Role of PDE10A in vascular smooth muscle cell hyperplasia and pathological vascular remodelling.

AIMS: Intimal hyperplasia is a common feature of vascular remodelling disorders. Accumulation of synthetic smooth muscle cell (SMC)-like cells is the main underlying cause. Current therapeutic approaches including drug-eluting stents are not perfect due to the toxicity on endothelial cells and novel therapeutic strategies are needed. Our preliminary screening for dysregulated cyclic nucleotide phosphodiesterases (PDEs) in growing SMCs revealed the alteration of PDE10A expression. Herein, we investigated the function of PDE10A in SMC proliferation and intimal hyperplasia both in vitro and in vivo. METHODS AND RESULTS: RT-qPCR, immunoblot, and in situ proximity ligation assay were performed to determine PDE10A expression in synthetic SMCs and injured vessels. We found that PDE10A mRNA and/or protein levels are up-regulated in cultured SMCs upon growth stimulation, as well as in intimal cells in injured mouse femoral arteries. To determine the cellular functions of PDE10A, we focused on its role in SMC proliferation. The anti-mitogenic effects of PDE10A on SMCs were evaluated via cell counting, BrdU incorporation, and flow cytometry. We found that PDE10A deficiency or inhibition arrested the SMC cell cycle at G1-phase with a reduction of cyclin D1. The anti-mitotic effect of PDE10A inhibition was dependent on cGMP-dependent protein kinase Iα (PKGIα), involving C-natriuretic peptide (CNP) and particulate guanylate cyclase natriuretic peptide receptor 2 (NPR2). In addition, the effects of genetic depletion and pharmacological inhibition of PDE10A on neointimal formation were examined in a mouse model of femoral artery wire injury. Both PDE10A knockout and inhibition decreased injury-induced intimal thickening in femoral arteries by at least 50%. Moreover, PDE10A inhibition decreased ex vivo remodelling of cultured human saphenous vein segments. CONCLUSIONS: Our findings indicate that PDE10A contributes to SMC proliferation and intimal hyperplasia at least partially via antagonizing CNP/NPR2/cGMP/PKG1α signalling and suggest that PDE10A may be a novel drug target for treating vascular occlusive disease.

Baseline sleep as a predictor of delirium after surgical aortic valve replacement: A feasibility study.

OBJECTIVE: The goal is to assess the feasibility of conducting unattended (type II) sleep studies before surgical aortic valve replacement (SAVR) to examine the relationship between baseline sleep measures and postoperative delirium. METHODS: This single-site study recruited 18 of 20 study referrals with aortic stenosis undergoing first lifetime SAVR. Subjects completed a home-based type II sleep study. Delirium was assessed postoperative days 1-5. Exact logistic regression was used to determine whether sleep efficiency or apnea/hypopnea index predicts delirium. RESULTS: Of 18 study participants, 15 successfully completed a home sleep study (mean age: 71.7 +/- 8.1 years old; 10 male subjects). Five subjects (33.3%) developed delirium. Preliminary analyses found that greater sleep efficiency was associated with a large reduction in delirium odds but was not statistically significant (OR = 0.31, 95% CI: 0.06, 1.03, p = 0.057). The point estimate of the relationship between apnea/hypopnea index and delirium was not similarly sizeable (OR 1.10, 95% CI: 0.35, 3.37, p = 0.85). CONCLUSIONS: Our findings suggest that home type II sleep studies before SAVR are feasible, and they support adequately powered studies investigating type II home sleep studies as a predictor of postoperative delirium and other important postsurgical outcomes.

A Novel Subxiphoid Approach for Bilateral Internal Thoracic Artery Harvesting.

OBJECTIVE: Bilateral internal thoracic artery (BITA) bypass can enable more complete arterial revascularization procedures. Minimally invasive cardiac surgery (MICS) can offer significant patient benefits. New minimally invasive technology for sternal retraction and tissue manipulation is needed to enable ergonomic and reliable minimally invasive ITA harvesting. The goal of this research was to develop technology and techniques, along with experimental testing and training models, for a sternal-sparing approach to in situ BITA harvesting through a small subxiphoid access site. METHODS: This study focused on optimizing custom equipment and methods for subxiphoid BITA harvesting initially in a porcine model (19 pig carcasses, 36 ITAs) and subsequently in 7 cadavers (14 ITAs). RESULTS: Fifty consecutive ITAs were successfully harvested using this remote access approach. The last 20 ITA specimens harvested from the porcine model were explanted and measured; the average length of the free ITA grafts was 12.8 ± 0.9 cm (range 10.8 to 14.2 cm) with a mean time of 23.3 ± 5.2 minutes (range 13 to 25 minutes) for each harvest. CONCLUSIONS: Early results demonstrate that both ITAs can be reliably harvested in a skeletonized fashion in situ through sternal-sparing, small subxiphoid access in 2 experimental models. This innovative approach warrants further exploration toward facilitating complete arterial revascularization and the further adoption of minimally invasive coronary artery bypass graft surgery.

