Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial.

BACKGROUND: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs. METHODS: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing. FINDINGS: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI -0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI -3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups. INTERPRETATION: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves. FUNDING: Abbott.

Cardiovascular Outcomes Assessment of the MitraClip in Patients with Heart Failure and Secondary Mitral Regurgitation: Design and rationale of the COAPT trial.

BACKGROUND: Patients with heart failure (HF) and symptomatic secondary mitral regurgitation (SMR) have a poor prognosis, with morbidity and mortality directly correlated with MR severity. Correction of isolated SMR with surgery is not well established in this population, and medical management remains the preferred approach in most patients. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial was designed to determine whether transcatheter mitral valve (MV) repair with the MitraClip device is safe and effective in patients with symptomatic HF and clinically significant SMR. STUDY DESIGN: The COAPT trial is a prospective, randomized, parallel-controlled, open-label multicenter study of the MitraClip device for the treatment of moderate-to-severe (3+) or severe (4+) SMR (as verified by an independent echocardiographic core laboratory) in patients with New York Heart Association class II-IVa HF despite treatment with maximally tolerated guideline-directed medical therapy (GDMT) who have been determined by the site's local heart team as not appropriate for MV surgery. A total of 614 eligible subjects were randomized in a 1:1 ratio to MV repair with the MitraClip plus GDMT versus GDMT alone. The primary effectiveness end point is recurrent HF hospitalizations through 24 months, analyzed when the last subject completes 12-month follow-up, powered to demonstrate superiority of MitraClip therapy. The primary safety end point is a composite of device-related complications at 12 months compared to a performance goal. Follow-up is ongoing, and the principal results are expected in late 2018. CONCLUSIONS: HF patients with clinically significant SMR who continue to be symptomatic despite optimal GDMT have limited treatment options and a poor prognosis. The randomized COAPT trial was designed to determine the safety and effectiveness of transcatheter MV repair with the MitraClip in symptomatic HF patients with moderate-to-severe or severe SMR.

A single-center experience with the Sorin Mitroflow pericardial aortic valve: hemodynamics up to five years.

BACKGROUND AND AIM OF THE STUDY: The authors' institution participated in a 28-center FDA Investigational Device Exemption study to evaluate the Sorin Mitroflow pericardial aortic bioprosthesis. Six high-enrolling sites evaluated patients on an annual basis as part of an ongoing hemodynamic study. These data represent patients followed for an average of five years after implant, with annual echocardiography. METHODS: Seventy-one patients were entered into the study and constitute the basis of this review. Mean follow up was 3.3 +/- 2.0 years (range: 0-5.5 years), with a cumulative follow up of 233 patient-years. The mean patient age was 73.8 years (range: 45-89 years), and 52% were males. The majority of aortic valve lesions were stenosis (63%) or mixed (30%), and nine patients (12.7%) were reoperations. Sixty-one patients (86%) had concomitant procedures, the most common being coronary artery bypass grafting (70%). RESULTS: A total of 281 echocardiograms was obtained from the patients over a five-year period. The largest number of echocardiograms was obtained with 23-mm valve implants (n = 122), followed by 25 mm valve implants (n = 87). The early baseline (30-day) mean gradient was < or = 10 mm in all patients. The mean gradient decreased as the valve size increased (21 mm valve gradient = 10.0 +/- 5.6 mmHg; 27 mm valve gradient = 6.2 +/- 2.2 mmHg). The mean increase in gradient at five years was < 7 mmHg, with a trend towards increased gradients at smaller valve sizes. The effective orifice area (EOA) showed a trend to decline slightly with 21 mm valves (from 1.5 to 1.2 cm2) and 23 mm valves (1.4 to 1.2 cm2), but there was either no change or a slight increase in larger-size valves. Left ventricular mass regression occurred mainly within the first year (18.9%), but then remained stable throughout the study period. No greater than mild prosthetic aortic valve regurgitation was observed over the study period. CONCLUSION: The Sorin Mitroflow aortic valve provides excellent hemodynamic results up to five years, with minimal increase in mean gradients, acceptable peak gradients, and good EOAs with all valves sizes.

