Contemporary Outcomes and Trends for the Transseptal Mitral Valve-in-Valve Procedure Using Balloon Expandable Transcatheter Valves in the United States.

BACKGROUND: Previous transcatheter valve therapy registry analyses of transcatheter mitral valve in valve (MViV) replacement of degenerated bioprosthesis reported early experience in the United States. Given recent increases in transseptal MViV volumes and introduction of the SAPIEN 3 Ultra valve, it is important to determine contemporary outcomes for patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV replacement. METHODS: The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry was used to extract data for all patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV from 2015 to September 2022. Primary efficacy outcome was 1-year all-cause mortality. Secondary end points included 30-day mortality, functional class, quality of life, and mitral valve performance. Primary safety outcomes were device success and in-hospital complications. RESULTS: A total of 4243 patients with a mean STS score of 9.2±7.7 underwent transseptal MViV at 455 sites. The rate of Mitral Valve Academic Research Consortium technical (96.6%) success was high, and procedural complications were low. All-cause in-hospital, 30-day, and 1-year mortality rates were 3.2%, 4.3%, and 13.4%, respectively. Significant improvements in New York Heart Association class (New York Heart Association I/II, 18% to 87%) and quality of life (Kansas City Cardiomyopathy Questionnaire score, 38 to 78) were noted at 1 year (P<0.0001 for both) after MViV. Upon stratifying by STS scores, it was observed that the low-risk group (STS<4) had a significantly lower in-hospital mortality rate of 0.4%, whereas the intermediate-risk group (STS, 4-8) had an in-hospital mortality rate of 1.9%. From 2015 to 2022, the number of transseptal MViV cases/year increased significantly, whereas procedure times, length of stay, and intensive care unit hours shortened significantly. At the same time, there was a significant trend toward reduced in-hospital (P=0.0005), 30-day (P=0.004), and 1-year mortality rates (P=0.01). CONCLUSIONS: This multicenter, prospective study reports excellent procedural outcomes, 1-year mortality rates, and a significant improvement in quality of life for patients undergoing transseptal MViV in the contemporary era. Patients in the low-risk and intermediate-risk STS score categories had significantly better outcomes compared with those in the high-risk category. MViV is a reasonable therapy for the majority of patients with degenerated bioprosthetic mitral valves, who are anatomical candidates.

Outcomes of transcatheter aortic valve replacement in patients with cardiogenic shock.

AIMS: The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed. METHODS AND RESULTS: CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 h prior to TAVR. The control group was comprised of all the other patients undergoing TAVR. Baseline characteristics, all-cause mortality, and major complications at 30-day and 1-year outcomes were reported. Landmark analysis was performed at 30 days post-TAVR. Cox-proportional multivariable analysis was performed to determine the predictors of all-cause mortality at 1 year. A total of 309 505 patients underwent TAVR with balloon-expandable valves during the study period. Of these, 5006 patients presented with CS prior to TAVR (1.6%). The mean Society of Thoracic Surgeons score was 10.76 ± 10.4. The valve was successfully implanted in 97.9% of patients. Technical success according to Valve Academic Research Consortium-3 criteria was 94.5%. In a propensity-matched analysis, CS was associated with higher in-hospital (9.9% vs. 2.7%), 30-day (12.9% vs. 4.9%), and 1-year (29.7% vs. 22.6%) mortality compared to the patients undergoing TAVR without CS. In the landmark analysis after 30 days, the risk of 1-year mortality was similar between the two groups [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.95-1.21]. Patients who were alive at 1 year noted significant improvements in functional class (Class I/II 89%) and quality of life (ΔKCCQ score +50). In the multivariable analysis, older age (HR 1.02, 95% CI 1.02-1.03), peripheral artery disease (HR 1.25, 95% CI 1.06-1.47), prior implantation of an implantable cardioverter-defibrillator (HR 1.37, 95% CI 1.07-1.77), patients on dialysis (HR 2.07, 95% CI 1.69-2.53), immunocompromised status (HR 1.33, 95% CI 1.05-1.69), New York Heart Association class III/IV symptoms (HR 1.50, 95% CI 1.06-2.12), lower aortic valve mean gradient, lower albumin levels, lower haemoglobin levels, and lower Kansas City Cardiomyopathy Questionnaire scores were independently associated with 1-year mortality. CONCLUSION: This large observational real-world study demonstrates that the TAVR is a safe and effective treatment for aortic stenosis patients presenting with CS. Patients who survived the first 30 days after TAVR had similar mortality rates to those who were not in CS.

