Impact of preventive substrate catheter ablation on implantable cardioverter-defibrillator interventions in patients with ischaemic cardiomyopathy and infarct-related coronary chronic total occlusion.

AIMS: Primary prevention patients with ischaemic cardiomyopathy and chronic total occlusion of an infarct-related coronary artery (CTO) are at a particularly high risk of implantable cardioverter-defibrillator (ICD) therapy occurrence. The trial was designed to evaluate the efficacy of preventive CTO-related substrate ablation strategy in ischaemic cardiomyopathy patients undergoing primary prevention ICD implantation. METHODS AND RESULTS: The PREVENTIVE VT study was a prospective, multicentre, randomized trial including ischaemic patients with ejection fraction ≤40%, no documented ventricular arrhythmias (VAs), and evidence of scar related to the coronary CTO. Patients were randomly assigned 1:1 to a preventive substrate ablation before ICD implantation or standard therapy with ICD implantation only. The primary outcome was a composite of appropriate ICD therapy or unplanned hospitalization for VAs. Secondary outcomes included the primary outcome's components, the incidence of appropriate ICD therapies, cardiac hospitalization, electrical storm, and cardiovascular (CV) mortality. Sixty patients were included in the study. During the mean follow-up of 44.7 ± 20.7 months, the primary outcome occurred in 5 (16.7%) patients undergoing preventive substrate ablation and in 13 (43.3%) patients receiving only ICD [hazard ratio (HR): 0.33; 95% confidence interval (CI): 0.12-0.94; P = 0.037]. Patients in the preventive ablation group also had fewer appropriate ICD therapies (P = 0.039) and the electrical storms (Log-rank: P = 0.01). While preventive ablation also reduced cardiac hospitalizations (P = 0.006), it had no significant impact on CV mortality (P = 0.151). CONCLUSION: Preventive ablation of the coronary CTO-related substrate in patients undergoing primary ICD implantation is associated with the reduced risk of appropriate ICD therapy or unplanned hospitalization due to VAs.

A novel use of small ballons to reduce the risk of subintimal hematoma formation during recanalization of chronic total occlusion: two case reports.

BACKGROUND: Subintimal hematoma remains a major challenge associated with unnecessary technical complexity, failure of the antegrade approach or imperfection of revascularization in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Some techniques and devices release the hematoma after its formation. Here, we describe a novel use of small ballons to prevent the hematoma formation during antegrade approach in two cases. CASE PRESENTATION: We report two cases of CTO-PCI in which balloon occlusion was successfully applied to prevent haematoma formation. The first case, a 72-year-old female with diabetes, was hospitalized because of unstable angina. Angiography showed right coronary artery (RCA) CTO, which initiated from the proximal part to the trifurcation at the distal part of the RCA. Considering the high likelihood and serious consequences of subintimal haematoma, a small balloon is employed to prevent subintimal hematoma formation. A balloon and microcatheter or double-lumen microcatheter are placed in the proximal coronary CTO lesion; then the balloon was dilated beside the catheter, most of the antegrade blood flow was sealed which reduced the likelihood of haematoma formation. The procedure was successfully completed without subintimal hematoma formation. The second case a 62-year-old male with unstable angina, was hospitalized for PCI. Angiography showed left anterior descending coronary artery CTO. Similar to case 1, we also used a small balloon to prevent hematoma formation. Both patients underwent PCI, which employed a small balloon to prevent hematoma formation and both procedures were successful without complications. CONCLUSION: In patients who underwent CTO-PCI, balloon occlusion offers an alternative for reducing the incidence of subintimal haematomas.

Perfusion Balloon Is Useful for Preventing Obstruction of Left Main Coronary Artery During Transcatheter Aortic Valve Implantation.

