Fate and long-term prognostic implications of mitral regurgitation in patients undergoing transcatheter aortic valve replacement

Background: The management of patients with mitral regurgitation (MR) undergoing transcatheter aortic valve replacement (TAVR) is challenging. We sought to investigate the evolution and long-term prognostic impact of residual post-TAVR MR. Methods: The severity of MR was assessed at baseline and at 30 days and six months post-TAVR. Left ventricular mass and volumes were assessed by magnetic resonance imaging at two weeks and six months post-TAVR. Results: The study included 970 patients (age, 80.6 ± 6.2 years; female, 53.2%; Society of Thoracic Surgeons score, 5.2 ± 4.6). Moderate-severe MR at baseline improved at 30-day post-TAVR in 60% of cases, and TAVR with the Medtronic CoreValve (OR: 0.44 [0.23–0.86]) was associated with a lower likelihood of improvement. Further MR improvement continued beyond 30 days post-TAVR especially in patients with a significant improvement of left ventricular volume and mass. Stratified by the severity of MR at 30 days post-TAVR, the 5-year cumulative incidence of the composite of cardiovascular mortality or heart failure hospitalization was 37.5%, 40.0%, and 58.2% in patients with none-mild, moderate, and severe MR, respectively (log rank p < .001; adjusted hazard ratio of severe vs. none-mild MR: 4.83 [2.49–9.38]. Conclusions: MR improves in a majority of patients early after TAVR, and its evolution continues thereafter in line with reverse cardiac remodeling. Residual post-TAVR severe MR is associated with adverse long-term outcome. Therefore, intervention to treat severe MR persisting after TAVR should be considered by the heart team

Human recombinant activated protein C-coated stent for the prevention of restenosis in porcine coronary arteries

Activated protein C (APC), an endogenous protein, inhibits inflammation and thrombosis and interrupts the coagulation cascade. Here, we investigated the effect of human recombinant APC on the development of neointimal hyperplasia in porcine coronary arteries. Yukon Choice bare metal stents were coated with 2.6 mu g APC/mm(2). Under general anesthesia, APC-coated and bare stents were implanted in the left anterior descending and circumflex coronary arteries of 10 domestic pigs. During the 4-week follow-up, animals were treated with dual antiplatelet therapy and neointimal hyperplasia was evaluated via histology. Scanning electron microscopy indicated successful but unequal coating of stents with APC; nearly complete drug release occurred within 4 h. Enzyme-linked immunosorbent assay revealed that intracoronary stent implantation rapidly increased the levels of monocyte chemoattractant protein-1, an effect that was inhibited by APC release from the coated stent. Fibrin deposition and adventitial inflammation were significantly decreased 1 month after implanting APC-coated stents versus bare stents, paralleled by significantly smaller neointimal area (0.98 +/- 0.92 vs. 1.44 +/- 0.91 mm(2), P = 0.028), higher lumen area (3.47 +/- 0.94 vs. 3.06 +/- 0.91 mm(2), P = 0.046), and lower stenosis area (22.2 +/- 21.2 % vs. 32.1 +/- 20.1 %, P = 0.034). Endothelialization was complete with APC-coated but not bare (90 %) stents. P-selectin immunostaining revealed significantly fewer activated endothelial cells in the neointima in the APC group (4.6 +/- 1.9 vs. 11.6 +/- 4.1 %, P < 0.001). Thus, short exposure of coronary arteries to APC reduced inflammatory responses, neointimal proliferation, and in-stent restenosis, offering a promising therapy to improve clinical outcomes of coronary stenting. However, coating stents with APC for prolonged, controlled drug release remains technically challenging

Reduced histologic neo in-stent restenosis after use of a paclitaxel-coated cutting balloon in porcine coronary arteries

The incidence of in-stent restenosis (ISR) has declined dramatically, but once it develops, no current treatment option, such as drug-eluting stents, drug-coated balloons, or cutting balloons (CBs), prevents re-narrowing of the stented atherosclerotic artery. In this preclinical study, we aimed to improve the efficacy of ISR treatment by coating CBs with paclitaxel (paclitaxel-eluting cutting balloon; PECB) and to characterize the histological features of neo-ISRs that arise after ISR treatment. ISR was induced by bare metal stent (BMS) implantation in coronary arteries in pigs. After one month of follow-up, BMS-induced ISR was treated with either CB or PECB. After another month, we performed quantitative coronary angiography, explanted the treated arteries and assessed histopathological and histomorphometric parameters. In addition, we compared histological features of neo-ISRs with pre-treatment ISRs. Injury, inflammation, fibrin deposition, and endothelialization scores were similar between the CB and PECB groups at one month after ISR treatment. Neointimal area (0.87±0.61 vs. 1.95±1.14 mm 2, p=0.02), mean neointimal thickness (0.40±0.39 vs. 0.99±0.56 mm, p=0.01), and percent area stenosis (27.3±20.4 vs. 48.3±22.9%, p=0.04) were decreased in PECB-treated coronary arteries compared to CB-treated arteries, respectively. Density of cells (predominantly smooth muscle cells; SMCs) was increased in neo-ISRs (3.51±3.05×10 3 vs. 6.35±2.57×10 3 cells/mm 2 , p<0.01),but significantly more CD68 + and CD20 + cells were found in pre-treatment ISRs. In conclusion, PECB treatment of ISRs led to better results in terms of smaller neointimal area and %area stenosis of neo-ISR. SMC density was increased in neo-ISRs in contrast with higher percentage of CD68 + and CD20 + cells in pre- treatment ISRs

Impact of prosthesis-iteration evolution and sizing practice on the incidence of prosthesis–patient mismatch after transcatheter aortic valve replacement