Does valve size impact hemodynamic, left ventricular mass regression, and prosthetic valve deterioration with a sutureless aortic valve?

OBJECTIVE: To assess the mid-term clinical outcomes, hemodynamics, left ventricular (LV) mass regression, and structural valve deterioration (SVD) in patients implanted with the Perceval aortic sutureless valve across valve sizes. METHODS: Data were obtained from a multicenter European trial and a US Investigational Device Exemption trial. Echocardiography data were analyzed by an echocardiography core lab. A mixed-effects regression model was used to assess relationships between hemodynamic outcomes, time from the procedure, and valve sizes. The Valve Academic Research Consortium (VARC)-3 definition for bioprosthetic valve failure was applied. RESULTS: A Perceval sutureless valve was implanted in 970 patients. The median patient age was 77.8 years, 57.2% were female, the median Society of Thoracic Surgeons predicated risk of mortality was 3.3% (range, 2.1%-6.2%), and 33.4% had a concomitant procedure. The median clinical follow-up was 45.7 months (range, 28.2-76.1 months). Small and medium valves were implanted more commonly in women than in men (16.9% vs 1.9% for small and 55.1% vs 19.5% for medium; P < .001). The mean aortic valve gradients decreased significantly postimplantation and remained stable across all valve sizes throughout the follow-up period. All patients were free from severe patient-prosthesis mismatch (with an effective orifice area/m2 of >0.8). Significant LV mass regression was documented regardless valve sizes, plateaued at -9.1% at 5 years. Freedom from SVD and reintervention were 95.2% and 96.3%, respectively, at 5 years and were independent of implanted valve size (P = .22). The VARC-3 stage 3 bioprosthetic valve failure rate was low, 2.8% at 5 years. CONCLUSIONS: The Perceval valve demonstrated low and stable mean gradients, significant LV mass regression, and low SVD and reintervention rates across all valve sizes.

Mid-term outcomes of the COMMENCE trial investigating mitral valve replacement using a bioprosthesis with a novel tissue.

Objective: Novel tissue leaflets (RESILIA tissue) may improve durability of bioprosthetic heart valves. The COMMENCE trial is an ongoing prospective study to evaluate valve replacement using RESILIA tissue. This report describes mid-term outcomes in the mitral cohort of COMMENCE. Methods: Adult patients requiring mitral valve replacement were enrolled in a prospective, single-arm trial at 17 sites in the United States and Canada. An independent clinical events committee adjudicated safety events using definitions from established guidelines, and hemodynamic performance was evaluated by an independent echocardiographic core laboratory. Results: Eighty-two patients (median age 70 years) successfully underwent mitral valve replacement with the study valve. Five-year event-free probabilities for all-cause mortality, structural valve deterioration, and reoperation were 79.9%, 98.7%, and 97.1%, respectively. Hemodynamic valve function measurements were stable through the 5-year follow-up period; valvular leaks were infrequently observed and primarily clinically insignificant/mild. Conclusions: Mitral valve replacement patients implanted with a RESILIA tissue bioprosthesis had a good safety profile and clinically stable hemodynamic performance.

Seven-year outcomes following aortic valve replacement with a novel tissue bioprosthesis.

OBJECTIVE: As bioprosthetic aortic valve replacement (AVR) extends to younger cohorts, tissue durability is of paramount importance. We report 7-year outcomes from an AVR bioprosthesis utilizing novel tissue. METHODS: This was an international investigational device exemption trial for novel AVR with annual follow-up and a subset re-consented at 5 years for extended 10-year follow-up. Safety end points and echocardiographic measurements were adjudicated by an independent clinical events committee and by a dedicated core laboratory, respectively. RESULTS: Between January 2013 and March 2016, 689 patients underwent AVR with the study valve. Mean age was 66.9 ± 11.6 years, Society of Thoracic Surgeons risk score was 2.0% ± 1.8%, and 74.3% of patients were New York Heart Association functional class II and III. Five-year follow-up was completed by 512 patients, and 225 re-consented for extended follow-up. Follow-up duration was 5.3 ± 2.2 years (3665.6 patient-years), and 194 and 195 patients completed 6- and 7-year follow-ups, respectively. One-, 5-, and 7-year freedom from all-cause mortality was 97.7%, 89.4%, and 85.4%, respectively. Freedom from structural valve deterioration at 7 years was 99.3%. At 7 years, effective orifice area and mean gradients were 1.82 ± 0.57 cm2 (n = 153), and 9.4 ± 4.5 mm Hg (n = 157), respectively. At 7 years, predominantly none (96.8% [152 out of 157]) or trivial/trace (2.5% [4 out of 157]) paravalvular regurgitation and none (84.7% [133 out of 157]) or trivial/trace (11.5% [18 out of 157]) transvalvular regurgitation were observed. CONCLUSIONS: We report the longest surgical AVR follow-up with novel tissue in an investigational device exemption trial utilizing an independent clinical events committee and an echocardiography core laboratory. This tissue demonstrates excellent outcomes through 7 years and is the benchmark for future surgical and transcatheter prostheses.

