Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE).

BACKGROUND: Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), a substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, was a prospective, double-blind, 3x2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients. METHODS AND RESULTS: A total of 732 patients >/=55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were randomly assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E (RRR-alpha-tocopheryl acetate) 400 IU/d or their matching placebos. Average follow-up was 4.5 years. Atherosclerosis progression was evaluated by B-mode carotid ultrasound. The progression slope of the mean maximum carotid intimal medial thickness was 0.0217 mm/year in the placebo group, 0.0180 mm/year in the ramipril 2.5 mg/d group, and 0.0137 mm/year in the ramipril 10 mg/d group (P=0.033). There were no differences in atherosclerosis progression rates between patients on vitamin E and those on placebo. CONCLUSIONS: Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression. Vitamin E had a neutral effect on atherosclerosis progression.

Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).

BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

Primary stenting versus balloon angioplasty in occluded coronary arteries: the Total Occlusion Study of Canada (TOSCA).

BACKGROUND: Balloon angioplasty (PTCA) of occluded coronary arteries is limited by high rates of restenosis and reocclusion. Although stenting improves results in anatomically simple occlusions, its effect on patency and clinical outcome in a broadly selected population with occluded coronary arteries is unknown. METHODS AND RESULTS: Eighteen centers randomized 410 patients with nonacute native coronary occlusions to PTCA or primary stenting with the heparin-coated Palmaz-Schatz stent. The primary end point, failure of sustained patency, was determined at 6-month angiography. Repeat target-vessel revascularization, adverse cardiovascular events, and angiographic restenosis (>50% diameter stenosis) constituted secondary end points. Sixty percent of patients had occlusions of >6 weeks' duration, baseline flow was TIMI grade 0 in 64%, and median treated segment length was 30.5 mm. With 95.6% angiographic follow-up, primary stenting resulted in a 44% reduction in failed patency (10.9% versus 19.5%, P=0.024) and a 45% reduction in clinically driven target-vessel revascularization at 6 months (15.4% versus 8.4%, P=0.03). The incidence of adverse cardiovascular events was similar for both strategies (PTCA, 23.6%; stent, 23.3%; P=NS). Stenting resulted in a larger mean 6-month minimum lumen dimension (1.48 versus 1.23 mm, P<0.01) and a reduced binary restenosis rate (55% versus 70%, P<0.01). CONCLUSIONS: Primary stenting of broadly selected nonacute coronary occlusions is superior to PTCA alone, improving late patency and reducing restenosis and target-vessel revascularization.

Role of transesophageal echocardiography in the diagnosis and management of prosthetic valve thrombosis.

Thrombosis is a serious complication of heart valve replacement. Diagnosis is often difficult with previously reported techniques, including precordial two-dimensional echocardiography, suffering from low sensitivity and specificity. Management is similarly difficult, with a 40% to 50% reported mortality rate in early surgical series. Three cases are presented in which thrombosis of a left-sided prosthetic valve (one aortic, three mitral) was diagnosed by means of transesophageal echocardiography. All three patients were treated with streptokinase and had clinical and echocardiographic resolution. In one patient, who had recurrent thrombosis and received a second course of streptokinase, the course was complicated by a massive embolic stroke and death. Another patient with a recurrence underwent successful valve replacement. Transesophageal echocardiography is ideal for the diagnosis and follow-up of patients with prosthetic valve thrombosis. Although effective, thrombolysis in this setting is associated with a high risk of thromboembolic phenomena and significant risk of death. Thrombolytic therapy may be considered in highly selected patients who have an unacceptable risk for reoperation.

Absence of gender differences in clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction. A report from the SHOCK Trial Registry.

