Intermittent upper and lower body perfusion during circulatory arrest is safe for aortic repair.

INTRODUCTION: We report our initial surgical experience of intermittent upper and lower body retrograde perfusion during aortic repair under circulatory arrest. METHODS: Between 2007 and 2015, 148 consecutive patients underwent surgical aortic repair using moderate hypothermic circulatory arrest with intermittent upper and lower body retrograde perfusion. RESULTS: All patients underwent ascending aorta replacement; eight had hemiarch replacement (5.4%) and 92 had aortic root surgery (62.2%). Twenty-nine patients (19.6%) had re-operations and 60 patients (40.5%) had concomitant procedures. The mean duration of circulatory arrest was 23.2 ± 5.4 minutes (range 13-48 minutes). Hospital length of stay was 11.3 ± 16.9 days (median 7.0 days; interquartile range [IQR] 6 days). Complications included death in 0.7%, stroke in 3.4%, respiratory failure in 12.8%, renal replacement therapy in 2.0% and re-exploration for bleeding in 0.7%. Peak renal and hepatic biomarkers were: creatinine 1.2 ± 0.3 mg/dL, aspartate aminotransferase (AST) 291 ± 1112 U/L (IQR 91.8 U/L), alanine aminotransferase (ALT) 212 ± 924 U/L (IQR 43.0 U/L) and total bilirubin 1.2 ± 0.9 mg/dL. Peak lactate was 5.0 ± 3.3 mmol/L (IQR 3.3 mmol/L) and the mean time to normalization (<2 mmol/L) was 14.3 ± 14.0 hours. CONCLUSIONS: Intermittent upper and lower body retrograde perfusion during circulatory arrest is safe for aortic repair, resulting in low morbidity and mortality. There were only modest rises in hepatic and renal injury biomarkers as well as the rapid clearance of lactate. These findings support the continued study of this technique to reduce end-organ dysfunction during circulatory arrest, including expansion to patients with longer circulatory arrest duration and a direct comparison with conventional circulatory arrest without retrograde upper and lower body perfusion.

Ross Procedure Following a Dislodged Transcatheter Aortic Valve Replacement.

A 36-year-old pregnant woman with a history of rheumatic heart disease and prior aortic valve replacement and mitral valve repair presented to an outside hospital with severe aortic stenosis. The patient had a cardiac arrest upon labor induction and underwent a transcatheter aortic valve replacement (TAVR), which dislodged two days later. Five months later, the patient underwent removal of the dislodged TAVR and a Ross procedure at the authors' institution. The patient was stable upon discharge, with minimal aortic and pulmonary regurgitation. To the authors' knowledge, the present report is the first of the Ross procedure being used under such circumstances. It is suggested that caution be taken when using bioprosthetic and transcatheter aortic valves in young patients, and primary use of the Ross procedure is encouraged at experienced centers.

Right coronary artery obstruction following transcatheter aortic valve replacement by aortic valve mass.

A 93-year-old woman with symptomatic severe aortic stenosis and normal biventricular function was referred for transcatheter aortic valve replacement (TAVR) evaluation. Cardiac computed tomography revealed safe coronary heights and multiple large calcified mobile mass-like structures attached to the aortic valve (AV), confirmed also by transesophageal echocardiography, which were thought to be prominent Lambl's excrescences.

Coronary artery bypass grafting using the radial artery: clinical outcomes, patency, and need for reintervention.

