Lawrence Ang

Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel.

OBJECTIVES The goal of this study was to identify factors associated with lower platelet inhibition (PI) with clopidogrel in subjects with cardiovascular disease (CVD). BACKGROUND A heterogeneous platelet reactivity response to clopidogrel exists, and the clinical or biochemical predictors of suboptimal PI with clopidogrel remain unclear. METHODS This study prospectively enrolled subjects with CVD requiring treatment with clopidogrel (75 mg daily for > or =7 days or 600-mg bolus > or =24 h before recruitment). A bedside rapid platelet function assay (VerifyNow, Acccumetrics, San Diego, California) to measure maximal and clopidogrel-mediated platelet reactivity was utilized, and factors associated with lower PI were identified. RESULTS A heterogeneous, normally distributed PI (mean 40.8 +/- 26.2%) response to clopidogrel was observed in 157 subjects (age 67.2 +/- 12.2 years; 59.9% men). Multiple variable analysis of clinical and biochemical factors known to affect platelet reactivity revealed lower PI in patients with an elevated plasma fibrinogen level (> or =375 mg/dl), diabetes mellitus, and increased body mass index (BMI) (> or =25 kg/m(2)). On testing for interaction, elevated fibrinogen level was associated with diabetic status, resulting in lower PI in diabetic patients (23.9 +/- 3.9% vs. 45.1 +/- 4.5%, p < 0.001), but not nondiabetic patients (44.7 +/- 4.4% vs. 46.3 +/- 4.8%, p = 0.244). Increased BMI remained independently associated with lower PI after clopidogrel therapy regardless of diabetic status or fibrinogen level (36.8 +/- 9.0% vs. 49.0 +/- 7.0%, p < 0.001). CONCLUSIONS Elevated plasma fibrinogen (> or =375 mg/dl) in the presence of diabetes mellitus and increased BMI (> or =25 kg/m(2)) are associated with lower PI with clopidogrel in patients with CVD.

Clinical efficacy of drug-eluting stents in diabetic patients: a meta-analysis

OBJECTIVES The purpose of this study was to compare estimates for revascularization and major adverse cardiac events (MACE) (death, myocardial infarction, repeat revascularization) in diabetic patients treated with paclitaxel- and sirolimus-eluting stents (PES and SES). BACKGROUND Outcomes in diabetic patients treated with PES and SES have not been adequately evaluated. METHODS We searched MEDLINE/EMBASE from January 2002 to February 2007 and identified abstracts/presentations from this period at major cardiology conferences. Randomized controlled trials (RCTs) and registries were included if data for diabetic patients treated with PES or SES were available. Point estimates with 95% confidence intervals (CIs) were computed as summary statistics. RESULTS In RCTs (13 trials; n = 2,422) similar point estimates for target lesion revascularization (TLR) (PES: 8.6%, 95% CI 6.5% to 11.3%; SES: 7.6%, 95% CI 5.8% to 9.9%) and MACE (PES: 15.4%, 95% CI 12.4% to 19.1%; SES: 12.9%, 95% CI 8.5% to 19.2%) were observed. In head-to-head trials (4 RCTs), no difference in the likelihood of TLR (PES vs. SES) was observed (odds ratio [OR] 1.37, 95% CI 0.64 to 2.9, p = 0.42). In registries (16 registries; n = 10,156), point estimates for target vessel revascularization (TVR) (PES: 5.8%, 95% CI 3.9% to 8.5%; SES: 7.2%, 95% CI 4.6% to 11.2%) and MACE (PES: 10.1%, 95% CI 7.3% to 13.8%; SES: 11.9%, 95% CI 8.6% to 16.4%) were also similar. In registries reporting outcomes with both stents (8 registries for TVR and 7 registries for MACE), the likelihood of TVR (PES vs. SES) (OR 0.77, 95% CI 0.54 to 1.10, p = 0.15) and MACE (OR 0.83, 95% CI 0.68 to 1.01, p = 0.056) were nonsignificantly lower with PES. CONCLUSIONS This analysis of over 11,000 diabetic patients treated with drug-eluting stents demonstrates single-digit revascularization rates. Furthermore, revascularization and MACE estimates are similar with both PES and SES.

