Imaging of the Mitral Valve.

Echocardiographic imaging is the foundation for the evaluation of mitral valve dysfunction. Both transthoracic and transesophageal echocardiography provide insight into the anatomy, pathology, and classification mitral valve dysfunction. Echocardiography also provides a multi-parametric approach with semi-quantitative and quantitative parameters to assess the severity of mitral regurgitation and mitral stenosis. Transesophageal imaging is essential in the assessment of patients considered for surgical or transcatheter interventional strategies to treat mitral valve dysfunction. Cardiac computed tomography (CT) and cardiac MRI are useful adjunctive imaging techniques in mitral valve disease with CT providing detailed procedural specificity and MRI providing detailed ventricular and regurgitant flow analysis.

Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

BACKGROUND: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR). OBJECTIVES: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+. METHODS: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression. RESULTS: In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively). CONCLUSIONS: The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833).

Mortality Associated With Proportionality of Secondary Mitral Regurgitation After Transcatheter Mitral Valve Repair: North American Mitraclip for Functional Mitral Regurgitation Registry.

The association, if any, between the effective regurgitant orifice area (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients who undergo mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip system (Abbott Vascular, Santa Clara, CA). This study's objective was to determine the association between EROA/LVEDV and 1-year mortality in patients who undergo m-TEER with MitraClip. In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. We studied 525 patients with secondary MR who underwent m-TEER. Most patients were male (63%) and were New York Heart Association class III (61%) or IV (21%). Mitral regurgitation was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely, with median = 0.19 mm2/ml, interquartile range [0.12,0.28] mm2/ml, and 187 patients (36%) had values <0.15 mm2/ml. Postprocedural mitral regurgitation severity was substantially alleviated, being 1+ or less in 74%, 2+ in 20%, 3+ in 4%, and 4+ in 2%; 1-year mortality was 22%. After adjustment for confounders, the logarithmic transformation (Ln) of EROA/LVEDV was associated with 1-year mortality (odds ratio 0.600, 95% confidence interval 0.386 to 0.933, p = 0.023). A higher Society of Thoracic Surgeons risk score was also associated with increased mortality. In conclusion, lower values of Ln(EROA/LVEDV) were associated with increased 1-year mortality in this multicenter registry. The slope of the association is steep at low values but gradually flattens as Ln(EROA/LVEDV) increases.

Mitral Valve Transcatheter Edge-to-Edge Repair Volumes and Trends.

Background: Despite an association between operator volumes and procedural success, there remains an incomplete understanding of the contemporary utilization and procedural volumes for mitral valve transcatheter edge-to-edge repair (MTEER). We aimed to identify annual operator procedural volumes, temporal trends, and geographic variability for MTEER among Medicare patients in the United States (US). Methods: We queried the National Medicare Provider Utilization and Payment Database for a CPT code (33418) specific for MitraClip device from 2015 through 2019. We analyzed annual operator procedural volumes and incidence and identified longitudinal and geographic trends in MTEER utilization. Results: From 2015 through 2019, a total of 27,034 MTEER procedures were performed among Medicare patients in the US. The nationwide incidence increased from 6.2 per 100,000 patients in 2015 to 23.8 per 100,000 patients in 2019, a 283% increase over the study period (Ptrend < 0.001). The incidence of MTEER by state varied by nearly 900% (range 5.5 to 54.9 per 100,000 person-years). In 2019, the mean annual MTEER operator annual volume was 9.1 MTEER procedures and had grown from 6.2 per year in 2015. Conclusions: In this nationwide study of Medicare beneficiaries in the United States, we identified a significant and sustained increase in the utilization of MTEER devices and operators and growth in annual procedural volumes from 2015 through 2019 with considerable variability in utilization by state. Further studies are needed to understand the clinical impact of variability in utilization and the optimal procedural volumes to ensure high efficacy outcomes and maintain critical access to MTEER therapies.

Intermediate-Term Outcomes Following Transcatheter Aortic Valve Implantation in Patients with a History of Chest Radiation Therapy: A Propensity Score Matched Analysis.

Chest radiation therapy (XRT) has been associated with a higher rate of mortality following surgical aortic valve replacement. We performed a single-center retrospective analysis of patients with severe AS who underwent TAVI from January 1 2012 to July 31 2020 comparing patients with and without XRT. A total of 915 patients met inclusion criteria, with a total of 50 patients found to have a history of XRT. At a mean follow-up of 2.4 years, unadjusted and propensity score matching analysis demonstrated no differences in mortality, heart failure or bleeding-related hospitalization, overall stroke, and 30-day pacemaker implantation in patients with and without XRT.

