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 (n=588) and >/=75 years (n=277), 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 (p=0.002) and 48 vs. 81% for those aged >/=75 years (p=0.0003). After exclusion of 65 early deaths and covariate adjustment, the relative risk was 0.76 (0.59, 0.99; p=0.045) in patients aged <75 years and 0.46 (0.28, 0.75; p=0.002) 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.

Trends in cardiogenic shock: report from the SHOCK Study. The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

AIMS: We analysed time trends in patient characteristics, management, and outcomes of cardiogenic shock complicating acute myocardial infarction in the international, prospective SHOCK Trial Registry and pre-study Registry. BACKGROUND: Despite therapeutic advances in its management, the incidence and high mortality of this complication has remained unchanged for decades. However, in recent years mortality was reported to decrease in one community concomitant with increasing use of revascularization. METHODS: Thirty-six centres registered 1380 patients with suspected cardiogenic shock complicating acute myocardial infarction from January 1992 to August 1997. Patient and myocardial infarction characteristics, haemodynamics, medications, procedure use, and vital status at discharge were recorded. RESULTS: In all, 79% of patients had shock due to predominant pump failure (non-mechanical aetiology). The aetiology, patient profile, and clinical characteristics of cardiogenic shock did not differ over time, except for increases in the incidence of prior bypass surgery (P=0.054) and transfers to tertiary centres (P=0.008). In all, 44% underwent revascularization (n=485), with angioplasty performed more often than bypass surgery (69% vs 31%). The revascularization rate increased over time (P=0.006) with a significant decrease in the time to revascularization (P=0.033). The use of Swan-Ganz catheterization decreased over time (P=0.018), as did the mean length of hospitalization (P=0.034). Overall in-hospital mortality was high (63%) but decreased over time in all patients (P=0.004) and those with pump failure (P=0.018). Mortality was lower for patients who underwent revascularization compared to those who were not revascularized (41% vs 79%, P<0.001). CONCLUSIONS: Cardiogenic shock complicating acute myocardial infarction is associated with a high mortality rate, but mortality decreased significantly from 1992 to 1997. This partly reflects the greater use of revascularization, which was associated with better outcomes. The reported international trend towards shorter admissions for myocardial infarction was also observed in this cohort.

Diabetes mellitus 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 examine the role of diabetes mellitus in cardiogenic shock (CS) complicating acute myocardial infarction (AMI) in the SHOCK Trial Registry. BACKGROUND: The characteristics, outcomes and optimal treatment of diabetic patients with CS complicating AMI have not been well described. METHODS: Baseline characteristics, clinical and hemodynamic measures, treatment variables, shock etiologies and comorbid conditions were compared for 379 diabetic and 784 nondiabetic patients. Logistic regression was used to examine the association between diabetes and in-hospital mortality, after adjustment for baseline differences. RESULTS: Diabetics were less likely than nondiabetics to undergo thrombolysis (28% vs. 37%; p = 0.002) or attempted revascularization (40% vs. 49%; p = 0.008). The survival benefit for diabetics selected for percutaneous or surgical revascularization (55% vs. 19% without revascularization) was similar to that for nondiabetics (59% vs. 25%). Overall unadjusted in-hospital mortality was significantly higher for diabetics (67% vs. 58%; p = 0.007), but diabetes was only a borderline predictor of mortality after adjustment for baseline and treatment differences (odds ratio for death, 1.36; 95% confidence interval, 1.00 to 1.84; p = 0.051). CONCLUSIONS: Diabetics with CS complicating AMI have a higher-risk profile at baseline, but after adjustment, diabetics have an in-hospital survival rate that is only marginally lower than that of nondiabetics. Diabetics who undergo revascularization derive a survival benefit similar to that of nondiabetics.

Near-maximal fractional oxygen extraction by active skeletal muscle in patients with chronic heart failure.

Systemic oxygen uptake and deep femoral vein oxygen content were determined at peak exercise in 53 patients with chronic heart failure with impaired systolic function (mean left ventricular ejection fraction 0.18; n = 41) or preserved systolic function (mean left ventricular ejection fraction 0.70; n = 12) and in 6 age-matched sedentary normal subjects. At peak exercise, deep femoral vein oxygen content in heart failure patients with impaired systolic function and preserved systolic function were similar, both significantly lower than that of normal subjects (2.5 +/- 0.1, 2.9 +/- 0.2, and 5.0 +/- 0.1 ml/100 ml, respectively; P < 0.05). Deep femoral venous oxygen content was lower in patients with the greater impairment of aerobic capacity, regardless of the underlying systolic function (r = 0.72, P < 0.01). Fractional oxygen extraction in the skeletal muscle at peak exercise is enhanced in patients with chronic heart failure when compared with normal subjects, in proportion to the degree of aerobic impairment.

