Integrative echocardiographic assessment of patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge repair.

OBJECTIVES: To investigate whether the integrative echocardiographic criteria used in the cardiovascular outcomes assessment of the mitraclip percutaneous therapy (COAPT) for heart failure patients with functional mitral regurgitation study predict outcomes after edge-to-edge trancatheter mitral valve repair (TMVr) for the treatment of secondary mitral regurgitation (SMR). BACKGROUND: Two randomized controlled trials comparing TMVr to medical treatment reported conflicting findings. Differences in patient selection criteria may have contributed to these diverging results. METHODS: Patients undergoing TMVr were stratified following the integrative COAPT echocardiographic criteria in noneligible and eligible patients who were further classified into three tiers according to effective regurgitant orifice (EROA) (Tier 1: EROA ≥ 0.3cm2 ; Tier 2: EROA 0.2cm2 and 0.29cm2 ; Tier 3: EROA<0.2cm2 ) combined with several other severity criteria. We assessed between group differences in all-cause mortality, successful SMR reduction, and symptom relief from baseline to 2-year follow-up. RESULTS: Between March 2011 and March 2018, 138 patients (mean age 75 years) satisfying the inclusion criteria underwent TMVr for treatment of symptomatic SMR. The mean EROA area was 0.35 ± 0.17 mm2 . Ten patients (7%) died within 30 days, 29 (21%) within 12 months, and 41 (30%) within 2 years. After stratification according to the COAPT echocardiographic criteria that were fulfilled in 72% of the studied population, Tier 2 patients (45%), as well as noneligible patients (38%) had a higher mortality rate compared to those in Tier 1 (19%). CONCLUSIONS: SMR patients stratified into tiers according to the COAPT integrative echocardiographic criteria have diverging prognostic and symptomatic benefit after edge-to-edge TMVr.

Compassionate use of the PASCAL transcatheter mitral valve repair system for patients with severe mitral regurgitation: a multicentre, prospective, observational, first-in-man study.

BACKGROUND: Severe mitral regurgitation is associated with impaired prognosis if left untreated. Using the devices currently available, transcatheter mitral valve repair (TMVr) remains challenging in complex anatomical situations. We report the procedural and 30-day results of the first-in-man study of the Edwards PASCAL TMVr system. METHODS: In this multicentre, prospective, observational, first-in-man study, we collected data from seven tertiary care hospitals in five countries that had a compassionate use programme in which patients underwent transcatheter mitral valve repair using the Edwards PASCAL TMVr system. Eligible patients were those with symptomatic, severe functional, degenerative, or mixed mitral regurgitation deemed at high risk or inoperable. Safety and efficacy of the procedure were prospectively assessed at device implantation, discharge, and 30 days after device implantation. The key study endpoints were technical success assessed at the end of the procedure and device success 30 days after implantation using the Mitral Valve Academic Research Consortium definitions. FINDINGS: Between Sept 1, 2016, and March 31, 2017, 23 patients (median age 75 years [IQR 61-82]) had treatment for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the Edwards PASCAL TMVr system. At baseline, the median EuroScore II score was 7·1% (IQR 3·6-12·8) and the median Society of Thoracic Surgeons predicted risk of mortality for mitral valve repair was 4·8% (2·1-9·0) and 6·8% (2·9-10·1) for mitral valve replacement. 22 (96%) of 23 patients were New York Heart Association (NYHA) class III or IV at baseline. The implantation of at least one device was successful in all patients, resulting in procedural residual mitral regurgitation of grade 2+ or less in 22 (96%) patients. Six (26%) of 23 patients had two implants. Periprocedural complications occurred in two (9%) of 23 patients (one minor bleeding event and one transient ischaemic attack). Despite the anatomical complexity of mitral regurgitation in the patients in this compassionate use cohort, technical success was achieved in 22 (96%) of 23 patients, and device success at 30 days was achieved in 18 (78%) patients. Three patients (13%) died during the 30 day follow-up. 19 (95%) of 20 patients alive 30 days after implantation were NYHA class I or II. INTERPRETATION: This study establishes feasibility of the Edwards PASCAL TMVr system with a high rate of technical success and reduction of mitral regurgitation severity. Further research is needed on procedural and long-term clinical outcomes. FUNDING: None.

Predictors of permanent pacemaker implantation in patients with severe aortic stenosis undergoing TAVR: a meta-analysis.