Objectives: To investigate the impact of the introduction of the next generation self-expanding (SE) and balloon-expandable (BE) transcatheter heart valves (THVs) on the incidence of prosthesis–patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR). Background: PPM is a risk factor for accelerated degeneration of bioprosthetic aortic valves. Data on PPM after TAVR are derived mainly from studies of older generation THVs. Methods: PPM was assessed at 30 days post-TAVR with the older generation (Medtronic CoreValve, n = 120 and Edwards Sapien XT, n = 121) and the next generation THVs (Medtronic Evolut R/Pro, n = 136 and Edwards Sapien 3, n = 363). Results: The incidence of any and severe PPM was 15.1% and 0.0% for the older generation THVs, and 42.8% and 12.1% for the next generation THVs. The incidence of moderate and severe PPM was 23.3% and 3.5% in patients who received an Evolut R/Pro vs. 33.1% and 14.7% in those who received a Sapien 3 (P < 0.001). On multivariable analysis, TAVR with the Sapien 3 THV was not associated with PPM, while left ventricular ejection fraction (0.97 [0.95–0.99], P = 0.002), history of myocardial infarction (2.09 [1.00–4.34], P = 0.049), annulus maximum diameter (0.84 [0.77–0.92], P < 0.001), and THV oversizing (0.90 [0.87–0.94], P < 0.001) were independently associated with PPM. In Sapien 3, the risk of any and severe PPM was higher in those with no oversizing (odds ratio: 3.25 [1.23–8.53], P = 0.017 and 5.79[2.33–14.36], P < 0.001). Conclusions: The incidence of PPM in contemporary TAVR is significant, especially with the next generation BE THV without adequate oversizing

Impact of Lesion Preparation Technique on Side Branch Compromise in Calcified Coronary Bifurcations: A Subgroup Analysis of the PREPARE-CALC Trial

Objectives. To analyze the impact of different techniques of lesion preparation of severely calcified coronary bifurcation lesions. Background. The impact of different techniques of lesion preparation of severely calcified coronary bifurcation lesions is poorly investigated. Methods. We performed an as-treated analysis on 47 calcified bifurcation lesions treated with scoring/cutting balloons (SCB) and 68 lesions treated with rotational atherectomy (RA) in the PREPARE-CALC trial. Compromised side branch (SB) as assessed in the final angiogram was the primary outcome measure and was defined as any significant stenosis, dissection, or thrombolysis in myocardial infarction flow <3. Results. True bifurcation lesions were present in 49% vs. 43% of cases in the SCB and RA groups, respectively. After stent implantation, SB balloon dilatation was necessary in around one-third of cases (36% vs. 38%; p=0.82), and a two-stent technique was performed in 21.3% vs. 25% (p=0.75). At the end of the procedure, the SB remained compromised in 15 lesions (32%) in the SCB group and 5 lesions (7%) in the RA group (p=0.001). Large coronary dissections were more frequently observed in the SCB group (13% vs. 2%; p=0.02). Postprocedural levels of cardiac biomarkers were significantly higher in patients with a compromised SB at the end of the procedure. Conclusions. In the PREPARE-CALC trial, side branch compromise was more frequently observed after lesion preparation with SCB as compared with RA. Consequently, in calcified bifurcation lesions, an upfront debulking with an RA-based strategy might optimize the result in the side branch

Patients with higher-atherothrombotic risk vs. lower-atherothrombotic risk undergoing coronary intervention with newer-generation drug-eluting stents: an analysis from the randomized BIOFLOW trials.

BACKGROUND Patients with atherothrombotic risk are at high hazard of ischemic events. Preventive medicine plays a major role in modifying their outcomes. Whether the choice of a BP-SES or DP-EES can contribute to the occurrence of events remains unclear. We sought to investigate the outcomes of patients with higher atherothrombotic risk (H-ATR) versus lower atherothrombotic risk (L-ATR) undergoing percutaneous coronary intervention (PCI) with either bioresorbable-polymer sirolimus-eluting stent (BP-SES) or durable-polymer everolimus-eluting stent (DP-EES). METHODS Patients (n = 2361) from BIOFLOW-II, -IV, and -V randomized trials were categorized into H-ATR vs. L-ATR. L-ATR patients had ≤ 1 and H-ATR ≥ 2 of the following criteria: presentation in ACS, diabetes mellitus, previous myocardial infarction, previous PCI/CABG, or previous stroke. Endpoints were target lesion failure (TLF: cardiac death, target-vessel myocardial infarction [TV-MI], target lesion revascularization [TLR]) and stent thrombosis (ST) at three years. RESULTS H-ATR patients (n = 1023) were more morbid than L-ATR patients (n = 1338). TLF rate was significantly higher in H-ATR patients as compared with L-ATR (11.6% vs. 7.0%; HR 1.67, 95% CI 1.27-2.20, p < 0.0001). With BP-SES TLF rates were numerically lower as compared with DP-EES in H-ATR (10.5% vs. 13.5%; HR 0.78, 95% CI 0.54-1.14, p = 0.20) and significantly lower in L-ATR (5.6% vs. 9.8%; HR 0.57, 95% CI 0.38-0.85, p = 0.006). CONCLUSION In the era of newer-generation DES, patients with H-ATR still are at hazard for ischemic events. Patients with BP-SES had lower TLF rates as compared with DP-EES, most consistent in L-ATR whereas in H-ATR patients most probably secondary preventive strategies are of higher value. CLINICAL TRIAL REGISTRATION Clinicaltrial.gov. NCT01356888, NCT01939249, NCT02389946. https://clinicaltrials.gov/show/NCT01356888 , https://clinicaltrials.gov/show/NCT01939249 , https://clinicaltrials.gov/show/NCT02389946