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.

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.

Understanding post-surgical decline in left ventricular function in primary mitral regurgitation using regression and machine learning models.

Background: Class I echocardiographic guidelines in primary mitral regurgitation (PMR) risks left ventricular ejection fraction (LVEF) < 50% after mitral valve surgery even with pre-surgical LVEF > 60%. There are no models predicting LVEF < 50% after surgery in the complex interplay of increased preload and facilitated ejection in PMR using cardiac magnetic resonance (CMR). Objective: Use regression and machine learning models to identify a combination of CMR LV remodeling and function parameters that predict LVEF < 50% after mitral valve surgery. Methods: CMR with tissue tagging was performed in 51 pre-surgery PMR patients (median CMR LVEF 64%), 49 asymptomatic (median CMR LVEF 63%), and age-matched controls (median CMR LVEF 64%). To predict post-surgery LVEF < 50%, least absolute shrinkage and selection operator (LASSO), random forest (RF), extreme gradient boosting (XGBoost), and support vector machine (SVM) were developed and validated in pre-surgery PMR patients. Recursive feature elimination and LASSO reduced the number of features and model complexity. Data was split and tested 100 times and models were evaluated via stratified cross validation to avoid overfitting. The final RF model was tested in asymptomatic PMR patients to predict post-surgical LVEF < 50% if they had gone to mitral valve surgery. Results: Thirteen pre-surgery PMR had LVEF < 50% after mitral valve surgery. In addition to LVEF (P = 0.005) and LVESD (P = 0.13), LV sphericity index (P = 0.047) and LV mid systolic circumferential strain rate (P = 0.024) were predictors of post-surgery LVEF < 50%. Using these four parameters, logistic regression achieved 77.92% classification accuracy while RF improved the accuracy to 86.17%. This final RF model was applied to asymptomatic PMR and predicted 14 (28.57%) out of 49 would have post-surgery LVEF < 50% if they had mitral valve surgery. Conclusions: These preliminary findings call for a longitudinal study to determine whether LV sphericity index and circumferential strain rate, or other combination of parameters, accurately predict post-surgical LVEF in PMR.

Percutaneous debulking of tricuspid valve endocarditis in severe COVID-19 pneumonia after prolonged venovenous extracorporeal membrane oxygenation with right-ventricular support: a case series.

Background: Over the past 2 years, the utilization of venovenous extracorporeal membrane oxygenation (VV-ECMO) for the treatment of coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) has increased. While supporting respiratory function, VV-ECMO requires large-bore indwelling venous cannulas, which risk bleeding and infections, including endocarditis. Case summary: We describe two adults hospitalized for COVID-19 pneumonia who developed ARDS and right-ventricular failure, requiring VV-ECMO and ProtekDuo cannulation. After over 100 days with these devices, both patients developed tricuspid valve vegetations. Our first patient was decannulated from ECMO and discharged, but re-presented with a segmental pulmonary embolism and tricuspid mass. The Inari FlowTriver system was chosen to percutaneously remove both the tricuspid mass and pulmonary thromboembolism. Pathological examination of the mass demonstrated Candida albicans endocarditis in the setting of Candida fungemia. Our second patient developed a tricuspid valve vegetation which was also removed with the FlowTriever system. Pathological examination demonstrated endocarditis consistent with Pseudomonas aeruginosa in the setting of Pseudomonas bacteremia. Both patients experienced resolution of fungemia and bacteremia after percutaneous vegetation removal. After ECMO decannulation and percutaneous debulking, both patients experienced prolonged hospital stays for ventilator weaning and were eventually discharged with supplemental oxygen. Discussion: VV-ECMO and right-ventricular support devices are invasive and create various risks, including bloodstream infection and infective endocarditis. Percutaneous debulking of valvular vegetations associated with these right-sided indwelling devices may be an effective means of infection source control. It is unclear whether prolonged use of VV-ECMO provides a mortality benefit in COVID-19 ARDS.

Complications Associated With Transesophageal Echocardiography in Transcatheter Structural Cardiac Interventions.