BACKGROUND: Radial artery (RA) grafts are an attractive second arterial conduit after the left internal thoracic artery (LITA) for coronary artery bypass graft (CABG) surgery. However, long-term outcomes and the need for subsequent reintervention have not been defined. METHODS AND RESULTS: We performed a retrospective cohort study of our single institution's 16-year experience with 1851 consecutive patients (average age, 58 years; 82% men, 36% diabetic) undergoing primary, isolated CABG with the LITA, RA, and saphenous vein as needed. Average grafts per patient were 3.8, with 2.4 arterial grafts per patient. Survival was determined using the Social Security Death Index. Grafts were nonpatent if they had a >50% stenosis, a string sign, or were occluded. Five patients (0.3%) died in hospital and 0.8% had a myocardial infarction, 1.1% a stroke, and 0.6% renal failure. Kaplan-Meier-estimated 1-, 5-, 10-, and 15-year survival was 99%, 96%, 89%, and 75%, respectively. Of the cohort, 278 symptomatic patients underwent cardiac catheterization at our institution an average of 5.0±3.8 years (range, 0.1-12 years) after CABG. Overall RA (n=420 grafts) patency was 82% and SV (n=364 grafts) patency, 47% (P<0.0001). LITA (n=287 grafts including 9 sequential grafts) patency was 85% and right internal thoracic artery (n=15 grafts) patency was 80% (P=0.6). RA patency was not different from LITA patency (P=0.3). Overall freedom from catheterization, percutaneous coronary intervention, and CABG was 85%, 97%, and 99%, respectively. CONCLUSIONS: RA grafting is a highly effective revascularization strategy providing excellent short and long-term outcomes with very low rates of reintervention. RA patency is similar to LITA patency and is much better than SV patency. RA grafting should be more widely utilized in patients undergoing CABG.

Operative mortality and morbidity after the Ross procedure: a 26- year learning curve.

BACKGROUND AND AIM OF THE STUDY: The role of the Ross procedure in adults is controversial. In comparison with prosthetic aortic valve replacement (AVR), its greater technical complexity has been associated with increased operative mortality. The aim of the present study was to evaluate the impact of surgeon experience on early outcomes after the Ross procedure. METHODS: Using multivariate analysis, the details of 530 consecutive patients who had undergone the Ross operation between 1987 and 2013 were analyzed according to whether they had surgery during the early, middle, or later phases of a single-surgeon experience. RESULTS: Cumulative sum analysis revealed an initial learning curve of around 100 cases. There was no operative mortality in the later phase of 305 cases, compared to 3% (3/100) in the early phase and 2.4% (3/125) in the middle phase (p = 0.04). The mean EuroSCORE did not change significantly across the series (2.3-3.2%, p = 0.4), whereas the patient mix did change. A decreasing incidence of comorbidities, such as acute endocarditis (from 10% to 1.3%, p = 0.02), congestive heart failure (from 8% to 2.3%, p = 0.03) and coronary artery disease (from 11% to 2.3%, p = 0.001), occurred in parallel with increasing case complexity. Isolated Ross procedures were performed less frequently later in the series (42%, n = 130) compared to the early stage (68%, n = 68; p < 0.001), and concomitant ascending aortic or arch replacement were significantly more likely to be performed in later patients (33.8%, n = 103) compared to early-stage patients (1%, n = 1; p <0.001). Independent predictors of operative mortality and major morbidity included endocarditis (odds ratio (OR) 5.2, 95% confidence interval (CI) 1.3-21.5), diabetes (OR 4.3, 95% CI 1.2-15.5), and concomitant coronary artery bypass (OR 3.2, 95% CI 1.2-8.4). Residents or junior faculty performed the surgery in 26 cases, under direct supervision and without patient mortality. CONCLUSION: The Ross procedure can be performed with early outcomes comparable to that of isolated AVR in adults. The impact of the learning curve on patient outcomes may be mitigated by careful patient selection and experienced supervision.

What are the barriers to training residents in aortic root surgery?

