Blood flow assessment technology in aortic surgery: a narrative review.

Background and Objective: Blood flow assessment is an emerging technique that allows for assessment of hemodynamics in the heart and blood vessels. Recent advances in cardiovascular imaging technologies have made it possible for this technique to be more accessible to clinicians and researchers. Blood flow assessment typically refers to two techniques: measurement-based flow visualization using echocardiography or four-dimensional flow magnetic resonance imaging (4D flow MRI), and computer-based flow simulation based on computational fluid dynamics modeling. Using these methods, blood flow patterns can be visualized and quantitative measurements of mechanical stress on the walls of the ventricles and blood vessels, most notably the aorta, can be made. Thus, blood flow assessment has been enhancing the understanding of cardiac and aortic diseases; however, its introduction to clinical practice has been negligible yet. In this article, we aim to discuss the clinical applications and future directions of blood flow assessment in aortic surgery. We then provide our unique perspective on the technique's translational impact on the surgical management of aortic disease. Methods: Articles from the PubMed database and Google Scholar regarding blood flow assessment in aortic surgery were reviewed. For the initial search, articles published between 2013 and 2023 were prioritized, including original articles, clinical trials, case reports, and reviews. Following the initial search, additional articles were considered based on manual searches of the references from the retrieved literature. Key Content and Findings: In aortic root pathology and ascending aortic aneurysms, blood flow assessment can elucidate postoperative hemodynamic changes after surgical reconfiguration of the aortic valve complex or ascending aorta. In cases of aortic dissection, analysis of blood flow can predict future aortic dilatation. For complicated congenital aortic anomalies, surgeons may use preoperative imaging to perform "virtual surgery", in which blood flow assessment can predict postoperative hemodynamics for different surgical reconstructions and assist in procedural planning even before entering the operating room. Conclusions: Blood flow assessment and computational modeling can evaluate hemodynamics and flow patterns by visualizing blood flow and calculating biomechanical forces in patients with aortic disease. We anticipate that blood flow assessment will become an essential tool in the treatment planning and understanding of the progression of aortic disease.

Long-term outcomes after aortic root replacement for bicuspid aortic valve-associated aneurysm.

OBJECTIVE: Patients with congenital bicuspid aortic valve often require root replacement. This study aims to describe their long-term rates of mortality and reoperation. METHODS: This is a multicenter retrospective study of 747 patients with bicuspid aortic valve who underwent aortic root replacement for aortic aneurysm between 2004 and 2020. Cumulative incidence curves for aortic valve and aortic reoperations were graphed. A Kaplan-Meier survival curve for the patient cohort was created alongside an age- and sex-matched curve for the US population. Multivariable Cox regression was used to determine characteristics associated with long-term mortality. RESULTS: The median age of our cohort was 54 [43-64] years old, and 101 (13.5%) patients were female. In patients with bicuspid aortic valve dysfunction, 274 (36.7%) had aortic insufficiency, 187 (25.0%) had aortic stenosis, and 142 (19.0%) had both. In-hospital mortality occurred in 10 (1.3%) patients. There were 56 aortic valve reoperations and 19 aortic reoperations, with a combined cumulative incidence of 35% (95% confidence interval [CI], 23%-46%) at 15 years. In addition, there was comparable survival between the patient cohort and the age- and sex-matched US population. Age (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06), concomitant CABG (HR, 2.28; 95% CI, 1.29-4.04), and bypass time (HR, 1.01; 95% CI, 1.00-1.01) were associated with increased mortality. CONCLUSIONS: Patients who undergo aortic root replacement with bicuspid aortic valve have an increased rate of aortic reoperation (35%; 95% CI, 23%-46%) while their survival appears to be comparable to the general US population (79%; 95% CI, 73%-87%) at 15 years.

Utility of structured follow-up imaging after aortic surgery.

