Transient receptor potential vanilloid 4 channel inhibition attenuates lung ischemia-reperfusion injury in a porcine lung transplant model.

OBJECTIVE: Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel important in many physiological and pathophysiological processes, including pulmonary disease. Using a murine model, we previously demonstrated that TRPV4 mediates lung ischemia-reperfusion injury, the major cause of primary graft dysfunction after transplant. The current study tests the hypothesis that treatment with a TRPV4 inhibitor will attenuate lung ischemia-reperfusion injury in a clinically relevant porcine lung transplant model. METHODS: A porcine left-lung transplant model was used. Animals were randomized to 2 treatment groups (n = 5/group): vehicle or GSK2193874 (selective TRPV4 inhibitor). Donor lungs underwent 30 minutes of warm ischemia and 24 hours of cold preservation before left lung allotransplantation and 4 hours of reperfusion. Vehicle or GSK2193874 (1 mg/kg) was administered to the recipient as a systemic infusion after recipient lung explant. Lung function, injury, and inflammatory biomarkers were compared. RESULTS: After transplant, left lung oxygenation was significantly improved in the TRPV4 inhibitor group after 3 and 4 hours of reperfusion. Lung histology scores and edema were significantly improved, and neutrophil infiltration was significantly reduced in the TRPV4 inhibitor group. TRPV4 inhibitor-treated recipients had significantly reduced expression of interleukin-8, high mobility group box 1, P-selectin, and tight junction proteins (occludin, claudin-5, and zonula occludens-1) in bronchoalveolar lavage fluid as well as reduced angiopoietin-2 in plasma, all indicative of preservation of endothelial barrier function. CONCLUSIONS: Treatment of lung transplant recipients with TRPV4 inhibitor significantly improves lung function and attenuates ischemia-reperfusion injury. Thus, selective TRPV4 inhibition may be a promising therapeutic strategy to prevent primary graft dysfunction after transplant.

Extracorporeal Life Support Organization Center of Excellence recognition is associated with improved failure to rescue after cardiac arrest.

OBJECTIVE: The influence of Extracorporeal Life Support Organization (ELSO) center of excellence (CoE) recognition on failure to rescue after cardiac surgery is unknown. We hypothesized that ELSO CoE would be associated with improved failure to rescue. METHODS: Patients undergoing a Society of Thoracic Surgeons index operation in a regional collaborative (2011-2021) were included. Patients were stratified by whether or not their operation was performed at an ELSO CoE. Hierarchical logistic regression analyzed the association between ELSO CoE recognition and failure to rescue. RESULTS: A total of 43,641 patients were included across 17 centers. In total, 807 developed cardiac arrest with 444 (55%) experiencing failure to rescue after cardiac arrest. Three centers received ELSO CoE recognition, and accounted for 4238 patients (9.71%). Before adjustment, operative mortality was equivalent between ELSO CoE and non-ELSO CoE centers (2.08% vs 2.36%; P = .25), as was the rate of any complication (34.5% vs 33.8%; P = .35) and cardiac arrest (1.49% vs 1.89%; P = .07). After adjustment, patients undergoing surgery at an ELSO CoE facility were observed to have 44% decreased odds of failure to rescue after cardiac arrest, relative to patients at non-ELSO CoE facility (odds ratio, 0.56; 95% CI, 0.316-0.993; P = .047). CONCLUSIONS: ELSO CoE status is associated with improved failure to rescue following cardiac arrest for patients undergoing cardiac surgery. These findings highlight the important role that comprehensive quality programs serve in improving perioperative outcomes in cardiac surgery.

Current Transthoracic Supra-Aortic Trunk Surgical Reconstruction Has Similar 30-Day Cardiovascular Outcomes Compared to Extra-Anatomic Revascularization but With Higher Morbidity Burden.

