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.

Houston Methodist cardiovascular learning health system (CVD-LHS) registry: Methods for development and implementation of an automated electronic medical record-based registry using an informatics framework approach.

Objectives: To investigate the potential value and feasibility of creating a listing system-wide registry of patients with at-risk and established Atherosclerotic Cardiovascular Disease (ASCVD) within a large healthcare system using automated data extraction methods to systematically identify burden, determinants, and the spectrum of at-risk patients to inform population health management. Additionally, the Houston Methodist Cardiovascular Disease Learning Health System (HM CVD-LHS) registry intends to create high-quality data-driven analytical insights to assess, track, and promote cardiovascular research and care. Methods: We conducted a retrospective multi-center, cohort analysis of adult patients who were seen in the outpatient settings of a large healthcare system between June 2016 - December 2022 to create an EMR-based registry. A common framework was developed to automatically extract clinical data from the EMR and then integrate it with the social determinants of health information retrieved from external sources. Microsoft's SQL Server Management Studio was used for creating multiple Extract-Transform-Load scripts and stored procedures for collecting, cleaning, storing, monitoring, reviewing, auto-updating, validating, and reporting the data based on the registry goals. Results: A real-time, programmatically deidentified, auto-updated EMR-based HM CVD-LHS registry was developed with ∼450 variables stored in multiple tables each containing information related to patient's demographics, encounters, diagnoses, vitals, labs, medication use, and comorbidities. Out of 1,171,768 adult individuals in the registry, 113,022 (9.6%) ASCVD patients were identified between June 2016 and December 2022 (mean age was 69.2 ± 12.2 years, with 55% Men and 15% Black individuals). Further, multi-level groupings of patients with laboratory test results and medication use have been analyzed for evaluating the outcomes of interest. Conclusions: HM CVD-LHS registry database was developed successfully providing the listing registry of patients with established ASCVD and those at risk. This approach empowers knowledge inference and provides support for efforts to move away from manual patient chart abstraction by suggesting that a common registry framework with a concurrent design of data collection tools and reporting rapidly extracting useful structured clinical data from EMRs for creating patient or specialty population registries.

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.

Noninvasive Prediction of Pulmonary Capillary Wedge Pressure in Patients With Normal Left Ventricular Ejection Fraction: Comparison of Cardiac Magnetic Resonance With Comprehensive Echocardiography.

BACKGROUND: Cardiac magnetic resonance (CMR) was recently reported to predict mean pulmonary capillary wedge pressure (PCWP). However, there is a paucity of data on its accuracy for estimation of PCWP in patients with normal left ventricular (LV) ejection fraction (EF). We sought to examine its accuracy against the invasive gold standard and to compare it with the accuracy of comprehensive echocardiography. METHODS: Stable patients with EF of ≥50% who underwent right heart catheterization, CMR, and echocardiographic imaging within 1 week were included. Pulmonary capillary wedge pressure was estimated by CMR using a previously validated equation where PCWP is estimated based on the left atrial maximum volume and LV mass. Echocardiographic estimation of PCWP was based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines, taking into account the presence of myocardial disease. RESULTS: The mean age of the 79 patients was 55 ± 15 years, and 58.2% were female. There were 33 patients with PCWP >15 mm Hg by right heart catheterization. Cardiac magnetic resonance prediction of PCWP had an area under the curve (AUC) = 0.72. In comparison, echocardiographic prediction of PCWP showed a higher accuracy (AUC = 0.87 vs AUC = 0.72; P = .008). CONCLUSIONS: In patients with normal LV EF, CMR estimation of mean PCWP based on LV mass and left atrial volume has modest accuracy for detecting patients with mean PCWP >15 mm Hg. Comprehensive echocardiography predicts elevated PCWP with higher accuracy in comparison with CMR.

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.