Modeling Antiretrovial Treatment to Mitigate HIV in the Brain: Impact of the Blood-Brain Barrier.

Current research in Human Immunodeficiency Virus (HIV) focuses on eradicating virus reservoirs that prevent or dampen the effectiveness of antiretroviral treatment (ART). One such reservoir, the brain, reduces treatment efficacy via the blood-brain barrier (BBB), causing an obstacle to drug penetration into the brain. In this study, we develop a mathematical model to examine the impact of the BBB on ART effectiveness for mitigating brain HIV. A thorough analysis of the model allowed us to fully characterize the global threshold dynamics with the viral clearance and persistence in the brain for the basic reproduction number less than unity and greater than unity, respectively. Our model showed that the BBB has a significant role in inhibiting the effect of ART within the brain despite the effective viral load suppression in the plasma. The level of impact, however, depends on factors such as the CNS Penetration Effectiveness (CPE) score, the slope of the drug dose-response curves, the ART initiation timing, and the number of drugs in the ART protocol. These results suggest that reducing the plasma viral load to undetectable levels due to some drug regimen may not necessarily indicate undetectable levels of HIV in the brain. Thus, the effect of the BBB on viral suppression in the brain must be considered for developing proper treatment protocols against HIV infection.

Trends in utilization, outcomes, and readmissions after transcatheter mitral valve replacement.

BACKGROUND: There is a paucity of real-world data regarding the temporal trends and outcomes of trans-septal transcatheter mitral valve replacement (TS-TMVR) in the United States (US). METHODS: We queried the Nationwide Readmissions Database (October 2015 to December 2018) for patients undergoing TS-TMVR procedures. We reported the temporal trends in the utilization, in-hospital outcomes and 30-day readmissions after TS-TMVR. The main study outcome was in-hospital mortality. RESULTS: There was an increase in the number of TS-TMVR procedures over time (48 in 2015 vs. 978 in 2018, Ptrend < 0.001), with a notable increase in the proportion of women (Ptrend  = 0.04) and the prevalence of diabetes (Ptrend  = 0.03). There was an increase in the number of centers performing TS-TMVR (21 in 2015 vs. 164 in 2018, Ptrend < 0.001). The overall in-hospital mortality was 7.2% with no change over time (6.3% in 2015 vs. to 5.2% in 2018, Ptrend  = 0.67). There was no change in the frequency of in-hospital complications after TS-TMVR; however, the median length of stay has decreased over time. The overall 30-day readmission rate was 17.8%, with no change during the study years. The most frequent cause for 30-day readmission after TS-TMVR was acute heart failure followed by bleeding and infection-related complications. Prior coagulopathy and small-sized hospitals were independently associated with higher in-hospital mortality and 30-day readmissions. CONCLUSION: This nationwide observational analysis of real-world data showed an increase in the number of TS-TMVR procedures over time, which is now performed at a greater number of centers. There was no change in the rate of in-hospital mortality, complications or 30-day readmissions; but a significant reduction in the length of hospital stay over time was noted. As the number of TS-TMVR continue to expand, these data provide a perspective on the early experience with this procedure.

Modeling HIV-1 infection in the brain.

While highly active antiretroviral therapy (HAART) is successful in controlling the replication of Human Immunodeficiency Virus (HIV-1) in many patients, currently there is no cure for HIV-1, presumably due to the presence of reservoirs of the virus. One of the least studied viral reservoirs is the brain, which the virus enters by crossing the blood-brain barrier (BBB) via macrophages, which are considered as conduits between the blood and the brain. The presence of HIV-1 in the brain often leads to HIV associated neurocognitive disorders (HAND), such as encephalitis and early-onset dementia. In this study we develop a novel mathematical model that describes HIV-1 infection in the brain and in the plasma coupled via the BBB. The model predictions are consistent with data from macaques infected with a mixture of simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV). Using our model, we estimate the rate of virus transport across the BBB as well as viral replication inside the brain, and we compute the basic reproduction number. We also carry out thorough sensitivity analysis to define the robustness of the model predictions on virus dynamics inside the brain. Our model provides useful insight into virus replication within the brain and suggests that the brain can be an important reservoir causing long-term viral persistence.

Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification.

Aims: We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results: From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion: The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

Optimal positioning of self-expanding valves before deployment decreases paravalvular regurgitation following transcatheter aortic valve replacement.