BACKGROUND: Operative risk for supra-aortic trunk (SAT) surgical revascularization for occlusive disease, particularly transthoracic reconstruction (TR), remains ill-defined. This study sought to describe and compare 30-day outcomes of TR and extra-anatomic (ER) SAT surgical reconstruction for an occlusive indication across the United States over a contemporary 15-year period. METHODS: Using the National Surgical Quality Improvement Program, TR and ER performed during 2005-2019 were identified. Procedures performed for nonocclusive indications and those concomitant with coronary or valve operations were excluded. Rates of stroke, death, myocardial infarction (MI) and these as composite outcome (S/D/M) were compared. Logistic regression with stabilized inverse probability weighting (IPW) was used to compare groups via average treatment effect (ATE) while adjusting for covariate imbalances. RESULTS: Over the 15-year period, 166 TR and 1,900 ER patients were identified. The majority of ERs were carotid-subclavian bypass (n = 1,344; 70.7%) followed by carotid-carotid bypass (n = 261; 13.7%) and subclavian/carotid transpositions (n = 123; 6.5%). TR consisted of aorto-SAT bypass (n = 120; 72.3%) and endarterectomy (n = 46; 27.7%). The median age was 64 years for TR and 65 years in ER (P = 0.039). Those undergoing TR were more often women (69.0% vs. 56.9%; P = 0.001) and less likely to have undergone previous cardiac surgery (9.2% vs. 20.8%; P = 0.006). TR were also less frequently hypertensive (68.1% vs. 75.4%; P = 0.038) and had statistically lower preoperative creatinine levels (0.86 vs 0.91; P = 0.002). Unadjusted rates of MI (0.6% vs. 1.3%; P = 0.72) and stroke (3.6% vs. 1.9%; P = 0.15) were similar between groups with mortality (3.6% vs. 1.5%; P = 0.05) and S/D/M (6.6% vs. 3.9%; P = 0.10) trending higher with TR. IPWs could be calculated for 1,754 patients (148 TR; 1,606 ER). The estimated probability of S/D/M was 3.8% in the ER group and 6.2% in TR; no difference was seen in ATE (2.4%; 95% confidence interval [CI]: -1.5 to 6.2; P = 0.23). No differences were seen in individual component ATEs (stroke: 3.0% vs. 1.7%; ATE = 1.3%; 95% CI: -3.9 to 1.3; P = 0.32; mortality: 3.8% vs. 1.4%; ATE = 2.4%; 95% CI: -5.6 to 0.7; P = 0.13). Secondary outcomes showed TR patients were more likely to have non-home discharge (18.7% vs. 6.6%; ATE = 12.1%; 95% CI: 5.0-19.2; P < 0.001) and longer lengths of stay (6.1 vs. 4.0; ATE = 2.2 days; 95% CI: 0.9-3.4; P < 0.001). Moreover, TR patients were more likely to require transfusion (22.7% vs. 5.0%; ATE = 17.7%; 95% CI: 10.2-25.2; P < 0.001) and develop sepsis (2.7% vs. 0.2%; ATE = 2.5%; 95% CI: 0.1-5.0; P = 0.04). CONCLUSIONS: Transthoracic and extra-anatomic surgical reconstruction of the SATs for occlusive disease have similar operative cardiovascular risk. However, morbidity tends to be higher with TR due to higher transfusion requirements, sepsis risk, and need for facility stay. These results suggest ER as a first-line approach in those with proper disease anatomy is reasonable with lower morbidity, while TR remains justified in appropriate patients.

Unplanned postoperative catheterization during admission for coronary artery bypass grafting is neither cheap nor benign, but may rescue patients.

OBJECTIVE: Literature describing outcomes of myocardial ischemia after coronary artery bypass grafting is sparse. We hypothesized these patients had more complications and incurred higher costs of care. METHODS: Using adult cardiac surgery data and cardiac catheterization (CathPCI) data from the Virginia Cardiac Services Quality Initiative, we identified patients who underwent unplanned cardiac catheterization after coronary artery bypass grafting from 2018 to 2021. Adult cardiac surgery data were matched to CathPCI data examining earliest in-hospital catheterization. Patients not requiring catheterization served as the control group. RESULTS: We identified 10,597 patients who underwent isolated coronary artery bypass grafting, of whom 41 of 10,597 underwent unplanned cardiac catheterization. A total of 21 of 41 patients (51%) received percutaneous coronary intervention, most commonly for non-ST-elevation myocardial infarction (n = 7, 33%) and ST-elevation myocardial infarction (n = 6, 29%). Postoperative cardiac arrest occurred in 14 patients (40%). In patients who underwent percutaneous coronary intervention, 14 (67%) had a single lesion, 4 (19%) had 2 lesions, and 3 (14%) had 3 lesions. The left anterior descending artery (38%) was the most frequently intervened upon vessel. Patients who underwent catheterization were more likely to require balloon pump support (26% vs 11%), to have prolonged ventilation (57% vs 20%), to have renal failure (17% vs 7.1%), and to undergo reintubation (37% vs 3.8%, all P < .04). There was no statistical difference in operative mortality (4.9% vs 2.3%, P = .2) or failure to rescue (4.9% vs 1.6%, P = .14). Total costs were higher in patients who underwent unplanned catheterization ($81,293 vs $37,011, P < .001). CONCLUSIONS: Unplanned catheterization after coronary artery bypass grafting is infrequent but associated with more complications and a higher cost of care. Therefore, determination of an association with operative mortality in patients with suspected ischemia after coronary artery bypass grafting requires additional study.