BACKGROUND: Although postoperative follow-up after aortic surgery is recommended by guidelines, its clinical utility is not well documented. We hypothesized that structured follow-up imaging by an aortic program would improve outcomes. We then documented radiologic findings on asymptomatic postoperative imaging. METHODS: All patients who survived to discharge after open thoracic aortic surgery between January 2017 and July 2021 were included, excluding endocarditis. Patients who followed at our center and received scheduled imaging were compared with patients who did not. Survival was analyzed by the method of Kaplan-Meier, and reintervention was assessed using the Fine-Gray subhazard function. Routine imaging was reviewed for aortic growth, pseudoaneurysm, and perigraft density. RESULTS: After aortic surgery, the cumulative incidence of follow-up was 38.6% at 3 years postoperatively. Patients with follow-up were more likely to have a dissection and fewer comorbidities but were similar in regards to socioeconomic factors and distance to hospital. After matching and accounting for immortal time bias, patients with follow-up had a greater reintervention rate (26.0% vs 9.0%) with similar survival (98.7% vs 95.2%, P = .110) at 4 years. The cumulative incidence of pseudoaneurysm, significant perigraft density, and growth ≥3 mm/year on routine imaging was 49.7% at 3 years. CONCLUSIONS: Implementation of structured follow-up imaging by an aortic program resulted in low clinical compliance. Follow-up was associated with increased rates of aortic reintervention. Clinically relevant radiologic findings were common on asymptomatic imaging and increased throughout 5-year follow-up rather than plateauing in the early postoperative period.

Significance of isolated postoperative atrial fibrillation in thoracic aortic aneurysm repair.

OBJECTIVE: Although postoperative atrial fibrillation has been shown to be associated with worse survival after thoracic aortic surgery, its effect on outcomes independently from other postoperative complications is not well understood. METHODS: This is a single-center retrospective study of patients who underwent open thoracic aortic aneurysm repair between March 2005 and March 2021. Postoperative atrial fibrillation was defined as new-onset atrial fibrillation that developed during the index hospital stay. Patients with preoperative atrial fibrillation were excluded. Postoperative major complications included reoperation for bleeding, respiratory failure, acute renal failure, and stroke. Variables associated with postoperative atrial fibrillation were analyzed with multivariable regression. Survival of patients without major complications was compared between patients without atrial fibrillation and patients with postoperative atrial fibrillation after propensity score matching for baseline and intraoperative characteristics. RESULTS: Of 1454 patients, 520 (35.8%) were observed to have postoperative atrial fibrillation. Patients with postoperative atrial fibrillation had a higher rate of postoperative major complications than those without atrial fibrillation (20.2% vs 12.2%, P < .001). Ten-year survival was 82.0% in patients with postoperative atrial fibrillation and 87.0% in patients without atrial fibrillation (P = .008). In the cohort of patients without complications, 10-year survival was similar between patients with and without postoperative atrial fibrillation after propensity score matching (83.6% vs 83.8%, P = .75). CONCLUSIONS: Postoperative atrial fibrillation is common after open proximal thoracic aortic aneurysm repair. Although development of major postoperative complications is associated with postoperative atrial fibrillation and decreased long-term survival, isolated postoperative atrial fibrillation does not appear to influence long-term survival.

Long-term autograft dilation and durability after the Ross procedure are similar in infants, children, and adolescents with primary aortic stenosis.

BACKGROUND: Autograft durability and remodeling are thought to be superior in younger pediatric patients after the Ross operation. We sought to delineate the fate of autografts across the pediatric age spectrum in patients with primary aortic stenosis (AS). METHODS: We retrospectively reviewed patients age ≤18 years with primary AS who underwent the Ross operation between 1993 and 2020. Patients were categorized by age. The primary endpoint was autograft dimensional change, and secondary endpoints were severe neo-aortic insufficiency (AI) and autograft reintervention. RESULTS: A total of 119 patients underwent the Ross operation, including 37 (31.1%) in group I (age <18 months), 24 (20.2%) in group II (age 18 months-8 years), and 58 (48.7%) in group III (age 8-18 years). All groups exhibited similar annular growth rates within the first 5 postoperative years, followed by a collective decrease in annulus growth rates from year 5 to year 10. Group III experienced rapid sinus dilation in the first 5 years, followed by stabilization of the sinus z-score from year 5 to year 10, whereas groups I and II demonstrated stable sinus z-scores over 10 years. There were 4 early deaths (3.4%) and 2 late deaths (1.7%) at a median follow-up of 8.1 years (range, 0.01-26.3 years). At 15 years, the incidences of severe neo-AI (0.0 ± 0.0% vs 0.0 ± 0.0% vs 3.9 ± 3.9%; P = .52) and autograft reintervention (8.4 ± 6.0% vs 0.0 ± 0.0% vs 2.4 ± 2.4%; P = .47) were similar in the 3 groups. CONCLUSIONS: Age at the time of Ross operation for primary AS does not influence long-term autograft remodeling or durability. Other physiologic or technical factors are likely greater determinants of autograft fate.

Reintervention after valve-sparing aortic root replacement: A comprehensive analysis of 781 David V procedures.

