MYC Controls the Epstein-Barr Virus Lytic Switch.

Epstein-Barr virus (EBV) is associated with multiple human malignancies. To evade immune detection, EBV switches between latent and lytic programs. How viral latency is maintained in tumors or in memory B cells, the reservoir for lifelong EBV infection, remains incompletely understood. To gain insights, we performed a human genome-wide CRISPR/Cas9 screen in Burkitt lymphoma B cells. Our analyses identified a network of host factors that repress lytic reactivation, centered on the transcription factor MYC, including cohesins, FACT, STAGA, and Mediator. Depletion of MYC or factors important for MYC expression reactivated the lytic cycle, including in Burkitt xenografts. MYC bound the EBV genome origin of lytic replication and suppressed its looping to the lytic cycle initiator BZLF1 promoter. Notably, MYC abundance decreases with plasma cell differentiation, a key lytic reactivation trigger. Our results suggest that EBV senses MYC abundance as a readout of B cell state and highlights Burkitt latency reversal therapeutic targets.

Impact of untreated chronic obstructive coronary artery disease on outcomes after transcatheter aortic valve replacement.

BACKGROUND AND AIMS: In transcatheter aortic valve replacement (TAVR) recipients, the optimal management of concomitant chronic obstructive coronary artery disease (CAD) remains unknown. Some advocate for pre-TAVR percutaneous coronary intervention, while others manage it expectantly. The aim of this study was to assess the impact of varying degrees and extent of untreated chronic obstructive CAD on TAVR and longer-term outcomes. METHODS: The authors conducted a retrospective cohort study of TAVR recipients from January 2015 to November 2021, separating patients into stable non-obstructive or varying degrees of obstructive CAD. The major outcomes of interest were procedural all-cause mortality and complications, major adverse cardiovascular events, and post-TAVR unplanned coronary revascularization. RESULTS: Of the 1911 patients meeting inclusion, 75%, 6%, 10%, and 9% had non-obstructive, intermediate-risk, high-risk, and extreme-risk CAD, respectively. Procedural complication rates overall were low (death 0.4%, shock 0.1%, extracorporeal membrane oxygenation 0.1%), with no difference across groups. At a median follow-up of 21 months, rates of acute coronary syndrome and unplanned coronary revascularization were 0.7% and 0.5%, respectively, in the non-obstructive population, rising in incidence with increasing severity of CAD (P < .001 for acute coronary syndrome/unplanned coronary revascularization). Multivariable analysis did not yield a significantly greater risk of all-cause mortality or major adverse cardiovascular events across groups. One-year acute coronary syndrome and unplanned coronary revascularization rates in time-to-event analyses were significantly greater in the non-obstructive (98%) vs. obstructive (94%) subsets (Plog-rank< .001). CONCLUSIONS: Transcatheter aortic valve replacement can be performed safely in patients with untreated chronic obstructive CAD, without portending higher procedural complication rates and with relatively low rates of unplanned coronary revascularization and acute coronary syndrome at 1 year.

Sarcopenia and Frailty in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Skeletal muscle mass (SMM) plays a crucial role in risk assessment in transcatheter aortic valve replacement (TAVR) candidates, yet it remains underutilized. Traditional methods focus on weakness or performance but omit SMM. This study compared traditional and novel markers of sarcopenia and frailty in terms of their ability to predict adverse outcomes post-TAVR. METHODS: Three risk models were evaluated for the composite outcome of perioperative complications, 1-year rehospitalization, or 1-year mortality: (1) sarcopenia by combining low muscle mass (LMM) and weakness/performance assessed by hand grip strength or gait speed; (2) frailty by an Adapted Green score; and (3) frailty by the Green-SMI score incorporating LMM by multi-level opportunistic pre-TAVR thoracic CT segmentation. RESULTS: In this study we included 184 eligible patients from January to December of 2018, (96.7%) of which were balloon expandable valves. The three risk models identified 22.8% patients as sarcopenic, 63.6% as frail by the Adapted Green score, and 53.8% as frail by the Green-SMI score. There were higher rates of the composite outcome in patients with sarcopenia (54.8%) and frailty (41.9% with the Adapted Green and 50.5% with the Green-SMI score) compared to their non-sarcopenic (30.3%) and non-frail counterparts (25.4% with the Adapted Green and 18.8% with the Green-SMI score). Sarcopenia and frailty by Green-SMI, but not by the Adapted Green, were associated with higher risks of the composite outcome on multivariable adjustment (HR 2.2 [95% CI: 1.25-4.02], p=0.007 and HR 3.4 [95% CI: 1.75-6.65], p<0.001, respectively). CONCLUSIONS: The integration of pre-operative CT-based SMM to a frailty score significantly improves the prediction of adverse outcomes in patients undergoing TAVR.

Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas.

Activated B-cell-like diffuse large B-cell lymphomas (ABC-DLBCLs) are characterized by constitutive activation of nuclear factor κB driven by the B-cell receptor (BCR) and Toll-like receptor (TLR) pathways. However, BCR-pathway-targeted therapies have limited impact on DLBCLs. Here we used >1,100 DLBCL patient samples to determine immune and extracellular matrix cues in the lymphoid tumour microenvironment (Ly-TME) and built representative synthetic-hydrogel-based B-cell-lymphoma organoids accordingly. We demonstrate that Ly-TME cellular and biophysical factors amplify the BCR-MYD88-TLR9 multiprotein supercomplex and induce cooperative signalling pathways in ABC-DLBCL cells, which reduce the efficacy of compounds targeting the BCR pathway members Bruton tyrosine kinase and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1). Combinatorial inhibition of multiple aberrant signalling pathways induced higher antitumour efficacy in lymphoid organoids and implanted ABC-DLBCL patient tumours in vivo. Our studies define the complex crosstalk between malignant ABC-DLBCL cells and Ly-TME, and provide rational combinatorial therapies that rescue Ly-TME-mediated attenuation of treatment response to MALT1 inhibitors.

A comprehensive overview of surgical and transcatheter therapies to treat tricuspid regurgitation in patients with heart failure.

PURPOSE OF REVIEW: The unique pathophysiologic considerations of severe tricuspid regurgitation (TR) have led to advancements in surgical and transcatheter treatments. The purpose of this review is to highlight the current surgical and transcatheter tricuspid valve interventions (TTVI) to functional TR. RECENT FINDINGS: Surgical repair with ring annuloplasty consistently demonstrates better outcomes than surgical replacement or other repair approaches. However, surgical uptake of TR correction remains relatively low, and operative mortality rates are still high owing to multiple comorbidities and advanced tricuspid valve disease/right ventricular dysfunction at time of referral. Pivotal trials for tricuspid transcatheter edge-to-edge repair (T-TEER) and transcatheter TV replacement (TTVR) indicate improved quality of life compared to medical therapy alone for high-surgical-risk patients with severe symptomatic TR. Trials are underway to assess caval valve implantation (CAVI), which holds hope for many severe TR patients who are not ideal candidates for T-TEER or orthotopic TTVR. Peri-procedural optimization of right ventricular function remains critical to promote both device success and patient outcomes. SUMMARY: Clinical outcomes after surgical TV intervention are poor, often due to intervening late in the disease course of TR. TTVI covers a treatment gap for patients deemed inoperable or high-surgical-risk, but earlier referral for TV interventions is still important prior to patients developing multiorgan dysfunction from chronic untreated TR.

Sex-related characteristics and short-term outcomes of patients undergoing transcatheter tricuspid valve intervention for tricuspid regurgitation.