Center case volume is associated with Society of Thoracic Surgeons-defined failure to rescue in cardiac surgery.

OBJECTIVE: Our understanding of the impact of a center's case volume on failure to rescue (FTR) after cardiac surgery is incomplete. We hypothesized that increasing center case volume would be associated with lower FTR. METHODS: Patients undergoing a Society of Thoracic Surgeons index operation in a regional collaborative (2011-2021) were included. After we excluded patients with missing Society of Thoracic Surgeons Predicted Risk of Mortality scores, patients were stratified by mean annual center case volume. The lowest quartile of case volume was compared with all other patients. Logistic regression analyzed the association between center case volume and FTR, adjusting for patient demographics, race, insurance, comorbidities, procedure type, and year. RESULTS: A total of 43,641 patients were included across 17 centers during the study period. Of these, 5315 (12.2%) developed an FTR complication, and 735 (13.8% of those who developed an FTR complication) experienced FTR. Median annual case volume was 226, with 25th and 75th percentile cutoffs of 136 and 284 cases, respectively. Increasing center-level case volume was associated with significantly greater center-level major complication rates but lower mortality and FTR rates (all P values < .01). Observed-to-expected FTR was significantly associated with case volume (P = .040). Increasing case volume was independently associated with decreasing FTR rate in the final multivariable model (odds ratio, 0.87 per quartile; confidence interval, 0.799-0.946, P = .001). CONCLUSIONS: Increasing center case volume is significantly associated with improved FTR rates. Assessment of low-volume centers' FTR performance represents an opportunity for quality improvement.

Delirium is associated with failure to rescue after cardiac surgery.

Objective: Postoperative delirium after cardiac surgery is associated with long-term cognitive decline and mortality. We investigated whether increased ICU Confusion Assessment Method scores were associated with greater 30-day mortality and failure to rescue after cardiac surgery. Methods: We studied 4030 patients who underwent a Society of Thoracic Surgeons index operation at the University of Virginia Health System from 2011 to 2021. We obtained all ICU Confusion Assessment Method scores recorded during patients' admission and summarized scores for the first 7 postoperative days. Univariate and multivariable logistic regression analyzed the association between ICU Confusion Assessment Method score/delirium presence and postoperative complications, operative mortality, and failure to rescue. Results: Any episode of ICU Confusion Assessment Method screen-positive delirium and nearly all components of the score were associated with increased 30-day mortality on univariate analysis. We found that a single episode of delirium was associated with increased mortality. Feature 2 (inattention) had the strongest association with poorer outcomes, including failure to rescue in our analysis, as were patients with higher peak Richmond Agitation Sedation Scale scores. Patients with higher mean Richmond Agitation Sedation Scale scores had an association with decreased failure to rescue. Conclusions: A single episode of delirium, as measured using ICU Confusion Assessment Method scores, is associated with increased mortality. Inattention and higher peak Richmond Agitation Sedation Scale scores were associated with failure to rescue. Screening may clarify diagnosing delirium and assessing its implications on mortality and failure to rescue. Our findings suggest the importance of identifying and managing risk factors for delirium to improve patient outcomes and reduce mortality and failure to rescue rates.

Commentary: Small patients with big wounds.

