High platelet reactivity on clopidogrel therapy correlates with increased coronary atherosclerosis and calcification: a volumetric intravascular ultrasound study.

OBJECTIVES: This study sought to evaluate the relationship between platelet reactivity and atherosclerotic burden in patients undergoing percutaneous coronary intervention (PCI) with pre-intervention volumetric intravascular ultrasound (IVUS) imaging. BACKGROUND: Atherosclerosis progresses by the pathologic sequence of subclinical plaque rupture, thrombosis, and healing. In this setting, increased platelet reactivity may lead to more extensive arterial thrombosis at the time of plaque rupture, leading to a more rapid progression of the disease. Alternatively, abnormal vessel wall biology with advanced atherosclerosis is known to enhance platelet reactivity. Therefore, it is possible that by either mechanism, increased platelet reactivity may be associated with greater atherosclerotic burden. METHODS: This study included patients who underwent PCI with pre-intervention IVUS imaging and platelet reactivity functional assay (P2Y(12) reaction units) performed >16 h after PCI, after the stabilization of clopidogrel therapy (administered before PCI). Platelet reactivity >230 P2Y(12) reaction units defined high on-treatment platelet reactivity (HPR). RESULTS: Among 335 patients (mean age 65.0 years, 71% men), there were 109 patients with HPR (32.5%) and 226 without HPR (67.5%), with HPR being associated with diabetes and chronic renal insufficiency. By IVUS analysis, patients with HPR had significantly greater target lesion calcium lengths, calcium arcs, and calcium indexes. Furthermore, patients with HPR tended to have longer lesions and greater volumetric dimensions, indicating higher plaque volume, larger total vessel volume, and also greater luminal volume, despite similar plaque burden. By multivariate analysis controlling for baseline clinical variables, HPR was the single consistent predictor of all IVUS parameters examined, including plaque volume, calcium length, and calcium arc. CONCLUSIONS: Increased platelet reactivity on clopidogrel treatment, defined as >230 P2Y(12) reaction units, is associated with greater coronary artery atherosclerotic disease burden and plaque calcification.

Long-term outcome of percutaneous coronary intervention for chronic total occlusions.

OBJECTIVES: The aim of this study was to evaluate long-term clinical outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). BACKGROUND: Despite technical advancements, there is a paucity of data on long-term outcomes after PCI of CTO. METHODS: We evaluated long-term clinical outcomes in 1,791 patients who underwent PCI of 1,852 CTO at 3 tertiary care centers in the United States, South Korea, and Italy between 1998 and 2007. Median follow-up was 2.9 years (interquartile range: 1.5 to 4.6 years). RESULTS: Procedural success was obtained in 1,226 (68%) patients. Stents were implanted in 1,160 patients (95%); 396 patients (34%) received bare-metal stents (BMS), and 764 patients (66%) received drug-eluting stents (DES). After multivariable analysis, successful CTO PCI was an independent predictor of a lower cardiac mortality (hazard ratio [HR]: 0.40, 95% confidence interval [CI]: 0.21 to 0.75, p < 0.01) and reduced need for coronary artery bypass graft surgery (HR: 0.21, 95% CI: 0.13 to 0.40, p < 0.01); it also correlated with a strong trend toward lower all-cause mortality (HR: 0.63, 95% CI: 0.40 to 1.00, p = 0.05) at 5-year follow-up. Among patients who underwent stent implantation, treatment with DES rather than BMS resulted in less target vessel revascularization at long-term follow-up (17.2% vs. 31.1%, p < 0.01); definite/probable stent thrombosis rates were similar (DES 1.7%, BMS 2.3%, p = 0.58). Within the DES subgroup, patients treated with paclitaxel-eluting stents and sirolimus-eluting stents had similar clinical outcomes. CONCLUSIONS: Successful CTO PCI is associated with reduced long-term cardiac mortality and need for coronary artery bypass graft surgery. Treatment of CTO with DES rather than BMS is associated with a significant reduction in target vessel revascularization with similar rates of stent thrombosis. Paclitaxel-eluting stents and sirolimus-eluting stents had similar long-term safety and efficacy outcomes.

Successful use of nitazoxanide in the treatment of recurrent Clostridium difficile infection.

A 78-year-old, retired Caucasian male presented in emergency room with 3 days history of progressive watery diarrhoea. Two weeks earlier, he received intravenous levofloxacin for community acquired pneumonia. The patient was diagnosed as severe Clostridium difficile infection based on clinical presentation, labs and imaging studies. The patient was initially treated with intravenous metronidazole and oral vancomycin. While awaiting subacute rehabilitation placement, the patient relapsed twice. After first recurrence the patient was treated with 2 weeks of oral nitazoxanide. After second recurrence, the patient was treated 2 weeks of nitazoxanide followed by tapering dose of vancomycin. The patient was followed and no relapse was reported at 1 year follow-up visit.

Myoblast transfer in ischemic heart failure: effects on rhythm stability.

Skeletal myoblast (SM) implantation promotes recovery of myocardial function after ischemic injury. Clinical observations suggest an association of SM implantation and ventricular arrhythmias. Support for this link has been sought in animal studies, but none employing models of congestive heart failure. In a canine model of postinfarction congestive heart failure (CHF) we compared the frequency of rhythm disturbances using ambulatory electrocardiography monitoring following skeletal myoblast or saline (SAL) implantation. In 19 mongrel dogs ischemic injury and CHF were induced by intracoronary microsphere infusions. Direct intramyocardial injection of autologous skeletal myoblasts (ASM) (2.7-8.3 x 10(8) cells) or SAL controls was administered to 11 and 8 dogs, respectively. Serial echocardiography and 24-h ambulatory electrocardiography were recorded at baseline (after CHF induction) and at 4 weeks and at 8-10 weeks after injection. Comparisons between groups of left ventricular ejection fraction (LVEF) and the frequency of ventricular arrhythmias, supraventricular arrhythmias, and measures of heart rate variability (HRV) were made at each of the three time points. LVEF increased from 41 +/- 6% to 47 +/- 2% (p < 0.03) in the ASM group, and did not change (42 +/- 6% to 40 +/- 2%, p = ns) in SAL. After injection, no differences were seen in the number of dogs demonstrating ventricular tachycardia (n = 3 vs. n = 2, p = ns) or frequent PVCs (n = 3 vs. n = 3, p = ns) in the ASM versus SAL groups, respectively. Significant changes were observed in a time-domain measure of HRV, standard deviation of normal-to-normal RR interval (in ms: 4 weeks 174 +/- 95 vs. 242 +/- 19; 8 weeks 174 +/- 78 vs. 276 +/- 78, ASM vs. SAL), but not in other time domain parameters. In this canine model of ischemic CHF, ASM implantation did not result in a significant increase in ventricular arrhythmias compared to controls animals. The potential for ASM implantation to affect time-domain parameters of HRV merits further study.