Curriculum in Cardiology
Interventional procedures in acute myocardial
Vincent S. DeGeare, MD, FACC,a George Dangas, MD, PhD, FACC,b Gregg W. Stone, MD, FACC,b and Cindy L.
Grines, MD, FACCc Fort Sam Houston, Tex, New York, NY, and Royal Oak, Mich
Background Acute myocardial infarction (MI) remains a leading cause of death in the United States. There is evidence
that primary (direct) percutaneous intervention (PCI) may improve survival and reduce morbidity in patients with acute MI.
Methods We present a concise, comprehensive, evidence-based literature review of modern techniques of primary PCI
in patients with acute MI. A comparison to thrombolytic therapy, especially in selected patient subgroups is made. Rescue
angioplasty is also addressed. Adjunctive pharmacology, economic implications, and feasibility of implementation are dis-
cussed. A brief discussion of experimental therapies is included.
Results Primary PCI is an acceptable alternative to thrombolytic therapy in patients with acute MI and may result in supe-
rior outcomes in select patient populations, especially the elderly, patients with prior coronary artery bypass surgery, those
with congestive heart failure, and those in cardiogenic shock.
Conclusions Clinical trials support the use of primary PCI as first-line therapy for acute myocardial infarction. Patients
in whom thrombolytic therapy is contraindicated or known to have reduced efficacy are also excellent candidates for this
therapy. Ongoing advancements in equipment and adjunctive therapies continue to enhance delivery of this treatment as
well as improve patient outcome. (Am Heart J 2001;141:15-24.)
Acute myocardial infarction (MI) occurs nearly 1.5 mil- (Kansas City, Mo) in November 1980.2 Since these ini-
lion times and claims more than 450,000 lives each year tial reports many other institutions began to incorporate
in the United States.1 In addition, many patients are this strategy and subsequent observational data,3 and
severely disabled as a consequence of severe MI. In the randomized trials suggested that primary angioplasty
early 1980s the widespread use of thrombolytic therapy was at least as effective as thrombolytic therapy and
revolutionized management of MI from a mostly support- may be applicable to a wider variety of patients.4-7
ive role to one of active intervention directed at myocar- O’Keefe et al8 reported that 96% of 1000 consecutive
dial salvage. However, the use of thrombolytic therapy is patients with acute MI were acceptable candidates for
limited in that many patients have important contraindi- percutaneous intervention, whereas nearly two thirds of
cations to its administration. In addition, the number of the group had at least relative contraindications to
patients who fail to reperfuse the infarct-related artery or thrombolytic therapy. In addition, because of actual or
have recurrrent ischemia or infarction is substantial and perceived contraindications, it has been documented
the incidence of complications is not trivial. Primary per- that many patients with acute ST elevation MI are not
cutaneous intervention (PCI) has emerged as an accept- treated with thrombolytic therapy and that these “lytic-
able alternative therapy for patients with acute MI. ineligible” patients have a higher mortality rate.9-11 Pri-
mary PCI can be performed in nearly all these patients
with a success rate greater than 90%.
Primary percutaneous intervention Overall, primary PCI has been associated with higher
versus thrombolytic therapy infarct-related artery patency, higher Thrombolysis in
The first reported cases of primary angioplasty for Myocardial Infarction (TIMI) flow grades, less recurrent
acute MI are from the Mid America Heart Institute ischemia/infarction, and less intracranial bleeding.12 In
fact, there were no hemorrhagic strokes in the percuta-
From the aDepartment of Cardiology, Brooke Army Medical Center, Fort Sam Hous- neous transluminal coronary angioplasty (PTCA) arms of
ton, Tex, the bCardiology Research Foundation, Lenox Hill Hospital, New York, NY, the Primary Angioplasty in Myocardial Infarction (PAMI)
and the cDivision of Cardiology, William Beaumont Hospital, Royal Oak, Mich.
Submitted April 28, 2000; accepted October 6, 2000.