Some would argue that kids aren't just little adults, but what about their sternums? We are reviewing a manuscript by Horriat, McCandless, and colleagues in the Journal of Cardiac Surgery describing their experience with managing sternal wound infections (SWI) after congenital heart surgery. They report encouraging results in 14 patients who required plastic surgery consultation to manage their sternal wounds. The nature of congenital cardiac abnormalities and the necessary steps to repair them leads to physiologic derangements predisposing patients to SWI. Rates of SWI vary and have been reported at 1.53% in this population. There is little guidance on how the management of the congenital cardiac surgery patient should differ from the adult patient.

Wound location is independently associated with adverse outcomes following first-time revascularization for tissue loss.

OBJECTIVE: Few studies adequately evaluate the impact of wound location on patient outcomes after lower extremity revascularization. Consequently, we evaluated the relationship between lower extremity wound location and long-term outcomes. METHODS: We reviewed all patients at our institution undergoing any first-time open surgical bypass or percutaneous transluminal angioplasty with or without stenting for tissue loss between 2005 and 2014. We categorized wounds into three distinct groups: forefoot (ie, toes and metatarsal heads), midfoot (ie, dorsal, plantar, lateral, medial surfaces excluding toes, metatarsal heads, or heel), and heel. Limbs with multiple wounds were excluded from analyses. We compared rates of perioperative complications, wound healing, reintervention, limb salvage, amputation-free survival, and survival using χ2, Kaplan-Meier, and Cox regression analyses. RESULTS: Of 2869 infrainguinal revascularizations from 2005 to 2014, 1126 underwent a first-time revascularization for tissue loss, of which 253 patients had multiple wounds, 197 had wounds proximal to the ankle, 100 had unreliable wound information, and 576 (forefoot, n = 397; midfoot, n = 61; heel, n = 118) fit our criteria and had a single foot wound with reliable information regarding wound specifics. Patients with forefoot, midfoot, and heel wounds had similar rates of coronary artery disease, hypertension, diabetes, and smoking history (all P > .05). Conversely, there were significant differences in patient age (71 vs 69 vs 70 years), prevalence of gangrene (41% vs 5% vs 21%), and dialysis dependence (18% vs 17% vs 30%) (all P < .05). There were no statistically significant differences in perioperative mortality (1.3% vs 4.9% vs 4.2%; P = .06) or postoperative complications among the three groups. Between forefoot, midfoot, and heel wounds, there were significant differences in unadjusted 6-month rates of complete wound healing (69% vs 64% vs 53%), 3-year rates of amputation-free survival (54% vs 57% vs 35%), and survival (61% vs 72% vs 41%) (all P < .05). After adjustment, compared with forefoot wounds, heel wounds were associated with higher rates of incomplete 6-month wound healing (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.]), major amputation or mortality (HR, 1.7; 95% CI, 1.1-2.7), and all-cause mortality (HR, 1.8; 95% CI, 1.1-3.0), but not major amputation alone (HR, 2.1; 95% CI, 0.9-4.5). In open surgical bypass-first patients, heel wounds were solely associated with an increased risk of all-cause mortality (HR, 1.7; 95% CI, 1.1-2.8), whereas heel wounds in percutaneous transluminal angioplasty-first patients were associated with an increased risk of incomplete wound healing (HR, 2.2; 95% CI, 1.3-3.7), major amputation or mortality (HR, 2.3; 95% CI, 1.1-5.4), and all-cause mortality (HR, 2.8; 95% CI, 1.1-7.2). CONCLUSIONS: Heel wounds confer considerably higher short- and long-term morbidity and mortality compared with midfoot or forefoot wounds in patients undergoing any first-time lower extremity revascularization.

Significance of Interstitial Lung Disease on Outcomes Following Cardiac Surgery.

