Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling.

We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far-field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting. Porcine (n = 9) and human (n = 4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. A total of 1 mM of carbenoxolone was administered at 5 ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed. We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt)max increased between baseline and carbenoxolone (47.9 ± 4.1-67.2 ± 2.7 ms) indicating conduction slowing. The features with the largest percentage change between baseline and carbenoxolone were fractionation + 185.3%, endpoint amplitude - 106.9%, S-endpoint gradient + 54.9%, S point - 39.4%, RS ratio + 38.6% and (-dV/dt)max - 20.9%. The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically induced pro-arrhythmic substrates.

Comparison of warfarin versus DOACs in patients with concomitant indication for oral anticoagulation undergoing TAVI; results from the ATLAS registry.

The optimal antithrombotic therapy for patients undergoing TAVI with concomitant indication for oral anticoagulation remains unclear. In this high-risk population group, there is a paucity of data with regards to the use of DOACs. In the present study we compared long-term clinical outcomes of TAVI patients requiring anticoagulation, treated with warfarin versus DOACs. Consecutive patients, who underwent TAVI with indication for oral anticoagulation from the multicenter ATLAS registry were studied and divided in two groups depending on the chosen anticoagulation regimen, warfarin vs. DOACs. 30-day survival, as well as estimated 1 and 2-year all-cause mortality were compared between groups. The secondary endpoint included in-hospital major or life-threatening bleeding. The study group included 217 patients (102 treated with warfarin; 115 treated with DOACs). Kaplan-Meier estimated survival was found to be statistically similar in the warfarin and DOAC groups (90.6% vs. 93.7% for 1-year and 84.5% vs. 88.5%, for 2-year survival, respectively, Plog-rank = 0.984). Adjusted hazard ratio for all cause mortality was similar between the two groups (HRwarfarin vs. DOAC = 1.15; 95% CI 0.33 to 4.04, p = 0.829). Propensity matching revealed similar results. At 30-days, all-cause mortality was found to be comparable between the two groups. With regards to BARC defined bleeding complications, major and life-threatening complications did not differ between the two anticoagulation groups (6% vs. 8% for warfarin and DOACs respectively, p = 0.857). DOACs seem to demonstrate a similar safety and efficacy profile compared to warfarin in TAVI patients with a concomitant indication for oral anticoagulation.

Percutaneous left atrial appendage occlusion with the Amulet device: The impact of device disc position upon periprocedural and long-term outcomes.

OBJECTIVE: To investigate the effect of left atrial appendage (LAA) occlusion device positioning upon periprocedural and long-term outcomes. BACKGROUND: The Amulet device is designed to cover the ostium of the LAA. Prolapse of the device into the neck of the LAA is not uncommon resulting in incomplete coverage of the ostium. The clinical consequences of this remain uncertain. METHODS: Outcomes of 87 patients with successful LAA closure were analyzed according to Amulet disc position: group A (n = 45) had complete LAA ostium coverage; group B (n = 42) had incomplete ostium coverage because of disc prolapse. Periprocedural major adverse events (MAE) (composite of all cause death, tamponade, device/air embolization, cerebrovascular events, myocardial infarction, and major bleeding not related to vascular access complications) and total device-related periprocedural adverse events (defined as MAE and pericardial effusion) were evaluated. All patients were followed up longitudinally with long-term events defined as a composite of: cardiovascular death, cerebrovascular events, systemic embolization, and major bleeding requiring transfusion or intervention. RESULTS: Median follow-up was 234 days (IQR 150-436 days). There was a trend toward more periprocedural MAE in group B (P = 0.07) with deep implantation of the Amulet device associated with significantly more periprocedural adverse events (P = 0.03). There were no differences in reposition attempts (P = 0.9) or long-term events (P = 0.57). CONCLUSIONS: Our data suggest that suboptimal device positioning may be associated with worse periprocedural outcomes but no difference in long-term clinical outcomes. The results of this relatively small cohort does not seem to be affected by repositioning attempts during the index procedure.

Bioresorbable vascular scaffold implantation for severely calcified lesions after excimer laser lesion preparation.