BACKGROUND: Atrioventricular (AV) conduction disturbances requiring permanent pacemaker (PPM) implantation may complicate transcatheter aortic valve replacement (TAVR). Available evidence on predictors of PPM is sparse and derived from small studies. OBJECTIVES: The objective of this study was to provide summary effect estimates for clinically useful predictors of PPM implantation after TAVR. METHODS: We performed a systematic search for studies that reported the incidence of PPM implantation after TAVR and that provided raw data for the predictors of interest. Data on study, patient, and procedural characteristics were abstracted. Crude risk ratios (RRs) and 95% confidence intervals for each predictor were calculated by use of random effects models. Stratified analyses by type of implanted valve were performed. RESULTS: We obtained data from 41 studies that included 11,210 TAVR patients, of whom 17% required PPM implantation after intervention. The rate of PPM ranged from 2% to 51% in individual studies (with a median of 28% for the Medtronic CoreValve Revalving System [MCRS] and 6% for the Edwards SAPIEN valve [ESV]). The summary estimates indicated increased risk of PPM after TAVR for men (RR: 1.23; p < 0.01); for patients with first-degree AV block (RR: 1.52; p < 0.01), left anterior hemiblock (RR: 1.62; p < 0.01), or right bundle branch block (RR: 2.89; p < 0.01) at baseline; and for patients with intraprocedural AV block (RR: 3.49; p < 0.01). These variables remained significant predictors when only patients treated with the MCRS bioprosthesis were considered. The data for ESV were limited. Unadjusted estimates indicated a 2.5-fold higher risk for PPM implantation for patients who received the MCRS than for those who received the ESV. CONCLUSIONS: Male sex, baseline conduction disturbances, and intraprocedural AV block emerged as predictors of PPM implantation after TAVR. This study provides useful tools to identify high-risk patients and to guide clinical decision making before and after intervention.

Impact of stent overlap on long-term clinical outcomes in patients treated with newer-generation drug-eluting stents.

AIMS: Early-generation drug-eluting stent (DES) overlap (OL) is associated with impaired long-term clinical outcomes whereas the impact of OL with newer-generation DES is unknown. Our aim was to assess the impact of OL on long-term clinical outcomes among patients treated with newer-generation DES. METHODS AND RESULTS: We analysed the three-year clinical outcomes of 3,133 patients included in a prospective DES registry according to stent type (sirolimus-eluting stents [SES; N=1,532] versus everolimus-eluting stents [EES; N=1,601]), and the presence or absence of OL. The primary outcome was a composite of death, myocardial infarction (MI), and target vessel revascularisation (TVR). The primary endpoint was more common in patients with OL (25.1%) than in those with multiple DES without OL (20.8%, adj HR=1.46, 95% CI: 1.03-2.09) and patients with a single DES (18.8%, adj HR=1.74, 95% CI: 1.34-2.25, p<0.001) at three years. A stratified analysis by stent type showed a higher risk of the primary outcome in SES with OL (28.7%) compared to other SES groups (without OL: 22.6%, p=0.04; single DES: 17.6%, p<0.001), but not between EES with OL (22.3%) and other EES groups (without OL: 18.5%, p=0.30; single DES: 20.4%, p=0.20). CONCLUSIONS: DES overlap is associated with impaired clinical outcomes during long-term follow-up. Compared with SES, EES provide similar clinical outcomes irrespective of DES overlap status.

First clinical experience with Celt ACD(®) : a femoral arterial puncture closure device.

INTRODUCTION: This prospective nonrandomized study compared the safety and efficacy of a novel arterial closure device (ACD) in common femoral artery procedures to that of the FDA submitted historical manual pressure control group, who underwent either a diagnostic angiogram (DA) or a percutaneous coronary intervention (PCI) procedure. METHODS AND RESULTS: A total of 55 patients were enrolled in this study of the novel ACD. Of the 55 patients, 39 were enrolled in the DA group and 16 were enrolled in the PCI group. Six patients were excluded. A device was deployed in 49 patients. Time to hemostasis (TTH), time to ambulation (TTA), device function, and device-related vascular complications were measured. In the device group, the TTH for the combined DA and PCI patients was 32 seconds (0.54 ± 0.93 minutes), significantly lower when compared with 16.0 ± 12.2 minutes (P<0.0001) for the control group. Overall major vascular complication rate did not differ significantly, device group (1/49) and the historical control group (1/217). TTA in the combined PCI and DA device group was 226.4 ± 231.9 at the German site (site ambulation policy). In the Irish site, the average TTA in the PCI group was 187 minutes (n=8) and 85 minutes (n=14) in the DA group. CONCLUSION: The Celt ACD® device is safe, effective, and significantly decreases the TTH compared to manual pressure and has a low vascular complications rate. The device may be effective in early ambulation and discharge of patients postcoronary intervention procedures.

Second valve implantation for the treatment of a malpositioned transcatheter aortic valve.

