Staged Versus One-time Complete Revascularization With Percutaneous Coronary Intervention for Multivessel Coronary Artery Disease Patients Without ST-Elevation Myocardial Infarction
Background— There are evidence-based guidelines for staging of patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), but we are not aware of any evidence comparing the strategy of complete revascularization (CR) with PCI in the index admission versus the strategy of staging in a subsequent admission for patients with coronary artery disease without STEMI. Methods and Results— PCI patients without STEMI undergoing PCI in New York between 2007 and 2009 were separated into 2 groups: those with acute coronary syndrome but no STEMI, and those without acute coronary syndrome. For each group, patients who underwent CR in the index admission were then propensity matched to patients staged within 60 days to obtain CR based on 17 patient risk factors related to longer-term mortality, and 3-year mortality rates were compared for the propensity-matched groups. Outcomes were also compared for preselected subgroups. For propensity-matched patients without acute coronary syndrome, the all-cause mortality rates at 3 years for patients who underwent CR in the index hospitalization and patients staged for CR within 60 days of discharge were 5.62% and 5.97%, P =0.93, respectively. For propensity-matched patients with acute coronary syndrome but without STEMI, the all-cause mortality rates at 3 years for patients who underwent CR in the index hospitalization and patients staged for CR within 60 days of discharge were 6.59% and 5.92%, P =0.41, respectively. Conclusions— Patients with coronary artery disease without STEMI do not have significantly lower 3-year mortality rates with staged PCI than when they undergo CR in the index admission.
Survival After Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy
Background— The clinical efficacy of alcohol septal ablation for obstructive hypertrophic cardiomyopathy (HCM) has been demonstrated, but the long-term effects of the procedure remain uncertain. This study examined the survival of patients after septal ablation performed in a tertiary HCM referral center. Methods and Results— We examined 177 patients (mean age, 64 years; 68% women) who underwent septal ablation at our institution. Over a follow-up of 5.7 years, survival free of all mortality was no different than the expected survival for a comparable general population, and similar to that of age- and sex-matched patients who underwent isolated surgical myectomy (8-year survival estimate, 79% versus 79%; P =0.64). For the end point of documented sudden cardiac death or unknown cause of death, the incidence per 100 person-year follow-up was 1.31 (95% confidence interval, 0.60–2.38). Residual left ventricular outflow tract gradient after ablation was an independent predictor of long-term survival free of any death. Conclusions— In this nonrandomized study of carefully selected patients undergoing septal ablation by experienced operators in a tertiary referral HCM center, long-term survival was favorable and similar to that of an age- and sex-matched general population, and to patients undergoing surgical myectomy, as well, without an increased risk of sudden cardiac death.
Complete Versus Incomplete Revascularization With Coronary Artery Bypass Graft or Percutaneous Intervention in Stable Coronary Artery Disease
Abstract —Insulin and insulin-like growth factor (IGF) 1 affect coronary vasoactivity. Experimental hypercholesterolemia is associated with coronary atherogenesis and altered vasomotor regulation. Because the IGF axis is altered during atherogenesis, we postulated that experimental hypercholesterolemia is associated with an altered coronary vasoactive response to IGF-1 in vitro. Coronary arteries and arterioles from pigs fed either a normal or high-cholesterol diet for 10 weeks were contracted with endothelin-1 and relaxed with cumulative concentrations of insulin or IGF-1 (10 −12 to 10 −7 mol/L). Control arterioles were also incubated with the nitric oxide synthase inhibitor 10 −4 mol/L N G -monomethyl- l -arginine (L-NMMA) or the potassium channel blocker 10 −2 mol/L tetraethylammonium (TEA), contracted with endothelin-1, and relaxed with insulin or IGF-1. Experimental hypercholesterolemia (1) increased serum cholesterol (9.5±1.0 versus 1.9±0.08 mmol/L; P <0.0001), (2) caused coronary arterial and arteriolar endothelial dysfunction in vitro (attenuated vasorelaxation to bradykinin), (3) did not alter the epicardial response to either insulin ( P =0.80) or IGF-1 ( P =0.12), and (4) significantly attenuated the arteriolar response to IGF-1 (maximal relaxation of 79±6% versus 42±8%; P =0.01) but not insulin (43±6% versus 53±7%; P =0.99). Control arteriolar vasorelaxation to IGF-1 was attenuated by both L-NMMA ( P <0.001) and TEA ( P =0.01), whereas only L-NMMA attenuated insulin ( P <0.001). Staining for IGF-1 and IGF binding protein 2 was increased ( P <0.05) in arterioles of cholesterol-fed pigs. IGF-1 and insulin are therefore coronary arteriolar vasorelaxants through different mechanisms. Experimental hypercholesterolemia is associated with resistance to the coronary arteriolar vasorelaxing effects of IGF-1 but not insulin, in conjunction with increased ligand and binding-protein expression. The IGF axis may contribute to the altered coronary vasoactivity in hypercholesterolemia.