Five-year Outcomes of the COMMENCE Trial Investigating Aortic Valve Replacement With RESILIA Tissue.

BACKGROUND: The COMMENCE trial was conducted to evaluate the safety and effectiveness of aortic valve replacement using a bioprosthesis with novel RESILIA tissue (Edwards Lifesciences). RESILIA tissue is incorporated in the INSPIRIS RESILIA aortic valve (Edwards Lifesciences). METHODS: Patients underwent clinically indicated surgical aortic valve replacement with a bovine pericardial bioprosthesis (model 11000A; Edwards Lifesciences) in a prospective, multinational, multicenter (n = 27), US Food and Drug Administration Investigational Device Exemption trial. Events were adjudicated by an independent clinical events committee, and echocardiograms were analyzed by an independent core laboratory. Outcomes through an observational period of 5 years are reported. RESULTS: Between January 2013 and March 2016, 689 patients received the study valve. Mean patient age was 66.9 ± 11.6 years; Society of Thoracic Surgeons Predicted Risk of Mortality was 2.0% ± 1.8%; and 23.8%, 49.9%, and 24.4% of patients were New York Heart Association functional class I, II, and III at baseline, respectively. Through December 11, 2020 the follow-up duration was 4.3 ± 1.4 years, and the completeness of follow-up over the observational period was 95.5%. Early (<30 days) all-cause mortality was 1.2%, stroke 1.6%, and major paravalvular leak 0.1%. Five-year actuarial freedom from all-cause mortality, structural valve deterioration, and all-cause reintervention were 89.2%, 100%, and 98.7%, respectively. At 5 years the effective orifice area was 1.6 ± 0.5 cm2, mean gradient was 11.5 ± 6.0 mm Hg, 97.8% of patients were class I/II, and 97.8% and 96.3% of patients had none/trace paravalvular and transvalvular regurgitation, respectively. CONCLUSIONS: The safety and hemodynamic performance of this aortic bioprosthesis with RESILIA tissue through 5 years are encouraging, with clinically stable hemodynamics, minimal regurgitation, and no evidence of structural valve deterioration.

Transcarotid versus transthoracic access for transcatheter aortic valve replacement: A propensity-matched analysis.

OBJECTIVE: Transcarotid access for transcatheter aortic valve replacement is emerging as an alternative to more traditional nonfemoral access options such as transapical or transaortic; however, comparative data are limited. The purpose of the study was to analyze outcomes after transcatheter aortic valve replacement using transcatheter compared with transthoracic (transapical/transaortic) access. METHODS: The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was queried for patients who underwent transcarotid, transapical, or transaortic transcatheter aortic valve replacement with the SAPIEN 3 (Edwards Lifesciences, Irvine, Calif) transcatheter heart valve between June 2015 and July 2019. Thirty-day unadjusted outcomes were evaluated, and propensity score matching and logistic regression were used to compare transcatheter access with transthoracic access. RESULTS: In the propensity-matched analysis, 667 transcarotid transcatheter aortic valve replacement procedures were compared with 1334 transthoracic procedures. Transcarotid transcatheter aortic valve replacement was associated with lower mortality (4.2% vs 7.7%, P = .004), less new-onset atrial fibrillation (2.2% vs 12.1%, P < .0001), fewer readmissions at 30 days (9.8% vs 16.1%, P = .0006), shorter median length of stay (3.0 vs 6.0 days, P < .0001), shorter median intensive care unit stay (25 vs 47.2 hours, P < .0001), and greater 30-day Kansas City Cardiomyopathy Questionnaire score improvement from baseline (25.1 vs 20.8, P = .007). Stroke (4.3% vs 3.7%, P = .44) and major vascular complications (1.4% vs 1.9%, P = .40) were similar. CONCLUSIONS: Transcatheter aortic valve replacement using transcarotid access is associated with lower 30-day mortality, less atrial fibrillation, shorter intensive care unit and overall length of stay, fewer readmissions, greater improvement in Kansas City Cardiomyopathy Questionnaire scores, and no significant difference in stroke or major vascular complications compared with transthoracic access.

