Joshua P. Loh

Paclitaxel Drug-Coated Balloons : A Review of Current Status and Emerging Applications in Native Coronary Artery De Novo Lesions

The paclitaxel drug-coated balloon (DCB) is an emerging device in percutaneous coronary intervention, which has shown promising results by means of a high-concentration, rapid local release of an antirestenotic drug without the use of a durable polymer or metal scaffold. DCB have already proven effective in clinical trials for the treatment of in-stent restenosis. Its coronary applications may potentially be widened to a host of complex coronary de novo lesion subsets, such as small-caliber vessels, diabetes, and diffuse lesions, where the use of stents may be hampered by suboptimal results. Recently, this technology has rapidly evolved with newer studies added to assess the value of DCB in coronary applications other than in-stent restenosis. We present a review of the role of DCB in de novo coronary lesions based on this latest clinical evidence.

Overview of the 2011 Food and Drug Administration Circulatory System Devices Panel of the Medical Devices Advisory Committee Meeting on the CardioMEMS Champion Heart Failure Monitoring System.

The CardioMEMS Champion Heart Failure Monitoring System (CardioMEMS, Atlanta, Georgia) is a permanently implantable pressure measurement system designed to wirelessly measure and monitor pulmonary artery (PA) pressure and heart rate in heart failure (HF) patients to guide ambulatory HF management and to reduce HF hospital stays. On December 8, 2011, the Food and Drug Administration (FDA) Circulatory System Device Panel reviewed the CardioMEMS Champion HF Monitoring System premarket approval (PMA) application. The majority of Panel members agreed that that the discussed monitoring system is safe for use in the indicated patient population. However, new information reported by the FDA with regard to preferential support in management of patients in the treatment group raised concerns among the Panel members with regard to potential bias in analyzing the efficacy of the device itself. Additionally, Panel members raised concerns with regard to the efficacy of the device in certain patient subpopulations. Hence, most Panel members decided that there was not reasonable assurance that the discussed monitoring system is effective. This summary aims to describe the discussions and recommendations made during this meeting.

Two-Year Follow-Up of Outcomes of Second-Generation Everolimus-Eluting Stents Versus First-Generation Drug-Eluting Stents for Stenosis of Saphenous Vein Grafts Used as Aortocoronary Conduits

Second-generation everolimus-eluting stents (EESs) have demonstrated superiority in efficacy and safety compared with first-generation drug-eluting stents (DESs) in the treatment of native coronary artery lesions. The present study evaluated and compared the safety and efficacy of EESs and first-generation DESs in saphenous vein graft lesions. The EES group consisted of 88 patients with 96 lesions, and the first-generation DES group consisted of 243 patients with 317 lesions (sirolimus-eluting stents, n = 212; paclitaxel-eluting stents, n = 105). The end points included target lesion revascularization, target vessel revascularization, major adverse cardiovascular events (composite of all-cause death, myocardial infarction, and target vessel revascularization), and definite stent thrombosis at 2 years. The groups had similar baseline characteristics and graft ages (128.1 ± 77.5 vs 132.4 ± 90.8 months, p = 0.686). The EES group had more type C lesions and less embolic protection device use. The peak postprocedure values of creatinine kinase-MB and troponin I were similar between the 2 groups. Overall, major adverse cardiovascular events occurred in 18.2% of EES patients and 35.0% of first-generation DES patients (p = 0.003), mainly driven by a lower target vessel revascularization rate (6.8% vs 24.5%, p <0.001). The target lesion revascularization rate was lower in the EES group (1.1% vs 11.6%, p = 0.005). Stent thrombosis was low and similar between the 2 groups (0% vs 0.8%, p = 1.000). On multivariate analysis, the type of DES implanted and graft age were the only independent predictors of major adverse cardiovascular events. In conclusion, the superiority of EESs compared with first-generation DESs shown in native artery lesions has been extended to saphenous vein graft lesions and should be considered as the DES of choice for this lesion type.

