GLIDE Score: Scoring System for Prediction of Procedural Success in Tricuspid Valve Transcatheter Edge-to-Edge Repair.

BACKGROUND: Tricuspid valve transcatheter edge-to-edge repair (T-TEER) is the most widely used transcatheter therapy to treat patients with tricuspid regurgitation (TR). OBJECTIVES: The aim of this study was to develop a simple anatomical score to predict procedural outcomes of T-TEER. METHODS: All patients (n = 168) who underwent T-TEER between January 2017 and November 2022 at 2 centers were included in the derivation cohort. Additionally, 126 patients from 2 separate institutions served as a validation cohort. T-TEER was performed using 2 commercially available technologies. Core laboratory assessment of procedural transesophageal echocardiograms was used to determine septolateral and anteroposterior coaptation gap, leaflet morphology, septal leaflet length and retraction, chordal structure density, tethering height, en face TR jet morphology and TR jet location, image quality, and the presence of intracardiac leads. A scoring system was derived using univariable and multivariable logistic regression. Endpoints assessed were immediate postprocedural TR reduction ≥2 grades and TR grade moderate or less. RESULTS: The median age was 82 years (Q1-Q3: 78-84 years); 48% of patients were women; and patients presented with severe (55%), massive (36%), and torrential (8%) TR. Five variables (septolateral coaptation gap, chordal structure density, en face TR jet morphology, TR jet location, and image quality) were identified as best predicting procedural outcome and were incorporated in the GLIDE (Gap, Location, Image quality, density, en-face TR morphology) score (range 0-5). TR reduction ≥2 grades and TR grade moderate or less were observed in >90% of patients with GLIDE scores of 0 and 1 and in only 5.6% and 16.7% of those with GLIDE scores ≥4. The GLIDE score was then externally validated in a separate cohort (area under the curve: 0.77; 95% CI: 0.69-0.86). TR reduction significantly correlated with functional improvement assessed by NYHA functional class and 6-minute walk distance at 3 months. CONCLUSIONS: The GLIDE score is a simple, 5-component score that is readily obtained during patient imaging and can predict successful T-TEER.

Left and Right Ventricular Longitudinal Systolic Function Following Aortic Valve Replacement in the PARTNER 2 Trial And Registry.

AIMS: Evaluation of left and right ventricular longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and right ventricular longitudinal systolic function and RV-pulmonary artery (RV-PA) coupling from baseline to 30-days and 1-year after aortic valve replacement (AVR). METHODS AND RESULTS: LV longitudinal strain (LS), tricuspid annulus plane systolic excursion (TAPSE), and RV-PA coupling were evaluated in patients from the PARTNER-2A surgical AVR (SAVR) arm (n=985) and from the PARTNER-2 SAPIEN-3 registry (n=719). TAPSE and RV-PA coupling decreased significantly following SAVR, but remained stable following TAVR. Lower LV LS, TAPSE, or RV-PA coupling at baseline were associated with increased risk of the composite of death, hospitalization, and stroke at 5-years (Adjusted-HRs for LV LS<15%: 1.24 95%CI 1.05-1.45, p=0.001; TAPSE<14mm: 1.44 95%CI 1.21-1.73, p<0.001; RV/PA coupling<0.55mm/mmHg: 1.32 95% CI 1.07-1.63, p=0.011). Reduced TAPSE at baseline was the most powerful predictor of the composite endpoint at 5-years. Patients with LV ejection fraction <50% at baseline had increased risk of the primary endpoint with SAVR (HR: 1.34, 95%CI 1.08-1.68, p=0.009) but not with TAVR (HR: 1.12, 95%CI 0.88-1.42). Lower RV-PA coupling at 30-days showed the strongest association with cardiac mortality. CONCLUSION: SAVR but not TAVR was associated with a marked deterioration in RV longitudinal systolic function and RV-PA coupling. Lower TAPSE and RV-PA coupling at 30-days were associated with inferior clinical outcomes at 5-years. In patients with LVEF<50%, TAVR was associated with superior 5-year outcomes.

Evaluation and Management of Mechanical Heart Valve Dysfunction and Thrombosis.

