Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

BACKGROUND: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina. METHODS: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery. RESULTS: There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1-139.5], +84.5 [95% CI, 34.1-134.9], and +115.5 [95% CI, 59.1-171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, -3.1% to 23.5%), 14.3% (95% CI, 2.8%-25.7%), and 10.2% (95% CI, -0.8% to -21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1-11.3), 6.6 (95% CI, 3.5-9.7), and 8.8 (4.6-13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months. CONCLUSIONS: XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04125732.

Dissemination and implementation analysis of the Ross procedure in adults: time to update the guidelines?

Background: The science of dissemination and implementation (D&I) aims to improve the quality and effectiveness of care by addressing the challenges of incorporating research and evidence-based practice into routine clinical practice. This lens of D&I has challenged the interpretation and incorporation of data, noting that failure of a given therapy may not reflect lack of efficacy, but instead reflect an imperfect implementation. The aim of this manuscript is to review the influence of the Ross procedure's historical context on its D&I. Methods: A contextual baseline of the Ross procedure was defined from the procedure's original description in the literature to major publications since the 2017 valvular heart disease guidelines. D&I evaluation was conducted using the Consolidated Framework for Implementation Research (CFIR), using constructs from each of the five respective domains to define the main determinants. Results: Each of the five CFIR domains appears to be correlated with a factor influencing the Ross procedure's varied history of enthusiasm and acceptance. The complex nature of Ross required adaptation for optimization, with a strong correlation of center volume on outcomes that were not considered in non-contemporary studies. Outcomes later published from those studies influenced social and cultural contexts within the aortic surgery community, and led to further organizational uncertainty, resulting in slow guideline incorporation. Conclusions: The D&I of the Ross procedure was a result of inadequate appreciation of technical complexity, effect of patient selection, and complex aortic surgery experience, resulting in dismissal of an efficacious procedure due to a misunderstanding of effectiveness.

Natural history of the distal aorta following elective root replacement in patients with Marfan syndrome.

OBJECTIVE: It is unclear if the addition of a prophylactic arch operation is beneficial at the time of root replacement in patients with Marfan syndrome (MFS). This project aims to understand the fate of the distal aorta following elective root replacement in patients with MFS. METHODS: Between 2000 and 2019, 124 adult patients with MFS were identified as having undergone elective aortic root replacement with a clamped distal aortic anastomosis during their lifetime. Serial axial imaging was analyzed. The primary outcome was a composite of subsequent type B aortic dissection (TBAD), aneurysmal degeneration (>4 cm), and aortic reintervention. Secondary outcomes included subsequent TBAD and mortality. RESULTS: Mean age at root replacement was 33.3 years. Median follow-up was 11.3 years. Thirty-one patients (25%) experienced the primary outcome, with no survival difference (P = .9). The crossclamp and aortic cannulation sites were stable (growth rate, 0.33 mm/year), and 2 patients (1.6%) required reintervention there. Twenty-three patients (19.8%) experienced subsequent TBAD. Patients with TBAD had a higher rate of distal degeneration (P < .001), but no significant change in survival (P = .2). Preoperative hypertension (odds ratio, 3.96; P < .05) and younger age at root replacement (odds ratio, 1.05; P < .05) increased the risk of TBAD, based on regression analysis. CONCLUSIONS: The distal aorta (including the clamp and cannulation site) overall appears stable in patients with MFS following elective root replacement without prophylactic arch operation. Development of TBAD seems to be the primary driver of distal degeneration. Factors associated with TBAD development included hypertension, underscoring the importance of strict blood pressure control in these patients.

A multidisciplinary multistage complete mega aorta replacement and utilization of extracorporeal membrane oxygenation in thoracoabdominal aneurysm repair.

A 49-year-old woman underwent a 11-month multistage complete replacement of a mega aorta. Replacement stages included ascending aorta and arch replacement in conjunction with a frozen elephant trunk thoracic endovascular aortic repair, extension of thoracic endovascular aortic repair to zone 5, and open repair of the thoracoabdominal aneurysm with the use of venoarterial extracorporeal membrane oxygenation for circulatory support. This case illustrates the complexity of repairing a mega aorta, the multidisciplinary care and staging needed for repair, and the use of peripheral venoarterial extracorporeal membrane oxygenation for circulatory perfusion during thoracoabdominal aneurysm repair.

Operative repair of right intrathoracic subclavian artery aneurysms in patients with genetic arteriopathy.

True intrathoracic subclavian artery aneurysms (SCAAs) are rare and have various etiologies. Right intrathoracic SCAAs pose specific anatomic challenges to repair. We present three different operative approaches, open, endovascular, and hybrid repair, for the repair of a right intrathoracic SCAA in three patients with genetic arteriopathy: Marfan syndrome, vascular Ehlers-Danlos syndrome, and unspecified Ehlers-Danlos syndrome, respectively. These cases demonstrate an individualized operative approach based on the genetic diagnosis for each patient presenting with a right intrathoracic SCAA.

Does valve size impact hemodynamic, left ventricular mass regression, and prosthetic valve deterioration with a sutureless aortic valve?

