Razi Khan

Novel anti-inflammatory therapies for the treatment of atherosclerosis

The underlying role of inflammation in atherosclerosis has been characterized. However, current treatment of coronary artery disease (CAD) predominantly consists of targeted reductions in serum lipoprotein levels rather than combating the deleterious effects of acute and chronic inflammation. Vascular inflammation acts by a number of different molecular and cellular pathways to contribute to atherogenesis. Over the last decades, both basic studies and clinical trials have provided evidence for the potential benefits of treatment of inflammation in CAD. During this period, development of pharmacotherapies directed towards inflammation in atherosclerosis has accelerated quickly. This review will highlight specific therapies targeting interleukin-1β (IL-1β), P-selectin and 5-lipoxygenase (5-LO). It will also aim to examine the anti-inflammatory effects of serpin administration, colchicine and intravenous HDL-directed treatment of CAD. We summarize the mechanistic rationale and evidence for these novel anti-inflammatory treatments at both the experimental and clinical levels.

Transradial Percutaneous Coronary Interventions in Acute Coronary Syndrome

Transradial access (TRA) is becoming increasingly used worldwide for percutaneous coronary intervention (PCI) after acute coronary syndromes (ACS). TRA compared with transfemoral access has been noted to improve clinical outcomes in clinical trials and large registry cohort studies. However, much of the benefits of TRA PCI are noted in patients with ST elevation myocardial infarction (STEMI) undergoing primary PCI, where TRA PCI has been associated with reductions in major bleeding events and potentially lower short- and long-term mortality rates. Although much less data exist for TRA PCI in unstable angina and/or non-ST elevation myocardial infarction, similar reductions in bleeding and mortality have not been consistently described. Differences in outcome benefit with TRA PCI among various ACS subtypes may be attributable to the potentially increased inherent risk of periprocedural bleeding in STEMI compared with unstable angina and/or non-ST elevation myocardial infarction. Pre- and intra-procedural factors associated with STEMI treatment, such as use of pharmacoinvasive therapy and aggressive antithrombotic regimens likely increase bleeding risk in patients. In conclusion, this review describes the evidence for TRA PCI across the spectrum of ACS and highlights why differences in clinical benefit may exist among ACS subtypes.

Impact of left ventricular function on clinical outcomes of functional mitral regurgitation patients undergoing transcatheter mitral valve repair.

To evaluate the impact of baseline left ventricular (LV) function on the clinical outcomes of patients with functional mitral regurgitation (FMR) treated with MitraClip.

Characterising and predicting bleeding in high-risk patients with an acute coronary syndrome

Objective In the Apixaban for Prevention of Acute Ischemic Events (APPRAISE-2) trial, the use of apixaban, when compared with placebo, in high-risk patients with a recent acute coronary syndrome (ACS) resulted in a significant increase in bleeding without a reduction in ischaemic events. The aim of this analysis was to provide further description of these bleeding events and to determine the baseline characteristics associated with bleeding in high-risk post-ACS patients. Methods APPRAISE-2 was a multinational clinical trial including 7392 high-risk patients with a recent ACS randomised to apixaban (5 mg twice daily) or placebo. Bleeding including Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding, International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding, and any bleeding were analysed using an on-treatment analysis. Kaplan–Meier curves were plotted to describe the timing of bleeding, and a Cox proportional hazards model was used to identify predictors of ISTH major or CRNM bleeding and any bleeding. Median follow-up was 241 days. Results The proportion of patients who experienced TIMI major or minor, ISTH major or CRNM, and any bleeding was 1.5%, 2.2% and 13.3%, respectively. The incidence of bleeding was highest in the immediate post-ACS period (0.11 in the first 30 days vs 0.03 after 30 days events per 1 patient-year); however, >60% of major bleeding events occurred >30 days after the end of the index hospitalisation. Gastrointestinal bleeding was the most common cause of major bleeding, accounting for 45.9% of TIMI major or minor and 39.5% of ISTH major or CRNM bleeding events. Independent predictors of ISTH major or CRNM bleeding events included older age, renal dysfunction, dual oral antiplatelet therapy, smoking history, increased white cell count and coronary revascularisation. Conclusions When compared with placebo, the use of apixaban is associated with an important short-term and long-term risk of bleeding in high-risk post-ACS patients, with gastrointestinal bleeding being the most common source of major bleeding. The baseline predictors of major bleeding appear to be consistent with those identified in lower-risk ACS populations with shorter-term follow-up. Clinical trial No NCT00831441.