OBJECTIVE: Studies of reintervention after valve-sparing aortic root replacement (VSRR) are limited by sample size and failure to evaluate all types of reinterventions, including distal aorta and transcatheter interventions. In this report, reintervention after VSRR using a large patient cohort was comprehensively analyzed. METHODS: In a series involving 2 academic aortic centers, 781 consecutive patients from 2005 to 2020 undergoing David V VSRR for aortic aneurysm (91%) or dissection (9%) were included. Median age was 50 years, and 23% had a bicuspid aortic valve (AV). Median follow-up was 7.0 years. Open or transcatheter reintervention on the AV, proximal, or distal thoracic aorta was identified. Cumulative incidence was calculated, and subdistribution hazard models identified factors associated with reintervention. Time-dependent incidence of reintervention was plotted using risk-hazard functions. RESULTS: Sixty-eight reinterventions (57 open, 11 transcatheter) were performed. Reinterventions were divided by indication into degenerative AV (n = 26, including 1 transcatheter aortic valve replacement), endocarditis (n = 11), proximal aorta (n = 8), and distal aorta (n = 23, including 10 thoracic endovascular aortic repairs). Risk of reintervention for endocarditis peaked 1 to 3 years after VSRR, whereas other indications had stable, low rates of occurrence throughout the follow-up period. The cumulative incidence of reintervention was 12.5% whereas the cumulative incidence of AV reintervention was 7.0% at 10 years and was associated with residual postoperative aortic insufficiency. In-hospital mortality after reintervention was 3%. CONCLUSIONS: Reintervention rates after VSRR are relatively low in long-term follow-up and can be performed with acceptable operative risk. The majority of reinterventions are performed for indications other than AV degeneration, with the timing of reintervention varying by the specific clinical indication.

A Knife Penetrating the Right Ventricle, Interventricular Septum, and 2 Valves: A Case Report.

Penetrating chest trauma may result in significant intracardiac injury. A traumatic ventricular septal defect is a rare complication that requires surgical management, particularly if heart failure ensues. We report a case of delayed repair of an outlet-type ventricular septal defect and perforation of the aortic and pulmonary valve leaflets following a stab wound. This report highlights diagnostic and surgical considerations and also presents an opportunity to review the conotruncal anatomy, which may be relatively unfamiliar to many adult cardiac surgeons.

Central aortic versus axillary artery cannulation for aortic arch surgery.

Objective: Central aortic cannulation for aortic arch surgery has become more popular over the last decade; however, evidence comparing it with axillary artery cannulation remains equivocal. This study compares outcomes of patients who underwent axillary artery and central aortic cannulation for cardiopulmonary bypass during arch surgery. Methods: A retrospective review of 764 patients who underwent aortic arch surgery at our institution between 2005 and 2020 was performed. The primary outcome was failure to achieve uneventful recovery, defined as having experienced at least 1 of the following: in-hospital mortality, stroke, transient ischemic attack, bleeding requiring reoperation, prolonged ventilation, renal failure, mediastinitis, surgical site infection, and pacemaker or implantable cardiac defibrillator implantation. Propensity score matching was used to account for baseline differences across groups. A subgroup analysis of patients undergoing surgery for aneurysmal disease was performed. Results: Before matching, the aorta group had more urgent or emergency operations (P = .039), fewer root replacements (P < .001), and more aortic valve replacements (P < .001). After successful matching, there was no difference between the axillary and aorta groups in failure to achieve uneventful recovery, 33% versus 35% (P = .766), in-hospital mortality, 5.3% versus 5.3% (P = 1), or stroke, 8.3% versus 5.3% (P = .264). There were more surgical site infections in the axillary group, 4.8% versus 0.4% (P = .008). Similar results were seen in the aneurysm cohort with no differences in postoperative outcomes between groups. Conclusions: Aortic cannulation has a safety profile similar to that of axillary arterial cannulation in aortic arch surgery.

Valve-sparing aortic root replacement versus composite valve graft with bioprosthesis in patients under age 50.