Clinical Predictors of Mortality and Heart Failure Hospitalization in Patients With Severe Tricuspid Regurgitation.

Background: There is an incomplete understanding of the predictors of morbidity and mortality in patients with severe tricuspid regurgitation (TR). This study sought to identify key risk factors for all-cause mortality and heart failure (HF) hospitalization among patients with severe TR. Methods: Patients with severe TR were identified from 2 centers, Oregon Health & Science University and Abrazo Health, from January 01, 2016 to December 31, 2018. Patients with any concomitant severe valvular diseases or prior valvular intervention were excluded. Multivariable regression was utilized to identify demographic, clinical, and echocardiographic variables independently associated with all-cause mortality or HF hospitalization. Results: 435 patients with severe TR were followed for a median of 2.8 years. The mean age of the population was 66.9 ± 18.5 years and 58% were female. All-cause mortality was identified in 20.5% of the population. Of the cohort, 35.4% of patients were hospitalized for HF. Isolated tricuspid valve intervention was performed in 2.5% of patients. Independent predictors of all-cause mortality included history of solid tumor (odds ratio [OR] 6.6, 95% confidence interval [CI] 2.1-19.1, p = 0.001), history of peripheral artery disease (OR 3.5, 95% CI 1.2-9.4, p = 0.013), and elevated international normalized ratio in the absence of anticoagulation (OR 1.9, 95% CI 1.2-3.2, p = 0.008). Predictors of HF hospitalization included history of diabetes mellitus (OR 2.2, 95% CI 1.1-4.0, p = 0.014) and history of reduced left ventricular ejection fraction (OR 5.7, 95% CI 2.9-11.7, p < 0.0001). Conclusions: Severe untreated TR is associated with high mortality and frequent HF hospitalizations. Understanding predictors of these outcomes is important to identify patients who may benefit from early tricuspid valve intervention to help improve outcomes in this patient population.

Severe MR With Prior Alfieri Stitch Treated With Transcatheter Edge-to-Edge Repair and a Vascular Plug.

We present a case of a high-risk surgical patient with prior surgical Alfieri stitch and recurrent severe mitral regurgitation. In cases with suitable anatomy, mitral valve transcatheter edge-to-edge repair and vascular plug closure of a small regurgitant orifice can be used with excellent results. (Level of Difficulty: Advanced.).

30-Day Outcomes Following Transfemoral Transseptal Transcatheter Mitral Valve Replacement: Intrepid TMVR Early Feasibility Study Results.

OBJECTIVES: The aim of this study was to evaluate outcomes of transcatheter mitral valve replacement (TMVR) with transfemoral access in patients at prohibitive or high surgical risk. BACKGROUND: Prohibitive surgical risk may preclude mitral valve replacement surgery in some patients. The investigational Intrepid TMVR system has previously been evaluated using transapical access for delivery of a self-expanding bioprosthetic valve. METHODS: This prospective, multicenter, nonrandomized early feasibility study evaluated the safety and performance of the Intrepid valve using transfemoral access enabling transseptal delivery in patients with moderate to severe or severe symptomatic mitral regurgitation at high surgical risk. Candidacy was determined by heart teams, with approval by a central screening committee. Echocardiographic data were evaluated by an independent core laboratory. Clinical events were adjudicated by a clinical events committee. RESULTS: Fifteen patients were enrolled at 6 sites from February 2020 to May 2021. The median age was 80 years, and median Society of Thoracic Surgeons Predicted Risk of Mortality was 4.7%; 87% of patients were men, and 53% had undergone prior sternotomy. Fourteen implants were successful. One patient was converted to surgery during the index procedure. Patients stayed a median of 5 days postprocedure. There were 6 access site bleeds (40%) and 11 iatrogenic atrial septal defect closures (73%). At 30 days, there were no deaths, strokes, or reinterventions. All patients undergoing implantation had trace or no valvular or paravalvular mitral regurgitation, and the mean gradient was 4.7 mm Hg (IQR: 3.0-6.7 mm Hg). CONCLUSIONS: Thirty-day results from the Intrepid transfemoral TMVR early feasibility study demonstrate excellent valve function and no mortality or stroke. Additional patients and longer follow-up are needed to confirm these findings. ([The Early Feasibility Study of the Intrepid™ TMVR Transseptal System]; NCT02322840).

