Depression of systolic and diastolic myocardial reserve during atrial pacing tachycardia in patients with dilated cardiomyopathy.

Previous reports have shown that increases in heart rate may result in enhanced left ventricular (LV) systolic and diastolic performance. To assess whether this phenomenon occurs in the presence of depressed LV function, the effects of pacing on LV pressure and volume were compared in seven patients with dilated cardiomyopathy (LV ejection fraction 0.19 +/- 0.11) and six patients with no or minimal coronary artery disease (LV ejection fraction 0.69 +/- 0.11). Patients with normal LV function demonstrated significant increases in LV peak-positive dP/dt, LV end-systolic pressure-volume ratio, LV peak filling rate, and a progressive leftward and downward shift of their pressure-volume diagrams, compatible with increased contractility and distensibility in response to pacing tachycardia. There was no change in LV peak-negative dP/dt or tau. Patients with dilated cardiomyopathy, in contrast, demonstrated no increase in either LV peak-positive dP/dt or the end-systolic pressure-volume ratio, and absence of a progressive leftward shift of their pressure-volume diagrams. Moreover, cardiomyopathy patients demonstrated no increase in LV peak-negative dP/dt or LV peak filling rate and a blunted downward shift of the diastolic limb of their pressure-volume diagrams. Tau, as determined from a derivative method, became abbreviated although never reaching control values. We conclude that patients with dilated cardiomyopathy may demonstrate little or no significant enhancement in systolic and diastolic function during atrial pacing tachycardia, suggesting a depression of both inotropic and lusitropic reserve.

Antithrombotic therapy and the transition to the catheterization laboratory in UA/NSTEMI.

The management of unstable angina/non ST elevation myocardial infarction (UA/NSTEMI) has evolved substantially in recent years. Multiple new antithrombotic options are available; in addition, the use of interventional strategies in patients with UA/NSTEMI has become the dominant strategy, particularly in tertiary centers. On the one hand, we are doing more percutaneous interventions more rapidly in ACS patients. On the other hand, we have an ever-expanding therapeutic armamentarium to apply in these complex clinical circumstances. Much of the controversy surrounding modern-day management is not so much about the specific the choice of agent or strategy, but rather how to use these agents most effectively in a clinical environment where patients may come forward to the catheterization laboratory, sometimes rapidly, and may require percutaneous or surgical revascularization. All available antithrombotic agents act on one (or more) of the four steps of coagulation: platelet activation, platelet aggregation, thrombin generation, and thrombin activity. The antiplatelet agents, aspirin, thieno-pyridines, and glycoprotein (GP) IIb/IIIa antagonists, target the early steps of platelet activation and aggregation. The antithrombin agents, unfractionated heparin, low molecular weight (LMW) heparin, Xa inhibitors, and direct thrombin antagonists, act specifically to target thrombin generation, thrombin activity, or both. We will review the major recent trials that comprise the current state of knowledge regarding these new antithrombotic agents in ACS, and discuss some of the near-future additions to our armamentarium, including prasugrel, Cangrelor, and AZD6140. The most recent ACC/AHA and ESC unstable angina guidelines have emphasized that multiple options are available, and no one agent can be recommended over the others in all cases. There is NOT one perfect antithrombotic regimen for all patients. Antithrombotic therapy needs to be individualized, and that so-called ''standard'' therapy may need to be supplemented (or even replaced) in specific circumstances. Ultimately, determining optimal therapy means understanding the physiology, understanding the therapeutic options - not just how they work, but how they may work together, and being able to interpret a never-ending supply of new clinical trial data that have to be applied in the ''real world''.

Comparison of Hemochron and HemoTec activated coagulation time target values during percutaneous transluminal coronary angioplasty.

