session highlights from the american college of cardiology meeting: march 16-19, 1997

AHJ at the Meetings

Session highlights from the American College of Cardiology Meeting: March 16-19, 1997 Karen Alexander, MD, Gregory W. Barsness, MD,Julie M. Miller, MD, and Chen Y.Tung, MD Durham, N.C.

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Electrophysiology Session Advances in Defibrillation/Inplantable Antiarrhythmic

Devices

Study: 720: Factors Associated With Shock Delivery in the MulticenterAutomatic Defibrillator ImplantationTrial (MADI13

Presenter: Dr. Sanjeev Saksena, Eastern Heart Institute,

Passaic, NJ.

Results: The MulticenterAutomatic Defibrillator Implantation Trial (MADIT)I was a randomized clinical trial comparing patients receiving prophylactic therapy for coronary disease with asymptomatic, nonsustalned ventricular tachycardia (3 to 30 beats) and an implanted defibrillator with conventional medical therapy in patients with previous myocardial infarction and left ventricular dysfunction. In this study, the pattern and predictors of shock delivery in the implantable defibrillator arm

of the trial were examined. Ninety patients with inducible but not suppressible ventricular tachycardia at electrophysiologic testing, mean age 62 _+ 9, mean left ventricular ejection fraction of 27% -+ 7%, who received an implantable defibrillator were followed-up for up to 5 years. Patients who received shocks (group 1, n = 44) were compared with those who did not receive shocks (group 2) regarding their demographic, clinical, arrhythmia, and electrophysiologic characteristics.The mean ejection fraction of patients receiving shocks was slightly lower (26% + 7%) than those who did not (28% + 6%, p = 0.09).At baseline, group 1 had a higher incidence of more than one myocardial infarct ion than did group 2 (49% vs 24%,p = 0.013) and a trend toward more diabetes.There was no other clinical difference between

groups and no significant difference in the use of drug therapy, coronary artery bypass grafting, or percutaneous

transltuninal coronary angioplasty. Both groups had simi-

From the Division of Cardiology, Department of Medicine, Duke University Medical Center. Reprint requests: Duke Clinical Research Institute, 2024 West Main St., Durham, NC 27705. Am Heart J 1997;13854. Copyright © 1997 by Mosby- Year Book, Inc. 0002-8703/97/$5.00 + 0 4/1/83110

lar ventricular tachycardia morphologic characteristics and cycle length at baseline. Shock delivery was not pre- dicted by age, sex, smoking, electrocardiogram abnormalities, New York Heart Association functional class, hyper-

tension, diabetes, or coronary revascularization.A total of 223 shocks were delivered in 44 patients, with a majority occurring in the first year. By using a Cox proportional hazard model at 1 year, shock delivery was significantly associated with >2 prior myocardial infarctions per year

(hazard ratio = 3), duration of index nonsustained ventricular tachycardia episode (mean number of consecutive beats of tachycardia of 12 _+ 10 in group 1 compared with 8.5 -+ 9 group 2), and diabetes (hazard ratio of approximately 10.6). Baseline ejection fraction of <25% was associated with shock delivery at 1 year but was insignificant beyopd 1 year.

Interpretation: In MADIT patients who received implantable defibrillators, history of recurrent myocardial infarction, diabetes mellitus, and longer ventricular tachycardia episodes were associated with an increased incidence of shock delivery.

References 1. Moss Aj, et ok Improved survival with an implanted defibrillator in

patients with coronary disease at high risk for ventricular arrhythmia N EngJ j Med 1996;335:1933-40.

Session Internal Defibrillation/Implantable Antiarrhythmic

Devices

Poster: 937-126:The Implantable Cardioverter Defibrillator Prolongs Survival in Yentricular Fibrillation Patients Who Are Revascularized

Presenter: Dr. M.S. Link, New England Medical Center, Boston, Mass.

Results: Twenty-nine consecutive survivors of ventricular fibrillation who underwent revascularization were followed-up long term (36 +- 21 months). Mean age was

64.5 years, mean ejection fraction was 35% -+ 12%. Twenty-one patients had documented ischemia before revascularizati0n. Programmed electrical stimulation

was performed in all patients, with seven patients with inducible and 22 with noninducible ventricular fibrillation or ventricular tachycardia. M1 inducible and 12

AH,j at the Meetings 139

noninducible patients received implantable cardio

defibrillator (ICD) devices.There were 11 recurrent arrhythmias and eight deaths over the follow-up peri-

od.There were three sudden deaths, two in patients without ICDs (at 5 and 12 months), and one that

occurred at 50 months in a patient with an ICD.A low ejection fraction was a significant predictor of recur-

rent arrhythmia.There was no significant predictive

value for recurrent arrhythmia based on induciblity at time of PES, treatment with ICD, or other arrhythmia

treatment.Treatment with an ICD was predictive of sur-

vival (p = 0.058).

Interpretation: Revascularization as the sole treatment of survivors of ventricular fibrillation with coronary

artery disease is controversial. In this small study- of long-term outcome of ventricular fibriUation survivors

who received revascularization, the risk of recurrent

arrhythmia and death remained high regardless of inducibility. Improved survival was observed in patients

treated with ICDs, but the borderline statistical signifi-

cance in this small observational study stimulates cau- tion.Treatment with ICDs could be considered in sur-

vivors of ventricular fibrillation, regardless of

inducibility or revascularization; further clinical trials are necessary, however.

Session: Late Breaking ClinicalTrials II

Study: Ibutilide forAFTerminationAfter Cardiac Surgery

Presenter: Dr. Peter R. Kowey, Lankenau Hospital and Medical Research Center, Wynnewood, Pa.

Results: Three hundred two patients with either atrial fibrillation (n = 201) or atrial flutter (n = 101) after car-

diac surgery were randomly assigned to three doses of

ibutilide or placebo for termination of their arrhythmia. At a dose of 1.0 mg ibutilide, sinus rhythm was achieved

in 57% of patients (44% with atrial fibriUation, 78% with

atrial flutter). Patients receiving digoxin had a higher likelihood of success.The mean time to conversion was

32 minutes, with no responders converting after 90 minutes. Maintenance of sinus rhythm persisted in 64%

of converters at 24 hours. Overall, ventricular arrhythmias occurred in 9.6% with ibutilide versus 1.2% with

placebo. The incidence of torsades de pointes was 1.8%

in patients treated with inbutilide(0.9% sustained and

0.9% nonsustained).

Interpretation: Ibutilide has a dose-dependent effect on

termination of postoperative atrial fibrillation and atrial

flutter, with 1.0 mg yielding initial success in 57% of

patients and persistence of sinus rhythm in two thirds of converters. Serious ventricular arrhythmias, conmaon

with many antiarrhythmic drugs, occurred in 1.8% of

patients treated with ibutilide. Ibutilide is a useful addi-

tion to current therapy for the treatment of atrial arrhythmias after cardiac surgery.

Session Advances in Defibrillation/Implantable Antiarrhythmic

Devices

Study: 720-2: Comparative Survival of MADIT-Eligible But

Noninducible Patients

Presenter: Dr. James P Danbert, University of Rochester,

N.Y.

Results: The Mult icenterAutomatic Defibrillator

Implantat ion Trial (MADIT)I was a randomized clini-

cal trial designed to study whe ther prophylactic ther-

apy with an implanted defibrillator, compared with

convent ional medical therapy, would improve survival

in patients with asymptomatic, nonsus ta ined ventricu-

lar tachycardia (3 to 30 beats), previous myocardial

infarction, and left ventr icular dysfunction (ejection

fraction <-0.35). Eligible patients unde rwen t electro-

physiologic study and qualified for enrol lment if sus-

tained ventr icular tachycardia or ventr icular fibrilla-

t ion was r>eproducibly induced and not suppressed

with intravenous procainamide. Over a 5-year period,

32 hospital centers randomly assigned 196 patients to

receive an implanted defibri l lator (n = 95) or con-

vent ional medical therapy (n = 101). Over the same

period of time, all patients screened at three hospital

centers and found to meet all other MADIT eligibility

criteria, but be noninduc ib le and therefore not ran-

domized, were followed-up unti l MADIT termination.

This non induc ib le cohort was compared with the

subgroup of patients who were inducible, nonsup-

pressible, and randomly assigned in the MADIT trial to

convent ional therapy (MADIT-CONV). Of MADIT-

CONV patients, 74% received amiodarone therapy

and 10% received a class 1A agent. Differences in

baseline characteristics be tween groups included

eject ion fraction (noninducible = 0.27 versus MADIT-

CONV 0.25,p = 0.035) and mean follow-up days

( n o n i n d u c i b l e = 592 versus MADIT-CONV = 755,

p = 0.025). Kaplan-Meier survival at 1, 2, and 3 years

in the noninducib le group was 98%, 96%, and 71% respectively, whereas that of the MADIT-CONV group

was 77%, 68%, and 57%.

Interpretation: The study suggests that patients with

noninducible ventricular tachycardia have an improved

survival up to 3 years, compared with patients with

inducible ventricular tachycardia treated with conven-

tional medical therapy.

