Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.

BACKGROUND: Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and a resulting lack of mechanistic understanding. Myocarditis is a major cause of sudden cardiac death in young adults, where current knowledge in the field is dominated by later disease phases and pathological immune responses. However, little is known regarding how infection can acutely induce an arrhythmogenic substrate before significant immune responses. Adenovirus is a leading cause of myocarditis, but due to species specificity, models of infection are lacking, and it is not understood how adenoviral infection may underlie sudden cardiac arrest. Mouse adenovirus type-3 was previously reported as cardiotropic, yet it has not been utilized to understand the mechanisms of cardiac infection and pathology. METHODS: We have developed mouse adenovirus type-3 infection as a model to investigate acute cardiac infection and molecular alterations to the infected heart before an appreciable immune response or gross cardiomyopathy. RESULTS: Optical mapping of infected hearts exposes decreases in conduction velocity concomitant with increased Cx43Ser368 phosphorylation, a residue known to regulate gap junction function. Hearts from animals harboring a phospho-null mutation at Cx43Ser368 are protected against mouse adenovirus type-3-induced conduction velocity slowing. Additional to gap junction alterations, patch clamping of mouse adenovirus type-3-infected adult mouse ventricular cardiomyocytes reveals prolonged action potential duration as a result of decreased IK1 and IKs current density. Turning to human systems, we find human adenovirus type-5 increases phosphorylation of Cx43Ser368 and disrupts synchrony in human induced pluripotent stem cell-derived cardiomyocytes, indicating common mechanisms with our mouse whole heart and adult cardiomyocyte data. CONCLUSIONS: Together, these findings demonstrate that adenoviral infection creates an arrhythmogenic substrate through direct targeting of gap junction and ion channel function in the heart. Such alterations are known to precipitate arrhythmias and likely contribute to sudden cardiac death in acutely infected patients.

Long-term outcomes of staged iliofemoral endoconduits prior to complex endovascular aortic aneurysm repair.

OBJECTIVE: Adverse iliofemoral anatomy may preclude complex endovascular aortic aneurysm repair (EVAR). In our practice, staged iliofemoral endoconduits (ECs) are planned prior to complex EVAR to improve vascular access and decrease operative time while allowing the stented vessel to heal. This study describes the long-term results of iliofemoral ECs prior to complex EVAR. METHODS: Between 2012 and 2023, 59 patients (44% male; median age, 75 ± 6 years) underwent ECs before complex EVAR using self-expanding covered stents (Viabahn). For common femoral artery (CFA) disease, ECs were delivered percutaneously from contralateral femoral access and extended into the CFA to preserve the future access site for stent graft delivery. Internal iliac artery patency was maintained when feasible. During complex EVAR, the EC extended into the CFA was directly accessed and sequentially dilated until it could accommodate the endograft. Technical success was defined as successful access, closure, and delivery of the endograft during complex EVAR. Endpoints were vascular injury or EC disruption, secondary interventions, and EC patency. RESULTS: Unilateral EC was performed in 45 patients (76%). ECs were extended into the CFA in 21 patients (35%). Median diameters of the native common iliac, external iliac, and CFA were 7 mm (interquartile range [IQR], 6-8 mm), 6 mm (IQR, 5-7 mm), and 6 mm (IQR, 6-7 mm), respectively. Internal iliac artery was inadvertently excluded in 10 patients (17%). Six patients (10%) had an intraoperative vascular injury during the EC procedure, and six patients (10%) had EC disruption during complex EVAR, including five EC collapses requiring re-stenting and one EC fracture requiring open cut-down and reconstruction with patch angioplasty. In 23 patients (39%), 22 Fr OD devices were used; 20 Fr were used in 22 patients (37%), and 18 Fr in 14 patients (24%). Technical success for accessing EC was 89%. There was no difference in major adverse events at 30 days between the iliac ECs and iliofemoral ECs. Primary patency by Kaplan-Meier estimates at 1, 3, and 5 years were 97.5%, 89%, and 82%, respectively. There was no difference in primary patency between iliac and iliofemoral ECs. Six secondary interventions (10%) were required. The mean follow-up was 34 ± 27 months; no limb loss or amputations occurred during the follow-up. CONCLUSIONS: ECs improve vascular access, and their use prior to complex EVAR is associated with low rates of vascular injury, high technical success, and optimal long-term patency. Complex EVAR procedures can be performed percutaneously by accessing the EC directly under ultrasound guidance and using sequential dilation to avoid EC disruption.