Renal Frame Count and Renal Blush Grade: Quantitative Measures That Predict the Success of Renal Stenting in Hypertensive Patients With Renal Artery Stenosis

OBJECTIVES This study sought to identify angiographic parameters of favorable clinical response to renal artery stenting. BACKGROUND Stenting improves blood pressure (BP) control in patients with renal artery stenosis (RAS), but markers predicting a favorable clinical response are limited. METHODS Renal perfusion was quantified in hypertensive patients (BP >or=140/90 mm Hg) without RAS by determining renal frame count (RFC) (angiographic frames [30 frames/s] for contrast to reach distal renal parenchyma after initial renal artery opacification) and renal blush grade (RBG) (0: none, 1: minimal, 2: normal, 3: hyperemic parenchymal blush). It was hypothesized that stenting unilateral RAS in hypertensive patients would result in decreased RFC and increased RBG, which might predict BP reduction. RESULTS The RFC in 17 consecutive hypertensive patients without RAS (control group) (64.4 +/- 14.2 years, 12 male, 22 kidneys) was 20.1 +/- 5.4, whereas RBG was 2.33 +/- 0.66. In 24 consecutive hypertensive patients with unilateral RAS (study group) (72.7 +/- 11.3 years, 8 male), reduced RFC (26.6 +/- 9.1 to 21.4 +/- 6.7, p < 0.001) and increased RBG (1.63 +/- 0.71 to 2.13 +/- 0.85, p = 0.03) were observed after renal stenting. At 6 months, reduced BP (systolic BP 150.6 +/- 15.6 mm Hg to 128.6 +/- 15.5 mm Hg, p < 0.001; diastolic BP 77.2 +/- 15.6 mm Hg to 68.3 +/- 10.4 mm Hg, p = 0.022) without change in number of hypertensive medications was observed. Clinical responders (systolic BP reduction >15 mm Hg) had a greater decrease in RFC (7.7 +/- 4.6 vs. 1.7 +/- 5.1, p = 0.009) and 78.6% of patients with >4 RFC decrease were responders (p = 0.024). CONCLUSIONS This study shows that quantitative indices of renal perfusion (RFC and RBG) are impaired in patients with RAS and improve after stenting, and that RFC reduction is associated with BP reduction.

Invasive Cardiologists Are Exposed to Greater Left Sided Cranial Radiation: The BRAIN Study (Brain Radiation Exposure and Attenuation During Invasive Cardiology Procedures).

OBJECTIVES This study sought to determine radiation exposure across the cranium of cardiologists and the protective ability of a nonlead, XPF (barium sulfate/bismuth oxide) layered cap (BLOXR, Salt Lake City, Utah) during fluoroscopically guided, invasive cardiovascular (CV) procedures. BACKGROUND Cranial radiation exposure and potential for protection during contemporary invasive CV procedures is unclear. METHODS Invasive cardiologists wore an XPF cap with radiation attenuation ability. Six dosimeters were fixed across the outside and inside of the cap (left, center, and right), and 3 dosimeters were placed outside the catheterization lab to measure ambient exposure. RESULTS Seven cardiology fellows and 4 attending physicians (38.4 ± 7.2 years of age; all male) performed diagnostic and interventional CV procedures (n = 66.2 ± 27 cases/operator; fluoroscopy time: 14.9 ± 5.0 min). There was significantly greater total radiation exposure at the outside left and outside center (106.1 ± 33.6 mrad and 83.1 ± 18.9 mrad) versus outside right (50.2 ± 16.2 mrad; p < 0.001 for both) locations of the cranium. The XPF cap attenuated radiation exposure (42.3 ± 3.5 mrad, 42.0 ± 3.0 mrad, and 41.8 ± 2.9 mrad at the inside left, inside center, and inside right locations, respectively) to a level slightly higher than that of the ambient control (38.3 ± 1.2 mrad, p = 0.046). After subtracting ambient radiation, exposure at the outside left was 16 times higher than the inside left (p < 0.001) and 4.7 times higher than the outside right (p < 0.001). Exposure at the outside center location was 11 times higher than the inside center (p < 0.001), whereas no difference was observed on the right side. CONCLUSIONS Radiation exposure to invasive cardiologists is significantly higher on the left and center compared with the right side of the cranium. Exposure may be reduced similar to an ambient control level by wearing a nonlead XPF cap. (Brain Radiation Exposure and Attenuation During Invasive Cardiology Procedures [BRAIN]; NCT01910272).

Elevated plasma fibrinogen rather than residual platelet reactivity after clopidogrel pre-treatment is associated with an increased ischemic risk during elective percutaneous coronary intervention.

