Thoracofemoral bypass outcomes in the Vascular Quality Initiative.

OBJECTIVE: Thoracofemoral bypass (TFB) has been used infrequently but is an alternative for select patients with aortoiliac occlusive disease. Limited data are available in the reported data regarding TFB, with all studies small, single-center series. We aimed to describe the perioperative and long-term survival, patency, and rate of major perioperative complications after TFB in a large national registry. METHODS: The Vascular Quality Initiative suprainguinal bypass module was used to identify patients who had undergone TFB for occlusive disease from 2009 to 2019. A descriptive analysis was performed to provide the rates of survival, patency, major complications, and freedom from major amputation in the perioperative period and at 1 year of follow-up. Major complications were compared by procedure indication, with categorical variables analyzed using χ2 tests and continuous variables using analysis of variance. Kaplan-Meier curve analysis was used to estimate survival at the 1- and 5-year follow-up intervals and freedom from major amputation at 1 year. RESULTS: A total of 154 TFB procedures were identified. Of the 154 patients, 59 (38.3%) had undergone previous inflow bypass and 22 (14.2%) had undergone previous leg bypass. The procedure indications included claudication (n = 66; 42.9%), rest pain (n = 59; 38.3%), tissue loss (n = 19; 12.3%), and acute limb ischemia (n = 10; 6.5%). Major complications (eg, wound infection, respiratory, major stroke, new dialysis, cardiac, embolic, major amputation, occlusion) occurred in 31.2% of the cohort. When examined by indication, the acute limb ischemia and claudication cohorts had an increased rate of major complications (acute limb ischemia, 60.0%; claudication, 34.8%; critical limb ischemia, 24.4%; P = .05). The survival rate at 30 days was 95.5%, with a Kaplan-Meier estimated 1-year survival rate of 92.7% ± 2.2%. Primary patency at discharge from the index hospitalization was 92.9% and 89.0% at 1 year. Postoperative major amputation was required for 1 patient during the index hospitalization, for a Kaplan-Meier estimated freedom from major amputation at 1 year of 97.1% ± 2.2%. Two patients developed in-hospital bypass occlusion and three patients developed occlusion within 1 year, for an overall freedom from occlusion rate of 96.8% at 1 year. CONCLUSIONS: TFB is associated with a high rate of perioperative major complications; however, the long-term survival and patency after TFB remained acceptable when performed for limb salvage. The high perioperative complication rates of TFB procedures performed for claudication suggest TFB should be used rarely in this population. These data can be used to counsel patients and aid in decision making before operative intervention.

The association between preoperative length of stay and surgical site infection after lower extremity bypass for chronic limb-threatening ischemia.

OBJECTIVE: Surgical site infection (SSI) is an important complication of lower extremity bypass (LEB) and the rate of SSI after LEB varies widely in the existing literature, ranging from 4% to 31%. Prolonged length of stay (LOS) has been implicated in the occurrence of SSI across multiple surgical disciplines. The impact of preoperative LOS in patients with chronic limb-threatening ischemia (CLTI) undergoing LEB is unknown. We examined the association of preoperative LOS on SSI after LEB. METHODS: A retrospective analysis of the Society for Vascular Surgery Vascular Quality Initiative Infrainguinal Bypass Registry identified patients undergoing elective LEB for chronic limb-threatening ischemia from 2003 to 2019. Patients undergoing LEB for acute limb ischemia, urgent/emergent procedures, aneurysm, or who had concomitant suprainguinal bypass were excluded. The primary outcome measure was postoperative SSI. Multivariable forward stepwise logistic regression was then performed including all variables with a P value of less than .10 in both matched and unmatched cohorts to evaluate for demographic and perioperative predictors of SSI. Propensity score matching was used to create matched cohorts of patients for each LOS group. RESULTS: A total of 17,883 LEB procedures were selected for inclusion: 0 days (12,362 LEB), 1 to 2 days (1737 LEB), and 3 to 14 days (3784 LEB). Patients with the greatest preoperative LOS were more likely to have vein mapping (0 days preoperative LOS, 66.3%; 1-2 days, 65.2%; 3-14 days, 73.2%; P < .01) or computed tomography angiography/magnetic resonance angiography (0 days, 32.1%; 1-2 days, 34.4%; 3-14 days, 38.4%; P < .01). Patients with 3 or more days of preoperative LOS had longer procedure lengths (0 days, 244 minutes; 1-2 days, 243 minutes; 3-14 days, 255 minutes; P < .01) and were more likely to have completion angiogram (0 days, 27.1%; 1-2 days, 29.5%; 3-14 days, 31.6%; P = .02). Multivariable logistic regression demonstrated that preoperative LOS of 3 to 14 days was associated with increased rate of SSI (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.20-3.07; P = .01). Transfusion of 3 or more units (OR, 2.87; 95% CI, 1.89-4.36; P < .01) and prolonged procedure length (>220 minutes; OR, 1.86; 95% CI, 1.26-2.73; P < .01) were also significantly associated with postoperative SSIs. CONCLUSIONS: Many factors including preoperative comorbidities and operative complexity covary with preoperative LOS as risk factors for SSI. However, when patients are matched based on comorbidities and factors that would predict overall clinical complexity, preoperative LOS remains important in predicting SSI.

