Wilson Y. Szeto

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 versus surgical valve replacement in intermediate-risk patients: a propensity score analysis

BACKGROUND Transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve demonstrates good 30 day clinical outcomes in patients with severe aortic stenosis who are at intermediate risk of surgical mortality. Here we report longer-term data in intermediate-risk patients given SAPIEN 3 TAVR and compare outcomes to those of intermediate-risk patients given surgical aortic valve replacement. METHODS In the SAPIEN 3 observational study, 1077 intermediate-risk patients at 51 sites in the USA and Canada were assigned to receive TAVR with the SAPIEN 3 valve [952 [88%] via transfemoral access) between Feb 17, 2014, and Sept 3, 2014. In this population we assessed all-cause mortality and incidence of strokes, re-intervention, and aortic valve regurgitation at 1 year after implantation. Then we compared 1 year outcomes in this population with those for intermediate-risk patients treated with surgical valve replacement in the PARTNER 2A trial between Dec 23, 2011, and Nov 6, 2013, using a prespecified propensity score analysis to account for between-trial differences in baseline characteristics. The clinical events committee and echocardiographic core laboratory methods were the same for both studies. The primary endpoint was the composite of death from any cause, all strokes, and incidence of moderate or severe aortic regurgitation. We did non-inferiority (margin 7·5%) and superiority analyses in propensity score quintiles to calculate pooled weighted proportion differences for outcomes. FINDINGS At 1 year follow-up of the SAPIEN 3 observational study, 79 of 1077 patients who initiated the TAVR procedure had died (all-cause mortality 7·4%; 6·5% in the transfemoral access subgroup), and disabling strokes had occurred in 24 (2%), aortic valve re-intervention in six (1%), and moderate or severe paravalvular regurgitation in 13 (2%). In the propensity-score analysis we included 963 patients treated with SAPIEN 3 TAVR and 747 with surgical valve replacement. For the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, TAVR was both non-inferior (pooled weighted proportion difference of -9·2%; 90% CI -12·4 to -6; p<0·0001) and superior (-9·2%, 95% CI -13·0 to -5·4; p<0·0001) to surgical valve replacement. INTERPRETATION TAVR with SAPIEN 3 in intermediate-risk patients with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at 1 year. The propensity score analysis indicates a significant superiority for our composite outcome with TAVR compared with surgery, suggesting that TAVR might be the preferred treatment alternative in intermediate-risk patients. FUNDING None.

5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial.

BACKGROUND Based on the early results of the Placement of Aortic Transcatheter Valves (PARTNER) trial, transcatheter aortic valve replacement (TAVR) is an accepted treatment for patients with severe aortic stenosis who are not suitable for surgery. However, little information is available about the late clinical outcomes in such patients. METHODS We did this randomised controlled trial at 21 experienced valve centres in Canada, Germany, and the USA. We enrolled patients with severe symptomatic inoperable aortic stenosis and randomly assigned (1:1) them to transfemoral TAVR or to standard treatment, which often included balloon aortic valvuloplasty. Patients and their treating physicians were not masked to treatment allocation. The randomisation was done centrally, and sites learned of the assignment only after a patient had been screened, consented, and entered into the database. The primary outcome of the trial was all-cause mortality at 1 year in the intention-to-treat population, here we present the prespecified findings after 5 years. This study is registered with ClinicalTrials.gov, number NCT00530894. FINDINGS We screened 3015 patients, of whom 358 were enrolled (mean age 83 years, Society of Thoracic Surgeons Predicted Risk of Mortality 11·7%, 54% female). 179 were assigned to TAVR treatment and 179 were assigned to standard treatment. 20 patients crossed over from the standard treatment group and ten withdrew from study, leaving only six patients at 5 years, of whom five had aortic valve replacement treatment outside of the study. The risk of all-cause mortality at 5 years was 71·8% in the TAVR group versus 93·6% in the standard treatment group (hazard ratio 0·50, 95% CI 0·39-0·65; p<0·0001). At 5 years, 42 (86%) of 49 survivors in the TAVR group had New York Heart Association class 1 or 2 symptoms compared with three (60%) of five in the standard treatment group. Echocardiography after TAVR showed durable haemodynamic benefit (aortic valve area 1·52 cm(2) at 5 years, mean gradient 10·6 mm Hg at 5 years), with no evidence of structural valve deterioration. INTERPRETATION TAVR is more beneficial than standard treatment for treatment of inoperable aortic stenosis. TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement to improve their survival and functional status. Appropriate selection of patients will help to maximise the benefit of TAVR and reduce mortality from severe comorbidities. FUNDING Edwards Lifesciences.

