conclusion: The PMR heart has a global ultra-structural and metabolic gene expression pattern of decreased glucose uptake along with increased glycogen and LDs. Further studies must determine whether this presentation is an adaptation or maladaptation in the PMR heart in the clinical evaluation of PMR.

Magnetic resonance imaging with 3-dimensional analysis of left ventricular remodeling in isolated mitral regurgitation: implications beyond dimensions.

BACKGROUND: Although surgery is indicated in patients with mitral regurgitation (MR) when left ventricular (LV) end-systolic (LVES) dimension is >40 mm, LV ejection fraction may decrease after mitral valve surgery. We hypothesize that significant LV remodeling before surgery is not reflected by standard echocardiographic parameters measured at the base of the heart. METHODS AND RESULTS: Ninety-four patients (age, 54 ± 11 years; 38% female) with degenerative isolated MR underwent cine magnetic resonance imaging with tissue tagging and 3-dimensional analysis. In 51 control subjects (age, 44 ± 14 years; 53% female), the relation between LVES volume (LVESV) and LVES dimension was quadratic, whereas in 94 MR patients, this relation was cubic, indicating a greater increase in LVESV per LVES dimension among MR patients. Moreover, magnetic resonance imaging LVESV from summated serial short-axis slices was significantly greater than LVESV assessed with the Bullet formula in MR patients, attributed to a more spherical remodeling distal to the tips of the papillary muscles (P<0.001). Thirty-five patients underwent mitral valve repair per current guideline recommendations. LV ejection fraction decreased from 61 ± 7% to 54 ± 8% (P<0.0001) and maximum shortening decreased significantly below normal at 1 year postoperatively (P<0.0001). Despite normalization of LV stroke volume and LV end-diastolic volume/mass ratio, there was a persistent significant increase in distal LVES 3-dimensional radius/wall thickness ratio and LVESV index after surgery. CONCLUSIONS: Despite apparently preserved LVES dimension, MR patients demonstrate significant spherical mid to apical LVES remodeling that contributes to higher LVESV than predicted by standard geometry-based calculations. Decreased LV strain after surgery suggests that a volumetric analysis of LV remodeling and function may be preferred to evaluate disease progression in isolated MR.