Impact of Left Atrial Pressure on Outcomes After Mitral Transcatheter Edge-to-Edge Repair.

Background: Increased left atrial pressure (LAP) has been associated with adverse outcomes after mitral transcatheter edge-to-edge repair (M-TEER). We sought to evaluate outcomes based on differences in post-procedural LAP measured after final clip deployment. Methods: We included consecutive patients who underwent M-TEER at our institution between 2014-2022 with LAP monitoring. Patients were stratified into 3 groups according to tertiles of post-TEER mean LAP. Outcomes were assessed using Kaplan-Meier analysis and Cox proportional hazard models. Results: We included 273 patients (mean age 76.8±10.8 years, 42.5% women, 78.4% Caucasian). The mean post-TEER LAP was 8.7±1.7 mmHg in tertile 1 (N=85), 14.4±1.6 mmHg in tertile 2 (N=95), and 21.9±3.8 mmHg in tertile 3 (N=93). In comparison with tertile 1, both tertiles 2 and 3 were associated with increased risk of all-cause mortality or heart failure hospitalization at 2 years (adjHR 2.27, 95% CI 1.25-4.12; and adjHR 3.00, 95% CI 1.59-5.64 respectively). Among patients with primary MR, higher LAP was associated with increased risk of 2-year all-cause mortality or heart failure hospitalization [tertile 2 vs. 1: adjHR 3.00, 95% CI 1.37-6.56; and tertile 3 vs. 1: adjHR 5.52, 95% CI 2.04-14.95). However, in patients with secondary MR, neither being in tertile 2 (adjHR 1.53; 95% CI 0.55-4.24), nor tertile 3 (adjHR 2.18; 95% CI 0.82-5.77) were associated with the composite outcome compared with tertile 1. Any degree of LAP reduction following M-TEER was associated with lower mortality or heart failure hospitalization compared with no LAP reduction (adjHR 0.59; 95% CI 0.39-0.88). Conclusions: Elevated LAP after M-TEER was associated with increased 2-year risk of mortality or heart failure hospitalization. Exploration of reasons for elevated LAP after M-TEER, and ways to lower it warrant further investigation.

Myocardial Blood Flow Reserve, Microvascular Coronary Health, and Myocardial Remodeling in Patients With Aortic Stenosis.

BACKGROUND: Coronary microvascular function and hemodynamics may play a role in coronary circulation and myocardial remodeling in patients with aortic stenosis (AS). We aimed to evaluate the relationship between myocardial blood flow and myocardial function in patients with AS, no AS, and aortic valve sclerosis. METHODS AND RESULTS: We included consecutive patients who had resting transthoracic echocardiography and clinically indicated positron emission tomography myocardial perfusion imaging to capture their left ventricular ejection fraction, global longitudinal strain (GLS), and myocardial flow reserve (MFR). The primary outcome was major adverse cardiovascular event (all-cause mortality, myocardial infarction, or late revascularization). There were 2778 patients (208 with aortic sclerosis, 39 with prosthetic aortic valve, 2406 with no AS, and 54, 49, and 22 with mild, moderate, and severe AS, respectively). Increasing AS severity was associated with impaired MFR (P<0.001) and GLS (P<0.001), even when perfusion was normal. Statistically significant associations were noted between MFR and GLS, MFR and left ventricular ejection fraction, and MFR and left ventricular ejection fraction reserve. After a median follow-up of 349 (interquartile range, 116-662) days, 4 (7.4%), 5 (10.2%), and 6 (27.3%) patients experienced a major adverse cardiovascular event in the mild, moderate, and severe AS groups, respectively. In a matched-control analysis, patients with mild-to-moderate AS had higher rates of impaired MFR (52.9% versus 39.9%; P=0.048) and major adverse cardiovascular event (11.8% versus 3.0%; P=0.002). CONCLUSIONS: Despite lack of ischemia, as severity of AS increased, MFR decreased and GLS worsened, reflecting worse coronary microvascular health and myocardial remodeling. Positron emission tomography-derived MFR showed a significant independent correlation with left ventricular ejection fraction and GLS. Patients with prosthetic aortic valve showed a high prevalence of impaired MFR.

Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis.

BACKGROUND: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines. OBJECTIVES: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm2 and peak aortic valve velocity <4.0 m/s. METHODS: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women. RESULTS: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women. CONCLUSIONS: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.

Association of Secondary Mitral Regurgitation and Right Ventricular Dysfunction among Patients with Non-Ischemic Cardiomyopathy.