Randomized Trials Are Needed for Transcatheter Mitral Valve Replacement.

Transcatheter mitral valve replacement (TMVR) is a new therapy for treating symptomatic mitral regurgitation (MR) and stenosis. The proposed benefit of TMVR is the predictable, complete elimination of MR, which is less certain with transcatheter repair technologies such as TEER (transcatheter edge-to-edge repair). The potential benefit of MR elimination with TMVR needs to be rigorously evaluated against its risks which include relative procedural invasiveness, need for anticoagulation, and chronic structural valve deterioration. Randomized controlled trials (RCTs) are a powerful method for evaluating the safety and effectiveness of TMVR against current standard of care transcatheter therapies, such as TEER. RCTs not only help with the assessment of benefits and risks, but also with policies for determining operator or institutional requirements, resource utilization, and reimbursement. In this paper, the authors provide recommendations and considerations for designing pivotal RCTs for first-in-class TMVR devices.

Transcarotid Versus Subclavian/Axillary Access for Transcatheter Aortic Valve Replacement With SAPIEN 3.

BACKGROUND: Subclavian/axillary (TAx) access has become the most frequently used alternative access route for transcatheter aortic valve replacement (TAVR). Transcarotid (TC) TAVR has grown in popularity recently. Comparative data between these 2 contemporary access methods is lacking. METHODS: Data were extracted from The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry™ (June 2015 to October 2019) for patients undergoing TAVR by TC or TAx access with the SAPIEN 3 and SAPIEN 3 Ultra (Edwards Lifesciences, Irvine, CA) transcatheter heart valves. Procedural, index hospitalization, and 30-day outcomes were analyzed for TC vs TAx groups after 1:2 propensity matching of patient baseline characteristics. RESULTS: The study included 3903 cases, of which 801 TC and 3102 TAx procedures were compared. After 1:2 propensity matching, TC TAVR was associated with similar 30-day mortality (4.3% vs 5.2%, P = .34) but a significantly lower risk of stroke (4.2% vs 7.4%; hazard ratio, 0.56; 95% confidence interval, 0.38-0.83; P = .003) compared with TAx access. Other outcomes that favored TC over TAx included shorter procedure time (117.0 vs 132.4 minutes; P < .001) and fluoroscopy time (16.6 vs 21.6 min; P < .001), lower contrast volume (78.5 vs 96.7 mL; P < .001), shorter length of stay in the intensive care unit (24.3 vs 25.0 hours; P = .02) and hospital (2.0 vs 3.0 days; P = .002), and more patients discharged to home (82.9% vs 74.6%; P < .001). CONCLUSIONS: TC TAVR is associated with similar mortality and a significant reduction in stroke compared with the TAx approach. If femoral access is precluded, TC may be a safe, or at times, preferred avenue of transcatheter valve delivery.

Prospective US investigational device exemption trial of a sutureless aortic bioprosthesis: One-year outcomes.