AIMS: The impact of sexuality in patients with significant tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI) is unknown. The aim of this study was to investigate sex-specific outcomes in patients with significant TR treated with TTVI vs. medical therapy alone. METHODS AND RESULTS: The Transcatheter Tricuspid Valve Therapies (TriValve) registry collected data on patients with significant TR from 24 centres who underwent TTVI from 2016 to 2021. A control cohort was formed by medically managed patients with ≥severe isolated TR diagnosed in 2015-18. The primary endpoint was freedom from all-cause mortality. Secondary endpoints were heart failure (HF) hospitalization, New York Heart Association (NYHA) functional status, and TR severity. One-year outcomes were assessed for the TriValve cohort and compared with the control cohort with the inverse probability of treatment weighting (IPTW). A total of 556 and 2072 patients were included from the TriValve and control groups, respectively. After TTVI, there was no difference between women and men in 1-year freedom from all-cause mortality 80.9% vs. 77.9%, P = 0.56, nor in HF hospitalization (P = 0.36), NYHA Functional Classes III and IV (P = 0.17), and TR severity >2+ at last follow-up (P = 0.42). Multivariable Cox-regression weighted by IPTW showed improved 1-year survival after TTVI compared with medical therapy alone in both women (adjusted hazard ratio 0.45, 95% confidence interval 0.23-0.83, P = 0.01) and men (adjusted hazard ratio 0.42, 95% confidence interval 0.18-0.89, P = 0.03). CONCLUSION: After TTVI in high-risk patients, there were no sex-related differences in terms of survival, HF hospitalization, functional status, and TR reduction up to 1 year. The IPTW analysis shows a survival benefit of TTVI over medical therapy alone in both women and men.

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.

Clinical and echocardiographic outcomes with new-onset left bundle branch block after SAPIEN-3 transcatheter aortic valve replacement.

BACKGROUND: New-onset left bundle branch block (LBBB) can develop after transcatheter aortic valve replacement (TAVR) resulting in worse outcomes. AIMS: Describe clinical and echocardiographic outcomes with new-onset LBBB after TAVR. METHODS: We included consecutive patients who underwent transfemoral-TAVR with SAPIEN-3 (S3) valve between April 2015 and December 2018. Exclusion criteria included pre-existing LBBB, right BBB, left anterior hemiblock, left posterior hemiblock, wide QRS ≥ 120ms, prior permanent pacemaker (PPM), and nontransfemoral access. RESULTS: Among 612 patients, 11.4% developed new-onset LBBB upon discharge. The length of stay was longer with new-onset LBBB compared with no LBBB [3 (2-5) days versus 2 (1-3) days; p < 0.001]. New-onset LBBB was associated with higher rates of 30-day PPM requirement (18.6% vs. 5.4%; p < 0.001) and 1-year heart failure hospitalizations (10.7% vs. 4.4%; p = 0.033). There was no difference in 3-year mortality between both groups (30.9% vs. 30.6%; p = 0.829). Further, new-onset LBBB was associated with lower left ventricular ejection fraction (LVEF) at both 30 days (55.9 ± 11.4% vs. 59.3 ± 9%; p = 0.026) and 1 year (55 ± 12% vs. 60.1 ± 8.9%; p = 0.002). These changes were still present when we stratified patients according to baseline LVEF (≥50% or <50%). New-onset LBBBs were associated with a higher 1-year LV end-diastolic volume index (51.4 ± 18.6 vs. 46.4 ± 15.1 ml/m2 ; p = 0.036), and LV end-systolic volume index (23.2 ± 14.1 vs. 18.9 ± 9.7 ml/m2 ; p = 0.009). Compared with resolved new-onset LBBB, persistent new-onset LBBB was associated with worse LVEF and higher PPM at 1 year. CONCLUSIONS: New-onset LBBB after S3 TAVR was associated with higher PPM requirement, worse LVEF, higher LV volumes, and increased heart failure hospitalizations, with no difference in mortality.

Novel devices for managing heart failure.

PURPOSE OF REVIEW: Despite advances in heart failure (HF) therapies, the associated morbidity, mortality, hospitalization rates, and healthcare expenditures remain high. A significant proportion of patients with HF remain symptomatic despite receiving optimal medical therapy. Consequently, there exists a large unmet clinical need for novel therapies for treating acute and chronic HF. With the exponential growth of transcatheter interventions in structural heart disease, novel applications of minimally invasive, device-based therapies have been sought in an effort to bridge this treatment gap. The rationale, development, and current data underscoring these therapies will be summarized in this review. RECENT FINDINGS: Recent studies have demonstrated the safety and efficacy of devices that alter left ventricular geometry (i.e., ventriculoplasty), create anatomic shunts to decompress the left atrium, and modulate vena caval and renal blood flow. However pivotal large trials evaluating clinical outcomes are ongoing. SUMMARY: Innovative device-based therapies may expand our armamentarium against the growing heterogeneous and morbid HF syndrome.

Surgical versus medical management of infective endocarditis after TAVR.

