Transcatheter Repair for Patients with Tricuspid Regurgitation.

BACKGROUND: Severe tricuspid regurgitation is a debilitating condition that is associated with substantial morbidity and often with poor quality of life. Decreasing tricuspid regurgitation may reduce symptoms and improve clinical outcomes in patients with this disease. METHODS: We conducted a prospective randomized trial of percutaneous tricuspid transcatheter edge-to-edge repair (TEER) for severe tricuspid regurgitation. Patients with symptomatic severe tricuspid regurgitation were enrolled at 65 centers in the United States, Canada, and Europe and were randomly assigned in a 1:1 ratio to receive either TEER or medical therapy (control). The primary end point was a hierarchical composite that included death from any cause or tricuspid-valve surgery; hospitalization for heart failure; and an improvement in quality of life as measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), with an improvement defined as an increase of at least 15 points in the KCCQ score (range, 0 to 100, with higher scores indicating better quality of life) at the 1-year follow-up. The severity of tricuspid regurgitation and safety were also assessed. RESULTS: A total of 350 patients were enrolled; 175 were assigned to each group. The mean age of the patients was 78 years, and 54.9% were women. The results for the primary end point favored the TEER group (win ratio, 1.48; 95% confidence interval, 1.06 to 2.13; P = 0.02). The incidence of death or tricuspid-valve surgery and the rate of hospitalization for heart failure did not appear to differ between the groups. The KCCQ quality-of-life score changed by a mean (±SD) of 12.3±1.8 points in the TEER group, as compared with 0.6±1.8 points in the control group (P<0.001). At 30 days, 87.0% of the patients in the TEER group and 4.8% of those in the control group had tricuspid regurgitation of no greater than moderate severity (P<0.001). TEER was found to be safe; 98.3% of the patients who underwent the procedure were free from major adverse events at 30 days. CONCLUSIONS: Tricuspid TEER was safe for patients with severe tricuspid regurgitation, reduced the severity of tricuspid regurgitation, and was associated with an improvement in quality of life. (Funded by Abbott; TRILUMINATE Pivotal ClinicalTrials.gov number, NCT03904147.).

Transcatheter mitral valve in ring, hazards of long anterior mitral leaflet and 3-dimensional rings.

OBJECTIVES: The purpose of this study was to define anterior mitral leaflet (AML) length and mitral ring characteristics associated with LVOT obstruction and PVL following MViR. BACKGROUND: Transcatheter Mitral Valve in Ring (MViR) procedural complications including parvalvular leak (PVL) and left ventricular outflow tract (LVOT) obstruction are frequent. METHODS: Clinical records, computer tomographic scans (CTs) and echocardiograms of consecutive MViR patients were retrospectively reviewed for anterior mitral leaflet length, CT-simulated neoLVOT, and aortomitral angle among patients with and without MViR-induced LVOT obstruction. Acute and 1-year outcomes are described. RESULTS: Twenty-two patients underwent MViR. Technical success was achieved in 13/22 (57.1%) patients, limited by paravalvular regurgitation requiring second transcatheter heart valves (THVs) in seven patients. Second valves were needed in 6/11 (54.5%) patients with 3-dimensional rings but 1/11 (9.1%, p = .06) of patients with planar rings. Procedure success at 30 days was achieved in 20/22 (90.9%) patients. There were no procedural, in-hospital, or 30-day deaths. Two patients developed significant LVOT obstruction, one managed with urgent surgery and one with elective alcohol septal ablation. Anterior mitral leaflets were longer among the two patients with LVOT obstruction than the 20 patients who did not develop LVOT obstruction when measured by TEE (30 mm vs. 21 mm, p = .009) or by CT (29 mm vs. 22 mm, p = .026). CONCLUSIONS: AML >25 mm increases the risk of MViR induced LVOT obstruction. PVL is common, particularly in 3-dimensional rings which can be managed with a second THV.

Impact of Diabetes Mellitus on the Evaluation of Stable Chest Pain Patients: Insights From the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) Trial.

BACKGROUND: The impact of diabetes mellitus on the clinical presentation and noninvasive test (NIT) results among stable outpatients presenting with symptoms suggestive of coronary artery disease (CAD) has not been well described. METHODS AND RESULTS: The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial enrolled 10 003 patients with known diabetic status, of whom 8966 were tested as randomized and had interpretable NIT results (1908 with diabetes mellitus, 21%). Differences in symptoms and NIT results were evaluated using logistic regression. Patients with diabetes mellitus (versus without) were similar in age (median 61 versus 60 years) and sex (female 54% versus 52%), had a greater burden of cardiovascular comorbidities, and had a similar likelihood of nonchest pain symptoms (29% versus 27%). The Diamond-Forrester/Coronary Artery Surgery Study score predicted that patients with diabetes mellitus (versus without) had similar likelihood of obstructive CAD (low 1.8% versus 2.7%; intermediate 92.3% versus 92.6%; high 5.9% versus 4.7%). Physicians estimated patients with diabetes mellitus to have a higher likelihood of obstructive CAD (low to very low: 28.3% versus 40.1%; intermediate 63.9% versus 55.9%; high to very high 7.8% versus 4.0%). Patients with diabetes mellitus (versus without) were more likely to have a positive NIT result (15% versus 11%; adjusted odds ratio, 1.23; P=0.01). CONCLUSIONS: Stable chest pain patients with and without diabetes mellitus have similar presentation and pretest likelihood of obstructive CAD; however, physicians perceive that patients with diabetes mellitus have a higher pretest likelihood of obstructive CAD, an assessment supported by increased risk of a positive NIT. Further evaluation of diabetes mellitus's influence on CAD assessment is required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.

