Learning curves for transfemoral transcatheter aortic valve replacement in the PARTNER-I trial: Success and safety.

OBJECTIVES: To identify number of cases needed to maximize device success and minimize adverse events after transfemoral transcatheter aortic valve replacement (TF-TAVR), and determine if adverse events were linked to the technical performance learning curve. BACKGROUND: TF-TAVR is a complex procedure with an incompletely characterized learning curve for clinical outcomes. METHODS: From 4/2007-2/2012, 1521 patients underwent TF-TAVR in the PARTNER-I trial. Outcomes learning curves were defined as number of cases needed to reach a plateau for device success, adverse events, and post-procedure length of stay. Institutional variation was accounted for by mixed-model non-linear techniques, which were also used to identify contribution of the procedure time learning curve to 30-day major adverse events and length of stay. RESULTS: Eighty percent device success was achieved after 22 cases; major vascular complications fell below 5% after 70 cases and major bleeding below 10% after 25 cases. It took an average of 28 cases to achieve a consistent low risk of 30-day major adverse events, but institutions entering in the middle of the trial achieved it after about 26. The most significant correlate of 30-day major adverse events and post-procedure length of stay was procedure time (P < 0.0001). However, this association was related to patient and unmeasured variables, not the procedure time learning curve (P = 0.6). CONCLUSIONS: By end of trial, a consistent low risk of adverse events was achieved after ∼26 cases. However, these improved results were due to change in patient risk profile; outcomes were not linked to the technical performance learning curve. © 2015 Wiley Periodicals, Inc.

Learning curves for transfemoral transcatheter aortic valve replacement in the PARTNER-I trial: Technical performance.

OBJECTIVES: To assess technical performance learning curves of teams performing transfemoral transcatheter aortic valve replacement (TF-TAVR). BACKGROUND: TF-TAVR is a new procedure for treating severe aortic stenosis. The number of cases required for procedural efficiency is unknown. METHODS: In the PARTNER-I trial, 1,521 patients underwent TF-TAVR from 4/2007-2/2012. Learning curve analysis of technical performance metrics was performed using institution-specific patient sequence number, interval between procedures, and institutional trial entry date. Learning curve characteristics were assessed using semi-parametric and parametric mixed-effects models. RESULTS: As patient sequence number increased, average procedure time decreased from 154 to 85 minutes (P < 0.0001), and fluoroscopy time from 28 to 20 minutes (P < 0.0001). Procedure time plateaued at an average of 83 minutes (range 52-140). Procedure time plateau was dynamic during the course of the trial, averaging 25 cases (range 21-52) by its end. The later institutions enrolled in the trial, the shorter the initial procedure time. During the trial, percutaneous rather than surgical access increased from 7.9% to 69%. CONCLUSIONS: Technical performance learning curves exist for TF-TAVR; procedural efficiency increased with experience, with concomitant decreases in radiation and contrast media exposure. The number of cases needed to achieve efficiency decreased progressively, with optimal procedural performance reached after approximately 25 cases for late-entering institutions. Knowledge and experience accumulated by early TF-TAVR institutions were disseminated, shortening the learning curve of late-entering institutions. Technological advances resulting from learning during the trial moved the field from initial conservative surgical cut-down to percutaneous access for most patients. © 2015 Wiley Periodicals, Inc.

The association between ischemic and jeopardized myocardia and all-cause mortality in patients with peripheral artery disease.

Peripheral artery disease (PAD) is associated with increased mortality and concomitant coronary artery disease (CAD). However, it is unclear whether uncovering the presence of functional coronary ischemia by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) would further help stratifying that excess risk. From January 2000 to 2009, 4294 individuals underwent cardiac stress testing within 180 days of ankle-brachial index (ABI) measurements. Of these, 645 had PAD and SPECT MPI stress testing. Abnormal ABI was defined as ⩽ 0.9 or prior lower extremity arterial revascularization. Myocardial ischemic burden and total jeopardized myocardium were represented by the summed difference score (SDS) and summed stress score (SSS), respectively. Univariate and multivariable Cox proportional hazard analyses were used to study the impact of SDS and SSS on all-cause mortality. Additionally, using a hierarchical approach, we examined the step-wise addition of post-stress test coronary and lower extremity arterial revascularizations as time-varying covariates on outcomes. We found no significant difference in all-cause mortality between patients with ischemic myocardium (SDS > 0) and those without (SDS = 0) (adjusted HR: 0.94, 95% CI: 0.53-1.69; p = 0.84). Similarly, the presence of jeopardized myocardium (SSS > 0) did not have a significant impact on mortality (adjusted HR: 1.16, 95% CI: 0.67-2.00; p = 0.59). Moreover, adjustment for post-testing coronary and lower extremity arterial revascularizations did not affect our results. In conclusion, ischemic and jeopardized myocardia are not predictors of all-cause mortality in PAD; thus, SPECT MPI does not appear to be a useful risk stratification tool in these patients.