We assessed the incidence of aortic valve surgery intervention in the treatment of infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) and compared the characteristics and outcomes of surgical intervention versus medical management alone in this cohort using a nationwide data set. We identified all the hospitalizations in patients undergoing TAVR who developed IE within 1-year (i.e., early IE) of the procedure from 2014 to 2017 using the Nationwide Readmission Database (NRD). The primary outcomes of the study were in-hospital mortality. A total of 906 hospitalizations were identified for IE amongst the TAVR patients from 2014 to 2017 of which 20 (2.21%) underwent aortic valve surgery during the hospitalization. Patients undergoing surgery were younger, more likely to have Staphylococcus aureus endocarditis, cardiogenic shock, and acute kidney injury (AKI) during the hospitalization. There were no significant differences in in-hospital mortality (9.9% vs. 12.4%, p = 0.824; adjusted odds ratio (aOR): 0.26 (0.01-1.58), p = 0.223) and 30-day readmissions. However, the length of stay and hospitalization costs were higher in surgical intervention group. The important predictors of in-hospital mortality in TAVR-related IE patients were dialysis during IE hospitalization, AKI, cardiogenic shock, Staphylococcus aureus endocarditis, stroke, and female sex. The utilization of surgical management for IE post-TAVR during the index hospitalization is low, and there is no significant mortality benefit with surgical intervention as compared with the medical management.

One-year clinical and echocardiographic outcomes of transcatheter aortic valve replacement with SAPIEN 3 Ultra versus SAPIEN 3.

BACKGROUND: The newest-generation balloon-expandable valve, SAPIEN 3 Ultra (S3U), is expected to function well with the enhanced sealing skirt compared with SAPIEN 3 (S3). However, current literature on the comparison between these two valves is limited to short-term follow-ups. Therefore, we aimed to evaluate the 1-year outcomes and echocardiographic changes of S3U compared with S3. METHODS: We retrospectively identified patients who underwent transfemoral-transcatheter aortic valve replacement with S3U or S3 (20/23/26 mm) at our institution in 2018-2020. Outcomes were 1-year clinical events and echocardiographic parameters, and were compared between S3U and S3 after adjustment with inverse probability of treatment weighting. RESULTS: The S3U and S3 groups included 297 (25.7%) and 858 (74.3%) patients, respectively. There were no significant differences between the two groups in clinical events (death 5.8% vs. 5.5%, hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.81-1.90; death or heart failure hospitalization 10.3% vs. 10.1%, HR 1.04, 95% CI 0.67-1.62). The S3U group had a lower prevalence of mild paravalvular leakage (PVL) (13.7% vs. 22.3%, p = 0.044), with similar moderate PVL (0.7% vs. 1.2%, p > 0.99). No significant differences were observed in aortic valve mean gradient and Doppler velocity index at 1 year. However, the S3U group had a larger increase in mean gradient from implantation to 1 year (median +4.70 vs. +1.63 mmHg, p < 0.001). CONCLUSIONS: S3U and S3 carried similarly favorable clinical event risks. Nonetheless, S3U was associated with less frequent mild PVL but a larger increase in transprosthetic gradient. Further studies are needed to determine the prognostic impact of these hemodynamic differences.

Incidence, treatment, and outcomes of acute myocardial infarction following transcatheter or surgical aortic valve replacement.

