Background Female patients have a higher incidence and greater severity of neurocognitive decline (NCD) after cardiac surgery. We investigated whether sex hormones play a role in this difference. Methods This was a retrospective cohort study at a single academic center. Sex hormone testing was performed on preoperative blood samples from 32 men and 30 postmenopausal women who underwent cardiac surgery. The Repeatable Battery for the Assessment of Neuropsychological Status measured patients’ preoperative and postoperative day 4 (POD4) neurocognitive function with scores scaled against normative data. Mann-Whitney U tests or t tests were applied as appropriate. Results There were 62 patients (48.4% women) who underwent cardiac surgery and completed preoperative and POD4 neurocognitive testing. As expected, 8 men (25.0%) vs 21 women (70.0%) had NCD. Compared with women, men had higher β-estradiol levels (P = .009) and testosterone levels (P < .001) but similar progesterone levels (P = .14). Neither β-estradiol nor testosterone levels were significantly associated with NCD incidence in either men or women. Progesterone levels were decreased in NCD male patients (P = .01) but not in female patients (P = .64). Conclusions In the context of this exploratory analysis, differential expressions in sex hormones did not explain the higher incidence and severity of NCD after cardiac surgery in women, and alternative explanation and mechanisms should be further explored.

BACKGROUND:Emerging data suggest women have worse outcomes than men following cardioplegia and cardiopulmonary bypass (CP/CPB). Altered coronary microvascular function affecting myocardial perfusion may contribute, but human translational studies are lacking. METHODS:Viable coronary microvessels (<200 μ m) were dissected from human atrial samples collected before and after CP/CPB from a subset of 108 patients enrolled. Ex vivo contractile responses to vasopressin were assessed using video microscopy. RNA deep-sequencing and immunoblotting were used to quantify gene and protein expression, respectively. RESULTS:Coronary microvessels exhibited increased vasopressin-induced contractile responses post-CP/CPB in males and females (p ​< ​0.0001). Females exhibited a decrease in microvascular contractile response versus males pre- (p ​= ​0.1) and post-CP/CPB (p ​= ​0.09) which approached significance. Myocardial vasopressin 1a receptor levels were increased in females versus males (p ​= ​0.001). Vasopressin-induced vasoconstriction predicted postoperative cardiac index. CONCLUSIONS:Impaired coronary microvascular contractile responses in females jeopardizing myocardial perfusion may underlie worse outcomes following cardiac surgery.

Objective: Vasoplegia and endothelial dysfunction are well-known complications of cardioplegia and cardiopulmonary bypass (CP/CPB). Our lab has previously shown that endothelial adherens junction impairment is driven by vascular endothelial (VE)-cadherin phosphorylation. In this study we investigate the interplay of hypertension and CP/CPB. Methods: Right atrial tissue was harvested pre- and post-CP/CPB from patients undergoing surgery. Patients were stratified into nonhypertensive, controlled hypertension, and uncontrolled hypertension groups based on history and in-office blood pressure measurements. Atrial tissue was sent for transcriptomics. Expression, phosphorylation, and localization of VE-cadherin was assessed by immunoblotting and immunohistochemistry. Atrial microvascular reactivity to adenosine diphosphate was assessed by videomicroscopy. Results: Several genes related to reactive oxygen species handling, nitric oxide signaling, and adherens junctions were suppressed in patients with uncontrolled hypertension versus nonhypertensive patients pre-CP/CPB. By immunoblotting, patients with uncontrolled hypertension had significantly higher levels of phosphorylated VE-cadherin (p-VE cadherin) and higher ratios of p-VE cadherin/VE-cadherin compared with nonhypertensive (P < .05). Perivascular p-VE cadherin density by immunofluorescence was higher in patients with uncontrolled hypertension compared with nonhypertensive patients and patients with controlled hypertension (P < .05). There were significant decreases in vasodilatory response to adenosine diphosphate after CP/CPB (P < .05) in patients with uncontrolled hypertension compared with nonhypertensive patients. Patients with uncontrolled hypertension had significantly higher increases in weight on postoperative day 1 compared with nonhypertensive patients (P < .05). Conclusions: Our study supports a 2-hit model in which hypertension primes the endothelium for dysfunction, and CP/CPB amplifies this injury through impaired reactive oxygen species handling, nitric oxide dysregulation, and adherens junction destabilization. These findings highlight the importance of preoperative hypertension management to improve postoperative outcomes.

