5-Year Outcomes of Anterior Mitral Leaflet Laceration to Prevent Outflow Obstruction.

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is a common, often fatal complication of transcatheter mitral valve replacement (TMVR). Laceration of the anterior mitral leaflet to prevent outflow obstruction (LAMPOON) was safe and effective at preventing LVOT obstruction at 30 days in the National Heart, Lung, and Blood Institute LAMPOON trial. OBJECTIVES: The authors report the 5-year outcomes of intentional anterior mitral leaflet laceration before SAPIEN 3 TMVR, in patients at risk of LVOT obstruction. METHODS: The National Heart, Lung, and Blood Institute LAMPOON trial was a prospective, multicenter, single-arm safety and feasibility study of LAMPOON and transseptal SAPIEN 3 TMVR in annuloplasty rings (valve-in-ring) or native mitral annular calcification (MAC) (valve-in-MAC). All subjects had high predicted risk for LVOT obstruction. Subjects were not excluded for excessive frailty or comorbidity. The primary endpoints were technical success and safety at 30 days. Secondary clinical and echocardiographic endpoints were assessed at 1 year and clinical follow-up at 5 years. RESULTS: Thirty subjects were enrolled between June 2017 and June 2018, equally between the valve-in-MAC and valve-in-ring arms. At 30 days, LAMPOON was successful in all 30 subjects, with no strokes, 1 (3%) death, and 1 (3%) moderate LVOT obstruction. Eighteen (65%) survived to 1 year, and 7 (25%) survived to 5 years. Six (20%) were hospitalized for heart failure in the first year. From baseline to 1 year, there was a 24-point improvement in Kansas City Cardiomyopathy Questionnaire score and a 60-m improvement in 6-minute walk distance. There was no significant change in N-terminal pro-brain natriuretic peptide. At 1 year, LVOT gradients remained low. CONCLUSIONS: LAMPOON enabled TMVR despite the risk for LVOT obstruction. There were no long-term complications associated with LAMPOON. The selection of inoperable patients limited assessment of long-term survival following TMVR. (NHLBI DIR LAMPOON Study: Intentional Laceration of the Anterior Mitral Leaflet to Prevent Left Ventricular Outflow Tract Obstruction During Transcatheter Mitral Valve Implantation; NCT03015194).

A Novel Presentation of Eclipsed Mitral Regurgitation.

Eclipsed mitral regurgitation (MR) is a rare phenomenon of transient severe MR in patients with normal left ventricular function. This paper presents a case of a patient with recurrent heart failure exacerbations and transient, positional severe MR consistent with eclipsed MR, which improved after mitral transcatheter edge-to-edge repair.

Flow quantification within the aortic ejection tract using 4D flow cardiac MRI in patients with bicuspid aortic valve: Implications for the assessment of aortic regurgitation.

PURPOSE: The purpose of this study was to evaluate the performance of four-dimensional (4D) flow cardiac MRI in quantifying aortic flow in patients with bicuspid aortic valve (BAV). MATERIALS AND METHODS: Patients with BAV who underwent transthoracic echocardiography (TTE) and 4D flow cardiac MRI were prospectively included. Aortic flow was quantified using two-dimensional phase contrast velocimetry at the sinotubular junction and in the ascending aorta and using 4D flow in the regurgitant jet, in the left ventricular outflow tract, at the aortic annulus, the sinotubular junction, and the ascending aorta, with or without anatomical tracking. Flow quantification was compared with ventricular volumes, pulmonary flow using Pearson correlation test, bias and limits of agreement (LOA) using Bland Altman method, and with multiparametric transthoracic echocardiography quantification using weighted kappa test. RESULTS: Eighty-eight patients (63 men, 25 women) with a mean age of 50.5 ± 14.8 (standard deviation) years (age range: 20.8-78.3) were included. Changes in flow with or without tracking were modest (< 5 mL). The best correlation was obtained at the aortic annulus for forward volume (r = 0.84; LOA [-28.4; 25.3] mL) and at the regurgitant jet and sinotubular junction for regurgitant volume (r = 0.68; LOA [-27.8; 33.8] and r = 0.69; LOA [-28.6; 24.2] mL). A combined approach for regurgitant fraction and net volume calculations using forward volume measured at ANN and regurgitant volume at sinotubular junction performed better than each level taken separately (r = 0.90; LOA [-20.7; 10.0] mL and r = 0.48, LOA [-33.8; 33.4] %). The agreement between transthoracic echocardiography and 4D flow cardiac MRI for aortic regurgitation grading was poor (kappa, 0.13 to 0.42). CONCLUSION: In patients with BAV, aortic flow quantification by 4D flow cardiac MRI is the most accurate at the annulus for the forward volume, and at the sinotubular junction or directly in the jet for the regurgitant volume.