Acute myocardial infarction complicated by systemic hypoperfusion without hypotension: report of the SHOCK trial registry.

BACKGROUND: Cardiogenic shock is usually characterized by inadequate cardiac output and sustained hypotension. However, following a large myocardial infarction, peripheral hypoperfusion can occur with relatively well maintained systolic blood pressure, a condition known as nonhypotensive cardiogenic shock. The aim of this study was to determine the characteristics of patients with this condition. METHODS: The SHOCK trial registry prospectively enrolled patients with suspected cardiogenic shock complicating acute myocardial infarction. We identified a group of 49 patients who presented with nonhypotensive shock, defined as clinical evidence of peripheral hypoperfusion with a systolic blood pressure >90 mm Hg without vasopressor circulatory support. Clinical characteristics, hemodynamic data, and outcomes in these patients were compared with a group of 943 patients with classic cardiogenic shock with hypotension. The age, gender, and distributions of coronary risk factors were similar in both groups. RESULTS: Patients with nonhypotensive shock were more likely to have an anterior wall myocardial infarction (71% versus 53%, P = 0.03). Both groups of patients had similar rates of treatment with thrombolytic therapy, angioplasty, and bypass surgery. Patients with nonhypotensive shock had an in-hospital mortality rate of 43% as compared with a rate of 66% among patients who had classic cardiogenic shock with hypotension (P = 0.001). Mortality among 76 patients who presented with a systolic blood pressure <90 mm Hg but no hypoperfusion was 26%. CONCLUSIONS: Even in the presence of normal blood pressure, clinical signs of peripheral hypoperfusion, which may be subtle, are associated with a substantial risk of in-hospital death following acute myocardial infarction.

Incidence and mechanism of creatine kinase-MB enzyme elevation after coronary intervention with different devices.

The present study was conducted to evaluate the incidence of CK-MB elevation and to identify the possible mechanisms of CK-MB release after various coronary interventional devices. We prospectively studied 1,675 consecutive patients following various coronary interventions for CK-MB elevation, from January 1997 to February 1998 and followed them for in-hospital events. CK-MB elevation was detected in 313 patients (18.7%); with 1-3 x normal in 12.8%, 3-5 x normal in 3.5%, and >5 x normal in 2.4%. CK-MB elevation was more common after nonballoon devices (19.5% vs. 11.5% after balloon angioplasty; P < 0.01). Among the newer nonballoon devices, rotational atherectomy alone had a lower CK-MB elevation compared to stent-alone group (16.0% vs. 20.5%; P = 0.07). On univariate analysis, due to selective use of abciximab in high-risk coronary interventions, there was higher incidence of CK-MB elevation with abciximab (24.5% vs. 15.0% without abciximab; P < 0.01). Some kind of procedural complication was observed in 49% of the CK-MB elevation group, with side-branch closure being the most frequent (22.7%). In conclusion, CK-MB elevation is common after successful coronary interventions and is higher after nonballoon devices. Cathet. Cardiovasc. Intervent. 48:123-129, 1999.

Creatine kinase-MB elevation after coronary intervention correlates with diffuse atherosclerosis, and low-to-medium level elevation has a benign clinical course: implications for early discharge after coronary intervention.