American Hearl journak Volume 134, Number 1

140 AHJ at the Meetings

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References 1. Moss AJ, et al. Jmproved survival with an implanted defibrillator in

patients with coronary disease at high risk for ventricular arrhythmio. N Eng[ j Med 1996;335:1933-40.

Secondary Prevention Session New Observations From Hypolipidemic Drug Trials for

Atherosclerosis

Study: 725-5 :The Influence of Serum Vitamin E on

Cardiac Risk in Patients With Advanced Coronary Disease: Data from the CHAOS Trial

Presenter: Dr. Nigel G. Stephens, Northwick Park Hospital, Harrow, United Kingdom

Results: To evaluate the association of increased, although unsupplemented, levels of the antioxidant vitamin E and cardiac risk, Stephens and collegues studied

855 patients receiving placebo in the Cambridge Heart AntiOxidant Study (CHAOS).They found an incremental, inverse relation be tween baseline vitamin E levels

and cardiac risk.

Interpretation: In this study low levels of antioxidant vitamin E were an independent risk factor for both death and myocardial infarction.This result is consistent with

the report of the full randomized trial, which showed a reduction in the composite of death and myocardial

infarction in patients randomly assigned to receive vita- minE.

Session Coronary Prevention: Cholesterol, Smoking,Aspirin, and

Wine

Study: 718-4: Lessons From The West of Scotland

Coronary Prevention Study (WOSCOPS):Who Should Be Treated?

Presenter: Dr.James Shepherd, Glasgow Royal Infirmary, Scotland

Results: The West of Scotland Coronary Prevention Study I showed that primary prevent ion with pravas-

tatin treatment for moderate hypercholeste'rolemia sig-

nificantly reduced the incidence of cardiovascular death (32% relative risk reduction) and nonfatal myocardial infarction (31% relative reduction).The

WOSCOPS population consisted of 6595 men aged 45 to 64 years with no history of myocardial infarction and total cholesterol of 6.5 to 8.0 mmol/L at initial screen-

ing who were randomly assigned to pravastatin (40 mg/day) treatment or placebo and followed-up for a mean of 4.9

years. Previous subgroup analysis showed that coronary event rates at 5 years were >10% (the current

European treatment threshold) in subgroups with pre-

existing vascular disease and in men ->55 years wi thout symptoms of coronary disease but with at least one other risk factor.t Significant univariate predictors of

outcome were minor electrocardiographic abnormali- ty, preexisting vascular disease, current smoking status, diabetes mellitus, history of hypertension, family histo-

ry of coronary heart disease, and nitrate consumption. Predictive cont inuous variables included age, height,

blood pressure, LDL and HDL cholesterol levels, and total cholesterol/HDL cholesterol ratio. Patients with the highest risk of death or nonfatal myocardial infarc-

tion (>10% 5-year risk) were those with minor electrocardiogram abnormalities, preexisting vascular disease, and

current smoking status. Patients >55 years also had a >10% event rate ff they had hypertension, HDL cholesterol level < 1.1 mmol/L, or a family history of coronary

heart disease. Over a 5-year period, 10,000 patients eligible forWOSCOPS would need to be treated to prevent

318 cardiovascular events (31.4 men treated to prevent one cardiovascular event), with a cost per life-year

saved of£20,375 (discounted at 6%). By using the predictors of outcome from the study, the model can identify high-risk patients. If only high-risk patients are treat-

ed, 444 cardiovascular events would be prevented per 10,000 treated (22.5 men treated to prevent one cardiovascular event) with a discounted cost per life-year

saved of£13,995.This is slightly less than the current accepted European cost of dialysis therapy and hor- mone replacement therapy.A targeted approach to

treatment would identify, in the top quartile of WOSCOPS patients at risk, 45% of primary end points

and 64% of deaths from coronary heart disease.

Interpretation: On the basis of theWOSCOPS data, patients with elevated cholesterol at high risk for cardiovascular events can be identified and selectively treated with

lipid-lowering therapy for primary prevention of coronary heart disease.Targeted treatment is more cost effective.

References 1. Shepherd j, Cobbe SM, et al. Prevention of coronary heart disease

with Pravastatin in men with hypercholesteroremia. N Engf J Med 1995:333;1301-Z

2. West of Scotland Coronary Prevention Group. WOSCOPS: identifica- tion of higbrisk groups and comparison with other cardiovascular inter vention triads [aacet 1996;348:1339-42.

Session New Observations From Hypolipidemic DrugTrials for

Atherosclerosis

Study: 725-6: Elevated Cholesterol in Elderly Survivors of Acute Myocardial Infarction Predicts Reinfarction in the Year After Discharge

American Heart Journal jury 1997

AHj at the Meetings 141

Presenter: Dr. H. M. Krumholz,Yale Univerisity School of

Medicine, New Haven, Conn.

Results: There are multiple competing risks in the elder-

ly that might limit long-term survival after myocardial

infarction (MI).To study the prognostic importance of

serum cholesterol in elderly survivors of MI, Krumholz

and collegues studied 5475 patients from the Cooperative

Cardiovascular Project cohort.After adjusting for multiple

clinical and demographic variables, patients with total

serum cholesterol levels >240 mg/dl were at significantly

increased risk for readmission with reinfarction within 1

year compared with patients with total serum choles-

terol levels <200 mg/dl.This association also held for

patients aged >_80 years.

Interpretation: Even in elderly survivors of MI, elevated

serum cholesterol is a predictor of increased 1-year risk

for reinfarction.

Session Coronary Prevention: Cholesterol, Smoking,Aspirin, and

Wine

Study: 718-1: Effect of Simvastatin on Ischemic Signs and

Symptoms in the Scandinavian Simvastatin Survival Study

(4S)

Presenter: Dr.John Kjekshus, National Hospital, Oslo,

Norway

Results: The Scandinavian Simvastatin Survival Study

(4S) ] was a multicenter trial randomly assigning 4444

patients with angina pectoris or previous myocardial

infarction and elevated total serum cholesterol levels

(>5.5 retool/L) to simvastatin (20 mg to 40 mg) or place-

bo.As previously reported, simvastatin reduced the rela-

tive risk of death by 30% (p = 0.0003) over a median fol-

low-up period of 5.4 years, accounted for by a 42%

reduction in coronary death (p = 0.001) for the treated

group.Annual follow-up visits included a physical exami-

nation and interview for new or worsening signs or

symptoms of atherosclerotic disease. Patients with a his-

tory of myocardial infarction who were randomly

assigned to simvastatin therapy had a significant reduc-

tion in the incidence of new angina (approximately 25%

relative risk reduction).There was no such significant

reduction in patients with a preexisting history of angi-

na. The relative risk of fatal or nonfatal cerebrovascular

events was 0.70 (95% confidence interval 0.52-0.96) in

the simvastatin group. In addition, new carotid bruits

were less likely to develop in patients who received treat-

ment: 2.0% placebo versus 1.1% simvastatin (p = 0.009),

relative risk 0.52 (95% confidence interval 0.32-0.85).

There was no significant difference in the development

of femoral bruits. Interestingly, symptoms of new or

worsening claudication were reduced from 3.6% to 2.3%

(p = 0.008), resulting in a 38% relative risk reduction.

Interpretation: Treatment with simvastatin appears to

reduce the risk of death and major cardiovascular events

as well as the development of cerebrovascular and

peripheral vascular symptoms.There appears to be a gen-

eral antiatherosclerotic effect from treatment with sim-

vastatin.

References 1 Scandinavian Simvas~atin Survival Study Group Randomized trial of

chdesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study. Lancet 1994;344:1383-9.

Session Late Breaking Clinical Trials II

Study: M-HART: Montreal Heart Attack Readjustment

Trial

Presenter: Dr. Nancy Frasure-Smith, Montreal Heart

Institute, Montreal, Canada

Results" This is the largest psychosocial intervention trial

performed to date in patients after myocardial infarction;

it was, designed to determine if interventions by trained

nursing personnel to reduce psychosocial stresses

reduced mortality rates in the year after myocardial

infarction. Patients responded to questionnaires to detect

their psychosocial stress level at i-month intervals. If

high levels of stress were detected, patients received

home visits from nurses trained to counsel patients and

lower stress levels. Because of lower than expected rates

of death at 1 year, this study was tmderpowered to detect

a difference between intervention and control in men in

whom no difference was seen. Surprisingly, intervention

was associated with a doubling of risk of mortality rate at

1 year in women. Most of the deaths in treated women

were in those with ejection fraction <35%, and women in

the intervention group had four times the number of

arnhythmic deaths as women in the control group.There

was no difference in in-hospital distress among women

who died and those who did not, but those who died

had increasing distress after their first nursing visit.

Interpretation: The results of this large trial of psycho-

social intervention were quite surprising. No difference

was detected in men undergoing psychosocial intervention,

but women who underwent psychosocial intervention

fared worse than those who did not.The possibility that

psychosocial intervention may be harmful, especially in

women, raises important questions for cardiac rehabilita-

tion programs.

