Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth.

PURPOSE OF REVIEW: The first successful pig to human cardiac xenotransplantation in January 2022 represented a major step forward in the fields of heart failure, immunology, and applied genetic engineering, using a 10-gene edited (GE) pig. This review summarizes the evolution of preclinical modelling data which informed the use of each of the 10 genes modified in the 10-GE pig: GGTA1, Β4GalNT2, CMAH, CD46, CD55, TBM, EPCR, CD47, HO-1, and growth hormone receptor. RECENT FINDINGS: The translation of the 10-GE pig from preclinical modelling to clinical compassionate xenotransplant use was the culmination of decades of research combating rejection, coagulopathy, inflammation, and excessive xenograft growth. Understanding these 10 genes with a view to their combinatorial effects will be useful in anticipated xenotransplant clinical trials.

Double diagnostic deviance: Case report of chest wall liposarcoma mimicking inflammatory myofibroblastic tumor mimicking costochondritis.

Inflammatory myofibroblastic tumor and liposarcoma very rarely present as tumors of the chest wall. Never have both been reported together in the same lesion. We present a case wherein a 72-year-old man with a rapidly progressing lesion initially mistaken for a local infection underwent resection with diagnosis of inflammatory myofibroblastic tumor. He experienced recurrence less than 6 months before radical resection revealed well to dedifferentiated liposarcoma with areas of inflammatory myofibroblastic tumor. He is now doing well with over 4 years of follow-up.

Transcatheter Treatment Options for Functional Mitral Regurgitation: Which Device for Which Patients?

Mitral regurgitation is the most common valvular disease in the developed world, with approximately 24.2 million people being affected worldwide and a higher prevalence in older age groups. Surgical correction of degenerative mitral regurgitation is the standard of care and can restore cardiac function and provide a lasting result, especially when the mitral valve can be repaired. Secondary mitral regurgitation, or functional mitral regurgitation (FMR), describes atrial or ventricular factors leading to poor coaptation of an otherwise non-diseased valve. For FMR, traditional surgery has not produced the same level of benefit. Transcatheter mitral repair and replacement techniques that mimic surgical correction are under investigation. Transcatheter edge-to-edge repair is the only approved catheter-based therapy for FMR in the US. Here, the transcatheter treatment options for FMR are reviewed.

Peripheral intravascular lithotripsy to facilitate transfemoral transcatheter aortic valve replacement - Defining optimal treatable peripheral arterial disease burden.

BACKGROUND: Transfemoral transcatheter aortic valve replacement (TF-TAVR) has proven superior to alternative access. However, some patients evaluated for TF-TAVR are unfit secondary to peripheral arterial disease (PAD). Peripheral intravascular lithotripsy (IVL) can facilitate femoral access. This study aimed to characterize optimal lesions that can be treated with IVL. METHODS: Single-center, retrospective analysis of an institutional database, queried from 1/2018 through 7/2023 for all patients who underwent TAVR. Patients who received IVL-facilitated transfemoral access were analyzed. RESULTS: Of 2862 TAVR cases identified, 92 (3.2 %) underwent lithotripsy. The IVL-facilitated cohort had a mean age of 78 ± 9.2 years and 45 % were female. The right common iliac artery was most treated (47). Most IVL was performed with 7-mm balloons (73.9 %). All cases were successful. 30-day mortality was 1.1 % (1/92). CONCLUSIONS: In our cohort, complications after IVL-facilitated TF-TAVR were more common with small vessel diameter (≤4.7 mm), significant luminal loss (>50 % stenosis), and heavy calcium burden (arc calcification >180°). The findings support the use of IVL to expand the population of patients who can undergo TF-TAVR without the increased risks associated with the various forms of alternative access. SUMMARY FOR ANNOTATED TABLE OF CONTENTS: IVL-facilitated TF-TAVR is safe and feasible. Despite its introduction to TAVR clinical practice in 2018, IVL-facilitated TF-TAVR is not regularly performed and could increase the population of patients eligible for TF-TAVR.

Trends in surgical aortic valve replacement in pre- and post-transcatheter aortic valve replacement eras at a structural heart center.