The incidence of acute coronary obstruction during transcatheter aortic valve implantation (TAVI) is low (< 1.0%); however, it is associated with high mortality. An 83-year-old female with a history of chest pain and syncope was diagnosed with severe aortic stenosis. Computed tomography showed severely calcified aortic leaflets with a low left coronary ostial height of 7.8 mm, which indicates a high risk of coronary obstruction. TAVI was performed using the right femoral artery approach under general anesthesia. To prevent coronary obstruction and minimize coronary flow obstruction, coronary protection of the left main tract (LMT) via the left radial artery was established with a perfusion balloon. We crossed a 23 mm Sapien 3 transcatheter heart valve and settled it at an appropriate position on the aortic valve. After inflation of the perfusion balloon at the LMT, we started rapid ventricular pacing, and deployed the Sapien 3 using the KBI technique. Hemodynamics were stable and aortography showed excellent coronary flow with no stenosis of the LMT ostium. This strategy may serve as a useful method to prevent coronary obstruction and minimize coronary ischemia.

Active Versus Conventional Side Branch Protection Strategy for Coronary Bifurcation Lesions.

The side branch (SB) provisional stenting strategy is currently the recommended approach for most coronary bifurcation lesions. However, this strategy may result in SB deterioration, which is associated with an increased incidence of periprocedural myocardial infarction (PMI) and may adversely affect the long-term prognosis. Various techniques for SB protection (SB-P) have been developed to reduce SB occlusion and improve the clinical prognosis. This meta-analysis was performed to compare the outcomes of an active SB-P strategy of jailed balloon technique, balloon-stent kissing technique, and jailed Corsair technique versus the conventional SB-P strategy based on jailed wire technique.This meta-analysis included 5 studies (4 randomized and 1 observational) involving a total of 1,174 patients in whom the active and conventional SB-P strategies were compared. Fixed- and random-effects models were used to calculate summary risk ratios (RRs).The risk of SB occlusion was significantly lower in active SB-P strategy [RR 0.47, 95% confidence interval (CI) 0.30-0.73 in fixed-effect model; RR 0.52, 95% CI 0.31-0.87 in random-effect model]. The risk of PMI was similar between the two strategies (RR 0.63, 95% CI 0.30-1.33 in fixed-effect model; RR 0.71, 95%CI 0.20-2.48 in random-effect model). The rate of long-term major adverse cardiovascular events was similar between the groups (RR 0.48, 95% CI 0.15-1.48 in fixed-effect model; RR 0.49, 95% CI 0.16-1.52 in random-effect model).The active SB-P strategy in coronary bifurcation lesions is associated with reduced SB deterioration, but it does not decrease PMI or improve the long-term prognosis.

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.

The Prophylactic Chimney Snorkel Technique for the Prevention of Acute Coronary Occlusion in High Risk for Coronary Obstruction Transcatheter Aortic Valve Replacement/Implantation Cases.

Coronary occlusion (immediate or delayed) is an uncommon but potentially devastating complication of transcatheter aortic valve replacement/implantation (TAVR/TAVI). Several patient-related, anatomical, device and procedural risk factors can be assessed to risk-stratify patients and assist in procedural planning. In patients at high risk for coronary occlusion, coronary protection measures should be employed. In the highest risk patients, consideration should be given to prophylactic techniques to prevent coronary occlusion. This how-to-do-it report provides a framework for risk assessment for coronary occlusion followed by a step-wise description of the emerging chimney snorkel coronary stenting technique as a predictable procedural approach for the management of this potentially challenging clinical scenario.

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.

Identification of Coronary Artery Orifice to Prevent Coronary Complications in Bioprosthetic and Transcatheter Aortic Valve Replacement.