American Heart Journal Volume 134, Number 1


Heart Failure Session Medical Management of Moderate to Severe Heart Failure

Study: 710-4: Preliminary Observations withVentricular

Remodeling Surgery for Refractory Congestive Heart Failure

Presenter: Dr. Randall Starling, Cleveland Clinic,

Cleveland, Ohio

Results: The results of 32 patients who underwent ven-

tricular remodeling procedure 03atista procedure) at the Cleveland Clinic were reported. Patients with dilated cardiomyopathy (leR ventricular internal dimension >7 cm)

and New York Heart Association class 3 or 4 were eligible

for the procedure if they did not have coronary disease or a history of myocardial infarction.The goal of the surgery was to reduce left ventricular size by resection of a portion of the free wall of the left ventricle (mean

weight of myocardinm removed: 89 gm). In addition, 30 of the 32 patients tmderwent mitral valve annuloplasty. Postoperatively, all patients were treated with amio-

darone and coumadin.The mean ejection fractions were 15% before operation (transesophageal echocardiogra-

play [TEE]), 33% after operation (TEE), and 23% 3 months after operation (transthoracic echocardiography). Mean left ventricular internal dimension decreased from 8.2 to

6.0 cm, whereas mean MR (echocardiography) decreased from 2.7 to 1.0 (on a scale of 0 to 4).There were no peri- operative deaths. In-hospital mortality rate was 0%, and

cumulative mortality rate at 6 months was 6.4%, which is not significantly different from previously reported series

of heart transplant recipients. During the follow-up period, 22% of patients required rescue therapy, either a left ventricular assist device (five patients) or heart transplantation (two patients), generally for early postoperative

failures. Functional capacity improved in 73% of patients discharged assessed at 2 months after operation.

Interpretation: These preliminary results suggest that

this procedure leads to significant improvement in left ventricular funct ion and functional capacity in patients with dilated cardiomyopathy. Short-term follow-up indi-

cates that the outcome is comparable with patients

undergoing heart transplantation. However, long-term follow-up and comparative studies versus mitral valve annuloplasty and cardiac transplantion will be needed

to determine the appropriate role for ventricular remodeling surgery in the management of end-stage dilated cardiomyopathy.

Session Natural History and Survival in Heart Failure

Study: 977-157:Alter'arian of Physician Behavior in the

Care of Congestive Heart Failure Patients in the Community

Hospital Setting Using American College of Cardiology/

American HeartAssociation Guidelines

Presenter: Dr. R.Andrew Rauh, Midwest Heart Research

Foundation, Lombard, Ill.

Results: Prior studies have shown that patients with con-

gestive heart failure cared for by family practitioners and

medical internists have longer and therefore more costly

lengths of stay compared with those cared for by cardiol-

ogists. Mean length of stay and mean cost per case for

fanlily practitioners and medical internists were assessed

before and after an intensive education program based

on the American College of Cardiology/American Heart

Association guidelines for management of congestive

heart failure.These results were compared with those for

cardiologists. For medical internists, both the mean

length of stay and the mean cost per case significantly

decreased after the education program. For family practi-

tioners, there was significant decrease of the mean length

of stay and a trend toward decreased cost.

Interpretation: Education programs based on the

ACC/AHA guidelines on management of congestive heart

failure ~ n reduce the mean length of stay and mean cost

per case of patient care by family practitioners and med-

ical internists.

Session Natural History and Survival in Heart Failure

Poster: 977-156:The Natural History of Heart Failure

with Preserved Left Ventricular Systolic Function

Presenter : Dr. Edward Philbin, Massachusetts General

Hospital, Boston, Mass.

Results: This was a prospective study of 801 patients (of

1402 consecutive patients) admitted at nonuniversity

hospitals for heart failure with left ventricular function

assessment. Diastolic dysfmaction, defined as ejection

fraction _>40%, occurred in 45% of the patients. During the

6 months of follow-up, the following outcomes were

observed: death (22%), hospital readmissions (43%), and func-

tional status. Outcomes were stratified by left ventricular

ejection fraction and adjusted for differences among the

groups. For all-cause mortality, those with ejection fraction

>40% had an odds ratio of 0.66 (p = O.04).There were no

significant differences in the mean length of stay, rehospi-

talization rates, functional status measures, and death

from congestive heart failure.

Interpretation: This study confirms the value of measur-

ing ejection fractin in elderly patients with congestive

heart failure treated in the community setting. However,

American Heart Journd July 1997

AHJ atthe Meetings I/[3

whether those with diastolic function have a different

prognosis requires further study.

Session Renal Function and Interventions in Heart Failure

Study: 785-5: Is It Safe to PrescribeAspifin to Patients on ACE-Inhibitors?

Presenter: Dr.Jonathan Lear, Ben Gurion University, Beer-Sheva, Israel

Results: In the SOLVD and CONSENSUS-II trials, a sub-

group analysis suggested that the benefits of enalapril in patients with heart failure might be attenuated by concomitant aspirin administration.Angiotensin-converting

enzyme (ACE) inhibitors cause a reduction in angiotensin

II and an increase in bradykinin.The increased bradykinin

and prostaglandins may mediate the vasodilatory effects of ACE inhibitors.The antiprostaglandin effects of aspirin might reduce this mechanism trACE inhibitors and

reduce their effectiveness for treatment of heart failure.

In an observational registry of 11,575 patients, all with known coronary artery disease, those patients who took

aspirin withACE inhibitors had a significant benefit in 5-year survival. In 5249 patients with NewYork Heart

Association class II or greater heart failure and coronary artery disease, those taking aspirin also had a significant

survival advantage at 4.2 years of follow-up (17% ASA, 32% noASA,p < 0.001) Even after adjustment for clinical

risk, the use of aspirin afforded a relative risk of death of

0.58.

Interpretation: In patients with coronary disease, those patients taking aspirin andACE inhibitors had a signifi-

cant reduction in mortality rate at 5 years of follow-up compared with those taking ACE inhibitors alone. In

patients with coronary disease and heart failure, the use of aspirin withACE inhibitors still afforded a mortality

benefit overACE inhibitors alone.Although this study does not provide a definitive answer to the question of

whether aspirin should be avoided in patients with non- ischemic heart failure taking ACE inhibitors, it does pro-

vide support for the importance of aspirin therapy in

patients with coronary artery disease, even ip the presence of heart failure with concomitant ACE inhibitor use.

Session Medical Management of Moderate to Severe Heart Failure

Study: 710-3: Hemodynamic Changes in Patients Undergoing Left Ventricular Diameter Reduction (Batista

Operation)

Presenter: Dr.Akira Kawaguchi, HospitalAngelina,

Caron, Curitiba, Brazil

Results: The Batista operation was performed in 24 patients with class III-IV heart failure from multiple causes as an alternative to cardiac transplantation.All patients had mitral or tricuspid valve annuloplasty and left ventricular diameter reduction performed. Hemodynamics were measured before and after surgery. Left ventricular

end-systolic volume was decreased more than left ventricular end-diastolic volume, with an associated increase in stroke volume and ejection fraction postoperatively. There was significant improvement in mitral regurgita-

tion postoperatively, but no change was seen in left ventricular end-diastolic pressure or pulmonary capillary

wedge pressure. Hospital mortality rate was 21.5% in this series.

Interpretation: The Batista operation results in greater reduction in left ventricular end-systolic volume than left ventricular end-diastolic volume and an improvement in the degree of mitral regurgitation, which result in improved ejection fraction postoperatively.This procedure

is performed in high-risk patients and has a high mortality rate. Comparisons need to be made between the Batista operation and mitral valve annuloplasty alone and between the Batista operation and aggressive medical therapy to determine the additive benefit of left ventricular diameter reduction in improving hemodynamics postoperatively. In addition, the high mortality rate causes an ascertainment bias in measures of left ventricular function (because only survivors are available for measurement) that is difficult to account for.

Session Medical Management of Moderate to Severe Heart Failure

Study: 710-1: Carvedilol Reduces Clinical Progression in Patients with Moderate to Severe Heart Failure

Presenter: Dr.Wilson S. Colucci, Boston University Medical Center, Boston, Mass.

Results: The U.S. Carvedilol Heart Failure Program stratified 1094 patients with New York Heart Association class II-IV heart failure, ejection fraction <35%, and maximized standard therapy (including angiotensin-converting enzyme inhibitor) into four categories on the basis of the 6-minute walk test.These patients were then randomly

assigned to receive carvedilol (dose titrated from 6.25 nag twice daily to 25 nag twice daily) or placebo to determine ff patients with moderate to severe heart failure had improvements in symptoms and survival with carvedilol.Treatment with carvedilol reduced disease

progression in moderate to severe heart failure as measured by the composite of death, hospitalization, and increase in heart failure medication dose. Patients with moderate to severe heart failure receiving carvedilol had


144 AHJ dt the Meetings

an overall composite event rate of 20% compared with

33% with placebo, a risk reduction of 0.58 (p < 0.0001).

Each of the individual end points was also significantly

improved by carvedilol.These benefits from carvedilol

remained for moderate and severe heart failure whether

patients were classified by the 6-minute walk test or by

New York Heart Association class.

