Vachaspathi Palakodeti

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).

Fibromuscular dysplasia of renal arteries: Percutaneous revascularization based on hemodynamic assessment with a pressure measurement guidewire

Fibromuscular dysplasia (FMD) leading to renal artery stenosis and hypertension is one of the most common treatable causes of secondary hypertension. However, frequently it can be difficult to judge the anatomical severity of a stenotic lesion with various noninvasive and invasive imaging modalities. We present two patients with poorly controlled hypertension and FMD affecting the renal arteries, in whom there were no anatomically significant stenoses by renal magnetic resonance angiography or selective renal artery angiography. Utilizing a 0.014″ high fidelity micromanometer tipped PressureWire XT (Radi, Reading, MA), to measure intravascular pressure gradients throughout the diseased renal arteries, we identified physiologically significant stenoses, and successfully treated both patients with percutaneous transluminal angioplasty.

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.