1 or Global Use of Strategies to Open Occluded Coro-
Reprint requests: Vincent S. DeGeare, MD, FACC, Department of nary Arteries in Acute Coronary Syndromes (GUSTO IIb)
Cardiology/MCHE-MDC, Brooke Army Medical Center, 3851 Roger Brooke Dr, trials or in PAMI 2.13
Fort Sam Houston, TX 78234-6200.
The risk of early infarct-related artery reocclusion
4/1/112091 manifesting as recurrent ischemic chest pain or recur-
doi:10.1067/mhj.2001.112091 rent MI is much lower with primary PCI than with
American Heart Journal
16 DeGeare et al January 2001
Comparison of complication rates of thrombolytic therapy and primary PTCA from a meta-analysis of 10 trials.
(Modified from Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intra-
venous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA 1997;278:2093-8.)
thrombolytic therapy. The incidence of recurrent Six-month follow-up of 10 randomized trials of pri-
ischemia was less than 10% in the PTCA arms of the mary PTCA versus thrombolytic therapy revealed that
PAMI, ZWOLLE, and GUSTO IIb trials and recurrent MI patients >60 years old (and diabetics) had the greatest
rates are generally <5% with primary PCI.12 The incor- relative reduction in death or nonfatal reinfarction
poration of intracoronary stenting and adjunctive phar- when treated with primary PTCA instead of throm-
macologic therapy may further reduce these complica- bolytic therapy.18 Another recent publication suggests
tions. that thrombolytic therapy is of limited benefit in
Weaver et al14 published a meta-analysis of 10 trials of patients >75 years old with an acute MI.19
primary PTCA versus thrombolytic therapy. They Despite these findings, elderly patients undergoing
showed a 34% relative decrease in mortality as well as primary PCI still have a higher mortality rate than their
significant reductions in death plus nonfatal MI, nonfa- younger counterparts do. A recent pooled analysis of
tal recurrent MI, total stroke, and hemorrhagic stroke the PAMI 2, Stent PAMI and PAMI No Surgery on Site
(Figure 1). (No SOS) trials showed that patients >75 years old had
an in-hospital mortality rate five times higher than those
<75 years old.20
Selected patient populations
Elderly patients Cardiogenic shock
Elderly patients are known to have a significantly Cardiogenic shock has a very poor prognosis if coro-
increased mortality rate after acute MI. In the GUSTO 1 nary perfusion cannot be quickly restored. Mortality
trial, the overall mortality rate was 7.0%, but for exceeds 80% without treatment. In the Society for Car-
patients >75 years old the mortality rate was 20.1%.12 diac Angiography Intracoronary Streptokinase Registry,
Elderly patients showed a similar increased incidence of 44 patients with cardiogenic shock were identified.21
stroke and intracranial hemorrhage. Overall mortality was 66% but reperfusion occurred in
In the PAMI 1 trial a patient aged >65 years was an only 19 (44%) of these patients. Of the 25 patients with
independent risk factor for the combined end point of occluded infarct-related arteries, mortality was 84%. In
death and nonfatal recurrent MI if treated with tissue plas- the Gruppo Italiano por lo Studio della Streptochinasi
minogen activator (tPA) instead of primary PTCA.15 In a nell’Infarto Miocardico (GISSI 1) and the International
pooled analysis of the PAMI 1, ZWOLLE, and Mayo Clinic Study Group (ISG) trials, the mortality rate for patients
trials, a marked reduction in mortality was noted in with cardiogenic shock was equal to placebo in
elderly patients treated with primary PTCA instead of patients treated with either tPA or streptokinase.22,23
thrombolytic therapy.16 Similar reductions in death were In a review of 14 series of patients with cardiogenic
seen in patients >70 years old in the GUSTO IIb trial.17 shock, primary PTCA resulted in reperfusion in 60% to
American Heart Journal
Volume 141, Number 1 DeGeare et al 17
100% of cases (average 73%). In patients with success- thrombolysis.27 Procedural success was 90% and sur-
ful PTCA mortality was 30% compared with 80% with- vival to hospital discharge was 96%.