Interpretation: Carvedilol has previously been shown

to reduce clinical progression in patients with heart failure and mild symptoms.These results extend the benefits

of carvedilol therapy in reduced symptom and disease

progression to patients with heart failure and moderate

to severe symptoms.The benefits of carvedilol in this

study were seen in patients already receiving maximum

doses of standard heart failure therapies. Despite these

findings, few data exist about the impact of carvedilol in

patients with class 1V heart failure.To address this issue, a

placebo-controlled trial in class IV patients is planned.

Aggressive Versus Conservative Treatments Session Late BreakingTrials III

Study: Transmyocardial Laser Revascularization (TMR)

versus Medical Management in Patients Unamenable to

Conventional Revascularization

Presenter: Dr.James E. Lowe, Duke University Medical

Center, Durham, N.C.

Results: Lowe presented the initial report from a 12-cen-

ter experience withTMR versus continued optimal med-

ical management for angina.The TMR procedure involves

drilling small transmyocardial holes with a carbon dioxide

laser through a left anterior thorax incision. One hundred

ninety-eight patients with class 3 or 4 angina, an ejection fraction _>20%, and demonstrated hibernating myocardium

were randomly assigned to continued medical therapy or

TMR. Patients ranged in age from 30 to 83 years, most having undergone multiple prior revascularizations. Cross-

over from the medical group was permitted after 6 months

from randomization.The TMR procedure led to significant

improvement in the primary end points of angina class

and myocardial perfusion at 3 months.A significant pro-

portion of patients improved by two angina classes afterTMR, and quality of life scores and mortality rates,

secondary end points of the trial, improved as well.The

group that crossed over from the medical group to

surgery did not fare as well, however, probably because

of a greater incidence of unstable angina at the time of

the procedure in these patients.

Interpretation: TMR is a viable alternative to continued

medical management of severe angina in selected patients without other options for revascularization.The procedure

appears to result in improved myocardial perfusion, decreased angina, and improved quality of life .There also may be a small mortality rate benefit.The procedure should be withheld in patients with unstable angina,

however, because these patients have a significantly greater mortality rate associated with the procedure.

Session Late Breaking Clinical Trials II

Study: VANQWISH:VeteransMfairs Non Q-Wave

Infarction Strategies In-Hospital

Presenter: Dr.William Baden, SyracuseVA Medical Center, Syracuse, N.Y.

Results: Nine hundred twenty male veterans with non- Q-wave myocardial infarctions were randomly assigned to either early invasive (initial catheteriza-

tion) or early conservative (initial functional study followed by catheterization only if positive or recurrent symptoms) management strategies. Mortality rate was higher in the invasively managed patients at 1 mon th an0~ 1 year.At 2-year follow-up, the event-free survival

favored conservative management over invasive management (9.5% mortality in invasive vs 8.2% mortality in conservative). Invasive management also involved

longer hospital stays.

Interpretation: Compared with conservative management, this male population with moderate to high risk non-

Q-wave myocardial infarction had a 71% excess mortality rate in-hospital, 60% excess rate at 1 month,and 30% excess rate at 1 year when treated with early invasive management. Despite initial expectations to the contrary, conservative management after non-Q-wave myocardial infarction

was associated with better outcomes than an early invasive

strategy.

Adjunctive Therapies Session Late Breaking Clinical Trials I

Study: PRISM-Plus: GP IIb/IIfaAntagonism withTirofiban

in High-risk Unstable Angina Trial

Presenter: Dr. Pierre Theroux, Montreal Heart Institute,

Canada

Results: PRISM-Plus was designed to determine the role

of the glycoprotein lib/Ilia inhibitors as an adjunct to standard therapy in the treatment of patients with unstable angina.A total of 1915 patients were randomly assigned to tirofiban alone, heparin alone, or the combination of

tirofiban and heparin and followed-up for end points of

American Heart Journal july 1997

AHJ at the Meetings 145

recurrent ischemia, myocardial infarction, and death at

7 days and 30 days. Patients treated with the combination of heparin and tirofiban had a 34% reduction in the combined risk of death, myocardial infarction, and refractory ischemia at 7 days compared with heparin alone (12.9% tirofiban and heparin vs 17.9% heparin).The majority of

this benefit was from the reduction in refractory ischemia (31%) and myocardial infarction (47%).This

benefit extended to 30 days, when patients treated with the combination of heparin and tirofiban had a 31% reduction in the combined risk of refractory ischemia, myocardial infarction, and death.Tirofiban resulted in a

small and nonsignificant increased risk of bleeding.

Interpretation: PRISM-Plus demonstrates the adjunctive role of the glycoprotein IIb/IIIa inhibitor tirofiban in the comprehensive treatment of patients with unstable angi-

na.All patients were receiving aspirin as standard therapy, but the addition of the more complete platelet inhibition provided by a GP lib/Ilia inhibitor improved clinical

outcomes at 7 days and 30 days. Because of the discontinuation of enrollment in the tirofiban arm alone, further

data are needed regarding the relative benefits of combination therapy compared with tirofiban alone in patients with unstable angina.

Session Late Breaking Clinical Trials III

Study: FLARE (Fluvastatin Angioplasty Restenosis Trial)

Presenter: Dr. Patrick Serruys,Thoraxcenter, Rotterdam, the Netherlands

Results: FLARE was a multicenter, randomized, placebo- controlled trial of fluvastatin (a HMG-CoA reductase inhibitor) in 1054 patients undergoing elective balloon

angioplasty for de nova lesions in native coronary arteries. Enrollment criteria included successful balloon angioplasty (no other devices used, residual stenosis <50%, and no periprocedural death, myocardial infarction, or coro-

nary artery bypass grafting), LDL cholesterol level <0.6 mmol, and fasting triglyceride level <4.5 mmol. Patients with myocardial infarction 3 months before the proce-

dure were excluded.There were no significant differences in the baseline characteristics of the patients. Therapy consisted of 80 mg of fluvastatin for 2 to 4

weeks before angioplasty and 6 months afterwards.The primary end point was change in minimal luminal diame-

ter at 6 months with a secondary composite end point of death, myocardial infarction, coronary artery bypass grafting or percutaneous transluminal angioplasty at 40 weeks. Fluvastatin therapy led to a 24% decrease in total

cholesterol, 33% decrease in LDL cholesterol, and 13% decrease in triglyceride levels.The cholesterol levels did

not significantly change in the placebo group.At the end

of the 6-month period, there were no significant angio-

graphic differences.After 40 weeks, a reduction was

observed for the combined end point of death and

myocardial infarction (6 vs 17): relative risk 0.37 (95%, confidence interval 0.14 to 0.92). However, if revascular-

izations were included, there was no longer a significant difference.

Interpretation: The use of fluvastatin in patients under-

going elective balloon angioplasty with moderate levels

of cholesterol did not lead to reduction in restenosis at 6

months but did lead to reduction in deaths and nonfatal

myocardial infarction at 40 weeks.

Session Late Breaking ClinicalTrials I

Study: PRISM: Platelet Receptor Inhibition for Ischemic

Syndrome Management

Presenter: Dr. Harvey White, Green Lane Hospital, Auckland, New Zealand

Results: The PRISM trial is the first large-scale compari-

son of glycoprotein lib/Ilia inhibition (tirofiban) with

heparin for the treatment of patients with unstable

angina/non-Q-wave myocardial infarction.A total of

3231 patients with an unstable chest pain pattern and

either electrocardiogram changes or known coronary

artery disease were randomly assigned to receive 48

hours of either heparin or tirofiban administration in a

head-to-head comparison.They were monitored for the

primary end points of recurrent ischemia, myocardial infarction, and death at 48 hours and 30 days.At 48

hours, patients receiving tirofiban had significantly tess

refractory ischemia (3.6% vs 5.3%,p = 0.017), and fewer

reached the composite end point of myocardial infarction/

death (3.8% vs 5.9%,p = 0.007).At 30 clays of follow-up,

rates of refractory ischemia were similar, and composite

end point of myocardial infarction/death was nonsignif-

icantly reduced by 21% (p = 0.10) with tirofiban.

Patients treated with tirofiban had a significant survival

advantage, with the rates of death being 2.3% for the.

tirofiban arm and 3.6% for the heparin arm (p = 0.02).

Although there was no difference in the rates of bleed-

ing between the two treatment arms, patients receiving tirofiban had a 1.2% rate of thrombocytopenia (platelets

< 90 k) compared with 0.4% in the heparin arm, but

this was found to be completely reversible on with- drawal of the study drug.

Interpretation: Glycoprotein IIb/IIIa inhibitors prevent

the activation of platelets, a crucial step in the pathogen-

esis of acute coronary thrombosis. In the PRISM trial,

American Heart Journal Volume 134, Number I


(

patients with unstable angina/non-Q-wave myocardial

infarction treated with tirofiban as opposed to heparin

had a 36% reduction in the risk of cardiac ischemia, myocardial infarction, and death at 48 hours and a 40%

reduction in death at 30 days.Although glycoprotein

IIb/IIIa inhibitors are already frequently used to treat

patients undergoing coronary intervention, PRISM has

demonstrated their role as an alternative and potentially superior treatment to heparin in the medical management

of patients with acute coronary syndromes.