OBJECTIVES This study was undertaken to determine the roles of serum fibrinogen and residual platelet reactivity after clopidogrel pre-treatment on ischemic events after elective percutaneous coronary intervention (PCI). BACKGROUND Both elevated serum fibrinogen and high platelet reactivity with thienopyridines are associated with ischemic cardiovascular events. Elevated fibrinogen also contributes to high on-clopidogrel platelet reactivity. It is unknown whether fibrinogen and residual platelet reactivity are associated with adverse cardiovascular events through independent or interactive effects. METHODS A total of 189 patients undergoing elective PCI with clopidogrel pre-treatment (75 mg daily for ≥7 days or a 600-mg bolus ≥12 h before recruitment) were prospectively enrolled. Baseline fibrinogen and platelet function using the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) were obtained. Markers of ischemic myocardial injury were measured every 8 h after PCI. RESULTS Incidence of troponin-defined periprocedural myocardial infarction (PPMI) (troponin I/T >3× upper limit of normal) was 13.9% and associated with elevated fibrinogen (363.1 ± 131.0 mg/dl vs. 309.1 ± 99.6 mg/dl; p = 0.017), higher age (68.2 ± 10.1 years vs. 63.0 ± 11.8 years; p = 0.040), and elevated platelet count. Fibrinogen level and age remained independently associated with PPMI following multiple variable and interaction testing. The incidence of creatine kinase-myocardial band (CK-MB)-defined PPMI (CK-MB >3× upper limit of normal) was 5.8% and associated with elevated fibrinogen (403.4 ± 128.0 mg/dl vs. 313.5 ± 104.6 mg/dl; p = 0.007). Platelet reactivity measurements were not associated with PPMI by either definition. Fibrinogen ≥345 mg/dl was significantly associated with both CK-MB-defined (p = 0.026) and troponin I/T-defined PPMI (p = 0.036). Fibrinogen effects were most prominent in the absence of systemic inflammation (C-reactive protein ≤0.5 mg/dl). CONCLUSIONS Elevated fibrinogen is independently associated with the risk of ischemic myocardial injury following elective PCI with clopidogrel pre-treatment regardless of platelet reactivity as measured by the VerifyNow assay.

Monitoring oral antiplatelet therapy: is it justified?

Platelets play a key role in the initial formation and progression of intravascular thrombus. During coronary and peripheral vascular interventions, antiplatelet therapy is used to impair platelet reactivity in order to minimize adverse ischemic events. Chronic antiplatelet therapy is also administered to decrease the long term risk of major adverse cardiovascular events in patients with high atherothrombotic burden. However, due to a heterogeneous response to antiplatelet agents, a substantial number of patients with cardiovascular disease remain at risk despite adherence to therapy. Since the availability of point-of-care rapid platelet function assays, quick and reproducible evaluation of platelet function after the administration of aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors is possible. Various definitions of suboptimal platelet inhibition with oral antiplatelet therapy and associated risk factors are presented here. An algorithm to guide optimal antiplatelet therapy based on rapid platelet function testing during cardiovascular interventions is also presented.

Renal frame count: a measure of renal flow that predicts success of renal artery stenting in hypertensive patients.

Renal artery (RA) stenting can improve control of hypertension yet predicting clinical response remains difficult. We sought to determine the role of the renal frame count (RFC) (number of angiographic frames for contrast to reach distal renal parenchyma after initial RA opacification) as a predictor of improvement in blood pressure (BP) after RA stenting.

Robotic technology in interventional cardiology: Current status and future perspectives

Robotic technology has been utilized in cardiovascular medicine for over a decade, and over that period, its use has been expanded to percutaneous coronary and peripheral vascular interventions. The safety and feasibility of robotically assisted percutaneous cardiovascular interventions has been demonstrated in studies including simple to complex coronary lesions, and both iliac and femoropopliteal lesions. These reports have shown that robotically assisted PCI significantly reduces operator exposure to harmful ionizing radiation without a detrimental effect on procedural success or clinical efficacy. Additionally, the use of robotics has the intuitive benefit of alleviating the risk of orthopedic injuries faced by interventional operators. In addition to the interventional operator benefits, robotically assisted intervention has the potential for patient level benefit by allowing more accurate lesion length measurement, precise stent placement, and lower patient radiation exposure. However, further investigation is required to fully elucidate these potential benefits.

Elevated Serum Fibrinogen Is Associated With 12-Month Major Adverse Cardiovascular Events Following Percutaneous Coronary Intervention.

Elevated fibrinogen and higher on-thienopyridine platelet reactivity increase short-term major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI), but longer-term effects are unclear [(1,2)][1]. The current study, approved by the UC San Diego Institutional Review

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with several risk factors but is most frequently seen as a rare consequence of an acute pulmonary embolism. Surgical pulmonary thromboendarterectomy (PTE) is potentially curative for CTEPH with the best outcomes seen for the treatment of primarily proximal, accessible lobar or segmental disease. For surgically inoperable patients, percutaneous balloon pulmonary angioplasty (BPA) is feasible and has good short- to mid-term efficacy outcomes. This review focuses on the technique and outcomes associated with BPA which has emerged as a new therapeutic option for CTEPH.