Predictors of mortality and outcomes of therapy in low-flow severe aortic stenosis a placement of aortic transcatheter Valves (PARTNER) trial analysis

Background— The prognosis and treatment of patients with low-flow (LF) severe aortic stenosis are controversial. Methods and Results— The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with severe aortic stenosis to medical management versus transcatheter aortic valve replacement (TAVR; inoperable cohort) and surgical aortic valve replacement versus TAVR (high-risk cohort). Among 971 patients with evaluable echocardiograms (92%), LF (stroke volume index ⩽35 mL/m2) was observed in 530 (55%); LF and low ejection fraction (<50%) in 225 (23%); and LF, low ejection fraction, and low mean gradient (<40 mm Hg) in 147 (15%). Two-year mortality was significantly higher in patients with LF compared with those with normal stroke volume index (47% versus 34%; hazard ratio, 1.5; 95% confidence interval, 1.25–1.89; P=0.006). In the inoperable cohort, patients with LF had higher mortality than those with normal flow, but both groups improved with TAVR (46% versus 76% with LF and 38% versus 53% with normal flow; P<0.001). In the high-risk cohort, there was no difference between TAVR and surgical aortic valve replacement. In patients with paradoxical LF and low gradient (preserved ejection fraction), TAVR reduced 1-year mortality from 66% to 35% (hazard ratio, 0.38; P=0.02). LF was an independent predictor of mortality in all patient cohorts (hazard ratio, ≈1.5), whereas ejection fraction and gradient were not. Conclusions— LF is common in severe aortic stenosis and independently predicts mortality. Survival is improved with TAVR compared with medical management and similar with TAVR and surgical aortic valve replacement. A measure of flow (stroke volume index) should be included in the evaluation and therapeutic decision making of patients with severe aortic stenosis. Clinical Trial Registration— URL: http://www.clinicaltrial.gov. Unique identifier: NCT0053089.4.

Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection : an alternative mechanism of allorecognition

Despite evidence that human non-hematopoietic cells, such as vascular endothelium, can activate allogeneic T lymphocytes in vitro, the prevailing view has been that hematopoietic antigen-presenting cells are required to trigger alloimmune responses in vivo. Here we report that mouse non-hematopoietic cells activate alloreactive CD8+ T lymphocytes in vitro and in vivo. We also show that vascularized cardiac allografts are acutely rejected via CD8+ direct allorecognition even if the alloantigen is not presented by hematopoietic professional antigen-presenting cells. Because activation of alloreactive CD8+ T cells by donor-type non-hematopoietic cells can continue for the life of the allograft, these findings present a new clinically relevant mechanism of allorecognition and should be taken into consideration when developing strategies to prevent allograft vasculopathy or to induce tolerance.

Predictors of Mortality and Outcomes of Therapy in Low Flow Severe Aortic Stenosis: A PARTNER Trial Analysis

Background— The prognosis and treatment of patients with low-flow (LF) severe aortic stenosis are controversial. Methods and Results— The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with severe aortic stenosis to medical management versus transcatheter aortic valve replacement (TAVR; inoperable cohort) and surgical aortic valve replacement versus TAVR (high-risk cohort). Among 971 patients with evaluable echocardiograms (92%), LF (stroke volume index ⩽35 mL/m2) was observed in 530 (55%); LF and low ejection fraction (<50%) in 225 (23%); and LF, low ejection fraction, and low mean gradient (<40 mm Hg) in 147 (15%). Two-year mortality was significantly higher in patients with LF compared with those with normal stroke volume index (47% versus 34%; hazard ratio, 1.5; 95% confidence interval, 1.25–1.89; P=0.006). In the inoperable cohort, patients with LF had higher mortality than those with normal flow, but both groups improved with TAVR (46% versus 76% with LF and 38% versus 53% with normal flow; P<0.001). In the high-risk cohort, there was no difference between TAVR and surgical aortic valve replacement. In patients with paradoxical LF and low gradient (preserved ejection fraction), TAVR reduced 1-year mortality from 66% to 35% (hazard ratio, 0.38; P=0.02). LF was an independent predictor of mortality in all patient cohorts (hazard ratio, ≈1.5), whereas ejection fraction and gradient were not. Conclusions— LF is common in severe aortic stenosis and independently predicts mortality. Survival is improved with TAVR compared with medical management and similar with TAVR and surgical aortic valve replacement. A measure of flow (stroke volume index) should be included in the evaluation and therapeutic decision making of patients with severe aortic stenosis. Clinical Trial Registration— URL: http://www.clinicaltrial.gov. Unique identifier: NCT0053089.4.

