Arjun Majithia

Registry-Based Prospective, Active Surveillance of Medical-Device Safety.

BACKGROUND The process of assuring the safety of medical devices is constrained by reliance on voluntary reporting of adverse events. We evaluated a strategy of prospective, active surveillance of a national clinical registry to monitor the safety of an implantable vascular‐closure device that had a suspected association with increased adverse events after percutaneous coronary intervention (PCI). METHODS We used an integrated clinical‐data surveillance system to conduct a prospective, propensity‐matched analysis of the safety of the Mynx vascular‐closure device, as compared with alternative approved vascular‐closure devices, with data from the CathPCI Registry of the National Cardiovascular Data Registry. The primary outcome was any vascular complication, which was a composite of access‐site bleeding, access‐site hematoma, retroperitoneal bleeding, or any vascular complication requiring intervention. Secondary safety end points were access‐site bleeding requiring treatment and postprocedural blood transfusion. RESULTS We analyzed data from 73,124 patients who had received Mynx devices after PCI procedures with femoral access from January 1, 2011, to September 30, 2013. The Mynx device was associated with a significantly greater risk of any vascular complication than were alternative vascular‐closure devices (absolute risk, 1.2% vs. 0.8%; relative risk, 1.59; 95% confidence interval [CI], 1.42 to 1.78; P<0.001); there was also a significantly greater risk of access‐site bleeding (absolute risk, 0.4% vs. 0.3%; relative risk, 1.34; 95% CI, 1.10 to 1.62; P=0.001) and transfusion (absolute risk, 1.8% vs. 1.5%; relative risk, 1.23; 95% CI, 1.13 to 1.34; P<0.001). The initial alerts occurred within the first 12 months of monitoring. Relative risks were greater in three prespecified high‐risk subgroups: patients with diabetes, those 70 years of age or older, and women. All safety alerts were confirmed in an independent sample of 48,992 patients from April 1, 2014, to September 30, 2015. CONCLUSIONS A strategy of prospective, active surveillance of a clinical registry rapidly identified potential safety signals among recipients of an implantable vascular‐closure device, with initial alerts occurring within the first 12 months of monitoring. (Funded by the Food and Drug Administration and others.)

Optimal Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Dual antiplatelet therapy (DAPT) is an essential component of treatment in patients with coronary artery disease treated with percutaneous coronary intervention (PCI). Recommendations for duration of DAPT after PCI should consider patient-specific risk, clinical presentation, stent characteristics, and procedural factors. Prolonged DAPT results in a reduction of stent thrombosis (ST) and myocardial infarction (MI) at the cost of increased bleeding. Studies of shorter-duration DAPT demonstrate similar mortality, MI, ST, and less bleeding when compared with longer DAPT duration. We review current evidence for strategies of prolonged DAPT and abbreviated DAPT following PCI.

Intracranial hemorrhage in a patient with sub-massive pulmonary embolism treated with EkoSonic endovascular system directed thrombolysis: ICH With EkoSonic System Directed Thrombolysis

Ultrasound‐assisted catheter‐directed thrombolysis therapy has emerged more recently as a management strategy for patients with intermediate risk pulmonary embolism and has shown promising results in clinical trials by early reversal of right ventricle dilation, reduced pulmonary hypertension, and decreased anatomic thrombus burden. This therapeutic strategy requires a small fraction of the systemic fibrinolytic dose and is therefore associated with a reduced bleeding risk. Although intracranial hemorrhage has not been reported in clinical trials, it is a possible complication. Here we report the first case of intracranial hemorrhage related to the use of EkoSonic™ Endovascular System directed thrombolysis in a patient with large bilateral pulmonary embolism without any identifiable bleeding risks.