Impact of head and neck radiation on long-term outcomes after carotid revascularization.

OBJECTIVE: Radiation-induced carotid artery stenosis (RICS) is a well-described phenomenon seen after head and neck cancer radiation. Previously published literature suggests that, compared with atherosclerotic disease, RICS may result in worse long-term outcomes and early restenosis. This study aims to evaluate the effect of radiation on long-term outcomes after various carotid revascularization techniques using a multi-center registry database. METHODS: Patients in the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) registry for carotid artery intervention (carotid endarterectomy [CEA]; transfemoral carotid artery stenting [CAS]; transcarotid artery revascularization [TCAR]), who are 65 years or older were included in the study. VQI Vascular Implant Surveillance and Interventional Outcomes Network (VISION) Medicare-linked database was used to obtain long-term procedure-specific outcomes. Primary endpoints were 3-year death, stroke, and reintervention. We performed propensity matching between patients with prior radiation and those without. Kaplan-Meier analysis and a multivariate logistic regression model were used to analyze the outcome variables. RESULTS: A total of 56,472 patients had undergone carotid revascularization (CEA, n = 48,307; TCAR, n = 4593; CAS, n = 3572), 1244 patients with prior radiation and 54,925 patients without prior radiation. The prior radiation group was more likely to be male (71.9% vs 60.3%; P < .01), to receive a stent (47.5% vs 13.5%; P < .01), and to be on P2Y12 inhibitor (55.2% vs 38.3%; P < .01). Propensity matching was performed on 1223 patients (CEA, n = 655; TCAR, n = 292; CAS, n = 287). There were no significant differences in 30-day outcomes for death, stroke, or major adverse cardiovascular events for all three procedures. The prior radiation group had higher rates of cranial nerve injury (3.7% vs 1.8%; P = .04) and 90-day readmission (23.5% vs 18.3%; P = .01) after CEA. For long-term outcomes, prior radiation significantly increased mortality risk for CEA and CAS (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.38-2.27 and HR, 1.56; 95% CI, 1.02-2.36, respectively). The 3-year risk of stroke for CEA in radiated patients was also significantly higher (HR, 1.47; 95% CI, 1.03-2.09) compared with non-radiated patients. Prior radiation did not significantly affect death and stroke in patients undergoing TCAR. Prior radiation also did not impact the rates of short and long-term reintervention after CEA, CAS, or TCAR. CONCLUSIONS: Prior head and neck radiation significantly increases the risk for mortality and stroke for CEA and the risk for mortality after CAS. Long-term outcomes for TCAR are not significantly affected by prior radiation. TCAR may be the preferred treatment modality for patients with radiation-induced carotid stenosis.

Early Experience with Patient-Specific Unibody Bifurcated Fenestrated-Branched Devices for Complex Endovascular Aortic Aneurysm Repair.

