Beyond Static Planning: Computational Predictive Modeling to Avoid Coronary Artery Occlusion in TAVR.

BACKGROUND: Coronary artery occlusion (CO) during transcatheter aortic valve replacement (TAVR) is a devastating complication. The objective is to assess the clinical impact of a novel computational predictive modeling algorithm for CO during TAVR planning. METHODS: From January 2020 to December 2022, 116 patients (7.6%) undergoing TAVR evaluation were deemed at increased risk of CO based on traditional criteria. Patients underwent prospective computational modeling (DASI Simulations) to assess risk of CO during TAVR; procedural modifications and clinical results were reviewed retrospectively. RESULTS: Of the 116 patients at risk for CO by traditional methodology, 53 had native aortic stenosis(45.7%), 47 a previous surgical AVR (40.5%), and 16 a prior TAVR (13.8%). Transcatheter valve choice, size, and/or implantation depth was modeled for all patients. Computational modeling predicted an increased risk of CO based in 39/116 (31.9%). Within this sub-cohort, 29 patients proceeded with TAVR. Procedural modifications to augment risk of CO included BASILICA (n=10), chimney coronary stents (n=8), coronary access without stent (n=3). There were no episodes of coronary compromise among patients following TAVR, either for those predicted to be at high risk of CO (with procedural modifications) or predicted low risk (standard TAVR). CONCLUSIONS: Utilization of preoperative simulations for TAVR in patient-specific geometry through computational predictive modeling of CO was an effective enhancement to procedure planning.

Early Intervention in Asymptomatic Aortic Stenosis: What Are We Waiting For?

Aortic stenosis (AS) contributes to significant cardiovascular morbidity and mortality worldwide, and the natural history from symptoms to ventricular decompensation, heart failure, and death has been well documented. For more than 2 decades, technologies including imaging and biomarkers have shown a promising ability to detect myocardial damage associated with AS before symptoms arise. Current treatment guidelines rely heavily on symptoms or ventricular decompensation as triggers for aortic valve intervention. There is increasing appreciation of the relationship between myocardial damage due to AS before the emergence of symptoms, and a number of published randomised trials suggest a benefit to early intervention in asymptomatic AS, with additional trials actively enrolling. Future treatment paradigms may incorporate early detection of ventricular damage by noninvasive new technologies as triggers for asymptomatic intervention. Enthusiasm for early aortic valve replacement should be tempered by consideration of the competing risks of early valve intervention, but an increasing preponderance of evidence continues to suggest that earlier intervention in AS is warranted.

Correlating oxygen delivery on cardiopulmonary bypass with Society of Thoracic Surgeons outcomes following cardiac surgery.

BACKGROUND: The relationship between low oxygen delivery (DO2) on cardiopulmonary bypass and morbidity and mortality following cardiac surgery remains unexamined. METHODS: We reviewed patients undergoing Society of Thoracic Surgeons index procedures from March 2019 to July 2020, coincident with implementation of a new electronic perfusion record that provides for continuous recording of DO2 and flow parameters. Continuous perfusion variables were analyzed using area-over-the-curve (AOC) calculations below predefined thresholds (DO2 <280 mL O2/min/m2, cardiac index <2.2 L/min, hemoglobin < baseline, and mean arterial pressure <65 mm Hg) to quantify depth and duration of potentially harmful exposures. Multivariable logistic regression adjusted by Society of Thoracic Surgeons predicted-risk scores were used to assess for relationship of perfusion variables with the primary composite outcome of any Society of Thoracic Surgeons index procedure, as well as individual Society of Thoracic Surgeons secondary outcomes (eg, mortality, renal failure, prolonged ventilation >24 hours, stroke, sternal wound infection, and reoperation). RESULTS: Eight hundred thirty-four patients were included; 42.7% (356) underwent isolated coronary artery bypass grafting (CABG), whereas 57.3% underwent nonisolated CABG (eg, valvular or combined CABG/valvular operations). DO2 <280-AOC trended toward association with the primary outcome across all cases (P = .07), and was significantly associated for all nonisolated CABG cases (P = .02)-more strongly than for cardiac index <2.2-AOC (P = .04), hemoglobin <7-AOC (P = .51), or mean arterial pressure <65-AOC (P = .11). Considering all procedures, DO2 <280-AOC was independently associated prolonged ventilation >24 hours (P = .04), an effect again most pronounced in nonisolated-CABG cases (P = .002), as well as acute kidney injury <72 hours (P = .04). Patients with glomerular filtration rate <65 mL/min and baseline hemoglobin <12.5 g/dL appeared especially vulnerable. CONCLUSIONS: Low DO2 on bypass may be associated with morbidity/mortality following cardiac surgery, particularly in patients undergoing nonisolated CABG. These results underscore the importance of goal-directed perfusion strategies.