BACKGROUND AND AIM OF THE STUDY: Aortic root surgery is a technically demanding procedure that is performed infrequently by most surgeons, with national mortality rates over 10%. The study aim was to identify the barriers to training residents in this operation. METHODS: By using univariate and multivariate logistic regression analysis, all consecutive adults (n = 356) undergoing aortic root reconstruction at The Mount Sinai Medical Center between 2007 and 2011 were retrospectively compared according to whether a resident or faculty surgeon performed the procedure. Surveys were then conducted to determine reasons why residents did not perform cases, and to evaluate outcomes of aortic root surgery performed by recent graduates of the program. RESULTS: Surgical techniques among patients included: root replacement (81%, n = 290) using homograft, composite bioprosthetic or mechanical valved conduits; Ross procedures (17%, n = 53); and other root surgery such as valve-sparing procedures (2%, n = 7). Residents performed 32% (n = 66/204) of cases when they were scrubbed. The incidence of mortality was lower for cases performed by residents (2%, n = 2) compared to faculty (4%, n = 12) (p=0.335), and no significant differences in cardiopulmonary bypass or cross-clamp times, early morbidity or late survival were observed. The most common reasons given why scrubbed residents did not perform cases were a mismatch between the skill of the resident and case complexity (46%, n = 94), followed by the faculty surgeon's preference (41%, n = 83). Recent program graduates had collectively performed 30 aortic root procedures independently as faculty surgeons, and with no mortality; however, most expressed a continued preference for more senior help on such cases. CONCLUSION: Residents can safely perform aortic root surgery under appropriate supervision. The greatest challenge involved in improving resident training in aortic root surgery lies in routinely matching resident skills with case complexity and teaching expertise.

Postoperative cardiac homograft involvement in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare multisystem disorder which is known to affect the skin, lungs, bone, pituitary gland, retroperitoneum and cardiovascular system. The case is described of a patient with ECD who had previously undergone a Ross procedure for presumed endocarditis involving the aortic valve and aortic root. The patient subsequently developed arthralgias, abdominal pain (requiring an exploratory laparotomy) and polydipsia. Furthermore, he developed progressive, symptomatic stenosis of the pulmonic homograft. A reoperative replacement of the homograft was required. The clinically suspected diagnosis of ECD was confirmed by a pathologic analysis of the explanted pulmonary homograft, and also (retrospectively) of previously resected mesenteric tissue. It is postulated that the patient may have developed ECD as a result of an immunologic reaction to the homograft tissue used for the Ross procedure.

Propensity-Matched Comparison of the Ross Procedure and Prosthetic Aortic Valve Replacement in Adults.

BACKGROUND: There has recently been renewed interest in the Ross procedure in adults. OBJECTIVES: The goal of this study was to compare long-term outcomes after the Ross procedure vs biological and mechanical aortic valve replacement (AVR) in adults (aged 18-50 years) undergoing aortic valve surgery. METHODS: Mandatory California and New York databases were queried between 1997 and 2014. Exclusion criteria included: ≥1 concomitant procedure, reoperations, infective endocarditis, intravenous drug use, hemodialysis, and out-of-state residency. Propensity matching (1:1:1) was used, resulting in 434 patients per group. The primary endpoint was all-cause mortality. Secondary endpoints were stroke, major bleeding, reoperation, and endocarditis. Median follow-up was 12.5 years (IQR: 9.3-15.7 years). RESULTS: At 15 years, actuarial survival after the Ross procedure was 93.1% (95% CI: 89.1%-95.7%), similar to that of the age-, sex-, and race-matched U.S. general population. It was significantly lower after biological AVR (HR: 0.42; 95% CI: 0.23-0.075; P = 0.003) and mechanical AVR (HR: 0.45; 95% CI: 0.26-0.79; P = 0.006). At 15 years, the Ross procedure was associated with a lower cumulative risk of reintervention (P = 0.008) and endocarditis (P = 0.01) than biological AVR. In contrast, at 15 years, the Ross procedure was associated with a higher cumulative incidence of reoperation (P < 0.001) but lower risks of stroke (P = 0.03) and major bleeding (P = 0.016) than mechanical AVR. Thirty-day mortality after valve-related complications was lowest after a reintervention. CONCLUSIONS: In young adults, the Ross procedure is associated with better long-term survival and freedom from valve-related complications compared with prosthetic AVR. This confirms the notion that a living valve substitute in the aortic position translates into improved clinically relevant outcomes.

Total aortic arch replacement using a frozen elephant trunk device: Results of a 1-year US multicenter trial.