BACKGROUND: Although the unique risks of implanting a prosthetic valve after aortic valve (AV) surgery in young patients are well established, studies of aortic root replacement (ARR) are lacking. We investigated long-term outcomes after valve-sparing root replacement (VSRR) versus the use of a composite valve graft with bioprosthesis (b-CVG) in patients age <50 years. METHODS: A total of 543 patients age <50 years underwent VSRR (n = 335) or b-CVG (n = 208) between 2004 and 2021 from 2 aortic centers, excluding those with dissection or endocarditis. Endpoints included mortality over time, reoperative aortic valve replacement (AVR), and development of greater than moderate aortic insufficiency (AI) or aortic stenosis (AS). Fine and Gray competing risk regression was used to compare the risk of reintervention. Propensity score matching (PSM) balanced patient comorbidities, and landmark analysis isolated outcomes beginning 4 years postoperatively. RESULTS: Compared with VSRR, b-CVG was associated with lower 12-year survival (88.6% vs 92.9%; P = .036) and a higher rate of AV reintervention (37.6% vs 12.0%; P = .018). After PSM, survival was similar in the 2 arms (93.4% for b-CVG vs 93.0% for VSRR; P = .72). However, both Fine and Gray multivariable risk regression and PSM showed that b-CVG was independently associated with AV reintervention at >4 years postoperatively (Fine and Gray: subdistribution hazard ratio, 4.3 [95% confidence interval, 1.8-10.2; P = .001]; PSM: 35.7% for b-CVG versus 14.3% for VSRR; P = .024]). PSM rates of greater than moderate AI/AS at 10 years were more than 2-fold greater in the b-CVG arm compared with the VSRR arm (37.1% vs 15.9%; P = .571). CONCLUSIONS: b-CVG in young patients is associated with early valvular degeneration, with increasing rates of reoperative AVR occurring even within 10 years. In contrast, VSRR is durable with excellent survival. In eligible young patients, every effort should be made to retain the native AV.

Bicuspid aortic valve durability with valve-sparing aortic root replacement: comparison to tricuspid valve.

OBJECTIVES: Outcomes beyond 10 years for David V valve-sparing aortic root replacement (VSARR) in bicuspid aortic valve (BAV) patients have yet to be explored. We investigated long-term outcomes after BAV VSARR compared to VSARR for tricuspid aortic valve (TAV) patients. METHODS: A total of 677 patients with BAV (n = 171) and TAV (n = 506) underwent VSARR between 2005 and 2020 from 2 aortic centres, excluding those with dissection, endocarditis, stenosis or prior aortic valve (AV) surgery. Multivariable Cox regression compared adjusted survival over a 12-year period. Fine and Gray competing risk regression compared risk and cumulative incidence of reoperation/reintervention. Propensity score matching created balanced groups, and landmark analysis isolated outcomes beginning 4 years postoperatively. Finally, longitudinal mixed modelling assessed AV deterioration on echocardiogram. RESULTS: No difference was observed in 12-year survival of BAV versus TAV (propensity score matching 92.0% vs 89.9%, P = 0.97; multivariable hazard ratio 0.76, 95% confidence interval 0.34-1.69, P = 0.51). Adjusted 12-year cumulative incidence and risk of AV and/or proximal aorta reoperation/reintervention were not observed to be different (15.7% BAV vs 5.7% TAV, P = 0.37; subdistribution hazard ratio 1.54, 95% confidence interval 0.60-3.94, P = 0.36); however, landmark analysis showed increased incidence of late reoperation/reintervention in BAV versus TAV (11.7% vs 0.0%, P = 0.04). BAV was not associated with AV deterioration over time (BAV coefficient ± standard error: 0 ± 0.30, P = 1). CONCLUSIONS: VSARR for BAV patients has excellent 12-year survival and low reoperation/reintervention rates, which were not observed to be different from TAV patients. However, higher incidence of reoperation/reintervention was observed in the late years after BAV VSARR. Our study provides key information for surgical consultation of patients with bicuspid aortopathy.

Long-term outcomes of surgery for obstructive hypertrophic cardiomyopathy in a pediatric cohort.