Predictors and Clinical Outcomes of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement: The PARTNER (Placement of AoRtic TraNscathetER Valves) Trial and Registry

OBJECTIVES The purpose of this study was to identify predictors and clinical implications of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). BACKGROUND Cardiac conduction disturbances requiring PPM are a frequent complication of TAVR. However, limited data is available regarding this complication after TAVR with a balloon-expandable valve. METHODS The study included patients without prior pacemaker who underwent TAVR in the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry and investigated predictors and clinical effect of new PPM. RESULTS Of 2,559 TAVR patients, 586 were excluded due to pre-existing PPM. A new PPM was required in 173 of the remaining 1,973 patients (8.8%). By multivariable analysis, predictors of PPM included right bundle branch block (odds ratio [OR]: 7.03, 95% confidence interval [CI]: 4.92 to 10.06, p < 0.001), prosthesis diameter/left ventricular (LV) outflow tract diameter (for each 0.1 increment, OR: 1.29, 95% CI: 1.10 to 1.51, p = 0.002), LV end-diastolic diameter (for each 1 cm, OR: 0.68, 95% CI: 0.53 to 0.87, p = 0.003), and treatment in continued access registry (OR: 1.77, 95% CI: 1.08 to 2.92, p = 0.025). Patients requiring PPM had a longer mean duration of post-procedure hospitalization (7.3 ± 2.7 days vs. 6.2 ± 2.8 days, p = 0.001). At 1 year, new PPM was associated with significantly higher repeat hospitalization (23.9% vs. 18.2%, p = 0.05) and mortality or repeat hospitalization (42.0% vs. 32.6%, p = 0.007). There was no difference between groups in LV ejection fraction at 1 year. CONCLUSIONS PPM was required in 8.8% of patients without prior PPM who underwent TAVR with a balloon-expandable valve in the PARTNER trial and registry. In addition to pre-existing right bundle branch block, the prosthesis to LV outflow tract diameter ratio and the LV end-diastolic diameter were identified as novel predictors of PPM after TAVR. New PPM was associated with a longer duration of hospitalization and higher rates of repeat hospitalization and mortality or repeat hospitalization at 1 year. (THE PARTNER TRIAL: Placement of AoRtic TraNscathetER Valves Trial; NCT00530894).

2015 SCAI/ACC/HFSA/STS clinical expert consensus statement on the use of percutaneous mechanical circulatory support devices in cardiovascular care: Endorsed by the American Heart Assocation, the Cardiological Society of India, and Sociedad Latino Americana de Cardiologia intervencion; Affirmation of value by the Canadian Association of Interventional Cardiology-Association Canadienne de Cardiologie d'intervention

Although historically the intra-aortic balloon pump has been the only mechanical circulatory support device available to clinicians, a number of new devices have become commercially available and have entered clinical practice. These include axial flow pumps, such as Impella(®); left atrial to femoral artery bypass pumps, specifically the TandemHeart; and new devices for institution of extracorporeal membrane oxygenation. These devices differ significantly in their hemodynamic effects, insertion, monitoring, and clinical applicability. This document reviews the physiologic impact on the circulation of these devices and their use in specific clinical situations. These situations include patients undergoing high-risk percutaneous coronary intervention, those presenting with cardiogenic shock, and acute decompensated heart failure. Specialized uses for right-sided support and in pediatric populations are discussed and the clinical utility of mechanical circulatory support devices is reviewed, as are the American College of Cardiology/American Heart Association clinical practice guidelines.

Results of a New Surgical Paradigm: Endovascular Repair for Acute Complicated Type B Aortic Dissection

BACKGROUND Conventional open repair of acute complicated type B aortic dissection is associated with significant morbidity and mortality. This study examined the results of thoracic endovascular aortic repair (TEVAR) in acute type B aortic dissection complicated with rupture or malperfusion syndrome. METHODS From 2004 through 2007, 35 patients (22 men) with acute complicated type B aortic dissection were treated with TEVAR. Indications included rupture in 18 (51.4%) and malperfusion syndrome in 17 (48.6%; mesenteric or renal, 5;lower extremities, 3; both, 9). Three types of endograft devices were used (mean per patient, 1.9 devices). Intravascular ultrasound imaging was used in 15 patients (42.8%). In patients with malperfusion syndrome, distal adjunct procedures to expand the true lumen included infrarenal aortic stents in 4, mesenteric/renal stents in 4, and iliofemoral stents in 7. Follow-up was 93.9% during a period of 18.3 months (range, 3 to 47 months). RESULTS The mean age was 58.6 +/- 13.4 years. Technical success (coverage of the primary tear site) was achieved in 34 patients (97.1%). Coverage of the left subclavian artery was required in 25 patients (71.4%). Thirty-day mortality was 2.8%. One-year survival was 93.4% +/- 4.6%. Complications included permanent renal failure (2.8%), stroke (2.8%), spinal cord ischemia (transient [5.7%], permanent [(2.8%]), and vascular access (14.2%). The mean intensive care unit and hospital stay were 4.7 +/- 2.6 and 16.7 +/- 12.0 days, respectively. CONCLUSIONS Endovascular repair of acute complicated type B aortic dissection is associated with low morbidity and mortality and has emerged as the surgical therapy of choice.