OBJECTIVES: The aim of this study was to determine whether activated coagulation time measurements from Hemochron and HemoTec machines can be used interchangeably and whether similar activated coagulation time target ranges for adequate anticoagulation can be applied to both machines. BACKGROUND: Adequate anticoagulation is necessary for the safe performance of intravascular interventions such as percutaneous transluminal coronary angioplasty. In current practice, anticoagulation status is frequently assessed by way of the activated coagulation time with one of two commercially available systems, HemoTec and Hemochron. Each one employs a different technique to determine the time of clot formation; however, the same target activated coagulation time values for adequate anticoagulation have been used interchangeably in published studies. METHODS: A total of 311 paired samples were compared in 113 high risk patients undergoing angioplasty enrolled in a randomized trial of a platelet glycoprotein IIb/IIIa receptor antibody. Simultaneous activated coagulation time measurements were obtained before and after administration of heparin, and the difference between the values of both machines was calculated. The relation between the Hemochron and HemoTec values was determined by using linear regression analysis. All activated coagulation time measurements were classified as either therapeutic or subtherapeutic using an arbitrary activated coagulation time target of 300 s. RESULTS: There was a correlation between values from the two machines (r = 0.86), but the Hemochron values were consistently higher than the HemoTec values by a mean value +/- SD of 28 +/- 29%, with wide individual variation. After heparin administration, there was a significant (p < 0.0001) difference between the number of measurements classified as therapeutic by HemoTec (53%) and by Hemochron (94%). CONCLUSIONS: HemoTec and Hemochron activated coagulation time measurements cannot be used interchangeably. Appropriate target activated coagulation time ranges to determine adequate anticoagulation during coronary angioplasty need to be established for both machines; the target range for one machine should not be extrapolated to the other.

Efficacy of multiple balloon aortic valvuloplasty procedures. The Mansfield Scientific Aortic Valvuloplasty Registry Investigators.

To determine the efficacy of a second balloon aortic valvuloplasty procedure in comparison with the original procedure, 47 patients (18 men, 29 women; mean age 77 +/- 10 years) who underwent two balloon aortic valvuloplasty procedures over a mean interval of 6.4 months between procedures (range 2 days to 15 months) were retrospectively examined. The mean pressure gradient across the aortic valve was significantly higher before the first than before the second valvuloplasty procedure (62 +/- 21 vs. 53 +/- 21 mm Hg; p less than 0.05) and after the first compared with after the second procedure (32 +/- 13 vs. 28 +/- 14 mm Hg; p less than 0.05). The cardiac output and stroke volume after the first procedure were significantly greater than the values for these variables after the second procedure (4.4 +/- 1.1 vs. 3.8 +/- 1.1 liters/min; p less than 0.05; and 54 +/- 17 vs. 47 +/- 15 ml/beat; p less than 0.05, respectively). There were no significant differences in the change observed in any variable between the first and second procedures. At a mean follow-up interval of 5.3 months (range 6 days to 15 months) after the second procedure 18 (38%) of the 47 patients had died, 12 (25%) required surgical valve replacement and 4 (8%) required a third valvuloplasty procedure. Overall, 31 (66%) of 47 patients met clinical failure end points after the second procedure. Three patients had two failure end points. The 47 patients were divided into two groups on the basis of the interval between valvuloplasty procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia.

The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of right atrial pressure-volume relations in patients with and without an atrial septal defect.

Assessment of the complex relations between pressure and volume in the right atrium has been hampered in the past by difficulties in the measurement of atrial volume. Accordingly, in the present study the dynamics of right atrial pressure-volume relations were examined (with the use of an impedance catheter to measure right atrial volume) in patients with and without an atrial septal defect. Right atrial pressure and impedance volume were measured in 16 patients at the time of cardiac catheterization with the use of a multi-electrode impedance catheter to provide continuous, on-line, pressure-volume data. Eleven patients without evidence of an interatrial shunt were examined during normal respiration and during the Valsalva maneuver and contrasted with five patients with an atrial septal defect documented by oxygen saturation step-up and echocardiographic studies. Right atrial pressure-volume diagrams in patients without an atrial septal defect exhibited the normal figure eight pattern, with an A loop (atrial contraction) and a V loop (passive filling), corresponding to the A wave and V wave of right atrial pressure, respectively. During inspiration, mean right atrial pressure decreased and mean right atrial volume increased, consistent with augmented venous return. With the Valsalva maneuver, right atrial pressure increased and both right atrial stroke volume and mean right atrial volume decreased compared with baseline. Patients with an atrial septal defect demonstrated baseline pressure-volume diagrams similar to those of patients without an interatrial shunt. However, no change in mean right atrial volume occurred with either respiration or the Valsalva maneuver despite changes in right atrial pressure similar to those seen inpatients without an atrial septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of left ventricular end-systolic pressure-volume relations with an impedance catheter and transient inferior vena cava occlusion: use of this system in the evaluation of the cardiotonic effects of dobutamine, milrinone, Posicor and epinephrine.