OBJECTIVES: The study evaluated the incidence and predictors of creatine kinase-MB isoenzyme (CK-MB) elevation after successful coronary intervention using current devices, and assessed the influence on in-hospital course and midterm survival. BACKGROUND: The CK-MB elevation after coronary intervention predominantly using balloon angioplasty correlates with late cardiac events of myocardial infarction (MI) and death. Whether CK-MB elevation after nonballoon devices is associated with an adverse short and midterm prognosis is unknown. METHODS: The incidence and predictors of CK-MB elevation after coronary intervention were prospectively studied in 1,675 consecutive patients and were followed for in-hospital events and survival. RESULTS: CK-MB elevation was detected in 313 patients (18.7%), with 1-3x in 12.8%, 3-5x in 3.5% and >5x normal in 2.4% of patients. Procedural complications or electrocardiogram changes occurred in only 49% of the CK-MB-elevation cases; CK-MB elevation was more common after nonballoon devices (19.5% vs. 11.5% after percutaneous transluminal coronary angioplasty; p < 0.01). Predictors of CK-MB elevation on multivariate analysis were diffuse coronary disease (p = 0.02), systemic atherosclerosis (p = 0.002), stent use (p = 0.04) and absence of beta-blocker therapy (p = 0.001). Adverse in-hospital cardiac events were more frequent in patients with >5x CK-MB elevation, with no significant difference between 1-5x CK-MB elevation versus normal CK-MB group. During a mean follow-up of 13 +/- 3 months, the incidence of death in the CK-MB-elevation group was 1.6% versus 1.3% in the normal CK-MB group (p = NS). CONCLUSIONS: The CK-MB elevation after coronary intervention was observed even in the absence of discernible procedural complications and was more common in patients with diffuse atherosclerosis. In-hospital clinical events requiring prolonged monitoring were higher in >5x CK-MB-elevation patients only. Midterm survival of CK-MB-elevation patients was similar to those with normal CK-MB. Our prospective analysis shows a lack of adverse in-hospital cardiac events and suggests that early discharge of stable 1-5x normal CK-MB-elevation patients after successful coronary intervention is safe.

The effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling.

BACKGROUND: Patients with angina after a Q-wave myocardial infarction benefit from elective revascularization, but it is not known whether asymptomatic patients, including those with a totally occluded infarct-related artery, improve after revascularization. OBJECTIVE: To determine the effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling. METHODS: We prospectively studied 31 consecutive asymptomatic patients (aged 57 +/- 2 years, 24 with anterior infarcts) after Q-wave myocardial infarction with > or = 70% stenosis of the infarct-related artery (IRA) who underwent early elective revascularization (days 4-10 after myocardial infarction). Group I consisted in patients with a totally occluded IRA (n = 10), and group II consisted in patients with a patent, though stenosed, IRA (n = 21). Resting echocardiography and low-dose dobutamine echocardiography were performed at baseline (day 3 +/- 1), and rest echocardiography was repeated after an 8-week follow-up. Significant myocardial viability was defined as > or = 2 wall segments improved (in a 16-segment model of left ventricle) versus baseline, and significant functional recovery as > or = 2 segments improved versus baseline on follow-up examination. Left ventricular end-systolic volume indices (ESVI) and end-diastolic volume indices and ejection fractions were measured by using a modified version of Simpson's rule (using apical two-chamber and four-chamber views). RESULTS: The left ventricular ESVI of patients in group I had decreased by 4.2 +/- 1.9 ml/m2, whereas for patients in group II the left ventricular ESVI had increased by 4.2 +/- 1.7 ml/m2 (P = 0.006). Similarly, the left ventricular end-diastolic volume index had decreased by 0.7 +/- 2.4 ml/m2 versus baseline at follow-up for patients in group I and increased by 7.8 +/- 2.1 ml/m2 for patients in group II (P = 0.02). The left ventricular ejection fraction increased by 7.3 +/- 3% for patients in group I and decreased by 0.4 +/- 2% for patients in group II (P = 0.04). CONCLUSION: There is less global left ventricular remodeling, a potentially deleterious process, after elective revascularization early after Q-wave myocardial infarction in asymptomatic patients who had had a totally occluded IRA before revascularization than there is in patients who had already had a patent, though stenosed, IRA before revascularization. These results suggest that restoration of patency of IRA after a Q-wave myocardial infarction is beneficial even for asymptomatic patients.

Histopathological correlates of early arterial recoil following directional coronary atherectomy.