INTRODUCTION:Vasoplegia is a well-established risk after cardiopulmonary bypass. Angiotensin II is a polypeptide integral to blood pressure and intravascular volume regulation, yet limited evidence explores angiotensin II in post-cardiopulmonary bypass vasoplegia. This study aims to investigate microvascular functional and mechanistic changes to angiotensin II response after cardiopulmonary bypass. METHODS:Skeletal muscle samples were collected from the left internal mammary bed before and after cardiopulmonary bypass in patients undergoing cardiac surgery. Skeletal muscle arterioles were dissected and mounted on microvessel arrays, and internal diameter changes in response to angiotensin II were noted by videomicroscopy. Paired skeletal muscle tissue was sent for deep RNA sequencing per third-party company protocol, and angiotensin II type 1 and type2 receptor expression was quantified by immunoblotting. RESULTS:Microvascular constriction to angiotensin II in microvessels isolated from skeletal muscle (n = 7) was significantly attenuated in post-cardiopulmonary bypass vessels (P < .05 at 10-8 [M], 5 × 10-8 [M], 5 × 10-7 [M], and 10-6 [M], P < .01 at 10-7 [M]). Twelve paired pre-cardiopulmonary bypass and post-cardiopulmonary bypass samples used for deep transcriptomics demonstrated decreased RNA transcripts of Gq/11, a G-protein involved in angiotensin II type 1 receptor-mediated vasoconstriction, in post-cardiopulmonary bypass tissue. There were no significant differences in angiotensin II receptor expression by immunoblotting. DISCUSSION:These novel findings demonstrate a significant decrease in functional microvascular response to angiotensin II after cardiopulmonary bypass, which may explain postoperative vasoplegia and blood pressure dysregulation. Although there were no changes in angiotensin II receptor expression, changes in G-protein-related signaling may explain this diminished response.

INTRODUCTION:Patients frequently experience transient postoperative neurocognitive decline (NCD) after cardiac surgery with cardiopulmonary bypass. The goal of this study is to describe preoperative high blood pressure as a risk factor for NCD and use genomic expression to uncover its contribution to the pathophysiology of NCD. METHODS:This is a retrospective analysis of cohort study at a single academic center. Patients undergoing cardiac surgery with the use of cardiopulmonary bypass were administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) preoperatively, at postoperative day four, and four weeks postoperatively. Electronic medical records were reviewed for all recorded blood pressure from the year preceding surgery and intraoperative blood pressures. Blood samples were collected six hours preoperatively and six hours postoperatively to assess messenger ribonucleic acid expression. RESULTS:Eighty-seven patients completed postoperative day four testing, of whom thirty-seven experienced NCD (42.5%). Chronically elevated systolic blood pressure over the year preceding surgery was correlated with greater negative change in RBANS score at postoperative day four (P=0.03). Upon genomic analysis, macrophage markers were upregulated preoperatively, and anti-inflammatory and neuroprotective genes were downregulated postoperatively among patients who had a mean systolic blood pressure ≥ 130 mmHg. CONCLUSION:Chronic exposure to elevated preoperative systolic blood pressure may increase the risk of NCD. The contributing role of preoperative hypertension in NCD may be partly explained by reduced attenuation of oxidative stress, increased inflammation, and reduced neuroprotection and heme metabolism postoperatively. This must be considered when assessing patient risks for cardiac surgery.