The end-systolic pressure-volume relation has been postulated as a load-independent measure of cardiac contractility, but has been difficult to measure because of technical problems associated with the serial measurement of intracardiac volume over a physiologic range of ventricular loading conditions. Utilizing a multielectrode impedance catheter to assess continuous, on-line left ventricular relative volume during transient inferior vena cava occlusion, a method is described for determining the end-systolic pressure-volume relation and for assessing changes in this relation secondary to inotropic modulation. In particular, using this method, the relative inotropic properties were determined of four drugs: dobutamine, milrinone, epinephrine and an experimental cardiotonic agent (Ro 13-6438, Posicor). Left ventricular micromanometer pressure and impedance catheter volume were measured continuously in 10 open chest, anesthetized dogs and 14 pigs. Arterial pressure was altered over a range of 20 to 60 mm Hg by brief inferior vena cava constriction. A linear end-systolic pressure-volume relation was observed in pressure-volume diagrams constructed from on-line pressure and impedance catheter recordings. Administration of dobutamine, milrinone and epinephrine resulted in a leftward shift and an increase in the slope of the end-systolic pressure-volume relation as compared with baseline; Posicor did not alter the slope over a range of doses, despite an increase in the cardiac output secondary to arterial vasodilation. Volume changes as measured by the impedance method closely paralleled simultaneous changes in the ultrasonic crystal-determined segment length, and the impedance end-systolic pressure-volume relation slope was reproducible with repeated load-altering maneuvers.(ABSTRACT TRUNCATED AT 250 WORDS)

Diastolic function in patients with aortic stenosis: influence of left ventricular load reduction.

Pressure overload hypertrophy of the left ventricle due to aortic stenosis is associated with abnormalities of left ventricular isovolumic relaxation and early diastolic filling. The relative contribution of the hemodynamic load on the left ventricle to the impairment of diastolic function observed in this disorder remains poorly understood. To study this relation, the vasodilator nitroprusside was administered to eight patients with aortic stenosis and normal systolic function. The effect of a short-term reduction in left ventricular preload and afterload on left ventricular isovolumic relaxation and early diastolic filling was assessed by analysis of simultaneous micromanometer left ventricular pressure and radionuclide angiographic volume measurements. At baseline, left ventricular systolic and end-diastolic pressures were markedly elevated, and associated with prolongation of the time constant of left ventricular relaxation and depression of the left ventricular peak filling rate. Infusion of nitroprusside resulted in reduction of left ventricular systolic (204 +/- 31 to 176 +/- 31 mm Hg, p less than 0.05) and end-diastolic (31 +/- 8 to 18 +/- 6 mm Hg, p less than 0.05) pressures, with no associated improvement in time constant of left ventricular pressure decay (T) (68 +/- 25 to 80 +/- 37 ms, p = NS), T 1/2 (34 +/- 8 to 34 +/- 14 ms, p = NS), left ventricular peak filling rate (2.3 +/- 0.5 to 2.3 +/- 0.8 end-diastolic volume/s, p = NS) or time to left ventricular peak filling rate (150 +/- 50 to 144 +/- 37 ms, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Endoluminal reconstruction of the arterial wall with endothelial cell/glue matrix reduces restenosis in an atherosclerotic rabbit.

