Todd M. Dewey

Transcatheter versus Surgical Aortic-Valve Replacement in High-Risk Patients

BACKGROUND The use of transcatheter aortic-valve replacement has been shown to reduce mortality among high-risk patients with aortic stenosis who are not candidates for surgical replacement. However, the two procedures have not been compared in a randomized trial involving high-risk patients who are still candidates for surgical replacement. METHODS At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either transcatheter aortic-valve replacement with a balloon-expandable bovine pericardial valve (either a transfemoral or a transapical approach) or surgical replacement. The primary end point was death from any cause at 1 year. The primary hypothesis was that transcatheter replacement is not inferior to surgical replacement. RESULTS The rates of death from any cause were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% and 26.8%, respectively, at 1 year (P=0.44), a reduction of 2.6 percentage points in the transcatheter group (upper limit of the 95% confidence interval, 3.0 percentage points; predefined margin, 7.5 percentage points; P=0.001 for noninferiority). The rates of major stroke were 3.8% in the transcatheter group and 2.1% in the surgical group at 30 days (P=0.20) and 5.1% and 2.4%, respectively, at 1 year (P=0.07). At 30 days, major vascular complications were significantly more frequent with transcatheter replacement (11.0% vs. 3.2%, P<0.001); adverse events that were more frequent after surgical replacement included major bleeding (9.3% vs. 19.5%, P<0.001) and new-onset atrial fibrillation (8.6% vs. 16.0%, P=0.006). More patients undergoing transcatheter replacement had an improvement in symptoms at 30 days, but by 1 year, there was not a significant between-group difference. CONCLUSIONS In high-risk patients with severe aortic stenosis, transcatheter and surgical procedures for aortic-valve replacement were associated with similar rates of survival at 1 year, although there were important differences in periprocedural risks. (Funded by Edwards Lifesciences; Clinical Trials.gov number, NCT00530894.).

Two-year outcomes after transcatheter or surgical aortic-valve replacement.

BACKGROUND The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits. METHODS At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation. RESULTS The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). CONCLUSIONS A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients

BACKGROUND Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. METHODS We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. RESULTS The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. CONCLUSIONS In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Transcatheter Aortic-Valve Replacement for Inoperable Severe Aortic Stenosis

BACKGROUND Transcatheter aortic-valve replacement (TAVR) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The outcomes beyond 1 year in such patients are not known. METHODS We randomly assigned patients to transfemoral TAVR or to standard therapy (which often included balloon aortic valvuloplasty). Data on 2-year outcomes were analyzed. RESULTS A total of 358 patients underwent randomization at 21 centers. The rates of death at 2 years were 43.3% in the TAVR group and 68.0% in the standard-therapy group (P<0.001), and the corresponding rates of cardiac death were 31.0% and 62.4% (P<0.001). The survival advantage associated with TAVR that was seen at 1 year remained significant among patients who survived beyond the first year (hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.92; P=0.02 with the use of the log-rank test). The rate of stroke was higher after TAVR than with standard therapy (13.8% vs. 5.5%, P=0.01), owing, in the first 30 days, to the occurrence of more ischemic events in the TAVR group (6.7% vs. 1.7%, P=0.02) and, beyond 30 days, to the occurrence of more hemorrhagic strokes in the TAVR group (2.2% vs. 0.6%, P=0.16). At 2 years, the rate of rehospitalization was 35.0% in the TAVR group and 72.5% in the standard-therapy group (P<0.001). TAVR, as compared with standard therapy, was also associated with improved functional status (P<0.001). The data suggest that the mortality benefit after TAVR may be limited to patients who do not have extensive coexisting conditions. Echocardiographic analysis showed a sustained increase in aortic-valve area and a decrease in aortic-valve gradient, with no worsening of paravalvular aortic regurgitation. CONCLUSIONS Among appropriately selected patients with severe aortic stenosis who were not suitable candidates for surgery, TAVR reduced the rates of death and hospitalization, with a decrease in symptoms and an improvement in valve hemodynamics that were sustained at 2 years of follow-up. The presence of extensive coexisting conditions may attenuate the survival benefit of TAVR. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

Transapical Minimally Invasive Aortic Valve Implantation: Multicenter Experience

Background— To evaluate initial multicenter results with minimally invasive transapical aortic valve implantation (TAP-AVI) for high risk patients with aortic stenosis. Methods and Results— TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoro-femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Edwards SAPIEN THV, Edwards Lifesciences) was used. Fifty-nine consecutive patients (81±6 years, 44 female) were operated on from 02/06 until 10/06 at 4 centers using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27±14%. TAP valve positioning was performed successfully in 53 patients, 4 required early conversion to sternotomy. Implantation (23-mm valves in 19 and 26-mm valves in 40 patients) was performed on the beating heart during brief periods of rapid ventricular pacing. Thirty-one patients were operated on without cardiopulmonary bypass. Neither coronary artery obstruction nor migration of the prosthesis was observed, and all valves had good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 26 patients (trace in 11, mild in 12, and severe in 3). Eight patients died in-hospital (13.6%) without any valve dysfunction. Actuarial survival was 75.7±5.9% at a follow-up interval of 110±77 days (range 1 to 255 days). Conclusions— TAP-AVI can be performed safely with good early results in high risk patients. Long-term valve performance as well as broader based applications of this promising approach will need to be studied.