Guidelines for the Evaluation of Prosthetic Valve Function With Cardiovascular Imaging: A Report From the American Society of Echocardiography Developed in Collaboration With the Society for Cardiovascular Magnetic Resonance and the Society of Cardiovascular Computed Tomography.

In patients with significant cardiac valvular disease, intervention with either valve repair or valve replacement may be inevitable. Although valve repair is frequently performed, especially for mitral and tricuspid regurgitation, valve replacement remains common, particularly in adults. Diagnostic methods are often needed to assess the function of the prosthesis. Echocardiography is the first-line method for noninvasive evaluation of prosthetic valve function. The transthoracic approach is complemented with two-dimensional and three-dimensional transesophageal echocardiography for further refinement of valve morphology and function when needed. More recently, advances in computed tomography and cardiac magnetic resonance have enhanced their roles in evaluating valvular heart disease. This document offers a review of the echocardiographic techniques used and provides recommendations and general guidelines for evaluation of prosthetic valve function on the basis of the scientific literature and consensus of a panel of experts. This guideline discusses the role of advanced imaging with transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance in evaluating prosthetic valve structure, function, and regurgitation. It replaces the 2009 American Society of Echocardiography guideline on prosthetic valves and complements the 2019 guideline on the evaluation of valvular regurgitation after percutaneous valve repair or replacement.

Aortic Regurgitation: Review of the Diagnostic Criteria and the Management Guidelines.

PURPOSE OF REVIEW: The evaluation of aortic regurgitation (AR) has advanced from physical examination and angiography towards evidence based non-invasive quantitative methods, primarily with echocardiography and more recently with cardiac magnetic resonance (CMR). This review highlights the guidelines and recent evidence in the diagnosis and management of AR; and outlines future areas of research. RECENT FINDINGS: Contemporary large cohorts of AR patients studied with echocardiography and CMR suggest that the left ventricular remodeling and systolic function triggers for intervention may be lower than previously recommended in the guidelines and emphasize the importance of LV volumes in risk stratification. Important gaps of knowledge in the quantitation of AR severity and patient risk stratification were fulfilled recently. Potential thresholds for intervention using ventricular volumes and CMR quantitative findings were recently described. The criteria for what constitutes hemodynamically significant AR and the optimal timing of intervention AR deserve further study.

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.

Coronary microvascular health in symptomatic patients with prior COVID-19 infection: an updated analysis.

AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with endothelial dysfunction. We aimed to determine the effects of prior coronavirus disease 2019 (COVID-19) on the coronary microvasculature accounting for time from COVID-19, disease severity, SARS-CoV-2 variants, and in subgroups of patients with diabetes and those with no known coronary artery disease. METHODS AND RESULTS: Cases consisted of patients with previous COVID-19 who had clinically indicated positron emission tomography (PET) imaging and were matched 1:3 on clinical and cardiovascular risk factors to controls having no prior infection. Myocardial flow reserve (MFR) was calculated as the ratio of stress to rest myocardial blood flow (MBF) in mL/min/g of the left ventricle. Comparisons between cases and controls were made for the odds and prevalence of impaired MFR (MFR < 2). We included 271 cases matched to 815 controls (mean ± SD age 65 ± 12 years, 52% men). The median (inter-quartile range) number of days between COVID-19 infection and PET imaging was 174 (58-338) days. Patients with prior COVID-19 had a statistically significant higher odds of MFR <2 (adjusted odds ratio 3.1, 95% confidence interval 2.8-4.25 P < 0.001). Results were similar in clinically meaningful subgroups. The proportion of cases with MFR <2 peaked 6-9 months from imaging with a statistically non-significant downtrend afterwards and was comparable across SARS-CoV-2 variants but increased with increasing severity of infection. CONCLUSION: The prevalence of impaired MFR is similar by duration of time from infection up to 1 year and SARS-CoV-2 variants, but significantly differs by severity of infection.

Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.

