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Dynamic perioperative platelet activity and cardiovascular events in peripheral artery disease

Kennedy, Natalie N; Xia, Yuhe; Barrett, Tessa; Luttrell-Williams, Elliot; Berland, Todd; Cayne, Neal; Garg, Karan; Jacobowitz, Glenn; Lamparello, Patrick J; Maldonado, Thomas S; Newman, Jonathan; Sadek, Mikel; Smilowitz, Nathaniel R; Rockman, Caron; Berger, Jeffrey S
OBJECTIVE:Patients with peripheral artery disease (PAD) undergo lower extremity revascularization (LER) for symptomatic relief or limb salvage. Despite LER, patients remain at increased risk of platelet-mediated complications, such as major adverse cardiac and limb events (MACLEs). Platelet activity is associated with cardiovascular events, yet little is known about the dynamic nature of platelet activity over time. We, therefore, investigated the change in platelet activity over time and its association with long-term cardiovascular risk. METHODS:Patients with PAD undergoing LER were enrolled into the multicenter, prospective Platelet Activity and Cardiovascular Events study. Platelet aggregation was assessed by light transmission aggregometry to submaximal epinephrine (0.4 μmol/L) immediately before LER, and on postoperative day 1 or 2 (POD1 or POD2) and 30 (POD30). A hyperreactive platelet phenotype was defined as >60% aggregation. Patients were followed longitudinally for MACLEs, defined as the composite of death, myocardial infarction, stroke, major lower extremity amputation, or acute limb ischemia leading to reintervention. RESULTS:Among 287 patients undergoing LER, the mean age was 70 ± 11 years, 33% were female, 61% were White, and 89% were on baseline antiplatelet therapy. Platelet aggregation to submaximal epinephrine induced a bimodal response; 15.5%, 16.8%, and 16.4% of patients demonstrated a hyperreactive platelet phenotype at baseline, POD1, and POD30, respectively. Platelet aggregation increased by 18.5% (P = .001) from baseline to POD1, which subsequently returned to baseline at POD30. After a median follow-up of 19 months, MACLEs occurred in 165 patients (57%). After adjustment for demographics, clinical risk factors, procedure type, and antiplatelet therapy, platelet hyperreactivity at POD1 was associated with a significant hazard of long-term MACLE (adjusted hazard ratio, 4.61; 95% confidence interval, 2.08-10.20; P < .001). CONCLUSIONS:Among patients with severe PAD, platelet activity increases after LER. Platelet hyperreactivity to submaximal epinephrine on POD1 is associated with long-term MACLE. Platelet activity after LER may represent a modifiable biomarker associated with excess cardiovascular risk.
PMID: 39362415
ISSN: 1097-6809
CID: 5766582

Presence of Atherosclerosis in Multiple Arterial Beds is Associated with Increased Mortality in Patients Undergoing Endovascular Aortic Aneurysm Repair

Ratner, Molly; Chang, Heepeel; Rockman, Caron B; Pearce, Benjamin J; Siracuse, Jeffrey J; Cho, Jae S; Cayne, Neal; Maldonado, Thomas; Patel, Virendra; Garg, Karan
OBJECTIVE:Patients with polyvascular disease are considered high risk for major adverse cardiac events (MACEs). This retrospective study utilised the Vascular Quality Initiative (VQI) database to quantify the effect of polyvascular disease on outcomes after endovascular aneurysm repair (EVAR). METHODS:The VQI database was queried from to 2012 - 2022 for elective EVAR. Patients were identified as having peripheral arterial disease, coronary artery disease, or cerebrovascular disease, and then stratified based on the number of arterial beds involved (one to three). Primary outcomes were peri-operative death and MACEs. Multivariate analysis was performed to find associations between comorbidities and primary outcomes. RESULTS:Of the 21 160 patients with arterial disease included in the study, 83.7% were male and the mean age was 73.73 ± 8.57 years. After stratification, 16 892 patients had atherosclerosis in one arterial bed, 3 869 in two arterial beds, and 399 in three arterial beds. Pre-operatively, patients with atherosclerosis in three arterial beds were more likely to have hypertension, diabetes, and renal failure (all p < .001). Post-operatively, patients with disease in three arterial beds were more likely to experience a post-operative complication (11.5% vs. 8.3% vs. 5.4%; p < .001), including MACE (4.6% vs. 4.1% vs. 2.8%; p < .001) and death (3.0% vs. 2.5% vs. 1.7%; p < .010). On multivariate analysis, polyvascular disease was associated with MACEs (odds ratio 1.54, 95% confidence interval 1.29 - 1.84; p < .001). Kaplan-Meier analysis estimates showed statistically significant differences in survival at approximately the three year follow up (p < .001). CONCLUSION/CONCLUSIONS:In this review of patients undergoing elective EVAR, patients with polyvascular disease experienced worse peri-operative outcomes, including death and MACEs, the latter of which was confirmed on multivariable analysis. These patients should be considered high risk and managed accordingly.
PMID: 39395529
ISSN: 1532-2165
CID: 5730262