Comparison of Adverse Outcomes After Contemporary Percutaneous Coronary Intervention in Women Versus Men With Acute Coronary Syndrome

Previous studies have shown a relation between female gender and adverse outcomes after percutaneous coronary intervention (PCI). The aim of this study was to determine whether there are differences in correlates between genders for these long-term adverse outcomes in patients with acute coronary syndromes. Gender differences were evaluated in the clinical outcomes of 6,929 consecutive patients with acute coronary syndromes from a large, contemporary PCI registry. Rates of major adverse cardiovascular events, defined as all-cause mortality, myocardial infarction, and target lesion revascularization at 1-year follow-up, are reported. Independent correlates of adverse outcomes were identified using multivariate proportional-hazards regression analysis. Women were older (p <0.001); had a higher prevalence of diabetes mellitus (p <0.001), systemic hypertension (p <0.001), chronic renal insufficiency (p = 0.02), peripheral arterial disease (p <0.001), and congestive heart failure (p <0.001); had lower body surface areas (p <0.001); and had higher body mass indexes (p <0.001). Acute coronary syndrome presentation in women tended to be unstable angina pectoris with Canadian Cardiovascular Society class III and IV symptoms, whereas men had more acute myocardial infarctions. At 1 year, the unadjusted rates of all-cause mortality (10.7% vs 7.5%, p <0.001) and major adverse cardiovascular events (16.4% vs 12.7%, p <0.001) were higher in women. There was a stark difference between the genders in independent correlates of mortality and major adverse cardiovascular events at 1 year. Moreover, the traditional correlates did not have the same impact in women as in men. In conclusion, although there are differences in clinical outcomes after PCI for women compared with men, there are different correlates for these adverse outcomes. These gender-based differences should be taken into account when women undergo contemporary PCI.

Safety of Reloading Prasugrel in Addition to Clopidogrel Loading in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) commonly receive a loading dose of either clopidogrel or prasugrel, in addition to aspirin. The present study aimed to assess the safety of reloading prasugrel in patients who had initially received a loading dose of clopidogrel compared to prasugrel loading alone. The study included a cohort of 606 consecutive patients with acute coronary syndrome who had received a 60-mg loading dose of prasugrel before PCI. These patients were then categorized into clopidogrel preloading (300 or 600 mg) followed by prasugrel reloading (CP-load group, n = 90) and prasugrel loading only (P-load group, n = 516). Both groups received a 10-mg maintenance dose of prasugrel after PCI. The primary end point was in-hospital Thrombolysis In Myocardial Infarction-defined major bleeding. The secondary end points were other in-hospital bleeding complications and major cardiovascular events. Patients in the CP-load group compared to the P-load group were younger, with lower rates of cardiovascular risk factors. Significantly more patients in the CP-load group presented with biomarker-positive myocardial infarction (80.0% vs 30.6%, p ≤0.001) and cardiogenic shock (5.6% vs 1.4%, p = 0.022). No significant differences (p = NS) were seen in Thrombolysis In Myocardial Infarction major bleeding (2.6% vs 2.8%), Thrombolysis In Myocardial Infarction major or minor bleeding (12.2% vs 7.0%), the need for blood transfusion (2.6% vs 2.1%), and vascular complications (1.3% vs 2.0%) between groups. The CP-load group experienced more in-hospital major adverse cardiac events (5.6% vs 1.6%, p = 0.031), urgent coronary artery bypass grafting (3.3% vs 0.2%, p = 0.011), and longer hospital and intensive care unit stays. In conclusion, preloading with clopidogrel should not be prohibitive to reloading with prasugrel in patients presenting with acute coronary syndrome and undergoing PCI with respect to bleeding and vascular complications.