Evolution of serious and life-threatening COVID-19 pneumonia as the SARS-CoV-2 pandemic progressed: an observational study of mortality to 60 days after admission to a 15-hospital US health system.

OBJECTIVE: In order to predict at hospital admission the prognosis of patients with serious and life-threatening COVID-19 pneumonia, we sought to understand the clinical characteristics of hospitalised patients at admission as the SARS-CoV-2 pandemic progressed, document their changing response to the virus and its variants over time, and identify factors most importantly associated with mortality after hospital admission. DESIGN: Observational study using a prospective hospital systemwide COVID-19 database. SETTING: 15-hospital US health system. PARTICIPANTS: 26 872 patients admitted with COVID-19 to our Northeast Ohio and Florida hospitals from 1 March 2020 to 1 June 2022. MAIN OUTCOME MEASURES: 60-day mortality (highest risk period) after hospital admission analysed by random survival forests machine learning using demographics, medical history, and COVID-19 vaccination status, and viral variant, symptoms, and routine laboratory test results obtained at hospital admission. RESULTS: Hospital mortality fell from 11% in March 2020 to 3.7% in March 2022, a 66% decrease (p<0.0001); 60-day mortality fell from 17% in May 2020 to 4.7% in May 2022, a 72% decrease (p<0.0001). Advanced age was the strongest predictor of 60-day mortality, followed by admission laboratory test results. Risk-adjusted 60-day mortality had all patients been admitted in March 2020 was 15% (CI 3.0% to 28%), and had they all been admitted in May 2022, 12% (CI 2.2% to 23%), a 20% decrease (p<0.0001). Dissociation between observed and predicted decrease in mortality was related to temporal change in admission patient profile, particularly in laboratory test results, but not vaccination status or viral variant. CONCLUSIONS: Hospital mortality from COVID-19 decreased substantially as the pandemic evolved but persisted after hospital discharge, eclipsing hospital mortality by 50% or more. However, after accounting for the many, even subtle, changes across the pandemic in patients' demographics, medical history and particularly admission laboratory results, a patient admitted early in the pandemic and predicted to be at high risk would remain at high risk of mortality if admitted tomorrow.

Isolated mitral valve endocarditis: Patient, disease, and surgical factors that influence outcomes.

OBJECTIVE: The objectives of this study were to investigate patient characteristics, valve pathology, bacteriology, and surgical techniques related to outcome of patients who underwent surgery for isolated native (NVE) or prosthetic (PVE) mitral valve endocarditis. METHODS: From January 2002 to January 2020, 447 isolated mitral endocarditis operations were performed, 326 for NVE and 121 for PVE. Multivariable analysis of time-related outcomes used random forest machine learning. RESULTS: Staphylococcus aureus was the most common causative organism. Of 326 patients with NVE, 88 (27%) underwent standard mitral valve repair, 43 (13%) extended repair, and 195 (60%) valve replacement. Compared with NVE with standard repair, patients who underwent all other operations were older, had more comorbidities, worse cardiac function, and more invasive disease. Hospital mortality was 3.8% (n = 17); 0 (0%) after standard valve repair, 3 (7.0%) after extended repair, 8 (4.1%) after NVE replacement, and 6 (5.0%) after PVE re-replacement. Survival at 1, 5, and 10 years was 91%, 75%, and 62% after any repair and 86%, 62%, and 44% after replacement, respectively. The most important risk factor for mortality was renal failure. Risk-adjusted outcomes, including survival, were similar in all groups. Unadjusted extended repair outcomes, particularly early, were similar or worse than replacement in terms of reinfection, reintervention, regurgitation, gradient, and survival. CONCLUSIONS: A patient- and pathology-tailored approach to surgery for isolated mitral valve endocarditis has low mortality and excellent results. Apparent superiority of standard valve repair is related to patient characteristics and pathology. Renal failure is the most powerful risk factor. In case of extensive destruction, extended repair shows no benefit over replacement.

Thoracoabdominal Esophagectomy: Then and Now.