Transapical aortic valve implantation: step by step.

PURPOSE Transapical aortic valve implantation is a new minimally invasive technique for beating heart, off-pump, aortic valve implantation in high-risk patients. DESCRIPTION The procedure involves antegrade aortic valve implantation using an oversizing technique with direct access and accurate positioning of a stent-based transcatheter xenograft. Procedural steps include placement of femoral arterial and venous access wires, anterolateral mini-thoracotomy, epicardial pacing, and apical pursestring suture placement. Valve positioning is performed under fluoroscopic and echocardiographic guidance during rapid ventricular pacing. EVALUATION Patient screening, especially regarding native aortic annulus diameter and pattern of calcification, is essential for success. Since imaging is crucial, implantations are optimally performed in a hybrid operative theater by an experienced team of cardiac surgeons, cardiologists, and anesthetists. CONCLUSIONS The aim of this article is to outline the technical aspects of the new technique of minimally invasive transapical aortic valve implantation.

Effect of Concomitant Coronary Artery Disease on Procedural and Late Outcomes of Transcatheter Aortic Valve Implantation

BACKGROUND Previous coronary artery bypass grafting increases predicted operative risk for conventional valve replacement, according to the Society of Thoracic Surgeons risk algorithm. Additionally, the presence of coronary artery disease (CAD) has been demonstrated to increase procedural risk with conventional aortic valve replacement. Significant coexisting CAD requires preemptive percutaneous coronary intervention (PCI) in patients under consideration for transcatheter aortic valve implantation (TAVI). This study examined the impact of previous coronary artery bypass grafting or PCI on procedural outcomes and overall survival in patients having TAVI. METHODS Two hundred and one high-risk patients were enrolled in two international feasibility studies from December 2005 to February 2008 for the treatment of aortic stenosis using TAVI. Thirty patients were excluded from analysis due to failure to successfully deploy the valve in the aortic annulus. Data were collected concurrently using an ad hoc database that included operative and long-term survival. Previous cardiovascular intervention prior to TAVI was used to identify the existence of concomitant CAD. Logistic regression along with Kaplan-Meier estimates were employed to establish the association between CAD and survival from TAVI. RESULTS Overall mortality after TAVI was significantly higher among the CAD group (35.7%) in contrast with the non-CAD patients (18.4%), p = 0.01. Logistic regression analysis found that patients who had CAD were 10.1 times more likely to die (95% confidence interval 2.1 to 174.8) within 30 days of the procedure than those who did not. Proportional hazards analysis established that the risk of dying at any point in time was 2.3 times higher among the patients with CAD (95% confidence interval 1.29 to 4.17). Kaplan-Meier survival curves demonstrate improved long-term survival among patients without CAD. CONCLUSIONS Coexisting coronary artery disease negatively impacts procedural outcomes and long-term survival in patients undergoing TAVI, and implies that risk assessment and anticipated outcomes might be inaccurate due to stratification as isolated aortic valve replacement rather than AVR+CABG. Comparison of procedural outcomes, based on operative approach without controlling for unequal distribution of CAD in the cohorts, are likely invalid.

Elimination of cardiopulmonary bypass improves early survival for multivessel coronary artery bypass patients.