Background: Septal reduction therapy via septal myectomy or a modified Konno procedure is the mainstay of therapy for drug-refractory obstructive hypertrophic cardiomyopathy (HCM), although outcomes data on septal myectomy in pediatric patients are limited. We evaluated long-term outcomes following surgery for obstructive HCM in a pediatric cohort. Methods: We retrospectively reviewed patients age ≤18 years with obstructive HCM who underwent a left and/or right ventricular septal myectomy at our institution between 1992 and 2022. Primary endpoints were transplantation-free survival, freedom from HCM-related death, and cumulative probability of HCM-related reintervention. We further evaluated outcomes in patients with and without Noonan syndrome or other RASopathies. Results: Thirty-seven patients (median age, 7.4 years; interquartile range [IQR], 3.4-12.9 years) underwent transaortic septal myectomy. A combined modified Konno procedure was performed in 5 patients (13.9%). Sixteen patients (43.2%) had a RASopathy. A concomitant right ventricular outflow tract resection was performed in 9 patients (24.3%). There was 1 (2.7%) in-hospital death and 4 late deaths at a median follow-up of 10.5 years (IQR, 0.1-29.3). Twenty-year transplant-free survival and freedom from HCM-related death were 80.6% (95% confidence interval [CI], 64.2%-100%) and 87.1% (95% CI, 71.8%-100%), respectively. The 20-year cumulative probability of HCM-related reintervention was 34.2% (95% CI, 12.8%-57.1%). Seven patients required a septal reintervention. There was no difference in any primary endpoints between patients with and without a RASopathy. Conclusions: Surgery for obstructive HCM, including septal myectomy with and without a modified Konno procedure, may be performed with low morbidity and good long-term outcomes in pediatric patients. Recurrent outflow tract obstruction is not uncommon.

A novel dosing strategy of del Nido cardioplegia in aortic surgery.

Objective: While del Nido (DN) cardioplegia is increasingly used in cardiac surgery, knowledge is limited in its safety profile for operations with prolonged crossclamp time (CCT). We have introduced a unique redosing strategy for aortic surgery: all operations use DN with a 1000-mL initiation dose (750 mL antegrade, 250 mL retrograde) composed of 1:4 blood:DN crystalloid. At 90 minutes CCT and every 30 minutes thereafter, a 250-mL dose was introduced retrograde in a 4:1 ("reverse") ratio. Additionally, at 90 minutes CCT and every 90 minutes thereafter, a reverse ratio dose of approximately 100 to 400 mL was introduced via the right coronary artery. Here, we analyze the outcomes of our unique redosing strategy used. Methods: In total, 440 patients underwent aortic surgery between January 2015 and March 2021 under a single surgeon and received DN. Our primary end points were change in left ventricular ejection fraction (LVEF) and right ventricular systolic function based on echocardiography. Multivariable linear regression was used to analyze the relationship between CCT and outcomes. Results: The median was 61 years old (interquartile range, 51-69), and 23% were female. Indication was aneurysm in 65% and dissection in 24%. Median preoperative LVEF was 60% (55%-62%). Median CCT and cardiopulmonary bypass times were 135 minutes (93-165 minutes) and 181 minutes (142-218 minutes), respectively. In-hospital mortality occurred in 3%. Multivariable linear regression showed CCT was not associated with change in LVEF or change in right ventricular systolic function. Conclusions: Our unique method of redosing DN cardioplegia appears to provide safe and effective myocardial protection for aortic surgery.

Photoenzymatic Hydrogenation of Heteroaromatic Olefins Using 'Ene'-Reductases with Photoredox Catalysts.

Flavin-dependent 'ene'-reductases (EREDs) are highly selective catalysts for the asymmetric reduction of activated alkenes. This function is, however, limited to enones, enoates, and nitroalkenes using the native hydride transfer mechanism. Here we demonstrate that EREDs can reduce vinyl pyridines when irradiated with visible light in the presence of a photoredox catalyst. Experimental evidence suggests the reaction proceeds via a radical mechanism where the vinyl pyridine is reduced to the corresponding neutral benzylic radical in solution. DFT calculations reveal this radical to be "dynamically stable", suggesting it is sufficiently long-lived to diffuse into the enzyme active site for stereoselective hydrogen atom transfer. This reduction mechanism is distinct from the native one, highlighting the opportunity to expand the synthetic capabilities of existing enzyme platforms by exploiting new mechanistic models.

Photoenzymatic Catalysis Enables Radical-Mediated Ketone Reduction in Ene-Reductases.

Flavin-dependent ene-reductases (EREDs) are known to stereoselectively reduce activated alkenes, but are inactive toward carbonyls. Demonstrated here is that in the presence of photoredox catalysts, these enzymes will reduce aromatic ketones. Mechanistic experiments suggest this reaction proceeds through ketyl radical formation, a reaction pathway that is distinct from the native hydride-transfer mechanism. Furthermore, this reactivity is accessible without modification of either the enzyme or cofactors, allowing both native and non-natural mechanisms to occur simultaneously. Based on control experiments, we hypothesize that binding to the enzyme active site attenuates the reduction potential of the substrate, enabling single-electron reduction. This reactivity highlights opportunities to access new catalytic manifolds by merging photoredox catalysis with biocatalysis.