Early Outcomes of Isolated Aortic Valve Replacement Through Right Anterior Minithoracotomy Using the Latest-Generation Biological Prosthesis.

OBJECTIVE: The aim of this study is to evaluate early and intermediate outcomes and hemodynamics of the latest-generation Trifecta valve implanted using right anterior minithoracotomy. METHODS: We performed a single-center, retrospective, observational study including 175 individuals who underwent isolated minimally invasive aortic valve replacement with the latest-generation Trifecta valves through a right anterior minithoracotomy between January 2016 and January 2019. Exclusion criteria for follow-up echocardiographic study included concomitant procedures, conversion to median sternotomy, and nonsurvival during the index admission. Analyses addressed implantation safety, 30-day and intermediate-term survival and hemodynamic performance of the valves. RESULTS: Overall, patients were followed with duration ranging from 0.5 to 3 years. Early (<30 days) mortality occurred in 2 patients (1.1%), and there were 9 (5.1%) late (>30 days) deaths. Early thromboembolic events and postoperative bleeding requiring reoperation occurred at a rate of 4.0% (n = 7) and 6.2% (n = 11), respectively. Overall in 175 patients who met inclusion criteria for the follow-up echocardiography study, mean gradients across all valve sizes were 41.3 ± 14.9 (standard deviation) mm Hg preoperatively and remained low at 7.2 ± 3.9 mm Hg with mean effective orifice area of 1.8 ± 0.5 cm2 on the last follow-up echo. There was 1 case of infective prosthetic endocarditis, which did not require valve explant. There were no reoperations due to valve-related problems during the study period. CONCLUSIONS: This is the largest series reporting on outcomes of the latest-generation Trifecta valve implanted using right anterior minithoracotomy. Our results demonstrate that this valve can be safely implanted via a minimally invasive approach with excellent early and intermediate outcomes and hemodynamic performance.

Routine Placement of Temporary Epicardial Pacing Leads Is Not Required After Minimally Invasive Aortic Valve Replacement.

OBJECTIVE: Our objective is to identify the incidence of urgent transvenous (TV) pacing wire placement following minimally invasive aortic valve replacement (mini-AVR). METHODS: This is a single-center, retrospective, observational study including 359 individuals who underwent isolated mini-AVR through right anterior mini-thoracotomy between January 2015 and September 2019. Patients were grouped according to avoidance or insertion of epicardial pacing wires, and further subdivided based on the requirement for postoperative emergent temporary TV pacing or permanent pacemaker (PPM) placement during the index admission. RESULTS: Two hundred forty-two (67.4%) had acceptable rate and no high-degree atrioventricular (AV) block prior to chest closure and did not have insertion of epicardial pacing wires. Of those patients, only 3 (1.2%) required emergent TV pacing and 6 (2.5%) required nonemergent TV pacing with or without PPM placement during the index admission. Sixty-two (17.3%) patients received only atrial epicardial pacing leads secondary to sinus bradycardia or junctional rhythm and 3 (4.8%) of those patients required PPM placement due to sick sinus syndrome and 1 (1.6%) patient required nonemergent TV pacing and PPM due to high-grade AV heart block. Fifty-five (15.3%) patients received ventricular leads due to high-grade AV heart block and 7 (12.7%) of those patients required PPM placement during the index admission. CONCLUSIONS: Temporary epicardial lead insertion is not routinely required in mini-AVR in patients with normal rate and acceptable AV conduction prior to chest closure. In the absence of epicardial ventricular lead insertion, the chance of requiring urgent TV pacing wire placement during the index admission is 0.99%.

Cadaveric Simulation Training in Cardiothoracic Surgery: A Systematic Review.