BACKGROUND: Open approaches for esophagectomy are often still useful; of these, left thoracoabdominal esophagectomy (TAE) is poorly understood and often criticized. Hence, we examined TAE's worldwide utilization, survival, and present-day use and outcomes at our institution compared with contemporary national averages. METHODS: The Worldwide Esophageal Cancer Collaboration database includes 8854 patients who underwent esophagectomy for cancer between 2005 and 2014, a period when TAE was our center's most common approach. Two propensity score-matched models were constructed: worldwide TAE vs worldwide non-TAE (751 matched pairs); and our high-volume center TAE vs worldwide non-TAE (273 matched pairs). All-cause mortality was compared between matched groups. Institutional TAE data from 2017 to 2021 were assessed for present-day use and outcomes. RESULTS: Worldwide, propensity score-matched patients undergoing TAE had a median of 20 lymph nodes resected vs 17 after non-TAE (P < .0001). Five-year survival was 34% for worldwide TAE vs 42% for worldwide non-TAE groups (P = .04). Three-year matched survival was 52% for high-volume TAE compared with 54% for worldwide non-TAE groups (P = .1). From 2017 to 2021 at our institution, 90 (26%) of 346 esophagectomies were performed by TAE. Pneumonia developed in 5 patients (5.6%), with 88 patients (98%) alive at 30 days, comparable to contemporary averages of The Society of Thoracic Surgeons. CONCLUSIONS: When it is performed as the primary approach in high volumes, TAE can have comparable outcomes to non-TAE with low morbidity. At present, we find that TAE is most useful in patients with truncal obesity, prior abdominal operations, and locally advanced cardia tumors with potential for variable extent of resection.

Atrial Fibrillation after Descending Aorta Repair: Occurrence, Risk Factors, and Impact on Outcomes.

BACKGROUND: As risks of repairing the descending thoracic and thoracoabdominal aorta diminish, common complications that may prolong hospital stay, or actually increase risk, require attention. One such complication is postoperative atrial fibrillation (AF). Therefore, we characterized prevalence of, risk factors for, and effects of postoperative atrial fibrillation (PoAF) after descending and thoracoabdominal aorta repair. METHODS: From January 2000 to January 2011, 696 patients underwent open descending or thoracoabdominal aorta repair at Cleveland Clinic. Operations approached via median sternotomy (n = 178) and patients treated preoperatively for arrhythmias (32 amiodarone, 9 paced) or in AF on preoperative electrocardiogram (n = 14) were excluded, leaving 463. Logistic regression analysis identified risk factors for PoAF. Temporal relation of PoAF with postoperative morbidities was determined, and outcomes following PoAF were compared between propensity-matched pairs. RESULTS: New-onset PoAF occurred in 101 patients (22%) at a median 68 hours of postincision. Risk factors included older age (p = 0.002) and history of remote AF (p = 0.0004) but not operative details, such as pericardiotomy for cardiac cannulation. Hypoperfusion and neurologic complications tended to precede PoAF, whereas sepsis, respiratory failure, and dialysis followed. Among 94 propensity-matched patient pairs, those developing PoAF were more likely to experience hypoperfusion (p = 0.006), respiratory failure (p = 0.009), dialysis (p = 0.04), paralysis (p < 0.0001), longer intensive care unit stay (median 7 vs. 5 d, p = 0.02), and longer postoperative hospital stay (median 15 vs. 13 d, p = 0.004). However, hospital death was similar (6/94 PoAF [6.4%] vs. 7/94 no PoAF [7.4%], p = 0.8). CONCLUSION: PoAF after descending thoracic aorta surgery is relatively common and a part of a constellation of other serious complications prolonging postoperative recovery. While PoAF was associated with adverse events, it did not impact postoperative cost and mortality. Descending thoracic aorta surgery is by itself comorbid enough, which is likely why PoAF does not have a more significant effect on postoperative recovery and cost.

Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid.

Congenital diaphragmatic hernia (CDH) is a severe birth defect frequently associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and treatment response. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. Amniotic fluid was obtained at term (37-39 weeks) from women with normal pregnancies (n = 5) or carrying fetuses with CDH (n = 5). After immuno-depletion of the highest abundance proteins, off-line fractionation and high-resolution tandem mass spectrometry were performed and quantitative differences between the proteomes of the groups were determined. Of 1036 proteins identified, 218 were differentially abundant. Bioinformatics analysis showed significant changes in GP6 signaling, in the MSP-RON signaling in macrophages pathway and in networks associated with cardiovascular system development and function, connective tissue disorders and dermatological conditions. Differences in selected proteins, namely pulmonary surfactant protein B, osteopontin, kallikrein 5 and galectin-3 were validated by orthogonal testing using ELISA in larger cohorts and showed statistically significant differences aiding in the diagnosis and prediction of CDH. The findings provide potential tools for clinical management of CDH.