PURPOSE OF REVIEW: Dysfunction and thrombosis of mechanical heart valves, although uncommon, represents a challenge that requires multidisciplinary expertise for diagnosis and management. The aim of this review is to summarize strengths and weaknesses of diagnostic methods and therapeutic strategies for this uncommon but potentially life-threatening pathology. RECENT FINDINGS: Expeditious diagnosis of mechanical valve thrombosis and exclusion of other diagnostic considerations, often with incorporation of multimodality imaging, can inform the best treatment strategy. Presentation of mechanical valve thrombosis can be asymptomatic or can include heart failure, life-threatening embolic events, or cardiogenic shock. Echocardiography, fluoroscopy and computed tomography are important in the evaluation of mechanical valve dysfunction. Therapeutic strategies for thrombosis include anticoagulation, systemic thrombolysis, and surgery. Choice of treatment depends on multiple factors including thrombus size, degree of valve dysfunction, clinical presentation, and available surgical expertise.

Acute Heart Valve Emergencies.

Within the cardiac intensive care unit, prompt recognition of severe acute valvular lesions is essential because hemodynamic collapse can occur rapidly, especially when cardiac chambers have not had time for compensatory remodeling. Within this context, optimal medical management, considerations for temporary mechanical circulatory support and decisive treatments strategies are addressed. Fundamental concepts include an appreciation for how sudden changes in flow and pressure gradients between cardiac chambers can impact hemodynamic and echocardiographic findings differently compared to similarly severe chronic lesions, as well as understanding the main causes for decompensated heart failure and cardiogenic shock for each valvular abnormality.

Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept.

BACKGROUND: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment. METHODS AND RESULTS: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001). CONCLUSIONS: In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

Modulating Phase Behavior in Fatty Acid-Modified Elastin-like Polypeptides (FAMEs): Insights into the Impact of Lipid Length on Thermodynamics and Kinetics of Phase Separation.

Although post-translational lipidation is prevalent in eukaryotes, its impact on the liquid-liquid phase separation of disordered proteins is still poorly understood. Here, we examined the thermodynamic phase boundaries and kinetics of aqueous two-phase system (ATPS) formation for a library of elastin-like polypeptides modified with saturated fatty acids of different chain lengths. By systematically altering the physicochemical properties of the attached lipids, we were able to correlate the molecular properties of lipids to changes in the thermodynamic phase boundaries and the kinetic stability of droplets formed by these proteins. We discovered that increasing the chain length lowers the phase separation temperature in a sigmoidal manner due to alterations in the unfavorable interactions between protein and water and changes in the entropy of phase separation. Our kinetic studies unveiled remarkable sensitivity to lipid length, which we propose is due to the temperature-dependent interactions between lipids and the protein. Strikingly, we found that the addition of just a single methylene group is sufficient to allow tuning of these interactions as a function of temperature, with proteins modified with C7-C9 lipids exhibiting non-Arrhenius dependence in their phase separation, a behavior that is absent for both shorter and longer fatty acids. This work advances our theoretical understanding of protein-lipid interactions and opens avenues for the rational design of lipidated proteins in biomedical paradigms, where precise control over the phase separation is pivotal.

Incidence, Risk Factors, and Outcomes Associated With Permanent Pacemaker Implantation Following Tricuspid Valve Surgery.

BACKGROUND: Data regarding permanent pacemaker (PPM) implantation following tricuspid valve surgery (TVS) are limited. We sought to evaluate its incidence, risk factors, and outcomes. METHODS AND RESULTS: Medicare beneficiaries who underwent TVS from 2013 to 2020 were identified. Patients who underwent TVS for endocarditis were excluded. The primary exposure of interest was new PPM after TVS. Outcomes included all-cause mortality and readmission with endocarditis or heart failure on follow-up. Among the 13 294 patients who underwent TVS, 2518 (18.9%) required PPM placement. Risk factors included female sex (relative risk [RR], 1.26 [95% CI, 1.17-1.36], P<0.0001), prior sternotomy (RR, 1.12 [95% CI, 1.02-1.23], P=0.02), preoperative second-degree heart block (RR, 2.20 [95% CI, 1.81-2.69], P<0.0001), right bundle-branch block (RR, 1.21 [95% CI, 1.03-1.41], P=0.019), bifascicular block (RR, 1.43 [95% CI, 1.06-1.93], P=0.02), and prior malignancy (RR, 1.23 [95% CI, 1.01-1.49], P=0.04). Tricuspid valve (TV) replacement was associated with a significantly higher risk of PPM implantation when compared with TV repair (RR, 3.20 [95% CI, 2.16-4.75], P<0.0001). After a median follow-up of 3.1 years, mortality was not different in patients who received PPM compared with patients who did not (hazard ratio [HR], 1.02 [95% CI, 0.93-1.12], P=0.7). PPM placement was not associated with a higher risk of endocarditis but was associated with a higher risk of heart failure readmission (HR, 1.28 [95% CI, 1.14-1.43], P<0.001). CONCLUSIONS: PPM implantation frequently occurs after TVS, notably in female patients and patients undergoing TV replacement. Although mortality is not increased, it is associated with higher rates of heart failure rehospitalization.

