Successful Concomitant Pulmonary Thromboendarterectomy and Heart Transplant.

Heart transplantation remains the gold standard of therapy for patients with end-stage heart failure. Submassive pulmonary embolism in a patient with heart failure is generally considered a contraindication to immediate heart transplantation, given the risk of right heart failure posttransplant. Generally patients must wait for extended periods of time to recover from pulmonary embolism therapies before being listed for transplant. We report a case of successful concomitant pulmonary thromboendarterectomy and heart transplantation.

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.).

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.

Cannulation-Related Complications on Veno-Arterial Extracorporeal Membrane Oxygenation: Prevalence and Effect on Mortality.

Cannulation-related complications are a known source of morbidity in patients supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite its prevalence, little is known regarding the outcomes of patients who suffer such complications. This is a single institution review of cannulation-related complications and its effect on mortality in patients supported on VA-ECMO from January 2010-2015 using three cannulation strategies: axillary, femoral, and central. Complications were defined as advanced if they required major interventions (fasciotomy, amputation, site conversion). Patients were divided into two groups (complication present vs. not present) and Kaplan-Meier analysis was performed to determine any differences in their survival distributions. There were 103 patients supported on VA-ECMO: 41 (40%), 36 (35%), and 26 (25%) were cannulated via axillary, femoral, and central access, respectively. Cannulation-related complications occurred in 33 (32%) patients and this did not differ significantly between either axillary (34%), femoral (36%), or central (23%) strategies (P = 0.52). The most common complications encountered were hemorrhage and limb ischemia in 19 (18%) and 11 (11%) patients. Hemorrhagic complications did not differ between groups (P = 0.37), while limb ischemia and hyperperfusion were significantly associated with femoral and axillary cannulation, at a rate of 25% (P < 0.01) and 15% (P = 0.01), respectively. There was no difference in the incidence of advanced complications between cannulation groups: axillary (12%) vs. femoral (14%) vs. central (8%; P = 0.75). In addition, no increase in mortality was noted in patients who developed a cannulation-related complication by Kaplan-Meier estimates (P = 0.37). Cannulation-related complications affect a significant proportion of patients supported on VA-ECMO but do not differ in incidence between different cannulation strategies and do not affect patient mortality. Improved efforts at preventing these complications need to be developed to avoid the additional morbidity in an already critical patient population.

An Automated Expanded Polytetrafluoroethylene Suturing and Coaxial Fastener System for Mitral Chordae Replacement: Strength, Feasibility, and Healing.

OBJECTIVE: Mitral valve (MV) chordae replacements can be technically challenging. Technology that remotely delivers and accurately secures artificial chordae may reduce the learning curve and improve the reliability of MV repairs. METHODS: The technology involved two devices: a remote suturing device for delivery of expanded polytetrafluoroethylene (ePTFE) suture to the papillary muscle and a Coaxial titanium suture fastener (TF) device with integrated saline infusion for real-time determination of chordae length during fixation. A mechanical model simulating MV chordae tension in a beating heart quantified the durability of 120 coaxially fastened ePTFE sutures using TF over time. Investigation of the technology was performed in ex vivo porcine, ovine, and in situ cadaver hearts, whereas live-tissue testing was conducted in a survivor ovine model. Mitral valve repair procedures involved the iatrogenic induction of mitral regurgitation by the resection of one to two native MV chordae, followed by implantation of ePTFE suture using the technology. Epicardial echocardiography, saline infusion testing, and histologic analysis evaluated MV competence, repair integrity, and long-term healing. RESULTS: Durability testing of ePTFE suture secured with TF demonstrated no degradation of TF pull-apart forces of for 440 million cycles. Mitral valve repairs using the technology were performed in eight sheep; four demonstrating proof of concept and four survived for an average of 6.5 months after completion of the procedure. At reoperation, echocardiography demonstrated trace to no mitral regurgitation with near complete endothelialization of the TF and artificial chordae. CONCLUSIONS: This technology successfully enabled the implantation of artificial chordae while providing real-time adjustment of chordae length during MV repair. These results encourage further investigation of its use clinically.

Prosthetic Aortic Valve Fixation Study: 48 Replacement Valves Analyzed Using Digital Pressure Mapping.

OBJECTIVE: Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). METHODS: Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 × 4-mm, 12 × 4-mm, or 9 × 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand-tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. RESULTS: Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 × 4-mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 × 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 × 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 × 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). CONCLUSIONS: Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security.

Comparison of strength, consistency, and speed of COR-KNOT versus manually hand-tied knots in an ex vivo minimally invasive model.

OBJECTIVE: This study compared the strength, consistency, and speed of prosthetic attachment sutures secured with automated fasteners with those of manual knots using an ex vivo porcine mitral valve annuloplasty model. A novel miniature pressure transducer system was developed to quantify pressures between sutured prosthetic rings and underlying cardiac tissue. METHODS: Sixteen mitral annuloplasty rings were sewn into ex vivo pig hearts. Eight rings were secured with the COR-KNOT device; and eight rings, with hand-tied knots using a knot pusher. A cardiac surgeon and a surgery resident each completed four manually tied rings and four COR-KNOT rings via a thoracotomy trainer. The total time to knot and cut each ring's sutures was recorded. Suture attachment pressures were measured within (intrasuture) and between (extrasuture) each suture loop using a 0.5 × 2.0-mm microtransducer probe system. RESULTS: The suture holding pressures for the COR-KNOT fasteners were significantly greater than for the manually tied knots (median, 1008.9 vs 415.8 mm Hg, P < 0.001). All automated fasteners measured greater than 500 mm Hg, whereas 56% of the hand-tied knots were less than 500 mm Hg, and 14% were less than 75 mm Hg. There was less variation in attachment pressures for the COR-KNOT fasteners than for the hand-tied knots (SD, 401.6 vs 499.3 mm Hg, P = 0.04). Significant time savings occurred with the use of the COR-KNOT compared with manual tying (12.4 vs 71.1 seconds per knot, P = 0.001). CONCLUSIONS: The novel microtransducer technology provided an innovative means of evaluating cardiac prosthetic anchoring sutures. In this model, mitral annuloplasty ring sutures secured with the COR-KNOT device were stronger, more consistent, and faster than with manually tied knots.