Background: The advent of transcatheter aortic valve replacement (TAVR) has directly impacted the lifelong management of patients with aortic valve disease. The U.S. Food and Drug Administration has approved TAVR for all surgical risk: prohibitive (2011), high (2012), intermediate (2016), and low (2019). Since then, TAVR volumes are increasing and surgical aortic valve replacements (SAVR) are decreasing. This study sought to evaluate trends in isolated SAVR in the pre- and post-TAVR eras. Methods: From January 2000 to June 2020, 3,861 isolated SAVRs were performed at a single academic quaternary care institution which participated in the early trials of TAVR beginning in 2007. A formal structural heart center was established in 2012 when TAVR became commercially available. Patients were divided into the pre-TAVR era (2000-2011, n = 2,426) and post-TAVR era (2012-2020, n = 1,435). Data from the institutional Society of Thoracic Surgeons National Database was analyzed. Results: The median age was 66 years, similar between groups. The post-TAVR group had a statistically higher rate of diabetes, hypertension, dyslipidemia, heart failure, more reoperative SAVR, and lower STS Predicted Risk of Mortality (PROM) (2.0% vs. 2.5%, p < 0.0001). There were more urgent/emergent/salvage SAVRs (38% vs. 24%) and fewer elective SAVRs (63% vs. 76%), (p < 0.0001) in the post-TAVR group. More bioprosthetic valves were implanted in the post-TAVR group (85% vs. 74%, p < 0.0001). Larger aortic valves were implanted (25 vs. 23 mm, p < 0.0001) and more annular enlargements were performed (5.9% vs. 1.6%, p < 0.0001) in the post-TAVR era. Postoperatively, the post-TAVR group had less blood product transfusion (49% vs. 58%, p < 0.0001), renal failure (1.4% vs. 4.3%, p < 0.0001), pneumonia (2.3% vs. 3.8%, p = 0.01), shorter lengths of stay, and lower in-hospital mortality (1.5% vs. 3.3%, p = 0.0007). Conclusion: The approval of TAVR changed the landscape of aortic valve disease management. At a quaternary academic cardiac surgery center with a well-established structural heart program, patients undergoing isolated SAVR in the post-TAVR era had lower STS PROM, more implantation of bioprosthetic valves, utilization of larger valves, annular enlargement, and lower in-hospital mortality. Isolated SAVR continues to be performed in the TAVR era with excellent outcomes. SAVR remains an essential tool in the lifetime management of aortic valve disease.

Hybrid Closure of Postinfarction Apical Ventricular Septal Defect Using Septal Occluder Device and Right Ventricular Free Wall: The Apical BASSINET Concept.

BACKGROUND: Postinfarction ventricular septal defect (VSD) is a catastrophic complication of myocardial infarction. Surgical repair still has poor outcomes. This report describes clinical outcomes after a novel hybrid transcatheter/surgical repair in patients with apical VSD. METHODS: Seven patients with postmyocardial infarction apical VSD underwent hybrid transcatheter repair via subxiphoid surgical access. A transcatheter occluder (Amplatzer Septal Occluder) with a trailing premounted suture was deployed through the right ventricular wall and through the ventricular septum into the left ventricular apex. The trailing suture was used to connect an anchor external to the right ventricular wall. Tension on the suture then collapses the right ventricular free wall against the septum and left ventricular occluder, thereby obliterating the VSD. Outcomes were compared with 9 patients who underwent surgical repair using either patch or primary suture closure. RESULTS: All patients had significant left-to-right shunt (Qp:Qs 2.5:1; interquartile range [IQR, 2.1-2.6] hybrid repair versus 2.0:1 [IQR, 2.0-2.5] surgical repair), and elevated right ventricular systolic pressure (62 [IQR, 46-71] versus 49 [IQR, 43-54] mm Hg, respectively). All had severely depressed stroke volume index (22 versus 21 mL/m2) with ≈45% in each group requiring mechanical support preprocedurally. The procedure was done 15 (IQR, 10-50) versus 24 (IQR, 10-134) days postmyocardial infarction, respectively. Both groups of patients underwent repair with technical success and without intraprocedural death. One patient in the hybrid group and 4 in the surgical group developed multiorgan failure. The hybrid group had a higher survival at discharge (86% versus 56%) and at 30 days (71% versus 56%), but similar at 1 year (57% versus 56%). During follow-up, 1 patient in each group required reintervention for residual VSD (hybrid: 9 months versus surgical: 5 days). CONCLUSIONS: Early intervention with a hybrid transcatheter/surgical repair may be a viable alternative to traditional surgery for postinfarction apical VSD.

First-in-Human Multicenter Experience of the Newest Generation Supra-Annular Self-Expanding Evolut FX TAVR System.

