H. Rashid

Incidence and predictors of permanent pacemaker implantation following treatment with the repositionable Lotus™ transcatheter aortic valve

Objectives To determine the incidence and predictors of permanent pacemaker (PPM) requirement following transcatheter aortic valve replacement (TAVR) with the mechanically expanded LotusTM Valve System (Boston Scientific). Background Pacemaker implantation is the most common complication following TAVR. Predictors of pacing following TAVR with the Lotus valve have not been systematically assessed. Methods Consecutive patients with severe aortic stenosis who underwent Lotus valve implantation were prospectively recruited at a single-centre. Patients with a pre-existing PPM were excluded. Baseline ECG, echocardiographic and multiple detector computed tomography as well as procedural telemetry and depth of implantation were independently analyzed in a blinded manner. The primary endpoint was 30-day incidence of pacemaker requirement (PPM implantation or death while pacing-dependent). Multivariate analysis was performed to identify independent predictors of the primary endpoint. Results A total of 104 consecutive patients underwent TAVR with the Lotus valve with 9/104 (9%) with a pre-existing PPM excluded. New or worsened procedural LBBB occurred in 78%. Thirty-day incidence of the primary pacing endpoint was 28%. The most common indication for PPM implantation was complete heart block (CHB) (69%). Independent predictors of the primary endpoint included pre-existing RBBB (hazard ratio [HR] 2.8, 95% CI 1.1–7.0; P = 0.032) and depth of implantation below the noncoronary cusp (NCC) (HR 2.4, 95% CI 1.0–5.7; P = 0.045). Conclusions Almost a third of Lotus valve recipients require pacemaker implantation within 30 days. The presence of pre-existing RBBB and the depth of prosthesis implantation below the NCC were significant pacing predictors.

Subclinical Leaflet Thrombosis in Transcatheter Aortic Valve Replacement Detected by Multidetector Computed Tomography ― A Review of Current Evidence ―

Subclinical leaflet thrombosis (SLT) following transcatheter aortic valve replacement (TAVR) has been increasingly recognized. SLT has the hallmark features of hypo-attenuated leaflet thickening (HALT) on multidetector computed tomography (MDCT), which may result in hypoattenuation affecting motion (HAM). The actual prevalence of this condition is uncertain, with limited observational registries. SLT has caught the attention of the cardiovascular community because of concerns regarding its clinical sequelae, specifically the potential increased incidence of cerebrovascular events. There are available, albeit sparse, data to suggest that when left untreated, SLT may lead to valve deterioration with potential hemodynamic compromise and potentially clinically overt prostheses thrombosis. Some clinicians have opted to treat patients with SLT with anticoagulation. Although anticoagulation may be a rational treatment option, little data exist on the safety and efficacy of this treatment. This is particularly important considering TAVR patients also have higher bleeding risk than the standard population. In this review, we aim to summarize the current evidence on SLT, explore its pathophysiological mechanism, discuss the current treatment options and future trials that may clarify the optimal antithrombotic strategies of SLT.

Safety and efficacy of valve repositioning during transcatheter aortic valve replacement with the Lotus Valve System.

OBJECTIVE To determine the safety and efficacy of valve repositioning following transcatheter aortic valve replacement (TAVR) with the Lotus Valve System (Boston Scientific, Marlborough, MA, USA). INTRODUCTION TAVR is a well-established treatment for severe aortic stenosis. The Lotus Valve System is fully repositionable and retrievable. Valve repositioning has the potential to minimize TAVR-related complications caused by valve malposition; however, the effect on adverse event rates such as stroke is unknown. METHODS Consecutive patients with severe aortic stenosis treated with the Lotus Valve System (n=125) were prospectively recruited. Patients who did not require valve repositioning (Group A) were compared to patients who required one or more valve repositions (Group B). The primary end-point was 30-day occurrence of major adverse cardiovascular and cerebrovascular events (MACCE). Secondary end-points included each component of the primary end-point, new pacemaker insertion, and procedural or 30-day major adverse events, defined according to VARC-2 definitions. RESULTS Valve repositioning was utilized in 60.8% (76/125) of patients including 17.1% (13/76) who required full valve resheathing. The most frequent indications for valve repositioning were altering the depth and angulation of initial implantation (69.7%), reducing paravalvular regurgitation (13.2%), and attempt to correct new or worsened heart block (7.9%). Baseline characteristics were similar in both groups. The primary end-point occurred in 12.2% and 6.6% of Group A and B, respectively (p=0.10). Thirty-day new pacemaker implantation was 34.1% and 18.8% in Group A and B, respectively (p=0.06). The secondary end-point measures were not significantly different between the groups. CONCLUSION Repositioning facilitated correct anatomical positioning of all devices leading to optimal prosthesis hemodynamics and a trend to lower pacemaker rate without increased risk of MACCE.