OBJECTIVE: Short distances between the lowest visceral/renal artery and the aortic bifurcation are technically challenging during complex endovascular aortic aneurysm repair (EVAR), particularly after previous infrarenal repair. Traditionally, inverted limb bifurcated devices have been used in addition to fenestrated-branched (FB) endografts, but short overlap, difficult cannulation, and potential crushing of bridging stents are limitations for their use. This study reviews the early experience of patient-specific company manufactured devices (PS-CMD) with a unibody bifurcated FB design for complex EVAR. METHODS: Consecutive complex EVAR procedures over a 34-month period with unibody bifurcated FB-devices as part of physician-sponsored investigational device exemption studies at two institutions were reviewed. Unibody bifurcated FB-designs included fenestrated-branched bifurcated or fenestrated inverted limb devices. Endpoints included technical success, survival, frequency of type I or III endoleaks, limb occlusion, and secondary interventions. RESULTS: Among 168 patients undergoing complex EVAR, 33 (19.6%) patients (78.7% male; mean age 77) received unibody bifurcated FB PS-CMDs. Fenestrated-branched bifurcated and fenestrated inverted limb devices were used in 31 (93.9%) and 2 (6.06%) patients, respectively. Median maximum aneurysm diameter was 61 mm (interquartile range [IQR] 55-69). Prior EVAR was reported by 29 (87.9 %) patients, of which 2 (6.06%) had suprarenal stents. A short distance between the lowest renal artery and aortic bifurcation was demonstrated in 30 (90.9%) patients, with median distance of 47 mm (IQR 38-54). Preloaded devices were used in 23 patients (69.7%). A total of 128 fenestrations were planned; 22 (17.2%) were preloaded with guidewires, and 5 (3.9%) with catheters. The median operative time was 238 min (226-300), with a median fluoroscopy time of 65.5 min (IQR 56.0-77.7) and a median dose area product of 147 mGy*cm2 (IQR 105-194). Exclusive femoral access was used in 14 (42.4%) procedures. Technical success was 100%. Target vessel primary patency was 100% at median follow-up time of 11.7 months (IQR 3.5-18.6). Two (6.06%) patients required reintervention for iliac occlusion; one patient required stenting and the other a femoral-femoral bypass. No aortic-related deaths occurred after the procedure. During follow-up, 11 (33.3 %) type II endoleaks and one (3.03%) type Ib endoleak were detected; the latter was treated with leg extension. No type Ia or III endoleaks occurred. CONCLUSION: Complex EVAR using unibody bifurcated FB-PS-CMDs is a simple, safe, and cost-effective alternative for the treatment of patients with short distances between the renal arteries and the aortic bifurcation. Further studies are required to assess benefits and durability of unibody bifurcated FB-devices.

Postdissection aortic aneurysm sac enlargement after fenestrated and branched endovascular aortic aneurysm repair.

OBJECTIVES: Aneurysm sac changes after fenestrated-branched endovascular aneurysm repair (FBEVAR) for postdissection thoracoabdominal aortic aneurysms (PD-TAAs) are poorly understood. Partial thrombosis of the false lumen and endoleaks may impair sac regression. To characterize sac changes after FBEVAR for PD-TAAs, this study examined midterm results and predictors for sac enlargement. METHODS: FBEVARs performed for PD-TAAs in 10 physician-sponsored investigational device exemption studies from 2008 to 2023 were analyzed. The maximum aortic aneurysm diameter was compared between the 30-day computed tomography angiogram and follow-up imaging studies. Aneurysm sac enlargement was defined as an increase in diameter of ≥5 mm. Kaplan-Meier curves and Cox regression were used to evaluate sac enlargement and midterm FBEVAR outcomes. RESULTS: Among 3296 FBEVARs, 290 patients (72.4% male; median age, 68.4 years) were treated for PD-TAAs. Most aneurysms treated were extent II (72%) and III (12%). Mean aneurysm diameter was 66.5 ± 11.2 mm. Mortality at 30 days was 1.4%. At a mean follow-up of 2.9 ± 1.9 years, at least one follow-up imaging study revealed sac enlargement in 43 patients (15%), sac regression in 115 patients (40%), and neither enlargement nor regression in 137 (47%); 5 (2%) demonstrated both expansion and regression during follow-up. Freedom from aneurysm sac enlargement was 93%, 82%, and 80% at 1, 3, and 5 years, respectively. Overall, endoleaks were detected in 27 patients (63%) with sac enlargement and 143 patients (58%) without enlargement (P = .54). Sac enlargement was significantly more frequent among older patients (mean age at the index procedure, 70.2 ± 8.9 years vs 66.5 ± 11 years; P = .04) and those with type II endoleaks at 1 year (74% vs 52%; P = .031). Cox regression revealed age >70 years at baseline (hazard ratio [HR], 2.146; 95% confidence interval [CI], 1.167-3.944; P = .010) and presence of type II endoleak at 1 year (HR, 2.25; 95% CI, 1.07-4.79; P = .032) were independent predictors of sac enlargement. Patient survival was 92%, 81%, and 68% at 1, 3, and 5 years, respectively. Cumulative target vessel instability was 7%, and aneurysm-related mortality was 2% at 5 years. At least 42% of patients required secondary interventions. Sac enlargement did not affect patient survival. CONCLUSIONS: Aneurysm sac enlargement occurs in 15% of patients after FBEVAR for PD-TAAs. Elderly patients (>70 years at baseline) and those with type II endoleaks at 1 year may need closer monitoring and secondary interventions to prevent sac enlargement. Despite sac enlargement in some patients, aneurysm-related mortality at 5 years remains low and overall survival was not associated with sac enlargement.

