Prognostic Value of Left Ventricular Global Longitudinal Strain in Transcatheter Edge-to-Edge Repair for Chronic Primary Mitral Regurgitation.

AIMS: Left ventricular global longitudinal strain (LVGLS) is a known outcome predictor in transcatheter edge-to-edge repair (TEER) for functional mitral regurgitation (MR). We aimed to assess its prognostic yield in the setting of TEER for chronic primary MR. METHODS AND RESULTS: We conducted a single-center, retrospective analysis of 323 consecutive patients undergoing isolated, first-time procedures. Stratified by baseline LVGLS quartiles (≤-19%, -18.9-(-16)%, -15.9-(-12)%, > -12%), the cohort was evaluated for the primary composite outcome of all-cause mortality or heart failure hospitalizations, as well as secondary endpoints consisting of mitral reinterventions and the persistence of significant residual MR and/or functional disability - all along the first year after intervention. Subjects with worse (i.e., less negative) LVGLS exhibited higher comorbidity, more advanced HF, and elevated procedural risk. Post-TEER, those belonging to the worst LVGLS quartile group sustained increased mortality (16.9 vs 6.3%, Log-Rank p = 0.005, HR 1.75, 95% CI 1.08-4.74, p = 0.041) and, when affected by LV dysfunction/dilatation, more primary outcome events (21.1 vs 11.5%, Log-Rank p = 0.037, HR 1.68, 95% CI 1.02-5.46, p = 0.047). No association was demonstrated with other endpoints. Upon exploratory analysis, 1-month postprocedural LVGLS directly correlated with and was worse than its baseline counterpart by 1.6%, and a more impaired 1-month value - but not the presence/extent of deterioration - conferred heightened risk for the primary outcome. CONCLUSION: TEER for chronic primary MR is feasible, safe, and efficacious irrespective of baseline LVGLS. Yet, worse baseline LVGLS forecasts a less favorable postprocedural course, presumably reflecting a higher-risk patient profile.

Implications of Mitral Annular Disjunction in Patients Undergoing Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation.

BACKGROUND: Little is known about mitral transcatheter edge-to-edge repair (TEER) in patients with mitral annular disjunction (MAD). OBJECTIVES: The authors sought to explore TEER for degenerative mitral regurgitation (MR) according to MAD status. METHODS: We retrospectively analyzed 271 consecutive patients (median age 82 [Q1-Q3: 75-88] years, 60.9% men) undergoing an isolated, first-ever TEER for whom there were viewable preprocedural echocardiograms. Stratified by MAD status at baseline, the cohort was evaluated for all-cause mortality, heart failure hospitalizations, and mitral reinterventions-the composite of which constituted the primary outcome-as well as functional capacity and residual MR, all along the first postprocedural year. RESULTS: Individuals with (n = 62, 22.9%) vs without MAD had more extensive prolapse and larger valve dimensions. Although the former's procedures were longer, utilizing more devices per case, technical success rate and residual MR were comparable. MAD presence was associated with higher mortality risk (HR: 2.64; 95% CI: 1.82-5.52; P = 0.014), and increased MAD length-with lower odds of functional class ≤II (OR: 0.65; 95% CI: 0.47-0.88; P = 0.006). Among 47 MAD patients with retrievable 1-month data, MAD regressed in 91.5% and by an overall 50% (Q1-Q3: 22%-100%) compared with baseline (P < 0.001). A greater MAD shortening conferred attenuated risk for the primary outcome. CONCLUSIONS: In our experience, TEER for degenerative MR accompanied by MAD was feasible and safe; however, its postprocedural course was somewhat less favorable. MAD shortening following TEER was observed in most patients and proved prognostically beneficial.

Preprocedural transthoracic echocardiography for predicting outcomes of transcatheter edge-to-edge repair for chronic primary mitral regurgitation.

INTRODUCTION AND OBJECTIVES: Limited data exist on the prognostic usefulness of transthoracic echocardiography preceding MitraClip for chronic primary mitral regurgitation (MR). We evaluated the predictive ability of transthoracic echocardiography in this setting. METHODS: A total of 410 patients (median age, 83 years, 60.7% males) were included in the study. The primary outcome was the 1-year composite of all-cause mortality or heart failure hospitalization. Secondary endpoints encompassed individual elements of the primary outcome, the persistence of significant functional impairment or above-moderate MR at 1 year, and above-mild MR at 1-month. RESULTS: Left ventricular end-systolic diameter index of ≥ 2.1cm/m2, corresponding to the cohort's 4th quartile (HR, 2.44; 95%CI, 1.09-4.68; P=.022). Concurrently, higher left atrial volume index (LAVi) and a mid-diastolic medial-lateral mitral annular diameter (MAD) equal to or above the cohort's median of 32.2mm were linked to a higher probability of death and heart failure hospitalization, respectively. LAVi of ≥ 60mL/m2, above-mild mitral annular calcification, and above-moderate tricuspid regurgitation conferred higher odds of functional class III-IV or above-moderate MR persistence. All variables except LAVi and MAD, as well as indexed mid-diastolic medial-lateral MAD of ≥ 20.2mm/m2 and mitral effective regurgitant orifice area of ≥ 0.40 cm2, were associated with greater-than-mild MR at 1 month. CONCLUSIONS: Preprocedural increased indexed left heart dimensions, mainly left ventricular end-systolic diameter index, MAD, mitral annular calcification, mitral effective regurgitant orifice area, and tricuspid regurgitation mark a less favorable course post-MitraClip for chronic primary MR.