OBJECTIVES: To evaluate the association between measurements performed during Medtronic CoreValve (MCV) deployment and paravalvular leak (PVL). BACKGROUND: The MCV can be recaptured and repositioned, allowing the TAVR operator to implant at a more favorable position. The association between angiographic measurements of MCV position while the valve is recapturable and PVL post deployment has not been investigated. METHODS: 493 patients undergoing TAVR with MCV (January 2011-July 2017) were included. PVL was defined as intraprocedural aortic regurgitation that was judged clinically to require balloon postdilation. Depth of the valve at the left coronary cusp (LCC) and noncoronary cusp (NCC) were measured when the valve was 80% deployed. An optimal cutoff value for the ratio LCC/NCC for PVL was identified in 40 patients. Using this cutoff value, the association between LCC/NCC and PVL was then validated in 453 patients. RESULTS: The median LCC/NCC was 1.51 (interquartile range 1.06-1.89).The optimal cutoff value for LCC/NCC was 1.48 (93% sensitivity, 77% specificity, AUC0.85). In the validation group 112 (24.7%) patients had PVL. For LCC/NCC ≥ 1.48, the incidence of PVL was lower compared to LCC/NCC < 1.48 (9.58% vs. 41.78%, P < 0.0001). LCC/NCC of 1.48 had a sensitivity of 79.5% and specificity of 63.6% for PVL (AUC0.72). In a multivariate model, LCC/NCC < 1.48 independently predicted PVL (OR = 6.67, 95% CI 3.96-11.23, P < 0.0001). CONCLUSION: Positioning the MCV such that the LCC/NCC is ≥1.48 may result in less PVL.

Clinical trials in transcatheter aortic valve replacement.

PURPOSE OF REVIEW: Clinical trials in transcatheter aortic valve replacement (TAVR) have been essential in establishing the effectiveness as well as the limitations of this exciting and disruptive technology. This review will focus on clinical trials related to TAVR that have been presented in the past year or are currently enrolling, as well as future trials that are in the planning stages. RECENT FINDINGS: The currently available devices have gone through iterations to improve safety and outcomes, including lower profiles to reduce bleeding complications as well as adding a sealing skirt or allowing for re-positioning in order to decrease para-valvular regurgitation and need for a permanent pacemaker. The intermediate-risk clinical trials will be finishing soon and will be followed by low-risk trials. Ancillary devices will likely continue to expand the access to this therapy. One of the main challenges moving forward will be the post-TAVR pharmacotherapy. SUMMARY: Recently, improvements in first-generation devices have led to improved outcomes. Current trials evaluating novel TAVR platforms and lower risk patients as well as ancillary devices will likely continue to expand the access to this therapy.

Vascular complication can be minimized with a balloon-expandable, re-collapsible sheath in TAVR with a self-expanding bioprosthesis.

OBJECTIVE: This study evaluates the feasibility and safety of a balloon-expandable, re-collapsible sheath for TAVR patients, including those with small iliofemoral access (≤5.0 mm). BACKGROUND: The recommended iliofemoral diameter for the CoreValve TAVR system is ≥6.0 mm, but the lowest limit has not been determined. METHODS: Of 322 consecutive patients who underwent TAVR from 1/2014 to 8/2015 at two institutions, 64 underwent transfemoral CoreValve implantation, using an 11/19-French balloon-expandable, re-collapsible sheath, which has a 4.45 mm outer diameter (OD) on arterial entry, expands to 7.67 mm, then re-collapses upon removal. Valve sizing and vascular access were determined by computed tomography, and outcomes were assessed using the Valve Academic Research Consortium 2 (VARC-2) definitions. RESULTS: Thirteen of 64 patients had a minimal iliofemoral artery luminal diameter (MLD) of ≤5.0 mm (mean 4.38+/-0.59 mm, range 3.1-5.0 mm), with vessel calcification ≤90° to 360° and tortuosity <45° to >90°. At the MLD point, the sheath-to-artery ratios, based on the fully expanded 7.67 mm OD, ranged 1.53-2.47, higher than previously reported ratios that risk vascular complications. Major comorbidities included chronic renal failure, severe chronic obstructive pulmonary disease, extreme thrombocytopenia, cirrhosis, prior cardiac surgery, poor ventricular function, and frailty. All 64 patients had TAVR with IV sedation and local anesthesia, with 0% sheath malfunction, 0% vascular complications, and 0% bleeding in-hospital and at 30 days per VARC-2 definitions. CONCLUSIONS: TAVR using a balloon-expandable, re-collapsible sheath is safe, including in small iliofemoral access ≤5.0 mm, thus considerably expanding the population suitable for transfemoral approach. © 2015 Wiley Periodicals, Inc.