Background MANTA is an effective vascular closure device (VCD) in patients undergoing transcatheter aortic valve replacement (TAVR); however, the lack of a convenient bailout for device-related vascular complications is a limitation. The objective of this study is to examine the safety and efficacy of ipsilateral safety wire (ISW) as a bailout for MANTA failure in patients undergoing TAVR. Methods Our institutional Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) registry and EPIC chart system were queried to identify patients who underwent TAVR with MANTA and ISW from July 1, 2022, to June 30, 2023. The ISW involves ipsilateral arterial access distal to primary access and placement of a 0.018" wire in a retrograde fashion in the descending aorta. The primary safety outcome was the absence of complications related to the ISW technique. The primary efficacy outcome was successful MANTA closure, with or without the utilization of the ISW technique, defined as achieving hemostasis without impairment of distal perfusion or need for surgical vascular intervention. Results Eighty-nine patients were included (mean age 81.1 years, 32.6% women, 98.9% White). Most procedures were performed electively (95.5%) in a hybrid operating room (83.1%) with conscious sedation (82.0%), using balloon-expandable valves (98.9%). The primary safety and efficacy outcomes were achieved in all patients. Two patients (2.2%) required utilization of the ISW technique for bailout; 1 for inadequate hemostasis, and 1 for severe common femoral artery stenosis. No major bleeding or surgical vascular intervention occurred. Conclusions The ISW technique is a safe and effective bailout technique for MANTA in patients undergoing TAVR.

BACKGROUND:Patients with bicuspid aortic stenosis who receive transcatheter aortic valve replacement (TAVR) may require subsequent valve interventions in their lifetime; however, the feasibility of redo-TAVR in this population is uncertain. We aimed to assess redo-TAVR feasibility in bicuspid patients and develop a predictive virtual valve planning algorithm. METHODS:We studied computed tomography scans of bicuspid patients who received a balloon-expandable transcatheter heart valve (THV) in the LRT trial (Low Risk TAVR). Redo-TAVR feasibility, determined by valve-to-coronary and valve-to-aorta measurements on 30-day computed tomography, was assessed according to raphe location and calcification. A virtual valve planning algorithm was developed using baseline and 30-day computed tomography scans. RESULTS:Among 42 patients (left/right cusp fusion: n=34; right/noncusp fusion: n=4; 2-sinus: n=4), redo-TAVR was feasible in 64%, while 36% would likely require leaflet modification to prevent coronary obstruction. Patients with left/right fusion and calcified raphe had higher redo-TAVR feasibility (88% versus 35%, P<0.001) due to favorable shifting of the THV away from the coronary ostia. A bicuspid virtual planning algorithm accounting for 83.4% THV underexpansion, resulting in an 11.9% taller frame and translation of the THV away from the calcified raphe (mean valve shift 6.6 mm) achieved 86.7% sensitivity and 88.9% specificity for predicting redo-TAVR feasibility. CONCLUSIONS:Calcified raphe in left/right cusp fusion shifts the THV away from the coronary ostia, reducing coronary obstruction risk during redo-TAVR. Underexpansion causing increased THV frame height and valve shifting is common in bicuspid patients; a virtual planning algorithm accounting for these aspects can accurately assess redo-TAVR risk. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02628899.

Background: Recent randomized studies have broadened the indication of transcatheter aortic valve replacement (TAVR) to also include low-surgical-risk patients. However, the data on self-expanding (SE) and balloon-expandable (BE) valves in low-risk patients remain sparse.Methods: The current study is a post hoc analysis of combined data from both LRT 1.0 and 2.0 trials comparing BE and SE transcatheter heart valves.Results: A total of 294 patients received a BE valve, and 102 patients received an SE valve. The 30-day clinical outcomes were similar across both groups except for stroke (4.9% vs. 0.7%, p = 0.014) and permanent pacemaker implantation (17.8% vs. 5.8%, p < 0.001), which were higher in the SE cohort than the BE cohort. No difference was observed in terms of paravalvular leak (>= moderate) between the groups (0% vs. 1.5%, p = 0.577). SE patients had higher aortic valve area (1.92 +/- 0.43 mm(2) vs. 1.69 +/- 0.45 mm(2), p < 0.001) and lower mean gradient (8.93 +/- 3.53 mmHg vs. 13.41 +/- 4.73 mmHg, p < 0.001) than BE patients. In addition, the rate of subclinical leaflet thrombosis was significantly lower in SE patients (5.6% vs. 13.8%, p = 0.038).Conclusion: In this non-randomized study assessing SE and BE valves in low-risk TAVR patients, SE valves are associated with better hemodynamics and lesser leaflet thrombosis, with increased rates of stroke and permanent pacemaker implantation at 30 days; however, this could be due to certain patient-dependent factors not fully evaluated in this study. The long-term implications of these outcomes on structural valve durability remain to be further investigated.