OBJECTIVES: We performed a prospective, single-arm clinical trial approved under a Food and Drug Administration Investigational Device Exemption to assess safety and efficacy of Perceval, a sutureless bovine pericardial aortic valve representing the initial US experience. METHODS: From June 2013 to January 2015, 300 patients (mean age 76.7 ± 7.7 years, 54.3% men, 37.3% ≥80 years, median Society of Thoracic Surgeons Predicted Risk of Mortality 2.8%), underwent Perceval valve implantation at 18 centers across the United States. Twenty patients (6.7%) had a bicuspid aortic valve and 5 (1.7%) patients had previous aortic valve replacement. A minimally invasive approach was used in 80 (26.7%) and concomitant procedures were performed in 113 (37.8%) patients. RESULTS: Two hundred eighty-nine patients (96.3%) were successfully implanted. Operative mortality (≤30 days) was 1.3% (n = 4) (observed to expected ratio of 0.40). One-year results included all-cause mortality in 5.2% (n = 15), stroke in 1% (n = 3), and endocarditis in 1.7% (n = 5). New permanent periprocedural pacemaker rate was 10.7% (n = 30/281); 2.5% (n = 7/281) resulted from third-degree atrioventricular block. One-year valve-related reoperation was 2.1% (n = 6). At 1-year follow-up, 98% of patients were in New York Heart Association class I/II, left ventricular mass index decreased from 103.5 ± 30.1 g/m2 at discharge to 95.8 ± 27.1 g/m2 (P = .001), and 3 (1.3%) moderate paravalvular leaks were identified. Health-related quality of life score increased from 62.7 ± 21.8 before surgery to 85.5 ± 17.8 at 1 year (P < .001). CONCLUSIONS: These results confirm the safety and effectiveness of the Perceval sutureless aortic valve replacement in study patients with lower mortality than expected from a risk prediction model. Persistent hemodynamic benefit and improvement in quality of life at 1 year support the importance of this device in the management of aortic valve disease.

Pivotal Clinical Study to Evaluate the Safety and Effectiveness of the MANTA Percutaneous Vascular Closure Device.

BACKGROUND: Open surgical closure and small-bore suture-based preclosure devices have limitations when used for transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or percutaneous thoracic endovascular aortic aneurysm repair. The MANTA vascular closure device is a novel collagen-based technology designed to close large bore arteriotomies created by devices with an outer diameter ranging from 12F to 25F. In this study, we determined the safety and effectiveness of the MANTA vascular closure device. METHODS AND RESULTS: A prospective, single arm, multicenter investigation in patients undergoing transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, or thoracic endovascular aortic aneurysm repair at 20 sites in North America. The primary outcome was time to hemostasis. The primary safety outcomes were accessed site-related vascular injury or bleeding complications. A total of 341 patients, 78 roll-in, and 263 in the primary analysis cohort, were entered in the study between November 2016 and September 2017. For the primary analysis cohort, transcatheter aortic valve replacement was performed in 210 (79.8%), and percutaneous endovascular abdominal aortic aneurysm repair or thoracic endovascular aortic aneurysm repair was performed in 53 (20.2%). The 14F MANTA was used in 42 cases (16%), and the 18F was used in 221 cases(84%). The mean effective sheath outer diameter was 22F (7.3 mm). The mean time to hemostasis was 65±157 seconds with a median time to hemostasis of 24 seconds. Technical success was achieved in 257 (97.7%) patients, and a single device was deployed in 262 (99.6%) of cases. Valve Academic Research Consortium-2 major vascular complications occurred in 11 (4.2%) cases: 4 received a covered stent (1.5%), 3 had access site bleeding (1.1%), 2 underwent surgical repair (0.8%), and 2 underwent balloon inflation (0.8%). CONCLUSIONS: In a selected population, this study demonstrated that the MANTA percutaneous vascular closure device can safely and effectively close large bore arteriotomies created by current generation transcatheter aortic valve replacement, percutaneous endovascular abdominal aortic aneurysm repair, and thoracic endovascular aortic aneurysm repair devices. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02908880.

The COMMENCE trial: 2-year outcomes with an aortic bioprosthesis with RESILIA tissue.