Bioresorbable vascular scaffolds (Absorb BVS, Abbott Vascular, Santa Clara, CA) temporarily elute antiproliferative drugs and provide vessel support, which then subsequently resorb to allow restoration of normal vessel function and architecture. To attain the best possible results with BVS, a dedicated implantation technique (PSP: adequate lesion preparation, proper sizing, postdilatation) is considered mandatory, and calcified lesions are one of the most challenging lesion subsets for BVS implantation. In five cases with severe calcifications refractory to balloon predilatation, we performed excimer laser catheter ablation (ELCA: Turbo Elite catheter; Spectranetics Corporation, Colorado Springs, CO, USA), which facilitated adequate lesion expansion with high-pressure noncompliant balloon inflation and BVS implantation. During the follow-up period (481 days [interquartile range: 445-579]), all patients continued dual antiplatelet therapy (DAPT) and there were no cases of cardiac death, myocardial infarction, or scaffold thrombosis. For treatment of severely calcified lesions with bioresorbable scaffolds, ELCA could be considered an effective potential strategy. After the procedure, prolonged DAPT was prescribed.

Definite stent thrombosis after drug-eluting stent implantation in coronary bifurcation lesions: A meta-analysis of 3,107 patients from 14 randomized trials.

BACKGROUND: Bifurcation percutaneous coronary intervention (PCI) is a challenging procedure, but there are currently inadequate data about definite stent thrombosis (ST) rates of single-stent versus double-stent strategies (SS and DS, respectively). METHODS AND RESULTS: Randomized clinical trials (RCTs) comparing SS and DS strategies were searched through PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Fourteen RCTs involving 3,107 patients were analyzed. Owing to the high crossover rate (16.49%), both intention-to-treat (ITT) and as-treated (AT) analyses were performed. In the ITT population, there was a significantly lower rate of early definite ST in the SS group (0.26%; DS group 1.14%; P = 0.021). Similarly, in the AT population, there was a significantly lower rate of early definite ST in the SS group (0.23%, DS group 1.07%; P = 0.042). True bifurcation subgroup analysis also showed a significantly lower early definite ST in the SS group (OR = 0.36, 95% CI = 0.15-0.86, P = 0.042) in the ITT population. There was no significant difference of overall, acute, subacute, and late definite ST between the 2 groups. CONCLUSIONS: Early definite ST is reduced when a SS strategy is used in bifurcation lesions.

Safety and efficacy of rotational atherectomy for the treatment of undilatable underexpanded stents implanted in calcific lesions.

OBJECTIVES: Coronary stent underexpansion is a known risk factor for in-stent restenosis and stent thrombosis. There are limited options once noncompliant balloons have failed to achieve optimal stent expansion. Excimer Laser Coronary Angioplasty with contrast medium injection is one possibility, but not readily available. Rotational atherectomy is an alternative, and has been described in case reports, but concerns exist regarding safety. METHODS: All consecutive patients undergoing rotational atherectomy for symptomatic in-stent restenosis due to stent underexpansion resistant to noncompliant balloon postdilatation between January 2005 and December 2015 were analysed. RESULTS: A total of 16 patients underwent treatment during the study period and the procedure was successful in 14 cases (87.5%). The mean postprocedural minimal lumen diameter increased by 2.3 ± 0.8 mm and percentage diameter stenosis decreased from 82.17% ± 17.2% to 11.9% ± 9.1%. Intraprocedural complications occurred in two patients (burr entrapment successfully managed percutaneously and periprocedural myocardial infarction). At 1-year follow-up, the incidence of target lesion revascularisation was 13.3% (2 out of 15 patients), and one patient died from noncardiac death. CONCLUSION: In this small series of underexpanded stents, rotational atherectomy was an effective treatment for resistant stent underexpansion with acceptable outcomes. © 2016 Wiley Periodicals, Inc.

Bioresorbable vascular scaffolds: From patient selection to optimal scaffold implantation; tips and tricks to minimize device failure.

Bioresorbable vascular scaffolds (BVS) have become an attractive option in the field of percutaneous coronary intervention due to the complete resorption process that occurs over a few years. On the other hand, current generation devices have several limitations when compared to metallic drug-eluting stents including bulky struts and relatively less radial strength, and it has been indicated that an optimized implantation strategy is required. In this article, various tips and tricks to optimize implantation of current generation BVS are discussed. © 2016 Wiley Periodicals, Inc.