Development of a Severe Mitral Valve Stenosis Secondary to the Treatment of Mitral Regurgitation with a Single MitraClip.

We report a patient with class III heart failure symptoms due to mitral regurgitation (MR) subsequent to nonischemic cardiomyopathy. The patient underwent percutaneous transcatheter mitral valve repair using a single MitraClip, which reduced the MR; however it created mild-to-moderate mitral stenosis, which progressed to severe mitral stenosis. Subsequently the patient underwent mitral valve replacement surgery.

Renal Denervation: Past, Present, and Future.

Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide. It is estimated that 12.8% of hypertensive adults have resistant hypertension. The sympathetic nervous system is a well-known contributor to the pathophysiology of resistant hypertension. Renal denervation has emerged as an effective procedure to treat resistant hypertension by blocking the sympathetic nervous system. The medical device industry has developed various catheters in an effort to achieve better denervation in the absence of available testing to document adequate denervation. By adding a sham control group to the study design, researchers found that the results of the Renal Denervation in Patients With Uncontrolled Hypertension study (SYMPLICITY HTN-3) showed that renal denervation was not superior to placebo in decreasing systolic blood pressure. Although SYMPLICITY HTN-3 successfully addressed many issues that might have biased the previously published data, incomplete denervation caused by limited operator experience, catheter design, and the radiofrequency ablation technology may have accounted for the discrepancy of the results. This, along with differences in the study design and population, should direct future renal denervation studies. This article reviews the available literature and proposes future directions for renal denervation studies. It also provides a detailed comparison of the available catheters and their respective clinical data.

Short-Term Outcomes with Direct Aortic Access for Transcatheter Aortic Valve Replacement.

BACKGROUND AND AIM OF THE STUDY: Transcatheter aortic valve replacement (TAVR) requires a safe route of access to the aortic valve. A direct aortic route has been used as alternate access approach in patients where ileo-femoral access is unsafe due to size, calcification and/or tortuosity. The study aim was to review the authors' results obtained with a direct aortic (DA) TAVR, examining in particular the safety and effectiveness of this approach. METHODS: A retrospective analysis was performed of all prospectively collected TAVR data from January 2011 to March 2015 at the authors' institution. DA-TAVRs were performed using either an upper mini- sternotomy (MST) into the second right intercostal space, or via a right anterior mini-thoracotomy (RAT) at the second intercostal space. The choice between MST and RAT approaches was made by the surgeon, based on aortic imaging, patent bypass grafts and pulmonary function. Both, Medtronic CoreValve and Edwards SAPIEN devices were used. All relevant perioperative and clinical outcomes were collected based on Valve Academic Research Consortium 2 (VARC-2) definitions. Median numerical values were used. RESULTS: Seventy-eight consecutive patients underwent DA-TAVR with 100% intraoperative survival and 92% 30-day survival. The procedural success was 97%. The majority of patients (79%) underwent DA-TAVR with the Medtronic CoreValve, via MST (92%). All patients were classified either as extreme (74%) or high risk (26%) for surgical aortic valve replacement. CONCLUSION: DA-TAVR provides a safe and viable alternate access approach for patients with inadequate ileo-femoral access. The clinical outcomes were acceptable in this very high-risk group of patients.

Direct Aortic Access Transcatheter Aortic Valve Replacement: Three-Dimensional Computed Tomography Planning and Real-Time Fluoroscopic Image Guidance.