Total Contact Casting Remains an Effective Modality for Treatment of Diabetic Foot Ulcers

Zhang, Jason; Sadek, Mikel; Iannuzzi, Lou; Rockman, Caron; Garg, Karan; Taffet, Allison; Ratner, Molly; Berland, Todd; Maldonado, Thomas; Jacobowitz, Glenn; Ross, Frank
OBJECTIVES/OBJECTIVE:Total contact casting (TCC) is used to promote wound closure in diabetic foot ulcers (DFUs); however, this technique is underused today. This study aims to further evaluate the efficacy of TCC in a large cohort, including patients with peripheral artery disease (PAD). METHODS:This was a retrospective analysis of patients with DFUs who underwent TCC from 2017 to 2021. PAD was defined as absence of pedal pulse or ABI <0.9. Demographic data, DFU characteristics, and peripheral arterial intervention were evaluated. Outcomes included complete healing, healing time, and rate of major amputation. Subgroup analysis was performed on patients undergoing peripheral intervention. RESULTS:= .0008) compared to patients without intervention. CONCLUSIONS:TCC remains an effective option for treatment of DFUs, as most were completely healed. Patients with PAD may benefit from TCC and revascularization, however, healing rates are lower in this cohort, necessitating the need for close observation.
PMID: 39530741
ISSN: 1938-9116
CID: 5752822

Supra-Inguinal Inflow for Distal Bypasses Have Acceptable Patency and Limb Salvage Rates