Sex-Specific Prognosis of Left Ventricular Size and Function Following Repair of Degenerative Mitral Regurgitation.

BACKGROUND: Prior studies have demonstrated worse long-term outcomes for women after surgery for severe mitral regurgitation (MR). The current Class I indications for surgery for severe degenerative MR use cutoffs of left ventricular end-systolic dimension (LVESD) and left ventricular ejection fraction (EF) that do not account for known sex-related differences. OBJECTIVES: The primary objective of this study was to assess long-term mortality following mitral valve repair in women compared with men on the basis of preoperative left ventricular systolic dimensions and EF. METHODS: Consecutive patients who underwent isolated mitral valve repair for degenerative MR at a single institution between 1994 and 2016 were screened. Adjusted HRs for all-cause mortality were compared according to baseline LVESD, LVESD indexed to body surface area (LVESDi), and EF for men and women. RESULTS: Among 4,589 patients, 1,825 were women (40%), and after a median follow-up period of 7.2 years, 344 patients (7.5%) had died. The risk for mortality for women increased from the baseline hazard at an LVESD of 3.6 cm, whereas an inflection point for increased risk with LVESD was not evident in men. Regarding LVESDi, the risk for women increased at 1.8 cm/m2 compared with 2.1 cm/m2 in men. For EF, women and men had a similar inflection point (58%); however, mortality was higher for women as EF decreased. CONCLUSIONS: After mitral valve repair, women have a higher risk for all-cause mortality at lower LVESD and LVESDi and higher EF. These results support consideration of sex-specific thresholds for LVESDi in surgical decision making for patients with severe MR.

Cardiac Sarcoidosis.

Cardiac involvement is a major cause of morbidity and mortality in patients with sarcoidosis. It is important to distinguish between clinical manifest diseases from clinically silent diseases. Advanced cardiac imaging studies are crucial in the diagnostic pathway. In suspected isolated cardiac sarcoidosis, it's key to rule out alternative diagnoses. Therapeutic options can be divided into immunosuppressive agents, guideline-directed medical therapy, antiarrhythmic medications, device/ablation therapy, and heart transplantation.

Optimal antiplatelet strategy following coronary artery bypass grafting: a meta-analysis.

OBJECTIVE: Coronary artery bypass grafting (CABG) is an established revascularisation strategy for multivessel and left main coronary artery disease. Although aspirin is routinely recommended for patients with CABG, the optimal antiplatelet regimen after CABG remains unclear. We evaluated the efficacies and risks of different antiplatelet regimens (dual (DAPT) versus single (SAPT), and dual with clopidogrel (DAPT-C) versus dual with ticagrelor or prasugrel (DAPT-T/P)) after CABG. METHODS: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and performed a comprehensive literature search using PubMed, Ovid Medline, Ovid Embase and Cochrane Central Register of Controlled Trials. Data were extracted and pooled using random-effects models and Review Manager (V.5.4). RESULTS: Among the 2970 article abstracts screened, 215 full-text articles were reviewed and 38 studies totaling 77 447 CABG patients were included for analyses. DAPT compared with SAPT was associated with significantly lower all-cause mortality (OR 0.65 with 95% CI 0.50 to 0.86; p=0.002), cardiovascular mortality (OR 0.53, 95% CI 0.33 to 0.84; p=0.008), and major adverse cardiac and cerebrovascular events (MACCE) (OR 0.68, 95% CI 0.51 to 0.91; p=0.01), but higher rates of major (OR 1.30, 95% CI 1.08 to 1.56; p=0.007) and minor bleeding (OR 1.87, 95% CI 1.28 to 2.74; p=0.001) after CABG. DAPT-T/P compared with DAPT-C was associated with significantly lower all-cause (OR 0.43, 95% CI 0.29 to 0.65; p≤0.0001) and cardiovascular mortality (OR 0.44, 95% CI 0.24 to 0.80; p=0.008), and no differences on other cardiovascular or bleeding outcomes after CABG. CONCLUSION: In patients with CABG, DAPT compared with SAPT and DAPT-T/P compared with DAPT-C were associated with reduction in all-cause and cardiovascular mortality, especially in patients with acute coronary syndrome. Additionally, DAPT was associated with reduction in MACCE, but higher rates of major and minor bleeding. An individualised approach to choosing antiplatelet regimen is necessary for patients with CABG based on ischaemic and bleeding risks.