Circumflex distortion following mitral valve repair.

Mitral valve repair or replacement poses a potential risk of injury to the left circumflex coronary artery (LCx). Such injuries can arise from either direct LCx injury caused by encircling or transfixing stitches, or indirect occlusion resulting from the distortion of adjacent tissues. We provide and illustrate a representative image depicting LCx distortion. Additionally, we offer guidance to aid angiographers in comprehending the angiographic appearance and the underlying mechanism of occlusion.

Predictive value of left atrial volumes assessed using real-time three-dimensional echocardiography for pulmonary hypertension in dogs with myxomatous mitral valve disease.

Introduction: Left atrial volume (LAV) obtained using real-time three-dimensional echocardiography (RT3DE) is an independent predictor of post-capillary pulmonary hypertension (PH) in humans; however, no studies have investigated LAV obtained using RT3DE as a predictor of post-capillary PH in dogs with myxomatous mitral valve disease (MMVD). Therefore, we aimed to evaluate the clinical applicability of LAV obtained using RT3DE compared to that obtained using two-dimensional echocardiography (2DE) in dogs with MMVD, with or without PH. Methods: Medical records and echocardiographic images of 237 privately owned dogs with naturally occurring MMVD with or without PH were retrospectively reviewed. A total of 49 privately owned dogs with naturally occurring MMVD, with or without PH, were finally included (35 MMVD without PH, 14 MMVD with PH). The LAV and left ventricular volumes were obtained using 2DE and RT3DE. Echocardiographic parameters were analyzed to identify independent predictors of post-capillary PH. Results: We found that the left atrial and left ventricular volumes obtained using 2DE and RT3DE indexed to body weight and several 2DE-derived variables were univariately associated with post-capillary PH. Furthermore, multivariable logistic regression analysis revealed that the RT3DE minimum LAV indexed to body weight (LAVi min) was the only significant independent predictor of post-capillary PH (odds ratio, 12.86; 95% confidence interval [CI], 2.40-68.99; p = 0.003), with the highest area under the curve value of 0.86 (95% CI, 0.75-0.96; p < 0.001). Discussion: In conclusion, LAV indexed to body weight obtained using 2DE and RT3DE, can be a useful predictor of post-capillary PH in dogs with MMVD. In particular, the RT3DE LAVi min was observed to be the strongest predictor of post-capillary PH.

Resolution of Severe Ulcerative Colitis Secondary to Nickel Allergy Following Explantation of Amplatzer Septal Occluder Device: A Delayed Presentation.

Nickel is a component of nitinol, an alloy used in several medical devices. Allergy to nickel may place patients at a high risk for severe hypersensitivity reactions. We report a rare case of a patient who developed severe ulcerative colitis ten years following closure of an atrial septal defect with the Amplatzer Septal Occluder device.

Bicuspid Aortic Valve Disease: From Pathophysiology to Treatment.

The Bicuspid Aortic Valve (BAV) is the most common congenital anomaly in adults, with a global incidence of 1.3%. Despite being well documented, BAV presents significant clinical challenges due to its phenotypic heterogeneity, diverse clinical manifestations, and variable outcomes. Pathophysiologically, BAV differs from tricuspid valves in calcification patterns and hemodynamic effects, leading to increased shear stress and aortic root dilatation, while it is influenced by genetic and hemodynamic factors. This is why therapeutically, BAV presents challenges for both surgical and transcatheter interventions, with surgical approaches being traditionally preferred, especially when aortopathy is present. However, transcatheter aortic valve implantation (TAVI) has emerged as a viable option, with studies showing comparable outcomes to surgery in selected patients, while advancements in TAVI and a better understanding of BAV's genetic and pathophysiological nuances are expanding treatment options. The choice between mechanical and bioprosthetic valves also presents considerations, particularly regarding long-term durability and the need for anticoagulation. Future research should focus on long-term registries and genetic studies to refine therapeutic strategies and improve patient outcomes. This review aims to evaluate current approaches in the surgical and interventional management of BAV, focusing on its anatomy, pathogenesis, pathophysiology, and therapeutic strategies.

Evaluation of right ventricular function using conventional and real-time three-dimensional echocardiography in healthy dogs and dogs with myxomatous mitral valve disease.