out successful PCI.23 The Randomized Evaluation of Salvage angioplasty
The recently published Should We Emergently Revas- with a Combined Utilization of Endpoints (RESCUE)
cularize Occluded Coronaries for Cardiogenic Shock trial enrolled 151 patients with a first anterior wall MI
(SHOCK) trial randomized 302 patients to emergency treated with thrombolytic therapy and angiographically
revasculariztion (PCI in 64% or coronary artery bypass demonstrated occlusion of the infarct-related artery
grafting [CABG] in 36%) or “initial stabilization,” which within 8 hours of chest pain onset. Patients were ran-
included the use of intra-aortic balloon counterpulsa- domized to conservative therapy (aspirin, heparin, and
tion or thrombolytic therapy.24 Overall, all-cause mor- coronary vasodilators) or to this therapy plus angio-
tality was the same in both groups at 30 days but sig- plasty (with or without additional thrombolytic ther-
nificantly lower in the revascularization group at 6 apy). PTCA was successful in 92%. The combined end
months. Patients <75 years old benefitted from early point of death or severe heart failure at 30 days was
revascularization at both time end points. PCI of the less in the angioplasty group (6% vs 17%, P = .05).13
infarct-related occlusion was successful in 78%, and In the TIMI 4 study, 95 (24%) patients had an
those patients had a 38% mortality rate at 30 days com- occluded infarct-related vessel at 90-minute angiogra-
pared with 79% in whom the procedure was unsuc- phy. Fifty-eight patients underwent rescue PTCA (90%
cessful. successful). Successful rescue PTCA resulted in supe-
rior coronary flow and an adverse outcome rate of 29%
Congestive heart failure compared with 83% if rescue PTCA was unsuccessful
There are data to suggest that the efficacy of throm- (P = .01).28
bolytic therapy is reduced in patients with congestive Ross et al29 studied 464 patients with failed thrombol-
heart failure (CHF).23 This may be due to decreased car- ysis enrolled in the GUSTO 1 trial compared with 1058
diac output resulting in reduced levels of thrombolytic with successful thrombolytic therapy. One hundred
agents reaching the site of intracoronary thrombus, ninety-eight patients underwent rescue PTCA. Patients
especially when the drugs are given intravenously. In offered PTCA were more likely to be diabetic and had
GISSI 1 in-hospital mortality was reduced in class II lower left ventricular ejection fractions (LVEF) than did
patients but not in class III patients. At the 6-month fol- those managed conservatively. LVEF and 30-day mortal-
low-up there was no survival benefit over placebo in ity were similar among patients with successful rescue
either group. In the ISG trial no survival benefit was PTCA and those managed conservatively.
seen in either group. Finally, Miller et al30 studied the effectiveness of
A recent pooled analysis of the PAMI 2, Stent PAMI, PTCA with or without abciximab for failed thromboly-
and PAMI No SOS databases revealed that in-hospital sis in 392 patients enrolled in the GUSTO III trial.
and 6-month mortality rates were 7% and 16% for class There was no difference in the composite end point of
II patients and 11% and 26% for class III patients, rates death, stroke, or reinfarction (at 30 days) although
considerably lower than in historic controls.24 there were trends for lower 30-day mortality and
increased severe bleeding in patients treated with
Patients with prior CABG abciximab. On the basis of these data we generally
The mechanism of acute MI in patients with prior offer catheter-based reperfusion therapy to patients
CABG is frequently thrombotic occlusion of a saphe- with failed thrombolytic therapy, especially if any evi-
nous vein graft (SVG). Because the thrombus is often dence of hemodynamic compromise or electrical insta-
large, it is not surprising that thrombolytic therapy is bility is present, with the goal of symptom relief and
less effective in these patients. In one small series intra- obtaining clinical stability.
venous thrombolytic therapy restored graft patency in
only 25% of cases.26 With use of primary PCI, O’Keefe
et al8 reported successful recanalization in 86% of Device therapy in acute MI
infarct-related SVGs. In-hospital mortality was the same Intracoronary stents
in patients with and without prior CABG. Initially it was felt that stenting should be avoided in
acute MI because of the presence of intracoronary
“Rescue” PCI thrombus and the associated systemic hypercoagulable
Rescue PCI refers to procedures performed after fail- state. With better antiplatelet therapy and reports of
ure of full-dose thrombolytic therapy. Multiple trials successful bailout stenting during PCI for acute MI
have shown that success is lower and complications are available, randomized trials of stenting for acute MI
higher in this setting. The Cohort of Rescue Angioplasty were undertaken.