Clinical outcomes following bifurcation double-stenting with bioresorbable scaffolds.

OBJECTIVES: To investigate outcomes following bifurcation double-stenting utilizing a bioresorbable scaffold (BRS) in the main branch (MB) and either a BRS or metallic drug-eluting stent (DES) in the side branch (SB). BACKGROUNDS: Data on outcomes of bifurcation lesions treated with BRSs, especially with double-stenting, are currently lacking. METHODS: Data were examined from 42 de novo bifurcation lesions (41 patients) treated with double-stenting utilizing Absorb BRS in MB and BRS/DES in SB. Clinical outcomes including cardiac death, follow-up myocardial infarction, target lesion revascularization (TLR), and definite scaffold/stent thrombosis (ST) were investigated. RESULTS: The majority of target lesions were left anterior descending artery (LAD) bifurcations, and intravascular imaging was used in the majority of cases (92.9%). In SBs, BRSs were utilized in 19 lesions (19 patients) and DESs in 23 lesions (22 patients). Angiographic success was achieved in all lesions. The median follow-up was 594 days (interquartile range 214 - 838 days). The overall TLR-rates were 9.7% at 1 year and 14.0% at 2 years (MB-TLR: 6.9% at 1 year and 11.1% at 2 years; SB TLR: 9.7% at 1 year and 14.0% at 2 years). No definite ST was observed during follow-up. TLR rates in both the MB and SB tended to be higher in the SB-BRS group when compared to the SB-DES group. CONCLUSION: Mid-term clinical outcomes following double-stenting using BRS were acceptable. Bifurcation lesions treated with DES in SB tended to have lower TLR rates in both the MB and SB when compared to implanting BRS in both branches. © 2016 Wiley Periodicals, Inc.

Preliminary Report of Clinical Outcomes After Single Crossover Bioresorbable Scaffold Implantation Without Routine Side Branch Strut Dilation.

OBJECTIVES: The objective of this study was to investigate clinical outcomes following single crossover bioresorbable scaffold (BRS) implantation without routine side branch (SB) strut dilation. BACKGROUND: It is unknown whether SB strut dilation is routinely required after single crossover BRS implantation if there is no compromise of the jailed SB. METHODS: Among 187 bifurcation lesions treated with Absorb BRS, 115 lesions (101 patients) were treated with single crossover BRS implantation. Strut dilation toward SB was considered only when SB was compromised (SB TIMI flow < 3 or SB ostium > 75%) after main branch (MB) BRS implantation. Clinical outcomes including cardiac death, follow-up myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and definite scaffold thrombosis (ST) were investigated. RESULTS: The majority of target lesions were in the left anterior descending artery (73.0%) and the rate of true bifurcation lesions was 42.6%. SB strut dilation was performed in only 20% of lesions (n = 23), and intravascular imaging was used in most cases (90.4%). The rates of TLR per lesion at 1-year was 3.1% in MB, and 0% in SB. In all patients, the cumulative rate of cardiac death was 1.1% at 1-year, follow-up MI 2.2%, TVR 3.5%, and definite ST 1.0%. CONCLUSION: Clinical outcomes were acceptable in bifurcation lesions treated with single crossover BRS implantation without routine SB strut dilation. © 2016 Wiley Periodicals, Inc.

Does one size really fit all? The case for personalized antiplatelet therapy in interventional cardiology.

Cardiovascular disease is the leading cause of death worldwide. Dual antiplatelet therapy (DAPT), with aspirin plus a P2Y12 inhibitor, is currently recommended as a default for patients after acute coronary syndrome (ACS) and following percutaneous coronary intervention (PCI). However, controversies arise over the role of aspirin, the optimal duration of DAPT after drug-eluting stent (DES) implantation, the choice of P2Y12 inhibitor and the variability in individual responses to antiplatelet agents. Recent data indicate that monotherapy with a P2Y12 inhibitor may have adequate anti-ischemic effects with lower bleeding risk. Additionally, discrepancies in DAPT duration recommendations and the optimal P2Y12 inhibitor, provides more uncertainty. We ask the question "does one size really fits all?" or should a more personalized strategy should be implemented.