Three-Dimensional Intracardiac Echocardiography for Tricuspid Transcatheter Edge-to-Edge Repair.

Patients with severe symptomatic tricuspid regurgitation face a significant dilemma in treatment options, as the yearly mortality with medical therapy and the surgical mortality for tricuspid repair or replacement are high. Transcatheter edge-to-edge repair (TEER) for the tricuspid valve is becoming a viable option in patients, although procedural success is dependent on high-quality imaging. While transesophageal echocardiography remains the standard for tricuspid TEER procedures, intracardiac echocardiography (ICE) with three-dimensional (3D) multiplanar reconstruction (MPR) has many theoretical and practical advantages. The aim of this article was to describe the in vitro wet lab-based imaging work done to facilitate the best approach to 3D MPR ICE imaging and the procedural experience gained with 3D MPR ICE in tricuspid TEER procedures with the PASCAL device.

Bioprosthetic valve oversizing is associated with increased risk of valve thrombosis following TAVR.

BACKGROUND: Hypoattenuating leaflet thickening (HALT), the radiographic manifestation of transcatheter heart valve thrombosis, is commonly identified following transcatheter aortic valve replacement (TAVR) and associated with increased risk of stroke and structural valve deterioration. While anticoagulation effectively resolves HALT, routine use remains controversial. We aimed to identify hemodynamic, anatomic, and comorbid predictors of HALT. METHODS: We evaluated consecutive patients with severe aortic stenosis who underwent TAVR with Edwards SAPIEN 3 bioprosthesis at a single center between June 1, 2018 and October 30, 2019. Patients on anticoagulation and those receiving valve-in-valve were excluded. Clinically driven computed tomography (CT) imaging was performed to assess for HALT at the discretion of the treating valve team. RESULTS: A total of 78 patients with a mean age of 78 ± 10 years and STS risk score 5.5 ± 3.3% were analyzed. HALT was identified in 11 (14.1%) patients. Compared to controls, those with HALT had smaller annular areas, 435 ± 57 mm2 vs. 489 ± 79 mm2 (p = .032), but received comparable size valves. In multivariate regression, valve oversizing by more than 20% was associated with increased risk of HALT, OR 23.5, 95% CI 2.5-223, (p = .006). After initiation of anticoagulation, patients with HALT had similar rates of stroke, major bleeding, and all-cause mortality out to an average of 243 days. CONCLUSIONS: In this pragmatic study of patients undergoing TAVR with SAPIEN 3 valves, we report the novel finding that oversizing by more than 20% was independently associated with increased risk of HALT. These findings warrant confirmation in larger and prospective trials.

Late Type A Dissection After Transfemoral Aortic Valve Replacement.

An 87-year-old woman had residual moderate to severe aortic insufficiency following transcatheter aortic valve replacement. A year later, she developed extensive Stanford type A aortic dissection originating at the supra-annular aortic edge of the transcatheter aortic valve replacement nitinol frame. Dissection repair, frozen elephant trunk with exclusion of prior insufficiency while preserving the transcatheter aortic valve replacement valve was performed. (Level of Difficulty: Beginner.).

Clinical and Echocardiographic Predictors of Outcomes in Patients With Moderate (Mean Transvalvular Gradient 20 to 40 mm Hg) Aortic Stenosis.

