Risk and Mitigation of Coronary Obstruction in Transcatheter Aortic Valve Replacement.

Acute coronary artery occlusion is a rare but devastating complication of transcatheter aortic valve replacement. Coronary obstruction is angiographic evidence of a new-partial or complete-obstruction of a coronary artery. Key factors identifying patients at risk are aortic root anatomy, type of aortic valve, and type of transcatheter heart valve. Techniques to prevent coronary obstruction include intentional leaflet laceration. If acute coronary obstruction does occur, bailout stenting can be challenging and conversion to emergent open heart surgery may be required, both of which are associated with high morbidity and mortality.

Aortic Root Replacement to Accommodate Future Valve-in-Valve Transcatheter Aortic Valve Replacement.

Coronary obstruction is a feared complication associated with valve-in-valve transcatheter aortic valve replacement (TAVR) that may prevent patients with high anatomical risk from being considered. Aortic root replacement at the time of the index TAVR allows higher coronary implantation and augmentation of transcatheter heart valve to coronary ostial distance. This approach permits future valve-in-valve TAVR and may be an important strategy in lifetime valve selection management, particularly in young patients.

Transcatheter aortic valve replacement in patients with anomalous left circumflex coronary artery.

The anomalous left circumflex artery can be a risk for coronary stenosis or obstruction during transcatheter aortic valve replacement; however, the best procedural management has not been clarified. We describe three patients with severe aortic valve stenosis as well as anomalous left circumflex artery. In the first patient, a coronary guidewire with balloon was placed before deploying a SAPIEN 3 transcatheter heart valve, as protection from the coronary occlusion or stenosis. For the second and third patients, no coronary protection was used. All procedures were completed safely and no complications were detected at one-year follow-up.

An alternative solution for patient with high risk of coronary obstruction underwent TAVI procedure using a novel second-generation device - a case series.

BACKGROUND: Obstruction of the left or right coronary artery is a rare but lethal complication during transcatheter aortic valve implantation (TAVI). The new J-Valve™ prosthesis is a new second generation TAVI device which has several features to avoid the coronary obstruction such as low profile design and clip fixation of the native leaflets. The aim of this study is to report our initial experience of using this valve in treating patient with high risk factors for coronary obstruction during TAVI procedure. CASE PRESENTATION: Three high surgical risk patients (All females with 77, 76, and 75 years old) with symptomatic aortic stenosis were enrolled. All patients have the common feature of low coronary ostium height (< 10 mm) with narrowed aortic sinus (< 30 mm) on CT angiogram and marked leaflet calcification. Three 25 mm J-Valve prostheses were successfully implanted through trans-apical approach. No coronary obstruction was noted for these patients. Effective aortic open area was significantly increased after valve implantation (Preoperative 0.7, 0.7 and 0.65 cm2 - Postoperative 1.8, 1.9 and 2.0 cm2). Only one patient was noted to have trivial degree paravalvular leakage. CONCLUSION: The new J-Valve prosthesis is a new second generation TAVI device. This system may provide another safety treatment option for patient with high risk factor for coronary obstruction underwent TAVI procedure.

Preventive left main and right coronary artery stenting to avoid coronary ostia occlusion in high-risk stentless valve-in-valve transcatheter aortic valve implantation.

Transcatheter aortic valve implantation is becoming an attractive and promising alternative to redo surgery for aortic bioprosthetic valves degeneration, especially in high-risk patients. However, valve-in-valve transcatheter aortic valve implantation itself carries some procedural risks and potential challenges that interventionists must be aware of. An accurate preprocedural planning is fundamental for the prevention of potentially fatal complications. This case describes a novel strategy of simultaneous right and left coronary artery stenting preventing bilateral coronary obstruction in a patient with a stentless surgical aortic valve and extremely low origin of the 2 coronary arteries.

Cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury in coronary artery occlusion-induced rats and Langendorff-perfused rat hearts.

BACKGROUND/OBJECTIVES: The current study was designed to investigate the protective role of salisroside on rats through the study of energy metabolism homeostasis and inflammation both in ex vivo and in vivo. METHODS: Energy metabolism homeostasis and inflammation injury were respectively assessed in global ischemia of isolated hearts and coronary artery ligated rats. RESULTS: Excessive release of cardiac enzymes and pro-inflammatory cytokines was inhibited by salidroside in coronary artery occlusion-induced rats. ST segment was also restored with the treatment of salidroside. Triphenyltetrazolium chloride staining (TTC) staining and pathological analysis showed that salidroside could significantly alleviate myocardial injury in vivo. Accumulated data in ex vivo indicated that salidroside improved heart function recovery, which was reflected by enhanced myocardial contractility and coronary flow in isolated hearts. The contents of ATP and glycogen both in ex vivo and in vivo were restored by salidroside compared with those in the model group. Besides, the expressions of p-AMPK, PPAR-α and PGC-1α in rats and isolated hearts subjected to salidroside were significantly elevated, while the levels of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKß were dramatically reduced by salidroside. CONCLUSIONS: The present study comprehensively elaborated the protective effects of salidroside on myocardial injury and demonstrated that AMPK/PGC-1α and AMPK/NF-κB signaling cascades were implicated in the myocardial ischemia-reperfusion injury (I/R) model.