Endocarditis after Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) use is gaining momentum as the mainstay for the treatment of aortic stenosis compared to surgical aortic valve replacement (SAVR). Unfortunately, TAVR-related infective endocarditis (TAVR-IE) is expected to be detected more and more as a result of the ever-expanding indications in younger patients. Given the overall poor prognosis of TAVR-IE, it is imperative that clinicians familiarize themselves with common presentations, major risk factors, diagnostic pitfalls, therapeutic approaches, and the prevention of TAVR-IE. Herein, we review all of the above in detail with the most updated available literature.

Solvation Behavior of Elastin-like Polypeptides in Divalent Metal Salt Solutions.

The effects of CaCl2 and MgCl2 on the cloud point temperature of two different elastin-like polypeptides (ELPs) were studied using a combination of cloud point measurements, molecular dynamics simulations, and infrared spectroscopy. Changes in the cloud point for the ELPs in aqueous divalent metal cation solutions were primarily governed by two competing interactions: the cation-amide oxygen electrostatic interaction and the hydration of the cation. In particular, Ca2+ cations can more readily shed their hydration shells and directly contact two amide oxygens by the formation of ion bridges. By contrast, Mg2+ cations were more strongly hydrated and preferred to partition toward the amide oxygens along with their hydration shells. In fact, although hydrophilic ELP V5A2G3 was salted-out at low concentrations of MgCl2, it was salted-in at higher salt concentrations. By contrast, CaCl2 salted the ELP sharply out of solution at higher salt concentrations because of the bridging effect.

Lymphocytic Perimyocarditis Masquerading as Steroid-Dependent Recurrent Pericarditis.

Lymphocytic myocarditis is a pattern of myocardial inflammation typically associated with viral, autoimmune, or idiopathic causes. We present a case of lymphocytic perimyocarditis masquerading as steroid-dependent recurrent pericarditis. This case shows the advantages of using multimodal cardiac imaging and endomyocardial biopsy in clarifying diagnosis in treatment-resistant cases. (Level of Difficulty: Advanced.).

Optimal left ventricular ejection fraction in risk stratification of patients with cardiac sarcoidosis.

AIMS: Identifying patients with cardiac sarcoidosis (CS) who are at an increased risk of sudden cardiac death (SCD) poses a clinical challenge. We sought to identify the optimal cutoff for left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmia (VA) and all-cause mortality and to identify clinical and imaging risk factors in patients with known CS. METHODS AND RESULTS: This retrospective cohort included 273 patients with well-established CS. The primary endpoint was a composite of VA and all-cause mortality. A modified receiver operating curve analysis was utilized to identify the optimal cutoff for LVEF in predicting the primary composite endpoint. Cox proportional hazard regression analysis was used to identify independent risk factors of the outcomes. At median follow-up of 7.9 years, the rate of the primary endpoint was 38% (83 VAs and 32 all-cause deaths). The 5-year overall survival rate was 97%. The optimal cutoff LVEF for the primary composite endpoint was 42% in the entire cohort and in subjects without a history of VA. Younger age, history of VA, lower LVEF, and any presence of scar by cardiac magnetic resonance (CMR) imaging and/or positron emission tomography (PET) were found to be independent risk factors for the primary endpoint and for VA, whereas lower LVEF, baseline NT-proBNP, and any presence of scar were independent risk factor of all-cause mortality. CONCLUSION: Among patients with CS, a mild reduction in LVEF of 42% was identified as the optimal cutoff for predicting VA and all-cause mortality. Prior VA and scar by CMR or PET are strong risk factors for future VA and all-cause mortality.

Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 56 Results From the VALOR-HCM Randomized Clinical Trial.