Risk factors for adverse clinical outcomes in patients with moderate aortic stenosis are not well defined. Previous studies have suggested that certain patients with moderate AS may be at an increased risk of heart failure (HF) or death. All patients with moderate AS seen in our institution during the study period (6/1/2014 to 6/30/2017) with a minimum 1-year follow-up were included. Clinical and echocardiographic data were collected retrospectively. End points were defined as HF hospitalization, aortic valve replacement (AVR), or death. Kaplan-Meier and multivariable Cox proportional hazard models analyses were conducted using composite outcomes of (1) HF hospitalization or AVR and (2) HF hospitalization, AVR, or all-cause death. A total of 151 subjects met the inclusion criteria. The most significant risk factors associated with the composite outcomes were an ejection fraction (EF) <50% ((1) hazard ratio [HR]: 4.1; 95% confidence interval [CI]: 2.34, 7.12; (2) HR: 3.8; 95% CI: 2.2, 6.6), atrial fibrillation ((1) HR: 2.0; 95% CI: 1.2, 3.2; (2) HR: 2.1; 95% CI: 1.43, 3.2), left ventricular hypertrophy ((1) HR: 5.85; 95% CI: 2.0, 15.8; (2) HR: 3.2; 95% CI: 1.4, 7.4), aortic valve area ((1) HR: 0.3; 95% CI: 0.1, 0.6; (2) HR: 0.32; 95% CI: 0.1, 0.65), and abnormal right ventricular function ((1) HR: 4.3; 95% CI: 2.5, 7.5; (2) HR: 5.5; 95% CI: 3.0, 9.8). In conclusion, presence of reduced ejection fraction, atrial fibrillation, left ventricular hypertrophy, and abnormal right ventricular function are associated with an increased risk of HF hospitalization, AVR, and death in patients with moderate aortic stenosis.

Temporal Changes in Skeletal Muscle Capillary Responses and Endothelial-Derived Vasodilators in Obesity-Related Insulin Resistance.

The inability of insulin to increase skeletal muscle capillary blood volume (CBV) reduces glucose uptake in insulin resistance (IR). We hypothesized that abnormalities in endothelial-derived vasodilator pathways are temporally associated with the development of IR and an impaired ability to increase skeletal muscle CBV. A comprehensive metabolic and vascular screening assessment was performed on 10 adult rhesus macaques at baseline and every 4-6 months for 2 years after starting a high-fat diet supplemented with fructose. Diet changes resulted in an 80% increase in truncal fat by 4 months. Hyperinsulinemia and decreased glucose utilization were observed from 4 to 18 months. At 24 months, pancreatic secretory function and the glucose utilization rate declined. CBV at rest and during an intravenous glucose tolerance test demonstrated a sustained increase from 4 to 18 months and then abruptly fell at 24 months. Nitric oxide bioavailability progressively decreased over 2 years. Conversely, endothelial-derived vasodilators progressively increased over 18 months and then abruptly decreased at 24 months in concert with the CBV. The increase in basal and glucose-mediated CBV early in IR may represent a compensatory response through endothelial-derived vasodilator pathways. The inability to sustain a vascular compensatory response limits glucose-mediated increases in CBV, which correlates with the severity of IR.

Ischemic memory imaging in nonhuman primates with echocardiographic molecular imaging of selectin expression.

BACKGROUND: Selectins are adhesion molecules that are expressed by the vascular endothelium upon activation and may be an imaging target for detecting myocardial ischemia long after resolution. The aim of this study was to test the hypothesis that molecular imaging of selectins with myocardial contrast echocardiographic (MCE) molecular imaging could be used to detect recent brief ischemia in closed-chest nonhuman primates. METHODS: Myocardial ischemia was produced in anesthetized adult rhesus macaques (n = 6) by percutaneous balloon catheter occlusion of the left anterior descending or circumflex coronary artery for 5 to 10 min. Three separate macaques served as nonischemic controls. MCE perfusion imaging was performed during coronary occlusion to measure risk area and at 100 to 110 min to exclude infarction. MCE molecular imaging was performed at 30 and 90 min after reperfusion using a lipid microbubble bearing dimeric recombinant human P-selectin glycoprotein ligand-1 (MB-YSPSL). Collection of blood for safety data, electrocardiography, and echocardiography were performed at baseline and before and 10 min after each MB-YSPSL injection. RESULTS: Vital signs, oxygen saturation, electrocardiographic results, ventricular systolic function, pulmonary vascular resistance, and serum safety markers were unchanged by intravenous injection of MB-YSPSL. On echocardiography, left ventricular dysfunction in the risk area had resolved by 30 min, and there was no evidence of infarction on MCE perfusion imaging. On selectin-targeted MCE molecular imaging, signal enhancement was greater (P < .05) in the risk area than remote territory at 30 min (25 ± 11 vs 11 ± 4 IU) and 90 min (13 ± 3 vs 3 ± 2 IU) after ischemia. There was no enhancement (<1 IU) in control nonischemic subjects. CONCLUSIONS: In primates, MCE molecular imaging of selectins using MB-YSPSL, a recombinant ligand appropriate for humans, is both safe and effective for imaging recent myocardial ischemia. This technique may be useful for detecting recent ischemia in patients with chest pain even in the absence of necrosis.