OBJECTIVES: This study aimed to evaluate the incidence, treatment, and outcomes of acute myocardial infarction (AMI) following transcatheter or surgical aortic valve replacement (TAVR or SAVR). BACKGROUND: Coronary artery disease is common in patients who undergo aortic valve replacement. However, little is known about differences in clinical features of post-TAVR or post-SAVR AMI. METHODS: We retrospectively identified post-TAVR or post-SAVR (including isolated and complex SAVR) patients admitted with AMI using the Nationwide Readmissions Database 2012-2017. Incidence, invasive strategy (coronary angiography or revascularization), and in-hospital outcomes were compared between post-TAVR and post-SAVR AMIs. RESULTS: The incidence of 180-day AMI was higher post-TAVR than post-SAVR (1.59% vs. 0.72%; p < 0.001). Post-TAVR AMI patients (n = 1315), compared with post-SAVR AMI patients (n = 1344), were older, had more comorbidities and more frequent non-ST-elevation AMI (NSTEMI: 86.6% vs. 78.0%; p < 0.001). After propensity-score matching, there was no significant difference in in-hospital mortality between post-TAVR and post-SAVR AMIs (14.7% vs. 16.1%; p = 0.531), but the mortality was high in both groups, particularly in ST-elevation AMI (STEMI: 38.8% vs. 29.2%; p = 0.153). Invasive strategy was used less frequently for post-TAVR AMI than post-SAVR AMI (25.6% vs. 38.3%; p < 0.001). Invasive strategy was associated with lower mortality in both post-TAVR (adjusted odds ratio = 0.40; 95% confidence interval = [0.24-0.66]) and post-SAVR groups (0.60 [0.41-0.88]). CONCLUSIONS: AMI, albeit uncommon, was more frequent post-TAVR than post-SAVR. Patients commonly presented with NSTEMI, but the mortality of STEMI was markedly high. Further studies are needed to understand why a substantial percentage of patients do not receive invasive coronary treatment, particularly after TAVR, despite seemingly better outcomes with invasive strategy.

Two-year outcomes after transcatheter aortic valve-in-valve implantation in degenerated surgical valves.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has emerged in recent years as a safe alternative to redo surgery in high-risk patients. Although early results are encouraging, data beyond short-term outcomes are lacking. Herein, we aimed to assess the 2-year outcomes after ViV-TAVI. METHODS: Patients undergoing ViV-TAVI for degenerated surgical valves between 2013 and 2019 at the Cleveland Clinic were reviewed. The coprimary endpoints were all-cause mortality and congestive heart failure (CHF) hospitalizations. We used time-to-event analyses to assess the primary outcomes. Further, we measured the changes in transvalvular gradients and the incidence of structural valve deterioration (SVD). RESULTS: One hundred and eighty-eight patients were studied (mean age = 76 years; 65% males). At 2 years of follow-up, all-cause mortality and CHF hospitalizations occurred in 15 (8%) and 28 (14.9%) patients, respectively. On multivariable analysis, the postprocedural length of stay was a significant predictor for both all-cause mortality (hazard ratio [HR] = 1.1; 95% confidence interval [CI]: 1.01, 1.19) and CHF hospitalization (HR = 1.16; 95% CI: 1.07, 1.27). However, the internal diameter of the surgical valve was not associated with significant differences in both primary endpoints. For hemodynamic outcomes, nine patients (4.8%) developed SVD. The mean and peak transvalvular pressure gradients remained stable over the follow-up period. CONCLUSION: ViV-TAVI for degenerated surgical valves was associated with favorable 2-year clinical and hemodynamic outcomes. Further studies are needed to better understand the role of ViV-TAVI as a treatment option in the life management of aortic valve disease.

Cerebral embolic protection and severity of stroke following transcatheter aortic valve replacement.

BACKGROUND: The cerebral embolic protection (CEP) device captures embolic debris during transcatheter aortic valve replacement (TAVR). However, the impact of CEP on stroke severity following TAVR remains unclear. Therefore, we aimed to examine whether CEP was associated with reduced severity of stroke following TAVR. METHODS: This was a retrospective cohort study of 2839 consecutive patients (mean age: 79.2 ± 9.5 years, females: 41.5%) who underwent transfemoral TAVR at our institution between 2013 and 2020. We categorized patients into Sentinel CEP users and nonusers. Neuroimaging data were reviewed and the final diagnosis of a cerebrovascular event was adjudicated by a neurologist blinded to the CEP use or nonuse. We compared the incidence and severity (assessed by the National Institutes of Health Stroke Scale [NIHSS]) of stroke through 72 h post-TAVR or discharge between the two groups using stabilized inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: Of the eligible patients, 1802 (63.5%) received CEP during TAVR and 1037 (36.5%) did not. After adjustment for patient characteristics by stabilized IPTW, the rate of overall stroke was numerically lower in CEP users than in CEP nonusers, but the difference did not reach statistical significance (0.49% vs. 1.18%, p = 0.064). However, CEP users had significantly lower rates of moderate-or-severe stroke (NIHSS ≥ 6: 0.11% vs. 0.69%, p = 0.013) and severe stroke (NIHSS ≥ 15: 0% vs. 0.29%, p = 0.046). Stroke following CEP use (n = 8), compared with stroke following CEP nonuse (n = 15), tended to carry a lower NIHSS (median [IQR], 4.0 [2.0-7.0] vs. 7.0 [4.5-19.0], p = 0.087). Four (26.7%) out of 15 patients with stroke following CEP nonuse died within 30 days, with no death after stroke following CEP use. CONCLUSIONS: CEP use may be associated with attenuated severity of stroke despite no significant difference in overall stroke incidence compared with CEP nonuse. This finding is considered hypothesis-generating and needs to be confirmed in large prospective studies.

