Vladimir Dzavik

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, 3×2 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-&agr;-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.

Routine Early Angioplasty after Fibrinolysis for Acute Myocardial Infarction

BACKGROUND Patients with a myocardial infarction with ST-segment elevation who present to hospitals that do not have the capability of performing percutaneous coronary intervention (PCI) often cannot undergo timely primary PCI and therefore receive fibrinolysis. The role and optimal timing of routine PCI after fibrinolysis have not been established. METHODS We randomly assigned 1059 high-risk patients who had a myocardial infarction with ST-segment elevation and who were receiving fibrinolytic therapy at centers that did not have the capability of performing PCI to either standard treatment (including rescue PCI, if required, or delayed angiography) or a strategy of immediate transfer to another hospital and PCI within 6 hours after fibrinolysis. All patients received aspirin, tenecteplase, and heparin or enoxaparin; concomitant clopidogrel was recommended. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening congestive heart failure, or cardiogenic shock within 30 days. RESULTS Cardiac catheterization was performed in 88.7% of the patients assigned to standard treatment a median of 32.5 hours after randomization and in 98.5% of the patients assigned to routine early PCI a median of 2.8 hours after randomization. At 30 days, the primary end point occurred in 11.0% of the patients who were assigned to routine early PCI and in 17.2% of the patients assigned to standard treatment (relative risk with early PCI, 0.64; 95% confidence interval, 0.47 to 0.87; P=0.004). There were no significant differences between the groups in the incidence of major bleeding. CONCLUSIONS Among high-risk patients who had a myocardial infarction with ST-segment elevation and who were treated with fibrinolysis, transfer for PCI within 6 hours after fibrinolysis was associated with significantly fewer ischemic complications than was standard treatment. (ClinicalTrials.gov number, NCT00164190.)

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

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.

Long-Term Effects of Cholesterol Lowering and Angiotensin-Converting Enzyme Inhibition on Coronary Atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT)

BackgroundThis long-term, multicenter, randomized, double-blind, placebo-controlled, 2×2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. Methods and ResultsThere 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. ConclusionsThis 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.

Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry☆

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.

Classification of coronary artery bifurcation lesions and treatments: Time for a consensus!

Background: Percutaneous coronary intervention (PCI) of coronary bifurcation lesions remains a subject of debate. Many studies have been published in this setting. They are often small scale and display methodological flaws and other shortcomings such as inaccurate designation of lesions, heterogeneity, and inadequate description of techniques implemented. Methods: The aim is to propose a consensus established by the European Bifurcation Club (EBC), on the definition and classification of bifurcation lesions and treatments implemented with the purpose of allowing comparisons between techniques in various anatomical and clinical settings. Results: A bifurcation lesion is a coronary artery narrowing occurring adjacent to, and/or involving, the origin of a significant side branch. The simple lesion classification proposed by Medina has been adopted. To analyze the outcomes of different techniques by intention to treat, it is necessary to clearly define which vessel is the distal main branch and which is (are) the side branche(s) and give each branch a distinct name. Each segment of the bifurcation has been named following the same pattern as the Medina classification. The classification of the techniques (MADS: Main, Across, Distal, Side) is based on the manner in which the first stent has been implanted. A visual presentation of PCI techniques and devices used should allow the development of a software describing quickly and accurately the procedure performed. Conclusion: The EBC proposes a new classification of bifurcation lesions and their treatments to permit accurate comparisons of well described techniques in homogeneous lesion groups.

Inotropes and Vasopressors Review of Physiology and Clinical Use in Cardiovascular Disease

Inotropic and vasopressor agents have increasingly become a therapeutic cornerstone for the management of several important cardiovascular syndromes. In broad terms, these substances have excitatory and inhibitory actions on the heart and vascular smooth muscle, as well as important metabolic, central nervous system, and presynaptic autonomic nervous system effects. They are generally administered with the assumption that short- to medium-term clinical recovery will be facilitated by enhancement of cardiac output (CO) or vascular tone that has been severely compromised by often life-threatening clinical conditions. The clinical efficacy of these agents has been investigated largely through examination of their impact on hemodynamic end points, and clinical practice has been driven in part by expert opinion, extrapolation from animal studies, and physician preference. Our aim is to review the mechanisms of action of common inotropes and vasopressors and to examine the contemporary evidence for their use in important cardiac conditions.