Diseases affecting the heart and blood circulation are the leading cause of death worldwide. Treatment with drugs that prevents platelets from clumping (called antiplatelets) like aspirin plus another drug group (called P2Y12 inhibitors) like clopidogrel, ticagrelor and prasugrel, is currently recommended as a default for patients after heart attack and/or in whom coronary stents are inserted. However, it is very well documented that the response of any individual to these drugs is highly variable, and that the patients who don't respond as well to them are at increased risk of having clot events in their coronary arteries. On the other hand, people who respond to the drugs very sensitively have a higher bleeding risk. Despite these observations, there is no attempt to test the response of individuals patients to their antiplatelet drugs in routine practice. This review article looks in detail and whether the currently used strategy of "One size fits all" should be changed, given that there may well now be the chance to perform routine testing on everyone, and personalize their treatment accordingly.

National Institute for Health and Care Excellence guidelines on myocardial revascularisation.

Cardiologists in the UK predominantly use the National Institute for Health and Care Excellence (NICE) and European Society of Cardiology guidelines to help guide decision-making. This article will appraise the current recommendations from NICE regarding myocardial revascularisation and compare them with other major international guidelines. While there are many similarities, subtle differences exist. These differences arise in part due to the evidence base at time of publication, as well as from the different healthcare systems that they are designed for, and from the cost-effectiveness models that dominate the methodology used by NICE. The clinical implications of the differences between the international guidelines will be analysed.

Is It Really Safe to Discontinue Antiplatelet Therapy 12 Months After Percutaneous Coronary Intervention in Patients with Atrial Fibrillation?

The prevalence of AF in patients with coronary artery disease is high. The guidelines from many professional groups, including the European Society of Cardiology, American College of Cardiology/American Heart Association and Heart Rhythm Society, recommend a maximum duration of 12 months of combination single antiplatelet and anticoagulation therapy in patients who undergo percutaneous coronary intervention and who have concurrent AF, followed by anticoagulation alone beyond 1 year. However, the evidence that anticoagulation alone without antiplatelet therapy adequately reduces the well-documented attritional risk of stent thrombosis after coronary stent implantation is relatively sparse, particularly given that very late stent thrombosis (>1 year from stent implantation) is the commonest type. By contrast, the elevated risk of bleeding from combined anticoagulation and antiplatelet therapy is clinically important. The aim of this review is to assess the evidence for long-term anticoagulation alone without antiplatelet therapy 1 year post-percutaneous coronary intervention in patients with AF.

How do we ensure that more patients receive stroke thrombectomy in the UK?

Stroke is a major cause of death in the UK. Mechanical thrombectomy is the most effective treatment for large vessel ischaemic strokes. Despite this, very few patients in the UK receive mechanical thrombectomy. This editorial explores the main barriers to mechanical thrombectomy use and mechanisms to improve uptake.

Midterm Outcomes in Patients With Aortic Stenosis Treated With Contemporary Balloon-Expandable and Self-Expanding Valves: Does Valve Size Have an Impact on Outcome?

Background No data currently exist comparing the contemporary iterations of balloon-expandable (BE) Edwards SAPIEN 3/Ultra and the self-expanding (SE) Medtronic Evolut PRO/R34 valves. The aim of the study was the comparison of these transcatheter heart valves with emphasis on patients with small aortic annulus. Methods and Results In this retrospective registry, periprocedural outcomes and midterm all-cause mortality were analyzed. A total of 1673 patients (917 SE versus 756 BE) were followed up for a median of 15 months. A total of 194 patients died (11.6%) during follow-up. SE and BE groups showed similar survival at 1 (92.6% versus 90.6%) and 3 (80.3% versus 85.2%) years (Plog-rank=0.136). Compared with the BE group, patients treated with the SE device had lower peak (16.3±8 mm Hg SE versus 21.9±8 mm Hg BE) and mean (8.8±5 mm Hg SE versus 11.5±5 mm Hg BE) gradients at discharge. Conversely, the BE group demonstrated lower rates of at least moderate paravalvular regurgitation postoperatively (5.6% versus 0.7% for SE and BE valves, respectively; P<0.001). In patients treated with small transcatheter heart valves (≤26 mm for SE and ≤23 mm for BE; N=284 for SE and N=260 for BE), survival was higher among patients treated with SE valves at both 1 (96.7% SE versus 92.1% BE) and 3 (91.8% SE versus 82.2% BE) years (Plog-rank=0.042). In propensity-matched patients treated with small transcatheter heart valve, there remained a trend for higher survival among the SE group at both 1 (97% SE versus 92.3% BE) and 3 years (91.8% SE versus 78.7% BE), Plog-rank=0.096). Conclusions Real-world comparison of the latest-generation SE and BE devices demonstrated similar survival up to 3 years' follow-up. In patients with small transcatheter heart valves, there may be a trend for improved survival among those treated with SE valves.