in Myocardial Infarction (CORAMI) investigators The GR II Stent (Cook, Inc) in Acute MI (GRAMI) trial
attempted rescue PTCA on 72 patients who failed initial randomized 65 patients (preliminary results) to primary
American Heart Journal
18 DeGeare et al January 2001
PTCA with (40 patients) or without (25 patients) atherectomy (DCA) (Devices for Vascular Intervention,
planned stenting.31 There were no technical failures, Redwood City, Calif) is a method of selectively remov-
reocclusions, or deaths in the stent group. The com- ing intraluminal debris from within a coronary artery or
bined end point of technical failure or death (in-hospi- graft. There are limited data on the use of DCA as a
tal) was significantly lower in the stent group. At the method of primary percutaneous revascularization in
12-month follow-up, event-free survival was signifi- the setting of acute MI. Saito et al35 compared the
cantly higher in the stent group. results of primary DCA in 21 patients with the results of
The Florence Randomized Elective Stenting in Acute PTCA in 43 patients with acute MI in which the culprit
Coronary Occlusions (FRESCO) trial randomized 150 lesion was in the proximal portion of a nontortuous
patients with acute MI and successful PTCA to subse- native coronary artery. Primary DCA was immediately
quent stenting versus no further intervention.32 At 6 successful in 86% of patients and resulted initially in a
months the composite end point of death, reinfarction, larger minimum luminal diameter than did primary
or reintervention was 9% in the stent group and 28% in PTCA. However, a high rate of restenosis and reocclu-
the PTCA group (P = .003). sion at the 3-month angiographic follow-up negated the
The Stent PAMI trial randomized 900 patients with an beneficial effects of primary DCA.
infarct-related native coronary artery suitable for stent- Extraction atherectomy. Transluminal extraction
ing to PTCA only or to PTCA followed by intracoronary atherectomy (TEC, Interventional Technologies, San
stenting. At 6 months the composite end point of Diego, Calif) is a method in which thrombus is aspi-
death, nonfatal MI, disabling stroke, or tricuspid valve rated from within the vessel into an extracorporeal col-
replacement (TVR) was lower for the stent group, lection chamber, thus possibly reducing the risk for dis-
entirely the result of a lower incidence of ischemia- tal embolization and no reflow.
driven TVR in the stent group. At the 12-month follow- The TOPIT (TEC vs PTCA in Thrombus) trial random-
up the composite end point remained significantly ized patients with acute MI to one of the above thera-
lower in the stent group. There was a disturbing trend pies. Preliminary results from 250 patients reveal equal
toward increased mortality in the stent group (5.8% vs efficacy with a lower incidence of major adverse car-
3.7%, P = .07), which may be due to the slightly lower diac events (MACE) and fewer non-Q-wave MIs in the
initial TIMI 3 flow rate seen after stenting and thought TEC group.36
to be due to microembolization of thrombus protruding
between the stent struts.33 Whether this phenomenon Rheolytic thrombectomy
will persist with the use of glycoprotein IIb/IIIa recep- The Possis AngioJet (Possis Medical Systems, Inc)
tors is unknown. consists of a catheter that emits saline jets backward
Although no mortality benefit has been shown, there from the tip into an aspiration chamber.37 The resulting
is a very significant reduction in the need for repeat tar- vortex draws thrombus into the catheter. Nakagawa et
get vessel intervention with stenting. Given the large al37 published their experience in 31 patients with
number of procedures performed, this may result in acute or recent MI. Procedural success was 94% with
great economic savings. adjunctive PTCA in 97% and stenting in 40%. Follow-up
angiography at 3 to 6 months revealed TIMI 3 flow in
Atherectomy devices all patients and angiographic restenosis in 21% of
Rotational atherectomy. In general, rotational patients with PTCA and 8% of stented patients.