Simulation training has become increasingly relevant in the educational curriculum of surgical trainees. The types of simulation models used, goals of simulation training, and an objective assessment of its utility and effectiveness are highly variable. The role and effectiveness of cadaveric simulation in cardiothoracic surgical training has not been well established. The objective of this study was to evaluate the current medical literature available on the utility and the effectiveness of cadaveric simulation in cardiothoracic surgical residency training. A literature search was performed using PubMed, Cochrane Library, Embase, Scopus, and CINAHL from inception to February 2019. Of the 362 citations obtained, 23 articles were identified and retrieved for full review, yielding ten eligible articles that were included for analysis. One additional study was identified and included in the analysis. Extraction of data from the selected articles was performed using predetermined data fields, including study design, study participants, simulation task, performance metrics, and costs. Most of these studies were only descriptive of a cadaveric or perfused cadaveric simulation model that could be used to augment clinical operative training in cardiothoracic surgery. There is a paucity of evidence in the literature that specifically evaluates the utility and the efficacy of cadavers in cardiothoracic surgery training. Of the few studies that have been published in the literature, cadaveric simulation does seem to have a role in cardiothoracic surgery training beyond simply learning basic skills. Additional research in this area is needed.

Role of Automated Suturing Technology in Minimally Invasive Aortic and Mitral Valve Surgery.

Minimally invasive cardiac surgery continues to evolve and expand as technology and surgeon experience develops. Among the barriers to the adoption of non-sternotomy minimally invasive valve surgery are the challenges associated with suture placement. Automated technology enables ergonomic remote suture placement that allows for reproducible results while shortening the learning curve. The objective of this review is to describe the latest advancements in automated suturing technology for minimally invasive valve surgery.

Concomitant Annular Enlargement in Minimally Invasive Aortic Valve Replacement.

OBJECTIVE: Aortic root enlargement may be necessary to implant adequately sized valves to avoid patient-prosthetic mismatch. Our objective was to assess the feasibility of annular enlargement during aortic valve replacement via a right anterior minithoracotomy. METHODS: Twelve consecutive patients undergoing elective minimally invasive aortic valve replacement requiring annular enlargement over a 2-year period were retrospectively reviewed. A right anterior minithoracotomy was performed in all patients. Cardiopulmonary bypass and aortic crossclamp times, hospital length of stay, postoperative complications, rate of reoperation, echocardiographic data, and mortality were analyzed. RESULTS: Mean age was 66 years ± 14. Mean body mass index was 34 ± 7.8 kg/m2. All patients had normal preoperative ejection fractions. Indications for aortic valve replacement were severe (3/12, 25%) or critical (9/12, 75%) aortic stenosis due to degenerative aortic valve disease (10/12, 83%) and congenitally bicuspid aortic valve (2/12, 17%). Cardiopulmonary bypass and aortic crossclamp times were 144.7 ± 14.7 minutes and 111.7 ± 10.6 minutes, respectively. The median postoperative length of stay was 4 days. Peak and mean aortic valve gradients on postreplacement intraoperative transesophageal echocardiography were 14.5 ± 9.4 mmHg and 7.2 ± 4.2 mmHg, respectively, with no perivalvular leak on intraoperative or follow-up transthoracic echocardiogram. Postoperative transthoracic echocardiography had peak and mean aortic valve gradients of 12.1 ± 6.9 mmHg and 6.3 ± 3.7 mmHg, respectively. There were no postoperative mortalities. Freedom from reoperation was 100%. CONCLUSIONS: Annular enlargement performed during minimally invasive aortic valve replacement is feasible. Basic minimally invasive skills are recommended prior to instituting these more advanced techniques.

A Randomized Controlled Trial of Liposomal Bupivacaine Parasternal Intercostal Block for Sternotomy.

