Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus.

BACKGROUND: Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR). METHODS: We randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority). RESULTS: A total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan-Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, -1.2 percentage points; 90% confidence interval [CI], -4.9 to 2.5; P<0.001 for noninferiority). The Kaplan-Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, -32.2 percentage points; 95% CI, -38.7 to -25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis-patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups. CONCLUSIONS: Among patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.).

Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aortic root or ascending/descending aorta. TAA is a heritable disease that can be potentially life threatening. While 10%-20% of TAA cases are caused by rare, pathogenic variants in single genes, the origin of the majority of TAA cases remains unknown. A previous study implicated common variants in FBN1 with TAA disease risk. Here, we report a genome-wide scan of 1,351 TAA-affected individuals and 18,295 control individuals from the Cardiovascular Health Improvement Project and Michigan Genomics Initiative at the University of Michigan. We identified a genome-wide significant association with TAA for variants within the third intron of TCF7L2 following replication with meta-analysis of four additional independent cohorts. Common variants in this locus are the strongest known genetic risk factor for type 2 diabetes. Although evidence indicates the presence of different causal variants for TAA and type 2 diabetes at this locus, we observed an opposite direction of effect. The genetic association for TAA colocalizes with an aortic eQTL of TCF7L2, suggesting a functional relationship. These analyses predict an association of higher expression of TCF7L2 with TAA disease risk. In vitro, we show that upregulation of TCF7L2 is associated with BCL2 repression promoting vascular smooth muscle cell apoptosis, a key driver of TAA disease.

Renal Dysfunction at Discharge and Long-Term Survival in Acute Type A Aortic Dissection.

INTRODUCTION: We aimed to investigate the association between renal dysfunction at discharge and long-term survival in acute type A aortic dissection (ATAAD) patients following surgery. METHODS: From 2000 to 2021, 784 patients underwent aortic repair for an ATAAD. Patients were stratified based on creatinine (Cr) level at discharge alive or dead: normal Cr (n = 582) and elevated Cr defined as >1.3 mg/dL for males and >1.0 mg/dL for females or on dialysis at discharge (n = 202). RESULTS: Preoperatively, both groups had similar rates of comorbidities except for the elevated-Cr group which had more diabetes, chronic obstructive pulmonary disease, and chronic and acute renal insufficiency. Both groups had similar open ATAAD repair procedures. Postoperative outcomes in the elevated-Cr group were significantly worse, including six times higher operative mortality (20% versus 3.4%, P < 0.0001). The landmark long-term survival after discharge alive was significantly worse in the elevated-Cr group than the normal-Cr group (10-y survival: 48% versus 69%, P = 0.0009). The elevated Cr on dialysis at discharge group had significantly worse five-year survival (40%) than the elevated Cr not on dialysis at discharge group (80%, P = 0.02) and the normal-Cr group (87%, P < 0.0001). Additionally, the elevated Cr not on dialysis had a worse five-year survival than the normal-Cr group (80% versus 87%, P = 0.02). Elevated Cr at discharge on dialysis was a significant risk factor for late mortality (hazard ratio = 4.22, 95% confidence interval: [2.07, 8.61], P < 0.0001). CONCLUSIONS: Renal dysfunction at discharge was associated with significantly decreased short-term and long-term survival following open ATAAD repair. Surgeons should aggressively prevent renal dysfunction, especially new-onset dialysis, at discharge as it is correlated with significantly worse short-term and long-term outcomes.

Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is known about TAVR in low-risk patients. METHODS: We performed a randomized noninferiority trial in which TAVR with a self-expanding supraannular bioprosthesis was compared with surgical aortic-valve replacement in patients who had severe aortic stenosis and were at low surgical risk. When 850 patients had reached 12-month follow-up, we analyzed data regarding the primary end point, a composite of death or disabling stroke at 24 months, using Bayesian methods. RESULTS: Of the 1468 patients who underwent randomization, an attempted TAVR or surgical procedure was performed in 1403. The patients' mean age was 74 years. The 24-month estimated incidence of the primary end point was 5.3% in the TAVR group and 6.7% in the surgery group (difference, -1.4 percentage points; 95% Bayesian credible interval for difference, -4.9 to 2.1; posterior probability of noninferiority >0.999). At 30 days, patients who had undergone TAVR, as compared with surgery, had a lower incidence of disabling stroke (0.5% vs. 1.7%), bleeding complications (2.4% vs. 7.5%), acute kidney injury (0.9% vs. 2.8%), and atrial fibrillation (7.7% vs. 35.4%) and a higher incidence of moderate or severe aortic regurgitation (3.5% vs. 0.5%) and pacemaker implantation (17.4% vs. 6.1%). At 12 months, patients in the TAVR group had lower aortic-valve gradients than those in the surgery group (8.6 mm Hg vs. 11.2 mm Hg) and larger effective orifice areas (2.3 cm2 vs. 2.0 cm2). CONCLUSIONS: In patients with severe aortic stenosis who were at low surgical risk, TAVR with a self-expanding supraannular bioprosthesis was noninferior to surgery with respect to the composite end point of death or disabling stroke at 24 months. (Funded by Medtronic; ClinicalTrials.gov number, NCT02701283.).

Comparison of a Complete Percutaneous Versus Surgical Approach to Aortic Valve Replacement and Revascularization in Patients at Intermediate Surgical Risk: Results From the Randomized SURTAVI Trial.

BACKGROUND: For patients with severe aortic stenosis and coronary artery disease, the completely percutaneous approach to aortic valve replacement and revascularization has not been compared with the standard surgical approach. METHODS: The prospective SURTAVI trial (Safety and Efficiency Study of the Medtronic CoreValve System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement) enrolled intermediate-risk patients with severe aortic stenosis from 87 centers in the United States, Canada, and Europe between June 2012 and June 2016. Complex coronary artery disease with SYNTAX score (Synergy Between PCI with Taxus and Cardiac Surgery Trial) >22 was an exclusion criterion. Patients were stratified according to the need for revascularization and then randomly assigned to treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). Patients assigned to revascularization in the TAVR group underwent percutaneous coronary intervention, whereas those in the SAVR group had coronary artery bypass grafting. The primary end point was the rate of all-cause mortality or disabling stroke at 2 years. RESULTS: Of 1660 subjects with attempted aortic valve implants, 332 (20%) were assigned to revascularization. They had a higher Society of Thoracic Surgeons risk score for mortality (4.8±1.7% versus 4.4±1.5%; P<0.01) and were more likely to be male (65.1% versus 54.2%; P<0.01) than the 1328 patients not assigned to revascularization. After randomization to treatment, there were 169 patients undergoing TAVR and percutaneous coronary intervention, 163 patients undergoing SAVR and coronary artery bypass grafting, 695 patients undergoing TAVR, and 633 patients undergoing SAVR. No significant difference in the rate of the primary end point was found between TAVR and percutaneous coronary intervention and SAVR and coronary artery bypass grafting (16.0%; 95% CI, 11.1-22.9 versus 14.0%; 95% CI, 9.2-21.1; P=0.62), or between TAVR and SAVR (11.9%; 95% CI, 9.5-14.7 versus 12.3%; 95% CI, 9.8-15.4; P=0.76). CONCLUSIONS: For patients at intermediate surgical risk with severe aortic stenosis and noncomplex coronary artery disease (SYNTAX score ≤22), a complete percutaneous approach of TAVR and percutaneous coronary intervention is a reasonable alternative to SAVR and coronary artery bypass grafting. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT01586910.

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

BACKGROUND: Although transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk. METHODS: We evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement. RESULTS: A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, -5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic-valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group. CONCLUSIONS: TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910 .).

Endovascular Fenestration/Stenting First Followed by Delayed Open Aortic Repair for Acute Type A Aortic Dissection With Malperfusion Syndrome.