OBJECTIVE: To assess the mid-term clinical outcomes, hemodynamics, left ventricular (LV) mass regression, and structural valve deterioration (SVD) in patients implanted with the Perceval aortic sutureless valve across valve sizes. METHODS: Data were obtained from a multicenter European trial and a US Investigational Device Exemption trial. Echocardiography data were analyzed by an echocardiography core lab. A mixed-effects regression model was used to assess relationships between hemodynamic outcomes, time from the procedure, and valve sizes. The Valve Academic Research Consortium (VARC)-3 definition for bioprosthetic valve failure was applied. RESULTS: A Perceval sutureless valve was implanted in 970 patients. The median patient age was 77.8 years, 57.2% were female, the median Society of Thoracic Surgeons predicated risk of mortality was 3.3% (range, 2.1%-6.2%), and 33.4% had a concomitant procedure. The median clinical follow-up was 45.7 months (range, 28.2-76.1 months). Small and medium valves were implanted more commonly in women than in men (16.9% vs 1.9% for small and 55.1% vs 19.5% for medium; P < .001). The mean aortic valve gradients decreased significantly postimplantation and remained stable across all valve sizes throughout the follow-up period. All patients were free from severe patient-prosthesis mismatch (with an effective orifice area/m2 of >0.8). Significant LV mass regression was documented regardless valve sizes, plateaued at -9.1% at 5 years. Freedom from SVD and reintervention were 95.2% and 96.3%, respectively, at 5 years and were independent of implanted valve size (P = .22). The VARC-3 stage 3 bioprosthetic valve failure rate was low, 2.8% at 5 years. CONCLUSIONS: The Perceval valve demonstrated low and stable mean gradients, significant LV mass regression, and low SVD and reintervention rates across all valve sizes.

Use of a sutureless aortic valve in reoperative aortic valve replacement.

Objectives: Management of degenerated bioprosthetic aortic valves remains a challenge. Valve-in-valve transcatheter aortic valve replacement (AVR) has limited utility in the presence of small annuli/prosthetic valves. Sutureless valves may offer an advantage over traditional redo AVR by maximizing effective orifice area due to their unique design as well as ease of implant. Methods: Twenty-two patients undergoing redo AVR received a sutureless valve in our institution over the past 5 years. All patients were determined to be poor candidates for valve-in-valve transcatheter AVR due to a combination of small annulus size, low coronary heights, and/or underlying valve characteristics (ie, mechanical valves). Results: Median time from implant to redo AVR was 8 years. One patient died within 30 days. In the 13 patients who had a 21 mm or smaller valve explanted, 5 small, 7 medium, and 1 large Perceval valves were implanted (all with larger internal diameters than the explanted valve). The average postoperative gradient of the cohort valves was 14.8 mm Hg compared with 38.8 mm Hg preoperatively. Conclusions: In addition to their ease of use and rapid deployment, sutureless bioprosthetic aortic valves offer significant physiological advantages in patients with degenerated prosthetic aortic valves and small anatomical annuli. It can also simplify the surgical approach to redo AVR following a Bentall procedure. If long-term durability is confirmed, sutureless valves should be considered in a broader population of patients for both redo and primary aortic valve replacement surgery.

Aortic valve repair for isolated right coronary leaflet prolapse.

Objectives: Isolated right coronary leaflet prolapse is a common cause of nonaneurysmal aortic insufficiency, but can rarely occur in patients with proximal aortic aneurysms. Standardized techniques for routine autologous repair of this disorder are presented. Methods: Most aortic valve leaflet prolapse is isolated to the right coronary leaflet, with hypertension and annular dilatation being contributory. Echocardiographically, a posteriorly eccentric aortic insufficiency jet together with "fracture" of the right leaflet tip are diagnostic. Primary repair includes internal geometric ring annuloplasty to downsize and reshape the annulus, together with central plication of the prolapsing leaflet. Thickened, scarred, or retracted noduli are released using an ultrasonic aspirator. The goal is to achieve equivalent coaptation heights of ≥8 mm for all 3 leaflets. Results: Three videos of 6 cases are provided to illustrate these techniques. In the first, 3 patients are shown with classic isolated right leaflet prolapse. In the second and third videos, alternative pathologies are presented for contrast. Applying the reconstructive approaches of geometric ring annuloplasty, leaflet plication, and ultrasonic nodular release, excellent early and late repair outcomes are obtainable in most patients. Conclusions: The combination of aortic ring annuloplasty, central leaflet plication, and ultrasonic nodular release allows routine and standardized repair of right coronary leaflet prolapse, either isolated or concomitant with aneurysm surgery.

Implementation of telemedicine in the care of patients with aortic dissection.