Relationship of intraoperative perfusion parameters to the need for immediate extracorporeal support following heart transplantation.

PURPOSE: We sought to assess the relationship of intraoperative perfusion parameters while on cardiopulmonary bypass, including oxygen delivery (DO2), to the need for ECMO following orthotopic heart transplantation (OHT). METHODS: We included all adult (>18 years old) OHTs performed at our institution since implementation of an electronic perfusion record (March 2019-February 2020). Multi-organ transplants were excluded. The primary outcome was the need for immediate venoarterial ECMO in the OR following OHT. Univariable statistics were computed across demographic, clinical, operative, and perfusion variables, including oxygen delivery (DO2) measured each minute. RESULTS: Fifty-three OHT were included with a median age of 54 years (interquartile range, 45-61). The primary outcome occurred in eight patients (15.1%). A significantly greater proportion of patients requiring ECMO had ischemic cardiomyopathy (50.0% (4/8) vs. 15.6% (7/45), p = 0.02) and had preoperative ventricular assist devices (37.5% (3/8) vs. 8.9% (4/45), p = 0.03). Median bypass times were longer in the ECMO group (217 vs. 147 minutes, p = 0.001). Phenylephrine doses were nonsignificantly higher in ECMO patients (4.1 vs. 1.9 mg, p = 0.10). No significant differences were observed in single-point median DO2 (275 vs. 294 mL O2/min/m2 BSA, p = 0.17) and nadir DO2 (226 vs. 222, p = 0.94), but increasing time and depth of DO2 below a threshold of 300 mL O2/min/m2 BSA (i.e. area over the DO2 curve (AOC) but below threshold) was significantly associated with the need for postoperative ECMO (p = 0.04). CONCLUSION: This is the first study to examine the relationship of perfusion parameters, including oxygen delivery, to outcomes following heart transplantation. We note that DO2 < 300-AOC was significantly associated with the need for postoperative ECMO following heart transplant. Further study will clarify whether potential DO2 differences in patients who require post-OHT ECMO reflect vasoplegia, or a more causative relationship which might be leveraged to improve outcomes.

Impact of the New Pulmonary Hypertension Definition on Heart Transplant Outcomes: Expanding the Hemodynamic Risk Profile.

BACKGROUND: At the recent 6th World Symposium on Pulmonary Hypertension (PH), the definition of PH was redefined to include lower pulmonary artery pressures in the setting of elevated pulmonary vascular resistance (PVR). However, the relevance of this change to subjects with PH due to left-heart disease as well as the preoperative assessment of heart transplant (HT) recipients is unknown. METHODS: The United Network for Organ Sharing database was queried to identify adult recipients who underwent primary HT from 1996 to 2015. Recipients were subdivided into those with mean pulmonary artery pressure (mPAP) < 25 mm Hg and ≥ 25 mm Hg. Exploratory univariable analysis was undertaken to identify candidate risk factors associated with 30-day and 1-year survival (conditional on 30-day survival) in recipients with mPAP < 25 mm Hg, and subsequently, parsimonious multivariable Cox proportional hazards models were constructed to assess the independent association with PVR. RESULTS: Over the study period, 32,465 patients underwent HT, including 12,257 (38%) with mPAP < 25 mm Hg. The median age was 55 years (interquartile range, 47-62) and the median PVR was 1.5 Wood units (WU) (interquartile range, 1-2.2) in recipients with mPAP < 25 mm Hg. After controlling for confounders, PVR was independently associated with increased risk for 30-day mortality (hazard ratio, 1.16; 95% CI, 1.05-1.27; P < .01), but not conditional 1-year mortality (hazard ratio, 1.03; 95% CI, 0.94-1.12; P = .55). PVR ≥ 3 WU was associated with an absolute 1.9% increase in 30-day mortality in those with mPAP < 25 mm Hg, a similar risk to recipients with PVR ≥ 3 WU and mPAP ≥ 25 mm Hg. CONCLUSIONS: Elevated PVR remains associated with a significant increase in the hazard for 30-day mortality after cardiac transplantation, even in the setting of lower pulmonary artery pressures. These data support the validity of the new definition of pulmonary hypertension.

Outcomes after heart transplantation in sensitized patients bridged with ventricular assist devices.