BACKGROUND: The aim of this study was to identify anatomical variations in coronary artery orifices among high-risk patients with a small aortic root undergoing bioprosthetic aortic valve replacement (BAVR) and transcatheter aortic valve replacement (TAVR) in order to prevent coronary orifice obstruction perioperatively. METHODS AND RESULTS: Coronary orifice and root structure were identified in 400 patients using aortic multidetector-row computed tomography (MDCT). We measured the aortic root diameter; intercommissural distances; and distance from coronary orifice to valve annulus, commissure, and sinotubular junction. We examined positional relationships between the coronary orifice and stent post, or sewing cuff of the bioprosthetic valve and leaflet of the transcatheter aortic valve. Most left coronary artery orifices were distributed near the center of the non-left and left-right commissures; right ones were relatively distributed on the non-right commissural side. Thirty-four patients (8.5%) with BAVR (coronary orifice near the commissure: 31, 7.8%; low takeoff: 5, 1.3%; and both: 2) and 39 (9.8%) with TAVR were at risk for coronary orifice obstruction. During BAVR, one-stitch rotation of the stent and one-stitch rotation with intra-annular implantation were used in near-commissure and low takeoff cases, respectively. During TAVR, percutaneous coronary intervention may be required in the height of the coronary orifice was ≤10 mm from the base of the ventricle aortic junction. CONCLUSIONS: Potential coronary complications during BAVR and TAVR in high-risk patients for coronary obstruction were identified using preoperative aortic MDCT. Choice of appropriate surgical technique or valve is essential.

[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.

Pre-emptive positioning of a coronary stent in the left anterior descending artery for left main protection: a prerequisite for transcatheter aortic valve-in-valve implantation for failing stentless bioprostheses?

Transcatheter aortic valve-in-valve (VIV) implantation in high-risk patients with degenerative surgical bioprosthetic aortic valves is a novel application of transcatheter aortic valve replacement technology. Although transcatheter aortic VIV procedure is clinically effective in most patients, it is a more demanding procedure in terms of the technical aspects of procedural planning. VIV carries a higher risk of coronary occlusion which is associated with a higher rate of in-hospital mortality. We hereby report a technique of pre-emptive left main (LM) protection, by positioning a coronary stent in the proximal left anterior descending artery prior to VIV implantation. The patient treated was considered to be at an increased risk of LM occlusion as a result of the procedure. The technique was performed in anticipation of emergent bailout stenting of the LM. As predicted, the LM occluded during the procedure and LM protection facilitated the safe and effective treatment of an otherwise life-threatening procedure.

First-in-Human Dedicated Leaflet Splitting Device for Prevention of Coronary Obstruction in Transcatheter Aortic Valve Replacement.

BACKGROUND: Coronary artery obstruction is a life-threatening complication of transcatheter aortic valve replacement (TAVR) procedures. Current preventive strategies are suboptimal. OBJECTIVES: The aim of this study was to describe bench testing and clinical experience with a novel device that splits valve leaflets that are at risk for causing coronary obstruction after TAVR, allowing normal coronary flow. METHODS: The ShortCut device was initially tested in vitro and preclinically in a porcine model for functionality and safety. The device was subsequently offered to patients at elevated risk for coronary obstruction. Risk for coronary obstruction was based on computed tomography-based anatomical characteristics. Procedure success was determined as patient survival at 30 days with a functioning new valve, without stroke or coronary obstruction. RESULTS: Following a successful completion of bench testing and preclinical trial, the device was used in 8 patients with failed bioprosthetic valves (median age 81 years; IQR: 72-85 years; 37.5% man) at 2 medical centers. A total of 11 leaflets were split: 5 patients (63.5%) were considered at risk for left main obstruction alone, and 3 patients (37.5%) were at risk for double coronary obstruction. All patients underwent successful TAVR without evidence of coronary obstruction. All patients were discharged from the hospital in good clinical condition, and no adverse neurologic events were noted. Procedure success was 100%. CONCLUSIONS: Evaluation of the first dedicated transcatheter leaflet-splitting device shows that the device can successfully split degenerated bioprosthetic valve leaflets. The procedure was safe and successfully prevented coronary obstruction in patients at risk for this complication following TAVR.

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.

Chinese herbal medicine Naoxintong capsule combined with dual antiplatelet therapy in a rat model of coronary microembolization induced by homologous microthrombi.