OBJECTIVES: The COMMENCE trial was conducted to evaluate the safety and effectiveness of a novel bioprosthetic tissue for surgical aortic valve replacement (AVR). METHODS: Patients underwent clinically indicated surgical AVR with the Carpentier-Edwards PERIMOUNT™ Magna Ease™ aortic valve with RESILIA™ tissue (Model 11000A) in a prospective, multinational, multicentre (n = 27), single-arm, FDA Investigational Device Exemption trial. Events were adjudicated by an independent Clinical Events Committee; echocardiograms were analysed by an independent Core Laboratory. RESULTS: Between January 2013 and February 2016, 689 patients received the study valve. Mean age was 67.0 ± 11.6 years; 71.8% were male; 26.3% were New York Heart Association Class III/IV. Mean STS PROM was 2.0 ± 1.8 (0.3-17.5). Isolated AVR was performed in 59.1% of patients; others had additional concomitant procedures, usually CABG. Thirty-day outcomes for all patients included all-cause mortality 1.2%, thromboembolism 2.2%, bleeding 0.9%, major paravalvular leak 0.1% and permanent pacemaker implantation 4.7%. Median intensive care unit and hospital length of stay were 2 (range: 0.2-66) and 7 days (3.0-121.0), respectively. At 2 years, New York Heart Association class improved in 65.7%, effective orifice area was 1.6 ± 0.5 cm2; mean gradient was 10.1 ± 4.3 mmHg; and paravalvular leak was none/trivial in 94.5%, mild in 4.9%, moderate in 0.5% and severe in 0.0%. One-year actuarial freedom from all-cause mortality for isolated AVR and for all patients was 98.2% and 97.6%, respectively. Two-year actuarial freedom from mortality in these groups was 95.3% and 94.3%, respectively. CONCLUSIONS: These data demonstrate excellent early safety and effectiveness of aortic valve replacement with a novel bioprosthetic tissue (RESILIA™). CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT01757665.

North American trial results at 1 year with the Sorin Freedom SOLO pericardial aortic valve.

OBJECTIVES: A North American prospective, 15-centre Food and Drug Administration (FDA) valve trial was designed to assess the safety and effectiveness of the Freedom SOLO stentless pericardial aortic valve in the treatment of surgical aortic valve disease. METHODS: Beginning in 2010, 251 patients (mean: 74.7 ± 7.5 years), were recruited in the Freedom SOLO aortic valve trial. One hundred eighty-nine patients have been followed for at least 1 year and are the basis for this review. Preoperatively, 54% of patients had NYHA functional class III or IV symptoms, and the majority of patients had a normal ejection fraction (EF) (median EF = 61%). Concomitant procedures were performed in 61.9% of patients, with coronary artery bypass grafting (CABG) (48.7%) being the most common followed by a MAZE procedure (13.7%). Reoperations were performed in 8.5% of patients in the study. RESULTS: The entire cohort of 251 patients enrolled had 7 deaths prior to 30 days, 2 of which were valve-related (aspiration pneumonia and sudden death) and 5 were not valve-related. There were 11 deaths after 30 days, 1 valve-related (unknown cardiac death) and 10 not valve-related. Five valves were explanted, 3 early (endocarditis, acute insufficiency and possible root dissection) and 2 late (endocarditis). Thirty-day adverse events include arrhythmias requiring permanent pacemaker (4.2%), thromboembolic events (3.7%) and thrombocytopenia (7.4%). One-year follow-up of all 189 patients demonstrated mean gradients for valve sizes 19, 21, 23, 25 and 27 mm of 11.7, 7.8, 6.3, 4.6 and 5.0 mmHg, respectively. Effective orifice areas for the same valve sizes were 1.2, 1.3, 1.6, 1.8 and 1.9 cm(2), respectively. Ninety-six percent of patients (181/189) were in NYHA class I or II at the 1-year follow-up. CONCLUSIONS: The Freedom SOLO stentless pericardial aortic valve demonstrated excellent haemodynamics and a good safety profile out to the 1 year of follow-up.

Clinical and haemodynamic outcomes in 804 patients receiving the Freedom SOLO stentless aortic valve: results from an international prospective multicentre study.