Biomarkers enter the world of peripheral artery disease

Atherosclerotic disease is a pan-vascular process involving the coronary, cerebral, and peripheral arteries. Peripheral artery disease (PAD) is under-recognized by patients and health care providers alike, affects greater than 200 million people worldwide, and is strongly associated with incident coronary and cerebrovascular morbidity and mortality. Though classical descriptions of PAD symptoms invoke exertional extremity pain relieved by rest, accounts of claudication by the patient are in reality an exception. Instead, most patients are asymptomatic, present with atypical pain, and an additional unfortunate minority present with a threatened limb. Nonetheless, for those diagnosed with PAD, a range of evidence-based treatment options, including cardiovascular preventive measures, supervised exercise, antithrombotic medications, and catheter interventions or surgery to restore circulation are available. These treatments can improve quality of life, functional status, alleviate symptoms, and reduce mortality. The asymmetry between the recognition of PAD and the ability to offer meaningful treatments to patients suggests that tools that aid in the early identification of patients with or at risk of PAD may support efforts toward preventive, medical, and, when appropriate, interventional treatment strategies. To this end, there has been escalating interest in the potential role of cardiovascular biomarkers to improve the identification of patients with PAD. In this issue of the European Heart Journal, Matsushita and colleagues present their study exploring the utility of high-sensitivity cardiac troponin (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) as predictors of incident PAD and critical limb ischaemia (CLI). These candidate biomarkers, which have demonstrated utility in predicting cardiovascular risk in stable settings and beyond the coronary bed in prior studies, were evaluated in a diverse cohort of 12 288 patients without prevalent PAD from the Atherosclerotic Risk in Communities (ARIC) Study. The mean age of study patients was nearly 57 years, 55.7% were women, and 24.7% were black patients. The hs-cTnT and NT-proBNP levels were measured using prospectively collected serum samples, and clinical PAD and CLI were identified using previously validated ICD-9 discharge codes. The association between each cardiac biomarker with incident PAD and CLI was quantified according to five assay level categories, and adjusted for potential confounders using three different models incorporating cardiovascular risk factors. An independent dose-response association of hs-cTnT and NT-proBNP with incident PAD was discovered, with an approximately eight-fold higher risk among patients in the highest biomarker level groups (corresponding to the 99th percentile of healthy subjects) with consistently higher hazard ratios for NT-proBNP compared with hs-cTnT. Among patients who were identified as having CLI, the highest category of hs-cTnT was associated with 24-fold risk, and NT-proBNP was associated with a 10-fold risk of CLI. Overall, both biomarkers were found to be more strongly correlated with CLI than PAD without CLI. The analysis was then repeated with stratification by demographic and clinical subgroups of particular interest, demonstrating consistent associations between biomarker levels and incident disease. Overall, this is a rigorously conducted observational study, using prospectively collected serum samples from a large historical cohort identifying significant associations between hs-cTnT and NT-proBNP levels and incident PAD and CLI. Among patients in the highest category of biomarker levels, after adjustment for some demographic factors, the association with incident disease was very strong. However, it should be noted that incorporating an adjustment model accounting for many traditional cardiovascular risk factors attenuated the final magnitude of association. Additionally, while the authors should be commended for formally evaluating the incremental change in risk discrimination utilizing these biomarkers, despite the strong association between hs-cTnT and CLI, hs-cTnT was unable to improve risk discrimination of CLI, and NT pro-BNP or both biomarkers together moved the needle only slightly. No combination of biomarkers led to significant changes in discrimination for PAD. This is likely because a model comprised of standard cardiovascular risk factors has relatively good discrimination for PAD and CLI, as

Transulnar angiography and intervention: The next frontier in vascular access?

This study demonstrates that in a single center, single operator experience, ulnar artery catheterization is feasible, though even compared to radial access, a significant learning curve remains. Although ulnar access is a reasonable alternative approach to catheterization, the true benefits of ulnar access, compared to radial are unclear. Further large randomized multicenter, multi‐operator trials are needed to assess the true feasibility and benefit of ulnar artery catheterization.

Drug eluting stents in primary PCI: Ready for prime-time?

Great advancements in the areas of both percutaneous coronary intervention (PCI) technology and acute coronary syndrome (ACS) treatments have occurred at an exponential pace over the past decade. Early generation (sirolimus [SES], paclitaxel [PES]) drug eluting stents (DES) were shown to significantly reduce the rate of in-stent restenosis (ISR) and the need for target lesion revascularization, but this occurred at a cost of an increase in late stent thrombosis (ST). The enthusiasm for using DES in STEMI was tempered by concern regarding a patient’s ability to maintain long term dual antiplatelet therapy (DAPT), and the fact that during a STEMI, it is difficult to get a full sense of the patient’s medical and social history with certainty. Given this, the most current iteration of the 2013 STEMI guidelines cite a Class I recommendation, that any patient who has a high risk of bleeding, inability to comply with 12 months of DAPT, or an upcoming surgical or invasive procedure, should be treated with a bare metal stent [1]. The current guidelines do not advocate a preference for DES in STEMI. Early studies of second generation (everolimus [EES], zotarolimus [ZES]) DES suggest equivalent efficacy with improved safety compared to the use of first generation DES, and even compared with BMS. Additionally, a recent meta-analysis suggests reduced risk of target vessel revascularization (TVR) and ST with newer generation DES in STEMI compared to bare metal stent (BMS) [2]. As this literature has been mounting, operators have begun to rethink the role of DES in STEMI. In this week’s issue of CCI [3], Garg et al. report an analysis of 3,464 STEMI patients treated with PCI using BMS, early generation (PES and SES) DES or new generation (EES and ZES) DES, at one of two busy primary PCI centers. The patients were prospectively enrolled into a database over an 8-year period, and the primary operator determined the choice of stent at the time of intervention. Interestingly, some of these patients received half dose lytic on transfer to the cath lab. Among patients receiving early generation DES, 1,094 received PES and 431 received SES. Of those receiving new generation DES, 679 received EES, and 73 received ZES; 1,187 patients received BMS. Unadjusted 30-day outcomes suggested reduced cardiac mortality and similar rates of reinfarction and ST with DES compared to BMS. This mortality benefit persisted over a 2 year follow up. The 2-year outcomes also suggested a lower rate of ST with new generation DES compared to BMS. Thirty day event rates were similar between new and old generation DES, with a trend toward reduced rate of ST at 2 years with new generation DES. A propensity adjusted analysis demonstrated reduction in cardiac mortality with new generation DES compared to BMS and early generation DES, and reduced rates of ST with DES compared to BMS. With this analysis, Garg et al. suggest not only equivalent but also enhanced safety with new generation DES, as demonstrated by reductions in mortality and rates of ST compared with BMS. By demonstrating these results in a real world population of acute MI patients, they feel this data supports the use of new generation DES for treatment of STEMI. Additionally, the data is consistent with the SCAAR registry, a recently published registry of 34,147 patients with STEMI, which echoed similar findings [4]. However, there are several important limitations to this study that warrant consideration. Despite prospective enrollment, patients were not randomized to BMS or DES. The unadjusted baseline variables among the three groups were markedly different in several important areas: patients who received new generation DES patients were younger, had less frequency of smoking, less cardiogenic shock, and less prior infarction, suggesting a significantly lower baseline risk. To reduce the effect of these covariates, the authors provided a