AIMS: The association between secondary mitral regurgitation (MR) and right ventricular (RV) dysfunction in heart failure patients with non-ischemic cardiomyopathy (NICM) is unclear. Hence, our objective was to study the association between secondary MR and the occurrence of RV dysfunction among patients with NICM using cardiac magnetic resonance (CMR). METHODS AND RESULTS: Patients with NICM were enrolled in a prospective observational registry between 2008-2019. CMR was used to quantify MR severity along with RV function. RV dysfunction was defined as RV ejection fraction <45%. The outcome of the study was a composite event of all-cause death, heart transplantation, or left ventricular assist device implantation at follow-up. In the study cohort of 241 patients, RV dysfunction (RVEF < 45%) was present in 148 (61%). In comparison to patients without RV dysfunction, those with RV dysfunction had higher median MR volume (23 ml [IQR 16-31ml] vs 18 ml [IQR 12-25 ml], P=0.002) and MR fraction (33% [IQR 25-43%] vs 22% [IQR 15-29%], P<0.001). Furthermore, secondary MR was independently associated with RV dysfunction: MR volume ≥ 24ml (OR 3.21, 95% CI 1.26-8.15, P= 0.01) and MR fraction≥ 30% (OR 5.46, 95% 2.23-13.35, P=0.002). Increasing RVEF (every 1% increase) was independently associated with lower risk of adverse events (HR 0.98, 95% 0.95, 1.00, P=0.047). CONCLUSIONS: In patients with NICM, the severity of secondary MR is associated with an increased prevalence of RV dysfunction. RV dysfunction is not only associated with the severity of LV dysfunction, but also with the severity of secondary MR.

Prognostic Value of Right Ventricular Afterload in Patients Undergoing Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Pulmonary hypertension (PH) and secondary mitral regurgitation (MR) are associated with adverse outcomes after mitral transcatheter edge-to-edge repair. We aim to study the prognostic value of invasively measured right ventricular afterload in patients undergoing mitral transcatheter edge-to-edge repair. METHODS AND RESULTS: We identified patients who underwent right heart catheterization ≤1 month before transcatheter edge-to-edge repair. The end points were all-cause mortality and a composite of mortality and heart failure hospitalization at 2 years. Using the receiver operating characteristic curve-derived threshold of 0.6 for pulmonary effective arterial elastance ([Ea], pulmonary artery systolic pressure/stroke volume), patients were stratified into 3 profiles based on PH severity (low elastance [HE]: Ea <0.6/mean pulmonary artery pressure (mPAP)) <35; High Elastance with No/Mild PH (HE-): Ea ≥0.6/mPAP <35; and HE with Moderate/Severe PH (HE+): Ea ≥0.6/mPAP ≥35) and MR pathogenesis (Primary MR [PMR])/low elastance, PMR/HE, and secondary MR). The association between this classification and clinical outcomes was examined using Cox regression. Among 114 patients included, 50.9% had PMR. Mean±SD age was 74.7±10.6 years. Patients with Ea ≥0.6 were more likely to have diabetes, atrial fibrillation, New York Heart Association III/IV status, and secondary MR (all P<0.05). Overall, 2-year cumulative survival was 71.1% and was lower in patients with secondary MR and mPAP ≥35. Compared with patients with low elastance, cumulative 2-year event-free survival was significantly lower in HE- and HE+ patients (85.5% versus 50.4% versus 41.0%, respectively, P=0.001). Also, cumulative 2-year event-free survival was significantly higher in patients with PMR/low elastance when compared with PMR/HE and patients with secondary mitral regurgitation (85.5% versus 55.5% versus 46.1%, respectively, P=0.005). CONCLUSIONS: Assessment of the preprocedural cardiopulmonary profile based on mPAP, MR pathogenesis, and Ea guides patient selection by identifying hemodynamic features that indicate likely benefit from mitral-transcatheter edge-to-edge repair in PH or lack thereof.

Physical and Computational Modeling for Transcatheter Structural Heart Interventions.

Structural heart disease interventions rely heavily on preprocedural planning and simulation to improve procedural outcomes and predict and prevent potential procedural complications. Modeling technologies, namely 3-dimensional (3D) printing and computational modeling, are nowadays increasingly used to predict the interaction between cardiac anatomy and implantable devices. Such models play a role in patient education, operator training, procedural simulation, and appropriate device selection. However, current modeling is often limited by the replication of a single static configuration within a dynamic cardiac cycle. Recognizing that health systems may face technical and economic limitations to the creation of "in-house" 3D-printed models, structural heart teams are pivoting to the use of computational software for modeling purposes.