Elastic recoil has been implicated in the pathophysiology of restenosis after conventional balloon angioplasty alone. Directional atherectomy may attenuate arterial recoil by removing the internal elastic lamina and medial smooth muscle cells and altering the vessel wall architecture. This study sought to evaluate early recoil after directional atherectomy and its relation with excision of deep arterial wall structures. We prospectively evaluated the correlation of the histopathologic evidence of media or adventitia as assessed in the atheroma retrieved during the procedure with the early changes in minimal lumen diameter after directional atherectomy followed by adjunct balloon dilatation in 50 consecutive cases. Recoil was assessed by routinely performed 1- and 15-min postprocedure angiograms, and patients were divided into two groups according to the absence (group I, n = 26) or presence (group II, n = 24) of recoil. The mean changes in minimal luminal diameter between 1 and 15 min was +0.22 mm in group I and -0.14 mm in group II. The absence of recoil was strongly associated with evidence of media tissue in the pathologic analysis as compared with cases with recoil (42 vs. 18%, respectively; p = 0.02). Similarly, retrieval of adventitia was seen exclusively in the group without recoil (15 vs. 0%; p = 0.06). Vessels that underwent recoil had significantly larger reference and immediate postprocedure minimal luminal diameters (3.62 +/- 0.57 and 3.02 +/- 0.45 mm, respectively) as compared with arteries with no recoil (3.28 +/- 0.35 and 2.75 +/- 0. 43 mm, respectively; p < 0.05 for both). Therefore, early luminal changes, likely related to elastic recoil, correlated with excision of deep wall structures during directional atherectomy. Arteries that showed recoil were larger, possibly due to thicker muscular layer and/or larger plaque burden as compared with arteries that did not recoil. Thus, optimal tissue debulking during directional atherectomy appears to attenuate recoil, providing an additional insight into the mechanism of action of this percutaneous revascularization device.

Risk factors for the development of slow flow during rotational coronary atherectomy.

We investigated the clinical and angiographic risk profile of slow flow during rotational atherectomy. Lesion length, angina at rest, and use of beta blockers correlated independently with slow flow in the univariate as well as in the multivariate analysis.

Prospective evaluation of a stiff shaft glide wire compared with the standard straight wire in crossing severely stenotic aortic valves.

In this prospective randomized study of the use of the Terumo glide wire compared with the standard straight wire for crossing of severely stenotic aortic valves, the glide wire was shown to significantly decrease the fluoroscopy time of the procedure and to lower by 3.4 times the need for crossover to the alternative technique.

Point mutagenesis of positively charged amino acids of cholesteryl ester transfer protein: conserved residues within the lipid transfer/lipopolysaccharide binding protein gene family essential for function.

The cholesteryl ester transfer protein (CETP) binds to plasma lipoproteins and transfers neutral lipids between them. Previous studies showed that lipoprotein binding involves ionic interactions between CETP and lipoproteins, with increased binding of CETP to lipoproteins carrying increased negative charge. In order to understand the molecular determinants of lipoprotein binding in CETP, site-directed mutagenesis was carried out on positively charged amino acids within and outside regions of conserved sequence in the putative family of lipid transfer/lipopolysaccharide (LPS) binding proteins (LT/LBP). Within the conserved regions, two mutant proteins, K233A and R259D, were well secreted by the transfected cells but showed markedly reduced cholesteryl ester transfer activity. Separating the bound from free CETP by gel filtration after incubation with HDL, HDL binding by K233A was found to be impaired, suggesting that the binding deficiency of the mutant may be responsible for decreased transfer activity. Kinetic analysis showed a marked increase in the apparent Km but no change in Vmax, consistent with a lipoprotein binding defect. Thus, within CETP, K233 and R259 play an essential role in cholesteryl ester transfer activity probably by mediating binding of CETP to lipoproteins. Sequence alignment of CETP, phospholipid transfer protein, LPS binding protein, and bactericidal permeability-inducing protein showed that K223 and R259 were strictly conserved as positively charged amino acids, suggesting a common function within the LT/LBP gene family.

Gender effects on the distribution of the cholesteryl ester transfer protein in apolipoprotein A-I-defined lipoprotein subpopulations.

Two subpopulations of apolipoprotein A-I-containing lipoproteins, those containing only apoA-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I/A-II), were isolated by immunoaffinity chromatography of plasma from 44 subjects, comprising four groups (male or female, with or without hyperlipidemia). ApoA-I-defined particles (LpAs) were assessed for their content of cholesteryl ester transfer protein (CETP) and for their ability to act as substrates for CETP. Although plasma CETP concentration was similar in all groups, the plasma concentration of LpA-I-associated CETP was significantly higher in females than in males (1.56 +/- 0.11 versus 0.93 +/- 0.13 mg/l, P < 0.05). In females, the major fraction of CETP was found in LpA-I, whereas in normolipidemic males CETP was evenly distributed between LpA-I and LpA-I/A-II, and in hyperlipidemic males the majority of CETP was found in LpA-I/A-II. In all groups, the percentage of CETP in LpA-I was correlated with the concentration of apoA-I in LpA-I (r = 0.64, P < 0.001). Native gradient gel electrophoresis of isolated LpAs showed that CETP was broadly distributed within different sized particles. LpA-I and LpA-I/A-II showed similar efficiency of CETP-mediated cholesteryl ester exchange with LDL. In conclusion, even though LpA-I has a much higher apparent affinity for CETP than LpA-I/A-II, both LpAs can bind CETP and act as equivalent CETP substrates in vitro. Thus, in subjects with low levels of LpA-I (notably hyperlipidemic males), most of the plasma neutral lipid exchange will involve LpA-I/A-II.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training decreases plasma cholesteryl ester transfer protein.

