The effect of sex on the efficacy and safety of dual antithrombotic therapy with dabigatran versus triple therapy with warfarin after PCI in patients with atrial fibrillation (a RE-DUAL PCI subgroup analysis and comparison to other dual antithrombotic therapy trials).

BACKGROUND: The RE-DUAL PCI trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), dual therapy with dabigatran and a P2Y12 inhibitor, either clopidogrel or ticagrelor, reduced the risk of bleeding without an increased risk of thromboembolic events as compared to triple therapy with warfarin in addition to a P2Y12 inhibitor and aspirin. What remains unclear is whether this effect is consistent between males and females undergoing PCI. HYPOTHESIS: The reduction in risk of bleeding without increased risk of thromboembolic events with dual therapy with dabigatran and a P2Y12 inhibitor in comparison to triple therapy with warfarin, a P2Y12 inhibitor and aspirin is consistent in females and males. METHODS: The primary safety endpoint was the first International Society on Thrombosis and Hemostasis (ISTH) major bleeding event (MBE) or clinically relevant non-major bleeding event (CRNMBE). The efficacy endpoint was the composite of death, thromboembolic event (stroke, myocardial infarction, and systemic embolism) or unplanned revascularization. Cox proportional hazard regression analyses were applied to calculate corresponding hazard ratios and interaction p values for each endpoint. RESULTS: A total of 655 women and 2070 men were enrolled. The risk of major or CRNM bleeding was lower with both dabigatran 110 mg dual therapy and dabigatran 150 mg dual therapy compared with warfarin triple therapy in female and male patients (for 110 mg: females: HR 0.69, 95% CI 0.47-1.01, males: HR 0.46, 95% CI 0.37-0.59, interaction p value: 0.084 and for 150 mg: females HR 0.74, 95% CI 0.48-1.16, males HR 0.71, 95% CI 0.56-0.90, interaction p value: 0.83). There was also no detectable difference in the composite efficacy endpoint of death, thromboembolic events or unplanned revascularization between dabigatran dual therapy and warfarin triple therapy, with no statistically significant interaction between sex and treatment (interaction p values: 0.73 and 0.72, respectively). CONCLUSIONS: Consistent with the overall study results, the risk of bleeding was lower with dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy, and risk of thromboembolic events was comparable with warfarin triple therapy independent of the patient's sex.

Late catch-up in lumen diameter at five-year angiography in MACE-free patients treated with sirolimus-eluting stents in the Primary Stenting of Totally Occluded Native Coronary Arteries: a randomised comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (PRISON II).

AIMS: The present study was designed to examine the five-year angiographic follow-up of MACE-free patients enrolled in the PRISON II study. METHODS AND RESULTS: In the PRISON II study a total of 200 patients were randomised to either bare metal stents (BMS) or sirolimus-eluting stents (SES) after successful recanalisation of total coronary occlusions (TCO). Patients free of MACE with available angiography at six months were approached for repeated angiography at five years. The primary endpoint was in-stent very late luminal loss (VLLL) at five years. The secondary endpoint was additional late luminal loss (ALLL) between six months and five years. At five years, repeated angiography was performed in 72 patients, 50/82 (61%) in the SES group and 22/58 (38%) in the BMS group. In-stent VLLL was lower in the SES group (0.19 mm ± 0.72 vs. 0.51 mm ± 0.71, p=0.09) compared to the BMS group and in-segment VLLL was comparable in both groups (0.01 mm±0.58 vs. 0.03 mm ± 0.73, p=0.89). Late catch-up in lumen diameter was observed in the SES group with a trend towards increased ALLL compared to the BMS group (in-stent, 0.35 mm ± 0.88 vs. 0.04 mm ± 0.81, p=0.16; in-segment, 0.20 mm ± 0.74 vs. -0.05 mm ± 0.73, p=0.19). CONCLUSIONS: At five-year angiographic follow-up, late catch-up was observed after successful recanalisation of TCOs treated with SES. Despite a late catch-up, the angiographic results of SES were superior in-stent and similar in-segment compared to BMS.

With the back against the wall: TAVI in a patient with endocarditis.

Transcatheter Aortic Valve Implantation (TAVI) is currently a well-established therapeutic option in patients with severe aortic stenosis considered at prohibitive risk for open heart aortic valve replacement (Cribier et al., Circulation 2002;106:3006-3008; Leon et al., Semin Thorac Cardiovasc Surg 2006;18:165-174). We report a case of a patient with endocarditis by severe homograft aortic stenosis for which a TAVI procedure was performed with an excellent result. The patient was undergoing a presurgery standard screening in preparation for a planned aortic valve replacement operation when he developed a Staphyloccocus aureus sepsis. Transoesophageal echocardiography demonstrated an aortic valve vegetation. A few days later, the patient developed a stroke probably due to embolization of a vegetation. Given the clinical severity of the case a standard open heart aortic valve replacement was considered too risky and the patient underwent a TAVI procedure. Postintervention the patient had a spectacular evolution with fast normalization of the septic shock parameters and clinical status. Antibiotics were continued for a total of nine weeks. By the ambulatory controls at three weeks, two months and six months postdischarge, the patient was completely asymptomatic and his echocardiography showed a normally functioning aortic valve without indications of endocarditis.