Association between troponin level and medium-term mortality in 20 000 hospital patients.

INTRODUCTION: Cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium-term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test. METHOD: This prospective observational study included 20 000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital. RESULTS: A total of 20 000 patients were included in the analysis and 18 282 of these (91.4%) did not have a clinical indication for cardiac troponin I (cTnI) testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% vs 12.3% p<0.001 log rank). Multivariable Cox analysis demonstrated that the log10 cTnI concentration was independently associated with mortality (HR 1.76 (95% CI 1.65 to 1.88)). Landmark analysis, excluding deaths within 30 days, showed the relationship between cTnI concentration and mortality persisted. CONCLUSION: In a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium-term cardiovascular and non-cardiovascular mortality in the statistical model tested.

Cardiac MRI in cardiomyopathies.

Heart failure affects 1-2% of the adult population and one of the main contributors to its development is cardiomyopathy. Assessing a patient's risk for adverse events in heart failure is challenging and made more difficult by the heterogenous phenotypic expression of the disease. Cardiac MRI has long been a gold standard measure of myocardial function and anatomy due to its high spatial and temporal resolution. More recently, it has been posited to play a more critical role in the diagnosis and prognosis of cardiomyopathy-related heart failure. Given the limitations of more commonly used imaging modalities, increasing the clinical use of cardiac magnetic resonance imaging could potentially improve the prognosis of specific subgroups of patients at risk of adverse cardiac events.

Lay abstract Heart failure is a condition where the heart is unable to pump out enough blood to meet the body's daily needs. It can affect up to 2% of the adult population. One of the causes of heart failure is an intrinsic disease of the heart muscle, called cardiomyopathy. Assessing a patient's risk for events such as hospitalization and death in heart failure is challenging, and made more difficult by the wide variety of ways a patient can present with heart failure clinically. Cardiac MRI has long been a highly regarded imaging technique for heart function and shape due to the high level of detail it can show. More recently, it has been thought to play a more important role in investigating and predicting the course of cardiomyopathy-related heart failure. Given the limitations of more commonly used measurement techniques, increasing the clinical use of cardiac magnetic resonance imaging would potentially improve the outcomes and quality of life for patients suffering with cardiomyopathy.

Balloon Nudge Technique: A Touch to Nonsteerable Valves.

Transfemoral transcatheter aortic valve replacement is an effective treatment for severe aortic stenosis with a high rate of procedural success with the current devices. However, anatomic factors and device limitations may increase technical difficulty. We describe the balloon nudge technique, a novel technique that improves coaxial alignment while crossing the aortic valve. (Level of Difficulty: Advanced.).

Percutaneous Devices for the Treatment of Complex Native Valve Mitral Leaflet and Aortomitral Continuity Defects: Review and Case Series.

Percutaneous closure of paravalvar leaks (PVLs) was once only performed in extreme or non-surgical risk cases not suitable for redo-surgery with tissue or mechanical valves. This technique is now the treatment of choice with long term outcomes that are better than redo operations.123 As interventionalists become more familiar with using PVL devices, more off label device use has been reported in non-surgical cases involving complex native mitral valve regurgitation (NVMR). In this review, we appraise the literature regarding percutaneous treatment of paravalvar leaks and more recently esoteric off label use. We also describe two recent challenging cases where percutaneous devices were used to treat severe leaks that developed as a sequela of previous infective endocarditis. We also provide specific recommendations regarding periprocedural strategy and focus on the importance of device choice to provide an optimal outcome.