Temporal trends in major angioplasty complications: technical issues and the case for on-site coronary surgery.

The need for on-site cardiac surgery has been a component of guidelines for the practice of elective and emergency percutaneous coronary intervention (PCI). However, proportions of cases requiring emergency coronary artery bypass grafting (CABG) post-PCI have fallen. This audit of complications of PCI confirms the very low incidence of need for emergency CABG, despite increasingly complex PCI caseload. Although the availability of stents/antiplatelet pharmacotherapy probably has contributed to improved PCI outcomes, the avoidance of emergency CABG is not contingent on either extensive use of glycoprotein IIb/IIIa inhibitors or strategies of universal stenting.

Stable angina and acute coronary syndromes are associated with nitric oxide resistance in platelets.

OBJECTIVES: The study examined possible clinical determinants of platelet resistance to nitric oxide (NO) donors in patients with stable angina pectoris (SAP) and acute coronary syndromes (ACS), relative to nonischemic patients and normal subjects. BACKGROUND: We have shown previously that platelets from patients with SAP are resistant to the antiaggregating effects of nitroglycerin (NTG) and sodium nitroprusside (SNP). METHODS: Extent of adenosine diphosphate (1 micromol/liter)-induced platelet aggregation (impedance aggregometry in whole blood) and inhibition of aggregation by NTG (100 micromol/liter) and SNP (10 micromol/liter) were compared in normal subjects (n = 43), nonischemic patients (those with chest pain but no fixed coronary disease, (n = 35) and patients with SAP (n = 82) or ACS (n = 153). Association of NO resistance with coronary risk factors, coronary artery disease (CAD), intensity of angina and current medication was examined by univariate and multivariate analyses. RESULTS: In patients with SAP and ACS as distinct from nonischemic patients and normal subjects, platelet aggregability was increased (both p < 0.01), and inhibition of aggregation by NTG and SNP was decreased (both p < 0.01). Multivariate analysis revealed that NO resistance occurred significantly more frequently with ACS than with SAP (odds ratio [OR] 2.3:1), and was less common among patients treated with perhexiline (OR 0.3:1) or statins (OR 0.45:1). Therapy with other antianginal drugs, extent of CAD, intensity of angina and coronary risk factors were not associated with variability in platelet responsiveness to NO donor. CONCLUSIONS: Patients with symptomatic ischemic heart disease, especially ACS, exhibit increased platelet aggregability and decreased platelet responsiveness to the antiaggregatory effects of NO donors. The extent of NO resistance in platelets is not correlated with coronary risk factors. Pharmacotherapy with perhexiline and/or statins may improve platelet responsiveness to NO.

Nitroglycerin tolerance in human vessels: evidence for impaired nitroglycerin bioconversion.

BACKGROUND: The basis for progressive attenuation of the effects of organic nitrates during long-term therapy (nitrate tolerance) remains controversial; proposed mechanisms include impaired nitrate bioconversion resulting in decreased release of nitric oxide (NO) from nitrates and/or increased NO clearance through a reaction with incrementally generated superoxide (O(2)(-)). METHODS AND RESULTS: Patients undergoing elective coronary artery bypass were randomized to receive 24 hours of intravenously infused nitroglycerin (NTG; nitrate group) or no nitrate therapy (control group). Discarded segments of the internal mammary artery and saphenous vein were used to examine (1) vascular responsiveness to NTG, sodium nitroprusside, and the calcium ionophore A23187; (2) bioconversion of NTG to 1,2- and 1,3-glyceryl dinitrate; and (3) the generation of O(2)(-). Responses to NTG were reduced 3- to 5-fold in vessels from the nitrate group compared with control vessels (P:<0. 01 for both types of segments), whereas responses to sodium nitroprusside and A23187 were unchanged. Tissue content of 1, 2-glyceryl dinitrate was lower (P:=0.012) in the saphenous veins from the nitrate group than in those from the control group. O(2)(-) generation was greater (P:<0.01) in internal mammary artery samples from the nitrate group than in those from the control group. However, incremental O(2)(-) generation induced by an inhibitor of superoxide dismutase did not affect NTG responses. CONCLUSIONS: NTG tolerance in patients with coronary artery disease is nitrate-specific and is associated with evidence of impaired NTG bioconversion. Tolerance was associated with incremental O(2)(-) generation, but short-term elevation of O(2)(-) did not affect NTG responsiveness, suggesting increased NO clearance by O(2)(-) has a minimal contribution to tolerance.

Early treatment with verapamil or diltiazem in patients with acute myocardial infarction: safety and possible beneficial effects.

While dihydropyridine calcium antagonists may be harmful in the immediate peri-infarction period, the effect of verapamil or diltiazem in these circumstances in uncertain. We utilized the GUSTO-1 formula to calculate the predicted 30-day mortality risk in a cohort of 352 patients with acute myocardial infarction presenting < 6 hours after onset of symptoms, with ECG changes consistent with eligibility for thrombolysis. All patients were treated with an intravenous bolus dose of verapamil followed by oral verapamil (240-360 mg/day) or diltiazem (180-360 mg/day), in the absence of specific contraindications. Predicted 30-day mortality risk was then compared with the actual 30-day mortality rate of the cohort. The actual 30-day mortality of the cohort was 3.7% (95% CI: 2.0,6.3); this was significantly lower than that predicted by the GUSTO-1 formula (7%). A similarly significantly lower mortality (7.5% vs 19.3%) was observed in a "high risk" subset of patients. Of the 13 patients who died, only 4 developed cardiogenic shock. It is concluded that verapamil and diltiazem can be administered safely in a selected patients with evolving acute transmural myocardial infarction. While the current data suggest that this form of treatment may be beneficial, definitive conclusions in this regard should await further randomized studies.