Choosing transcatheter aortic valve replacement in porcelain aorta: outcomes versus surgical replacement.

OBJECTIVES: Porcelain aorta complicates aortic valve replacement and is an indication for transcatheter approaches. No study has compared surgical and transcatheter valve replacement in the setting of porcelain aorta. We characterize porcelain aorta patients undergoing aortic valve replacement and the association of aortic calcification and outcomes. METHODS: Patients undergoing aortic valve replacement with porcelain aorta were identified. Aortic calcium volume was determined using 3D computed tomography thresholding techniques. Propensity scoring was performed to assess the effect of surgical versus transcatheter approaches. Risk factors for composite major hospital complications (death, stroke and dialysis) were identified using random forest machine learning. RESULTS: From January 2006 to January 2015, 164 patients with porcelain aorta underwent aortic valve replacement [105 (64%) surgical replacement, 59 (36%) transcatheter replacement]. Propensity scoring matched 29 pairs (49% of transcatheter patients). Before matching, 5-year survival was 41% [(43% surgical, 35% transcatheter, P(log-rank) = 0.9]. After matching, mortality for surgical versus transcatheter replacement was 3.4% (n = 1) vs 10% (n = 3), stroke 14% (n = 4) vs 3.4% (n = 1) and dialysis 6.9% (n = 2) versus 11% (n = 3). Matched 5-year survival was 40% after surgical replacement and 29% after transcatheter replacement [P(log-rank) = 0.4]. Total aortic calcium volume was greater in transcatheter than surgical patients [18 (8.0) vs 17 (7.7) ml] and was associated with more major hospital complications after either approach. CONCLUSIONS: Surgical and transcatheter approaches are complementary options for aortic stenosis with porcelain aorta. Surgical valve replacement remains an effective treatment for patients requiring concomitant procedures. Quantifying aortic calcium volume is a helpful risk predictor in all patients with porcelain aorta.

Longitudinal versus circumferential biomechanical behavior of the aneurysmal ascending aorta.

OBJECTIVES: We evaluate the independent effects of patient and aortic tissue characteristics on biaxial physiologic mechanical metrics in aneurysmal and nonaneurysmal tissues, and uniaxial failure metrics in aneurysmal tissue, comparing longitudinal and circumferential behavior. METHODS: From February 2017 to October 2022, 382 aortic specimens were collected from 134 patients; 268 specimens underwent biaxial testing, and 114 specimens underwent uniaxial testing. Biaxial testing evaluated Green-Lagrange transition strain and low and high tangent moduli. Uniaxial testing evaluated failure stretch, Cauchy stress, and low and high tangent moduli. Longitudinal gradient boosting models were implemented to estimate mechanical metrics and covariates of importance. RESULTS: On biaxial testing, nonaneurysmal tissue was less deformable and exhibited a lower transition strain than aneurysmal tissue in the longitudinal (0.18 vs 0.30, P < .001) and circumferential (0.25 vs 0.30, P = .01) directions. Older age and increasing ascending aortic length contributed most to predicting transition strain. On uniaxial testing, longitudinal specimens failed at lower stretch (1.4 vs 1.5, P = .003) and Cauchy stress (1.0 vs 1.9 kPa, P < .001) than circumferential specimens. Failure stretch and Cauchy stress were most strongly associated with tissue orientation and decreased sharply with older age. Age, ascending aortic length, and tissue thickness were the most frequent covariates predicting mechanical metrics across 10 prediction models. CONCLUSIONS: Age was the strongest predictor of mechanical behavior. After adjusting for age, nonaneurysmal tissue was less deformable than aneurysmal tissue. Differences in longitudinal and circumferential mechanics contribute to tissue dysfunction and failure in ascending aneurysms. This highlights the need to better understand the effects of age, ascending aortic length, and thickness on clinical aortic behavior.

A dynamic Norwood mortality estimation: Characterizing individual, updated, predicted mortality trajectories after the Norwood operation.