Echocardiographic Profiling Predicts Clinical Outcomes After Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Prior studies investigating the impact of residual mitral regurgitation (MR), tricuspid regurgitation (TR), and elevated predischarge transmitral mean pressure gradient (TMPG) on outcomes after mitral transcatheter edge-to-edge repair (TEER) have assessed each parameter in isolation. We sought to examine the prognostic value of combining predischarge MR, TR, and TMPG to study long-term outcomes after TEER. METHODS AND RESULTS: We reviewed the records of 291 patients who underwent successful mitral TEER at our institution between March 2014 and June 2022. Using well-established outcomes-related cutoffs for predischarge MR (≥moderate), TR (≥moderate), and TMPG (≥5 mm Hg), 3 echo profiles were developed based on the number of risk factors present (optimal: 0 risk factors, mixed: 1 risk factor, poor: ≥2 risk factors). Discrimination of the profiles for predicting the primary composite end point of all-cause mortality and heart failure hospitalization at 2 years was examined using Cox regression. Overall, mean age was 76.7±10.6 years, 43.3% were women, and 53% had primary MR. Two-year event-free survival was 61%. Predischarge TR≥moderate, MR≥moderate, and TMPG≥5 mm Hg were risk factors associated with the primary end point. Compared with the optimal profile, there was an incremental risk in 2-year event-rate with each worsening profile (optimal as reference; mixed profile: hazard ratio (HR), 2.87 [95% CI, 1.71-5.17], P<0.001; poor profile: HR, 3.76 [95% CI, 1.84-6.53], P<0.001). Echocardiographic profile was statistically associated with the 2-year mortality end point (optimal as reference; mixed profile: HR, 3.55 [95% CI, 1.81-5.96], P<0.001; poor profile: HR, 3.39 [95% CI, 2.56-7.33], P=0.02). CONCLUSIONS: The echocardiographic profile integrating predischarge TR, MR, and TMPG presents a novel prognostic stratification tool for patients undergoing mitral TEER.

Understanding Treatment Preferences for Patients with Tricuspid Regurgitation.

Background. Tricuspid regurgitation (TR) is a high-prevalence disease associated with poor quality of life and mortality. This quantitative patient preference study aims to identify TR patients' perspectives on risk-benefit tradeoffs. Methods. A discrete-choice experiment was developed to explore TR treatment risk-benefit tradeoffs. Attributes (levels) tested were treatment (procedure, medical management), reintervention risk (0%, 1%, 5%, 10%), medications over 2 y (none, reduce, same, increase), shortness of breath (none/mild, moderate, severe), and swelling (never, 3× per week, daily). A mixed logit regression model estimated preferences and calculated predicted probabilities. Relative attribute importance was calculated. Subgroup analyses were performed. Results. An online survey was completed by 150 TR patients. Shortness of breath was the most important attribute and accounted for 65.8% of treatment decision making. The average patients' predicted probability of preferring a "procedure-like" profile over a "medical management-like" profile was 99.7%. This decreased to 78.9% for a level change from severe to moderate in shortness of breath in the "medical management-like" profile. Subgroup analysis confirmed that patients older than 64 y had a stronger preference to avoid severe shortness of breath compared with younger patients (P < 0.02), as did severe or worse TR patients relative to moderate. New York Heart Association class I/II patients more strongly preferred to avoid procedural reintervention risk relative to class III/IV patients (P < 0.03). Conclusion. TR patients are willing to accept higher procedural reintervention risk if shortness of breath is alleviated. This risk tolerance is higher for older and more symptomatic patients. These results emphasize the appropriateness of developing TR therapies and the importance of addressing symptom burden. Highlights: This study provides quantitative patient preference data from clinically confirmed tricuspid regurgitation (TR) patients to understand their treatment preferences.Using a targeted literature search and patient, physician, and Food and Drug Administration feedback, a cross-sectional survey with a discrete-choice experiment that focused on 5 of the most important attributes to TR patients was developed and administered online.TR patients are willing to accept higher procedural reintervention risk if shortness of breath is alleviated, and this risk tolerance is higher for older and more symptomatic patients.

TAV-in-TAV in Failed Homograft: Redo TAVI in a Patient With 3 Previous Sternotomies.

A 59-year-old male patient with history of rheumatic heart disease with 3 previous surgical aortic valve replacements with the last one being homograft followed by transcatheter aortic valve implantation in failed homograft presented with severe aortic regurgitation and cardiogenic shock requiring urgent TAV-in-TAV-in homograft. (Level of Difficulty: Advanced.).