BACKGROUND Coronary artery bypass graft (CABG) surgery performed without cardiopulmonary bypass (CPB) is currently increasing in clinical practice. Decreased morbidity associated with off-pump (OP) CABG in selected risk groups examined in relatively small, single institution groups has been the focus of most recent studies. The purpose of this study was to determine the independent impact of CPB on early survival in all isolated multivessel CABG patients undergoing surgery in two large institutions with established experience in OPCABG techniques. METHODS A review of two large databases employed by multiple surgeons in the hospitals of two institutions identified 8,758 multivessel CABG procedures performed from January 1998 through July 2000. In all, 8,449 procedures were included in a multivariate logistic regression analysis to determine the relative impact of CPB on mortality independent of known risk factors for mortality. Procedures were also divided into two treatment groups based on the use of CPB: 6,466 had CABG with CPB (CABG-CPB), 1,983 had CABG without CPB (OPCABG). Disparities between groups were identified by univariate analysis of 17 preoperative risk factors and treatment groups were compared by Parsonnets risk stratification model. Finally, computer-matched groups based on propensity score for institution selection for OPCABG were combined and analyzed by a logistic regression model predicting risk for mortality. RESULTS CABG-CPB was associated with increased mortality compared with OPCABG by univariate analysis, 3.5% versus 1.8%, despite a lower predicted risk in the CABG-CPB group. CPB was associated with increased mortality by multiple logistic regression analysis with an odds ratio of 1.79 (95% confidence interval = 1.24 to 2.67). An increased risk of mortality associated with CPB was also determined by logistic regression analysis of the combined computer-matched groups based on OPCABG-selection propensity scores with an odds ratio of 1.9 (95% confidence interval = 1.2 to 3.1). CONCLUSIONS Elimination of CPB improves early survival in multivessel CABG patients. Rigorous attempts to statistically account for selection bias maintained a clear association between CPB and increased mortality. Larger multiinstitutional studies are needed to confirm these findings and determine the most appropriate application of OPCABG.

Conversion in Off-Pump coronary artery bypass grafting: an analysis of predictors and outcomes

BACKGROUND The incidence, predictive factors, and outcomes related to conversion from off-pump coronary artery bypass (OPCAB) to on-pump coronary artery bypass grafting (ONCAB) have not been well defined. We sought to determine the incidence of conversion, predictive factors, and any associated adverse consequences. METHODS From January 2000 through June 2002, 1,644 patients underwent nonemergent OPCAB with 61 patients requiring conversion from OPCAB to ONCAB. These groups were retrospectively compared by univariate and multivariate regression analysis. The converted group was then computer matched 1:3, to a cohort of ONCAB patients to determine differences in outcomes. RESULTS The overall conversion rate was 3.71%. Converted patients compared with a computer-matched ONCAB patients had a higher incidence of operative mortality (18.0% versus 2.7%, p < 0.001). Urgently converted patients had a higher incidence of postoperative cardiac arrest (25% versus 1.1%, p < 0.001), multisystem organ failure (10.7% versus 0.6%, p < 0.001), vascular complications (7.1% versus 1.1%, p = 0.03), and perioperative myocardial infarction (10.7% versus 1.1%, p = 0.02). Predictive factors for conversion were surgeon early in OPCAB experience (odds ratio [OR] 4.4), previous CABG (OR 2.8), and congestive heart failure (OR 2.0). The need for urgent-emergent conversion was highly predictive for operative mortality (OR 7.3) compared with elective conversion. CONCLUSIONS Patients undergoing urgent-emergent but not elective conversion from OPCAB to ONCAB had a significantly higher risk of mortality and morbidity compared with patients whose procedure was initially ONCAB. Variables predictive of conversion included previous CABG, congestive heart failure, and surgeons early in OPCAB experience.

Outcomes of Surgical Aortic Valve Replacement in High-Risk Patients: A Multiinstitutional Study

BACKGROUND The introduction of transcatheter aortic valves has focused attention on outcomes after open aortic valve replacement (AVR) in very high-risk patients. This study analyzes the short-term and midterm outcomes of AVR in this patient cohort in the current surgical era. METHODS A retrospective review was performed on 159 patients who underwent isolated, primary AVR with a STS PROM (Society of Thoracic Surgeons predicted risk of mortality) of 10% or greater from January 2002 to December 2007 at four US academic institutions. Patients with previous valve operations were excluded. A multivariable model was constructed to determine predictors of in-hospital mortality. Estimates of the cumulative event rate mortality were calculated by the Kaplan-Meier method. RESULTS The mean age of all patients was 76.1±11.2 years, most were men (92 of 159, 57.9%), and mean STS PROM was 16.3%±7.3%. Significant preoperative factors included the following: peripheral vascular disease, 33.3% (53 of 159); stroke, 23.3% (37 of 159); renal failure, 50.3% (80 of 159); New York Heart Association class III-IV heart failure, 78.0% (124 of 159); and previous coronary artery bypass grafting, 39.0% (62 of 159). Mean ejection fraction was 0.461±0.153 and median implanted valve size was 23 mm. Postoperative complications included the following: stroke, 4.4% (7 of 159); heart block, 5.0% (8 of 159); multisystem organ failure, 6.9% (11 of 159); pneumonia, 7.5% (12 of 159); and dialysis, 8.2% (13 of 159). Postoperative length of stay was 12.6±11.0 days and in-hospital mortality was 16.4% (26 of 159). One-, three-, and 5-year survival was 70.9%, 56.8%, and 47.4%, respectively. CONCLUSIONS In the current era, high-risk surgical patients undergoing open AVR have respectable short and mid-term survival. These results should serve as a benchmark for evaluating outcomes of transcatheter aortic valve implantation.