Objective: Post-Norwood mortality remains high and unpredictable. Current models for mortality do not incorporate interstage events. We sought to determine the association of time-related interstage events, along with (pre)operative characteristics, with death post-Norwood and subsequently predict individual mortality. Methods: From the Congenital Heart Surgeons' Society Critical Left Heart Obstruction cohort, 360 neonates underwent Norwood operations from 2005 to 2016. Risk of death post-Norwood was modeled using a novel application of parametric hazard analysis, in which baseline and operative characteristics and time-related adverse events, procedures, and repeated weight and arterial oxygen saturation measurements were considered. Individual predicted mortality trajectories that dynamically update (increase or decrease) over time were derived and plotted. Results: After the Norwood, 282 patients (78%) progressed to stage 2 palliation, 60 patients (17%) died, 5 patients (1%) underwent heart transplantation, and 13 patients (4%) were alive without transitioning to another end point. In total, 3052 postoperative events occurred and 963 measures of weight and oxygen saturation were obtained. Risk factors for death included resuscitated cardiac arrest, moderate or greater atrioventricular valve regurgitation, intracranial hemorrhage/stroke, sepsis, lower longitudinal oxygen saturation, readmission, smaller baseline aortic diameter, smaller baseline mitral valve z-score, and lower longitudinal weight. Each patient's predicted mortality trajectory varied as risk factors occurred over time. Groups with qualitatively similar mortality trajectories were noted. Conclusions: Risk of death post-Norwood is dynamic and most frequently associated with time-related postoperative events and measures, rather than baseline characteristics. Dynamic predicted mortality trajectories for individuals and their visualization represent a paradigm shift from population-derived insights to precision medicine at the patient level.

Age is superior to aortopathy phenotype as a predictor of aortic mechanics in patients with bicuspid valve.

OBJECTIVES: Bicuspid aortic valve (BAV) aortopathy is defined by 3 phenotypes-root, ascending, and diffuse-based on region of maximal aortic dilation. We sought to determine the association between aortic mechanical behavior and aortopathy phenotype versus other clinical variables. METHODS: From August 1, 2016, to March 1, 2023, 375 aortic specimens were collected from 105 patients undergoing elective ascending aortic aneurysm repair for BAV aortopathy. Planar biaxial data (191 specimens) informed constitutive descriptors of the arterial wall that were combined with in vivo geometry and hemodynamics to predict stiffness, stress, and energy density under physiologic loads. Uniaxial testing (184 specimens) evaluated failure stretch and failure Cauchy stress. Boosting regression was implemented to model the association between clinical variables and mechanical metrics. RESULTS: There were no significant differences in mechanical metrics between the root phenotype (N = 33, 31%) and ascending/diffuse phenotypes (N = 72, 69%). Biaxial testing demonstrated older age was associated with increased circumferential stiffness, decreased stress, and decreased energy density. On uniaxial testing, longitudinally versus circumferentially oriented specimens failed at significantly lower Cauchy stress (50th [15th, 85th percentiles]: 1.0 [0.7, 1.6] MPa vs 1.9 [1.3, 3.1] MPa; P < .001). Age was associated with decreased failure stretch and stress. Elongated ascending aortas were also associated with decreased failure stress. CONCLUSIONS: Aortic mechanical function under physiologic and failure conditions in BAV aortopathy is robustly associated with age and poorly associated with aortopathy phenotype. Data suggesting that the root phenotype of BAV aortopathy portends worse outcomes are unlikely to be related to aberrant, phenotype-specific tissue mechanics.

Ultra-Hybrid Repair: Open Thoracoabdominal Completion After Descending Stent Grafting.

To characterize patient risk profiles and outcomes associated with staged ultra-hybrid repair of extensive aortic disease, in which open thoracoabdominal completion was performed after thoracic stent grafting. From 1/2006 to 1/2021, 92 patients underwent open thoracoabdominal repair of chronic dissection (n=58, 63%), degenerative aneurysm (n=28, 30%), endoleak (n=4, 4.3%), or symptomatic acute type B dissection (n=2, 2.2%) after descending thoracic stent grafting (69, 75%), frozen elephant trunk (5, 5%), or both (18, 20%). The surgical graft was sewn to the distal endovascular device in situ, reducing the extent of the open procedure and eliminating the need for hypothermic circulatory arrest. Mean age was 58±13 years, 89 (97%) were hypertensive, 38 (43%) had chronic obstructive pulmonary disease, 63 (72%) were smokers, 20 (24%) had a prior stroke, and 33 (36%) had a suspected or confirmed heritable aortic condition. Hospital mortality was 7.6% (n=7). Complications included dialysis (16, 20%), tracheostomy (8, 8.7%), stroke (5, 5.7%), and permanent paralysis (6, 6.9%). Survival at 1, 3, and 5 years was 80%, 71%, and 66%, respectively. Mortality was associated with higher blood urea nitrogen and longer distance between the distal endograft edge and proximal patent visceral vessel (P=0.004 and .01, respectively). Patients with extensive aortic disease undergoing open aortic repair after thoracic stent grafting are often young with chronic dissection, multiple comorbidities, or a heritable aortic condition. Success of staged ultra-hybrid operations demonstrates open and endovascular repair strategies are complementary, even when performed in a high-risk patient population.