Antiplatelet Therapy in Diabetes

Cardiovascular disease (CVD) is a significant cause of morbidity and mortality among patients with diabetes mellitus (DM). Increased platelet reactivity among patients with DM contributes to disproportionately high levels of atherothrombotic CVD. Consequently, there has been tremendous interest in exploring the role of antiplatelet therapies in DM to reduce the development of and frequency of future cardiovascular events.

Public Reporting: Small Changes Lead to Minimal Impact

Public reporting policies have been implemented based, in part, on the belief that hospitals and providers will improve processes of care in response to the awareness of being observed (the Hawthorne effect) while simultaneously assuming that access to care will remain constant. Unfortunately, several reports have emerged, suggesting that public reporting may influence clinical treatment decisions and lead to avoidance of high-risk patients.1–3 Physicians in public reporting environments fear being labeled as negative outliers and express concern that current risk-adjustment models are inadequate to account for patients at the extremes of risk. In response to these concerns, regulators in some states have modified existing public reporting policies by introducing exceptions for uniquely high-risk patients. For example, in 2006, the New York State Department of Public Health began censoring patients with refractory cardiogenic shock from analysis of operator mortality after percutaneous coronary intervention (PCI). This resulted in an increase in rates of coronary angiography and PCI and overall decline in mortality of patients presenting with cardiogenic shock.4 In 2010, New York began censoring patients with cardiac arrest complicated by anoxic brain injury who subsequently died. The impact of this policy change had until now been unstudied. See Article by Strom et al In this issue of Circulation: Cardiovascular Interventions , Strom et al5 report their evaluation of the impact of excluding patients with anoxic brain injury after cardiac arrest from analysis of operator PCI mortality in the New York State public report. This retrospective, observational study used administrative claims data from State Inpatient Databases for New York and additional comparator states between 2003 and 2013 to compare rates of coronary angiography, revascularization, and mortality in patients with cardiac arrest after acute myocardial infarction (AMI) before and after introduction of the 2010 exclusion rule. Comparator states were …

Multivessel stent thrombosis with optical coherence tomography (OCT) utilization for therapeutic guidance

A 63 year old male presents with anterior ST elevation myocardial infarction. Two years prior he had PCI with DES to the proximal left anterior descending (LAD) and circumflex arteries following an abnormal stress test. Clopidogrel was discontinued several weeks prior to this presentation.

Catheter ablation as first-line treatment for paroxysmal atrial fibrillation: rarely a good value

This editorial refers to ‘The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from aMANTRA-PAF substudy?’ by M.A. Aronsson et al ., on page 48–55. Over the past 10–15 years, catheter ablation has become an established treatment for patients with atrial fibrillation (AF) who prefer rhythm control. Based on multiple randomized trials, ablation is now strongly recommended (Class I, level of evidence A)1,2 as a second-line treatment for paroxysmal AF. In the second-line setting, the evidence that ablation is more effective than antiarrhythmic drugs at maintaining sinus rhythm is overwhelming,3 and this superior efficacy is accompanied by meaningful gains in quality of life.4 Additionally, these trials have formed the foundation for several cost-effectiveness (CE) models, which have consistently reported that ablation provides reasonable if not exceptional value in health economic terms. Previously published studies have found that the CE of AF ablation is contingent on the therapy improving the quality of life (and possibly reducing the risk of stroke) and sensitive to assumptions about time horizon.5,6 In contrast to the second-line setting, available data suggest that catheter ablation is only marginally more effective than antiarrhythmic drugs as a first-line treatment for paroxysmal AF. Data on this topic derive primarily from two completed multi-centre trials: Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF)7 and Radiofrequency Ablation vs. Antiarrhythmic drugs for atrial …