Insulin and Insulin-like Growth Factor-I Cause Coronary Vasorelaxation In Vitro
Abstract—Insulin and insulin-like growth factor-I (IGF-I) may play a role in the modulation of coronary artery tone, yet there are few data regarding their vasoactive effects on the coronary vascular bed. We evaluated the vasorelaxation effects of insulin and IGF-I on porcine coronary epicardial vessels in vitro and elucidated possible mechanisms. Porcine epicardial arteries were contracted with 10−7mol/L endothelin-1 and relaxed with cumulative concentrations of either insulin or IGF-I (10−12to 10−7mol/L). The above experiments were repeated in vessels without endothelium. Vessels were also incubated with the nitric oxide synthase inhibitorNG-monomethyl-l-arginine (L-NMMA; 10−4mol/L) with and without 10−3.5mol/Ll-arginine, the potassium channel blocker tetraethylammonium (TEA; 10−2mol/L), and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-α]quinoxalin-1-one (ODQ; 10−5.5mol/L); vessels were then contracted with endothelin-1 and relaxed with insulin or IGF-I. Insulin and IGF-I were also added after contraction with 60 mmol/L KCl. Insulin and IGF-I caused a similar decrease in coronary epicardial tension after contraction with endothelin-1 (relaxation of 28±4% [n=7] and 25±3% [n=8] with insulin and IGF-I, respectively;P<0.0001 for both peptides). Removal of the endothelium did not affect these responses. Incubation with L-NMMA, but not ODQ, attenuated the vasorelaxation response to insulin and IGF in vessels without endothelium.l-Arginine did not reverse this effect of L-NMMA. KCl and TEA attenuated the vasorelaxation effect of both insulin and IGF-I. Thus, both insulin and IGF-I caused non–endothelium-dependent coronary vasorelaxation in vitro, probably through a mechanism involving the activation of potassium channels. These findings suggest that insulin and IGF-I participate in the regulation of coronary vasomotor tone.
One-Year Survival Among Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock, and its Relation to Early Revascularization
Background —Although 30-day survival is increased in patients with acute myocardial infarction complicated by cardiogenic shock who undergo coronary revascularization, the longer-term outcome in such patients and the duration of benefit from revascularization are unknown. Methods and Results —We analyzed 30-day survivors of acute myocardial infarction in the Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial and identified 36 333 who had not had cardiogenic shock (systolic blood pressure <90 mm Hg for ≥1 hour, group 1) and 1321 patients who had shock (group 2). Group 2 patients were older and sicker. At 1 year, 97.4% of group 1 patients were alive versus 88.0% of group 2 ( P =0.0001). Among group 2 patients, 578 (44%) had undergone revascularization within 30 days (group 2A) and 728 (56%) had not (group 2B). Revascularization was not required by protocol but was selected by the attending physicians. At 1 year, 91.7% of group 2A patients were alive versus 85.3% of group 2B ( P =0.0003). With the use of multivariable logistic regression analysis to adjust for differences in baseline characteristics of shock patients alive at 30 days, revascularization within 30 days was independently associated with reduced 1-year mortality (odds ratio 0.6, [95% confidence interval 0.4, 0.9], P =0.007). Conclusions —Most patients (88%) with acute myocardial infarction complicated by cardiogenic shock who are alive at 30 days survived at least 1 year. Shock patients who underwent revascularization within 30 days had improved survival at 1 year compared with shock patients who did not receive revascularization, even after adjustment for differences in baseline characteristics between the 2 groups.
Safety and Efficacy of Ticlopidine for Only 2 Weeks After Successful Intracoronary Stent Placement
Background —In patients receiving intracoronary stents, stent thrombosis is reduced when ticlopidine therapy is combined with aspirin after the procedure. However, ticlopidine causes neutropenia in 1% of patients when administered for >2 weeks, and little is known about the duration that ticlopidine needs be administered to prevent stent thrombosis. Methods and Results —We analyzed 827 patients undergoing successful stent placement in 1061 coronary segments at Mayo Clinic who were treated between May 1, 1996, and October 31, 1997. Chronic warfarin therapy, cardiogenic shock, and enrollment in research protocols requiring 4 weeks of ticlopidine were exclusion criteria; ticlopidine was discontinued after 14 days in all remaining patients. The mean age of the study population was 64±11 years; 49% had suffered a prior infarction, 20% had undergone coronary artery bypass surgery, and 65% had multivessel disease. The indication for stent placement was dissection or abrupt closure in 31% of patients and suboptimal results from balloon angioplasty in 18%. Placement was elective in 51% of patients, and 10.3% of patients were treated within 12 hours of an acute myocardial infarction. Mean nominal stent size was 3.3±0.5 mm. High-pressure inflations (≥12 atm) were performed in all patients (mean, 17±4 atm). Intravascular ultrasound was used to facilitate stent placement in 8.8% of patients. Abciximab was administered to 38% of patients; 11% of patients who were at increased risk of stent thrombosis were treated with enoxaparin for 10 to 14 days. Adverse cardiovascular events in the 14 days after stent placement occurred in 11 patients (1.3%). Two patients died of nonischemic causes (sepsis and renal failure) in the 15th through 30th days after ticlopidine was stopped. However, there were no cardiovascular deaths, myocardial infarctions, coronary artery bypass operations, or repeat angioplasty procedures between the 15th and 30th days; stent thrombosis did not occur in any patient after ticlopidine had been stopped. No patient developed neutropenia, although 1.8% of the first 489 patients who were closely monitored for side effects from ticlopidine developed side effects requiring its discontinuation, and milder side effects occurred in 4.7%. Conclusions —In patients receiving intracoronary stents, the discontinuation of ticlopidine therapy 14 days after stent placement is associated with a very low frequency of stent thrombosis and other adverse events.