Session Glycoprotein lib/Ilia Receptor Blockade

Poster: 974-85:The Reduction in Rate of Peri-angioplasty

Myocardial Infarction AfterTreatment with IIb/IIIa ReceptorAntagonists Is Dependent on MI Definition

Presenter : Dr.W.DouglasWeaver, Henry Ford Hospital,

Detroit, Mich.

Results: The RESTORE trial was a comparison of

tirofiban vs placebo in 2139 patients undergoing angio-

plasty considered to be high risk, with end points of death and myocardial infarction.The predefined defini-

tion for myocardial infarction was clinical (pain, electrocardiogram, and enzymes) or creatine kinase MB eleva-

tion ->3 x nl in hospital or >2 × upper nl after

discharge to day 30. On the basis of these definitions,

there was a statistically insignificant 26% reduct ion in

myocardial infarction in the tirofiban group (p = 0.113) If an alternative definition of postprocedure myocardial

infarction was used, such as creatine kinase MB >33%

from previous valley (valley defined as at least a 25% reduct ion from the previous value), or creatine kinase

MB more than four times normal, the reduct ion in

myocardial infarction in the tirofiban group would be statistically significant.The alternative definitions of

myocardial infarction also inf luenced the composite

end point.

Interpretation: Outcomes of interventional clinical tri-

als and other trials are markedly influenced by criteria

used to define myocardial infarction.The optimal defini- t ion of myocardial infarction after procedure should be

determined.

Devices Session Rotational Ablation: Costs/Cutting Balloon

Study: 1012-7: (1) Study to Determine Rotoblator and

Transluminal Angioplasty StrategyTrial (STRATAS)

(2) Influence of Vessel Caliber on RotationalAtherectomy

Results

Presenters: Dr. Patricia L.Whitlow, Cleveland Clinic

Foundation, Cleveland, Ohio, and Dr.Ted Feldman, University of Chicago, Chicago, Ill.

Results: The STRATAS trial was designed to evaluate

whether a strategy of optimal rotational atherectomy

followed by minimal balloon disrupUon at 1 atm pressure

was superior to a strategy of less aggressive "debulking,'

followed by 4 to 8 atm balloon dilatation. Five hundred

patients were randomly assigned to aggressive rotational atherectomy to acheive a burr/artery ratio of >70% or rou-

tine rotational atherectomy with a burr/artery ratio <70%

followed by PTCA with a 0.25 nun oversized balloon.

Overall angiographic success was 97% in both treatment

arms, although with twice the rate of transiently slow

flow during aggressive rotoblation. Despite larger pre-

procedural and postprocedural minimal lumen diameter,

residual stenosis was actually greater in larger vessels

when measured by quantitative coronary angiography,

with increased acute success rates and decreased complications in patients with smaller vessels. In addition,

investigators found a strong association be tween burr "decelerations" and an increased risk for major compli-

cations , including dissection, myocardial infarction, and

deatl~.There was no significant difference be tween

treatment strategies in the primary end point of mini-

mal lumen diameter at 6-month follow-up angiogram.

Interpretation: Aggressive rotational atherectomy offers

no clear benefit over achieving burr/artery ratios of _<70%

followed by percutaneous transluminal coronary angio-

plasty.Visual estimates of minimal lumen diameter were

more accurate in smaller vessels in this trial, and optimal

postprocedural minimal lumen diameter is the most important factor in preventing restenosis after rotational

atherectomy.

Session intravascular Ultrasound Guidance of Coronary Stenting

Study: 707-3: Intravascular Ultrasound Prediction of

Stent Thrombosis: Insights From the POST Registry

Presenter : Dr. Neal G. Uren, Stanford University, Stanford,

Calif.

Resolts'. The Predictors and Outcomes of Stent

Thrombosis (POST) Registry was designed to evaluate

the role of intravascular ultrasound (IVUS) in predicting

stentt thrombosis.This retrospective registry enrolled

patients with stent thrombosis after IVUS-guided stent

deployment at 16 centers in North America, Europe, and

Japan. For the 55 cases enrolled to date, core lab readings

identified abnormalities in the vast majority of IVUS stud-

ies, including underexpansion, malapposition, inflow

American Heart Journal july 1997


obstruction, thrombus, or dissection, whereas angiogra-

phy revealed suggestive abnormalities in only about one

third of cases.\Vhen stent thrombosis occurred, it was

associated with significant morbidity and mortality rates

in this study, leading to myocardial infarction or death in

67% and 10% of cases, respectively.

Interpretation: On retrospective analysis, qualitative

evaluation of 1VUS images is beneficial in detecting risk factors for stent thrombosis. Its prospective value

remains to be established.

Session Carotid stents

Study: 778-3: Percutaneous Carotid Intervention in

PatientsWith Symptomatic CoronaryArtery Disease

Presenter: Dr. Fayaz Shawl,Washington Adventist Hospital,Takoma Park, Md.

Results: Seventy-seven patients with symptomatic coro-

nary disease and either symptomatic or asymptomatic

carotid disease underwent a staged procedure with both

carotid and coronary stenting with 100% procedural suc-

cess.There were no deaths or myocardial infarctions, two

minor strokes on short-term follow-up, and no restenosis in those patients who underwent follow-up angiography.

Interpretation: These results in a small number of

patients suggest that in highly selected patients both

carotid and coronary stenting can be performed in a

staged procedure with acceptable success and good clinical outcome.

Session Stents: New Devices and Techniques

Study: 728-2: BENESTENT-II Trial-Final Results of Visit I:A 15 Day Follow-up

Presenter: Dr. Patrick W. Serruys, Erasmus University, Rotterdam,The Netherlands

Results: The BENESTENT-II trial was designed to com-

pare clinical outcome after balloon angioplasty with

that of the heparin-coated Palmaz-Schatz stent on major

adverse cardiac events (death, myocardial il~farction, tar-

get lesion revascularization) in patients with stable or

stabilized unstable angina pectoris and a de nova lesion

in a native coronary artery. Eight hundred twenty-seven

patients were randomly assigned to treatment with

stent (414) or balloon (413). Baseline characteristics

were similar be tween groups. 51% of patients had stable

angina, with 43% of patients with unstable symptoms.

Fifty-four percent of lesions were B2 lesions. In the bal-

loon group, 55 (13.4%)patients received a bailout stent.

Procedural success rate was 97% in the stent group and

86% in the balloon group. Bleeding or vascular compli-

cation incidence was similar be tween groups, but suba-

cute occlusion occurred in 0.2% of stent patients versus

1.9% of the percutaneous transluminal coronary angio-

plasty group.At 15-day follow-up there were fewer

major adverse cardiac events in the stent group (4.3%

vs 6.5%), with a 46% reduction in the rate of restenosis

in the stem group at 6 months.The minimal lumen

diameter in the stent group was greater than that in the

balloon group (2.69 mm vs 2.15 mm).At 7 months of

follow-up, the stent group had a 27% reduction in the

composite end point of death, myocardial infarction,

coronary artery bypass grafting or percutaneous trans-

luminal coronary angioplasty.The benefits of stenting

were not as pronounced in the subgroup of patients

who had angiographic follow-up.

Interpretation: There is a probable improvement in out-

come in patients receiving heparin-coated Palmaz-Schatz

stents compared with angioplasty.The benefits of stenting

on restenosis and need for repeat percuatneous translun~i-

nal coronary angioplasty are less in the subgroup of patients

who received angiographic follow-up.The reason for this is

unknown, but suggests that visualization of a lesion at the

time of follow-up prompted repeat intervention based on

angiography alone.

Session [ate BreakingTrials III

Study: Beta Energy Restenosis Trial (BERT-I)

Presenter : Dr. Spencer B. King, Emory University, Atlanta,

Ga.

Results: The BERT-I is a feasibility study of beta radiation to

reduce restenosis after balloon angioplasty.There were 23

patients enrolled. Beta radiation has been suggested as a

way of decreasing restenosis by interfering with cellular

proliferation at the site of injury after anginplasty. In addi-

tion, beta radiation is absorbed over a short distance, pro-

riding greater safety for patients and operators than gamma

radiation. In this study, a beta-radiation source in one of

three doses is delivered to the site of stenosis for 2.2 to 3.4

minutes and then removed. In the patients available for fol-

low-up, restenosis and late lumen loss have been dramati-

cally reduced compared with historical controls.

Interpretation: Beta radiation shows promise in signifi-

cantly decreasing restenosis by interfering with the nor-

mal reparative process after percutaneous transluminal

coronary angioplasty with a satisfactory safety pmfde.A

large, randomized follow-up trial is planned for later this year.

American HeartJournar Volume 134, Number 1

148 AHJ atthe Meetings

Session Angioplasty Stents: Drugs for Prevention of Subacute

Thrombosis

Study: 771-1 :Ticlopidine Administration After Stent Placement: Frequency of Adverse Reactions

Presenter: Dr. Robert J. Russo, Scripps Clinic & Research Foundation, La Jolla, Calif.