OBJECTIVES: The aim of this study was to assess the impact of gender on clinical course and in-hospital mortality in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated higher mortality for women compared with men with ST elevation myocardial infarctions and higher rates of CS after AMI. The influence of gender and its interaction with various treatment strategies on clinical outcomes once CS develops is unclear. METHODS: Using the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? (SHOCK) Registry database of 1,190 patients with suspected CS in the setting of AMI, we examined shock etiologies by gender. Among the 884 patients with predominant left ventricular (LV) failure, we compared the patient demographics, angiographic and hemodynamic findings, treatment approaches as well as the clinical outcomes of women versus men. This study had a 97% power to detect a 10% absolute difference in mortality by gender. RESULTS: Left ventricular failure was the most frequent cause of CS for both gender groups. Women in the SHOCK Registry had a significantly higher incidence of mechanical complications including ventricular septal rupture and acute severe mitral regurgitation. Among patients with predominant LV failure, women were, on average, 4.6 years older, had a higher incidence of hypertension, diabetes and a lower cardiac index. The overall mortality rate for the entire cohort was high (61%). After adjustment for differences in patient demographics and treatment approaches, there was no significant difference in in-hospital mortality between the two gender groups (odds ratio = 1.03, 95% confidence interval of 0.73 to 1.43, p = 0.88). Mortality was also similar for women and men who were selected for revascularization (44% vs. 38%, p = 0.244). CONCLUSIONS: Women with CS complicating AMI had more frequent adverse clinical characteristics and mechanical complications. Women derived the same benefit as men from revascularization, and gender was not independently associated with in-hospital mortality in the SHOCK Registry.

Cardiogenic shock complicating acute myocardial infarction--etiologies, management and outcome: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: This SHOCK Study report seeks to provide an overview of patients with cardiogenic shock (CS) complicating acute myocardial infarction (MI) and the outcome with various treatments. The outcome of patients undergoing revascularization in the SHOCK Trial Registry and SHOCK Trial are compared. BACKGROUND: Cardiogenic shock is the leading cause of death in patients hospitalized for acute MI. The randomized SHOCK Trial reported improved six-month survival with early revascularization. METHODS: Patients with CS complicating acute MI who were not enrolled in the concurrent randomized trial were registered. Patient characteristics were recorded as were procedures and vital status at hospital discharge. RESULTS: Between April 1993 and August 1997, 1,190 patients with CS were registered and 232 were randomized in the SHOCK Trial. Predominant left ventricular failure (78.5%) was most common, with isolated right ventricular shock in 2.8%, severe mitral regurgitation in 6.9%, ventricular septal rupture in 3.9% and tamponade in 1.4%. In-hospital Registry mortality was 60%, with ventricular septal rupture associated with a significantly higher mortality (87.3%) than all other categories (p < 0.01). The risk profile and mortality were lower for Registry patients who were managed with thrombolytic therapy and/or intra-aortic balloon counter-pulsation, coronary angiography, angioplasty and/or coronary artery bypass surgery. After adjusting for these differences, the extent to which survival was improved with early revascularization was similar to that observed in the randomized SHOCK Trial. CONCLUSIONS: In this prospective Registry the etiology of CS was a mechanical complication in 12%. The similarity of the beneficial treatment effect in patients undergoing early revascularization in the SHOCK Trial Registry and SHOCK Trial provides strong support for the generalizability of the SHOCK Trial results.

Cardiogenic shock due to cardiac free-wall rupture or tamponade after acute myocardial infarction: a report from the SHOCK Trial Registry. Should we emergently revascularize occluded coronaries for cardiogenic shock?

OBJECTIVES: We sought to compare the characteristics and outcomes of patients with acute myocardial infarction (MI) and cardiogenic shock (CS) caused by rupture of the ventricular free wall or tamponade versus shock from other causes. BACKGROUND: Free-wall rupture is a recognized cause of mortality in patients with acute MI. Some of these patients present subacutely, which provides an opportunity for intervention. Recognition of factors that distinguish them from the overall shock cohort would be beneficial. METHODS: The international SHOCK Trial Registry enrolled patients concurrently with the randomized SHOCK Trial. Thirty-six centers consecutively enrolled all patients with suspected CS after MI, regardless of trial eligibility. RESULTS: Of the 1,048 patients studied, 28 (2.7%) had free-wall rupture or tamponade. These patients had less pulmonary edema, less diabetes, less prior MI, and less prior congestive heart failure (all p < 0.05). They more often had new Q waves in two or more leads (51.9% vs. 31.5%, p < 0.04), but MI location and time to shock onset after MI did not differ. Of patients with rupture or tamponade, 75% had pericardial effusions. No hemodynamic characteristics identified patients with rupture/tamponade. Most patients with rupture/tamponade had surgery and/or pericardiocentesis (27/28); their in-hospital survival rate was identical to that of the group overall (39.3%). Women and older patients with rupture/tamponade tended to survive intervention less often. CONCLUSIONS: Free-wall rupture and tamponade may present as CS after MI, and survival after intervention is similar to that of the overall shock cohort. All patients with CS after MI should have echocardiography in order to detect subacute rupture or tamponade and initiate appropriate interventions.

Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: We wished to assess the profile and outcomes of patients with ventricular septal rupture (VSR) in the setting of cardiogenic shock (CS) complicating acute myocardial infarction (MI). BACKGROUND: Cardiogenic shock is often seen with VSR complicating acute MI. Despite surgical therapy, mortality in such patients is high. METHODS: We analyzed 939 patients enrolled in the SHOCK Trial Registry of CS in acute infarction, comparing 55 patients whose shock was associated with VSR with 884 patients who had predominant left ventricular failure. RESULTS: Rupture occurred a median 16 h after infarction. Patients with VSR tended to be older (p = 0.053), were more often female (p = 0.002) and less often had previous infarction (p < 0.001), diabetes mellitus (p = 0.015) or smoking history (p = 0.033). They also underwent right-heart catheterization, intra-aortic balloon pumping and bypass surgery significantly more often. Although patients with rupture had less severe coronary disease, their in-hospital mortality was higher (87% vs. 61%, p < 0.001). Surgical repair was performed in 31 patients with rupture (21 had concomitant bypass surgery); 6 (19%) survived. Of the 24 patients managed medically, only 1 survived. CONCLUSIONS: There is a high in-hospital mortality rate when CS develops as a result of VSR. Ventricular septal rupture may occur early after infarction, and women and the elderly may be more susceptible. Although the prognosis is poor, surgery remains the best therapeutic option in this setting.

Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to investigate the potential benefit of thrombolytic therapy (TT) and intra-aortic balloon pump counterpulsation (IABP) on in-hospital mortality rates of patients enrolled in a prospective, multi-center Registry of acute myocardial infarction (MI) complicated by cardiogenic shock (CS). BACKGROUND: Retrospective studies suggest that patients suffering from CS due to MI have lower in-hospital mortality rates when IABP support is added to TT. This hypothesis has not heretofore been examined prospectively in a study devoted to CS. METHODS: Of 1,190 patients enrolled at 36 participating centers, 884 patients had CS due to predominant left ventricular (LV) failure. Excluding 26 patients with IABP placed prior to shock onset and 2 patients with incomplete data, 856 patients were evaluated regarding TT and IABP utilization. Treatments, selected by local physicians, fell into four categories: no TT, no IABP (33%; n = 285); IABP only (33%; n = 279); TT only (15%; n = 132); and TT and IABP (19%; n = 160). RESULTS: Patients in CS treated with TT had a lower in-hospital mortality than those who did not receive TT (54% vs. 64%, p = 0.005), and those selected for IABP had a lower in-hospital mortality than those who did not receive IABP (50% vs. 72%, p < 0.0001). Furthermore, there was a significant difference in in-hospital mortality among the four treatment groups: TT + IABP (47%), IABP only (52%), TT only (63%), no TT, no IABP (77%) (p < 0.0001). Patients receiving early IABP (< or = 6 h after thrombolytic therapy, n = 72) had in-hospital mortality similar to those with late IABP (53% vs. 41%, n = 64, respectively, p = 0.172). Revascularization rates differed among the four groups: no TT, no IABP (18%); IABP only (70%); TT only (20%); TT and IABP (68%, p < 0.0001); this influenced in-hospital mortality significantly (39% with revascularization vs. 78% without revascularization, p < 0.0001). CONCLUSIONS: Treatment of patients in cardiogenic shock due to predominant LV failure with TT, IABP and revascularization by PTCA/CABG was associated with lower in-hospital mortality rates than standard medical therapy in this Registry. For hospitals without revascularization capability, a strategy of early TT and IABP followed by immediate transfer for PTCA or CABG may be appropriate. However, selection bias is evident and further investigation is required.