OBJECTIVES: The objectives of this study were 1) to improve the attachment of reimplanted endothelial cells (EC) using a fibrin glue, and 2) to assess the impact of endothelial reseeding on restenosis eight weeks after balloon angioplasty. BACKGROUND: A possible mechanism contributing to restenosis after balloon angioplasty is the loss of the EC lining. Previous attempts to reseed EC had little effect due to rapid loss of the seeded cells. METHODS: Twelve atherosclerotic rabbits were subjected to angioplasty of iliac arteries and reseeding procedure. One iliac artery was subjected to EC/glue reconstruction and a contralateral site to EC seeding without glue. The animals were sacrificed after 4 h. In another series 12 rabbits were treated in the same fashion and were restudied at eight weeks. Additionally, in 10 animals one iliac was subjected to glue treatment, and another served as control. RESULTS: Histological examination demonstrated the ability of this method to reattach the EC/glue matrix circumferentially to 68.0 +/- 6.7% of the arterial wall in comparison with 13.5 +/- 3.9% reattachment after EC seeding. Morphometry at eight weeks showed that the lumen area was significantly greater in the EC/glue group (1.23 +/- 0.35 mm2) than in the EC seeding alone (0.65 +/- 0.02 mm2) and 0.72 +/- 0.41 mm2 in the glue group. This was principally accounted for by the statistically significant differences in the intimal area (0.76 +/- 0.18 mm vs. 1.25 +/-0.26 mm2 and 1.01 +/- 0.53 mm2, respectively). CONCLUSIONS: The attachment of EC after angioplasty can be greatly improved with fibrin glue matrix. The near 70% endothelial coverage achieved by this method resulted in a significant reduction of restenosis in atherosclerotic rabbit.

Influence of insurance type on the use of procedures, medications and hospital outcome in patients with unstable angina: results from the GUARANTEE Registry. Global Unstable Angina Registry and Treatment Evaluation.

OBJECTIVES: The purpose of this study was to investigate whether or not there is an association between managed care insurance and the delivery and outcome of care in patients presenting with unstable angina. BACKGROUND: The proportion of U.S. patients with managed care health insurance is increasing. This may be associated with recent improvements in the control of health care costs. It is unknown whether or not there is a difference in process of care in angina patients presenting with managed care versus fee-for-service health insurance. METHODS: We compared baseline characteristics, process and outcome of care in 636 patients with managed care insurance (MC) and 1,404 patients with fee-for-service (FFS) insurance who presented with unstable angina to 35 hospitals participating in the global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry. RESULTS: Although, there was little difference in baseline characteristics and hospital treatments between cohorts, MC patients were more likely to be discharged on guideline-recommended medications (aspirin and beta-adrenergic blocking agents). In addition, FFS patients were more likely to undergo cardiac catheterization (odds ratio = 1.25 95% confidence interval = 1.1 to 1.5), but not revascularization during the hospitalization. There was no difference in hospital mortality (0.9% versus 1.2% in MC versus FFS; p = 0.60). CONCLUSIONS: In patients admitted with suspected unstable angina, MC patients are less likely to undergo coronary angiography, but are more likely to be discharged on indicated medications.

Relation between procedural activated coagulation time and outcome after percutaneous transluminal coronary angioplasty.

OBJECTIVES: The purpose of this study was to determine whether a low procedural activated coagulation time is associated with a high rate of in-hospital complications and to identify whether there is an activated coagulation time range that may be associated with a low rate of complications. BACKGROUND: In recent years the activated coagulation time has come into widespread use for monitoring anticoagulation in the catheterization laboratory. However, considerable controversy exists as to the standards by which to judge "adequate" anticoagulation for interventional procedures. METHODS: From a total of 1,469 consecutive patients with percutaneous transluminal coronary angioplasty, we retrospectively identified 103 (Group I, 7% of the overall population) with major complications of death or emergency or urgent coronary artery bypass graft surgery and compared them with 400 patients without complications (Group II). Group I patients had more high risk clinical characteristics, such as type B and C lesions, class III and IV angina, recent myocardial infarction and recent thrombolytic treatment. Activated coagulation times were compared between Groups I and II at baseline, after administration of 10,000 U of heparin and at the end of the procedure. RESULTS: There were no differences in baseline activated coagulation times between Groups I and II. Group I had significantly lower activated coagulation times after heparin therapy and at the end of the procedure: 61% < 250 s, 20% between 250 and 275 s, 11% between 275 and 300 s and 8% > 300 s; 279 of Group II had activated coagulation times 27% < 250 s, 17% between 250 and 275 s, 35% between 275 and 300 s and 21% > 300 s (p < 0.0001). Complications occurred in all patients with final activated coagulation times < 250 s but in only 0.3% of patients with final activated coagulation times > 300 s. CONCLUSIONS: A diminished activated coagulation time response to an initial bolus of heparin is associated with major in-hospital complications after coronary angioplasty, although patients with complications did have a higher risk before the procedure. It remains to be determined whether there is an ideal "target" activated coagulation time for interventional procedures.