BACKGROUND: Optimal pain control continues to be a concern in cardiac surgery. Current strategies for postoperative pain management often yield suboptimal results. The superiority of Exparel (Pacira Pharmaceuticals, Inc, Parsippany, NJ) in providing postoperative pain control and opioid sparing is equivocal. This prospective, randomized, double-blind study examines the efficacy of Exparel as a novel single-dose application parasternal nerve block in postoperative pain control and opioid sparing. METHODS: This single-surgeon study included 79 patients undergoing median sternotomy for coronary revascularization. Study participants were randomized to either the drug or a control arm. Each participant received Exparel or normal saline placebo administered as a parasternal nerve block. Postoperative pain was rated according to the nonverbal pain scale or numeric rating scale. Total amount of narcotic pain medication used and patients' pain scores within the first 72 hours postoperatively were compared. Secondary outcomes compared the intensive care unit length of stay, hospital length of stay, time to extubation, time to return of bowel function, and time to return to work or daily activities. RESULTS: The primary endpoint of pain levels between the two groups demonstrated no significant difference when analyzing the individual time points postoperatively. However, overall pain levels were significantly lower in the study drug group (p = 0.04). There was no significant difference in the amount of analgesics required postoperatively or in secondary endpoints between the groups. CONCLUSIONS: Exparel does not provide an opioid-sparing benefit or any secondary outcome benefit compared with placebo. Exparel may be associated with a marginal decrease in postoperative pain levels. (Parasternal Nerve Bock in Cardiac Patients; NCT01826851.).

Right Mini-Thoracotomy Subaortic Membrane Resection.

OBJECTIVE: Subaortic membrane is an anatomical intracardiac anomaly that may cause discrete subaortic stenosis and aortic insufficiency. Patients requiring subaortic membrane resection may benefit from a minimally invasive approach; however, subaortic membranes are typically resected through a median sternotomy. We present our initial clinical experience of adult patients who have undergone a mini-thoracotomy subaortic membrane resection. METHODS: Eight patients who underwent an elective subaortic membrane resection performed through a mini-thoracotomy were retrospectively reviewed. A 5-cm mini-thoracotomy incision was made in the 2nd intercostal space; a videoscope was inserted through a separate incision within the same interspace. Cardiopulmonary bypass (CPB) was instituted via central arterial and peripheral venous cannulation and an aortotomy was made. The subaortic membrane was resected with shafted instruments. The left ventricular outflow tract was inspected and CPB was weaned. Thirty-day mortality, intensive care and hospital length of stay, ventilation time, operative times, postoperative morbidity, and need for additional procedures were evaluated. RESULTS: The median CPB and cross-clamp times were 60 and 42 minutes, respectively. The median time to extubation was 3.6 hours. The median intensive care unit and hospital stay were 22 hours and 3 days, respectively. The postoperative left ventricular outflow tract mean gradients decreased significantly (26.5 vs. 9.4 mm Hg, P = 0.001). There were no conversions to sternotomy, perioperative strokes, or 30-day mortality. CONCLUSIONS: Subaortic membranes can be resected through a mini-thoracotomy approach with excellent clinical results.

Titanium Fastener Utilization During HeartMate 3 Left Ventricular Assist Device Implantation.

OBJECTIVE: The objective of this study was to investigate the feasibility of using titanium fasteners for securement of the inflow sewing ring during HeartMate 3 implantation. The secondary objective was to compare cardiopulmonary bypass and total operative times between the titanium fastener and hand-tied knot groups. METHODS: Clearance between the sewing ring and the HeartMate 3 device was assessed in vitro. Thirty-one patients undergoing HeartMate 3 implantation via median sternotomy at a single center from April 2017 to February 2018 were reviewed. The sewing ring was secured with hand-tied knots (n = 18) or titanium fasteners (n = 13). Cannulation strategy and implantation technique were otherwise identical between groups. Central arterial and venous cannulation was performed for cardiopulmonary bypass. The left ventricular apex was cored, and the sewing ring was attached with hand-tied knots or titanium fasteners. RESULTS: There was adequate clearance for the titanium fastener to secure the inflow sewing ring and then connect to the HeartMate 3 in vitro. The inflow sewing ring was successfully secured during HeartMate 3 implantation in the titanium fastener group. Cardiopulmonary bypass time was 75 and 92 minutes for the titanium fastener and hand-tied groups, respectively (P < 0.03). Total operative time was 177 and 193 minutes for the titanium fastener and hand-tied groups, respectively (P = 0.513). CONCLUSIONS: The inflow sewing ring of the HeartMate 3 was efficiently secured using titanium fasteners. Titanium fasteners resulted in shorter cardiopulmonary bypass times compared with the hand-tied group. There was no difference in total operative time.

Right Mini-thoracotomy Bentall Procedure.