BACKGROUND AND AIM OF THE STUDY: Direct aortic access for transcatheter aortic valve replacement (DA-TAVR) is an important alternative approach in patients with hostile ileo-femoral vessels. Planning the transaortic puncture site and an 'ideal' trajectory towards the annulus plane is important for safe and successful valve implantation. The feasibility of three-dimensional (3D) planning and real-time fluoroscopic image guidance for DA-TAVR was evaluated using pre-procedural multi-detector computed tomography (MDCT) and intra-procedural Dyna CT co-registration approaches. METHODS: Between May 2012 and August 2014, a total of 44 patients (40 mini-sternotomies, four mini-thoracotomies) was selected for DA-TAVR using the authors' MDCT-Dyna CT co-registration approach (32 CoreValve, 12 SAPIEN). Pre-procedural contrast-enhanced multi-slice CT (MSCT) and intra- procedural non-contrast Dyna CT images were co-registered based on cardiac outline and aortic root calcifications. Using a prototype software, the aortic root was segmented and relevant landmarks identified automatically. The intersection of a virtual perpendicular trajectory from the annulus with the greater curvature of the aorta was marked as the planned DA puncture site. The planned DA puncture site, trajectory and relevant landmarks were overlaid onto real-time fluoroscopic images for image guidance during DA-TAVR. RESULTS: Real-time fluoroscopic overlay of planned trajectory was feasible in all 44 cases of DA-TAVR. The mean 2D projection distance error between the actual and planned aortic puncture sites was 1.60 +/- 1.1 cm. The mean angular difference error (measure of co-axiality) between actual and planned DA trajectory was 11.86 +/- 9.3. Errors in distance and co-axiality were lower with the mini-thoracotomy than with the mini-sternotomy approach. The Multi-Slice CT (MSCT)-Dyna CT co-registration technique resulted in significantly less contrast usage, and trended towards shorter fluoroscopy and operative times. There was also a trend towards a reduction in acute kidney injury, but no difference was identified in the degree of paravalvular regurgitation or mortality. CONCLUSION: 3D access planning and real-time image guidance for DA-TAVR is feasible using an MDCT/non-contrast Dyna CT image co-registration-based approach. Such image co-registration strategies improve the accuracy of case planning and safety of valve deployment with a direct aortic approach. Further studies are necessary to determine if these enhancements translate into an improvement in clinical outcomes.

Transcatheter Treatment of Apicoaortic Conduit Dysfunction.

We report a 77-year-old male patient with a history of aortic valve bypass with an apicoaortic conduit 11 years ago for severe aortic stenosis, presenting with acute decompensated congestive heart failure. Severe conduit valve regurgitation and was successfully treated with transcatheter aortic valve replacement (TAVR) of the native aortic valve using a self-expanding bioprosthesis followed by transcatheter closure of the apicoaortic conduit.

Bioprosthetic Mitral Transcatheter Transapical Valve-in-Valve Implantation for Mitral Stenosis in an End-Stage Renal Disease Patient.

Transcatheter mitral valve-in-valve implantation (TMVIV) is an option for patients with mitral prosthetic valve dysfunction who are at high risk for surgical valve replacement. Efficacy and safety of TMVIV is at its infancy. We report a high-risk symptomatic dialysis-dependent end-stage renal disease patient with severe bioprosthetic mitral valve stenosis who had TMVIV performed successfully.

Evaluation of steam penetration and sterilization of natural latex wraps.

OBJECTIVE: To evaluate the efficacy of steam and ethylene oxide (EtO) sterilization of Vetrap™ bandages. STUDY DESIGN: Prospective experimental study. SAMPLE POPULATION: Vetrap™ bandages (n = 70; 35 as supplied by the manufacturer, 35 unwound and tightly rewound). METHODS: Vetrap™ bandage rolls (n = 60) marked with a 1 cm square were inoculated with 0.1 mL Geobacillus stearothermophilus spores, packaged in a pouch together with independent sterilization indicators and assigned into 3 sub-groups for sterilizer type: dynamic air removal, gravity displacement, and bench-top pre-vacuum and further sub-divided into 2 sterilization temperatures. Vetrap™ bandages rolls (n = 10) were inoculated with 0.1 mL Bacillus atrophaeus spores in the same manner and underwent EtO sterilization. After sterilization, the 1 cm marked square was aseptically resected to the level of the cardboard tube and enriched in a flask containing 10 mL tryptic soy broth for 24 hours at 60°C for G. stearothermophilus and 37°C for B. atrophaeus. Aliquots were subsequently plated on a Petri dish of tryptic soy agar and incubated at 60°C for G. stearothermophilus and 37°C for B. atrophaeus for 24 hours. Samples were scored positive if colonies of indicator organism were present on the nutrient agar after 24 hours. RESULTS: Three Vetrap™ bandages yielded post-sterilization growth of G. stearothermophilus: 2 from the dynamic air removal sterilizer at 134°C for 3.5 minutes, and 1 from the bench-top pre-vacuum sterilizer at 121°C for 15 minutes. After EtO sterilization, no positive samples were detected. CONCLUSIONS: Steam sterilization may be incomplete for Vetrap™ bandages whereas EtO showed complete destruction of resistant bacterial spores.