BACKGROUND: The latest-generation Evolut FX TAVR system (Medtronic) offers several potential design improvements over its predecessors, but early reported experience has been limited. OBJECTIVES: This study sought to report our multicenter, limited market release, first-in-human experience of transcatheter aortic valve replacement (TAVR) with the Evolut FX system and compare it with a single-center PRO+ (Medtronic) experience. METHODS: From June 27 to September 16, 2022, 226 consecutive patients from 9 US centers underwent transfemoral TAVR with the Evolut FX system for native aortic stenosis (89.4%) or prosthetic valve degeneration (10.6%). Commissural alignment was defined as 0° to 30° between native and FX commissures. Patient, anatomical, and procedural characteristics were retrospectively reviewed, and 30-day clinical and echocardiographic outcomes per Valve Academic Research Consortium-3 definitions were reported. RESULTS: Of 226 patients, 34.1% were low risk, 4% had a bicuspid valve, and 11.5% had a horizontal root (≥60°). Direct Inline sheath (Medtronic) was used in 67.6% and Lunderquist stiff wire (Cook Medical) in 35.4% of cases. Optimal hat marker orientation during deployment was achieved in 98.4%, with commissural alignment in 96.5%. At 30 days, 14.3% mild, 0.9% moderate, and no severe paravalvular leak were observed. Compared with the Evolut PRO+ experience from 1 center, FX had a more symmetrical implantation with shallower depth at the left coronary cusp (P < 0.001), fewer device recaptures (26.1% vs 39.5%; P = 0.004), and improved commissural alignment (96.5% vs 80.2%; P < 0.001). CONCLUSIONS: The Evolut FX system demonstrated favorable 30-day outcomes with a significant improvement over PRO+ in achieving commissural alignment, fewer device recaptures, and more symmetrical implantation. These features may benefit younger patients undergoing TAVR with the supra-annular, self-expanding valve, where lifetime management would be important.

Surgical Transcatheter Aortic Valve Replacement Explantation Technique.

As transcatheter aortic valve replacement (TAVR) indications expand, cardiac surgeons need to be prepared to manage heretofore rare TAVR complications requiring explantation, such as acute type A dissection, in these typically high-risk patients. This report describes the successful use of an explantation technique that is ready to hand, efficient, and effective at avoiding further injury to the aortic root and coronary ostia.

Surgical management of locally invasive basaloid carcinoma of thymic gland.

Thymic basaloid carcinoma is an extremely rare thymic tumor variant, and the most common presentations have been an incidental finding on a routine chest X-ray and dyspnea on exertion. Given its rarity, no treatment modalities have been demonstrated to improve survival. This rare case describes a patient with locally advanced thymic basaloid carcinoma treated by en bloc resection of phrenic nerve and left upper lobe with the tumor followed by adjuvant radiation therapy. Patient had no respiratory complaints at 10 months follow-up, and 10-month post-operative surveillance radiological study showed no objective sign of tumor recurrence.

Taking the Next Step: a Neural Coaptation Orthotopic Hind Limb Transplant Model to Maximize Functional Recovery in Rat.

Limb transplant in particular and vascularized composite allotransplant (VCA) in general have wide therapeutic promise that have been stymied by current limitations in immunosuppression and functional neuromotor recovery. Many animal models have been developed for studying unique features of VCA, but here we present a robust reproducible model of orthotopic hind limb transplant in rats designed to simultaneously investigate both aspects of current VCA limitation: immunosuppression strategies and functional neuromotor recovery. At the core of the model rests a commitment to meticulous, time-tested microsurgical techniques such as hand sewn vascular anastomoses and hand sewn neural coaptation of the femoral nerve and the sciatic nerve. This approach yields durable limb reconstructions that allow for longer lived animals capable of rehabilitation, resumption of daily activities, and functional testing. With short-term treatment of conventional immunosuppressive agents, allotransplanted animals survived up to 70 days post-transplant, and isotransplanted animals provide long lived controls beyond 200 days post-operatively. Evidence of neurologic functional recovery is present by 30 days post operatively. This model not only provides a useful platform for interrogating immunological questions unique to VCA and nerve regeneration, but also allows for in vivo testing of new therapeutic strategies specifically tailored for VCA.

Opioid creep in burn center discharge regimens: Doubled amounts and complexity of narcotic prescriptions over seven years.

Prescription opioid misuse is an epidemic international health crisis. Although burn providers are increasingly mindful of balancing pain relief with risk of opioid dependence, several burn centers have noticed their patients are still receiving an increased amount of opioids, termed "opioid creep." We examined discharge narcotic prescriptions at a single burn center in the Midwest United States and found that patients discharged in 2015 received nearly twice the amount of narcotics (mean=600 morphine equivalents [ME]) than those discharged in 2008 (mean=350 ME), with a significantly increased likelihood of a more complex narcotic discharge regimen. The increase in ME remained significant even after controlling for age, burn size, intensive care unit stay, discharge day, substance abuse, comorbidity status, insurance, language, race, and ethnicity. The data do not clearly explain such a significant increase. Although such increase in opioid prescription is undesirable, so too is regression to historical under-treatment of burn pain. Protocoled pain-management order sets on admission and discharge, as well as incorporation of alternatives adjuncts to lessen pain, may allow for better pain control with less opioid misuse.