BACKGROUND:We previously found that cardioplegic arrest and cardiopulmonary bypass are associated with altered coronary arteriolar response to serotonin in patients undergoing cardiac surgery. In this study, we investigated the effects of hypertension on coronary microvascular vasomotor tone in response to serotonin and alterations in serotonin receptor protein expression in the setting of cardioplegic arrest and cardiopulmonary bypass. METHODS:Coronary arterioles were dissected from harvested pre- and post-cardioplegic arrest and cardiopulmonary bypass right atrial tissue samples of patients undergoing cardiac surgery with normotension, well-controlled hypertension, and uncontrolled hypertension. Vasomotor tone was assessed by video-myography, and protein expression was measured with immunoblotting. RESULTS:Pre-cardioplegic arrest and cardiopulmonary bypass, serotonin induced moderate relaxation responses of coronary arterioles in normotension and well-controlled hypertension patients, whereas serotonin caused moderate contractile responses in uncontrolled hypertension patients. Post-cardioplegic arrest and cardiopulmonary bypass, serotonin caused contractile responses of coronary arterioles in all 3 groups. The post-cardioplegic arrest and cardiopulmonary bypass contractile response to serotonin was significantly higher in the uncontrolled hypertension group compared with the normotension or well-controlled hypertension groups (P < .05). Pre-cardioplegic arrest and cardiopulmonary bypass, expression of the serotonin 1A receptor was significantly lower in the uncontrolled hypertension group compared with the well-controlled hypertension and normotension groups (P = .01 and P < .001). Serotonin 1B receptor expression was higher in the uncontrolled hypertension group compared with the normotension or well-controlled hypertension groups post-cardioplegic arrest and cardiopulmonary bypass (P = .03 and P = .046). CONCLUSION:Uncontrolled hypertension is associated with an increased coronary contractile response of coronary microvessels to serotonin and altered serotonin receptor protein expression after cardioplegic arrest and cardiopulmonary bypass. These findings may contribute to a worse postoperative coronary spasm and worsened recovery of coronary perfusion in patients with uncontrolled hypertension after cardioplegic arrest and cardiopulmonary bypass and cardiac surgery.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of rare autoimmune disorders associated with the presence of ANCA autoantibodies. We present the first reported case of acute ANCA-associated vasculitis following coronary artery bypass grafting in a 74-year-old male presenting on postoperative day 13 with shortness of breath, orthopnea, and acute kidney injury. Renal biopsy ultimately showed focal necrotizing and crescentic glomerulonephritis, and the patient was successfully managed with corticosteroids and outpatient rituximab. This rare case highlights the importance of having an expanded differential for uncommon causes of cardiovascular disease and unexpected outcomes after coronary artery bypass grafting.

BACKGROUND:In 2019, the US Food and Drug Administration (FDA) approved transcatheter aortic valve replacement (TAVR) for low-risk patients with symptomatic severe tricuspid aortic stenosis. However, bicuspid aortic valve (BAV) patients were included only in single-arm registries of pivotal low-risk TAVR trials, resulting in limited data for this subgroup. METHODS:The LRT (Low Risk TAVR) trial was an investigator-initiated, prospective, multicenter study and the first FDA-approved investigational device exemption trial to evaluate the feasibility of TAVR with balloon-expandable or self-expanding valves in low-risk patients with symptomatic severe BAV stenosis. This analysis reports 2-year follow-up, assessing the primary outcome of all-cause mortality and evaluating clinical outcomes. RESULTS:From 2016 to 2019, a total of 72 low-risk patients diagnosed with symptomatic, severe BAV stenosis underwent TAVR across six centers. Six patients were lost to follow-up. At 2-year follow-up, mortality was 1.5% (1 of 66 patients). Among the remaining 65 patients, four experienced nondisabling strokes (6.2%), while 2 (3.1%) developed infective endocarditis. No new permanent pacemakers were required beyond the 30-day follow-up, and no patients, including those with endocarditis, needed aortic valve re-intervention. At the 2-year echocardiography follow-up (n = 65), 27.8% of BAV patients showed mild aortic regurgitation, with none exhibiting moderate or severe regurgitation. The mean aortic gradient was 12.1 ± 4.1 mmHg, and the mean valve area was 1.7 ± 0.5 cm². CONCLUSION:The 2-year follow-up confirms commendable clinical outcomes of TAVR in patients with bicuspid aortic stenosis, establishing its evident safety.

