Efficacy and safety of a transaortic approach to midventricular and apical septal myectomy.

OBJECTIVE: The study objective was to evaluate the safety and efficacy of a transaortic approach to midventricular and apical septal myectomy in patients with hypertrophic cardiomyopathy with left ventricular outflow tract or midventricular obstruction. METHODS: From January 2018 to August 2023, 940 patients underwent transaortic septal myectomy at the Cleveland Clinic, of whom 682 (73%) had midventricular or apical resection. Patients who underwent isolated basal myectomies were excluded. Templated operative reports designated septal regions resected as basal (opposition to mitral valve up to the leaflet tips), midventricular (leaflet tips to just beyond the papillary muscle heads), and apical (apical third of the ventricle). Myocardial resection specimen weights, intraventricular gradients, and clinical outcomes were assessed. RESULTS: Of the 682 patients, 582 (85%) had basal plus midventricular resection and 78 (11%) had basal, midventricular, and apical resection. Mean preoperative intraventricular gradient was 102 ± 41 mm Hg. Median resection weight was 10 g (15th, 85th percentiles: 7, 15), and mean postoperative intraventricular gradient was 16 ± 10 mm Hg, with 625 (96%) patients achieving gradients 36 mm Hg or less. There were no iatrogenic mitral or aortic valve injuries. Permanent pacemaker placement was required in 38 patients (5.6%), of whom 8 (1.2%) had normal preoperative conduction. Operative mortality occurred in 1 patient (0.1%) after an intraoperative ventricular septal defect. CONCLUSIONS: Most patients undergoing septal myectomy for relief of obstruction required resection beyond the basal septum. With specialized instrumentation, detailed imaging and knowledge of variable septal anatomy, resecting midventricular and apical septal muscle can be safely and effectively achieved through a transaortic approach.

Pembrolizumab Improves Survival After Resection of Intracardiac Metastatic Cervical Carcinoma.

Intracardiac metastasis of cervical squamous cell carcinoma (C-SCC) is rare, with historically poor long-term survival. We report the case of a 55-year-old woman with prior metastatic C-SCC who was found to have a right ventricular mass causing functional pulmonic stenosis and multiple pulmonary emboli 19 months after her initial diagnosis. She underwent surgical resection to prevent further embolization and heart failure. Pathology confirmed metastatic C-SCC and she was maintained on adjuvant pembrolizumab. She remained well 32 months later without further disease progression. Surgical resection of intracardiac metastasis of C-SCC combined with pembrolizumab therapy may result in improved postoperative life expectancy.

Innominate Vein Injury Secondary to First-Time Sternotomy.

Innominate vein injury is a known potential complication of redo sternotomy, but transection of the innominate vein after first-time median sternotomy has not been previously described. A 71-year-old woman experienced left innominate vein transection upon division of the sternum for coronary artery bypass grafting. Subsequent massive bleeding required digital compression of the transected vessel ends, open manual cardiac massage, institution of a massive transfusion protocol, and pharmacologic support before hemodynamic control was gained by instituting cardiopulmonary bypass. Left innominate vein injury can occur with both first-time and redo sternotomy.

Underutilization of antiplatelet and statin therapy after postoperative myocardial infarction following vascular surgery.