Effect of Radial-to-Femoral Access Crossover on Adverse Outcomes in Primary Percutaneous Coronary Intervention

We aimed to describe the impact of the vascular access used when patients are treated with primary percutaneous coronary intervention (PPCI) and to assess whether this translates into differences in angiographic outcomes. Patients with ST-elevation myocardial infarction who underwent PPCI were divided into 3 groups: successful radial access (RA), successful femoral access (FA), and Crossover (failed RA with need for bailout FA) groups. Vascular access-related time (VART) was defined as the delay in PPCI that can be attributed to vascular access-related issues. Study end point was the final corrected Thrombolysis In Myocardial Infarction frame count. Multivariable analysis was used to identify predictors of RA failure (RAF: FA + Crossover). We included 241 patients (RA, n = 172; FA, n = 49; Crossover, n = 20). Mean VART was longer in Crossover (10.3 [8.8 to 12.4] minutes), relative to RA (4.1 [3.2 to 5.5] minutes) and FA (4.6 [3.4 to 8.4] minutes, p <0.001). A similar situation was found for time-to-first device (Crossover 22.5 [20.3 to 32.0], RA 15.0 [12.0 to 19.8]; FA 17.9 [13.5 to 22.3] minutes, p <0.001) and total procedure time (Crossover 60.3 [51.6 to 71.5], RA 46.8 [38.1 to 59.7], FA 52.3 [41.9 to 74.7] minutes, p <0.001). No differences in corrected Thrombolysis In Myocardial Infarction frame count were observed (Crossover 26 [18 to 32] frames, RA 24 [18 to 32] frames, FA 25 [16 to 34] frames, p = 0.625). Killip class IV (odds ratio [OR] 3.628, 95% confidence interval [CI] 1.098 to 11.981, p = 0.035), cardiopulmonary resuscitation before arrival (OR 3.572, 95% CI 1.028 to 12.407, p = 0.045), and glomerular filtration rate (OR 0.861, 95% CI 0.758 to 0.978, p = 0.021) were independent predictors of RA failure. In conclusion, in the setting of PPCI, radial-to-FA crossover can lead to VART delays that do not affect angiographic outcomes, in comparison with successful RA.

Ventricular Proarrhythmic Effects of Atrial Fibrillation are Modulated by Depolarization and Repolarization Anomalies in Patients with Left Ventricular Dysfunction

Background: Atrial fibrillation (AF) may have a ventricular proarrhythmic effect, particularly in the setting of heart failure. We assessed whether AF predicts appropriate implantable cardioverter‐defibrillator (ICD) shocks in patients with left ventricular dysfunction and explored modulators of risk.

Efficacy of a balloon-expandable vascular access system in transfemoral TAVI patients

Vascular complications (VC) are a serious and frequent complication of transfemoral transcatheter aortic valve implantation (TAVI) and result in increased morbidity and mortality. It has been suggested that newly developed vascular sheaths may increase the ability to perform transfemoral TAVI in patients with normal and access‐limiting peripheral artery disease (PAD) and reduce vascular complications. Aims: We sought to assess the safety and efficacy of the 19 French (F) SoloPath balloon‐expandable transfemoral vascular access system in patients who underwent transfemoral TAVI at our center between 2011 and 2014. Methods and results: Single‐center retrospective study of 90 patients who underwent transfemoral TAVI with the use of the SoloPath sheath. Patients were categorized into two groups according to a sheath to femoral artery ratio (SFAR) of less than or equal to 1.05, or greater than 1.05. Overall, the incidence of major bleeding complications was low, 4.4%. No significant differences were found in technical or procedural success rates (100% in both groups and 100% vs. 91.3; P = 0.09; respectively), total vascular complications (20.8 vs. 21.7; P = 0.92) or total bleeding complications (20.8 vs. 30.4; P = 0.36 between those with SFAR greater or less than 1.05. Conclusions: The use of the SoloPath balloon‐expandable sheath is feasible and safe even in patients with SFAR > 1.05, showing no increased vascular or bleeding complications compared to patients with larger vascular access.

Prognostic impact of the residual SYNTAX score on in-hospital outcomes in patients undergoing primary percutaneous coronary intervention

This study sought to assess the impact of residual coronary artery disease (CAD), using the residual SYNTAX score (rSS), on in‐hospital outcomes after primary percutaneous intervention (PPCI). The study also aimed to determine independent predictors for high rSS. Residual CAD has been associated with worsened prognosis in patients undergoing PCI for non‐ST acute coronary syndromes. The rSS is a systematic angiographic score that measures the extent and complexity of residual CAD after PCI.

Examining the Role of and Treatment Directed at IL-1β in Atherosclerosis

PurposeThe purpose of this review was to examine the role of IL-1β in the inflammatory process central to the development of atherosclerosis and to discuss current clinical evidence for treatments targeting IL-1β in coronary artery disease.Recent FindingsIL-1β has been shown to modulate atherosclerotic plaque progression by upregulating the synthesis of adhesion molecules on endothelial cells, as well increasing activation and proliferation of vascular smooth muscle cells. Animal studies have further suggested that alterations in the balance between agonists and antagonists of IL-1β are important in promoting atherosclerosis. In humans, preliminary assessment of therapy targeting IL-1β noted early reductions in serum inflammatory biomarkers among those with systemic inflammatory or coronary artery disease. The CANTOS trial, a large randomized double-blind study found that canakinumab, a monoclonal antibody targeting IL-1β, reduced ischemic events in patients being treated for secondary prevention.SummaryCellular, animal, and now clinical studies have suggested a role for therapies aimed at IL-1β for treatment of CAD. However, given potential side effects and costs of these medications, further study is required to determine which patients may be most suited for treatment above current standard of care.