atherectomy (Rotablator, Scimed, Boston Scientific, DeLago et al38 used the Anjiojet to treat 46 patients
Boston, Mass) is not recommended in patients with with acute MI. Forty-five percent of patients underwent
acute coronary syndromes because of the presence of the procedure for failed thrombolysis. Adjunctive stent-
an intracoronary thrombus at the lesion site, which has ing was performed in 89% and IIb/IIIa receptor block-
been shown to result in a high incidence of distal ers were used in 87% of patients. There were 2 deaths
embolization or the no-reflow phenomenon.34 How- and no strokes or emergency bypass operations during
ever, there are several scenarios where rotational the hospital stay.
atherectomy may be considered. The first is when the
culprit lesion cannot be dilated with use of conven- Laser angioplasty
tional techniques. Often rotational atherectomy (even There is very limited published experience with laser
with a small burr) can modify the lesion and facilitate angioplasty in acute MI. Topaz et al39 reported the
PCI. Rotational atherectomy can debulk proximal dis- results of a multicenter registry of 2038 lesions in 1862
ease to allow reaching the target lesion. Also, one may patients treated with a solid-state mid-infrared
elect to intervene on a native coronary artery lesion holmium:YAG laser. Six percent of these patients had
that may be heavily calcified and may benefit from rota- acute MI. Laser plus adjunct PTCA achieved a 93% clini-
tional atherectomy. cal success rate. However, at 6 months no benefit on
Directional atherectomy. Directional coronary reducing restenosis was observed.
American Heart Journal
Volume 141, Number 1 DeGeare et al 19
Ultrasonography Aspirin and Ticlopidine Trial after Intracoronary Stent-
Therapeutic ultrasonography delivered at the site of a ing (MATTIS) trial also showed less stent thrombosis
thrombus-containing lesion has been proposed as a and significant reductions in bleeding and vascular
method of selectively lysing thrombus with minimal dis- complications with aspirin plus ticlopidine.47,48
ruption of the adjacent arterial wall. Rosenschein and Recently, Berger has written an excellent review of
Roth40 performed ultrasonography in 15 consecutive these studies (Figure 2).49
patients with an acute anterior MI. Ultrasonography More recently, another thienopyridine derivative,
alone produced TIMI 3 flow in 87% of the patients. clopidogrel, has been used in place of ticlopidine. The
When it was coupled with adjunct therapy, 14 patients advantages of this compound include more rapid
had TIMI 3 flow and 1 patient had TIMI 2 flow. plasma levels after oral loading and substantially fewer
Hamm et al41 treated 14 patients with acute MI by side effects, most notably diarrhea, skin rash, and neu-
use of pulsed intracoronary ultrasonography. TIMI flow tropenia. Data are emerging to show that this substitu-
grade improved at least one grade in 13 of 14 patients tion is safe, although rare cases of thrombotic thrombo-
and was TIMI grade 3 after adjunctive PTCA (mean 6 ± cytopenic purpura (TTP) have been reported.50 The
2 atm) in all 13 of these patients. Clopidogrel Aspirin Stent Interventional Cooperative
Study (CLASSICS) revealed no difference in the com-
posite end point of death, MI, or target lesion revascu-
Adjunctive pharmacologic agents larization among 740 patients randomized to clopido-
Aspirin grel versus ticlopidine for 28 days (all patients received
All patients undergoing PCI should receive aspirin aspirin).51
(160 mg or greater) unless there is a strong contraindi-
cation. Aspirin has been shown to decrease the risk of Glycoprotein IIb/IIIa antagonists
abrupt closure after PTCA by as much as 50%.42 For The platelet glycoprotein IIb/IIIa receptor represents
patients who truly cannot take aspirin and are not can- the final common pathway in the formation of throm-
didates for desensitization, clopidogrel, 75 mg daily, bus. This integrin is responsible for binding to fibrino-
may be substituted. gen, thereby promoting platelet aggregation.