OBJECTIVE: Sensitization has been associated with worse outcomes following heart transplantation (HTx). The use of ventricular assist devices (VAD) is a risk factor for the development of sensitization. We investigated the impact of left ventricular assist devices (LVAD) and sensitization in HTx recipients. METHODS: We queried the UNOS database for all heart transplants performed from January 2000 through December 2016. Patients were considered highly sensitized and included if panel-reactive antibody (PRA) activity was 25% or higher. Patients were separated by pretransplant LVAD utilization and subgroup analysis was performed by device type (HeartMate II or HeartWare). Outcomes included Kaplan-Meier survival and episodes of rejection within 1 year of HTx. RESULTS: Of 18 009 recipients, 2434 (14%) were highly sensitized. 1055 (43.3%) were bridged with a VAD. In multivariate analysis, LVAD use did not impact 1-year (hazards ratio [HR], 1.30; P = 0.052) or 5-year survival (HR, 1.18; P = 0.112) in highly sensitized recipients. Furthermore, episodes of rejection were not affected by LVAD status (P = 0.765). Of the 1055 sensitized LVAD-bridged transplant recipients, 624 (59%) were implanted with a HeartMate II and 99 (9.4%) were bridged with a HeartWare device. In multivariate analysis, no differences were observed in 1-year survival (HR, 0.86; P = 0.664), 5-year survival (HR, 1.35; P = 0.209), or episodes of rejection (P = 0.497). CONCLUSIONS: The use of ventricular assist devices did not impact survival or rejection within 1 year of HTx in highly sensitized patients. Highly sensitized recipients have similar outcomes regardless of prior LVAD support or type of LVAD used as a bridge to transplantation.

Children's Heart Assessment Tool for Transplantation (CHAT) Score: A Novel Risk Score Predicts Survival After Pediatric Heart Transplantation.

BACKGROUND: Given the shortage of donor organs in pediatric heart transplantation (HTx), pretransplant risk stratification may assist in organ allocation and recipient optimization. We sought to construct a scoring system to preoperatively stratify a patient's risk of one-year mortality after HTx. METHODS: The United Network for Organ Sharing database was queried for pediatric (<18 years) patients undergoing HTx between 2000 and 2016. The population was randomly divided in a 4:1 fashion into derivation and validation cohorts. A multivariable logistic regression model for one-year mortality was constructed within the derivation cohort. Points were then assigned to independent predictors ( P < .05) based on relative odds ratios (ORs). Risk groups were established based on easily applicable, whole-integer score cutoffs. RESULTS: A total of 5,700 patients underwent HTx; one-year mortality was 10.7%. There was a similar distribution of variables between derivation (n = 4,560) and validation (n = 1,140) cohorts. Of the 12 covariates included in the final model, nine were allotted point values. The low-risk (score 0-9), intermediate-risk (10-20), and high-risk (>20) groups had a 5.18%, 10%, and 28% risk of one-year mortality ( P < .001), respectively. Both intermediate-risk (OR = 2.46, 95% confidence interval [95% CI]: 1.93-3.15; P < .001) and high-risk (OR = 9.24, 95% CI: 6.92-12.35; P < .001) scores were associated with an increased risk of one-year mortality when compared to the low-risk group. CONCLUSIONS: The Children's Heart Assessment Tool for Transplantation score represents a pediatric-specific, recipient-based system to predict one-year mortality after HTx. Its use could assist providers in identification of patients at highest risk of poor outcomes and may aid in pretransplant optimization of these children.

Five-Year Mortality Hazard Is Reduced In Chronic Obstructive Pulmonary Disease Patients Receiving Double- versus Single-Lung Transplants.

BACKGROUND: Previous studies suggest double-lung transplant (DLT) may be associated with superior survival compared to single-lung transplantation (SLT) in chronic obstructive pulmonary disease (COPD) recipients. The purpose of this study was to compare survival in patients with COPD undergoing DLT versus SLT since the inception of the lung allocation score. METHODS: We used the United Network for Organ Sharing database to retrospectively identify adult patients with COPD who underwent isolated lung transplantation from 5/4/2005-12/31/2014. We then separated patients into DLT versus SLT. Short-term (1 y) and long-term survival (5 y) were compared between DLT and SLT cohorts by the method of Kaplan-Meier, and Cox proportional hazards modeling was used to adjust for case mix. RESULTS: Four thousand eight hundred thirty-two COPD patients were listed, and 3554 underwent lung transplantation over the study period, including 1358 SLTs (38%) and 2196 DLTs (62%). Survival 1 y after listing was 93% for those remaining wait listed (n = 1892) versus 91% for SLT (n = 1093) versus 89% for DLT (n = 1847) (log-rank P < 0.01). Survival at 1 y after transplant was 88% for both SLT and DLT groups (log-rank P = 0.93); however, 5-y survival was significantly lower after SLT (51% versus 59%, log-rank P < 0.01). After risk adjustment, hazard for 1-y mortality after DLT was not significantly reduced compared to SLT (hazard ratio 0.89 [0.69-1.14], P = 0.36) but was significantly reduced 5 y after DLT (hazard ratio 0.88 [0.78-0.99], P = 0.04). CONCLUSIONS: In the largest survival analysis of COPD recipients since the inception of the lung allocation score, the hazard for 5-y mortality was significantly reduced in recipients who underwent DLT as compared to SLT.