OBJECTIVE: In the present study, the efficacy of Naoxintong capsule (NXT), a compound Chinese herbal medicine, combined with dual antiplatelet therapy (DA) in a rat model of coronary microembolization (CME) was evaluated. METHODS: CME in rats was developed by injecting a suspension of microthrombotic particles into the left ventricle when the ascending aorta was obstructed. Microthrombotic particles were generated from the clots of rats sized by filtration through a screen (aperture diameter, 38 µm). A total of 95 rats were randomly divided into six groups, including control group, sham-operation (sham) group, CME model (CME) group, and NXT, DA, and NDA (NXT plus DA) groups. Rats in treatment groups were administered intragastrically with NXT, DA, and NDA, respectively, from 3 d before to 7 d after operation. All rats were sacrificed on day 7 post-operationally, and samples of blood and heart were collected. The complete data of 69 rats were obtained. The incidence of CME (CME%) was evaluated by hematoxylin-eosin staining. Bleeding time (BT) and clotting time (CT) were measured by means of tail cutting and glass slide methods, respectively. Adenosine diphosphate-induced maximum platelet aggregation rate (PAR) was assessed with turbidimetry. Platelet counts were examined by an automated hematology analyzer. The levels of serum P-selectin, interleukin (IL)-6, IL-10, endothelin (ET-1) and endothelial nitric oxide synthase (eNOS) were all detected by enzyme-linked immunosorbent assay. RESULTS: Compared with control and sham groups, CME group had an increase in CME%, PAR, P-selectin, IL-6 and ET-1 (P<0.01, P<0.01), and a decrease in BT, CT, IL-10 and eNOS (P<0.01, P<0.01); compared with CME group, the groups receiving medications had an increase in BT, CT, IL-10 and eNOS (P<0.05 or P<0.01), and a decrease in CME%, PAR, P-selectin, IL-6 and ET-1 (P<0.05 or P<0.01), with DA group increasing most in BT and CT and decreasing most in PAR and P-selectin, and with NDA group increasing most in IL-10 and eNOS and decreasing most in CME%, IL-6 and ET-1. In terms of platelet counts, there was no statistically significant difference among groups (P>0.05). CONCLUSION: NXT combined with DA can decrease CME%. The probable mechanism is that this therapy can appropriately inhibit platelet aggregation, balance the pro- and anti-inflammatory cytokines as well as serum ET-1 and eNOS. This therapy can also reduce risk of intraoperative bleeding during DA therapy.

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.

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.

Ethnic variance on long term clinical outcomes of concomitant use of proton pump inhibitors and clopidogrel in patients with stent implantation: A PRISMA-complaint systematic review with meta-analysis.

BACKGROUND: Pharmacokinetic and pharmacodynamic study showed a lower clopidogrel response when coprescribed with proton pump inhibitors (PPIs). Despite this, PPIs is necessary for patients treated with long term dual antiplatelet therapy (DAPT). Ethnic variance also played a different effect on clopidogrel response. Our study evaluated the effect of concomitant use of DAPT and PPIs and assessed whether ethnic variance exert different effect on clinical outcomes. METHODS: We carefully searched EMBASE, PubMed/Medline databases, and the Cochrane library in April 2019. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) and individual endpoints reported. We also focused on bleeding events. Studies were excluded if the follow-up were <12 months and patients were not treated with clopidogrel after stent implantation. RESULTS: A total of 18 studies were included in the systematic review (involving 79,670 patients). No randomized controlled trials (RCTs) were included. PPIs comedication were associated with increased MACCE (odds ratio [OR] = 1.38; 95% confidence interval [CI] = 1.28-1.49) while not associated with decreased bleeding risks, such as gastrointestinal bleeding (OR = 1.05; 95% CI = 0.53-2.11). PPIs comedication were associated with increased risk for all endpoints among Caucasian population while not with increased risk for MACE (OR = 1.20; 95% CI = 0.99-1.39), all-cause death (OR = 1.24; 95% CI = 0.74-2.06), cardiac-death (OR = 1.29; 95% CI = 0.64-2.57) among Asian population. CONCLUSION: PPIs comedication were associated with adverse clinical outcomes, and ethnic variance may exert different effect on clinical outcomes. Subgroup analysis indicated that concomitant use of PPI might be suitable for Asian patients after stent implantation.

Recurrent coronary thrombotic events in a moderate case of COVID-19.