INTRODUCTION/OBJECTIVES: To compare conventional and three-dimensional (3D) echocardiographic indices of right ventricular (RV) systolic function in dogs with various stages of myxomatous mitral valve disease (MMVD), classified according to the 2009 guidelines of the American College of Veterinary Internal Medicine (ACVIM), with those from normal dogs. ANIMALS: Seventy-eight unsedated dogs (22 healthy controls, 23 ACVIM stage B1 MMVD, 20 ACVIM stage B2 MMVD, and 13 ACVIM stage C MMVD) were included in the study. MATERIALS AND METHODS: All dogs underwent conventional and 3D echocardiography. Three-dimensional RV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) were recorded. Right ventricular EDV, ESV, and SV were indexed to bodyweight. Echocardiographic variables were compared across groups using a Kruskal-Wallis test with subsequent post hoc analysis using Dunn's method for multiple comparisons between groups. A P-value of <0.05 was considered significant. RESULTS: Right ventricular EDV was smaller in stage B1 (P=0.012), stage B2 (P=0.035), and stage C (P=0.004) dogs than in controls. Stage B2 (P=0.003) and stage C (P<0.001) dogs had smaller RV ESV than controls. Stage B1 dogs had smaller RV SV than controls (P=0.012). Right ventricular EF was greater in stage C dogs than in controls (P=0.003) and in stage B1 (P=0.017) dogs. CONCLUSIONS: Several 3D echocardiographic indices of RV systolic function differ between dogs with advanced MMVD when compared with normal dogs. Further investigation is required to determine if these differences have clinical implications.

Lipoprotein(a) and cardiovascular disease.

Elevated plasma levels of lipoprotein(a) (Lp(a)) are a prevalent, independent, and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. Lp(a) consists of a lipoprotein particle resembling low density lipoprotein and the covalently-attached glycoprotein apolipoprotein(a) (apo(a)). Novel therapeutics that specifically and potently lower Lp(a) levels are currently in advanced stages of clinical development, including in large, phase 3 cardiovascular outcomes trials. However, fundamental unanswered questions remain concerning some key aspects of Lp(a) biosynthesis and catabolism as well as the true pathogenic mechanisms of the particle. In this review, we describe the salient biochemical features of Lp(a) and apo(a) and how they underlie the disease-causing potential of Lp(a), the factors that determine plasma Lp(a) concentrations, and the mechanism of action of Lp(a)-lowering drugs.

Challenges and Priorities for Children With Congenital Valvar Heart Disease: The Heart Valve Collaboratory.

The Heart Valve Collaboratory is a multidisciplinary, patient-centered community of stakeholders addressing complex problems and embracing innovation to help patients with heart valve disease achieve their fullest potential for health. The Scientific Council is composed of cardiologists, surgeons, ex-officio representatives of the Food and Drug Administration and Centers for Medicare and Medicaid Services, National Heart Lung Blood Institute, and representatives from industry partners. In October 2022, this group convened a workshop that included experts from stakeholder groups to address the unmet and clinical needs of patients with pediatric and congenital heart valve disease. The following document includes the discussion and summary of the current state of valve therapy and the needs being addressed for valve development.

High-Gradient Aortic Stenosis With Valve Area >1.0 cm2: The "Forgotten" Discordant Hemodynamic Phenotype.

BACKGROUND: Clinical features and outcomes in severe aortic stenosis (AS) have been described according to the hemodynamic phenotypes. OBJECTIVES: The aim of this study was to investigate the clinical features and prognosis of patients with high-gradient (HG) AS with aortic valve area (AVA) >1.0 cm2. METHODS: A total of 3,209 patients were identified according to AVA (cm2), peak velocity (m/s), systolic mean pressure gradient (MG) (mm Hg): HG-AVA >1 = >1.0, ≥4, and ≥40, HG-AVA ≤1 = ≤1.0, ≥4, and ≥40; LG-AVA ≤1 (low-gradient) = ≤1.0, <4, and <40; moderate AS = 1.0 1 accounted for 230 individuals (7.2%). Compared with others, patients with HG-AVA >1 were younger (70.2 ± 12.0 years), more frequently male (85.7%), had fewer comorbidities, larger body surface area and stroke volume (115 ± 19.3 mL), and had higher prevalence of bicuspid valve (39.6%). After a follow-up of 944 days (Q1-Q3: 27-2,212 days), 1,523 deaths occurred. Compared with the HG-AVA >1 group, all-cause mortality was higher in HG-AVA ≤1 (HR: 1.4; 95% CI: 1.1-1.7), LG-AVA ≤1 (HR: 2.8; 95% CI: 2.2-3.6), and moderate AS (HR: 1.4; 95% CI: 1.1-1.7). These differences were no longer significant after adjustment for age, comorbidities, bicuspid valve, and cardiac function. In the HG-AVA >1 group, patients with aortic valve replacement had better survival outcomes than those without aortic valve replacement (P < 0.001) after balancing the 2 groups. CONCLUSIONS: The underlying relative high-flow status is responsible for HG in patients with HG-AVA >1. This profile has better prognosis than others, being related to underlying younger age and better general and cardiac conditions, but aortic valve replacement may still benefit these patients.