Increased circulating monocyte activation in patients with unstable coronary syndromes.

OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.

Progress in percutaneous management of coronary bifurcation lesions.

Bifurcation lesions have been recognized as one of the most important challenges facing the interventional cardiologist since the beginnings of percutaneous coronary intervention (PCI). The potential of periprocedural occlusion of the side branch was discovered to be significant, leading to early attempts at protecting the side branch with a second guide wire and kissing balloon inflation in order to minimize this risk and thus improve the procedural and short-term success of the procedure. The advent of stenting significantly improved the safety of the procedure, although, side branch success continued to be a challenge. A variety of single as well as double stenting techniques were developed that improved the safety and short-term results of percutaneous coronary intervention involving side branches. Long-term success, however, continued to elude, due to an increased need for target lesion revascularization (TLR) and higher major adverse cardiac event (MACE) rates following PCI of bifurcation lesions. Of the techniques, main vessel stenting and balloon inflation of the side branch, T-stenting, and permutations of Y-stenting including the Culotte, emerged. The introduction of drug-eluting stents appears to have brought bifurcation PCI to a new level of long-term efficacy. Specialty bifurcation stents have been developed to provide easy access to the side branch, however, these have to date had little impact on practice and have not been adopted widely. New techniques such as crush stenting and its several permutations, and simultaneous kissing stenting developed specifically for drug-eluting stents have been developed. Debate continues as to which is the most efficacious technique. True randomized comparisons are, however, lacking. It is likely that all of the currently utilized techniques have a place in the interventional cardiologist's quiver and that each is appropriate in a particular anatomical scenario. Nonetheless, well-designed randomized trials evaluating the various bifurcation techniques especially in complex bifurcation lesions are needed.

Prognostic significance of diabetes as a predictor of survival after cardiac catheterization. APPROACH Investigators. Alberta Provincial Program for Outcome Assessment in Coronary Heart Disease.

PURPOSE: Diabetes is a recognized risk factor for the development of cardiac disease, but its importance as a prognostic factor among patients with known cardiovascular disease is less clear. We evaluated survival in patients with and without diabetes who underwent cardiac catheterization for presumed coronary artery disease. SUBJECTS AND METHODS: We analyzed data from a prospective cohort study that captures detailed clinical information and longitudinal outcomes for all patients who undergo cardiac catheterization in Alberta, Canada. We studied 11,468 patients, 1959 (17%) of whom had diabetes. Logistic regression was used to model predictors of 1-year mortality, and proportional hazards analysis was used to model predictors of survival up to 3 years after cardiac catheterization. RESULTS: One-year mortality was 7.6% for patients with diabetes versus 4.1% for those without diabetes (odds ratio = 1.9, 95% confidence interval [CI]: 1.6 to 2.3). After adjusting for other characteristics of the patients, including comorbid conditions, previous cardiac history, coronary anatomy, and renal function, the odds ratio for 1-year mortality was 1.1 (95% CI: 0.8 to 1.3). Similarly, the adjusted hazard ratio for longer term mortality was 1. 2 (95% CI: 1.0 to 1.4, mean follow-up of 702 days). CONCLUSIONS: These results suggest that there is little or no independent association between diabetes and mortality for up to 3 years after cardiac catheterization. Estimates of short- to intermediate-term prognosis for diabetic patients with coronary artery disease should be based on the presence of other prognostic factors associated with diabetes.

Does ticlopidine reduce reocclusion and other adverse events after successful balloon angioplasty of occluded coronary arteries? Results from the Total Occlusion Study of Canada (TOSCA).