Surgical Closure of Patent Ductus Arteriosus in Premature Neonates Weighing Less Than 1,000 grams: Contemporary Outcomes.

OBJECTIVE: The safety of surgical closure of patent ductus arteriosus (PDA) in very low birth weight premature neonates has been questioned because of associated morbidities. However, these studies are vulnerable to significant bias as surgical ligation has historically been utilized as "rescue" therapy. The objective of this study was to review our institutions' outcomes of surgical PDA ligation. METHODS: All neonates with operative weight of ≤1.00 kg undergoing surgical PDA ligation from 2003 to 2015 were analyzed. Records were queried to identify surgical complications, perioperative morbidity, and mortality. Outcomes included pre- and postoperative ventilator requirements, pre- and postoperative inotropic support, acute kidney injury, surgical complications, and 30-day mortality. RESULTS: One hundred sixty-six preterm neonates underwent surgical ligation. One hundred twenty-one (70.3%) had failed indomethacin closure. One hundred sixty-four (98.8%) patients required mechanical ventilation prior to surgery. At 17 postoperative days, freedom from the ventilator reached 50%. Of 109 (66.4%) patients requiring prolonged preoperative inotropic support, 59 (54.1%) were liberated from inotropes by postoperative day 1. Surgical morbidity was encountered in four neonates (2.4%): two (1.2%) patients had a postoperative pneumothorax requiring tube thoracostomy, one (0.6%) patient had a recurrent laryngeal nerve injury, and one (0.6%) patient had significant intraoperative bleeding. The 30-day all-cause mortality was 1.8% (n = 3); no deaths occurred intraoperatively. CONCLUSION: In this retrospective investigation, surgical PDA closure was associated with low 30-day mortality and minimal morbidity and resulted in rapid discontinuation of inotropic support and weaning from mechanical ventilation. Given the safety of this intervention, surgical PDA ligation merits consideration in the management strategy of the preterm neonate with a PDA.

Correlating Oxygen Delivery During Cardiopulmonary Bypass With the Neurologic Injury Biomarker Ubiquitin C-Terminal Hydrolase L1 (UCH-L1).

OBJECTIVE: The authors sought to assess the relationship between low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) and a neuron-specific biomarker of neurologic injury, ubiquitin C-terminal hydrolase L1 (UCH-L1). DESIGN: Retrospective analysis of patient charts and prospectively collected blood samples. SETTING: University-affiliated tertiary care hospital. PARTICIPANTS: Adult patients undergoing cardiac surgery on CPB. INTERVENTIONS: Serum UCH-L1 levels were drawn at baseline and 6 and 24 hours after CPB cessation. DO2 was computed from perfusion records, with area-under-the-curve (AUC) computations performed to account for distance of DO2 excursions below predefined DO2 thresholds and the amount of time spent below them. Strokes were defined radiographically using computed tomography and magnetic resonance imaging. MEASUREMENTS AND MAIN RESULTS: Forty-three adults were included (median age 65 y, interquartile range 59-72). Three patients experienced strokes (imaged at 2, 7, and 8 d postoperatively). Most patients underwent isolated coronary artery bypass grafting (41%, 18 patients) or isolated aortic valve replacement (30%, 13). Median UCH-L1 levels differed from baseline to 6 and 24 hours after CPB (40, 232, and 166 pg/mL, respectively; p < 0.001). On multivariable linear regression analysis controlling for baseline and surgical variables, only DO2 AUC <225 was significantly associated with 6-hour UCH-L1 levels (p = 0.001), whereas only DO2 AUC <300 was significantly associated with 24- hour levels (p < 0.001). The 3 patients who experienced radiographic strokes had nonsignificantly elevated 24-hour UCH-L1 levels compared with control patients (585 v 151 pg/mL, p = 0.11). CONCLUSIONS: This is the first study to demonstrate an independent association between DO2 during CPB and elevations of a brain injury biomarker; additional study is needed to clarify the clinical significance of these results.