Ratner, Molly; Chang, Heepeel; Johnson, William; Maldonado, Thomas; Cayne, Neal; Jacobowitz, Glenn; Siracuse, Jeffrey J; Rockman, Caron; Garg, Karan
BACKGROUND:There is a paucity of data evaluating outcomes of lower extremity bypass (LEB) using supra-inguinal inflow for revascularization of infra-inguinal vessels. The purpose of this study is to report outcomes after LEB originating from aortoiliac arteries to infra-femoral targets. METHODS:The Vascular Quality Initiative database (2003-2020) was queried for patients undergoing LEB from the aortoiliac arteries to the popliteal and tibial arteries. Patients were stratified into 3 cohorts based on outflow targets (above-knee [AK] popliteal, below-knee [BK] popliteal, and tibial arteries). Perioperative and 1-year outcomes including primary patency, amputation-free survival (AFS), and major adverse limb events (MALEs) were compared. A Cox proportional hazards model was used to estimate the independent prognostic factors of outcomes. RESULTS:Of 403 LEBs, 389 (96.5%) originated from the external iliac artery, while the remaining used the aorta or common iliac artery as inflow. In terms of the distal target, the AK popliteal was used in 116 (28.8%), the BK popliteal in 151 (27.5%), and tibial vessels in 136 (43.7%) cases. BK popliteal and tibial bypasses, compared to AK popliteal bypasses, were more commonly performed in patients with chronic limb-threatening ischemia (69.5% and 69.9% vs. 48.3%; P < 0.001). Vein conduit was more often used for tibial bypass than for AK and BK popliteal bypasses (46.3% vs. 21.9% and 16.3%; P < 0.001). In the perioperative period, BK popliteal and tibial bypass patients had higher reoperation rates (16.9% and 13.2% vs. 5.2%; P = 0.02) and lower primary patency (89.4% and 89% vs. 95.7%; P = 0.04) than AK bypass patients. At 1 year, compared with AK popliteal bypasses, BK and tibial bypasses demonstrated lower primary patency (81.9% vs. 56.7% vs. 52.4%, P < 0.001) and freedom from MALE (77.6% vs. 70.2% vs. 63.1%, P = 0.04), although AFS was not significantly different (89.7% vs. 90.6% vs. 83.8%, P = 0.19).On multivariable analysis, compared with AK popliteal bypasses, tibial bypasses were independently associated with increased loss of primary patency (hazard ratio 1.9, 95% confidence interval, 1.03-3.51, P = 0.04). Subanalysis of patients with chronic limb-threatening ischemia demonstrated significantly higher primary patency in the AK popliteal cohort at discharge and 1 year, but no difference in AFS or freedom from MALE between the cohorts at follow-up. CONCLUSIONS:LEB with supra-inguinal inflow appear to have acceptable rates of 1-year patency and limb salvage in patients at high risk of bypass failure. Tibial outflow target was independently associated with worse primary patency but not with MALE or AFS.
PMID: 38942374
ISSN: 1615-5947
CID: 5698152

Pushing the envelope… who reaps the benefits? [Editorial]

Rockman, Caron
PMID: 39174178
ISSN: 1097-6809
CID: 5681042

A Platelet Reactivity ExpreSsion Score derived from patients with peripheral artery disease predicts cardiovascular risk

Berger, Jeffrey S; Cornwell, Macintosh G; Xia, Yuhe; Muller, Matthew A; Smilowitz, Nathaniel R; Newman, Jonathan D; Schlamp, Florencia; Rockman, Caron B; Ruggles, Kelly V; Voora, Deepak; Hochman, Judith S; Barrett, Tessa J
Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses and RNA sequencing. Among patients with peripheral artery disease (PAD), those with a hyperreactive platelet response (>60% aggregation) to 0.4 µM epinephrine had a higher incidence of the 30 day primary cardiovascular endpoint (37.2% vs. 15.3% in those without hyperreactivity, adjusted HR 2.76, 95% CI 1.5-5.1, p = 0.002). PRESS performs well in identifying a hyperreactive phenotype in patients with PAD (AUC [cross-validation] 0.81, 95% CI 0.68 -0.94, n = 84) and in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 -0.79, n = 35). Following multivariable adjustment, PAD individuals with a PRESS score above the median are at higher risk for a future cardiovascular event (adjusted HR 1.90, CI 1.07-3.36; p = 0.027, n = 129, NCT02106429). This study derives and validates the ability of PRESS to discriminate platelet hyperreactivity and identify those at increased cardiovascular risk. Future studies in a larger independent cohort are warranted for further validation. The development of a platelet reactivity expression score opens the possibility for a personalized approach to antithrombotic therapy for cardiovascular risk reduction.
PMCID:11336089
PMID: 39164233
ISSN: 2041-1723
CID: 5680632

The substantial burden of iatrogenic vascular injury on the vascular surgery workforce at an academic medical center