OBJECTIVE: The objective of this study was to investigate adherence to practice guidelines for antiplatelet and statin use after postoperative myocardial infarction (POMI) and its effect on late mortality following vascular surgery in a multicenter registry. METHODS: Antiplatelet and statin use was examined in 1749 vascular surgery procedures with POMI within the Vascular Quality Initiative (VQI) from 2005 to 2015. Our primary aim was to assess cardiac medication (CM) use at discharge, defined as (1) single antiplatelet therapy (SAPT; aspirin or P2Y12 inhibitor) or dual antiplatelet therapy (DAPT; aspirin and P2Y12 inhibitor) and (2) statin therapy. Long-term mortality in patients with POMI was analyzed on the basis of discharge CM. A proportional hazards model was developed to control for factors associated with mortality. Regional differences in CM use at discharge after POMI were compared. RESULTS: Overall discharge CM use after POMI included aspirin (81%), P2Y12 inhibitor (38%), statin therapy (76%), and combined antiplatelet and statin (74%). At discharge, 26% of patients were not receiving combined antiplatelet and statin therapy. SAPT (50%) was more common than DAPT (35%; P < .001). Patients with POMI undergoing carotid endarterectomy were more likely to be discharged on CM (80%) compared with patients undergoing infrainguinal bypass (78%), suprainguinal bypass (72%), endovascular aneurysm repair (71%), and open abdominal aortic aneurysm repair (59%; P < .001). Patients receiving SAPT or DAPT plus statin therapy had improved survival (79%) compared with those receiving noncombination or no therapy (69%) with mean follow-up of 5.5 years and 4.9 years, respectively (log-rank, P = .001). After adjustment for covariates including preoperative medications, treatment with SAPT or DAPT plus statin at discharge was associated with lower late mortality compared with noncombination or no therapy (hazard ratio, 0.72; 95% confidence interval, 0.56-0.93; P = .01). Regional variation in CM at discharge following POMI was also observed with a range of 33% to 100% (P = .05). CONCLUSIONS: Within the VQI, regional and procedure-specific variation exists in CM regimen after POMI following vascular surgery. Absence of combined antiplatelet and statin therapy at discharge after POMI was associated with higher late mortality and represents an area for quality improvement in the care of these patients.

Artemisinin disrupts androgen responsiveness of human prostate cancer cells by stimulating the 26S proteasome-mediated degradation of the androgen receptor protein.

Androgen receptor (AR) expression and activity is highly linked to the development and progression of prostate cancer and is a target of therapeutic strategies for this disease. We investigated whether the antimalarial drug artemisinin, which is a sesquiterpene lactone isolated from the sweet wormwood plant Artemisia annua, could alter AR expression and responsiveness in cultured human prostate cancer cell lines. Artemisinin treatment induced the 26S proteasome-mediated degradation of the receptor protein, without altering AR transcript levels, in androgen-responsive LNCaP prostate cancer cells or PC-3 prostate cancer cells expressing exogenous wild-type AR. Furthermore, artemisinin stimulated AR ubiquitination and AR receptor interactions with the E3 ubiquitin ligase MDM2 in LNCaP cells. The artemisinin-induced loss of AR protein prevented androgen-responsive cell proliferation and ablated total AR transcriptional activity. The serine/threonine protein kinase AKT-1 was shown to be highly associated with artemisinin-induced proteasome-mediated degradation of AR protein. Artemisinin treatment activated AKT-1 enzymatic activity, enhanced receptor association with AKT-1, and induced AR serine phosphorylation. Treatment of LNCaP cells with the PI3-kinase inhibitor LY294002, which inhibits the PI3-kinase-dependent activation of AKT-1, prevented the artemisinin-induced AR degradation. Furthermore, in transfected receptor-negative PC-3 cells, artemisinin failed to stimulate the degradation of an altered receptor protein (S215A/S792A) with mutations in its two consensus AKT-1 serine phosphorylation sites. Taken together, our results indicate that artemisinin induces the degradation of AR protein and disrupts androgen responsiveness of human prostate cancer cells, suggesting that this natural compound represents a new potential therapeutic molecule that selectively targets AR levels.

Prospective Study of Postoperative Glycemic Control with a Standardized Insulin Infusion Protocol after Infrainguinal Bypass and Open Abdominal Aortic Aneurysm Repair.