Coil embolization of a symptomatic left internal mammary arteriovenous fistula.

Internal mammary artery (IMA) arteriovenous fistulae (AVF) are exceedingly rare. There have been a few case reports documenting incidences of IMA AVFs arising from traumatic, iatrogenic, and congenital causes. Recommendations for management of IMA AVFs vary from open surgical ligation-excision to transcatheter embolization to observation. We present an unusual case of a patient who presented with ventricular arrhythmias and heart failure symptoms due to a left IMA AVF that formed after open heart surgery. The patient ultimately underwent percutaneous embolization of the fistulous connection.

Endocarditis of Amplatzer occluder devices after percutaneous closure of a mitral paravalvular leak.

Symptomatic paravalvular leaks (PVL) are a relatively uncommon, but potentially significant postoperative complication of valve replacement surgery. Percutaneous repair of PVLs has become an increasingly utilized approach in patients whose comorbidities obviate surgical repair. We present an interesting case of a gentleman who underwent successful repair of a mitral PVL with Amplatzer devices following initial aortic and mitral valve replacements for bacterial endocarditis. He later developed fungal endocarditis that ultimately required re-operation to remove the devices and replace his mitral and aortic valves. This complication of closure devices, although reportedly rare, should be considered when contemplating a percutaneous approach. © 2012 Wiley Periodicals, Inc.

Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion.

The Timeless-Tipin protein complex has been reported to be important for replication checkpoint and normal DNA replication processes. However, the precise mechanisms by which Timeless-Tipin preserves genomic integrity are largely unclear. Here, we describe the roles of Timeless-Tipin in replication fork stabilization and sister chromatid cohesion. We show in human cells that Timeless is recruited to replication origin regions and dissociate from them as replication proceeds. Cdc45, which is known to be required for replication fork progression, shows similar patterns of origin association to those of Timeless. Depletion of Timeless-Tipin causes chromosome fragmentation and defects in damage repair in response to fork collapse, suggesting that it is required for replication fork maintenance under stress. We also demonstrate that depletion of Timeless-Tipin impairs sister chromatid cohesion and causes a defect in mitotic progression. Consistently, Timeless-Tipin co-purifies with cohesin subunits and is required for their stable association with chromatin during S phase. Timeless associates with the cohesion-promoting DNA helicase ChlR1, which, when overexpressed, partially alleviates the cohesion defect of cells depleted of Timeless-Tipin. These results suggest that Timeless-Tipin functions as a replication fork stabilizer that couples DNA replication with sister chromatid cohesion established at replication forks.

Elevated glucose induction of thrombospondin-1 up-regulates fibronectin synthesis in proximal renal tubular epithelial cells through TGF-beta1 dependent and TGF-beta1 independent pathways.

BACKGROUND: TGF-beta1 bioactivation, consequent to the interaction of latent TGF-beta1 with thrombospondin-1 (TSP-1), correlates with matrix accumulation in mesangial cells. Tubulointerstitial damage predicts poor renal survival. There is little data on TGF-beta1 bioactivation and matrix synthesis in human proximal renal tubular epithelial cells under the influence of high glucose concentrations. This study thus investigates the role of TSP-1 in mediating elevated glucose-induction of TGF-beta1 bioactivation and fibronectin (FN) synthesis in human proximal tubular epithelial cells. METHODS: Human proximal renal tubular epithelial cells (HK-2 cells) were incubated with 5, 10, 20 or 30 mM D-glucose for up to 3 weeks either in the presence or absence of TSP-1 blocking peptide. In separate studies HK-2 cells were incubated with exogenous TSP-1 (0-10 ng/ml) or TGF-beta1 (0-10 ng/ml) for 24 h. Cell proliferation was assessed by [(3)H]-thymidine incorporation. TGF-beta1 transcript, secretion and bioactivity were investigated by quantitative real-time PCR, ELISA and the MLEC bioassay respectively. TSP-1 and FN synthesis were assessed by quantitative real-time PCR, ELISAs and Western blot analysis. RESULTS: Elevated glucose concentrations increased TSP-1 synthesis, which was associated with reduced cell proliferation, increased TGF-beta1 bioactivity, and stimulation of FN synthesis. The inclusion of TSP-1 blocking peptide to cells stimulated with elevated glucose concentration abrogated activation of TGF-beta1 and induction of FN secretion. Exogenous TSP-1 increased bioactive TGF-beta1 in HK-2 cells to initiate FN accumulation. Of interest is our observation that TSP-1 also increased matrix synthesis through a mechanism independent of TGF-beta1. TGF-beta1 in turn modulated TSP-1 synthesis, indicative of an autocrine loop between TSP-1 and TGF-beta1. CONCLUSIONS: TSP-1 plays an important role in the induction of matrix synthesis by high glucose concentrations in human proximal renal tubular epithelial cells, through TGF-beta1 dependent and TGF-beta1 independent pathways. Pharmacological intervention targeting increased TSP-1 expression may interrupt the pathogenesis of diabetic nephropathy.