Rao, Abhishek; Ratner, Molly; Zhang, Jason; Wiske, Clay; Garg, Karan; Maldonado, Thomas; Sadek, Mikel; Jacobowitz, Glenn; Berland, Todd; Teter, Katherine; Rockman, Caron
OBJECTIVE:Vascular surgeons are often called upon to provide emergent surgical assistance to other specialties for iatrogenic complications, both intraoperatively and in the inpatient setting. The management of iatrogenic vascular injury remains a critical role of the vascular surgeon, especially in the context of the increasing adoption of percutaneous procedures by other specialties. This study aims to characterize consultation timing, management, and outcomes for iatrogenic vascular injuries. METHODS:This study identified patients for whom vascular surgery was consulted for iatrogenic vascular complications from February 1, 2022, to May 12, 2023. Patient information, including demographic information, injury details, and details of any operative intervention, was retrospectively collected from February 1, 2022, to October 13, 2022, and prospectively collected for the remainder of the study period. Analyses were performed with R (version 2022.02.03). RESULTS:There were 87 patients with consultations related to iatrogenic vascular injury. Of these, 42 (46%) were female and the mean age was 59 years (±18 years). The most common consulting services were cardiology (32%), cardiothoracic surgery (26%), general surgery (8%), and neurointerventional radiology (10%). Reasons for consultation included hemorrhage (36%), limb ischemia (36%), and treatment of pseudoaneurysm (23%). A total of 24% of consults were intraoperative, 20% of consults related to extracorporeal membrane oxygenation cannulation, and 16% of consults related to ventricular assist devices including left ventricular assist device and intra-aortic balloon pump. The majority of these consult requests (60%) occurred during evening and night hours (5 PM to 7 AM). Emergent intervention was required in 62% of cases and consisted of primary open surgical repair of arterial injury (54%), endovascular intervention (21%), and open thromboembolectomy (15%). Overall, in-hospital mortality for the patient cohort was 20% and the reintervention rate was 23%, reflecting the underlying complexity of the illness and nature of the vascular injury in this patient group. CONCLUSIONS:Vascular surgeons play an essential role in managing emergent life-threatening hemorrhagic and ischemic iatrogenic vascular complications in the hospitalized setting. The complications require immediate bedside or intraoperative consult and often emergent open surgical or endovascular intervention. Furthermore, many of these require urgent management in the evening or overnight hours, and therefore the high frequency of these events represents a potential significant resource utilization and workforce issue to the vascular surgery workforce.
PMID: 38641255
ISSN: 1097-6809
CID: 5697582

Optimal medical therapy is lacking in patients undergoing intervention for symptomatic carotid artery stenosis and protects against larger areas of cerebral infarction

Teter, Katherine; Willems, Loes; Harish, Keerthi; Negash, Bruck; Warle, Michiel; Rockman, Caron; Torres, Jose; Ishida, Koto; Jacobowitz, Glenn; Garg, Karan; Maldonado, Thomas
OBJECTIVES/OBJECTIVE:Carotid interventions are indicated for both patients with symptomatic and a subset of patients with severe asymptomatic carotid artery stenosis (CAS). Symptomatic CAS accounts for up to 12%-25% of overall carotid interventions, but predictors of symptomatic presentation remain poorly defined. The aim of this study was to identify factors associated with symptomatic CAS in our patient population. METHODS:Between January 2015 and February 2022, an institutional retrospective cohort study of prospectively collected data on patients undergoing interventions for CAS was performed. Procedures included carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TF-CAS). Demographic data, comorbidities, procedural details, and anatomic features from various imaging modalities were collected. Comparisons were made between symptomatic (symptoms within the prior 6 months) and asymptomatic patients. RESULTS:< .001), and symptomatic patients with ulcerated plaques more frequently had less than 50% compared to moderate/severe CAS. Nine patients who presented with symptoms had mild CAS and underwent intervention. CONCLUSIONS:Symptomatic CAS was associated with a history of remote prior symptoms and lack of anti-platelet therapy at time of presentation. Furthermore, symptomatic patients not on anti-platelet agents were more likely to have a greater area of parenchymal involvement when presenting with stroke and symptomatic patients with ulcerated plaques were more likely to have mild CAS, suggesting the role of plaque instability in symptomatic presentation. These findings underscore the importance of appropriate medical management and adherence in all patients with CAS and perhaps a role for more frequent surveillance in those with potentially unstable plaque morphology.
PMID: 38876778
ISSN: 1708-539x
CID: 5669572