Results: This retrospective evaluation of ticlopidine use in 682 patients after Palmaz-Schatz coronary stent placement was designed to evaluate the incidence of adverse reactions during 1 month of therapy. Patients had routine follow-up 1 week after discharge, a complete blood count at 2 weeks, and telephone follow-up at 1 month. In patients with serious adverse reactions within 1 week, ticlopidine was discontinued and enoxaparin was continued

for 30 days. In patients with adverse reactions occurring from days 7 to 14, the ticlopidine dose was decreased to 250 mg each day, when possible, and continued for 30 days. If adverse events occurred after 14 days, ticlopidine was discontinued.Adverse effects were experienced in 29 patients (4.25%), including rash, gastrointestinal upset,

neutropenia, hives, and gastrointestinal bleeding. Seventeen patients required early discontinuation of ticlopidine because of an adverse reaction.There were no cases of irreversible neutropenia.

Interpretation: Ticlopidine use after stenting is associat-

ed with a low incidence of adverse reactions, and in this large cohort of patients no permanent adverse reactions were observed. No variables accurately predict the occur- rence of adverse reactions.The rate of adverse reactions requiring dose modification may decrease as the course of ticlopidine is shortened to 10 days -after stent deployment.

Session Stents: In-Stent Restenosis II

Study: 1011-2: Optimal Coronary BalloonAngioplasty vs Stent (OCBAS):

Preliminary Results of a Randomized Trial

Presenter: Dr.Alfredo Rodrigues, Otamendi Hospital, Buenos Aires,Argentina

Results" This trial, performed at eight centers in

Argentina, Chile, and Uruguay, sought to evaluate the cost and long-term outcome associated with a strategy of provisional stenting based on an adequate initial angiogram. One hundred sixteen patients with a successful angioplasty, defined as -<30% residual stenosis by angiography

with no visible dissection, were randomly assigned to immediate stenting versus repeat angiography at 30 minutes and stenting only in cases of early lulninal loss. 80(%

of lesions were type B2 or C. Eight of 59 patients randomly assigned to provisional stenting required a stent because of early luminal loss.At 6-month follow-up, anglo- graphic restenosis and repeat revascularization were sim-

ilar in both groups.Although there was greater acute procedural gain in minimal lumen diameter among stented patients, there was also greater late minimal lumen diam-

eter loss in this group. Inhospital and overall costs were greater in the stent than the percutaneous transluminal coronary aJlgioplasty strategy.

Interpretation: This trial demonstrates that lesion stabil-

ity 30 minutes after percutaneous transluminal coronary angioplasty is predictive of a low risk of restenosis, and a strategy of provisional stenting based on the follow-up

angiogram may preserve the low restenosis rates associated with stenting while dramatically reducing costs.The predictive value of even shorter follow-up periods of

angiography, such as 5 or 10 minutes, remains to be evaluated.

Session Carotid Stents

Study: 778,-2: Procedural Results and Early Clinical Outcomes After Carotid Stent-SupportedAngioplasty in I-Iigh-Risl~ Patients.

Presenter: Dr.John R. Laird,Washington Hospital Center, Washington, D.C.

Results: The experience with carotid artery angioplasty

and stent placement at the Washington Heart Center was reported. Fifty-one patients underwent carotid stenting with a 98% technical success rate.At 1 month follow-up,

only one non-procedural-related death and five minor strokes had occurred.Three of these minor strokes resolved within 1 week.

Interpretation: Carotid stenting of extra cranial carotid

stenoses by experienced operators can have a high procedural success rate, and initial results suggest low rates of neurologic complications in selected patients.This technique may be especially useful in patients who are

unable to undergo carotid endarterectomy because of high-risk characteristics, although randomized trials are needed.

Session Glycoprotein IIb/IIIa Receptor Blockade

Poster: 974-86 Ticlopidine Potentiates Abciximab's Ability to Inhibit ADP-Induced Platelet Aggregation in

Vitro

Presenter: Dr. Neal S. Kleiman, Methodist Hospital, Houston,Texas

American Heart Journal July 1997

AHJ atthe Meetings 149

Results: The combined interaction between ticlopidine and abcixinaab was studied in vitro in 18 patients undergoing percutaneous transluminal coronary angioplasty or stent placement. Baseline concentration of adenosine

diphosphate producing the maximal aggregation response for each patient was determined. Inhibitory concentrations (IC50s) for exogenously added 7E3 were determined at baseline, at 18 to 36 hours, and at 7 to 10 days.A reduction in IC50s (of abciximab) required for full

antiplatelet effect occurred ha patients treated with ticlopidine.This potentiation of the antiplatelet effect of 7E3 by ticlopidine was present at 18 to 36 hours and even

more pronounced at days 7 through 10.

Interpretation: In vitro study of ticlopidine's effect on

adenosine diphosphate-induced platelet aggregation showed a potentiation of the effect of abciximab on platelet function in the presence of ticlopidine.This interaction is being explored further in a clinical trial.


Stud)l: 728-1:A Multicenter RandomizedTrial Comparing

the Second Generation Gianturco-Roubin (GR II) and the Palmaz-Schatz Coronary Stents

Presenter: Dr. EdwardT. Fry, Washington Hospital Center, Washington, D.C.

Results: Two stent designs, the second generation GRII

flat wire clamshell design, balloon-expandable coronary stem (20 and 40 mm lengths) and the Palmaz-Schatz (PS) tubular slotted (15 mm length) stent, are being studied in a multicenter randomized trial to compare angiographic, inhospital, and long-term clinical outcomes.The first 446

consecutive patients have been analyzed. Patients included in the study were those undergoing successful elective percutaneous transluminal coronary angioplasty of de novo lesions with a reference vessel diameter of 3 to 4 mm and lesion length of <30 ram. Patients with unpro- tected left main disease, residual thrombus in target lesion, recent (<7 days) myocardial infarction, or ejection

fraction <35% were excluded from the study.There was no exclusion for target vessel tortuosity, angfilation, or multivessel disease. Of 446 consecutive patients (sample size of 570 patients), 227 received the GRII stent with a

success rate of 98% (three lesions unable to cross, one crossover patient).The remaining 219 patients received PS stents with a 97% success rate.All stents were post dilated, with an average of 15.6 atm for the GRII and 16.8 for the PS stent (significant). For longer lesions that could

not be covered by a single 15 mm PS or 20 mm GRII stem, two PS or two 20 mm GRII stents were used.An average of 1.5 PS stents were used per lesion, as opposed

to 1.3 stents in the GRII group, with a significant differ-

ence in length stented (22 mm PS vs 29 mm GRII).

Freedom from major cardiac events (Q-wave myocardial

infarction, death, coronary artery bypass grafting, or

repeat percutaneous transluminal coronary angioplasty)

at 30 days was 98.7% in the GRII group vs 98.1% in the

PS group.

Interpretation: On the basis of preliminary data from

the first 446 patients (of 750 planned), the GRII stent

was comparable with the PS stem at 30 days follow-up for major cardiac events. However, further analysis must

be done after completion of the full study.


Study: 728-3: High Pressure Inflation in Conjunction

With Ticlopidine and Aspirin Following Coronary Stent Placement: Results of the STRESS Ill Trial

Presenter : Dr. David L. Fischman,Jefferson Medical

Center, Philadelphia, Pa.

Results: The STRESS III study is a multicenter trial

designed to assess both acute and long-term outcomes of

single Palmaz-Schatz stent placement for focal lesions in . ' x

native coronary arteries with high-pressure inflation in conjunction with aspirin and ticlopidine administration.

Baseline demographics of the 250 patients enrolled were

similar to those of the STRESS I trial, with the exception

of an increased proportion of women, a higher incidence

of hyperlipidemia, and a smaller baseline reference vessel

size (3.03 vs 2.84 mm,p < 0001). Compared with STRESS stent patients, STRESS III patients had fewer stent

thrombotic events and bleeding and vascular complica-

tions, and reduced hospital stay. Quantitative coronary

analysis on 176 of 226 patients eligible for follow-up

showed a greater acute gain and less residual stenosis in

the STRESS III patients compared with the STRESS

patients. However, there was a significantly greater late

loss in STRESS III patients (0.92 mm vs 0.76 nwn,p =

0.02) resulting in a similar net gain between groups, and

a (>month follow-up minimal lumen diameter that was

not significantly different from the STRESS-stent popula-

tion. In addition, there was no significant difference in

restenosis rates between the STRESS-stent and STRESS III

patients.

Interpretation:The use of Palmaz-Schatz stent place-

ment for new focal lesions with high-pressure inflation in

conjunction With aspirin and ticlopidine administration

compared with STRESS patients who receive stents

resulted in greater acute gain and improved early clinical

outcomes. However, the early angiographic benefit was


! 50 AHj at the Meelings

not sustained at 6 months, with no difference in net gain, minimal lumen diameter, or restenosis rate compared with STRESS patients.

Session Intravascular Ultrasound Guidance of Coronary Stenting

Sfu dy: 707-1: Factors Associated With Inadequate Stent Expansion: 1VUS Analysis of 225 Patients Enrolled in the AVID Study and Angiography Versus Intravascular Ultrasound-Directed Stent Placement

Presenters: Dr.Antonio Nicosia, and Dr. Robert J. Russo, Stanford University, Stanford, Calif.