OBJECTIVES: Ticlopidine reduces stent thrombosis and other adverse events among patients receiving coronary stents. Whether ticlopidine is beneficial after balloon angioplasty is unknown. Our purpose was to compare the clinical outcome of patients undergoing balloon angioplasty treated with both aspirin and ticlopidine versus aspirin alone. METHODS AND RESULTS: We performed a databank analysis of the Total Occlusion Study of Canada (TOSCA), a randomized trial with angiographic follow-up comparing the frequency of reocclusion after angioplasty of a subtotal or total coronary occlusion in patients receiving >/=1 heparin-coated Palmaz-Schatz stent versus balloon angioplasty alone. In TOSCA, 102 patients undergoing balloon angioplasty were treated with both aspirin and ticlopidine (generally for 15-30 days) and 94 were treated with aspirin alone, by physician preference. After 6 months, failure to sustain patency (less than Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow on follow-up angiography) occurred in 23% of patients on ticlopidine and aspirin versus 16% of patients on aspirin alone (P =.21); the frequency of target vessel revascularization was also similar in the 2 groups (32% vs 25%, P =.27). Myocardial infarction was infrequent in both groups (2.0% vs 1.1%, respectively, P not significant). Patients treated with aspirin and ticlopidine had more adverse angiographic and procedural characteristics, including longer lesions and treatment lengths. Multivariate analysis to adjust for these and other differences failed to reveal a benefit of ticlopidine in maintaining patency and reducing adverse clinical events. CONCLUSIONS: After balloon angioplasty of a subtotal or total coronary occlusion, no reduction in adverse events was observed among patients in whom ticlopidine was added to aspirin, even after adjustment for clinical and lesion characteristics.

Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE.

Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.

Effects of late percutaneous transluminal coronary angioplasty of an occluded infarct-related coronary artery on left ventricular function in patients with a recent (< 6 weeks) Q-wave acute myocardial infarction (Total Occlusion Post-Myocardial Infarction Intervention Study [TOMIIS]--a pilot study).

The effect of late percutaneous transluminal coronary angioplasty (PTCA) of an occluded infarct-related artery on left ventricular ejection fraction was studied in patients with a recent, first Q-wave myocardial infarction in a prospective, randomized study. Forty-four patients (31 men and 13 women, mean age 58 +/- 12 years) with an occluded infarct-related coronary artery were randomized to PTCA (n = 25) or no PTCA (n = 19). Patients received acetylsalicylic acid, a beta blocker and an angiotensin-converting enzyme inhibitor unless contraindicated. Left ventricular ejection fraction was determined at baseline and 4 months. Coronary angiography was repeated at 4 months. Baseline ejection fraction measured 20 +/- 12 days after myocardial infarction was 45 +/- 12% in both groups. PTCA was performed 21 +/- 13 days after the event. The primary PTCA success rate was 72%. One patient in each group died before angiographic follow-up, which was completed in 37 of the remaining 42 patients (88%; 21 with and 16 without PTCA). At 4 months, the infarct-related artery was patent in 43% of PTCA patients and in 19% of no PTCA patients (p = NS). Reocclusion occurred in 40% of patients after successful PTCA. Secondary analyses showed that the change in left ventricular ejection fraction was significantly greater in patients with a patent infarct-related artery (+9.4 +/- 6.2%) than in those with an occluded artery (+1.6 +/- 8.8%; p = 0.0096). Baseline ejection fraction also independently predicted improvement in left ventricular ejection fraction (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention and regression of coronary atherosclerosis. Is it safe and efficacious therapy?