Telemedicine uses telephone-based or any form of digital communication for remote clinical services. It has been a field of interest for the last century, with broader implementation of telemedicine technologies during the last 25 years. The COVID-19 pandemic was an impetus for the adoption of these technologies globally across all health care services, including patient care, surgical practice, and workflow. As part of the patient engagement work in the Aortic Dissection Collaborative, this topic was identified as an important patient-centered research topic. Telemedicine has been adopted increasingly in vascular surgery; however, there is little evidence on appropriate use of these technologies pertaining to treating patients with aortic dissection or aortopathy in general. This landscape review summarizes the uses of telemedicine applications pre and post pandemic in medicine and vascular surgery, with a particular focus on uses in aortopathy. Using common resource databases, we identified articles related to the history of telemedicine, its current utilization, and application to vascular surgery and/or aortopathy. We briefly review the history of telemedicine and illustrate a range of applications in medicine before the pandemic, along with its rapid uptake globally during the COVID-19 pandemic. The enablers and barriers to using telemedicine are explored, although as a whole there is satisfaction with its integration among patients and providers. To address these, we offer recommendations to address future research as it pertains to telemedicine technologies in aortic dissection.

Is Porcine Small Intestinal Submucosal Extracellular Matrix (ECM) a Suitable Material for Right Ventricular Outflow Tract Reconstruction in Association With Pulmonary Valve Replacement?

Pulmonary valve replacement (PVR) with right ventricular outflow tract (RVOT) reconstruction is a common congenital cardiac operation. Porcine submucosal intestinal-derived extracellular matrix (ECM) patches have been used for RVOT reconstruction. We present 2 adult patients with Tetralogy of Fallot who underwent PVR with RVOT reconstruction utilizing ECM. Both cases required reoperation due to patch dehiscence causing a large paravalvular leak. One patient also had a pseudoaneurysm associated with ECM dehiscence. There may be a propensity for ECM dehiscence in this application and, based on these cases, we recommend avoidance of ECM in RVOT reconstruction with PVR. PVR patients repaired with ECM should be monitored for this complication.

Traumatic Suprahepatic inferior vena cava injury survival of a rare case.

Traumatic supra-hepatic inferior vena cava (IVC) injury is rare and nearly universally fatal. We report an excellent outcome from a case involving severe injury of the suprahepatic and intra-pericardial IVC utilizing emergency cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest. The goal of this case report is to outline key factors that facilitated the patient's survival of extensive IVC injury. We conclude that aggressive prehospital fluid resuscitation, facile transfer to the operating room, early detection of anatomy and pathology of the injury, an early decision to call for perfusion and cardiothoracic surgery, and prompt blood transfusion were the key factors that allowed for the patient to survive without deficits.

Aortic arch stenting: current strategies, new technologies and future directions.

Operating on the aortic arch is a formidable challenge. Open operations remain the gold standard, but despite improvement in technique and outcomes, they are still associated with significant morbidity and mortality. The last 20 years have seen a remarkable reduction in the operative morbidity associated with treatment of the descending thoracic aorta using thoracic endovascular aneurysm repair (TEVAR). To improve outcomes following arch repair, new TEVAR devices, including both single-branched and multibranched designs, have come to clinical trial. This review discusses the modern state of open and hybrid repairs while introducing the reader to technology for endovascular therapy of the aortic arch. We describe important anatomical and operative considerations for the devices. Given these nuances, we believe the future of the aortic arch to be patient-individualised hybrid repairs, involving both open and endovascular options with a multidisciplinary 'thoracic aorta team' at the helm.

Outcomes of Adults with Congenital Heart Disease Supported with Extracorporeal Life Support After Cardiac Surgery.

Patients with adult congenital heart disease (ACHD) who undergo cardiac surgery may require extracorporeal life support (ECLS) for cardiopulmonary support, but outcomes after ECLS support have not been well described. This study aimed to identify risk factors for ECLS mortality in this population. We identified 368 ACHD patients who received ECLS after cardiac surgery between 1994 and 2016 in the Extracorporeal Life Support Organization (ELSO) database, a multicenter international registry of ECLS centers. Risk factors for mortality were assessed using multivariate logistic regression. Overall mortality was 61%. In a multivariate model using precannulation characteristics, Fontan physiology (odds ratio [OR]: 5.7; 95% CI: 1.6-20.0), weight over 100 kg (OR: 2.6; 95% CI: 1.3-5.4), female gender (OR: 1.6; 95% CI: 1.001-2.6), delayed ECLS cannulation (OR: 2.0; 95% CI: 1.2-3.2), and neuromuscular blockade (OR: 1.9; 95% CI: 1.1-3.3) were associated with increased mortality. Adding postcannulation characteristics to the model, renal complications (OR: 3.0; 95% CI: 1.7-5.2), neurologic complications (OR, 4.7; 95% CI: 1.5-15.2), and pulmonary hemorrhage (OR: 6.4; 95% CI: 1.3-33.2) were associated with increased mortality, whereas Fontan physiology was no longer associated, suggesting the association of Fontan physiology with mortality may be mediated by complications. Fontan physiology was also a risk factor for neurologic complications (OR: 8.2; 95% CI: 3.3-20.9). Given the rapid increase in ECLS use, understanding risk factors for ACHD patients receiving ECLS after cardiac surgery will aid clinicians in decision-making and preoperative planning.