Interstitial lung disease (ILD) is a known risk factor for noncardiac surgery due to acute pulmonary exacerbations but its impact after cardiac surgery is not known. We examined perioperative outcomes and risk factors for long-term survival in ILD patients who underwent cardiac surgery. From January 2002 to June 2017, 294 cardiac surgery patients with a previous ILD diagnosis, including 75 patients with idiopathic pulmonary fibrosis (IPF), were identified. A comparison cohort of 1,481 non-ILD patients was selected based on a priori variables. Long-term survival was evaluated using Cox proportional hazard modeling. Median follow-up was 6.4 years. ILD patients had higher postoperative mortality, reintubation rates, longer intensive care unit stay, and higher 30-day readmission rates (all p <0.05). Kaplan-Meier estimates of survival at 1, 5, and 10 years were 89%, 62%, and 37% for the non-IPF ILD cohort, 89%, 50%, and 13% for the IPF cohort, and 95%, 82%, and 67% for the comparison cohort, respectively (overall p <0.001). These significant differences in survival persisted in our risk-adjusted survival analysis. Adjusted survival analysis identified IPF (hazard ratio 3.04) and ILD (non-IPF; hazard ratio 1.78) as significant contributors to all-cause mortality. However, there were no changes in pulmonary function tests after 48 months postprocedure. In conclusion, ILD patients who underwent cardiac surgery have increased operative mortality, reintubation rates, longer intensive care unit, and higher 30-day readmissions compared with non-ILD patients. Moreover, severity of ILD, especially in IPF, appears to be associated with shorter long-term survival. In these patients, pulmonary risk stratification and multidisciplinary team approach are crucial.

Outcomes after first-time lower extremity revascularization for chronic limb-threatening ischemia in insulin-dependent diabetic patients.

OBJECTIVE: Historically, open surgical bypass provided a durable repair among diabetic patients with chronic limb-threatening ischemia (CLTI). In the current endovascular era, however, the difference in long-term outcomes between first-time revascularization strategies among patients with insulin-dependent diabetes mellitus (IDDM) is poorly understood. METHODS: We reviewed the records of all patients with IDDM undergoing a first-time infrainguinal bypass graft (BPG) or percutaneous transluminal angioplasty with or without stenting (PTA/S) for CLTI at our institution from 2005 to 2014. We defined IDDM as use of chronic insulin administration at baseline to control blood glucose levels and recorded the most recent glycated hemoglobin value available within 3 months before the procedure and fasting blood glucose level on the day of the procedure. We compared rates of wound healing, restenosis, reintervention, major amputation, and mortality between BPG and PTA/S in our population using χ2, Kaplan-Meier, and Cox regression analyses. As a sensitivity analysis, we calculated propensity scores and employed inverse probability weighting to account for nonrandom assignment to BPG vs PTA/S. RESULTS: Of 2869 infrainguinal revascularizations from 2005 to 2014, 655 limbs (316 BPG, 339 PTA/S) in 580 patients fit our criteria and underwent a first-time revascularization for CLTI. Patients undergoing BPG, compared with PTA/S, were similar in age (69 vs 68 years; P = .55), had similar rates of tissue loss (87% vs 91%; P = .07) and dialysis dependence (26% vs 28%; P = .55), were less likely to be hypertensive (84% vs 92%; P < .001), and were more likely to be current smokers (21% vs 14%; P = .02). There were no differences between BPG and PTA/S patients in mean glycated hemoglobin levels (8.1% vs 8.0%; P = .51) or mean fasting blood glucose levels (158 vs 150 mg/dL; P = .18). Although total hospital length of stay was significantly longer among BPG patients (11 vs 8 days; P < .001), perioperative complications did not differ, including acute kidney injury (19% vs 23%; P = .24), hematoma (6.0% vs 3.8%; P = .20), acute myocardial infarction (1.3% vs 2.1%; P = .43), and mortality (3.8% vs 3.0%; P = .55). BPG-first patients had significantly lower unadjusted 6-month rates of incomplete wound healing (49% vs 57%) and 5-year rates of restenosis (53% vs 72%) and reintervention (47% vs 58%; all P < .05). After adjustment, multivariable analysis suggested PTA/S-first intervention to be significantly associated with higher risk of restenosis (hazard ratio, 1.9; 95% confidence interval, 1.3-2.7) and reintervention (1.9 [1.2-2.7]). These results remained robust after inverse probability weighting. CONCLUSIONS: Among patients with IDDM and CLTI, a bypass-first strategy is associated with similar 30-day outcomes and lower restenosis and reintervention rates. These data suggest that a bypass-first approach may best serve appropriately selected, anatomically suitable patients with IDDM and pedal ischemia that requires revascularization.

Outcomes of repeat mitral valve replacement in patients with prior mitral surgery: A benchmark for transcatheter approaches.