Results: The AVID (Angiography versus Intravascular

Ultrasound Directed Coronary Stent PlacemenO trial is a multicenter, randomized study to assess the role of IVUS guidance on outcome after stent deployment with high- pressure balloon dilatation. Patients with adequate (< 10% residual stenosis) angiographic results after stenting were randomly assigned to further therapy based on intravascular ultrasound (IVUS) findings or blinded IVUS aqnisi-

tion. Patients with major dissections noted by blinded IVUS were allowed to cross over to the therapy arm. IVUS images of 360 Palmaz-Schatz stents delivered in 187

native vessels and 53 saphenous vein grafts in 225 patients were studied to evaluate correlates to suboptimal stent expansion. Only 24% of stents reached 90% expansion by IVUS, despite adequate angiographic results. Of the IVUS parameters studied, a larger reference lumen diameter, plaque calcification, and increased

plaque burden were all associated with incomplete stent expansion. IVUS-directed therapy led to improved stent expansion, but there was no difference in inhospital stent thrombosis or 30-day clinical events between 1VUS- and

angiography-driven therapy.

Interpretation: IVUS appears to have some incremental

benefit over angiography alone in identifying optimal stent expansion, but there is no associated early benefit in clinical outcome.The long-term clinical implications

(target lesion revascularization) of these findings await 6- month and 12-month clinical follow-up.

Session 0 Late BreakingTrials III

Study: BARATH Cutting Balloon Trial

Presenter : Dr. Raoul Bonan, Montreal Heart Institute, Montreal, Canada

Results: "Cut then dilate" the atherosclerotic plaque is

the concept behind the cutting balloon, aiming to control the dissection and reduce the dilatation pressure and therefore the wall trauma.This trial will seek to evaluate

the acute and long-term effects of the cutting balloon

compared with conventional balloon angioplasty in a

multicenter, randomized trial looking at 6-month resteno-

sis and 9-month clinical outcome. A total of 1245

patients were randomly assigned to conventional balloon

angioplasty or the cutting balloon, which delivers three

to four cuts into the plaque surface when deployed by a

single inflation at <_8 atm for -<90 sec. The acute results

available on 1028 patients with 1074 lesions demonstrate

comparable angiographic success with the cutting bal-

loon despite a shorter inflation time and lower pressure.

The study included >50% B2 lesions.

Interpretation: The cutting balloon appears to be a safe

and effective device for percutaneous revascularization.

Restenosis and clinical follow-up results are pending.

Session

Stents: New Devices and Techniques

Study: 728-4: Intravascular Ultrasound Results From the

Reduced Anticoagulation Vein Graft Study (RAVES)

Presenter: Dr.Alexandre Abizaid,Washington Hospital

Center, Washington, D.C.

Results: The ReducedAnticoagulationVein Graft Study

(RA~rES) was a multicenter registry designed to examine

the efficacy of antiplatelet therapy alone (aspirin and

ticlopidine) after Palmaz-Schatz coronary stent place-

ment followed by high-pressnre percutaneous translumi-

nal coronary angioplasty in patients with vein graft

lesions. In more than half of the 200 patients, intravascu-

lar ultrasound was performed at the end of the proce-

dnre to document final procedural results.Three IVUS

parameters were used to evaluate stent implantation:

stent expansion, apposition, and symmetry. 1VUS results

were compared with blinded quantitative coronary

angiography (QCA).Approximately 38% of stents placed

failed to meet 1 of the 3 criteria.There was a significant

discrepancy between IVUS and QCA measurements of ref-

erence diameter, minimal lumen diameter, and stenosis,

with IVUS showing consistently greater lumen dimensions

but greater stenosis when compared with QCA. There

were no acute clinical sequelae of suboptimal stent

deployment.

Interpretation: In the RAVES population, IVUS evalua-

tion after Palmaz-Schatz stent placement in vein graft

lesions shows a high proportion of stems to be subopti-

mally deployed by IVUS criteria, but this had little effect

on subacute thrombosis. In addition, IVUS measurement

of reference diameter and minimal lumen diameter is

consistently greater compared with QCA. Long-term clini-

American Heart ]ournd July 1997

AHJ atthe Meetings 151

cal and angiographic outcomes are needed to fldly evalu-

ate the significance of these IVUS and QCA findings.

Acute Ischemic Syndromes Session Late Breaking Clinical Trials I

Stud),: A Randomized Double-Blind Study of Argatroban

vs Placebo as Adjunctive Therapy to Streptokinase in

Acute Myocardial Infarction

Presenter: Dr. PierreTheroux, Montreal Heart Institute,

Montreal, Canada

Results: AMI was a phase 2 dose-finding study of arga-

troban, a direct antithromhin, used with streptokinase

in patients with ST-segment elevation myocardial infarc-

tions.A total of 910 patients were randomly assigned to

receive low-dose or high-dose argatroban compared

with placebo.There was no overall difference in the pri-

mary end point of 90-minute patency among treatment

groups.There was, however, a 50% improvement in 90-

minute patency favoring argatroban in patients treated

within 3 hours of the onset of chest pain. In addition,

there was no difference in death or myocardial infarc-

tion with argatroban compared with placebo.

Interpretation: This dose-finding trial of argatroban ver-

sus placebo in addition to streptokinase failed to show

any treatment advantage with argatroban, although the

trial was not powered to detect differences in outcome.

Argatroban did have an excellent safety profile at both

doses.Trends toward improved outcomes in patients

treated early with argatroban are intriguing, but results of

large trials powered to detect differences in clinical out-

comes are necessary to define the role of this direct

antithrombin in the treatment of acute myocardial infarc-

tion.

Session Late Breaking Clinical Trials I

Study: GUSTO-III: Global Use of Strategies to Open

Coronary Arteries Trial

Presenter: Dr. Eric J.Topol, Cleveland Clinic Foundation,

Cleveland, Ohio

Results: GUSTO III was a 15,060 patient randomized

trial comparing the thrombolytic agent RPA (reteptase),

given in two boluses, with the standard thrombolytic,

front loadedTPA (alteplase). Patients were monitored for

death and myocardial infarction at 24 hours and 30 days.

Mortality rate at 24 hours was 2.99% in the RPA group

compared with 2.67% in the TPA group, and mortality

rate at 30 days was 7.43% in the RPA group compared

with 7.22% in theTPA group, for an absolute difference

of 0.21% in favor of standard front-loaded TPA.These dif-

ferences were not statistically significant, although the

95% confidence intervals for mortality rates with RPA

extend to include the possibilities that RPA is anywhere

from 0.7% better thanTPA to 1.1% worse thanTPA. Rates

of stroke and safety end points were not significantly dif-

ferent between the therapies. Interestingly, despite the

increased use of thrombolytics in the 1990s, the average

time to treatment from onset of chest pain was 2.7 hours

in GUSTO III compared with 2.7 hours in GUSTO I

(1990-1993).

Interpretation: In the thrombolytic era, a consensus seems to be present in the clinical community that novel

thrombolytic agents must be equivalent or superior to the standard of care: front-loadedTPA. Equivalence must take into account the confidence intervals of the differences seen to prevent inaccurate conclusions regarding

novel therapies. Since a 1% mortality rate disadvantage with RPA is considered clinically significant (GUSTO I found a 1% improvement in mortality rate withTPA over streptokinase), RPA is on the border of reaching a techni-

cal and clinical definition of equivalence with TPA in this study.A 15% mortality rate benefit could be achieved by

\ improving our process of care and shortening the time to treatment with current thrombolytics by 1 hour.This is

the same benefit (15% reduction) sought with novel thrombolytic agents. The RAPID II study compared RPA

andTPA and showed superior coronary patency at 90 minutes with RPA.This improved coronary patency with RPA did not translate into improved clinical outcomes in GUSTO III, which emphasized the importance of per-

forming trials designed to measure outcomes regardless of the promise shown from surrogate end points.

Session Late Breaking ClinicalTriats II

Study" OASIS Registry: Organization to Assess Strategies

for Ischemic Syndromes

Presenter" Dr. SalimYusuf, Hamilton General Hospital,

Ontario, Canada

Results: This international prospective registry of 8000

patients with non-ST elevation acute myocardial ischemia

(unstable angina/non-Q-wave myocardial infarction)

compared patterns of use and outcomes associated with

invasive and noninvasive management strategies.The

international use of early (<7 days) cardiac catheterization

varies considerably across regions with a 60% to 70%

catheterization rate in the United States and Brazil and a

American Heart Journal Vdume 134, NumBer 1

152 AHJ at the Meeiings

20% catheterization rate in Australia, Hungary, Poland, and

Canada.The subsequent use of revascularization is also

higher in countries with high rates of initial catheteriza-

tion (15% percutaneous transluminal coronary angioplasty,

11% coronary artery bypass grafting in United States/Brazil

vs. 5% percutaneous transluminal coronary angioplasty,

1.6% coronary artery bypass grafting in Australia/Hungary/

Canada).At 6-month follow-up, cotmtries using more invasive

management had lower rates of refractory ischemia

(12.3% vs 17.6%) but a significant excess of bleeding and

stroke.These unadjusted data showed a trend toward high-

er mortality rates or nwocardial infarction with invasive

management. Further analysis indicated that hospitals with

a cardiac catheterization lab managed patients with more

angiography, percutaneous tmnsluminal coronary angioplasty,

coronary artery bypass grafting after stratifying for patient

risk.However, patients initially admitted to hospitals with a

catheterization lab had a twofold higher risk of stroke, a

1.2-fold higher risk of death/myocardial infarction but with

lower rates of angina.