Incidence and predictors of coronary stent thrombosis: evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses.

BACKGROUND: Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis. METHODS: PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥ 2000 patients undergoing stenting or reporting on ≥ 25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised. RESULTS: A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22 months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently. CONCLUSIONS: Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.

Five-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomised comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (PRISON II study).

AIMS: The aim of this study was to examine the five-year clinical outcome in patients enrolled in the Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II) study. METHODS AND RESULTS: Patients with totally occluded coronary arteries were randomised to either sirolimus-eluting stent (SES, n=100) or bare metal stent (BMS, n=100) implantation. At five years, patients in the SES group had significantly lower rates of target lesion revascularisation (12% vs. 30%, p=0.001), target vessel revascularisation (17% vs. 34%, p=0.009) and major adverse cardiac events (12% vs. 36%, p<0.001). There were no significant differences in death and myocardial infarction. Eight (8%) cases of stent thrombosis (seven definite and one probable; one early, one late, and six very late) were noticed in the SES group versus three cases (3%, one definite and two possible; all very late) in the BMS group (p=0.21). CONCLUSIONS: The results of the present study show that the documented superior short-term angiographic and clinical results of SES in patients with total coronary occlusions are maintained during long-term 5-year follow-up as compared with BMS. On the other hand, there is a trend to a higher stent thrombosis rate in the SES group.

Transapical treatment of paravalvular leaks in patients with a logistic EuroSCORE of more than 15%: acute and 3-month outcomes of a "proof of concept" study.

OBJECTIVE: We describe the short-term results of the patients who underwent transapical treatment of a paravalvular leak (PVL) in our centre. BACKGROUND: Increasing experience with transapical aortic valve implantation has inspired us to explore this approach for prosthetic paravalvular leak reduction in high risk patients. METHODS: All procedures were performed in the catheterization laboratory under general anesthesia, using a small anterolateral thoracotomy to expose the apex. Access through a 9-French sheath was necessary to introduce the Amplatzer Vascular III plug. Three-dimensional transesophageal echocardiography (3D-TEE) was used to guide the operator and evaluate the severity of regurgitation postimplantation. RESULTS: In total seven consecutive patients (mean age 72.8 ± 5.6 years, 86% male) with a history of mitral valve (n = 6) or aortic valve replacement and severe PVL, underwent transapical PVL reduction using seven plugs in total (diameter 10-14 mm). Preprocedural median logistic EuroSCORE was 28.5% (range 17.1-41.1%) and NYHA functional class was ≥3 in all patients. The procedure was successful in all patients, with a median fluoroscopic time of 18.7 min (range 10.1-29.6 min). Postprocedure 3D-TEE showed occlusion of PVL in three patients, and significant reduction in three patients. Postprocedural complication was a hematothorax requiring surgery in one patient. Median hospitalization duration after the procedure was 5 days (range 5-59 days). At 3-month follow-up one patient died, functional class and LDH did not differ significantly and there was a significant increase in hemoglobin. CONCLUSIONS: Transapical paravalvular leak reduction might be a good or rather attractive alternative in high-risk patients for major re-do cardiac surgery.

Transapical repair of mitral valve paravalvular leakage using 3-D transesophageal guidance.

We report a case where transapical access with real time 3D transesophageal echocardiographic guidance is used for repair of a mitral valve paravalvular leakage. The transapical approach is a new, elegant, and relative safe alternative for repair of a paravalvular defect in high-risk patients. The use of real time 3DTEE for guiding the procedure provides the operator fast and complete information about the leakage, and allowing online monitoring of the procedure.

Three-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomized comparison of bare-metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (Primary Stenting of Totally Occluded Native Coronary Arteries [PRISON] II study).

BACKGROUND: The purpose of this study was to examine the 3-year clinical outcome in patients enrolled in the Primary Stenting of Totally Occluded Native Coronary Arteries II study. METHODS: Patients with totally occluded coronary arteries randomized to either sirolimus-eluting Cypher stents (SESs) (Cordis, a Johnson & Joshson Company, Miami Lakes, FL) (100 patients) or bare-metal BxVelocity stents (BMSs) (Cordis) (100 patients) were followed clinically for 3 years. RESULTS: Between 1 and 3 years, there were infrequent additional clinical events that were equally distributed between the SES and the BMS group. After 3 years, target lesion revascularization was 7% in the SES group versus 27% in the BMS group (P < .001); and target vessel revascularization was seen in 11% in the SES group versus 30% in the BMS group (P = .002). Major adverse cardiac events were noted in 10% of the SES group versus 34% in the BMS group (P < .001). There were no statistically significant differences in death, myocardial infarction, and stent thrombosis according to the Academic Research Consortium criteria between the 2 groups. CONCLUSIONS: Clinical outcome up to 3 years after implantation of SESs for total coronary occlusions continues to demonstrate a significant reduction in adverse clinical events compared with BMSs without the evidence for either disproportionate late restenosis or late stent thrombosis.