OBJECTIVES: The Freedom SOLO™ valve (Sorin Group, Italy) is a stentless aortic bioprosthesis designed for simplified implantation. The present multicentre study is the largest prospective evaluation of this prosthesis. Herein, we report on outcomes at 3-year follow-up. METHODS: From March 2009 to February 2013, a total of 804 consecutive patients (mean age 74.9 ± 6.3 years; 45.1% females) underwent aortic valve replacement with the Freedom SOLO™ valve at 33 centres. Concomitant procedures (70.2% coronary artery bypass grafting) were performed in 376 patients. The cumulative follow-up included 1100 patient-years (mean 16.5 ± 10.8 months; range: 0-40.5 months). RESULTS: Sixty-four patients died (14 early, 50 late); 12 deaths (1 early, 11 late) were valve-related. Operative mortality (30 days) was 1.7%. At 3 years, overall survival was 82.6% [95% confidence interval (CI) 75.5-87.8%] and freedom from valve-related death was 95.5% (95% CI 89.2-98.2%). Linearized late event rates were 0.82%/patient-years for non-structural valve dysfunction, 0.55%/patient-years for structural valve deterioration, 1.55%/patient-years for endocarditis, 3.64%/patient-years for thromboembolism and 3.18%/patient-years for bleeding. In total, there were 22 reinterventions [19 valve explants, 2 refixations, 1 transcatheter aortic valve intervention (TAVI)] for endocarditis (11), non-structural dysfunction (9) and structural valve deterioration (2). Freedom from reintervention was 95.2% (95% CI 91.2-97.4%) at 3 years. There were no instances of valve thrombosis or haemolysis. At 1, 2 and 3 years, 97.0, 95.5 and 91.4% of patients were in NYHA class I or II. Between discharge and 3 years after surgery, mean transvalvular gradients exhibited a non-significant increase (6.5 ± 4.3 vs 8.7 ± 6.5 mmHg), whereas effective orifice area index remained stable (0.9 ± 0.2 vs 0.8 ± 0.3 cm(2)/m(2)). At 3 years, no patient presented with more than mild aortic regurgitation. Left ventricular mass index decreased significantly between discharge and 1 year after surgery (139.4 ± 40.9 vs 122.4 ± 35.3 g/m(2), P < 0.001) and remained unchanged thereafter. Left ventricular size and function did not change over time. CONCLUSIONS: The Freedom SOLO™ valve is a unique stentless pericardial bioprosthesis whose design favours haemodynamic performance and thus facilitates left ventricular reverse remodelling. In terms of survival, morbidity and functional status, it is associated with beneficial outcomes up to 3 years after surgery. Ongoing follow-up will assess the valve at the long-term course.

The ABLATE Trial: Safety and Efficacy of Cox Maze-IV Using a Bipolar Radiofrequency Ablation System.

BACKGROUND: The Cox Maze-IV procedure (CMP-IV) has replaced the Cox Maze-III procedure as the most common approach for the surgical treatment of atrial fibrillation (AF). The Food and Drug Administration-regulated AtriCure Bipolar Radiofrequency Ablation of Permanent Atrial Fibrillation (ABLATE) trial sought to demonstrate the safety and efficacy of the CMP-IV performed with the Synergy ablation system (AtriCure, Inc, Cincinnati, OH). METHODS: Fifty-five patients (aged 70.5 ± 9.3 years), 92.7% of whom had nonparoxysmal AF, underwent CMP-IV to terminate AF during a concomitant cardiac surgical procedure. Lesions were created using the AtriCure Synergy bipolar radiofrequency ablation system. All patients were seen for follow-up visits after 30 days, 3 months, and 6 months, with 24-hour Holter monitoring at 6 months. Late evaluation was performed by 48-hour Holter monitoring at an average of 21 months. RESULTS: The primary efficacy endpoint, absence of AF (30 seconds or less) at 6-month follow-up off antiarrhythmic medications (Heart Rhythm Society definition), indicated 76% (38 of 50) were AF free (95% confidence interval: 62.6% to 85.7%). The primary safety endpoint, the rate of major adverse events within 30 days, was 9.1% (5 of 55; 95% confidence interval: 3.9% to 19.6%), with 3.6% mortality (2 of 55). Secondary efficacy endpoints included being AF free with antiarrhythmic drugs (6 months, 84%; 21 months, 75%), successful pulmonary vein isolation (100%), and AF burden at 6 and 21 months. The results, together with those for the secondary safety endpoint (6-month major adverse events), demonstrated that the Synergy system performs comparably to the cut-and-sew Cox Maze-III procedure. CONCLUSIONS: The CMP-IV using the AtriCure Synergy system was safe and effective for cardiac surgical patients who had persistent and longstanding persistent AF.

Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation: 5-Year Results of EVEREST II.

BACKGROUND: In EVEREST II (Endovascular Valve Edge-to-Edge Repair Study), treatment of mitral regurgitation (MR) with a novel percutaneous device showed superior safety compared with surgery, but less effective reduction in MR at 1 year. OBJECTIVES: This study sought to evaluate the final 5-year clinical outcomes and durability of percutaneous mitral valve (MV) repair with the MitraClip device compared with conventional MV surgery. METHODS: Patients with grade 3+ or 4+ MR were randomly assigned to percutaneous repair with the device or conventional MV surgery in a 2:1 ratio (178:80). Patients prospectively consented to 5 years of follow-up. RESULTS: At 5 years, the rate of the composite endpoint of freedom from death, surgery, or 3+ or 4+ MR in the as-treated population was 44.2% versus 64.3% in the percutaneous repair and surgical groups, respectively (p = 0.01). The difference was driven by increased rates of 3+ to 4+ MR (12.3% vs. 1.8%; p = 0.02) and surgery (27.9% vs. 8.9%; p = 0.003) with percutaneous repair. After percutaneous repair, 78% of surgeries occurred within the first 6 months. Beyond 6 months, rates of surgery and moderate-to-severe MR were comparable between groups. Five-year mortality rates were 20.8% and 26.8% (p = 0.4) for percutaneous repair and surgery, respectively. In multivariable analysis, treatment strategy was not associated with survival. CONCLUSIONS: Patients treated with percutaneous repair more commonly required surgery for residual MR during the first year after treatment, but between 1- and 5-year follow-up, comparably low rates of surgery for MV dysfunction with either percutaneous or surgical therapy endorse the durability of MR reduction with both repair techniques. (EVEREST II Pivotal Study High Risk Registry; NCT00209274).

2-Year Outcomes After Iliofemoral Self-Expanding Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis Deemed Extreme Risk for Surgery.

BACKGROUND: We reported favorable 1-year outcomes in patients unsuitable for surgery who underwent self-expanding transcatheter aortic valve replacement (TAVR) compared with an objective performance goal. Longer-term outcomes in these patients are not known. OBJECTIVES: This study sought to evaluate the 2-year safety and efficacy in patients with severe aortic stenosis (AS) at extreme risk of surgery treated with self-expanding TAVR. METHODS: We performed a prospective, multicenter, controlled, nonrandomized investigation of self-expanding TAVR in patients with severe AS and prohibitive surgical risk. We report the 2-year clinical outcomes in these patients. RESULTS: A total of 489 extreme-risk patients were treated transfemorally with a self-expanding aortic bioprosthesis at 41 centers. The rate of all-cause mortality or major stroke was 38.0% at 2 years (all-cause mortality, 36.5%; major stroke, 5.1%). The rates of all-cause mortality, cardiovascular mortality, and major stroke were 36.6%, 26.2%, and 5.1%, respectively, at 2 years. Between 1 and 2 years, the incremental all-cause mortality, cardiovascular mortality, and major stroke rates were 12.3%, 7.9%, and 0.8%, respectively. Multivariable predictors of all-cause mortality at 2 years included the presence of coronary artery disease and admission from an assisted living center. A Society of Thoracic Surgeons score >15% was also predictive of 2-year all-cause mortality. At 2 years, 94% of patients had New York Heart Association functional class I or II symptoms. The frequency of moderate or severe paravalvular regurgitation (4.3% at 1 year; 4.4% at 2 years) was unchanged between the first and second year. CONCLUSIONS: Patients with severe AS at extreme surgical risk treated with self-expanding TAVR continued to show good clinical outcomes and hemodynamic valve performance at 2 years. The presence of comorbid conditions rather than valve performance affected 2-year outcomes in these patients. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902).