Interpretation: There is significant variation in the use

of procedures in unstable angina/non-Q-wave myocardial

infarction across countries, but this is largely based on

the availability of cardiac catheterization labs.Although

patients treated in regions with high use of catheteriza-

tion and revascularization have less refractory ischemia

on follow-up, other complications are increased (e.g., car-

diovascular death or myocardial infarction, bleeding,

stroke). Further analysis and evaluation of this question

are warranted.The authors conclude that until evidence

of benefit on cardiovascular death/myocardial infarction

from an aggressive policy is available from randomized

controlled trials, a more conservative approach to the

management of patients with unstable angina/non-Q-

wave myocardial infarction is warranted.

Session Emergency Department Evaluation of Unstable Angina

Study: Use of DiagnosticTools in a Chest Pain Evaluation

Unit:Value ofTroponin T Testing

Presenter: Dr. Kristin Newby, Duke University, Durham,

N.C.

Results: TroponinT was evaluated in 439 consecutive

patients admitted to the Chest Pain Unit at Duke. Entry

criteria included anginal symptoms, either normal or non-

diagnostic electrocardiogram and normal initial creatine

kinase MB.TroponinT was measured at 0, 4, and 8 hours

by an immunoassay on 396 patients. Levels _>0.1 ng/ml

were considered positive. Forty patients had positive tro-

poninT levels, including all eight patients in whom posi-

tive creatine kinase MB levels developed. Positive tro-

poninT was more often associated with positive stress

test (45% vs 13%,p = 0.014), coronary artery disease(89%

vs 43%,p = 0.003), and myocardial infarction (7 vs 0,p <

0.0001).

Interpretation: In patients admitted to the chest pain unit, negative t roponinT levels did not rule out coronary

artery disease. However, positive troponin T levels were

associated with both a higher likihood of coronary artery disease and greater severity.

Session Acute Myocardial Infarction:Today's Practice and

Tomorrow's Promise

Stud},: 738-3:The Paradigm forAnti-platelet Effect on

Continuous 12-Lead ST-Segment Recovery in Acute

Myocardial infarction

Presenter: Dr. Mitchell W. Krucoff, Duke UniversitT

Medical Center, Durham, N.C.

Results: Patients enrolled in the lamifiban (GP IIb/IIIa

inhibitor) dose-finding study of PARADIGM were moni-

tored wRh continuous 12dead ST-segment monitors to

assess clinically silent isehemie events and efficacy of

reperfusion. Patients treated with lamLfiban in acute

myocardial infarction had less reocelusion, recurrent ST

elevation, and a shorter time to stabilization as detected

by ST-segment stability than those receiving standard

therapy alone. Compared with placebo, patients given

lamifiban had a statistically superior 90-minute patency

rate and ST-segment stability by 30% to 50%. Lamifiban

improves ST parameters of speed and stability of reperfu-

sion, although there was no overall difference in out-

comes in this small dose finding trial.There was, howev-

er, a significant correlation between ST segment stability

and better clinical outcomes.

Interpretation: To date, studies of lamifiban have been

too small to detect significant differences in mortality rate with this GP IIb/IIIa inhibitor; however, surrogate

markers of improved blood flow, such as improved stability

and recovery of ST segments presented here, are up to 50% better with lamifiban, larger studies are warranted to determine the efficacy of this agent on improving clinically sig-

nificant outcomes in acute myocardial infarction.


Study: 756-3: Early Emergency Department

Eehoeardiograplay Is a Sensitive and Independent

American Heart Journal JuJy 1997


Predictor of Adverse Cardiac Outcomes in Chest Pain

Patients

Presenter: Dr. Michael Kontos, Medical College of Virginia,

Richmond,Va.

Results: This was a comparative study of two-dimen-

sional echocardiography (ECHO) and electrocardiogra-

phy (ECG) in 260 patients with possible cardiac

ischemia. ECHO was performed wi th in 4 hours of ED

presenta t ion.An abnormal ECHO was defined as ejec-

tion fraction _<40% or focal wall motion abnormalities

in 2 contiguous segments. ST deviation by _>lmm in the

initial ECG was considered abnormal. Myocardial

infarction and revascularizations were the end points

of the study. Sensitivity of ECHO was higher than that of

ECG (91% vs. 40%,p < 0.001), while specificity was lower

(75% vs 94%,p < 0.001). In multivariable analysis, only

male sex and abnormal ECHO were associated with

worse outcomes. Sensitivity and specificity of ECHO

were not significantly changed w h e n patients with

abnormal ECGs (n = 30) were excluded.

Interpretation: The authors conclude that an abnormal

ECHO done within 4 hours of presentation is more sensi-

tive in predicting adverse cardiac events than the initial

ECG.This promising study should stimulate larger studies

with more complete clinical characterization of the

patients to determine the circumstances in which ECHO is

worth the cost.


Tomorrow's Promise

Study: 73845: Does STAT Reporting of Serial Serum

Markers (CK-MB and Myoglobin)Aid in Early Detection

and Treatment Decisions for Acute MI?

Presenter : Dr.James W. Hoekstra, Ohio State University

Hospitals, Columbus, Ohio

Results: Both the process and the quality of care for

patients with acute myocardial infarction could be signifi-

cantly improved with a rapid and definitive diagnostic

strategy at the time of presentation to the Emergency

Department.The SMARTT investigators randomly

assigned 6388 patients to STAT reporting of creatine

kinase MB and myoglobin (within 1 hour) and standard

laboratory turnaround in an attempt to detect differences

in use and timing of thrombolytics and use of hospital

resources.They found no differences in reperfusion ther-

apy, catheterizations, or percutaneous transhiminal coro-

nary angioplasty between intervention groups.Those

with STAT reported markers of ischemia were slightly

less likely to be discharged from the emergency room.

Interpretation: Improving the speed of laboratory

reporting of myocardial markers of ischemia to the

emergency department does not in itseff change process

or quality of care.The availability of STAT serum markers

does not increase the speed or percentage of patients treated with thrombolytic therapy or primary percuta-

neous transluminal coronary angioplasty in the emer-

gency department.The availability of STAT serum mark-

ers did not adversely affect the percentage of patients

discharged from the emergency department. In fact, slightly fewer patients who had rapid reporting of crea-

tine kinase MB and myoglobin were discharged from the

emergency department.


Study: 756-5:The Effectiveness of a Chest Pain

Observation Unit (CPU) in EmergencyTriage of Patients

at Intermediate Risk for Coronary Events:The CHEER

Trial (CHest pain Evaluation in the ER)

Presenter : Dr. Michael Farkouh, Mayo Clinic, Rochester,

Minn.

Results: Patients with with acute chest pain were pros-

pectively classified byAgency for Health Care Policy and

Research unstable angina guidelines into low-, intermedi-

ate, and high-risk groups.A total of 347 patients at inter-

mediate risk were randomly assigned to either hospital

admission or observation in an emergency room-based

chest pain unit for 6 hours, during which time cardiac

enzymes were measured at O, 2, and 4 hours, ff appropri-

ate, a treadmill or stress imaging test was performed after

6 hours and, if negative, the patient was sent home.There

were no differences in the inhospital event rate (7.6% vs

3.4%, not significant). Forty-four percem of patients ran-

domly assigned for the chest pain unit were dismissed

home after their stress test.There were no cardiovascular

events in these patients at 1 month follow-up.

Interpretation: The outcomes of patients with chest

pain at intermediate risk (perAHCPR guidelines) treat-

ed according to an emergency room-based chest pain

unit strategy appear to be comparable to those admit-

ted for hospitalization.


Tomorrow's Promise

Study: 738-1: Early and Predischarge Aspirin



i i ~ ii

Administration Among Patients With Suspected Acute

Myocardial Infarction: Current Clinical Practice in the

United States

Presenter: Dr. Maureen Burns, University of

Massachusetts Medical Center, Worcester, Mass.

Results: The NRMI-2 (Second National Registry of

Myocardial Infarction) moni tored 220,171 patients wi th

suspected myocardial infarction to follow trends in

pract ice patterns.Analysis of these data for use of

aspirin administration revealed that only 75% of

patients wi th suspected myocardial infarction received

aspirin in the first 24 hours of hospital admission.Those

receiving aspirin were more likely to have typical chest pain

and be younger and male. Surprisingly, 17% of patients with ST elevation at admission did not receive aspirin therapy.

The use of aspirin declined, with only 69% being given it at the time of discharge.

Interpretation: Although adjustment for indications and contraindications to aspirin therapy is limited in this broad registry, it emphasizes a significant trend toward underuti l ization of aspirin therapy, which is known to improve mortali ty rate in patients with sus- pec ted myocardial infarction.The appropr ia te use of aspirin therapy must remain a priori ty in patient care, even as we add novel therapies.

American Heart Journai July 1997

session highlights from the american college of cardiology meeting: march 16-19, 1997

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