Introduction: Though marijuana use has been linked to an increase in heart failure admissions, no prior study has explored the association between its use and outcomes after coronary artery bypass grafting (CABG). This study examines the relationship between marijuana use and postoperative outcomes in CABG patients.Methods: We utilized data from the National Inpatient Sample database from 2008 to 2018 for CABG patients >18 y old. Patients were divided into two groups based on marijuana use (abuse/dependency versus nonuse). Primary outcomes include in-hospital mortality, favorable discharge, and length of stay (LOS). Secondary outcomes include acute kidney injury (AKI), acute myocardial infarction (AMI), and transient ischemic attack (TIA)/stroke. A multivariable model, adjusted for confounding variables, was utilized for each outcome.Results: A total of 343,796 patients met inclusion criteria for the study, 590 of which were marijuana users. In both marijuana user and nonuser groups, most patients were male and White with an average age of 56.0 and 66.3 y, respectively. There was a nonsignificant decreased odds of in-hospital mortality among marijuana users (odds ratio [OR] = 0.41, [0.141-1.124]). Marijuana users exhibited significantly decreased odds of home discharge (OR = 1.50, [1.24-1.81]), and increased odds of longer LOS (mean 10.4 d versus 9.8 d; OR = 1.14, [1.09-1.20]), AKI (OR = 1.40, [1.11-1.78]), AMI (OR = 1.56, [1.32-1.84]), and TIA/ stroke (OR = 1.64, [1.21-2.22]).Conclusions: Marijuana use and dependency are associated with increased nonhome discharge, AKI, AMI, TIA/stroke, and longer LOS. Further studies are needed to delineate the pathophysiologic derangements that contribute to these unfavorable post-CABG outcomes.(c) 2023 Elsevier Inc. All rights reserved.

BACKGROUND:Transfemoral (TF) access is the preferred approach for transcatheter aortic valve replacement (TAVR). Limited data exist regarding the outcomes of intravascular lithotripsy (IVL)-assisted TF TAVR in patients with peripheral artery disease. OBJECTIVES:This study sought to examine contemporary characteristics, trends, and outcomes of IVL TAVR in the United States. METHODS:The Vizient Clinical Database was queried for patients who underwent percutaneous TAVR between October 1, 2020, and November 30, 2023. Outcomes with IVL TAVR vs non-IVL TAVR were examined after propensity score matching. The primary outcome was a composite of in-hospital death, stroke, vascular complications, surgical vascular intervention, and major bleeding. RESULTS:Over the study period, 129,655 patients (mean age of 78.4 years, 42.2% women, 87.1% White) underwent percutaneous TAVR at 361 hospitals, 1,242 (0.96%) of whom underwent IVL TAVR. There was an uptrend in IVL TAVR, but the frequency remained low. IVL TAVR patients had a higher median Elixhauser comorbidity score (5 [Q1-Q3: 4-7] vs 4 [Q1-Q3: 3-6]) compared to non-IVL TAVR. TAVR was completed via the TF approach in 1,238 (99.7%) IVL TAVR patients. In a 3:1 propensity score matching analysis, IVL TAVR was associated with a higher rate of the primary composite outcome (21.9% vs 13.7%; P < 0.001) driven by higher rates of vascular complications, surgical vascular intervention, and major bleeding. In-hospital death and stroke were similar in both groups. CONCLUSIONS:In the United States, IVL is increasingly adopted to facilitate TF TAVR. IVL TAVR patients exhibited a higher burden of comorbidities and experienced more complications compared to non-IVL TAVR patients. Further studies are needed to identify appropriate anatomical and clinical use criteria for IVL TAVR and to compare its outcomes vs alternative non-TF TAVR.