BACKGROUND: Unfavorable immediate or delayed results after transcatheter aortic valve implantation (TAVI) may be a consequence of bioprosthesis malfunctioning, malpositioning, embolization, or degeneration. Deployment of a second valve within the first one implanted (TAVI-in-TAV) may be a potentially helpful therapeutic strategy. METHODS: Six out of 412 patients undergoing TAVI had TAVI-in-TAV implantation for the treatment of a too high (n = 4) or too low position (n = 2) of the first implanted valve. RESULTS: All TAVI-in-TAV procedures were successfully performed. The calculated valve area after second valve implantation was 1.6 ± 0.3 cm(2) with a mean gradient of 7.3 ± 2.2 mm Hg. Residual aortic regurgitation (AR) was mild in 5 patients and moderate in 1. At mid-term follow-up (30-724 days) neither the mean valve area (1.47 ± 0.31 cm(2)), the mean gradient (7.5 ± 3.6 mm Hg; 3.0-13.0 mm Hg) nor the degree of AR had changed significantly. CONCLUSION: TAVI-in-TAV for correction of malpositioned or embolized valves is technically feasible and leads to favorable functional results during mid-term follow-up.

Long-term comparison of everolimus- and sirolimus-eluting stents in patients with acute coronary syndromes.

OBJECTIVES: The goal of this study was to compare the long-term clinical outcome between everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) in patients with acute coronary syndromes (ACS). BACKGROUND: EES have not been directly compared with SES in ACS patients to date. METHODS: Between 2004 and 2009, 1,746 consecutive ACS patients (ST-segment elevation ACS [STE-ACS]: 33.5%; non-ST-segment elevation ACS [NSTE-ACS]: 66.5%) were treated with EES (n=903) or SES (n=843). Using propensity score matching, clinical outcome was compared among 705 matched pairs of ACS patients treated with EES and SES. RESULTS: Through 3 years, the primary endpoint-the composite of death, myocardial infarction (MI), and target vessel revascularization (TVR)-occurred in 13.8% of EES- and 17.7% of SES-treated ACS patients (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.54 to 0.95, p=0.02). The difference in favor of EES was driven by a lower risk of TVR (5.7% vs. 8.8%, HR: 0.65, 95% CI: 0.43 to 0.98, p=0.04) and a trend toward a lower risk of MI (2.1% vs. 3.3%, HR: 0.56, 95% CI: 0.29 to 1.12, p=0.10). The risk of death (7.2% vs. 8.8%, HR: 0.75, 95% CI: 0.50 to 1.10, p=0.14) showed no difference between EES and SES. The treatment effect in favor of EES for the primary endpoint was similar for patients with STE-ACS (16.4% vs. 18.5%, HR: 0.80, 95% CI: 0.50 to 1.27) and NSTE-ACS (12.4% vs. 17.3%; HR: 0.67, 95% CI: 0.47 to 0.96; pfor interaction=0.56) and across major subgroups. Definite (0.4% vs. 1.8%, p=0.03), and definite or probable stent thrombosis (3.4% vs. 6.1%, p=0.02) were less frequent among EES- than SES-treated ACS patients. CONCLUSIONS: Among patients with ACS, the unrestricted use of EES is associated with improved clinical outcome compared with SES during long-term follow-up to 3 years. Notably, the risk of stent thrombosis was lower among EES-treated ACS patients.

Clinical outcome and predictors for adverse events after transcatheter aortic valve implantation with the use of different devices and access routes.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a treatment option for high-risk patients with severe aortic stenosis. Previous reports focused on a single device or access site, whereas little is known of the combined use of different devices and access sites as selected by the heart team. The purpose of this study is to investigate clinical outcomes of TAVI using different devices and access sites. METHODS: A consecutive cohort of 200 patients underwent TAVI with the Medtronic CoreValve Revalving system (Medtronic Core Valve LLC, Irvine, CA; n = 130) or the Edwards SAPIEN valve (Edwards Lifesciences LLC, Irvine, CA; n = 70) implanted by either the transfemoral or transapical access route. RESULTS: Device success and procedure success were 99% and 95%, respectively, without differences between devices and access site. All-cause mortality was 7.5% at 30 days, with no differences between valve types or access sites. Using multivariable analysis, low body mass index (<20 kg/m(2)) (odds ratio [OR] 6.6, 95% CI 1.5-29.5) and previous stroke (OR 4.4, 95% CI 1.2-16.8) were independent risk factors for short-term mortality. The VARC-defined combined safety end point occurred in 18% of patients and was driven by major access site complications (8.0%), life-threatening bleeding (8.5%) or severe renal failure (4.5%). Transapical access emerged as independent predictor of adverse outcome for the Valve Academic Research Consortium-combined safety end point (OR 3.3, 95% CI 1.5-7.1). CONCLUSION: A heart team-based selection of devices and access site among patients undergoing TAVI resulted in high device and procedural success. Low body mass index and history of previous stroke were independent predictors of mortality. Transapical access emerged as a risk factor for the Valve Academic Research Consortium-combined safety end point.