The current practice of intra-aortic balloon counterpulsation: results from the Benchmark Registry.

OBJECTIVES: This study presents clinical data from the first large registry of aortic counterpulsation, a computerized database that incorporates prospectively gathered data on indications for intra-aortic balloon counterpulsation (IABP) use, patient demographics, concomitant medication and in-hospital outcomes and complications. BACKGROUND: The intra-aortic balloon pump (IABP) is widely used to provide circulatory support for patients experiencing hemodynamic instability due to myocardial infarction, cardiogenic shock, or in very high risk patients undergoing angioplasty or coronary artery bypass grafting. METHODS: Between June 1996 and August 2000, 203 hospitals worldwide (90% U.S., 10% non-U.S.) collected 16,909 patient case records (68.8% men, 31.2% women; mean age 65.9 +/- 11.7 years). RESULTS: The most frequent indications for use of IABP were as follows: to provide hemodynamic support during or after cardiac catheterization (20.6%), cardiogenic shock (18.8%), weaning from cardiopulmonary bypass (16.1%), preoperative use in high risk patients (13.0%) and refractory unstable angina (12.3%). Major IABP complications (major limb ischemia, severe bleeding, balloon leak, death directly due to IABP insertion or failure) occurred in 2.6% of cases; in-hospital mortality was 21.2% (11.6% with the balloon in place). Female gender, high age and peripheral vascular disease were independent predictors of a serious complication. CONCLUSIONS: This registry provides a useful tool for monitoring the evolving practice of IABP. In the modern-day practice of IABP, complication rates are generally low, although in-hospital mortality remains high. There is an increased risk of major complications in women, older patients and patients with peripheral vascular disease.

Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention.

OBJECTIVES: The goal of this study was to test: 1) if platelet glycoprotein IIb/IIIa (GP IIb/IIIa) blockade with abciximab bolus plus 12-h infusion reduces mortality after percutaneous coronary intervention (PCI); 2) if prevention of early myocardial infarction (MI) after PCI is a mechanism for reducing mortality; and 3) for risk factors for mortality after PCI. BACKGROUND: Studies of PCI suggest that MI after intervention is predictive of mortality. Abciximab, a platelet GP IIb/IIIa receptor inhibitor, has consistently reduced the incidence of MI among PCI patients in several trials. The presumed mechanism is prevention of platelet thrombus associated with vessel wall injury and downstream embolization into the microcirculation. METHODS: In eight trials, 5,154 patients were randomized to a regimen comprising conventional therapy plus a bolus of abciximab within 1 h before PCI followed by a 12-h infusion; 4,136 controls were randomized to conventional therapy alone. Patient follow-up from six months to three years was available. Survival differences are examined using proportional hazards regression and survival curves. RESULTS: A hazard ratio of 0.71 (95% confidence interval 0.57 to 0.89; p = 0.003) suggests a mortality benefit with abciximab. The absolute reduction in mortality was estimated to be 0.5% through 30 days, 0.7% through six months, 0.9% through one year and 1.8% through three years. Early MI explained 18% of the observed mortality benefit at one year. Multivariate regression suggests that patients with advanced cardiovascular disease may derive the greatest mortality benefit from abciximab. CONCLUSIONS: The evidence from 9,290 randomized PCI patients shows a mortality benefit provided by abciximab bolus plus 12-h infusion.