OBJECTIVE: Bentall procedures are traditionally performed through a median sternotomy. The right mini-thoracotomy approach is increasingly used in aortic valve replacement. This approach has been shown to have decreased blood loss and hospital length of stay compared with sternotomy. A right mini-thoracotomy approach may also be beneficial in selected patients requiring aortic root surgery. We present our initial clinical experience of patients who have undergone a right mini-thoracotomy Bentall. METHODS: This is a single-center retrospective review of seven patients who underwent a primary elective right anterior mini-thoracotomy Bentall. A thoracoscope was used in each case. Automated suturing technology was used for annular suturing in three of the seven patients. Clinical outcomes evaluated include 30-day mortality, intensive care and hospital length of stay, time to extubation, operative times, as well as postoperative sequelae including stroke, infection, and bleeding. RESULTS: Median cardiopulmonary bypass, cross-clamp, and circulatory arrest time were 217, 153, and 28 minutes, respectively. Median time to extubation was 10 hours and median intensive care unit and hospital stay was 1 and 4 days, respectively. One patient had a wound infection and one returned to the operating room for bleeding. There were no in-hospital or 30-day mortalities. CONCLUSIONS: The Bentall procedure can be performed through a right anterior mini-thoracotomy in selected patients with excellent clinical results.

Interactive translational research model and cadaveric simulation: where minimally invasive cardiac surgery and industry meet.

Focused research targeting an identified clinical problem may result in more rapid development of medical devices, technologies, and surgical techniques that directly impact patient care. These medical advances to improve patient care may be expedited by adopting an interactive translational research model in which inventors, designers, and engineers work in collaboration with surgeons. In addition, cadaveric simulation is a high-fidelity model that is bridging the translational and logistical gap to bring new surgical devices, technologies, and techniques to patients. We describe the partnership between the University of Rochester and LSI SOLUTIONS® in which an interactive translational research model utilizing cadaveric simulation has been successfully applied to accelerate bringing minimally invasive cardiac surgical techniques and innovative devices to patients.

Three-Year Survival Comparison Between Transcatheter and Surgical Aortic Valve Replacement for Intermediate- and Low-Risk Patients.

Transcatheter aortic valve implantation is a suitable therapeutic intervention for patients deemed inoperable or high risk for surgical aortic valve replacement. Current investigations question whether it is a suitable alternative to surgery for intermediate- and low-risk patients. The following meta-analysis presents a comparison between transcatheter versus surgical aortic valve replacement in patients that are intermediate and low risk for surgery. Articles were collected via an electronic search using Google Scholar and PubMed. Articles of interest included studies comparing the survival of intermediate- and low-risk patients undergoing transcatheter aortic valve implantation to those undergoing surgical aortic valve replacement. Primary end points included 1-, 2-, and 3-year survival. Secondary end points included postintervention thromboembolic events, stroke, transient ischemic attacks, major vascular complications, permanent pacemaker implantation, life-threatening bleeding, acute kidney injury, atrial fibrillation, and moderate-to-severe aortic regurgitation. Six studies met the criteria for the meta-analysis. One- and two-year survival comparisons showed no difference between the two interventions. Surgical aortic valve replacement, however, presented with favorable 3-year survival compared with the transcatheter approach. Transcatheter aortic valve implantation had more major vascular complications, permanent pacemaker implantation, and moderate-to-severe aortic regurgitation rates compared with surgery. Surgical aortic valve replacement presented more life-threatening bleeding, acute kidney injury, and atrial fibrillation compared with a transcatheter approach. There was no statistical difference between the two approaches in terms of thromboembolic events, strokes, or transient ischemic attack rates. Surgical aortic valve replacement presents favorable 3-year survival rates compared with transcatheter aortic valve implantation.

Right mini-thoracotomy Bentall with traditional and automated suturing devices.

Bentall procedures are traditionally performed through a median sternotomy. However, minimally invasive approaches are increasingly being utilized. A right mini-thoracotomy approach may improve postoperative recovery.  A 5-cm mini-thoracotomy is performed in the right 2nd intercostal space. A camera port is placed lateral to this incision. Peripheral cannulation is performed. The ascending aorta is cross-clamped. Cardioplegia is administered and the patient is placed in deep hypothermic circulatory arrest to construct the distal aortic anastomosis. Aortic leaflets are excised and the annulus is sized. Annular and prosthetic sutures are placed using shafted instruments or automated suturing devices. The coronary buttons are reimplanted and a graft-to-graft anastomosis is constructed.  The Bentall procedure can be done safely through a right mini-thoracotomy in select patients and we demonstrate our technique in this video tutorial. Automated suturing devices and video guidance may facilitate this procedure.