Aspirin Versus Dual Antiplatelet Therapy in Patients Undergoing Trans-Catheter Aortic Valve Implantation, Updated Meta-Analysis.

BACKGROUND: The Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic-Valve Implantation (POPular TAVI) trial reported comparable composite endpoints of ischemic events using aspirin compared to dual antiplatelet therapy (DAPT). However, this trial was not powered to detect individual differences in ischemic events. We sought to conduct a meta-analysis to compare aspirin to DAPT on ischemic and bleeding events following TAVI. METHODS: The MEDLINE database was searched from inception until September 2020 and only randomized clinical trials of patients receiving antiplatelet therapy following TAVI were included. The treatment effect was reported as rate ratios (RRs) with 95% confidence intervals. RESULTS: Four randomized clinical trials of 1086 TAVI patients were included. There was a 51% reduction in major or life-threatening bleeding with aspirin compared with DAPT [RR 0.49, (95%CI 0.31 to 0.78)]. Aspirin was not associated with an increased risk of death [RR 1.01, (95%CI 0.62 to 1.65)], cardiovascular death [RR 1.15, (95%CI 0.56 to 2.36)], ischemic stroke [RR 0.93, (95%CI 0.51 to 1.70)], or MI [RR 0.53, (95%CI 0.18 to 1.57)]. CONCLUSIONS: This meta-analysis supports the use of aspirin as the optimal antiplatelet strategy following TAVI procedures in reducing bleeding without an increase in ischemic events compared with dual antiplatelet therapy.

Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study.

AIMS: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. METHODS AND RESULTS: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.34). Similar results were shown when examining discordance across clinical cutpoints. CONCLUSIONS: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.

Impact of baseline conduction abnormalities on outcomes after transcatheter aortic valve replacement with SAPIEN-3.

BACKGROUND: Baseline conduction abnormalities are known risk factors for permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). We sought to determine the impact of baseline right bundle branch block (RBBB), left bundle branch block (LBBB), left anterior hemiblock (LAHB), first-degree atrioventricular block (AVB) and atrial fibrillation/flutter (AF) on TAVR outcomes. METHODS: Consecutive patients who underwent transfemoral TAVR with SAPIEN-3 (S3) were included. We excluded patients with prior PPM, nontransfemoral access or valve-in-valve. RESULTS: Among 886 patients, baseline RBBB was seen in 15.9%, LBBB in 6.3%, LAHB in 6.2%, first-degree AVB in 26.3% and AF in 37.5%. The rate of 30-day PPM was 10.1%. Baseline RBBB (OR 4.005; 95% CI 2.386-6.723; p < .001) and first-degree AVB (OR 1.847; 95% CI 1.133-3.009; p = .014) were independent predictors of 30 day PPM. LAHB also resulted in higher PPM rates but only in unadjusted analysis (21.8% vs. 9.4%; p = .003). Baseline LBBB and AF were associated with lower left ventricular ejection fraction (LVEF) at both baseline and 1 year after TAVR. However, Δ LVEF over time were noted to be similar with baseline LBBB (1.8% vs. 1.4%; p = .809) and AF (1.1% vs. 1.7%; p = .458). Moreover, baseline AF was also associated with higher stroke/transient ischemic attack (TIA) at 1 year (4.4% vs. 1.8%; p = .019), 1-year major adverse cardiac and cerebrovascular events (MACCE) (19.5% vs. 13.3%; p = .012) and 2 year mortality (23.5% vs. 15.2%; p = .016). None of the other baseline conduction defects affected long-term mortality or MACCE. CONCLUSION: In our S3 TAVR population, baseline RBBB and first-degree AVB predicted higher PPM risk. Prior LBBB and AF were associated with lower LVEF at both baseline and 1 year. Lastly, preexisting AF was associated with higher rates of mortality, stroke/TIA, and MACCE.