Carotid endarterectomy with concomitant distal endovascular intervention is associated with increased rates of stroke and death.

OBJECTIVE: Carotid endarterectomy (CEA) with concomitant distal endovascular intervention (CEA+D) is infrequently necessary but has often been used as a salvage maneuver when complications occur during CEA. The present study aimed to determine whether preoperative risk factors associated with CEA requiring CEA+D exist and to evaluate the outcomes compared with isolated CEA. METHODS: The Vascular Quality Initiative CEA registry was used to identify patients who had undergone CEA or CEA+D for asymptomatic or symptomatic carotid stenosis from 2013 to 2019. Data regarding distal intervention included whether angioplasty or stenting of the distal internal carotid artery (ICA) and/or bifurcation had been required. However, information regarding the indication or whether the intervention had been planned was not included. The χ2 test and analysis of variance were used to evaluate the categorical and continuous perioperative variables. Variables with P < .20 on univariate analysis were included in the multivariable analysis to assess for preoperative predictors of the need for CEA+D and the association with perioperative stroke. RESULTS: From 2013 to 2019, 327 CEA+D cases were identified and compared with 105,192 isolated CEA cases. The CEA+D patients were more likely to have undergone previous ipsilateral CEA (CEA, 1.8%; CEA+D, 4.9%; P < .01) and contralateral ICA occlusion (CEA, 4.6%; CEA+D, 11.0%; P < .01) but were less likely to have had ipsilateral stenosis ≥70% (CEA, 88.3%; CEA+D, 80.6%; P < .01). The preoperative factors associated with the need for CEA+D on multivariable analysis included previous peripheral vascular intervention, American Society of Anesthesiologists class ≥4, contralateral ICA occlusion, low-volume surgeon, and previous ipsilateral CEA. CEA+D was associated with significantly increased rates of stroke in both asymptomatic (CEA+D, 3.9%; CEA, 0.9%; P < .01) and symptomatic (CEA+D, 9.4%; CEA, 1.9%; P < .01) patients. CEA+D was associated with decreased rates of 30-day survival in both asymptomatic (CEA+D, 98.3%; CEA, 99.4%; P = .02) and symptomatic (CEA+D, 94.8%; CEA, 99.1%; P < .01) cohorts. On multivariable analysis, CEA+D remained significantly associated with stroke (odds ratio, 3.17; 95% confidence interval, 1.80-5.60; P < .01). Other factors significantly associated with perioperative stroke included procedure length >135 minutes, diabetes, hypertension, shunt for indication, symptomatic status, previous ipsilateral CEA, contralateral ICA occlusion, urgent or emergent procedure, intravenous medications for hemodynamic instability, and re-exploration at the initial operation. CONCLUSIONS: Although markers of more significant cardiovascular disease burden were associated with the use of CEA+D, their power to predict CEA+D use was limited. In cases in which CEA+D was used, CEA+D was associated with significantly greater rates of perioperative stroke and mortality compared with isolated CEA for both asymptomatic and symptomatic patients, which could be useful for framing the expected outcomes after these procedures.

Why Does Exercise "Trigger" Adaptive Protective Responses in the Heart?

Numerous epidemiological studies suggest that individuals who exercise have decreased cardiac morbidity and mortality. Pre-clinical studies in animal models also find clear cardioprotective phenotypes in animals that exercise, specifically characterized by lower myocardial infarction and arrhythmia. Despite the clear benefits, the underlying cellular and molecular mechanisms that are responsible for exercise preconditioning are not fully understood. In particular, the adaptive signaling events that occur during exercise to "trigger" cardioprotection represent emerging paradigms. In this review, we discuss recent studies that have identified several different factors that appear to initiate exercise preconditioning. We summarize the evidence for and against specific cellular factors in triggering exercise adaptations and identify areas for future study.

Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia.