Video assisted right mini-thoracotomy for aortic root replacement.

Aortic root replacement is typically performed through a median sternotomy. The right anterior mini-thoracotomy approach has been shown to decrease hospital length of stay in aortic valve surgery when compared to sternotomy. This approach is rare in ascending aortic surgery due to technical challenges which include exposure and annular suture placement. Automated suturing technology is now available to facilitate the placement of annular sutures. The use of a camera greatly enhances visualization of the aortic root. A right anterior mini-thoracotomy is performed via a 5 cm incision in the right second intercostal space with a camera port placed lateral to the incision. Peripheral arterial and venous cannulation are performed. The aortic cross clamp is placed through a 5 mm incision in the third interspace anterior to mid axillary line. Histidine tryptophan ketoglutarate (HTK) cardioplegia is administered and deep hypothermic circulatory arrest is achieved followed by completion of the distal anastomosis with a 4-0 polypropylene running suture. After aortic leaflet removal, annular and prosthetic sutures are placed with shafted instruments or with automated suturing technology. Coronary button suturing and graft-to-graft anastomoses are performed with shafted instruments. Aortic root procedures can be performed safely through a right anterior mini-thoracotomy. The use of a camera and automated suturing technology may further facilitate this procedure, enabling more surgeons to offer this less invasive approach to patients.

Video assisted right mini-thoracotomy for aortic valve replacement.

Aortic valve replacement through minimally invasive access is increasing. These procedures have several advantages over conventional sternotomy including decreased intensive care unit and hospital length of stay and decreased ventilation time. The right anterior mini-thoracotomy (RAM) approach is potentially attractive in that it completely spares the sternum leading to improved cosmesis, reduced blood loss, and improved patient satisfaction. However, this approach is underutilized due to anticipated technical challenges including difficulty with visualization and annular suture placement. We employ a camera and automated suturing technology for supra-annular valve implant. A RAM is performed via a 5 cm incision in the right second intercostal space with a camera port placed lateral to the incision. Peripheral venous cannulation is performed along with central arterial cannulation. Aortic cross clamp is placed through a 5 mm incision in the third interspace anterior to mid axillary line. Histidine tryptophan ketoglutarate (HTK) cardioplegia is administered. After aortic leaflet removal, annular and prosthetic sutures are placed with shafted instruments or with automated suturing technology. Aortic valve replacement can be performed safely through a RAM. The use of a camera and automated suturing technology facilitates this procedure, potentially enabling more surgeons to offer this less invasive approach to patients.

Comparison of Automated Titanium Fasteners to Hand-Tied Knots in Open Aortic Valve Replacement.

OBJECTIVE: Aortic cross-clamp and cardiopulmonary bypass times are independent predictors of postoperative morbidity and mortality. Reducing ischemic times with automated titanium fasteners may improve surgical outcomes. This study compared operative times and costs of titanium fasteners versus hand-tied knots for prosthesis securement in open aortic valve replacement. METHODS: A randomized control trial was conducted during a 16-month period at a single university medical center. Patients undergoing elective aortic valve replacement were randomized to the titanium fastener (n = 37) or hand-tied groups (n = 36). Knotting, aortic cross-clamp, cardiopulmonary bypass, and total operating room times were recorded. Hospital charges were also calculated for these procedures. RESULTS: Baseline characteristics, concomitant procedures, prosthetic valve size, and sutures were similar between groups. The titanium fastener group had significantly reduced knotting (7.4 vs. 13.0 minutes, P < 0.001), aortic cross-clamp (69 vs. 90 minutes, P < 0.05), cardiopulmonary bypass (86 vs. 114 minutes, P < 0.05), and total operating room times (234 vs. 266 minutes, P < 0.05). Intraoperative complications occurred more frequently in the hand-tied group compared with the titanium fastener group. Postoperative complications were similar between groups. Operating room costs were significantly higher in the titanium fastener group (US $10,428 vs. US $9671, P = 0.01). Hospitalization costs did not differ significantly between the titanium fastener and hand-tied group (US $23,987 vs. US $21,068, P = 0.12). CONCLUSIONS: Titanium fastener use was associated with shorter knotting, aortic cross-clamp, cardiopulmonary bypass, and operating room times and fewer intraoperative complications in open aortic valve replacement, without significantly increasing hospitalization cost.