Computed Tomographic Coronary Angiography–Derived Plaque Characteristics Predict Major Adverse Cardiovascular EventsCLINICAL PERSPECTIVE: A Systematic Review and Meta-Analysis

Background— Computed tomographic coronary angiography is a noninvasive imaging modality that permits identification and characterization of coronary plaques. Despite consensus statements supporting routine reporting of computed tomographic coronary angiography plaque characteristics, there remains uncertainty whether these data convey prognostic information. We performed a systematic review and meta-analysis assessing the strength of association between computed tomographic coronary angiography–derived plaque characterization and major adverse cardiovascular events (MACE). Methods and Results— Electronic databases were searched for studies reporting computed tomographic coronary angiography plaque characterization and MACE. Data were gathered on plaque morphology (noncalcified, partially calcified, and calcified) and high-risk plaque (HRP) features, including low-attenuation plaque, napkin-ring sign, spotty calcification, and positive remodeling. Of 5496 citations, 13 studies met inclusion criteria. Five hundred fifty-two (3.9%) MACE occurred in 13 977 patients with mean follow-up ranging between 1.3 and 8.2 years. In terms of plaque morphology, the strongest association was observed for noncalcified plaque (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.24–1.70; P<0.001), with weaker associations found for partially calcified (HR, 1.37; 95% CI, 1.18–1.60; P<0.001) and calcified plaques (HR, 1.23; 95% CI, 1.16–1.30; P<0.001). All HRP features were strongly associated with MACE, including napkin-ring sign (HR, 5.06; 95% CI, 3.23–7.94; P<0.001), low-attenuation plaque (HR, 2.95; 95% CI, 2.03–4.29; P<0.001), positive remodeling (HR, 2.58; 95% CI, 1.84–3.61; P<0.001), and spotty calcification (HR, 2.25; 95% CI, 1.26–4.04; P=0.006). The presence of ≥2 HRP features had highest risk of MACE (HR, 9.17; 95% CI, 4.10–20.50; P<0.001). Conclusions— These data demonstrate that HRP is most likely an independent predictor of MACE, which supports the inclusion of HRP reporting in clinical practice. However, at this point, it remains unclear whether HRP reporting has clinical implications.

Bleeding outcomes after non-emergency percutaneous coronary intervention in the very elderly

Background Octogenarians constitute an increasing proportion of patients presenting for non-emergency percutaneous coronary intervention (PCI). Methods This study evaluated the in-hospital procedural characteristics and outcomes, including the bleeding events of 293 octogenarians presenting between January 2010 and December 2012 for non-emergency PCI to a single large volume tertiary care Australian center. Comparisons were made with 293 consecutive patients aged less than or equal to 60 years, whose lesions were matched with the octogenarians. Results Non-ST elevation myocardial infarction was the most frequent indication for non-emergency PCI in octogenarians. Compared to the younger cohort, they had a higher prevalence of co-morbidities and more complex coronary disease, comprising more type C and calcified lesions. Peri-procedural use of low molecular weight heparin (LMWH; 1.0% vs. 5.8%; P < 0.001) and glycoprotein IIb/IIIa inhibitors (2.1% vs. 9.6%; P < 0.001) was lower, while femoral arterial access was used more commonly than in younger patients (80.9% vs. 67.6%; P < 0.001). Overall, there was a non-significant trend towards higher incidence of all bleeding events in the elderly (9.2% vs. 5.8%; P = 0.12). There was no significant difference in access site or non-access site bleeding and major or minor bleeding between the two cohorts. Sub-analysis did not reveal any significant influence on bleeding rates by the use of LMWH, glycoprotein IIb/IIIa inhibitors or femoral arterial access. In addition, there were no significant differences in the rates of in-hospital mortality, stroke or acute stent thrombosis between the two groups. Conclusions In this single center study, we did not observe significant increases in adverse in-hospital outcomes including the incidence of bleeding in octogenarians undergoing non-emergency PCI.

PCSK9 Monoclonal Antibodies in 2016: Current Status and Future Challenges

Cardiovascular disease remains the leading cause of morbidity and mortality in developed nations, with elevated low-density lipoprotein-cholesterol (LDL-C) levels being a major modifiable risk factor for coronary atherosclerosis. While lipid-lowering therapies such as statins are effective in lowering LDL-C, a proportion of patients do not achieve target LDL-C goals with statins or are intolerant to statins necessitating other treatment options. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of agents that reduce LDL-C beyond the maximum achievable LDL-C reductions with statins, and have been well studied in different patient groups. However, there are concerns regarding their potential adverse effects and cost, given that morbidity and mortality benefits have not yet been demonstrated. This state-of-the art review provides an overview of the development of PCSK9 inhibitors, the evidence regarding their clinical efficacy in specific target populations, and highlights future trials and challenges that need to be addressed before PCSK9 inhibitors are widely adopted into contemporary clinical practice.