Roles of Cardiac Computed Tomography in Guiding Transcatheter Tricuspid Valve Interventions.

PURPOSE OF REVIEW: The field of transcatheter tricuspid valve interventions (TTVI) is rapidly evolving to meet a well-defined but unmet clinical need. Severe tricuspid regurgitation is common and is associated with significant morbidity and mortality. Surgical options are limited and of high risk. The success of TTVI depends on careful procedural planning, and cardiac computed tomography (CCT) plays an emerging key role. RECENT FINDINGS: TTVI technologies have various targets, including the leaflets, annulus, and venae cavae, along with valve replacement. Based on the planned procedure, CCT allows for device sizing, careful assessment of the access route, and comprehensive analysis of relevant adjacent anatomic structures to enhance procedural safety. It can also evaluate right-sided heart function, and its data can be for fusion imaging and 3D printing. Procedural planning is key to TTVI's success and is highly dependent on high-quality CCT data. This review details the comprehensive roles of CCT, specifics of the dedicated TTVI protocol, and its limitations.

Progression of ultrasound plaque attenuation and low echogenicity associates with major adverse cardiovascular events.

AIMS: Intravascular ultrasound (IVUS) imaging can visualize vulnerable plaque features including attenuation (AP) and echolucency (ELP). While IVUS-derived vulnerable plaque features associate with microvascular obstruction during percutaneous coronary intervention, the relationship between these plaque features and clinical outcomes has not been established. This analysis aimed to evaluate the association of AP/ELP with cardiovascular events. METHODS AND RESULTS: Serial IVUS imaging was reviewed in 1497 patients, followed for 18-24 months, with coronary artery disease from two clinical trials. Attenuated plaque and ELP were identified to measure each characteristics (AP arc, ELP area, and lengths), which permitted calculation of an AP index (API) and ELP volume. Attenuated plaque/ELP progression was defined as patients with any increase of API or ELP volume on serial imaging. The major cardiovascular events (MACEs) were defined as death, myocardial infarction, stroke, and coronary revascularization. AP or ELP was identified in 282 patients (18.8%) at baseline and 160 (10.7%) patients demonstrated an increase in AP or ELP at follow-up. The incidence of MACE was higher in patients with baseline AP/ELP than those without (8.2% vs. 3.9%, P = 0.002). Patients with AP/ELP progression were more likely to be acute coronary syndrome (41.9 vs. 33.2%, P = 0.03) and have greater baseline percent atheroma volume (40.0% vs. 35.8%, P < 0.001) than those without. On multivariable analysis, AP/ELP progression was more strongly associated with MACE [baseline AP/ELP: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.05-2.97, AP/ELP progression: HR 2.19, 95% CI 1.24-3.86]. CONCLUSION: Attenuation/ELP progression was associated with a higher prevalence of cardiovascular events, supporting a potential role for the identification of high-risk vulnerable plaques in patients with coronary artery disease.

Statins in a Distorted Mirror of Media.

PURPOSE OF REVIEW: Statins have proven efficacy with a favorable safety profile yet, despite being widely affordable, remain profoundly underutilized. Statins have acquired a bad reputation, which is likely contributing to high rates of nonadherence and discontinuation. The degree to which negative media perceptions contribute to underutilization is unclear. RECENT FINDINGS: The media has a key role in informing discussion on the public agenda but also on how issues are framed. In this context, the majority of studies evaluating news coverage suggest that the content on statins is predominantly negative and focused on potential harm. Studies utilizing quasi-experimental and interrupted time series design have shown periods of negative news stories on statins in multiple countries are associated with (a) less statin commencement in eligible patients, (b) high rates of discontinuation, and (c) poor long-term adherence. This review highlights the deleterious impact of negative media coverage on statin utilization through misattribution of muscle complaints and the nocebo effect. Academia must work with the media to harmonize the public health messaging; however, individual physicians have a critical role in mitigating a harmful narrative of misinformation and actively discredit malinformation.