The state of the excimer laser for coronary intervention in the drug-eluting stent era

OBJECTIVES This study aims to determine how excimer laser coronary atherectomy (ELCA) performs in the drug-eluting stent (DES) era. BACKGROUND For more than 20 years, ELCA has been used for coronary intervention. With developments in the coronary intervention field, the role of ELCA is in question. METHODS The study includes 119 patients with 124 lesions who underwent percutaneous coronary intervention (PCI) with ELCA in our institution from January 2004 to May 2011. RESULTS The main indications for ELCA use were saphenous vein graft (SVG) (45 lesions), acute myocardial infarction (AMI) (7 lesions), chronic total occlusion (CTO) (32 lesions), in-stent restenosis (ISR) (15 lesions), and calcified de-novo lesions (25 lesions). High success rates were recorded for the SVG, AMI, CTO, ISR, and calcified lesion indications (91.1%, 85.7%, 93.8%, 86.7%, and 80%; respectively). ELCA related complications were reported in 10 patients (8%); four dissections, three no-reflow phenomena, two perforations, and one thrombus formation. CONCLUSION ELCA is an alternative solution with acceptable performance in the treatment of complex coronary lesions not ideally suitable for balloon angioplasty.

Acquired thrombocytopenia after transcatheter aortic valve replacement: clinical correlates and association with outcomes

AIMS This study aimed to evaluate incidence and correlates for low platelet count after transcatheter aortic valve replacement (TAVR) and to determine a possible association between acquired thrombocytopenia and clinical outcomes. METHODS AND RESULTS Patients undergoing TAVR from two medical centres were included in the study. They were stratified according to nadir platelet count post procedure: no/mild thrombocytopenia, ≥100 × 10(9)/L; moderate, 50-99 × 10(9)/L; and severe, <50 × 10(9)/L. A total of 488 patients composed of the study population (age 84.7 ± 7.5 years). At a median time of 2 days after TAVR, 176 patients (36.1%) developed significant thrombocytopenia: 149 (30.5%) moderate; 27 patients (5.5%) severe. Upon discharge, the vast majority of patients (90.2%) had no/mild thrombocytopenia. Nadir platelet count <50 × 10(9)/L was highly specific (96.3%), and a count <150 × 10(9)/L highly sensitive (91.2%), for predicting 30-day death (C-statistic 0.76). Patients with severe acquired thrombocytopenia had a significantly higher mortality rate at 1 year (66.7% for severe vs. 16.0% for no/mild vs. 20.1% for moderate; P < 0.001). In multivariate logistic regression, severe thrombocytopenia was independently associated with 1-year mortality (hazard ratio 3.44, CI: 1.02-11.6; P = 0.046). CONCLUSIONS Acquired thrombocytopenia was common after TAVR and was mostly resolved at patient discharge. The severity of thrombocytopenia after TAVR could be used as an excellent, easily obtainable, marker for worse short- and long-term outcomes after the procedure.

Clinical Presentation and Outcomes of Coronary In-Stent Restenosis Across 3-Stent Generations

Background—Clinical presentation of bare metal stent in-stent restenosis (ISR) in patients undergoing target lesion revascularization is well characterized and negatively affects on outcomes, whereas the presentation and outcomes of first- and second-generation drug-eluting stents (DESs) remains under-reported. Methods and Results—The study included 909 patients (1077 ISR lesions) distributed as follows: bare metal stent (n=388), first-generation DES (n=425), and second-generation DES (n=96), categorized into acute coronary syndrome (ACS) or non-ACS presentation mode at the time of first target lesion revascularization. ACS was further classified as myocardial infarction (MI) and unstable angina. For bare metal stent, first-generation DES and second-generation DES, ACS was the clinical presentation in 67.8%, 71.0%, and 66.7% of patients, respectively (P=0.470), whereas MI occurred in 10.6%, 10.1%, and 5.2% of patients, respectively (P=0.273). The correlates for MI as ISR presentation were current smokers (odds ratio, 3.02; 95% confidence interval [CI], 1.78–5.13; P<0.001), and chronic renal failure (odds ratio, 2.73; 95% CI, 1.60–4.70; P<0.001), with a protective trend for the second-generation DES ISR (odds ratio, 0.35; 95% CI, 0.12–1.03; P=0.060). ACS presentations had an independent effect on major adverse cardiac events (death, MI, and re-target lesion revascularization) at 6 months (MI versus non-ACS: adjusted hazard ratio, 4.06; 95% CI, 1.84–8.94; P<0.001; unstable angina versus non-ACS: adjusted hazard ratio, 1.98; 95% CI, 1.01–3.87; P=0.046). Conclusions—ISR clinical presentation is similar irrespective of stent type. MI as ISR presentation seems to be associated with patient and not device-related factors. ACS as ISR presentation has an independent effect on major adverse cardiac events, suggesting that ISR remains a hazard and should be minimized.