The first available agent in this class was abciximab, a
Heparin/thrombin inhibitors murine antibody that irreversibly binds to the glycopro-
Most patients undergoing primary PCI also receive tein IIb/IIIa receptor (among others). Later, competi-
unfractionated heparin (UFH) although there is evi- tive inhibitors of this ligand were developed (integrilin,
dence to suggest that the direct thrombin inhibitor tirofiban). There are limited published data with these
hirudin is an acceptable alternative (especially in agents in the setting of primary PCI for acute ST eleva-
patients with a history of heparin-induced thrombocy- tion MI.
topenia)43,44 undergoing percutaneous intervention. Lefkovits et al52 published an analysis of a subgroup
Furthermore, there is research into using low-molecu- of patients in the Evaluation of c7E3 for the Prevention
lar-weight heparin, which gives a more predictable of Ischemic Complications (EPIC) trial. Of the 2099
level of anticoagulation and obviates the need to moni- patients enrolled, 42 underwent primary PTCA for
tor activated clotting times. acute MI and 22 for failed thrombolysis. The composite
primary end point of death, reinfarction, and repeat
Ticlopidine/clopidogrel intervention or CABG at 6 months was reduced in
Patients who receive intracoronary stents require fur- those randomized to abciximab bolus plus 12-hour infu-
ther antiplatelet therapy. In 1996 Hall et al45 published sion compared with placebo. The greatest reduction
a study of 226 patients undergoing intravascular ultra- was in the need for repeat PTCA.
sonography (IVUS)–guided stent implantation. One The Reopro and Primary PTCA Organization and Ran-
hundred three patients received aspirin alone and 123 domized Trial (RAPPORT) randomized 483 patients
received aspirin plus ticlopidine. At the 1-month follow- with acute MI to placebo versus abciximab bolus plus
up, the rate of stent thrombosis was 2.9% and 0.8%, infusion.53 Abciximab significantly reduced the inci-
respectively. dence of death, reinfarction or urgent TVR at 7, 30, and
Schomig et al46 published a substudy of 123 patients 180 days. There was no benefit on restenosis. In addi-
with acute MI enrolled in the Intracoronary Stenting tion, “bailout stenting” was reduced by 42% in the
Antithrombotic Regimen (ISAR) study, which showed a abciximab group.
significant reduction in clinical and stent occlusion at The Abciximab Before Direct Angioplasty and Stent-
30 days. Bleeding complications were also markedly ing in Myocardial Infarction Regarding Acute and Long
reduced in the antiplatelet group. Term Follow-up (ADMIRAL) trial randomized 300
The Full Anticoagulation versus Aspirin and Ticlopi- patients with acute MI undergoing PTCA with or with-
dine (FANTASTIC) study and the the Multicenter out stenting to placebo versus abciximab bolus plus
American Heart Journal
20 DeGeare et al January 2001
Four randomized trials comparing aspirin and ticlopidine with aspirin alone or aspirin and warfarin in patients
undergoing coronary stent placement. (Modified from Berger PA. Aspirin, ticlopidine, and clopidogrel in and out
of the catheterization laboratory. J Invest Cardiol 1999;11:20-29A.)
infusion.54 Preliminary results reveal a 47% reduction in artery bypass surgery, can be identified and referred
the combined end point of death, recurrent MI, or need before hemodynamic compromise or further ischemic
for urgent revascularization. complications occur.