BACKGROUND: Transesophageal echocardiograms (TEEs) performed during transcatheter structural cardiac interventions may result in greater complications than those performed in the nonoperative setting or even those performed during cardiac surgery. However, there are limited data on complications associated with TEE during these procedures. We evaluated the prevalence of major complications among these patients in the United States. METHODS: A retrospective cohort study was conducted using an electronic health record database (TriNetX Research Network) from large academic medical centers across the United States for patients undergoing TEE during transcatheter structural interventions from January 2012 to January 2022. Using the American Society of Echocardiography-endorsed International Statistical Classification of Diseases and Related Health Problems Clinical Modifications (10th edition) codes, patients undergoing TEE during a transcatheter structural cardiac intervention, including transaortic, mitral or tricuspid valve repair, left atrial appendage occlusion, atrial septal defect closure, patent foramen ovale closure, and paravalvular leak repair, were identified. The primary outcome was major complications within 72 hours of the procedure (composite of bleeding and esophageal and upper respiratory tract injury). The secondary aim was the frequency of major complications, death, or cardiac arrest within 72 hours in patients who completed intraoperative TEE during surgical valve replacement. RESULTS: Among 12,043 adult patients (mean age, 74 years old; 42% female) undergoing TEE for transcatheter structural cardiac interventions, 429 (3.6%) patients had a major complication. Complication frequency was higher in patients on anticoagulation or antiplatelet therapy compared with those not on therapy (3.9% vs 0.5%; risk ratio [RR] = 8.09, P < .001). Compared with those patients <65 years of age, patients ≥65 years of age had a higher frequency of major complications (3.9% vs 2.2%; RR = 1.75, P < .001). Complication frequency was similar among male and female patients (3.5% vs 3.7%; RR = 0.96, P = .67). Among 28,848 patients who completed surgical valve replacement with TEE guidance, 728 (2.5%) experienced a major complication. CONCLUSIONS: This study found that more than 3% of patients undergoing TEE during transcatheter structural cardiac interventions have a major complication, which is more common among those on anticoagulant or antiplatelet therapy or who are elderly. With a shift of poor surgical candidates to less invasive percutaneous procedures, the future of TEE-guided procedures relies on comprehensive risk discussion and updating practices beyond conventional methods to minimize risk for TEE-related complications.

Endovascular Repair of an Ascending Aorta Dissection After Self-expanding TAVR by Suprasternal Approach.

Management of rare ascending aortic complications after transcatheter aortic valve replacement (TAVR) remains a poorly defined area of knowledge. Furthermore, because most patients undergoing TAVR are at intermediate to high surgical risk, the treatment of such complications often requires endovascular approaches. Herein, we present a novel technique of endovascular ascending aorta stent graft delivery from the innominate artery for the treatment of a type A aortic dissection after self-expandable TAVR implantation, specifically addressing the landing of the aortic stent within the crown of the TAVR valve.

Interstitial Collagen Loss, Myocardial Remodeling, and Function in Primary Mitral Regurgitation.

Interstitial collagen loss and cardiomyocyte ultrastructural damage accounts for left ventricular (LV) sphericity and decrease in LV twist and circumferential strain. Normal LV diastolic function belies significantly abnormal left atrial (LA) function and early LV diastolic untwist rate. This underscores the complex interplay of LV and LA myocardial remodeling and function in the pathophysiology of primary mitral regurgitation. In this study, we connect LA function with LV systolic and diastolic myocardial remodeling and function using cardiac magnetic resonance tissue tagging in primary mitral regurgitation.

Venous-Left Atrial Extracorporeal Membrane Oxygenation Configuration Use in Right Ventricular Failure and Tricuspid Ring.

Mechanical circulatory support devices are used to support the heart in cardiogenic shock. We present a case of demonstrating the feasible use of left ventricular assistive device with reverse configuration to support severe right ventricular failure in a patient with recent tricuspid annuloplasty ring.

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.

Transcatheter balloon dilatation of cor triatriatum dexter with percutaneous atrial septal defect closure.

Cor triatriatum dexter is an extremely rare congenital heart defect and cause of hypoxia in adults. We describe a case of cor triatriatum dexter discovered incidentally due to an iatrogenic atrial septal defect. The cor triatriatum dexter resolved with balloon dilation - a novel technique to manage this rare clinical condition. .

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.

Initial Experiences with the MitraClip G4: Review of the Novel Device Features.