Computer versus human-expert ranking of posterior pole vascular tortuosity and dilation using retinal vessel maps generated from bedside optical coherence tomography: a proof-of-concept study.

Semiautomated computer software (ie, ROPtool) can trace and analyze optical coherence tomography (OCT)-generated retinal vessel maps for plus/pre-plus disease with high reliability and accuracy. This proof-of-concept study found that ROPtool can reliably rank OCT-generated vessel maps for tortuosity and combined tortuosity/dilation, which correlated well with human-expert rankings and clinical examination.

Quantitative comparison of blood vessel changes after treatment of retinopathy of prematurity with laser versus bevacizumab.

Current therapies for treatment-indicated (type 1) retinopathy of prematurity mainly consist of laser photocoagulation and intravitreal anti-vascular endothelial growth factor (eg, bevacizumab) injection. The first visible signs of acute-phase regression are typically vascular, including decreased plus disease. Using a semiautomated computer program, we quantitatively compared posterior pole vascular changes following treatment with laser versus bevacizumab and found that in the first month following treatment, vascular dilation and tortuosity significantly decreased following either treatment modality, but tortuosity decreased earlier and faster after bevacizumab.

Semi-automated vessel analysis of en face posterior pole vessel maps generated from optical coherence tomography for diagnosis of plus or pre-plus disease.

En face retinal vessel maps generated from bedside optical coherence tomography (OCT) can show posterior pole vascular tortuosity and dilation (ie, plus/pre-plus disease). In this proof-of-concept study, we found that ROPtool could trace OCT-generated retinal vessel maps with high reliability and accuracy for detecting plus or pre-plus disease.

Prophylactic laser versus continued surveillance after initial bevacizumab treatment for retinopathy of prematurity.

Guidelines on managing infants after initial anti-vascular endothelial growth factor (VEGF) treatment (eg, bevacizumab) for retinopathy of prematurity (ROP) are limited. We found that following initial bevacizumab treatment for ROP, prophylactically lasering infant eyes before hospital discharge reduced the number and duration of outpatient ROP screening examinations compared with following infants, per current United States (US) ROP screening guidelines.

Quantitatively comparing weekly changes in retinal vascular characteristics of eyes eventually treated versus not treated for retinopathy of prematurity.

PURPOSE: To quantitatively compare retinal vascular characteristics over time in eyes eventually treated versus not treated for retinopathy of prematurity (ROP), using ROPtool analysis of narrow-field retinal images. METHODS: This longitudinal study used prospectively collected narrow-field retinal images of infants screened for ROP, prior to treatment, if needed. Images were analyzed using a methodology that combines quadrant-level measures from several images of the same eye. For the longitudinal analysis, one examination per postmenstrual age (PMA) was included per eye. We compared the following ROPtool indices and their change per week between eyes eventually treated versus not treated for ROP: tortuosity index (TI), dilation index (DI), sum of adjusted indices (SAI), and tortuosity-weighted plus (TWP). Analysis was performed on three levels: eye (mean value/eye), quadrant (highest quadrant value/eye), and blood vessel (highest blood vessel value/eye). RESULTS: Of 832 examinations (99 infants), 745 images (89.5%) had 3-4 quadrants analyzable by ROPtool. On the eye level, ROPtool indices differed between eyes eventually treated versus not treated at PMA of 33-35 and 37 weeks for TI, SAI, and TWP, and at PMA of 33-34 and 37 weeks for DI (P ≤ 0.0014), and change per week differed between eyes eventually treated versus not treated only for SAI at PMA of 32 weeks (P < 0.001). CONCLUSIONS: Quantitative analysis of retinal vascular characteristics using ROPtool can help predict eventual need for treatment for ROP as early as 32 weeks PMA. ROPtool index values were more useful than change in these indices to predict eyes that would eventually need treatment for ROP.

Production of Stealthin C Involves an S-N-Type Smiles Rearrangement.

The kinamycin family of aromatic polyketide natural products contains an atypical angucycline ring system substituted with a diazo group. The enzymatic chemistry involved in constructing both of these structural features has been largely unexplored. Here we report the in vivo and in vitro production of seongomycin, a shunt product from this pathway, and stealthin C, a proposed biosynthetic precursor to the kinamycins. We show that a single enzyme, the flavin-dependent monooxygenase AlpJ, can generate these metabolites from N-acetyl-l-cysteine and l-cysteine, respectively, and that the synthesis of stealthin C likely proceeds via a nonenzymatic S-N-type Smiles rearrangement. This unexpected route to stealthin C reveals a distinct approach to install aromatic amino groups in metabolites and raises questions about the intermediacy of this species in kinamycin production.