Observed and expected reliability of echocardiographic volumetric methods and critical change values for quantification of mitral regurgitant fraction in dogs.

BACKGROUND: Reliability of echocardiographic calculations for stroke volume and mitral regurgitant fraction (RFMR) are affected by observer variability and lack of a gold standard. Variability is used to calculate critical change values (CCVs) that are thresholds representing real change in a measure not associated with observer variability. HYPOTHESIS: Observed intra- and interobserver accuracy and variability in healthy dogs help model CCV for RFMR. ANIMALS: Reliability cohort of 34 healthy dogs; allometric scaling cohort of 99 dogs with heart disease and 25 healthy dogs. METHODS: Accuracy, variability, and CCV of 2 observers using geometric and flow-based echocardiography were prospectively compared against a standard of RFMR = 0% and extrapolated across a range of expected RFMR values in the reliability cohort partly derived from cardiac dimensions predicted by the allometric cohort. RESULTS: Accuracy of methods to determine RFMR in descending order was 4-chamber bullet (Bullet4CH), mitral inflow, cube formula, and Simpson's method of disks. Intraobserver variability was relatively high. The CCV for RFMR ranged from 28% to 88% and was inversely related to RFMR when extrapolated for use in affected dogs. For both observers, the Bullet4CH method had the lowest intraobserver CCV (Operator 1:28%, Operator 2:41%). Interobserver strength of agreement was low with intraclass correlation coefficients ranging from 0.210 to 0.413. CONCLUSIONS AND CLINICAL IMPORTANCE: Echocardiographic volumetric methods used to calculate stroke volume and RFMR have low accuracy and high variability in healthy dogs. Extrapolation of observed CCV to a range of expected RFMR suggests observers and methods are not interchangeable and variability might hinder routine clinical usage. Individual observers should be aware of their own variability and CCV.

Effectiveness and safety of emergency transcatheter aortic valve replacement in patients with severe aortic stenosis complicated by cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: The application of transcatheter aortic valve replacement (TAVR) has been developed on different populations in many clinical studies. However, research dedicated to the application of emergency TAVR in patients with aortic stenosis (AS) experiencing cardiogenic shock is limited. OBJECTIVE: To investigate the safety and effectiveness of emergency TAVR in AS patients with circulatory collapse. METHODS: Studies on the application of emergency TAVR in AS patients with cardiogenic shock were screened from PubMed, Web of Science, and Embase databases. Two researchers independently screened the literature-extracted data and conducted a meta-analysis was conducted using STATA 16.0 software. RESULTS: 17 studies comprising 36,886 patients undergoing emergency TAVR and 8,530 patients undergoing emergency SAVR or BAV. Emergency TAVR showed no difference in valve implantation success rate compared to elective TAVR. At 30-day endpoints comparison, emergency TAVR exhibited significantly higher all-cause mortality and readmission rates than elective TAVR (RR=2.73 95 %CI 2.04-3.65, P < 0.01; RR=1.2 95 %CI 0.9-1.6, P < 0.01), but reduced mortality risk compared to emergency SAVR/BAV (RD=-0.15 95 %CI -0.25 to -0.04, P = 0.005). At one year post-operation, people with emergency TAVR continued to have higher all-cause mortality than elective TAVR (RR=1.55 95 %CI 1.37-1.74, P < 0.01) but similar with emergency SAVR/BAV (RD=-0.04 95 %CI -0.33 to 0.25, P = 0.796). Rates of severe bleeding and new-onset renal dialysis were higher after emergency TAVR, compared to elective TAVR, while the incidences of permanent pacemaker implantation, severe paravalvular leakage and stroke were similar. CONCLUSION: Despite emergency TAVR having higher readmission and mortality rates compared to elective TAVR, it is a relatively safe and effective treatment in cases of cardiogenic shock compared to emergency BAV/SAVR.