We describe the case of a healthy patient with moderate COVID-19 infection without thrombophilia nor coronary disease background who presented with a relapsing thrombotic occlusion of the right coronary artery despite normal oxygenation, adequate antiaggregation and prophylactic anticoagulation. Prophylactic anticoagulation recommendations in COVID-19 were inadequate for this patient. Further data are needed to propose full-dose therapeutic anticoagulation for patients with coronary thrombosis and COVID-19 infection. This could nevertheless be considered even in mild forms of COVID-19.

Bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction technique in transcatheter aortic valve-in-valve procedures: a single-center initial experience.

AIM: To describe six cases using the bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction technique to prevent coronary artery obstruction during transcatheter aortic valve-in-valve procedures. METHODS: All patients presented degeneration of a bovine pericardium bioprosthesis [four Trifecta (19, 21, 23, and 25 mm); two Mitroflow (25 and 27 mm)] resulting in severe aortic stenosis (n = 5) or severe aortic regurgitation (n = 1). Procedures were performed under fluoroscopic and echocardiography guidance, and the transfemoral access was used to deliver a self-expanding valve. Data are expressed as frequency or median (Q1-Q3). RESULTS: Age, EuroScore II, and Society of Thoracic Surgeons score were 81 years (75-83.2), 2.9% (2.6-10.7), and 2.7% (2.3-3.2), respectively. Median left and right coronary heights were 9.1 mm (6.2-10.3) and 12.4 mm (10-13.5), respectively, with a median virtual transcatheter heart valve-to-coronary distance of 2.9 mm on the left and 4.6 mm on the right side. Isolated left leaflet laceration was planned in four patients, and bileaflet in two. One unsuccessful right leaflet laceration was reported, corresponding to the first patient (success rate 87.5%). All other seven leaflets lacerations were successfully performed, with no intraprocedure complications. No coronary obstruction, in-hospital death, valve complication, cardiovascular event, or pacemaker implantation were reported. All patients are being followed in routine outpatient visits, and no adverse events were registered. CONCLUSION: The high procedural success and low complication rate reported in this initial experience, demonstrates that the bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction technique can be a viable solution to prevent coronary obstruction in selected patients undergoing valve-in-valve procedures. Operator experience, periprocedural imaging and teamwork are essential to enable an accurate and successful procedure.

Prevention of coronary obstruction in patients at risk undergoing transcatheter aortic valve implantation: the Hamburg BASILICA experience.

OBJECTIVES: This study aimed to assess the clinical outcome of the bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary obstruction (BASILICA) technique in a single-center patient cohort considered at high or prohibitive risk of transcatheter aortic valve implantation (TAVI)-induced coronary obstruction. METHODS: Between October 2019 and January 2021, a total of 15 consecutive patients (age 81.0 [78.1, 84.4] years; 53.3% female; EuroSCORE II 10.6 [6.3, 14.8] %) underwent BASILICA procedure prior to TAVI at our institution. Indications for TAVI were degeneration of stented (n = 12, 80.0%) or stentless (n = 1, 6.7%) bioprosthetic aortic valves, or calcific stenosis of native aortic valves (n = 2, 13.3%), respectively. Individual risk of TAVI-induced coronary obstruction was assessed by pre-procedural computed tomography analysis. Procedural and 30-day outcomes were documented in accordance with Valve Academic Research Consortium (VARC)-2 criteria. RESULTS: BASILICA was attempted for single left coronary cusp in 12 patients (80.0%), for single right coronary cusp in 2 patients (13.3%), and for both cusps in 1 patient (6.7%), respectively. The procedure was feasible in 13 patients (86.7%) resulting in effective prevention of coronary obstruction, whilst TAVI was performed without prior successful bioprosthetic leaflet laceration in two patients (13.3%). In one of these patients (6.7%), additional chimney stenting immediately after TAVI was performed. No all-cause deaths or strokes were documented after 30 days. CONCLUSION: The BASILICA technique appears to be a feasible, safe and effective concept to avoid iatrogenic coronary artery obstruction during TAVI in both native and bioprosthetic valves of patients at high or prohibitive risk. ClinicalTrials.gov Identifier: NCT04227002 (Hamburg AoRtic Valve cOhoRt).