Initial experience with paclitaxel-coated stents.

Local delivery of immunosuppressive or antiproliferative agents using a drug-eluting stent is a new technology that is supposed to inhibit in-stent restenosis, thus providing a biological and mechanical solution. This technique is a very promising. To date, several agents have been used, including paclitaxel, QP-2, rapamycin, actinomycin D, dexamethason, tacrolimus, and everolimus. Several studies, published recently or still ongoing, have evaluated these drugs as to their release kinetics, effective dosage, safety in clinical practice, and benefit. These studies include: SCORE (paclitaxel derivative), TAXUS I-VI, ELUTES, ASPECT, DELIVER (paclitaxel), RAVEL, SIRIUS (sirolimus), ACTION (actinomycin), EVIDENT, PRESENT (tacrolimus), EMPEROR (dexamethason), and FUTURE (everolimus). Paclitaxel was one of the first stent-based antiproliferative agents under clinical investigation that provided profound inhibition of neointimal thickening depending on delivery duration and drug dosage. The randomized, multicenter SCORE trail (Quanam stent, paclitaxel-coated) enrolled 266 patients at 17 sites. At 6-month's follow-up, a drop of 83% in stent restenosis using the drug-eluting stent could be achieved (6.4% drug-eluting stent vs 36.9% control group), which was attributable to a remarkable decrease in intimal proliferation. Unfortunately, due to frequent stent thrombosis and side-branch occlusions, the reported 30-day MACE rate was 10.2%. The randomized TAXUS-I safety trial (BSC, NIRx, paclitaxel-coated) also demonstrated beneficial reduction of restenotic lesions at 6-month's follow-up (0% vs 10%) but was associated with the absence of thrombotic events presumably due to less drug dosage. The ongoing TAXUS II-VI trials are addressing additional insight regarding the efficacy of the TAXUS paclitaxel-eluting stent. ASPECT and ELUTES evaluated paclitaxel-coated stents (i.e., Cook and Supra G), including subgroups with different drug dosages. With respect to stent restenosis and neointimal proliferation, both studies demonstrated a clear dose response. The RAVEL and the SIRIUS trials evaluated sirolimus-coated stents (i.e., Cordis, Johnson & Johnson, and Bx VELOCITY stents). Results confirmed the beneficial findings regarding reduction of renarrowing using a drug-eluting stent without any major adverse effects. Although parameters such as drug toxicity, optimal drug dosage, or delayed endothelial healing still need to be evaluated, today's clinical experience indicates that drug-coated stents are extremely beneficial in the interventional treatment of coronary lesions.

[State of treatment of coronary artery disease by drug releasing stents]. / Aktueller Stand der Therapie der koronaren Herzkrankheit mit medikamentenbeschichteten Stents.

BACKGROUND: Despite improved technologies restenosis remains the main drawback of catheter-based interventions in coronary artery disease. Local application of anti-proliferative drugs through drug releasing stents is a promising concept addressed to solve this problem. DRUG RELEASING STENTS: Today, given the technical capabilities for controlled drug release from coronary stents, the development of drug eluting stents has emerged as one of the main research areas in interventional cardiovascular medicine. Several different approaches for drug loading on coronary stents as well as a variety of antiproliferative and anti-inflammatory agents, such as paclitaxel, actinomycin D, sirolimus, tacrolimus, everolimus and dexamethasone are under clinical investigation. RESULTS: Since the first enthusiastic reports from first in-man observations with drug coated stents, the success of the combination of both a biological and a mechanical approach has been proved in several controlled studies with restenosis rates between 0% in the RAVEL trial (sirolimus, Cordis Bx Velocity trade mark stent), 0% in the TAXUS I trial (paclitaxel, Boston Scientific NIRx trade mark stent) and 4% in the ASPECT Study (paclitaxel, Cook V-Flex plus trade mark stent). The risk of stent thrombosis seems to depend on the dose of the antiproliferative drug - in the SCORE trial stent thrombosis occurred in 6.3% of patients with high dose of QP2 and the antiplatelet therapy, in the ASPECT subgroup with cilostazol instead of clopidogrel and high dose of paclitaxel in up to 25%, whereas in RAVEL and TAXUS I no stent thrombosis was observed. CONCLUSION: If the "one digit" restenosis rate observed in clinical trials could be confirmed in clinical practice without increase of complications, especially stent thrombosis using multiple and/or long stents, we can expect in the near future that implanting drug eluting stents in larger patient groups and lesion subsets will cause a reduction of patients with need for surgical revascularization.