BACKGROUND: The aim of this study is to examine the effect of moderate postoperative glycemic control in diabetic and nondiabetic patients undergoing infrainguinal bypass (INFRA) or open abdominal aortic aneurysm (OAAA) repair. METHODS: In a single center prospective study, we investigated postoperative glycemic control using a standardized insulin infusion protocol after elective INFRA bypass (n = 53, 62%) and OAAA repair (n = 33, 38%) between January 2013 and March 2015. The primary end point was optimal glycemic control, defined as having ≥85% of blood glucose values within the 80-150 mg/dL target range. Suboptimal glycemic control was defined as <85% of blood glucose values within the blood glucose target range. Secondary end points included in-hospital and 30-day surgical site infection (SSI) rates, composite adverse events, length of stay (LOS), and hospital cost. RESULTS: Optimal glycemic control was achieved more commonly after OAAA repair than INFRA bypass (85% vs. 64%, P = 0.04). Moderate hypoglycemia (<70 mg/dL) was observed in 32 (37%) patients, while severe hypoglycemia (<50 mg/dL) was observed in 6 (7%) patients. SSI at 30 days was more common after INFRA bypass (n = 15, 29%) than OAAA repair (n = 2, 6%) (P = 0.01). In-hospital (6% vs. 6%, P = 1.0) and 30-day (24% vs. 22%, P = 1.0) SSI rates were similar for optimal versus suboptimal glycemic control patients after INFRA bypass. In-hospital (4% vs. 0%, P = 1.0) and 30-day (4% vs. 0%, P = 1.0) SSI rates were similar for optimal versus suboptimal glycemic control patients after OAAA repair. The percentage of blood glucose > 250 mg/dL was similar for patients with and without SSI (3% vs. 2%, P = 0.36). Adverse cardiac and pulmonary events after INFRA bypass were similar between groups (9% vs. 21%, P = 0.23; 0% vs. 5%, P = 0.36, respectively). Adverse cardiac and pulmonary events after OAAA repair were similar between groups (2% vs. 0%, P = 1.0; 4% vs. 0%, P = 1.0, respectively). Mean LOS was significantly lower in patients with optimal glycemic control after INFRA bypass (4.2 vs. 7.3 days, P = 0.02). Mean LOS was similar after OAAA repair for patients with optimal and suboptimal control (5.8 vs. 6.4 days, P = 0.46). Inpatient hospital costs after INFRA bypass were lower for the group with optimal (median $25,012, interquartile range [IQ] range $21,726-28,331) versus suboptimal glycemic control (median $28,944, IQ range 24,773-41,270, P = 0.02). CONCLUSIONS: Postoperative hyperglycemia is common after INFRA bypass and OAAA repair and can be effectively ameliorated with an insulin infusion protocol. The protocol was low risk with reduced LOS and cost after INFRA bypass. Complications including SSI were not reduced in patients with optimal perioperative glycemic control.

Regional Variation in Postoperative Myocardial Infarction in Patients Undergoing Vascular Surgery in the United States.

BACKGROUND: The aim of this study is to assess for regional variation in the incidence of postoperative myocardial infarction (POMI) following nonemergent vascular surgery across the United States to identify potential areas for quality improvement initiatives. METHODS: We evaluated POMI rates across 17 regional Vascular Quality Initiative (VQI) groups that comprised 243 centers with 1,343 surgeons who performed 75,057 vascular operations from 2010 to 2014. Four procedures were included in the analysis: carotid endarterectomy (CEA, n = 39,118), endovascular abdominal aortic aneurysm (AAA) repair (EVAR, n = 15,106), infrainguinal bypass (INFRA, n = 17,176), and open infrarenal AAA repair (OAAA, n = 3,657). POMI was categorized by the method of diagnosis as troponin-only or clinical/ECG and rates were investigated in regions with ≥100 consecutive cases. Regions with significantly different POMI rates were defined as those >1.5 interquartile lengths beyond the 75th percentile of the distribution. Risk-adjusted rates of POMI were assessed using the VQI Cardiac Risk Index all-procedures prediction model to compare the observed versus expected rates for each region. RESULTS: Overall rates of POMI varied by procedure type: CEA 0.8%, EVAR 1.1%, INFRA 2.7%, and OAAA 4.2% (P < 0.001). Significant variation in POMI rates was observed between regions, resulting in differing ranges of POMI rates for each procedure: CEA 0.5-2.0% (P = 0.001), EVAR 0.3-3.1% (P < 0.001), INFRA 1.1-4.8% (P < 0.001), and OAAA 2.2-10.0% (P < 0.001). A single region in 3 of the 4 procedure-specific datasets was identified as a statistical outlier with a significantly higher POMI rate after CEA, EVAR, and OAAA; this region was identical for the EVAR and OAAA datasets but was a different region for the CEA dataset. No significant variation in POMI was noted between regions after INFRA. Procedure-specific clinical POMI rates (mean; range) were significantly different between regions for EVAR (0.4%; 0-1.1%, P = 0.01) and INFRA (1.4%; 0.5-2.9%, P = 0.01), but not for CEA (0.4%; 0-0.8%, P = 0.53) or OAAA (1.6%; 0-3.8%, P = 0.23). Procedure-specific troponin-only POMI rates (mean; range) were significantly different between regions for all procedures: CEA (0.4%; 0.1-1.2%, P < 0.001), EVAR (0.7%; 0-2.1%, P < 0.001), INFRA (1.3%; 0.4-2.5%, P = 0.001), and OAAA (2.5%; 0-8.5%, P < 0.001). After risk adjustment, regional variation was again noted with 3 regions having higher and 4 regions having lower than expected rates of POMI. CONCLUSIONS: Significant variation in POMI rates following major vascular surgery exists across VQI regions even after risk adjustment. These findings may present an opportunity for focused regional quality improvement efforts.