The Role for Cardiovascular Remodeling in Cardiovascular Outcomes.

PURPOSE OF REVIEW: Ischemic and non-ischemic injury to the heart causes deleterious changes in ventricular size, shape, and function. This adverse remodeling is mediated by neurohormonal and hemodynamic alterations and is reflected in non-invasive measures of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). These measures are closely linked to cardiovascular outcomes and have become key surrogate endpoints for evaluating the therapeutic efficacy of contemporary treatments for heart failure with reduced ejection fraction (HFrEF). In this review, we critically evaluate recent published data (2015-2016) from randomized clinical trials (RCTs) and observational studies of HFrEF therapies to assess the role of ventricular remodeling on outcomes. RECENT FINDINGS: These data highlight the benefits of certain guideline-directed medical therapies (GDMT) such as cardiac resynchronization therapy, surgical revascularization, and mechanical circulatory support on remodeling, while revealing the limitations of other therapies-routine mitral valve repair for patients with moderate ischemic mitral regurgitation and adjuncts to percutaneous coronary intervention in patients with ST elevation myocardial infarction (cyclosporine A and bioabsorbable cardiac matrix). The new angiotensin receptor blocker/neprilysn inhibitor, sacubitril/valsartan, demonstrates convincing improvements in clinical outcomes with a study of remodeling parameters to follow; the new cardiac myosin activator, omecamtiv mecarbil, demonstrates improvement in remodeling parameters without a clear early clinical benefit. The concepts and contemporary trials reviewed in this paper reinforce the value of non-invasive measures of ventricular remodeling (LVEF, LVESV, and LVEDV) as important metrics across a range of cardiovascular therapies. Global non-invasive measures of cardiovascular remodeling have roughly paralleled or preceded hard clinical outcomes. Additionally, the capacity for reverse remodeling in HFrEF with GDMT motivates continued research in the fields of implementation science, diagnostic imaging, and gene-based therapeutics.

Comparison of demographic characteristics, surgical resection patterns, and survival outcomes for veterans and nonveterans with non-small cell lung cancer in the Pacific Northwest.

INTRODUCTION: Lung cancer is a leading cause of death in the United States and among veterans. This study compares patterns of diagnosis, treatment, and survival for veterans diagnosed with non-small cell lung cancer (NSCLC) using a recently established cancer registry for the Veterans Affairs Pacific Northwest Network with the Puget Sound Surveillance, Epidemiology, and End Results cancer registry. METHODS: A cohort of 1715 veterans with NSCLC were diagnosed between 2000 and 2006, and 7864 men were diagnosed in Washington State during the same period. Demographics, tumor characteristics, initial surgical patterns, and survival across the two registries were evaluated. RESULTS: Veterans were more likely to be diagnosed with stage I or II disease (32.8%) compared with the surrounding community (21.5%, p = 0.001). Surgical resection rates were similar for veterans (70.2%) and nonveterans (71.2%) older than 65 years with early-stage disease (p = 0.298). However, veterans younger than 65 years with early-stage disease were less likely to undergo surgical resection (83.3% versus 91.5%, p = 0.003). Because there were fewer late-stage patients among veterans, overall survival was better, although within each stage group veterans experienced worse survival compared with community patients. The largest differences were among early-stage patients with 44.6% 5-year survival for veterans compared with 57.4% for nonveterans (p = 0.004). CONCLUSIONS: The use of surgical resection among younger veterans with NSCLC may be lower compared with the surrounding community and may be contributing to poorer survival. Cancer quality of care studies have primarily focused on patients older than 65 years using Medicare claims; however, efforts to examine care for younger patients within and outside the Department of Veterans Affairs are needed.

A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtype 5 and blocks the effects of multiple allosteric modulators.

The metabotropic glutamate receptor subtype 5 (mGlu5) activates calcium mobilization via binding of glutamate, the major excitatory neurotransmitter in the central nervous system. Allosteric modulation of the receptor has recently emerged as a promising alternative method of regulation to traditional regulation through orthosteric ligands. We now report three novel compounds that bind to the allosteric 2-methyl-6-(phenylethynyl)-pyridine (MPEP) site on mGlu5 but have only partial inhibition or no functional effects on the mGlu5 response. Two of these compounds, 2-(2-(3-methoxyphenyl)ethynyl)-5-methylpyridine (M-5MPEP) and 2-(2-(5-bromopyridin-3-yl)ethynyl)-5-methylpyridine (Br-5MPEPy), act as partial antagonists of mGlu5 in that they only partially inhibit the response of this receptor to glutamate. The third compound, 5-methyl-6-(phenylethynyl)-pyridine (5MPEP), acts as a neutral allosteric site ligand that binds to the MPEP site and has no effects alone. However, 5MPEP blocks the effects of both the allosteric antagonist MPEP and potentiators 3,3'-difluorobenzaldazine and 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB). This compound also blocks depolarization effects of both MPEP and CDPPB in neurons in the subthalamic nucleus. These novel compounds provide valuable new insight into the pharmacology of allosteric sites on G protein-coupled receptors and provide valuable new tools for determining the effects of allosteric site ligands in native systems.