We recently showed that Bendavia, a novel mitochondria-targeting peptide, reduced infarction and no-reflow across several experimental models. The purpose of this study was to determine the therapeutic timing and mechanism of action that underlie Bendavia's cytoprotective property. In rabbits exposed to in vivo ischemia/reperfusion (30/180 min), Bendavia administered 20 minutes prior to reperfusion (0.05 mg/kg/h, intravenously) reduced myocardial infarct size by ∼50% when administered for either 1 or 3 hours of reperfusion. However, when Bendavia perfusion began just 10 minutes after the onset of reperfusion, the protection against infarction and no-reflow was completely lost, indicating that the mechanism of protection is occurring early in reperfusion. Experiments in isolated mouse liver mitochondria found no discernible effect of Bendavia on blocking the permeability transition pore, and studies in isolated heart mitochondria showed no effect of Bendavia on respiratory rates. As Bendavia significantly lowered reactive oxygen species (ROS) levels in isolated heart mitochondria, the ROS-scavenging capacity of Bendavia was compared to well-known ROS scavengers using in vitro (cell-free) systems that enzymatically generate ROS. Across doses ranging from 1 nmol/L to 1 mmol/L, Bendavia showed no discernible ROS-scavenging properties, clearly differentiating itself from prototypical scavengers. In conclusion, Bendavia is a promising candidate to reduce cardiac injury when present at the onset of reperfusion but not after reperfusion has already commenced. Given that both infarction and no-reflow are related to increased cellular ROS, Bendavia's protective mechanism of action likely involves reduced ROS generation (as opposed to augmented scavenging) by endothelial and myocyte mitochondria.

Stage of the estrous cycle does not influence myocardial ischemia-reperfusion injury in rats (Rattus norvegicus).

Even though cardiovascular disease is the leading cause of death for men and women, the vast majority of animal studies use male animals. Because female reproductive hormones have been associated with cardioprotective states, many investigators avoid using female animals because these hormones are cyclical and may introduce experimental variability. In addition, no studies have investigated the specific effects of the estrous cycle on cardiac ischemic injury. This study was conducted to determine whether the estrous cycle stage influences the susceptibility to ischemic injury in rat hearts. Estrous cycle stage was determined by using vaginal smear cytology, after which hearts underwent either in vivo (surgical) or ex vivo (isolated) ischemia-reperfusion injury. For in vivo studies, the left anterior coronary artery was ligated for 25 min of ischemia and subsequently released for 120 min of reperfusion. Infarct sizes were 42% ± 6%; 49% ± 4%; 40% ± 9%; 47% ± 9% of the zone-at-risk for rats in proestrus, estrus, metestrus, and diestrus, respectively. For ex vivo studies, isolated, perfused hearts underwent global ischemia and reperfusion for 25 and 120 min, respectively. Similar to our in vivo studies, the ex vivo rat model showed no significant differences in susceptibility to infarction or extent of cardiac arrhythmia according to estrous stage. To our knowledge, these studies provide the first direct evidence that the stage of estrous cycle does not significantly alter cardiac ischemia-reperfusion injury in rats.

Redox-dependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria.

AIMS: We have previously shown that exercise leads to sustainable cardioprotection through a mechanism involving improved glutathione replenishment. This study was conducted to determine if redox-dependent modifications in glutathione reductase (GR) were involved in exercise cardioprotection. Furthermore, we sought to determine if reactive oxygen species generated by NADPH oxidase and/or mitochondria during exercise were triggering events for GR modulations. METHODS AND RESULTS: Rats were exercised for 10 consecutive days, after which isolated hearts were exposed to ischaemia/reperfusion (25 min/120 min). Exercise protected against infarction and arrhythmia, and preserved coronary flow. The GR inhibitor BCNU abolished the beneficial effects. GR activity was increased following exercise in a redox-dependent manner, with no change in GR protein levels. Because fluorescent labelling of GR protein thiols showed lower amounts of reduced thiols after exercise, we sought to determine the source of intracellular reactive oxygen species that may be activating GR. Subsets of animals were exercised immediately after treatment with either NADPH-oxidase inhibitors apocynin or Vas2870, or with mitoTEMPO or Bendavia, which reduce mitochondrial reactive oxygen species levels. The cardioprotective effects of exercise were abolished if animals exercised in the presence of NADPH oxidase inhibitors, in clear contrast to the mitochondrial reagents. These changes correlated with thiol-dependent modifications of GR. CONCLUSION: Adaptive cardioprotective signalling is triggered by reactive oxygen species from NADPH oxidase, and leads to improved glutathione replenishment through redox-dependent modifications in GR.