Renin-angiotensin-aldosterone-system inhibition is safe in the preoperative period surrounding carotid endarterectomy.

OBJECTIVE: Discontinuation of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) medications before surgery has been suggested because of the potentially deleterious effects of hypotension. We investigated the effect of preoperative ACEI and/or ARB use on early outcomes after carotid endarterectomy (CEA). METHODS: We examined 3752 consecutive CEA patients within the Vascular Study Group of New England from September 2012 to September 2014 and compared outcomes for patients treated (n = 1772) or not treated (n = 1980) with ACEI and/or ARB preoperatively. Outcomes included perioperative need for intravenous vasoactive medication (IVBPmed) for hypotension or hypertension (HTN), major adverse cardiac events (MACEs), and the combined outcome of stroke or death. Adjusted analysis was performed using multivariable logistic regression of the crude cohort and by constructing a propensity score matched cohort (n = 1441). RESULTS: ACEI and/or ARB users were more likely to be male (64% vs 59%; P = .001), with a higher prevalence of diabetes (41% vs 28%; P < .0001), HTN (97% vs 82%; P < .0001), coronary artery disease (31% vs 25%; P = .0001), congestive heart failure (10% vs 8%; P = .02), and asymptomatic carotid disease (59% vs 54%; P = .004). Patients who received ACEI and/or ARB preoperatively were more likely to be treated with aspirin (92% vs 88%; P = .0002) and statins (89% vs 85%; P = .001) preoperatively. In the unadjusted analysis, no significant differences were identified in hypotension that required IVBPmed (12% vs 11%; odds ratio [OR], 1.1; 95% confidence interval [CI], 0.9-1.4; P = .22), MACE (3% vs 2%; OR, 1.3; 95% CI, 0.8-1.9; P = .32), or stroke or death (3% vs 3%; OR, 1.0; 95% CI, 0.7-1.6; P = .89) for preoperative ACEI and/or ARB treated and nontreated patients, respectively. Preoperative ACEI and/or ARB usage was, however, associated with HTN that required IVBPmed (13% vs 10%; OR, 1.3; 95% CI, 1.1-1.6; P = .01). Analysis of the propensity score matched cohort revealed no significant differences in hypotension that required IVBPmed (12% vs 12%; OR, 1.0; 95% CI, 0.8-1.3; P = .86), MACE (3% vs 2%; OR, 1.1; 95% CI, 0.7-1.8; P = .62; ), or stroke or death (3% vs 3%; OR, 1.0; 95% CI, 0.7-1.6; P = .91) for patients treated or not treated with preoperative ACEI and/or ARB, respectively. ACEI and/or ARB remained associated with HTN that required IVBPmed (13% vs 10%; OR, 1.3; 95% CI, 1.0-1.7; P = .02). Results were similar after adjustment using logistic regression. The incidence of hospital length of stay >1 day was similar between ACEI and/or ARB treated and not treated patients (29% vs 32%; OR, 0.9; 95% CI, 0.8-1.1; P = .21). CONCLUSIONS: Preoperative ACEI and/or ARB use was associated with marginally increased use of IVBPmed for HTN but not for hypotension and was not associated with increased MACE, stroke, or death. On the basis of these metrics, the use of preoperative ACEI and/or ARB appears safe before CEA.