Left Ventricular Diastolic Dysfunction and Pulmonary Hypertension: Outcomes in SAVR.

BACKGROUND: Severe pulmonary hypertension (PH) and left ventricular diastolic dysfunction (LVDD) are independently associated with poor outcomes in cardiac surgery. We evaluated the relationship of several measures of LVDD, PH, and hemodynamic subtypes of PH including precapillary pulmonary hypertension(pcPH) and isolated post-capillary pulmonary hypertension(ipcPH) and combined pre and post capillary pulmonary hypertension(cpcPH) capillary PH to postoperative outcomes in a cohort of patients who underwent elective isolated-AVR. METHODS: We evaluated (n = 206) patients in our local STS database who underwent elective isolated-AVR between 2014 and 2018, with transthoracic echocardiogram (n = 177) or right heart catheterization (n = 183) within 1 year of operation (or both, n = 161). The primary outcome was a composite end point of death, prolonged ventilation, ICU readmission, and hospital stay >14 days. RESULTS: Severe PH was associated with worse outcomes (moderate: OR, 1.1, p = 0.09; severe: OR, 1.28, p = 0.01), but degree of LVDD was not associated with worse outcomes. Across hemodynamic subtypes of PH, odds of composite outcome were similar (p = 0.89), however, patients with cpcPH had more postoperative complications (67 vs. 36%, p = 0.06) and patients with ipcPH had greater all-cause mortality at 1 (8 vs. 1%, p = 0.03) and 3 years (27 vs. 4%, p = 0.008). CONCLUSION: Severe PH conferred modestly greater risk of adverse events, and both LVDD grade and the combination of severe PH and LVDD were not associated with worse outcomes. However, hemodynamic stratification of PH revealed higher postoperative complications and worse long-term outcomes for those with cpcPH and ipcPH. Preoperative stratification of PH by hemodynamic subtype in valve replacement surgery may improve our risk stratification in this heterogenous condition. Further evaluation of the significance of LVDD and PH in other cardiac operations is warranted.

Early results of transcatheter electrosurgical aortic septotomy for endovascular repair of chronic dissecting aortoiliac aneurysms.