Well-functioning bicuspid aortic valves should be preserved during aortic replacement for the ascending aortopathy phenotype.

OBJECTIVES: Consensus has not been reached on whether or not to replace or preserve a well-functioning bicuspid aortic valve (BAV) in patients undergoing aortic replacement for the ascending phenotype of BAV aortopathy. We characterize morphology, evaluate progression of aortic regurgitation or aortic stenosis, and investigate the need for aortic valve replacement in patients whose well-functioning BAV was preserved during ascending aortic replacement ≥10 years prior. METHODS: From January 1991 to August 2011, 191 patients with a well-functioning BAV underwent supracoronary aortic replacement (113 valves were minimally repaired). Aortic morphology was evaluated, aortic regurgitation grade and transvalvular aortic gradient modeled parametrically, and survival assessed by the Kaplan-Meier method. Median follow-up was 10 years. RESULTS: Mean aortic diameter was 2.9 ± 0.53 cm at the annulus and 4.2 ± 0.55 cm at the sinuses. Mean maximum ascending diameter was 5.1 ± 0.49 cm. All patients exhibited a cusp-fusion BAV phenotype. Fifteen-year progression to severe aortic regurgitation was 3.2%. Mean aortic valve gradient began to rise 5 years postoperatively to 27 mm Hg by 14 years. Freedom from aortic valve replacement at 1, 5, 10, and 15 years was 100%, 95%, 83%, and 63%, respectively. Minimal valve repair was not associated with late aortic valve replacement. Fifteen-year survival was 74%. CONCLUSIONS: Preserving a well-functioning BAV should be considered in carefully selected patients undergoing aortic replacement for the ascending phenotype of BAV aortopathy. The valves remain durable in the long term, with slow progression of regurgitation or stenosis, and low probability of aortic valve replacement through 10 years.

Outcomes of mitral valve re-replacement for bioprosthetic structural valve deterioration.

OBJECTIVES: Reoperation for structural valve deterioration (SVD) of bioprosthetic mitral valves carries a presumed high operative risk, and transcatheter mitral valve-in-valve implantation has emerged as an alternative. However, surgical risk and long-term outcome following mitral valve re-replacement in these patients remain ill-defined. Hence, we sought to evaluate outcomes and long-term survival following surgical mitral valve re-replacement and to identify risk factors for mortality. METHODS: From January 1990 to January 2017, 525 patients underwent surgical mitral valve re-replacement at Cleveland Clinic for bioprosthetic SVD: 133 (25%) isolated operations and 392 (75%) with concomitant procedures. Surgical complications and modes of death were compiled, long-term mortality assessed, and risk factors identified using a multivariable nonproportional hazards model and random forest analysis. RESULTS: SVD was characterized by bioprosthetic regurgitation in 81% (425 out of 525) and stenosis in 44% (231 out of 525). One in-hospital death occurred after isolated valve re-replacement (0.75%) and 28 deaths occurred (7.1%; P = .003) after nonisolated re-replacement, 19 (68%) of which were from coagulopathy, vasoplegia, and multisystem organ failure. In the nonisolated group, incremental risk factors for time-related death after re-replacement included New York Heart Association functional class IV symptoms, concomitant coronary artery bypass grafting, prolonged cardiopulmonary bypass time, and transfusions. CONCLUSIONS: Mitral valve re-replacement for bioprosthetic SVD was associated with low surgical risk and excellent long-term survival. Isolated mitral valve re-replacement for bioprosthetic SVD had near-zero surgical risk. Excessive cardiopulmonary bypass duration and multiple transfusions correlated with increased early mortality in nonisolated procedures, as did preoperative severe heart failure. Optimal surgical plan and timing of surgery are keys to success.

Statin Therapy in Patients Undergoing Thoracic Aorta Replacement for Aortic Aneurysms.