The current status of drug-coated balloons in percutaneous coronary and peripheral interventions

Through continued innovation, percutaneous treatment of coronary and peripheral stenoses has evolved rapidly since balloon angioplasty was first introduced three decades ago. Significant advances were made with the introduction of bare metal stents and subsequently drug-eluting stents, which expanded the possibility of successful revascularisation in complicated lesions. Despite these advantages, efforts are still ongoing to improve patient outcomes further. In recent years, drug-coated balloons have emerged as an exciting technology developed to overcome the limitations faced by drug-eluting stents, such as stent thrombosis and dependency on prolonged dual antiplatelet therapy, and may prove efficacious in complex subsets such as small vessels and diffuse lesions where stent results are suboptimal. Several drug-coated balloons developed for coronary and peripheral applications were evaluated recently in preclinical and clinical studies with encouraging results. Drug-coated balloons have proven effective in treating in-stent restenosis; however, there is accumulating evidence on their utility in other clinical scenarios. We present a timely review of the mechanisms of action, key preclinical studies, emerging clinical indications, current clinical trial results, and future perspectives of this novel drug-coated balloon technology as it seeks to establish its role in percutaneous intervention.

Operator learning curve for transradial percutaneous coronary interventions: implications for the initiation of a transradial access program in contemporary US practice ☆ ☆☆

OBJECTIVES Our study aimed to assess the characteristics and outcomes of transfemoral approach (TFA) versus the initial steps of a transradial approach (TRA) program and to assess the learning curve of TRA in contemporary, US practice. BACKGROUND When compared to TFA, TRA has been shown to lower bleeding and vascular complications during percutaneous coronary intervention (PCI). However, use of TRA is still low. There are limited data regarding the characteristics of TRA learning curve, especially in an era with designated TRA equipment. METHODS Consecutive patients undergoing PCI in a single US center were divided into two cohorts according to vascular access approach: the last 250 TFA patients prior to the establishment of a TRA program and the initial 239 TRA patients following the establishment of a TRA program. Subgroup analysis of the TRA group, which was divided into five sequential case groups of 50 cases per group, was performed in order to assess TRA learning curve. RESULTS Overall, the baseline characteristics of TFA vs. TRA groups were comparable. Fluoroscopy time was significantly longer during TRA procedures (18±11 vs. 15±8min, respectively, p=0.002); however, contrast use was lower during TRA procedures (161±72 vs. 180±63ml, respectively, p=0.002). In-hospital outcomes were similar between the two groups, with low frequencies of mortality, myocardial infarction, and stent thrombosis. Subanalysis of TRA group for learning curve assessment showed no major differences in patient demographics among the five subgroups. In the initial cases, more PCI was performed among non-acute cases (62% in patients 1-50 vs. 8-27% in patients 51-239, p<0.001). Despite these differences, characteristics of the treated vessels were similar between groups. There was no significant change in fluoroscopy time or in the amount of iodinated contrast volume delivered. Similarly, no differences in procedural, in-hospital, and long-term outcomes were documented. CONCLUSIONS Adopting TRA as a default is feasible for high-volume operators without significant learning curve effects.