The Controlled Abciximab and Device Evaluation to
Lower Late Angioplasty Complications (CADILLAC) trial Economic considerations
is a randomized trial involving 2081 patients studying Studies of the cost-effectiveness of primary PCI have
PTCA versus stenting with and without abciximab in shown that this approach is no more costly than a strat-
patients with acute MI.55 Preliminary results have egy using thrombolytic therapy.57,58 Gibbons et al6 per-
shown a lower in-hospital incidence of recurrent formed a cost analysis of their study, which revealed a
ischemia and ischemia-driven TVR in both the PTCA trend toward lower hospital costs in the angioplasty
and stent groups when abciximab was used. group. Six-month follow-up costs were lower with
PTCA. Length of hospital stay and readmission rates
Additional benefits of primary PCI were also lower in the PTCA group. A detailed analysis
Up-front cardiac catheterization affords the opportu- of the PAMI 1 trial revealed that the charges were simi-
nity to assess noninfarct vessels. Both systolic and dias- lar in both groups. The ZWOLLE and GUSTO IIb trials
tolic function can be rapidly evaluated, as can left-sided also showed similar costs between the two treatment
valvular structures and the intraventricular septum. strategies.59
Right-heart catheterization adds information concerning In PAMI 2, low-risk patients (see above) could avoid
right-sided filling pressures, oximetry data, and determi- admission to a coronary care unit and noninvasive test-
nation of cardiac output. ing and could be discharged on the third hospital
These hemodynamic and angiographic data, when day.56 This strategy resulted in a very significant cost
combined with clinical assessment, can be extremely savings.
useful for post-MI risk stratification. Low-risk patients
(those aged <70 years with nonanterior MI, preserved Limitations of primary PCI
LVEF, favorable coronary anatomy, and stable hemody- Patients with significant renal insufficiency or pro-
namics) can often avoid admission to a coronary care teinuria may have a decrement in renal function after
unit and can be discharged expeditiously.56 High-risk the administration of contrast material. There is strong
patients, especially those who will require coronary evidence that adequate hydration, conservation of con-
American Heart Journal
Volume 141, Number 1 DeGeare et al 21
trast, and the use of low osmolar contrast can eliminate lished in >90% of patients, (3) emergency CABG rates
much of this risk.60,61 be <5%, (4) PTCA be performed in >85% of patients
The widespread use of metformin for the treatment with acute MI brought to the catheterization labora-
of type 2 diabetes mellitus has led to concern about the tory, and (5) mortality be <12%. With the exception of
development of lactic acidosis in patients with compro- time delays, these goals were easily achieved in most
mised renal function who receive intravascular con- primary PCI trials. Miller et al showed that these goals
trast. However, most patients with acute MI can pro- could also be obtained in the community hospital set-
ceed safely to emergency PCI with the immediate ting68 although not all hospitals consistently reach this
discontinuation of metformin and close monitoring of goal.69
renal function to ensure a return to baseline before the There is evidence that vessel patency rates and clini-
drug is restarted.62 cal outcome are not compromised by a time delay of
A non-life-threatening contrast reaction requiring up to 60 to 120 minutes.70 Berger et al71 showed that
therapy occurs in 0.2% to 0.4% of patients. Anaphylac- in the GUSTO IIb trial time from enrollment to first bal-
toid reactions occur in 0.04% of patients. Treatment loon inflation was an independent predictor of death
with corticosteroids and antihistamines and changing and that mortality began increasing after 60 minutes.
to a low osmolar contrast medium can lower the inci- Studies by Cannon et al72 and Liem et al73 suggest that
dence of repeat reactions to 0.5%.63 No more than 2 or mortality increases and myocardial salvage decreases
3 doses of steroids are generally given to avoid interfer- after a delay of 120 minutes.
ence with myocardial healing. It has been suggested that primary PCI should not be
Other procedural complications including death, performed by low volume operators (<75 cases per
stroke, bleeding, arterial injury (pseudoaneurysm, dis- year). However, an analysis of the PAMI 2 database
section, perforation), acute closure, stent thrombosis, revealed no significant differences in the rates of in-hos-
and distal embolization/no-reflow can occur. pital death, CABG, or acute PCI success.74 Similar find-
Perceived nonmedical limitations of primary PCI ings were reported in the GUSTO IIb trial.5 A larger
include availability of facilities and competent opera- study by Ellis et al75 found that, overall, high-volume
tors. Trials to assess the safety and efficacy of emer- operators have a lower incidence of major complica-
gency transport of patients with acute MI to a PCI cen- tions but that the difference was not consistent for all
ter have been performed. The Air-PAMI trial compared operators studied. There is evidence that institutional
outcomes in lytic-eligible high-risk patients randomized experience as a whole may influence procedural out-
either to transfer to a tertiary care center for primary come, with better results achieved in busier cen-
PTCA or to local thrombolysis with no routine ters.71,76
transfer.64 Despite a delay in time to treatment because
of transfer and transportation, there was a 44% Patient selection and periprocedural care
decrease in the composite end point of death, recur- Once the decision has been made to proceed to
rent MI, and disabling stroke in the PTCA group. This angiography and primary PCI, if appropriate, the
was not statistically significant as a result of the small patient is usually given 325 mg of soluble aspirin along
sample size. Although encouraging, this strategy cannot with heparin (American College of Cardiology/Ameri-
be recommended for routine management of acute MI. can Heart Association guidelines recommend a bolus of
There are data regarding the safety of performing 70 U/kg of UFH). Oxygen, nitrates, morphine, and β-
PTCA in centers without an on-site cardiac surgery blockers are administered as needed for double-product
back up.65 The PAMI No SOS trial documented the out- control and pain relief.