The role of antiplatelet drug resistance in subclinical leaflet thrombosis following transcatheter aortic valve replacement

We read with interest the article by Xiong et al. which described an association between gene polymorphisms and antiplatelet drug resistance in the development of leaflet thrombosis (LT) following transcatheter aortic valve replacement (TAVR) [1]. The authors found a strong correlation between a CYP2C19 gene polymorphism and the development of hypo-attenuated leaflet thickening (HALT). Aside from antiplatelet drug resistance, certain clinical risk factors have been linked to the development of HALT. Chronic kidney disease, diabetes, previous cerebrovascular events (CVE) and pro-inflammatory conditions such as active malignancy have been found to be associated with venous thromboembolism and HALT due to the pro-thrombotic nature of these conditions [2–4]. Likewise, prolonged blood stasis and reduction in trans-prosthetic flow such as in congestive cardiac failure has been shown to predispose to HALT [5, 6]. Prosthesis factors also play a role in the development of HALT. Valve crimping and aggressive ballooning have been showed to cause micro-filamentous TAVR leaflet injury and expose collagen fibers which are thrombogenic [4, 7]. Furthermore, the type of TAVR device and larger prostheses have been shown to increase the risk of HALT, whilst smaller prostheses are considered a protective factor [3, 8]. To appreciate the results presented by the authors in a better context, we hope the authors could provide the prevalence of these clinical (diabetes, hypertension, congestive cardiac failure and prior cerebrovascular event) and prosthesis (valve type, prostheses size and post-dilatation rate) risk factors for both HALT and non-HALT cohorts which have been associated with the development of LT in other studies. There are growing concerns regarding the potential clinical sequelae of HALT [9]. Pooled evidence suggests a strong correlation between bioprosthetic LT and CVE [10]. Although the results were primarily driven by transient ischaemic attacks (TIA), the rate of stroke reached borderline statistical significance. Could the authors could provide the readers the clinical outcomes in the HALT and non-HALT cohorts, especially mortality and CVE (TIA and stroke)? We commend the authors for a well-designed trial and for providing further insight into the pathophysiology of HALT. We believe future prospective trials are warranted to determine the mechanism and clinical sequelae of HALT.

Transcatheter Aortic Valve Replacement and Atrial Fibrillation: Impact of Antithrombotic Strategy on Clinical Outcomes

BACKGROUND Antithrombotic recommendations following transcatheter aortic valve replacement (TAVR) are largely based on previous trial protocols. The efficacy and risk of anticoagulation has not been systematically assessed. The aim of this study was to determine the efficacy and safety of oral anticoagulation in patients with atrial fibrillation (AF) following TAVR with the Lotus Valve System (Boston Scientific, Marlborough, MA, USA). METHODS Consecutive patients with severe aortic stenosis who underwent Lotus valve implantation were prospectively recruited (n=164). Atrial fibrillation patients prescribed oral anticoagulation (standard AF therapy) were compared to non-AF patients prescribed aspirin and clopidogrel (standard non-AF therapy). Twenty (20) of 164 patients were excluded, as they were not prescribed standard therapy. The primary endpoint was 6-month incidence of death, myocardial infarction, stroke/transient ischaemic attack (TIA) or major/life-threatening bleeding. Secondary endpoints included each component of the primary endpoint, defined according to VARC-2. RESULTS Overall, the primary endpoint occurred in 20.8% and 17.7% of the standard AF and standard non-AF therapy groups respectively (p=0.82). There was no statistically significant difference in bleeding (12.5% versus 9.4%, p=0.77) or stroke/TIA (2.1% versus 8.3%, p=0.27) between the standard AF and standard non-AF therapy groups respectively. CONCLUSIONS This study supports the safety of anticoagulation in AF patients, which did not result in excess risk of bleeding or stroke/TIA compared with dual antiplatelet therapy in non-AF patients.

Effect of aorto‐ventricular angulation on procedural success in transcatheter aortic valve replacements with the Lotus Valve system

To determine the effect of aorto‐ventricular angulation (AA) on procedural success with the Lotus Valve system.

Long-term pacemaker dependency and impact of pacing on mortality following transcatheter aortic valve replacement with the LOTUS valve

To determine permanent pacemaker (PPM) dependency following transcatheter aortic valve replacement (TAVR) with the Lotus™ valve system (Boston Scientific), and the impact of PPM implantation on long‐term morbidity and mortality.