Single Institution Experience With Transcatheter Valve-in-Valve Implantation Emphasizing Strategies for Coronary Protection.

BACKGROUND: Transcatheter valve-in-valve (VIV) implantation evolved as a therapeutic alternative, despite an increased risk of coronary obstruction in comparison with a regular transcatheter aortic valve implantation (TAVI). We report a comprehensive single-institution experience emphasizing strategies to reduce the risk of myocardial ischemia. METHODS: Since 2009, 639 patients underwent a TAVI procedure in our institution. All patients are prospectively collected into an institutional registry. In total 31 patients underwent a VIV procedure at our institution (age 77.8 ± 6.3 years; The Society or Thoracic Surgeons predicted risk of mortality 20.9% ± 8.8%; New York Heart Association (NYHA) 3.0 ± 0.6). Degenerated bioprostheses included 24 Mitroflow, 6 Edwards Perimount, and Cryo-Valve O' Brien with label sizes from 21 to 27 mm. The type of failure was mostly regurgitation with or without concomitant stenosis (78%). RESULTS: Patients were provided with 5 Medtronic CoreValves, 15 Edwards SapienXT, 1 Edwards Sapien 3, 7 Medtronic Engager, and 3 Symetis Acurate TA valves. The procedural success rate was 88%. The left main stem was occluded in 1 patient (Sapien XT 26 in a Mitroflow 25 mm) who underwent emergent revascularization. Two patients suffering from a degenerated Mitroflow prosthesis needed a second valve (Sapien XT). Two patients with a degenerated Mitroflow prosthesis treated with a Sapien XT developed postprocedural myocardial ischemia and deceased on postoperative days 1 and 2, accounting to an overall incidence of coronary insufficiency associated to the VIV procedure of 10%. With the introduction of valves allowing commissural alignment (Acurate TA) and leaflet capturing as well (Engager) no further coronary insufficiency occurred. The mean gradient decreased significantly from 39.3 ± 14.0 to 16.1 ± 7.2 mm Hg (p = 0.002). Post-procedural regurgitation was classified as trace in 7 patients (23%) and moderate in 4 patients (13%). The 30-day survival was 77% with a significantly improved NYHA class of 1.79 ± 0.58 (p = 0.001). CONCLUSIONS: Jeopardizing coronary blood flow is likely in stenotic and calcified bioprostheses, particularly in tubelike aortic sinuses. Planning, imaging, and the use of valves allowing commissural alignment as well as leaflet capturing seem to reduce the risk. Further studies are necessary to support this hypothesis.

[Transcatheter aortic valve replacement].

While transcatheter aortic valve replacement( TAVR) has spread rapidly all over the world for highrisk patients with severe aortic stenosis (AS), SAPIEN XT was approved in Japan in October 2013. Since that, approximately 400 TAVR cases were performed in Japan. In our institute, we have performed 164 cases since first case in Japan in 2009 and have achieved satisfactory early results(30-day mortality:1.2%). At the same time, however, simultaneously various TAVR-related complications including a paravalvular leak, stroke, vascular complications, and coronary obstruction were observed. A reduction in the incidence and severity of these complications had led technical improvements in various new devices(2nd generation TAVR device such as the SAPIEN 3, ACURATE, and JenaValve) and in implantation techniques including repositioning/recapturing features, paravalvular sealing technologies, and prevention of coronary obstruction. Furthermore, there is also increasing experience with special indications for TAVR such as pure aortic valve insufficiency or valve-in-valve techniques. Currently, an increasing number of publications of midterm results demonstrate good prosthetic valve function and durability, with good quality of life and low morbidity after TAVR. There are also some randomized trials such as PARTNER 2 or SURTAVI to investigate potential benefits of TAVR for intermediate-risk patients. These improvements in the TAVR devices promises the expansion of TAVR towards the treatment of lower-risk patients in the near future.

The thromboprotective effect of bortezomib is dependent on the transcription factor Kruppel-like factor 2 (KLF2).