Importance: There is an unmet need for novel medical therapies before recommending invasive therapies for patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM). Mavacamten has been shown to improve left ventricular outflow tract (LVOT) gradient and symptoms and may thus reduce the short-term need for septal reduction therapy (SRT). Objective: To examine the cumulative longer-term effect of mavacamten on the need for SRT through week 56. Design, Setting, and Participants: This was a double-blind, placebo-controlled, multicenter, randomized clinical trial with placebo crossover at 16 weeks, conducted from July 2020 to November 2022. Participants were recruited from 19 US HCM centers. Included in the trial were patients with obstructive HCM (New York Heart Association class III/IV) referred for SRT. Study data were analyzed April to August 2023. Interventions: Patients initially assigned to mavacamten at baseline continued the drug for 56 weeks, and patients taking placebo crossed over to mavacamten from week 16 to week 56 (40-week exposure). Dose titrations were performed using echocardiographic LVOT gradient and LV ejection fraction (LVEF) measurements. Main Outcome and Measure: Proportion of patients undergoing SRT, remaining guideline eligible or unevaluable SRT status at week 56. Results: Of 112 patients with highly symptomatic obstructive HCM, 108 (mean [SD] age, 60.3 [12.5] years; 54 male [50.0%]) qualified for the week 56 evaluation. At week 56, 5 of 56 patients (8.9%) in the original mavacamten group (3 underwent SRT, 1 was SRT eligible, and 1 was not SRT evaluable) and 10 of 52 patients (19.2%) in the placebo crossover group (3 underwent SRT, 4 were SRT eligible, and 3 were not SRT evaluable) met the composite end point. A total of 96 of 108 patients (89%) continued mavacamten long term. Between the mavacamten and placebo-to-mavacamten groups, respectively, after 56 weeks, there was a sustained reduction in resting (mean difference, -34.0 mm Hg; 95% CI, -43.5 to -24.5 mm Hg and -33.2 mm Hg; 95% CI, -41.9 to -24.5 mm Hg) and Valsalva (mean difference, -45.6 mm Hg; 95% CI, -56.5 to -34.6 mm Hg and -54.6 mm Hg; 95% CI, -66.0 to -43.3 mm Hg) LVOT gradients. Similarly, there was an improvement in NYHA class of 1 or higher in 51 of 55 patients (93%) in the original mavacamten group and in 37 of 51 patients (73%) in the placebo crossover group. Overall, 12 of 108 patients (11.1%; 95% CI, 5.87%-18.60%), which represents 7 of 56 patients (12.5%) in the original mavacamten group and 5 of 52 patients (9.6%) in the placebo crossover group, had an LVEF less than 50% (2 with LVEF ≤30%, one of whom died), and 9 of 12 patients (75%) continued treatment. Conclusions and Relevance: Results of this randomized clinical trial showed that in patients with symptomatic obstructive HCM, mavacamten reduced the need for SRT at week 56, with sustained improvements in LVOT gradients and symptoms. Although this represents a useful therapeutic option, given the potential risk of LV systolic dysfunction, there is a continued need for close monitoring. Trial Registration: ClinicalTrials.gov Identifier: NCT04349072.

Prevalence of ATTR-CA and high-risk features to guide testing in patients referred for TAVR.

PURPOSE: Transthyretin cardiac amyloidosis (ATTR-CA) is thought to be prevalent in patients with severe aortic stenosis (AS) who are referred for transcatheter aortic valve replacement (TAVR). However, prior studies were published when TAVR was only offered to elderly, inoperable, and high-risk patients. The aim of this study was to reevaluate the prevalence of ATTR-CA in a contemporary TAVR population and identify high-risk features to guide referral for technetium-99 pyrophosphate scan (99mTc-PyP scan) screening. METHODS: Patients seen in a multidisciplinary TAVR clinic for severe AS 70 years and older were referred for a 99mTc-PyP scan to evaluate for ATTR-CA. The primary outcome was the percent with a positive scan. The discriminatory ability of high-risk features was assessed to develop a more judicious screening system. RESULTS: Over the study period, 380 patients underwent screening, and 20 patients (5.3%) had a positive scan, with 17 patients having confirmed ATTR-CA, 1 patient deferring confirmatory testing (combined 4.7%), 1 having light chain amyloidosis, and 1 negative on biopsy. Compared to other patient and echocardiographic measures, elevated NT-pro BNP (> 1000 ng/L) was the best discriminator on who should be referred for 99mTc-PyP scan screening, with a sensitivity of 90% and a negative predictive value of 99%. CONCLUSION: The prevalence of ATTR-CA may be lower in a contemporary TAVR population due to its expanded indication for low-risk patients. NT-pro BNP is a simple test that can improve screening yield and more judiciously guide screening for ATTR-CA in this at-risk population. Comparison of the original versus the proposed algorithm.