Background: Transcatheter mitral valve replacement (TMVR) has emerged as a promising alternative to conventional redo-surgical intervention in patients presenting with mitral valve prosthesis failure. We conducted a meta-analysis to delineate efficacy and safety of transcatheter mitral valve replacement (TMVR), encompassing both valve-in-valve (ViV) and valve-in-ring (ViR) procedures, compared to redo-surgical mitral valve replacement (SMVR). Aim: The primary aim of our meta-analysis was to investigate the early clinical outcomes following either ViV/ViR TMVR or SMVR. Methods: PubMed/MEDLINE, Cochrane Library, and clinicaltrials.gov were systematically searched according to predefined inclusion and exclusion criteria. Several efficacy and safety outcomes were pooled and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Results: Fourteen retrospective cohort studies (patients=18,519) were evaluated in this analysis. Compared with redo-SMVR for mitral valve prosthesis failure, TMVR exhibited lower in-hospital mortality (OR=0.69; 95% CI 0.56–0.86; p<0.01). Moreover, stroke (OR=0.46; 95% CI 0.31–0.68; p=0.05), renal dysfunction (OR=0.49; 95% CI 0.38–0.63; p<0.01), need for pacemaker implantation (OR=0.28; 95% CI 0.23–0.34; p<0.01), major cardiac complications (OR=0.43; 95% CI 0.32–0.59; p<0.01), length of ICU stay (OR=-2.11; 95% CI -2.82 - -1.39; p< 0.01), and need for exploration for bleeding (OR=0.23; 95% CI 0.17–0.30; p<0.01) also revealed significant improvements in the TMVR cohort. To minimize heterogeneity, we performed subgroup analysis for in-hospital mortality, which remained significant (OR=0.42; 95% CI 0.34–0.51; P< 0.01) on propensity matching. Conversely, paravalvular leak (OR=22.12; 95% CI 2.81-174.16; p=0.003) generated results favoring SMVR. There was negligible and nonsignificant difference in mean mitral valve gradient (MD: -0.01; 95% CI: −0.57 to 0.5; P =0.97), 30-day mortality (OR: 0.86; 95% CI: 0.48–1.53; P = 0.60), and 1-year mortality (OR: 1.05; 95% CI: 0.68–1.61; P = 0.83) between the two groups. Conclusion: In patients experiencing mitral valve prosthesis failure, TMVR offers an efficacious, safe, and less invasive alternative to SMVR. However, the risk of paravalvular leak requires careful monitoring.

Background: Recent data demonstrated a temporal increase in adoption of transcatheter aortic valve replacement (TAVR) for treating aortic stenosis (AS) across all age groups. Whether there is a differential trend in adoption of TAVR vs. surgical AVR (SAVR) according to valve type, i.e., bicuspid (BAV) vs tricuspid aortic valve (TAV), is unknown. Methods: The Vizient Clinical Database was queried to identify patients who underwent TAVR vs SAVR between October 2015 and November 2023. Patients who underwent AVR for aortic regurgitation or underwent concomitant surgery during SAVR were excluded. The final cohort was divided according to the valve type into BAV and TAV cohorts. National trends in TAVR vs SAVR were examined overall and across BAV and TAV cohorts stratified by different age groups (<65, 65-80, >80 years) using linear regression analysis. Logistic regression analyses were performed to examine if age and valve type are predictors of TAVR use. Results: Among 365,985 patients who underwent isolated AVR for AS, 248,697 (67.95%) underwent TAVR. BAV was present in 42,754 (11.7%) of the final cohort and was treated with SAVR in 85% of patients. Across all age groups, there was an uptrend in the overall use of TAVR and among both BAV and TAV cohorts. The relative rise in all TAVR use was highest in patients <65 years (157%) and in TAVR for BAV was highest in patients 65-80 years (493.93%). In 2023, SAVR was the main AVR modality in all patients <65 years (76.80%), while TAVR was the main modality in patients >80 years (97.84%). In the BAV cohort, SAVR remained the main AVR modality in patients < 65 years (92.65%) and 65-80 years (69.47%), while TAVR was the main modality in patients >80 years (82.83%). In logistic regression analysis, patients 65-80 years and >80 years were more likely to receive TAVR than younger patients <65 years, and BAV patients were less likely to receive TAVR compared to TAV patients (p < 0.05 for all). Conclusion: TAVR is increasingly adopted across all age group and is more commonly performed for tricuspid vs bicuspid AS. Per these contemporary national trends, SAVR remains the main AVR modality in all patients <65 years, and in BAV patients <80 years, while TAVR remains the main AVR modality in all patients > 80 years.