OBJECTIVE: In this prospective US investigational device exemption trial, we assessed the safety and 1-year clinical outcomes of the Thoraflex Hybrid device (Terumo Aortic) for the frozen elephant trunk technique to repair the ascending aorta, aortic arch, and descending thoracic aorta. METHODS: For the trial, which involved 12 US sites, 65 patients without rupture were recruited into the primary study group, and 9 patients were recruited into the rupture group. All patients underwent open surgical repair of the ascending aorta, aortic arch, and descending thoracic aorta in cases of aneurysm and/or dissection. The primary end point was freedom from major adverse events (MAE), defined as permanent stroke, permanent paraplegia/paraparesis, unanticipated aortic-related reoperation (excluding reoperation for bleeding), or all-cause mortality. RESULTS: In the primary study group, 2 patients were lost to follow-up at 1 year. Freedom from MAE at 1 year was 81% (51/63). Seven patients (11%) died (including 2 before 30 days or discharge), 3 patients (5%) suffered permanent stroke, and 3 (5%) developed permanent paraplegia/paraparesis. Twenty-six patients (41%) underwent planned extension procedures, including 22 endovascular procedures within a median of 122 (interquartile range, 64-156) days. In the aortic rupture group, 2 patients were lost to follow-up at 1 year. Freedom from MAE at 1 year was 71% (5/7). One patient (14%) died, 2 patients (29%) had permanent stroke, and none had permanent paraplegia/paraparesis. No extension procedures were performed in the rupture group. CONCLUSIONS: One-year results with the Thoraflex Hybrid device are acceptable. Long-term data are necessary to assess the durability of these repairs.

Outcomes of reoperations after Ross procedure.

BACKGROUND: Potential for difficult reoperations has been a concern for patients undergoing a Ross procedure. Data regarding the outcomes of such reoperations is extremely limited. We examined our experience to define the current scope and risk of these operations. METHODS: Between 1996 and 2020, 83 patients who had a previous Ross procedure underwent 89 reoperative surgeries. There were 72 males and average age was 48 with a range of 18-76. Twenty-four patients had more than one prior reoperation, with five patients having more than one reoperation post Ross. Patients were stratified by primary reason for reoperation including autograft dysfunction, homograft dysfunction, or other cardiac surgical problems. Demographic, operative, and outcomes data were collected from clinical records and placed in a secure data base for analysis. RESULTS: A total of 176 procedures were done in the 89 operations. Autograft dysfunction affected 68 patients. Homograft dysfunction affected 27 patients. Both of these were seen in 17 patients. Other cardiac problems required 79 other procedures. There were two (2.2%) operative deaths, with perioperative morbidity affecting six patients (6.7%). Survival following reoperation after Ross was 82.3% and 77.5% (±2), at ten and fifteen years respectively. CONCLUSIONS: Reoperations after a Ross procedure can be challenging but can be done with a high degree of safety and long-term benefit in experienced hands.

Operative risks of the Ross procedure.

BACKGROUND: The risk of the Ross procedure continues to be debated. We sought to determine the immediate outcomes of the Ross procedure in a large consecutive cohort that included patients undergoing reoperative cardiac surgery and/or concomitant cardiac procedures. METHODS: Between March 1987 and September 2019, 702 patients underwent a full root Ross procedure. There were 530 male patients and 172 female patients, with a mean age of 41.6 years. One hundred and one patients had at least one previous sternotomy; 323 patients had concomitant procedures. Patients were stratified into 2 groups: simple and complex. Simple Ross patients were those who had no previous sternotomy and had only minor concomitant procedures performed at the time of their Ross, such as aortoplasty or closure of patent foramen ovale. The complex Ross group included patients with at least one previous sternotomy and/or additional procedures that we deemed complex, such as ascending aortic replacement and mitral valve repair. Complexity and group outcomes were evaluated in consecutive terciles of time. RESULTS: There were 7 (1%) operative deaths. Morbidity affected 46 other patients (6.6%). The simple Ross group comprised 419 patients (59.7%), with mortality in 3 (0.7%) and morbidity in 20 (4.8%). The complex Ross comprised 283 patients (40.3%), with mortality in 4 (1.4%) and morbidity in 26 (9.2%). Simple Ross cases decreased in volume over time, with complex cases increasing from 34% to 48%. CONCLUSIONS: Excellent results can be achieved with the Ross procedure despite broader indications that include patients with previous sternotomy and with the need for concomitant procedures.