BACKGROUND: Patients undergoing surgery for thoracic aortic aneurysms receive statin therapy out of proportion to cardiovascular comorbidity. We sought to determine the prevalence of statin use among patients presenting for thoracic aortic aneurysm surgery and investigate its effect on outcomes. METHODS: From January 1, 2005 to January 1, 2011, 1,839 consecutive patients underwent aortic replacement for degenerative thoracic aortic aneurysm at Cleveland Clinic. Of these, 771 (42%) were on statins preoperatively. Statin users (vs. nonstatin users) were older (65 ± 11 vs. 56 ± 16 years) and had more hypertension (78 vs. 59%). Propensity matching based on 56 preoperative variables other than lipid levels was used to compare outcomes among 570 matched patient pairs (74% of possible pairs). RESULTS: Propensity-matched statin and nonstatin users were aged 64 ± 11 years, 394 (69%) versus 387 (68%) were male, and 437 (77%) versus 442 (78%) had ascending aortic aneurysms, respectively. Overall, 25% of patients were followed for more than 8.2 years and 10% for more than 10 years. Perioperative outcomes were similar, including hospital mortality (11 [1.9%] vs. 5 [0.88%]) and stroke (22 [3.9%] vs. 13 [2.3%]), but 16 statin users (2.8%) versus 5 nonstatin users (0.88%) required temporary dialysis after surgery (p = 0.02). At 6 years, 3.7% of statin users versus 5.1% of nonstatin users (p[log-rank] = 0.5) underwent further aortic surgery, and at 10 years, mortality was 25% in both groups (p > 0.5). CONCLUSION: Patients presenting for thoracic aortic aneurysm surgery frequently receive unnecessary statins. Additionally, statin use was associated with more postoperative renal failure, but not less intermediate-term risk for aortic reintervention or all-cause mortality after surgery. Therefore, presence of a thoracic aortic aneurysm should not be considered an indication for statin therapy in the absence of well-established indications.

Evolution of Alternative-access Transcatheter Aortic Valve Replacement.

BACKGROUND: Transfemoral access is the most common approach for transcatheter aortic valve replacement (TAVR). However, a subset of patients require alternative access. This study describes the evolution and outcomes of alternative-access TAVR at Cleveland Clinic. METHODS: From January 2006 to January 2019, 2446 patients underwent TAVR, 414 (17%) through alternative access (247 transapical, 95 transaortic, 56 transaxillary, 2 transcarotid, 10 transiliac, 4 transcaval). Patients undergoing alternative-access TAVR had high preoperative risk. Propensity-matched comparisons were targeted at comparing transfemoral versus transaxillary approaches since 2012. RESULTS: Over time, the favored alternative-access approach shifted from transapical and transaortic to transaxillary. Pacemaker requirement was similar for alternative-access and transfemoral approaches. Compared with transfemoral access, major vascular injuries were higher in the alternative-access group (12 [2.9%] vs 27 [1.3%], P = .02), but minor vascular injuries were lower (13 [3.1%] vs 198 [9.8%], P < .0001). Non-risk-adjusted 5-year survival was lower in the alternative-access group (45% vs 59%). Compared with intrathoracic approaches (transapical and transaortic), transaxillary access was associated with fewer blood transfusions (12 [21%] vs 176 [51%], P < .0001), less prolonged ventilation (1 [1.8%] vs 38 [11%], P = .03), and shorter length of stay (median, 5 vs 7.5 days, P < .0001). Survival and major morbidity were similar in matched comparisons of the transfemoral and transaxillary approaches. No brachial plexus injuries occurred with transaxillary access. CONCLUSIONS: The transaxillary approach has emerged as our preferred alternative-access strategy for TAVR. It is associated with superior operative outcomes compared with transthoracic approaches, and results are comparable with those of the transfemoral approach.

Risk of adding prophylactic aorta replacement to a cardiac operation.