To assess the effect of exercise on the plasma concentration of cholesterol ester transfer protein (CETP) and its possible influence in mediating the exercise-associated redistribution of cholesterol among plasma lipoproteins, we measured plasma CETP in 57 healthy normolipidemic men and women before and after 9 to 12 months of exercise training. The training protocol resulted in significant changes in VO2max (mean +/- SD, +5.3 +/- 3.5 mL.kg-1 x min-1), body weight (-2.5 +/- 3.5 kg), plasma triglycerides (-25.7 +/- 36.3 mg/dL), high-density lipoprotein cholesterol (HDL-C) (+2.6 +/- 6.2 mg/dL), and ratios of total cholesterol to HDL-C (-0.30 +/- 0.52) and low-density lipoprotein cholesterol (LDL-C) to HDL-C (-0.18 +/- 0.45) (all P < or = .05) but no change in lipoprotein(a). CETP concentration (in milligrams per liter) fell significantly in response to training in both men (n = 28, 2.47 +/- 0.66 to 2.12 +/- 0.43; % delta = 14.2%; P < .005) and women (n = 29, 2.72 +/- 1.01 to 2.36 +/- 0.76; % delta = 13.2%; P < .047). The CETP change was observed both in subjects who lost weight (n = 28, delta mean weight = -5.0 kg; delta CETP = -0.42 +/- 0.79; % delta = 15.4%; P < .009) and in those who were weight stable (n = 29, delta mean weight = -0.12 kg; delta CETP = -0.29 +/- 0.78; % delta = 10.4%; P < .055).(ABSTRACT TRUNCATED AT 250 WORDS)

Contingent social reinforcement for fluid compliance in a hemodialysis patient.

Two approaches, (a) patient education and (b) compliance-contingent social reinforcement, were employed to improve compliance with fluid restrictions in a chronically noncompliant hemodialysis patient of borderline intellectual functioning. Results indicated that only social reinforcement led to improved compliance (i.e., decreased intersession weight gain). Treatment effects were well maintained at both 3- and 6-month follow-ups. Contingency management strategies are recommended as a potentially cost effective treatment for noncompliance in hemodialysis patients.

Hypoxia: a stimulus for tissue plasminogen activator release in humans?

Six healthy male volunteers between the ages of 22 and 33 years inspired normoxic (20.9% O2) and hypoxic (10% O2) gas mixtures continuously for 15 min on separate days while resting supine. The order of testing was counterbalanced. Heart rates (b.min-1), minute ventilation (L.min-1), transcutaneous PO2 (mm Hg) and euglobulin lysis times (min) were determined at the onset and at regular intervals. Heart rates and minute ventilation increased significantly with most of the change occurring by min 5. Transcutaneous PO2 declined exponentially but stabilized by min 10. Euglobulin lysis time response was highly variable with individual changes from 2-38% observed. Further, the group appeared to fall into two classes that could be described as responders versus non-responders. The variability of these data suggest that hypoxia may not be a direct cause of tissue plasminogen activator release into the circulation but that susceptible individuals may exhibit a substantial fibrinolytic response to hypoxia. Those factors that explain the variability require further elucidation.

A second domain of simian virus 40 T antigen in which mutations can alter the cellular localization of the antigen.

Previous studies have demonstrated that mutations at amino acid position 128 of the simian virus 40 large T antigen can alter the subcellular localization of the antigen. A second domain in which mutations can alter localization of the nuclear antigen has been identified by mutations at amino acid positions 185, 186, and 199. Mutations in this region cause the polypeptide to accumulate in both the nucleus and cytoplasm of monkey cells. These T-antigen variants accumulate to near normal levels, but they don't bind to the simian virus 40 origin of DNA replication and are unable to mediate DNA replication. Furthermore, the altered tumor antigens can no longer transform secondary rat cells at normal efficiency, but they retain the ability to transform established mouse and rat cell lines.