The Role of Adiponectin and Leptin in Fibro-Calcific Aortic Valve Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Fibro-calcific aortic valve disease (FCAVD) is a progressive disorder characterized by the thickening and calcification of the aortic valve, eventually leading to aortic stenosis. Adiponectin and leptin, known for their anti-inflammatory and proinflammatory properties, respectively, have been implicated in cardiovascular diseases, but their associations with FCAVD are controversial. This meta-analysis aims to evaluate the relationships between adiponectin and leptin levels and FCAVD, particularly in patients with severe aortic stenosis (AS). METHODS: A systematic search was conducted across the PubMed, Scopus, and Web of Science databases to identify studies on adiponectin and leptin levels in FCAVD. The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and publication bias was evaluated using Egger's test and funnel plots. RESULTS: Out of 191 articles identified, 10 studies involving 2360 patients (989 with FCAVD and 1371 controls) were included. The analysis suggested trends in the associations of lower adiponectin levels (SMD = -0.143, 95% CI: -0.344, 0.057, p = 0.161) and higher leptin levels (SMD = 0.175, 95% CI: -0.045, 0.395, p = 0.119) with FCAVD. The association remained a trend for low adiponectin but showed a significant correlation with high leptin in severe AS patients (SMD = 0.29, 95% CI: 0.036, 0.543, p = 0.025). CONCLUSION: This meta-analysis indicates a potential association between elevated leptin levels and severe aortic stenosis, while the relationship with adiponectin levels remains inconclusive. These findings highlight the need for further and dedicated research to clarify the roles of these adipokines in the pathogenesis of FCAVD and their potential roles as biomarkers for disease progression.

Rethinking Mitral Annular Calcification and Its Clinical Significance: From Passive Process to Active Pathology.

BACKGROUND: Mitral annulus calcification is a chronic degenerative condition affecting the fibrous base of the mitral valve. Historically viewed as an age-related phenomenon, recent studies suggest it is driven by active mechanisms involving systemic inflammation, hemodynamic stress, abnormal calcium-phosphorus metabolism, and lipid accumulation. Despite often being asymptomatic and incidentally detected, its clinical relevance stems from its strong association with increased cardiovascular disease risk, higher cardiovascular mortality, and elevated overall mortality. METHODS: This article investigates the complexities and controversies surrounding mitral annular calcification as a potential embolic source, focusing on its diagnosis, its relationship with systemic inflammation, and its links to metabolic and chronic disorders. RESULTS: The findings highlight that mitral annular calcification is not merely a passive marker of aging but an active indicator of atherosclerotic burden with significant implications for cardiovascular health. CONCLUSION: Mitral annulus calcification should be recognized as an important factor in cardiovascular risk assessment, offering insight into systemic inflammatory processes and metabolic dysregulation.

Alterations in Left Atrial and Ventricular Coupling in Mixed Aortic Valve Disease.

AIMS: To characterize left atrial (LA) and left ventricular (LV) function and atrioventricular (AV) coupling in patients with moderate mixed aortic valve disease (MMAVD) against those with isolated moderate or severe aortic valve disease and controls. METHODS & RESULTS: Retrospective LA and LV peak longitudinal strain (LS) analysis were performed on 260 patients (46 MMAVD, 81 moderate aortic stenosis (AS), 50 severe AS, 48 moderate aortic regurgitation (AR), and 35 severe AR) and 66 controls. Peak LV and LA LS and AV coupling, assessed by combined peak LA and LV strain, was compared between the groups. ANOVA and 2-sided t-tests were used and a p-value of <0.01 was considered significant.LV strain was significantly lower in those with MMAVD compared to controls and those with moderate or severe isolated AR but comparable to those with moderate or severe AS (-17.1±1.1% MMAVD vs. -17.7±1.5% moderate AS p=0.02; vs. -17.0%±1.5% severe AS, p=0.74). AV coupling was significantly lower in those with MMAVD compared to controls and those with moderate AS or AR but comparable to those with severe AS or AR (47.1±6.8% MMAVD vs. 45.1±5.6% severe AS, p=0.13; vs. 50.4±9% severe AR, p=0.07). CONCLUSIONS: Impairments in AV coupling are comparable for patients with MMAVD and those with severe isolated AS or AR. Impairments in LV GLS in MMAVD mirror those found in severe AS. These findings suggest that haemodynamic consequences and adverse remodelling are similar for patients with MMAVD and isolated severe disease.