OBJECTIVE: The study objective was to determine whether adding prophylactic aorta replacement increases the risk of a cardiac operation when cardiac rather than aortic disease is the primary indication for operation. METHODS: Patients undergoing cardiac operations with aorta replacement (cardioaortic group), with or without circulatory arrest, were propensity matched to identify patients whose combined operation was not primarily indicated by aortic disease (n = 684). These patients were further propensity matched without accounting for thoracic-aortic measurements to patients undergoing cardiac operations without aorta replacement (cardiac-surgery only group), 647 pairs, for comparing outcomes. RESULTS: Most (n = 431/503 [86%]) propensity-matched patients undergoing cardioaortic operations had ascending aorta dilatation with a maximum aortic diameter of less than 5.5 cm. There was no evidence of an incremental increase in risk of in-hospital stroke (cardioaortic, n = 9/1.4% vs cardiac only, n = 7/1.1%; P = .6) or mortality (cardioaortic, n = 6/0.93% vs cardiac only, n = 3/0.46%; P = .5). Unmatched patients undergoing concomitant aortic surgery had advanced aortic disease distal to the ascending aorta (arch, 3.8 ± 0.98 cm vs 3.2 ± 0.51 cm; descending, 4.4 ± 1.7 cm vs 3.2 ± 0.99 cm) as the primary indication for their operation and had a high occurrence of in-hospital stroke (6.5% vs 1.5%, P = .0007) and death (7% vs 1.2%, P = .0001). CONCLUSIONS: Prophylactic aorta replacement can be safely performed during a cardioaortic operation, without added penalty, when aortic disease is less severe and not the primary indication for surgery. Risks after an aorta replacement combined with cardiac surgery can be substantial, however, when advanced aortic disease is the primary indication for operation. These distinctive risks should be taken into consideration at the time of surgical decision-making.

Right versus left heart reverse remodelling after treating ischaemic mitral and tricuspid regurgitation.

OBJECTIVES: Repair outcomes of tricuspid regurgitation (TR) associated with ischaemic mitral regurgitation (IMR) are inferior to functional TR in terms of TR recurrence and right ventricular (RV) reverse remodelling. Our objective is to analyse right versus left heart reverse remodelling after surgery for IMR-associated TR. METHODS: From 2001 to 2011, 568 patients with severe IMR underwent mitral valve surgery (repair 87%, replacement 13%), and 131 had concomitant tricuspid valve repair. Median follow-up was 3.0 years; 25% of living patients were followed up for 6.3 years. Longitudinal analysis of 1527 follow-up echocardiograms was performed to assess ventricular reverse remodelling and function. RESULTS: Unlike the left heart, the right heart failed to reverse remodel (failed to recover ventricular function or halt dilatation). During follow-up after surgery, the right ventricle continued to dilate while the left ventricle regressed in size. RV ejection fraction decreased (46% at 1 month and 44% at 5 years), while left ventricular ejection fraction increased (33% and 37%, respectively). RV strain showed early (-11% at 1 month) and late (-12% at 5 years) dysfunction. Patients who underwent tricuspid valve repair had worse RV function. Mitral regurgitation remained stable after surgical intervention, and TR gradually recurred (37% moderate, 20% severe at 7 years). CONCLUSIONS: Surgical treatment of IMR and TR along with revascularization failed to induce reverse remodelling of the right heart. These findings warrant further investigations to identify optimal timing and approach of intervention for IMR-associated TR with respect to RV remodelling.

Inter- and intrasite variability of mortality and stroke for sites performing both surgical and transcatheter aortic valve replacement for aortic valve stenosis in intermediate-risk patients.

OBJECTIVES: Multisite procedure-based randomized trials may be confounded by performance variability and variability among sites. Therefore, we studied variability in mortality and stroke after patients were randomized to surgical (SAVR) or transcatheter aortic valve replacement (TAVR) in the Placement of Aortic Transcatheter Valves-2A (PARTNER-2A) randomized trial. METHODS: Patients at intermediate risk for SAVR were randomized to SAVR (n = 1017) or TAVR (n = 1011) with a SAPIEN XT device (Edwards Lifesciences, Irvine, Calif) at 54 sites. Patients were followed to 2 years. A mixed-effect model quantified variability at intersite and intrasite levels. RESULTS: There were 336 deaths (SAVR 170, TAVR 166) and 176 strokes (SAVR 85, TAVR 91). Intersite variability for mortality was similar across sites for SAVR (hazard ratios ranging from 0.52-1.93 among sites) and TAVR (hazard ratios ranging from 0.49-2.03), but intersite variability for stroke was greater for SAVR (hazard ratios ranging from 0.44-2.26) than for TAVR (no detectable variability). Case mix and lower site trial volume accounted for 37% of mortality intersite variability for SAVR and 73% for TAVR, but only 14% for stroke for SAVR. Intrasite mortality hazard ratios demonstrated all but 1 site's 95% confidence interval overlapped 1.0, indicating generally similar SAVR and TAVR mortalities within sites. CONCLUSIONS: Intersite variability was similar for mortality in SAVR and TAVR, but variability for stroke was greater for SAVR than for TAVR. Intrasite events were similar for both SAVR and TAVR. These findings suggest that in performance-based trials, site variability and its sources should be taken into account in analyzing and interpreting trial results.