Objective: Endovascular repair of chronic dissecting aortoiliac aneurysms is challenging given the rigid septum, compressed true lumen (TL), and target vessels frequently originating in the false lumen. We have used transcatheter electrosurgical aortic septotomy (TEAS) before stent graft implantation under intravascular ultrasound (IVUS) and fusion guidance. The purpose of this study is to assess the outcomes of TEAS during complex endovascular repair of dissecting aneurysms. Methods: From 2021 to 2023, 17 patients underwent TEAS. The primary end point was technical success, with secondary end points of proximal and distal seals, target vessel instability, aortic and iliac TL and cross-sectional area (CSA) expansion, and aortic-related death. During the procedure, the aortic septum is crossed through a pre-existing entry or via electrocautery-activated 0.018-in. Astato XS20 wire (Asahi-Intecc) under IVUS and fusion guidance. The penetrated wire is then snared in the false lumen and pulled through the ipsilateral femoral access. A 1-cm length of the middle of the Astato wire coating is kinked in a three-sided polygonal configuration, denuded the inner surface of the wire using a no. 15 blade, and positioned at the apex of the septum. Both ends of the Astato wire are insulated with 0.018-in. microcatheters, and the back end of the wire is denuded and connected to cautery. Gentle traction is applied to the wire, and short bursts of electrocautery cutting are applied at 60 to 80 W. Results: The technical success of the septotomy was 100%. No incidence of visceral or lower extremity malperfusion, vascular injury, or distal embolization occurred. Of the 17 patients, 4 underwent thoracic endovascular aneurysm repair, 2 underwent endovascular aortic repair, and 11 underwent fenestrated/branched endovascular aneurysm repair after septotomy. All target vessels were successfully stented. A distal landing zone seal with exclusion of the false lumen was achieved in 16 of the 17 patients (94.1%). One patient required embolization of the false lumen of the celiac artery after septotomy. The TL mean diameter and CSA of the descending thoracic aorta after septotomy was expanded by 7.01 ± 1.9 mm (relative mean diameter expansion, 42.3%; P < .0001) and 2.71 ± 0.4 cm2 (relative mean CSA expansion, 57.3%, P<.0001). For patients who required septotomy through the common iliac arteries, the mean TL was expanded by 8.1 ± 3.7 mm (relative mean diameter expansion, 76%; P < .0001) and 1.76 ± 0.91 cm2 (relative mean CSA expansion, 209%; P < .0001). The 1-year freedom from target vessel instability was 91%. Conclusions: The use of IVUS and fusion-guided TEAS offers a promising technique to facilitate TL expansion and false lumen exclusion in chronic dissecting aortic aneurysms before repair. The durability and long-term outcomes of this technique in a larger cohort remain to be elucidated.

Up and over staged endoconduit technique for endovascular aortic aneurysm repair.

Adverse iliofemoral anatomy can preclude complex endovascular aortic aneurysm repair. This study aims to describe the "up-and-over" staged endoconduit technique to improve access and avoid vascular injury before complex endovascular aneurysm repair. A staged procedure for complex endovascular aortic aneurysm repair is performed using an endoconduit (W.L. Gore & Associates). After obtaining contralateral femoral access, the extension of iliofemoral disease is assessed using angiography. The endoconduit is advanced "up and over" the aortic bifurcation and delivered percutaneously into the common femoral artery to treat a diseased access site and maintain intact the ipsilateral femoral access for future stent graft deployment. Internal iliac artery patency is maintained when feasible. During complex aneurysm repair, the endoconduit is accessed directly under ultrasound guidance using sequential dilation to avoid vascular injury. PerClose sutures (Abbott Vascular) are used to close the endoconduit femoral access site. This study found that staged "up and over" endoconduit creation is a useful technique before complex endovascular aneurysm repair in patients with adverse iliofemoral anatomy. Avoiding accessing the main femoral access site during the first stage prevents vascular or access site injuries and allows for both iliac and femoral disease to be addressed.

Reintervention Rate After Pigtail Catheter Insertion Compared to Surgical Chest Tubes.

BACKGROUND: Prior studies suggest similar efficacy between large-bore chest tube (CT) placement and small-bore pigtail catheter (PC) placement for the treatment of pleural space processes. This study examined reintervention rates of CT and PC in patients with pneumothorax, hemothorax, and pleural effusion. METHODS: This retrospective study examined patients from September 2015 through December 2020. Patients were identified using ICD codes for pneumothorax, hemothorax, or pleural effusion. Use of a pigtail catheter (≤14Fr) or surgical chest tube (≥20Fr) was noted. The primary outcome was overall reintervention rate within 30 days of tube insertion. Patients who died with a pleural drainage catheter in place, unrelated to complications from chest tube placement, were excluded. RESULTS: There were 1032 total patients in the study: 706 CT patients and 326 PC patients. The PC group was older with more comorbidities and more likely to have effusion as the indication for pleural drainage. Patients with PC were 2.35 times more likely to have the tube replaced or repositioned (P < .0001), 1.77 times more likely to require any reintervention (P = .001) and 2.09 times more likely to remain in the hospital >14 days (P < .0001) compared to patients with CT. CONCLUSION: PCs have a significantly higher reintervention rate compared to CT for the treatment of pneumothorax, hemothorax, and pleural effusion. Although PC are believed to cause less pain and tissue trauma, they do not necessarily drain the pleural space as well as CT. Decisions on which method of draining the chest should be made on a case-by-case basis.