Proteomic Architecture of Valvular Extracellular Matrix: FNDC1 and MXRA5 Are New Biomarkers of Aortic Stenosis.

This study analyzed the expression of extracellular matrix (ECM) proteins during aortic valve calcification with mass spectrometry, and further validated in an independent human cohort using RNAseq data. The study reveals that valve calcification is associated with significant disruption in ECM and metabolic pathways, and highlights a strong connection between metabolic markers and ECM remodeling. It also identifies FNDC1 and MXRA5 as novel ECM biomarkers in calcified valves, electing them as potential targets in the development and progression of aortic stenosis.

A plasma proteogenomic signature for fibromuscular dysplasia.

AIMS: Fibromuscular dysplasia (FMD) is a poorly understood disease that predominantly affects women during middle-life, with features that include stenosis, aneurysm, and dissection of medium-large arteries. Recently, plasma proteomics has emerged as an important means to understand cardiovascular diseases. Our objectives were: (i) to characterize plasma proteins and determine if any exhibit differential abundance in FMD subjects vs. matched healthy controls and (ii) to leverage these protein data to conduct systems analyses to provide biologic insights on FMD, and explore if this could be developed into a blood-based FMD test. METHODS AND RESULTS: Females with 'multifocal' FMD and matched healthy controls underwent clinical phenotyping, dermal biopsy, and blood draw. Using dual-capture proximity extension assay and nuclear magnetic resonance-spectroscopy, we evaluated plasma levels of 981 proteins and 31 lipid sub-classes, respectively. In a discovery cohort (Ncases = 90, Ncontrols = 100), we identified 105 proteins and 16 lipid sub-classes (predominantly triglycerides and fatty acids) with differential plasma abundance in FMD cases vs. controls. In an independent cohort (Ncases = 23, Ncontrols = 28), we successfully validated 37 plasma proteins and 10 lipid sub-classes with differential abundance. Among these, 5/37 proteins exhibited genetic control and Bayesian analyses identified 3 of these as potential upstream drivers of FMD. In a 3rd cohort (Ncases = 506, Ncontrols = 876) the genetic locus of one of these upstream disease drivers, CD2-associated protein (CD2AP), was independently validated as being associated with risk of having FMD (odds ratios = 1.36; P = 0.0003). Immune-fluorescence staining identified that CD2AP is expressed by the endothelium of medium-large arteries. Finally, machine learning trained on the discovery cohort was used to develop a test for FMD. When independently applied to the validation cohort, the test showed a c-statistic of 0.73 and sensitivity of 78.3%. CONCLUSION: FMD exhibits a plasma proteogenomic and lipid signature that includes potential causative disease drivers, and which holds promise for developing a blood-based test for this disease.

CD90 Identifies Adventitial Mesenchymal Progenitor Cells in Adult Human Medium- and Large-Sized Arteries.

Mesenchymal stem cells (MSCs) reportedly exist in a vascular niche occupying the outer adventitial layer. However, these cells have not been well characterized in vivo in medium- and large-sized arteries in humans, and their potential pathological role is unknown. To address this, healthy and diseased arterial tissues were obtained as surplus surgical specimens and freshly processed. We identified that CD90 marks a rare adventitial population that co-expresses MSC markers including PDGFRα, CD44, CD73, and CD105. However, unlike CD90, these additional markers were widely expressed by other cells. Human adventitial CD90+ cells fulfilled standard MSC criteria, including plastic adherence, spindle morphology, passage ability, colony formation, and differentiation into adipocytes, osteoblasts, and chondrocytes. Phenotypic and transcriptomic profiling, as well as adoptive transfer experiments, revealed a potential role in vascular disease pathogenesis, with the transcriptomic disease signature of these cells being represented in an aortic regulatory gene network that is operative in atherosclerosis.