OBJECTIVE: Percutaneous edge-to-edge mitral valve repair is an evolving procedure with increasing indications for use. The MitraClip™ G4 is the newest device with 4 device options, each with distinct characteristics. While the NTR and XTR clips have been in use, the G4 adds 2 new wider clips with additional features, the NTW and XTW. METHODS: We reviewed 26 cases employing the MitraClip G4 at our institution from November 2019 to March 2020. RESULTS: The NTR, XTR, NTW, and XTW clips were used in 3 (11.5%), 0 (0.0%), 16 (61.5%), and 11 (42.3%) cases, respectively. Median mitral regurgitation grade was reduced from 4+ to 1+, though 7 (27%) cases had 2+ residual mitral regurgitation. CONCLUSIONS: The new G4 device includes simplified instructions for use, the option of a wider clip, controlled gripper actuation, and potential left atrial pressure monitoring. The newest MitraClip G4 device allows for potential improved treatment options for patients with mitral regurgitation.

Suprasternal Versus Transfemoral Access for Transcatheter Aortic Valve Replacement: Insights From a Propensity Score Matched Analysis.

Background Suprasternal access is an alternative access strategy for transcatheter aortic valve replacement (TAVR) where the innominate artery is cannulated from an incision above the sternal notch. To date, suprasternal access has never been compared with transfemoral TAVR. Thus, we sought to assess safety, feasibility, and early clinical outcomes between suprasternal and transfemoral access for patients undergoing TAVR. Methods and Results We evaluated patients from 2 institutional prospective, observational registries containing 1348 patients. Patients were selected in a 2:1 ratio (transfemoral:suprasternal) on the basis of propensity score matching. The primary outcome was in-hospital mortality, and secondary outcomes included the incidence of ischemic stroke, major bleeding, vascular injury, left bundle-branch block, and permanent pacemaker implantation at 30-day follow-up. Propensity score matching identified 89 patients undergoing suprasternal TAVR and 159 patients undergoing transfemoral TAVR suitable for analysis. There was no significant difference between suprasternal TAVR and transfemoral TAVR with respect to in-hospital mortality (1.1% versus 0.6%; odds ratio [OR], 1.80; 95% CI, 0.11-29.06; P=0.680). No patients in either cohort suffered an ischemic stroke. The incidence of major bleeding (2.2% versus 2.5%; OR, 0.89; 95% CI, 0.16-4.96; P=0.895) and vascular injury (1.1% versus 1.9%; OR, 0.59; 95% CI, 0.06-5.77; P=0.651) did not differ significantly. The frequency of left bundle-branch block (9.4% versus 15.8%; OR, 0.56; 95% CI, 0.24-1.30; P=0.177) and permanent pacemaker implantation (11.2% versus 5.9%; OR, 2.01; 95% CI, 0.75-5.45; P=0.169) were not statistically significantly different. Conclusions Suprasternal TAVR was safe and achieved promising short-term clinical outcomes when compared with transfemoral TAVR. Future studies seeking to identify the optimal alternative access site should evaluate suprasternal TAVR access alongside other substitutes for transfemoral TAVR.

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.

Review of Published Cases of Syncope and Sudden Death in Patients With Severe Aortic Stenosis Documented by Electrocardiography.

The ECG findings during sudden collapse (syncope or sudden death) in severe aortic stenosis (AS) are not well defined. We conducted a comprehensive review of the literature for ECG data during sudden collapse in patients with AS and provided a case report of our own. There were 37 published cases of syncope or sudden death in patients with severe AS which were documented by ECG. Brady- or ventricular arrhythmias were documented in 34 cases (92%). Bradyarrhythmia (n = 24; 71%) was more common at the time of collapse than ventricular tachyarrhythmia (n = 10; 29%). There was slowing of the sinus rate before bradyarrhythmia in the vast majority of patients with bradyarrhythmia but not in those presenting with ventricular tachyarrhythmia (75% vs 0%; p <0.001). ECG evidence of ischemia (ST-segment depression or elevation) was present in most patients with bradyarrhythmia but not in those with ventricular tachyarrhythmia (75% vs 0%; p = 0.011). In conclusion, our findings suggest that left ventricular baroreceptor activation plays a dominant role in the pathophysiology of sudden collapse in patients with severe AS and suggest that ischemia may play a role as well.

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.

Snare-Assisted Delivery for Ascending Endovascular Repair of Acute Type A Dissection.

Endovascular stenting of the ascending aorta has been described for various aortic pathologies, including type A dissection in patients who are prohibitive risk for open surgery. Endovascular treatment of ascending aortic pathology poses unique anatomic and technical challenges related to aortic morphology. Herein, we present a novel technique of endovascular ascending stent graft delivery from a transfemoral approach for treatment of an acute type A dissection, utilizing a snare-guided deployment technique to facilitate favorable device deployment.

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.