Feasibility and Outcomes of Mitral Transcatheter Edge-To-Edge Repair in Patients With Variable Degrees of Mitral Annular Calcification.

Background The clinical significance of mitral annular calcification (MAC) in patients undergoing mitral transcatheter edge-to-edge repair is not well understood. There is limited evidence regarding the feasibility, durability of repair, and the prognostic value of MAC in this population. We sought to examine the prognostic value of MAC, its severity, and its impact on procedural success and durability of mitral transcatheter edge-to-edge repair. Methods and Results We reviewed the records of 280 patients with moderate-severe or severe mitral regurgitation who underwent mitral transcatheter edge-to-edge repair with MitraClip from March 2014 to March 2022. The primary end point was cumulative survival at 1 year. Independent factors associated with the primary end point were identified using multivariable Cox regression. Among 280 patients included in the final analysis, 249 had none/mild MAC, and 31 had moderate/severe MAC. Median follow-up was 23.1 months (interquartile range: 11.1-40.4). Procedural success was comparable in the MAC and non-MAC groups (92.6% versus 91.4%, P=0.79) with similar rates of residual mitral regurgitation ≤2 at 1 year (86.7% versus 93.2%, P=0.55). Moderate/severe MAC was associated with less improvement in New York Heart Association III/IV at 30 days when compared with none/mild MAC (45.8% versus 14.3%, P=0.001). The moderate/severe MAC group had lower cumulative 1-year survival (56.8% versus 80.0%, hazard ratio [HR], 1.98 [95% CI, 1.27-3.10], P=0.002). Moderate/severe MAC and Society of Thoracic Surgeons predicted risk of mortality for mitral valve repair were independently associated with the primary end point (HR, 2.20 [1.10-4.41], P=0.02; and HR, 1.014 [1.006-1.078], P=0.02, respectively). Conclusions Mitral TEER is a safe and feasible intervention in selected patients with significant MAC and associated with similar mitral regurgitation reduction at 1 year compared with patients with none/mild MAC. Patients with moderate/severe MAC had a high 1-year mortality and less improvement in their symptoms after TEER.

Now You See Me Now You Don't: Subaortic Membrane Causing a Diagnostic Dilemma.

Subaortic stenosis secondary to subaortic membrane is the second most common form of left ventricular outflow tract obstruction. We present the case of a 70-year-old male patient who presented with a 6-week history of progressive signs of heart failure. Multimodality imaging was required to confirm the presence of a subaortic membrane. (Level of Difficulty: Beginner.).

Tough Crossing: A Challenging Case of Valve-in-Valve Transcatheter Tricuspid Valve Replacement.

Transcatheter tricuspid valve replacement is a feasible treatment alternative in high-risk patients with degenerated tricuspid prosthesis. Either transjugular or transfemoral approaches are feasible, with the latter being used more commonly. We describe a challenging case of valve-in-valve transcatheter tricuspid valve replacement where we used a long sheath positioned in the right ventricular outflow tract to deliver the transcatheter heart valve.

When Echocardiography Is Challenging in Localizing Bioprosthetic Aortic Regurgitation: Dye Don't Lie.

Transesophageal echocardiography is the main imaging modality for localizing and quantifying prosthetic aortic regurgitation. We describe a case of bioprosthetic aortic paravalvular leak (PVL) where transesophageal echocardiography was inadequate; aortic root angiography and computed tomography fusion were critical in diagnosing and guiding closure. Multimodality imaging can be pivotal in localizing PVL and guiding transcatheter PVL closure. (Level of Difficulty: Intermediate.).

Role of Multimodality Imaging in Transcatheter Structural Interventions.

Cardiac imaging is the backbone for safe and optimal transcatheter structural interventions. Transthoracic echocardiogram is the initial modality to assess valvular disorders, while transesophageal echocardiogram is best to delineate the mechanism of valvular regurgitation, preprocedural assessment for transcatheter edge-to-edge repair, and for intraprocedural guidance. Cardiac computed tomography is the modality of choice for assessing calcifications, maneuvering multiplaner reconstruction of different cardiac structures, preprocedural planning for various transcatheter valve replacement, and assessing for hypoattenuated leaflet thickening and reduced leaflet motion. Cardiac magnetic resonance imaging is best known for most accurate volumetric assessment of valvular regurgitation and chamber size quantification. Cardiac positron emission tomography is the only modality that could assess active infection through using fluorine 18 fluorodeoxyglucose radiotracer.