Multiple myeloma confers a high risk for vascular thrombosis, a risk that is increased by treatment with immunomodulatory agents. Strikingly, inclusion of the proteasome inhibitor bortezomib reduces thrombotic risk, yet the molecular basis for this observation remains unknown. Here, we show that bortezomib prolongs thrombosis times in the carotid artery photochemical injury assay in normal mice. Cell-based studies show that bortezomib increases expression of the transcription factor Kruppel-like factor 2 (KLF2) in multiple cell types. Global postnatal overexpression of KLF2 (GL-K2-TG) increased time to thrombosis, and global postnatal deletion of KLF2 (GL-K2-KO) conferred an antiparallel effect. Finally, studies in GL-K2-KO mice showed that the thromboprotective effect of bortezomib is KLF2 dependent. These findings identify a transcriptional basis for the antithrombotic effects of bortezomib.

A new drug delivery system for intravenous coronary thrombolysis with thrombus targeting and stealth activity recoverable by ultrasound.

OBJECTIVES: The purpose of this study was to develop a new intelligent drug delivery system for intracoronary thrombolysis with a strong thrombolytic effect without increasing bleeding risk. BACKGROUND: Rapid recanalization of an occluded coronary artery is essential for better outcomes in acute myocardial infarction. Catheter-based recanalization is widely accepted, but it takes time to transport patients. Although the current fibrinolytic therapy can be started quickly, it cannot achieve a high reperfusion rate. Recently, we generated nanoparticles comprising tissue-type plasminogen activator (tPA), basic gelatin, and zinc ions, which suppress tPA activity by 50% with 100% recovery by ultrasound (US) in vitro. METHODS: The thrombus-targeting property of nanoparticles was examined by an in vitro binding assay with von Wilbrand factor and with a mouse arterial thrombosis model in vivo. The thrombolytic efficacy of nanoparticles was evaluated with a swine acute myocardial infarction model. RESULTS: Nanoparticles bound to von Wilbrand factor in vitro and preferentially accumulated at the site of thrombus in a mouse model. In a swine acute myocardial infarction model, plasma tPA activity after intravenous injection of nanoparticles was approximately 25% of tPA alone and was recovered completely by transthoracic US (1.0 MHz, 1.0 W/cm(2)). During US application, plasma tPA activity near the affected coronary artery was recovered and was higher than that near the femoral artery. Although treatment with tPA alone (55,000 IU/kg) recanalized the occluded coronary artery in only 1 of 10 swine, nanoparticles containing the same dose of tPA with US achieved recanalization in 9 of 10 swine within 30 min. CONCLUSIONS: We developed an intelligent drug delivery system with promising potential for better intravenous coronary thrombolysis.

Transcatheter aortic valve implantation for the treatment of surgical valve dysfunction ("valve-in-valve"): assessing the risk of coronary obstruction.

Acute coronary obstruction is one of the most feared complications associated with transcatheter aortic valve-in-valve implantation. Strategies for assessing the risk of coronary occlusion during these procedures as well as preventive measures are discussed.

Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of Coronary arteRY bypaSS occlusion After off-pump procedures) randomised study.

OBJECTIVE: To determine the individual variability in the response to aspirin and/or clopidogrel and its impact on graft patency after off-pump coronary artery bypass grafting. DESIGN: A single-centre prospective randomised controlled study designed according to the Consolidated Standards of Reporting Trials statement. Randomisation was obtained by a computer-generated algorithm. SETTING: University medical school in Italy. PATIENTS: 300 patients who underwent off-pump coronary artery bypass grafting were randomised to receive aspirin (n=150) or aspirin plus clopidogrel (n=150). INTERVENTION: Aspirin 100 mg or aspirin 100 mg plus clopidogrel 75 mg daily was initiated when postoperative chest tube drainage was ≤ 50 ml/h for 2 h and patients were followed up for 12 months. MAIN OUTCOME MEASURES: Qualitative and quantitative assessment of platelet function, angiographic evaluation of coronary revascularisation by 64-slice CT and clinical outcome. RESULTS: In the aspirin group, 49 patients (32.6%) were aspirin resistant and, in the aspirin-clopidogrel group, 19 patients (12.6%) were aspirin and clopidogrel resistant. The platelet response to aspirin was similar in all aspirin responders despite the study arm (Aspirin Reaction Units 313.2 ± 44.8 vs 323.6 ± 53.6; p=0.07). The platelet response to clopidogrel was enhanced by aspirin in patients responsive to both aspirin and clopidogrel (synergistic effect) compared with responders to clopidogrel only (P2Y12 Reaction Units 139.9 ± 15.5 vs 179.4 ± 18.5; p<0.001). Combined therapy was associated with a reduced vein graft occlusion rate (7.4% vs 13.1%; p=0.04). Antiplatelet resistance was a predictor of graft occlusion (RR 3.6, 95% CI 2.5 to 6.9; p<0.001). Synergistic aspirin and clopidogrel activity was a strong predictor of vein graft patency (RR 5.1, 95% CI 1.4 to 16.3; p<0.01). CONCLUSIONS: Combined clopidogrel and aspirin overcome single drug resistances, are safe for bleeding and improve venous graft patency.