OBJECTIVE: Atherosclerotic coronary heart disease (CHD) continues to be the dominant disease in Western society. A large body of evidence directly linking serum cholesterol levels and CHD risk has stimulated population treatment strategies designed to reduce cholesterol and CHD risk. Data indicating a relation between low cholesterol and non-CHD risk have, however, suggested that cholesterol reduction may not always be desirable. The primary goal of this evaluative review of the available evidence was to answer the following question: Is prevention/regression therapy for CHD safe and effective? DATA SOURCES: Three lines of evidence were reviewed: epidemiologic studies; primary and secondary prevention trials with clinical end points; and secondary prevention trials with quantitative coronary angiography as a surrogate end point for clinical CHD. STUDY SELECTION: Original studies and meta-analyses were reviewed. The principal selection criteria for the epidemiologic studies were large size and prolonged follow-up; for the trials, randomization and viable clinical (CHD events, CHD mortality, total mortality) or angiographic end points. DATA EXTRACTION: The data were initially extracted by a single reviewer using common qualitative guidelines. The data were then evaluated by all authors acting as a data interpretation team. DATA SYNTHESIS: Overall, the epidemiologic data revealed excess risk of fatal and nonfatal CHD events was directly related to total cholesterol and low-density lipoprotein (LDL) cholesterol levels, for both men and women and for both younger (< 65 years) and older (> or = 65 years) patients, over a wide range of serum cholesterol levels. The predictive value was higher in younger men than older men and women, although part of this quantitative interaction may be due to fewer studies, with fewer end points, in the older and female populations. The CHD events and CHD mortality, but not total mortality, were consistently reduced in trials of cholesterol-lowering therapy. The regression trials, predominantly in CHD patients with high cholesterol values (mean 7.1 mmol/L), demonstrated improvement in angiographic atherosclerosis in every study. The evidence for elevated risk of non-CHD death at very low levels of cholesterol is uncertain and controversial. The most likely possibilities for this apparent relationship are unknown confounding variables and the play of chance. CONCLUSIONS: Serum cholesterol levels are directly associated with CHD risk, and there is no threshold level below which there is no risk. Reduction of high serum cholesterol levels reduces CHD risk. Whether lipid-lowering and adjunctive antiatherosclerotic therapies are effective and safe in the majority of CHD patients who have desirable or borderline cholesterol levels remains undetermined.

Magnesium sulfate prophylaxis after cardiac operations.

One hundred patients undergoing elective cardiac operations were randomized into placebo (n = 54) and magnesium (n = 46) groups. The magnesium group received six doses of 2.4 g (19.2 mEq) magnesium sulfate intravenously in the first 24 hours after the cardiac operation. The magnesium group had higher serum magnesium concentrations postoperatively (1.09 +/- 0.20 versus 0.75 +/- 0.13 mmol/L; p < 0.0001), postoperative day 1 (1.49 +/- 0.34 versus 0.70 +/- 0.12 mmol/L; p < 0.0001) and postoperative day 2 (0.96 +/- 0.19 versus 0.76 +/- 0.07 mmol/L; p < 0.0001). Patients in the magnesium group had a lower incidence of ventricular tachyarrythmias (VTs) (17.3% versus 51.9%; p = 0.0006), less need for treatment (6.5% versus 20.3%; p < 0.0001), fewer VT episodes/patient (0.3 +/- 0.8 versus 1.39 +/- 1.9; p < 0.0001), and a reduction in the severity of VTs as measured by the modified Lown grade (p = 0.0002). No differences were demonstrated with respect to supraventricular tachyarrythmias. The magnesium group had reduced absolute creatine kinase-MB levels (5.3 +/- 4.2 versus 28.4 +/- 28 IU/L; p = 0.001) as well as creatine kinase-MB fraction (0.01 +/- 0.02 versus 0.05 +/- 0.04; p = 0.001) on postoperative day 1. Serum magnesium concentrations were lower during VTs than during periods of sinus rhythm (0.75 +/- 0.75 versus 1.02 +/- 0.35 mmol/L; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of half ironman competition on the development of late potentials.