Systolic, diastolic, and combined hypertension. Differences between groups.

We used a classification system of systolic, diastolic, and combined (both systolic and diastolic) hypertension to ascertain whether there were significant differences between the groups. The study involved 182 consecutive outpatients for whom no secondary cause of hypertension could be found. There were 96 male and 86 female patients, with a mean age of 45.8 years. There were significant differences in age, with the systolic group being the oldest and the diastolic group the youngest. There were also differences in the prevalence of complications among the categories. Peripheral vascular disease, retinopathy, and coronary artery disease were more prevalent in the systolic and combined groups, while diabetes was more prevalent in the systolic group. We conclude that there appear to be clinical differences between systolic, diastolic, and combined hypertension with respect to presenting characteristics and complications.

Optimal antithrombotic treatment for percutaneous coronary intervention.

Recent years have witnessed significant advances in the percutaneous treatment of patients with atherosclerotic vascular disease. Anti-platelet and anti-thrombotic agents are routinely administered to minimize the risk of peri-procedural myonecrosis, stent thrombosis and other procedural complications. This article presents a current view of optimal adjunctive antithrombotic therapy for percutaneous coronary interventions (PCI), recognizing that optimal is a necessarily subjective label. This article focuses specifically on anticoagulant agents such as unfractionated heparin (UFH), the low-molecular weight heparins (LMWH), and direct thrombin inhibitors, and antiplatelet agents, such as aspirin, thienopyridines, and glycoprotein IIb/IIIa antagonists. It starts with a general discussion of anticoagulation and percutaneous intervention, followed by a summary of the modern-day view of the coagulation process. The mechanism of action of the individual agents is then presented, followed by some of the evidence base of recent clinical trials of anticoagulant and antiplatelet agents in PCI. Finally, we present summary recommendations for procedural anticoagulation in low risk, not-low risk, and high risk PCI, and list what we feel are appropriate doses for the agents employed. Ultimately, though, it is the individual interventional cardiologists who must decide for themselves exactly what constitutes optimal antithrombotic therapy for PCI.

Complications associated with combined use of abciximab and an intracoronary thrombolytic agent (urokinase or tissue-type plasminogen activator).

A potent platelet inhibitor combined with an intracoronary thrombolytic agent is aggressive therapy that may be used for high-risk, complex, refractory thrombotic coronary lesions. A retrospective review of the records of 56 patients who received abciximab plus an intracoronary thrombolytic agent during a coronary interventional procedure did not reveal a prohibitive incidence of major bleeding with this combination therapy.

Significance of nitroglycerin-induced hypotension with inferior wall acute myocardial infarction.

Up to 60% of patients with inferior wall acute myocardial infarction (AMI) develop hypotension. In many cases, profound hypotension is precipitated by the administration of nitroglycerin. To test the hypothesis that this hypotensive response to nitroglycerin may be related to right ventricular (RV) involvement, we compared 20 patients with electrocardiographic and enzyme-documented inferior wall AMI and marked hypotension (greater than 30 mm Hg decrease in systolic blood pressure, with symptoms) after nitrate administration, to 20 patients with documented inferior AMI, but without hypotension after administration of nitroglycerin. The presence of RV involvement was determined by electrocardiographic criteria of 1 mm of ST-segment elevation in at least 2 right precordial chest leads. Fifteen of the 20 patients who demonstrated a marked hypotensive response to nitroglycerin had evidence of RV involvement, while in 18 of the 20 patients without hypotension after nitrates there was no evidence of RV involvement. In a separate analysis of 28 patients with documented RV involvement in an inferior AMI, 20 developed hypotension in response to nitrates. Thus, in the setting of an inferior AMI, a marked hypotensive response to nitrates suggests the presence of RV involvement. Moreover, hypotension after nitrate administration may be anticipated in patients with known RV infarction, and in such patients, nitrates should be administered carefully.

Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]).

Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n = 429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One fourth of patients were also assigned open-label adjunctive cholestyramine up to 12 g/day because prerandomization LDL cholesterol remained > or = 160 mg/dl. The primary end point, assessed by quantitative coronary angiography, was within-patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions. Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin patients (+/- cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients) showed significantly less lesion progression in all fluvastatin versus all placebo patients, deltaMLD -0.028 versus -0.100 mm (p <0.01), and for fluvastatin alone versus placebo alone, deltaMLD -0.024 versus -0.094 mm (p <0.02). A consistent angiographic benefit with treatment was seen whether baseline LDL cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment were also consistently seen in clinical event rates but were not statistically significant. Thus, lipid lowering by fluvastatin in patients with mildly to moderately elevated LDL cholesterol significantly slowed CHD progression.

Platelet glycoprotein IIb/IIIa receptor blockade with abciximab reduces ischemic complications in patients undergoing directional coronary atherectomy. EPILOG Investigators. Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa Receptor Blockade.

We determined the efficacy of abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, combined with low-dose weight-adjusted heparin in reducing ischemic complications in patients undergoing directional coronary atherectomy (DCA). The Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial demonstrated a reduction in the incidence of non-Q-wave myocardial infarction in DCA patients who were treated with abciximab bolus and infusion plus heparin. This benefit, however, was associated with increased bleeding complications. Of the 2,792 patients who had coronary intervention in the Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa receptor blockade (EPILOG) trial, 144 (5%) underwent DCA. Patients were randomly assigned to 3 treatment groups: placebo with standard-dose, weight-adjusted heparin; abciximab with low-dose weight-adjusted heparin; or abciximab with standard-dose weight-adjusted heparin. Study end points included 30-day and 6-month composite incidence of death, myocardial infarction, or revascularization. Compared with those undergoing percutaneous transluminal coronary angioplasty (PTCA), DCA patients had a higher rate of myocardial infarction (11.1 % vs 4.9%, p = 0.001) and predominantly non-Q-wave myocardial infarction (9.7% vs 4.4%, p = 0.004). Abciximab was associated with a 57% lower combined rate of death, myocardial infarction, or urgent revascularization within 30 days following DCA (20% placebo vs 8.7% abciximab with low-dose heparin) without excess risk of bleeding complications. A combined analysis of data from the EPIC and EPILOG trials demonstrates a reduction in the rate of death or myocardial infarction (19.9% vs 8.4%, p = 0.008) at 30 days that was sustained for up to 6 months in the abciximab-treated patients. These findings support the premise that non-Q-wave myocardial infarction in DCA patients are platelet mediated.

Differences between men and women in the management of unstable angina pectoris (The GUARANTEE Registry). The GUARANTEE Investigators.

Few data are available in prospectively collected cohorts of patients with unstable angina pectoris or on the use of appropriate medications or interventions. Accordingly, we evaluated 2,948 consecutive patients with unstable angina admitted to 35 hospitals in the United States in 1996, and comparing men and women (39% of the patients were women). Differences were seen in coronary risk profiles with a higher incidence of systemic hypertension, diabetes mellitus, and a family history of coronary disease in women. Women were less likely to receive Agency for Health Care Policy Research (AHCPR) recommended pharmacologic treatment than men. Cardiac catheterization, coronary angioplasty, and bypass was performed less often in women compared with men (44% vs. 53%, p = 0.002; 12% vs. 18%, p = 0.02; 7% vs. 10%, p = 0.001, respectively). At catheterization, women were more likely to have no significant coronary artery disease (25% vs. 14%, p = 0.001). Although fewer women than men fulfilled the AHCPR criteria for cardiac catheterization (54% vs. 64%, p = 0.001), a similar rate of men and women with positive criteria underwent catheterization and angioplasty. However, fewer women with positive criteria underwent bypass surgery (36% vs. 46%, p = 0.03). More men "ruled-in" for a myocardial infarction at admission (13% vs. 8%, p = 0.001), but there was no difference in recurrent angina, in-hospital myocardial infarction, or death. Despite different epidemiologic profiles and less evidence of coronary artery disease by noninvasive and invasive tests, women and men had similar outcomes.