Invasive Assessment of Coronary Artery Disease in Clonal Hematopoiesis of Indeterminate Potential.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) occurs due to acquired mutations in bone marrow progenitor cells. CHIP confers a 2-fold risk of atherosclerotic cardiovascular disease. However, there are limited data regarding specific cardiovascular phenotypes. The purpose of this study was to define the coronary artery disease phenotype of the CHIP population-based on coronary angiography. METHODS: We recruited 1142 patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed DNA sequencing to determine CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and angiography phenotypes. RESULTS: We found that 18.4% of patients undergoing coronary angiography had a CHIP mutation. Those with CHIP had a higher risk of having obstructive left main (odds ratio, 2.44 [95% CI, 1.40-4.27]; P=0.0018) and left anterior descending (odds ratio, 1.59 [1.12-2.24]; P=0.0092) coronary artery disease compared with non-CHIP carriers. We additionally found that a specific CHIP mutation, ten eleven translocase 2 (TET2), has a larger effect size on left main stenosis compared with other CHIP mutations. CONCLUSIONS: This is the first invasive assessment of coronary artery disease in CHIP and offers a description of a specific atherosclerotic phenotype in CHIP wherein there is an increased risk of obstructive left main and left anterior descending artery stenosis, especially among TET2 mutation carriers. This serves as a basis for understanding enhanced morbidity and mortality in CHIP.

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y12 Inhibitor Therapy: The CAMEO Registry.

Background: Little is known about the bleeding risk associated with cangrelor use in patients with myocardial infarction (MI) who are exposed to an oral P2Y12 inhibitor before coronary angiography. Methods: Cangrelor in Acute MI: Effectiveness and Outcomes (CAMEO) is an observational registry studying platelet inhibition for patients with MI. Upstream oral P2Y12 inhibition was defined as receipt of an oral P2Y12 inhibitor within 24 hours before hospitalization or in-hospital before angiography. Among cangrelor-treated patients, we compared bleeding after cangrelor use through 7 days postdischarge between patients with and without upstream oral P2Y12 inhibitor exposure. Results: Among 1802 cangrelor-treated patients with MI, 385 (21.4%) received upstream oral P2Y12 inhibitor treatment. Of these, 101 patients (33.8%) started cangrelor within 1 hour, 103 (34.4%) between 1 and 3 hours, and 95 (31.8%), >3 hours after in-hospital oral P2Y12 inhibitor administration; the remaining received an oral P2Y12 inhibitor before hospitalization. There was no statistically significant difference in rates of bleeding among cangrelor-treated patients with and without upstream oral P2Y12 inhibitor exposure (6.5% vs 8.8%; adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.01). Bleeding was observed in 5.0%, 10.7%, and 3.2% of patients treated with cangrelor <1, 1 to 3, and >3 hours after the last oral PY12 inhibitor dose, respectively; bleeding rates were not statistically different between groups (1-3 hours vs <1 hour: adjusted OR, 2.70; 95% CI, 0.87-8.32; >3 hours vs <1 hour: adjusted OR, 0.65; 95% CI, 0.15-2.85). Conclusions: Bleeding risk was not observed to be significantly higher after cangrelor treatment in patients with and without upstream oral P2Y12 inhibitor exposure.

Transcatheter Tricuspid Interventions: Past, Present, and Future.

Tricuspid regurgitation (TR) etiologies include primary valve pathology or secondary (functional) regurgitation from increased hemodynamic pressure or volume on the right side of the heart. Patients with severe TR have a worse prognosis independent of all other variables. Surgical treatment for TR has mostly been limited to patients undergoing concomitant left-sided cardiac surgery. The results and durability of surgical repair or replacement are not well defined. For patients with significant and symptomatic TR, transcatheter techniques would be beneficial, but these techniques and devices have been slow to develop. Much of the delay is a result of neglect and challenges in defining the symptoms associated with TR. In addition, the anatomic and physiological aspects of the tricuspid valve apparatus present unique challenges. Several devices and techniques are in various phases of clinical investigation. This review highlights the current landscape of transcatheter tricuspid interventions and future opportunities. It is imminent that these therapies become commercially available and widely adopted to have a significant positive impact on millions of patients that have been neglected.