Preoperative COVID-19 Vaccination is Associated with Decreased Perioperative Mortality after Major Vascular Surgery

Ratner, Molly; Garg, Karan; Chang, Heepeel; Nigalaye, Anjali; Medvedovsky, Steven; Jacobowitz, Glenn; Siracuse, Jeffrey J; Patel, Virendra; Schermerhorn, Marc; DiMaggio, Charles; Rockman, Caron B
OBJECTIVE:The objective of this study was to examine the effect of corona virus 2019 (COVID-19) vaccination on perioperative outcomes after major vascular surgery. BACKGROUND DATA/BACKGROUND:COVID-19 vaccination is associated with decreased mortality in patients undergoing various surgical procedures. However, the effect of vaccination on perioperative mortality after major vascular surgery is unknown. METHODS:This is a multicenter retrospective study of patients who underwent major vascular surgery between December 2021 through August 2023. The primary outcome was all-cause mortality within 30 days of index operation or prior to hospital discharge. Multivariable models were used to examine the association between vaccination status and the primary outcome. RESULTS:Of the total 85,424 patients included, 19161 (22.4%) were unvaccinated. Unvaccinated patients were younger compared to vaccinated patients (mean age 68.44 +/- 10.37 y vs 72.11 +/- 9.20 y, P <0.001) and less likely to have comorbid conditions, including hypertension, congestive heart failure, chronic obstructive pulmonary disease, and dialysis. After risk factor adjustment, vaccination was associated with decreased mortality (OR 0.7, 95% CI 0.62 - 0.81, P <0.0001). Stratification by procedure type demonstrated that vaccinated patients had decreased odds of mortality after open AAA (OR 0.6, 95% CI 0.42-0.97, P =0.03), EVAR (OR 0.6, 95% CI 0.43-0.83, p 0.002), CAS (OR 0.7, 95% CI 0.51-0.88, P =0.004) and infra-inguinal lower extremity bypass (OR 0.7, 95% CI 0.48-0.96, P =0.03). CONCLUSIONS:COVID-19 vaccination is associated with reduced perioperative mortality in patients undergoing vascular surgery. This association is most pronounced for patients undergoing aortic aneurysm repair, carotid stenting and infrainguinal bypass.
PMID: 38726660
ISSN: 1528-1140
CID: 5734032

Prior Authorization Requirements In The Office-Based Laboratory Setting Are Administratively Inefficient And Threaten Timeliness Of Care

Harish, Keerthi B; Chervonski, Ethan; Speranza, Giancarlo; Maldonado, Thomas S; Garg, Karan; Sadek, Mikel; Rockman, Caron B; Jacobowitz, Glenn R; Berland, Todd L
OBJECTIVE:The objective of this study was to investigate the administrative and clinical impacts of prior authorization (PA) processes in the Office-Based Laboratory (OBL) setting. METHODS:This single-institution retrospective analysis studied all OBL PAs pursued between January 2018 and March 2022. Case, PA, and coding information was obtained from the practice's scheduling database. RESULTS:Over the study period, 1,854 OBL cases were scheduled; 8% (n=146) required PA. Of these, 75% (n=110) were for lower extremity arterial interventions, 19% (n=27) were for deep venous interventions, and 6% (n=9) were for other interventions. Of 146 PAs, 19% (n=27) were initially denied but 74.1% (n=7) of these were overturned on appeal. Deep venous procedures were initially denied, at 43.8% (n=14) more often than were arterial procedures, at 11.8% (n=13). Of 146 requested procedures, 4% (n=6) were delayed due to pending prior authorization determination by a mean 14.2±18.3 working days. An additional 6% (n=8) of procedures were performed in the interest of time prior to final determination. Of the 7 terminally denied procedures, 57% (n=4) were performed at cost to the practice based on clinical judgment. CONCLUSIONS:Utilizing prior authorization appeals mechanisms, while administratively onerous, resulted in the overturning of most initial denials.
PMID: 38135169
ISSN: 1097-6809
CID: 5611912