OBJECTIVES: The primary purpose was to evaluate the prevalence of late potentials (LPs) in triathletes before and after a half ironman triathlon. The secondary purpose was to examine whether LPs are the electrocardiographic expression of a greater myocardial mass. METHODS: Nine asymptomatic male triathletes (mean age +/- SD, 32 +/- 5 yr) were examined using signal-averaged ECG (SAECG) 48-72 h before (PRE), immediately after (POST), and 24-48 h after the completion (RECOVERY) of a half ironman triathlon. Late potentials were considered to be present if two of the following SAECG anomalies were observed: 1) a prolonged filtered QRS (/QRS) complex (> or = 114 ms), 2) a lengthened low amplitude signal (LAS) duration (>38 ms), and/or 3) a low root mean square (RMS) voltage of the last 40 ms of the fQRS (<20 microV). Left ventricular dimensions were determined at PRE using M-mode echocardiography. RESULTS: There were no significant differences between PRE, POST, and RECOVERY in the fQRS duration, the LAS duration, or the RMS voltage. Two athletes displayed a single SAECG abnormality during PRE and two SAECG anomalies (i.e., LPs) during POST. Late potentials remained in one of the two athletes during RECOVERY. A moderate relationship existed between fQRS and left ventricular mass (r = 0.67, P < 0.05). CONCLUSIONS: Ultra-endurance training and/or events do not lead to LPs in the majority of triathletes who do not possess ventricular arrhythmias. However, a small subset of triathletes do display SAECG anomalies, which are augmented by an ultra-endurance event and may persist even after recovery from the event. Left ventricular mass does not affect overall SAECG parameters.

The need for revascularization procedures will remain the same or increase in the next decade.

It has been stated that cardiovascular risk-reduction strategies such as lipid-lowering drug therapy will significantly decrease the need for coronary revascularization procedures nationally and worldwide by the end of the next decade. Because of a number of factors this decrease is unlikely to occur. First, there is every indication that the growth of the Canadian population will remain at least linear in the next decade. In addition, the population is aging, with the greatest increase in population occurring in the 'baby boom' group and those older. This phenomenon will place an unprecedented level of stress not only on the health care system in general but also on all services related to the care of patients with symptomatic coronary artery disease. It has been suggested that these increases will be offset by proven therapies to reduce the risk of cardiovascular events. However, studies show that therapies such as lipid-lowering drugs continue to be underused, due to physician as well as patient factors. Furthermore, the indications for coronary revascularization are expanding with new evidence showing benefits of direct PTCA in the setting of myocardial infarction, as well as cardiogenic shock in selected patients. In addition, PTCA of totally occluded coronary arteries will be performed more frequently with new studies showing benefits in this setting. The greatest impact on need for revascularization procedures will occur worldwide. The coronary artery disease epidemic that affected western society is just now beginning to emerge in developing countries. Studies in India and China show an alarming rise in the prevalence of cardiovascular risk factors and with it the rise in the shift of the burden of disease from infectious to cardiovascular etiology. All of these factors are likely to result in an unprecedented rise in the need for coronary revascularization procedures.

The promise and practice of cardiovascular risk reduction: a disease management perspective. Clinical Quality Improvement Network (CQIN) Investigators.

OBJECTIVE: Interpretive analysis of epidemiological, clinical trials and practice pattern data for cardiovascular risk reduction in the contemporary setting of unprecedented demographic changes. DATA SOURCES: Literature review and audit results of the Clinical Quality Improvement Network (CQIN). DATA SYNTHESIS: Coronary artery disease (CAD) is the largest single cause of death in Canada. CAD is age-related and the population is rapidly ageing, a combination that threatens an epidemic of future CAD events. Epidemiological data demonstrate a direct relation of CAD risk and serum cholesterol levels and no threshold cholesterol level below which there is no CAD risk. The epidemiological data also suggest CAD risk can be reduced by lowering serum cholesterol and this hypothesis has now been incontrovertibly confirmed by repeated randomized clinical trials. Most recently, reduction of all-cause mortality with cholesterol-lowering therapy in high risk subjects has also been confirmed. Despite the overwhelming trials and epidemiological evidence, CQIN effectiveness analyses reveal far from optimal risk assessment and management practices among high risk patients. CONCLUSIONS: Serum cholesterol is directly related to CAD risk. Reduction of cholesterol reduces CAD, and all-cause, mortality in high risk patients. There is a large window of opportunity to improve lipid-lowering practices, and patient outcomes, for the most deadly diseases in our society.