BACKGROUND: Immediate open repair of acute type A aortic dissection is traditionally recommended to prevent death from aortic rupture. However, organ failure because of malperfusion syndrome (MPS) might be the most imminent life-threatening problem for a subset of patients. METHODS: From 1996 to 2017, among 597 patients with acute type A aortic dissection, 135 patients with MPS were treated with upfront endovascular reperfusion (fenestration/stenting) followed by delayed open repair (OR). We compared outcomes between the first and second decades and observed mortalities with those expected with an "upfront OR for every patient" approach, determined using prognostic models from the literature (Verona, Leipzig-Halifax, Stockholm, Penn, and GERAADA [German Registry for Acute Aortic Dissection Type A] models). RESULTS: Overall, in-hospital mortality improved between the 2 decades (21.0% versus 10.7%, P<0.001). In the second decade, for patients with MPS initially treated with fenestration/stenting, mortality from aortic rupture decreased from 16% to 4% ( P=0.05), the risk of dying from organ failure was 6.6 times higher than dying from aortic rupture (hazard ratio=6.63; 95% CI, 1.5-29; P=0.01), and 30-day mortality after OR for MPS patients was 3.7%. Compared to the expected mortalities with the upfront OR for every patient models, our observed 30-day and in-hospital mortalities (9% and 11%, respectively) of all patients with acute type A aortic dissection were significantly lower ( P≤0.03). CONCLUSIONS: Immediate OR is the strategy to prevent death from aortic rupture for the majority of patients with acute type A aortic dissection. However, relatively stable (no rupture, no tamponade) patients with MPS benefit from a staged approach: upfront endovascular reperfusion followed by aortic OR at resolution of organ failure.

Transcatheter aortic-valve replacement with a self-expanding prosthesis.

BACKGROUND: We compared transcatheter aortic-valve replacement (TAVR), using a self-expanding transcatheter aortic-valve bioprosthesis, with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery. METHODS: We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center. Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors. Eligible patients were randomly assigned in a 1:1 ratio to TAVR with the self-expanding transcatheter valve (TAVR group) or to surgical aortic-valve replacement (surgical group). The primary end point was the rate of death from any cause at 1 year, evaluated with the use of both noninferiority and superiority testing. RESULTS: A total of 795 patients underwent randomization at 45 centers in the United States. In the as-treated analysis, the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group (14.2% vs. 19.1%), with an absolute reduction in risk of 4.9 percentage points (upper boundary of the 95% confidence interval, -0.4; P<0.001 for noninferiority; P = 0.04 for superiority). The results were similar in the intention-to-treat analysis. In a hierarchical testing procedure, TAVR was noninferior with respect to echocardiographic indexes of valve stenosis, functional status, and quality of life. Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke. CONCLUSIONS: In patients with severe aortic stenosis who are at increased surgical risk, TAVR with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement. (Funded by Medtronic; U.S. CoreValve High Risk Study ClinicalTrials.gov number, NCT01240902.).

A 20-year experience with thoracic endovascular aortic repair.

BACKGROUND: Endovascular approaches (thoracic endovascular aortic repair) have revolutionized treatment of thoracic aortic disease. OBJECTIVE: We report our 20-year experience with this therapy. METHODS: Four hundred twenty patients (mean age = 69.0 years; 54% male) underwent thoracic endovascular aortic repair (1993-2013), predominantly for fusiform aneurysm (n = 144), saccular aneurysm (n = 94), acute (n = 64) or chronic (n = 36) dissection, or traumatic injury (n = 39). Rupture was present in 80 patients (19.1%). Most patients (78.3%) were at high risk for open repair. Mean aortic diameter was 5.5 cm. Extent of repair included arch in 218 patients, total descending aorta in 193 patients, and thoracoabdominal aorta in 35 patients. RESULTS: Thirty-day mortality occurred in 20 patients (4.8%). Neurologic events included stroke (5.0%) and spinal cord ischemia (permanent 1.7%, temporary 7.9%). Although dialysis was only required in 1.4% of the patients, 19% had renal failure by RIFLE (Risk, Injury, Failure) criteria. Endoleak occurred in 32.9% of the patients. Ten-year freedom from dissection, rupture, or need for reintervention in treated or adjacent aortic segments (ie, treatment failure) was 63.2%. Independent predictors included presentation with rupture, preexisting renal failure, or intervention on the arch aorta (all Ps < 0.03). Aortic pathology also independently predicted treatment failure (P = 0.026). The 15-year survival rate was 32.3%. Advancing age, presence of coronary artery disease, rupture, or postoperative renal failure (all Ps < 0.05), but not treatment failure (P = 0.926), independently predicted late mortality. CONCLUSIONS: Thoracic endovascular aortic repair can be performed with acceptable results in a high-risk population. The risk of treatment failure persists, underscoring the importance of continued long-term endograft surveillance, but this does not seem to impact late mortality.