Early revascularization is associated with improved survival in elderly patients with acute myocardial infarction complicated by cardiogenic shock: a report from the SHOCK Trial Registry

Aims The SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK (SHOCK) Trial showed no benefit of early revascularization in patients aged ≥75 years with acute myocardial infarction and cardiogenic shock. We examined the effect of age on treatment and outcomes of patients with cardiogenic shock in the SHOCK Trial Registry. Methods and results We compared clinical and treatment factors in patients in the SHOCK Trial Registry with shock due to pump failure aged <75 years \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((n=588)\) \end{document} and ≥75 years \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((n=277)\) \end{document}, and 30-day mortality of patients treated with early revascularization <18 hours since onset of shock and those undergoing a later or no revascularization procedure. After excluding early deaths covariate-adjusted relative risk and 95% confidence intervals were calculated to compare the revascularization strategies within the two age groups. Older patients more often had prior myocardial infarction, congestive heart failure, renal insufficiency, other comorbidities, and severe coronary anatomy. In-hospital mortality in the early vs. late or no revascularization groups was 45 vs. 61% for patients aged <75 years \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((p=0.002)\) \end{document} and 48 vs. 81% for those aged ≥75 years \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((p=0.0003)\) \end{document}. After exclusion of 65 early deaths and covariate adjustment, the relative risk was 0.76 (0.59, 0.99; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.045\) \end{document}) in patients aged <75 years and 0.46 (0.28, 0.75; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.002\) \end{document}) in patients aged ≥75 years. Conclusions Elderly patients with myocardial infarction complicated by cardiogenic shock are less likely to be treated with invasive therapies than younger patients with shock. Covariate-adjusted modeling reveals that elderly patients selected for early revascularization have a lower mortality rate than those receiving a revascularization procedure later or never.

Randomized Trial of Percutaneous Coronary Intervention for Subacute Infarct-Related Coronary Artery Occlusion to Achieve Long-Term Patency and Improve Ventricular Function. The Total Occlusion Study of Canada (TOSCA)-2 Trial

Background— In the present study, we sought to determine whether opening a persistently occluded infarct-related artery (IRA) by percutaneous coronary intervention (PCI) in patients beyond the acute phase of myocardial infarction (MI) improves patency and indices of left ventricular (LV) size and function. Methods and Results— Between May 2000 and July 2005, 381 patients with an occluded native IRA 3 to 28 days after MI (median 10 days) were randomized to PCI with stenting (PCI) or optimal medical therapy alone. Repeat coronary and LV angiography was performed 1 year after randomization (n=332, 87%). Coprimary end points were IRA patency and change in LV ejection fraction. Secondary end points included change in LV end-systolic and end-diastolic volume indices and wall motion. PCI was successful in 92%. At 1 year, 83% of PCI versus 25% of medical therapy–only patients had a patent IRA (P<0.001). LV ejection fraction increased significantly (P<0.001) in both groups, with no between-group difference: PCI 4.2±8.9 (n=150) versus medical therapy 3.5±8.2 (n=136; P=0.47). Median change (interquartile range) in LV end-systolic volume index was −0.5 (−9.3 to 5.0) versus 1.0 (−5.7 to 7.3) mL/m2 (P=0.10), whereas median change (interquartile range) in LV end-diastolic volume index was 3.2 (−8.2 to 13.3) versus 5.3 (−4.6 to 23.2) mL/m2 (P=0.07) in the PCI (n=86) and medical therapy–only (n=76) groups, respectively. Conclusions— PCI with stenting of a persistently occluded IRA in the subacute phase after MI effectively maintains long-term patency but has no effect on LV ejection fraction. On the basis of these findings and the lack of clinical benefit in the main Occluded Artery Trial, routine PCI is not recommended for stable patients with a persistently occluded IRA after MI.

Echocardiographic Predictors of Survival and Response to Early Revascularization in Cardiogenic Shock

Background—Although echocardiography is used in diagnosis and management of myocardial infarction, it has not been established whether specific features of cardiac structure or function early in the course of cardiogenic shock provide prognostic value. The purposes of this substudy of the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial were to describe the echocardiographic features of cardiogenic shock, identify findings on early echocardiograms associated with outcome, examine the interaction of such features with treatment, and determine whether these features could provide insights into the survival benefit observed with early revascularization and guide selection of patients for this strategy. Methods and Results—One hundred seventy-five echocardiograms performed within 24 hours of randomization to the early revascularization (ERV) or initial medical stabilization (IMS) arms of the trial were submitted for quantitative assessment, and 169 were suitable for analysis. The 2 groups were similar in terms of clinical and early echocardiographic characteristics. Mean left ventricular ejection fraction (LVEF) was 31%, and moderate or greater mitral regurgitation (MR) was noted in 39.1%. On multivariate analysis, the only independent predictors of survival were MR severity and LVEF. A survival benefit for the ERV strategy was observed at all levels of LVEF and MR. Conclusions—A wide range of cardiac structural and functional abnormalities exists in patients presenting with acute cardiogenic shock. Both short- and long-term mortality appear to be associated with initial left ventricular systolic function and MR as assessed by echocardiography, and a benefit of ERV is noted regardless of baseline LVEF or MR.