OBJECTIVES: With the emergence of transcatheter mitral valve-in-valve/ring replacement for deteriorated bioprostheses or failed repair, comparative clinical benchmarks for surgical repeat mitral valve replacement (re-MVR) are needed. We present in-hospital and survival outcomes of a 24-year experience with re-MVR. METHODS: From January 1992 to June 2015, 520 adult patients underwent re-MVR; 273 had undergone prior mitral valve repair (pMVP) and 247 had undergone prior MVR (pMVR). A benchmark cohort of isolated re-MVR was defined based on potential eligibility for transcatheter mitral valve-in-valve/ring replacement, resulting in 73 pMVPs with previous annuloplasty rings and 74 pMVRs with previous bioprosthetic valves for comparison. RESULTS: For the entire cohort, mean age was 64 ± 12 years for pMVP patients and 63 ± 15 years for pMVR patients (P = .281), which was similar for the benchmark cohort. Overall operative mortality was 14 out of 273 (5%) for pMVP versus 23 out of 247 (9%) for pMVR (P = .087). There were 3 operative deaths (4.1%) in both groups of the benchmark cohort (P = 1.0). For the benchmark cohort, median time to reoperation was 9.8 years for pMVP and 9.1 years for pMVR. Cox proportional hazard analysis showed that chronic kidney disease (hazard ratio [HR], 2.47; 95% CI, 1.77-3.44), endocarditis (HR, 1.49; 95% CI, 1.07-2.07), pMVR (HR, 1.45; 95% CI, 1.12-1.89), early reoperation ≤ 1 year (HR, 1.49; 95% CI, 1.02-2.17), and age (HR, 1.04/y; 95% CI, 1.03-1.05) were associated with decreased survival after re-MVR. CONCLUSIONS: A re-MVR is a high-risk operation, but in carefully selected patients such as our benchmark population, it can be performed with acceptable results. Patients undergoing pMVP also have better long-term survival compared with patients undergoing pMVR. These results will serve as a benchmark for transcatheter mitral valve-in-valve/ring replacement.

Novel fast-track recovery protocol for alternative access transcatheter aortic valve replacement: application to non-femoral approaches.

OBJECTIVES: Although the transfemoral approach for transcatheter aortic valve replacement is the preferred choice, alternative access remains indicated for inadequate iliofemoral vessels. We report the successful implementation of a novel fast-track (FT) protocol for patients undergoing alternative access transcatheter aortic valve replacement compared with conventional controls. METHODS: Between September 2014 and January 2017, 31 and 23 patients underwent alternative access transcatheter aortic valve replacement under FT and pre-fast-track (p-FT) protocols, respectively. Comparisons of outcomes (in terms of mortality, complications, readmissions and resource utilization) were made before and after the implantation of the FT protocol in September 2015. RESULTS: Overall, mean age was 78.7 years in FT and 79.6 years in p-FT patients (P = 0.71). There were no significant differences in procedural (3.2% vs 13.0%, P = 0.301) or 90-day mortality (3.2% vs 17.4%, P = 0.151) between the FT and p-FT groups, respectively. Compared with p-FT patients, FT patients had significantly shorter intensive care unit stays (12 h vs 27 h, P = 0.006) and a trend towards more discharges within 3 days (41.9% vs 17.4%, P = 0.081). Resource utilization analyses projected a 56% and 17% reduction in the mean intensive care unit time (hours) per 100 patients and the total length of stay (days) per 100 patients, respectively, with respect to the FT approach. CONCLUSIONS: This pilot study demonstrates the feasibility and safety of the novel FT protocol for alternative access transcatheter aortic valve replacement, resulting in shorter intensive care unit stays, without increasing procedural complications or readmissions. With the expected increase in transcatheter aortic valve replacement utilization, FT protocols should be integrated with a multidisciplinary heart team approach to enhance patient recovery and optimize resource utilization.

New approaches to cardiovascular surgery.

Modern treatment of cardiovascular disease requires a patient-centered approach. With several technological advances, the options for treatment must be carefully weighed and novel approaches tested for safety and efficacy. In this article, we outline some of the new approaches available to cardiothoracic surgeons for the treatment of cardiovascular diseases, including off-pump coronary artery bypass grafting, transcatheter valve replacement, and hybrid and robotic technology. We discuss current evidence and controversies and highlight the challenges that we face in training surgeons in an environment of ever-evolving surgical techniques.