BACKGROUND: The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. METHODS: We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. RESULTS: We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (P<0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; P<0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (P<0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (P value for trend <0.001), whereas they were unchanged across the spectrum of AR (P=0.24 and 0.42, respectively). CONCLUSIONS: Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

Influence of Cardiac Remodeling on Clinical Outcomes in Patients With Aortic Regurgitation.

BACKGROUND: Quantitative cardiac magnetic resonance (CMR) outcome studies in aortic regurgitation (AR) are few. It is unclear if volume measurements are beneficial over diameters. OBJECTIVES: This study sought to evaluate the association of CMR quantitative thresholds and outcomes in AR patients. METHODS: In a multicenter study, asymptomatic patients with moderate or severe AR on CMR with preserved left ventricular ejection fraction (LVEF) were evaluated. Primary outcome was development of symptoms or decrease in LVEF to <50%, development of guideline indications for surgery based on LV dimensions, or death under medical management. Secondary outcome was the same as the primary outcome, excluding surgery for remodeling indications. We excluded patients who underwent surgery within 30 days of CMR. Receiver-operating characteristic analyses for the association with outcomes were performed. RESULTS: We studied 458 patients (median age: 60 years; IQR: 46-70 years). During a median follow-up of 2.4 years (IQR: 0.9-5.3 years), 133 events occurred. Optimal thresholds were regurgitant volume of 47 mL and regurgitant fraction of 43%, indexed LV end-systolic (iLVES) volume of 43 mL/m2, indexed LV end-diastolic volume of 109 mL/m2, and iLVES diameter of 2 cm/m2. In multivariable regression analysis, iLVES volume of ≥43 mL/m2 (HR: 2.53; 95% CI: 1.75-3.66; P < 0.001) and indexed LV end-diastolic volume of ≥109 mL/m2 were independently associated with the outcomes and provided additional discrimination improvement over iLVES diameter, whereas iLVES diameter was independently associated with the primary outcome but not the secondary outcome. CONCLUSIONS: In asymptomatic AR patients with preserved LVEF, CMR findings can be used to guide management. CMR-based LVES volume assessment performed favorably compared to LV diameters.

Prevalence and Clinical Implications of Tricuspid Valve Prolapse Based on Magnetic Resonance Diagnostic Criteria.

BACKGROUND: Tricuspid valve prolapse (TVP) is an uncertain diagnosis with unknown clinical significance because of a scarcity of published data. OBJECTIVES: In this study, cardiac magnetic resonance was used to: 1) propose diagnostic criteria for TVP; 2) evaluate the prevalence of TVP in patients with primary mitral regurgitation (MR); and 3) identify the clinical implications of TVP with regard to tricuspid regurgitation (TR). METHODS: Forty-one healthy volunteers were analyzed to identify normal tricuspid leaflet displacement and propose criteria for TVP. A total of 465 consecutive patients with primary MR (263 with mitral valve prolapse [MVP] and 202 with nondegenerative mitral valve disease [non-MVP]) were phenotyped for the presence and clinical significance of TVP. RESULTS: The proposed TVP criteria included right atrial displacement of ≥2 mm for the anterior and posterior tricuspid leaflets and ≥3 mm for the septal leaflet. Thirty-one (24%) subjects with single-leaflet MVP and 63 (47%) with bileaflet MVP met the proposed criteria for TVP. TVP was not evident in the non-MVP cohort. Patients with TVP were more likely to have severe MR (38.3% vs 18.9%; P < 0.001) and advanced TR (23.4% of patients with TVP demonstrated moderate or severe TR vs 6.2% of patients without TVP; P < 0.001), independent of right ventricular systolic function. CONCLUSIONS: TR in subjects with MVP should not be routinely considered functional, as TVP is a prevalent finding associated with MVP and more often associated with advanced TR compared with patients with primary MR without TVP. A comprehensive assessment of tricuspid anatomy should be an important component of the preoperative evaluation for mitral valve surgery.