come of 492 high-risk acute MI patients seen at 19 com- If a glycoprotein IIb/IIIa receptor antagonist is to be
munity hospitals performing primary PTCA without car- used, it should be started before the lesion is crossed
diac surgery available. A successful result was achieved and the activated clotting time (ACT) titrated to
in 97% of patients undergoing PCI. In-hospital mortality approximately 250 seconds77; otherwise we attempt to
was 2.8% and disabling stroke occurred in 0.4%. At 6 keep the ACT between 300 and 350 seconds. In gen-
months the composite end point of death, recurrent eral, we use ionic, low-osmolar contrast medium to
MI, or disabling stroke was 7.7%, similar to results minimize hemodynamics. We place an intra-aortic bal-
obtained in experienced interventional laboratories loon pump only in patients with evidence of sustained
with cardiovascular surgery on site. hemodynamic compromise or intractable arrhythmias.
The 1999 American College of Cardiology/American Most patients undergo initial PTCA often followed by
Heart Association Guidelines on the Management of placement of an intracoronary stent. Usually only the
Acute Myocardial Infarction66 recommend that (1) bal- culprit lesion is intervened upon in the acute setting.
loon dilation occur within 90 ± 30 minutes of the diag- Other significant stenoses may be treated with a staged
nosis of acute MI (increased from ≤90 minutes in the procedure once the patient has recovered from the
1996 guidelines67), (2) TIMI grade 2 or 3 flow be estab- index event.
American Heart Journal
22 DeGeare et al January 2001
All patients should be placed on aspirin (usually 3. Tiefenbrunn AJ, Chandra NC, French WJ. Clinical experience with
indefinitely) after PCI unless a definitive contraindica- primary percutaneous transluminal coronary angioplasty compared
tion is present. Heparin is generally not continued after with Ateplase (recombinant tissue-type plasminogen activator) in
the procedure unless balloon counterpulsation is used patients with acute myocardial infarction: a report from the second
national registry of myocardial infarction (NRMI). J Am Coll Cardiol
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American Heart Journal
Volume 141, Number 1 25
The following articles are an AHJ Online Exclusive.
Full text of these articles is available at no charge at our website:
Progress in Cardiology
The emerging concept of mitochondrial cardiomyopathies
Filippo M. Santorelli, MD,a Alessandra Tessa, PhD,a Giulia d’Amati, MD,b and Carlo Casalic, MD, PhD Rome, Italy
Objective Our purpose was to present an updated review on the Results and Conclusions Mitochondrial DNA defects and
spectrum of mitochondrial DNA–related syndromes relevant to car- faulty oxidative phosphorylation are infrequently considered as
diac disturbances. causes of cardiomyopathies. This is surprising given the heavy depen-
Background The advent of molecular genetics has provided dence of the heart on oxidative metabolism and the recent advances
important insight into the mechanisms underlying a variety of inher- in understanding the molecular features of mitochondrial disorders.
ited heart disorders, including cardiac arrhythmias and cardiomy- This remarkable progress and the implications it may have for more
opathies. These studies pointed to defects in ion channels, contractile common forms of cardiovascular disease are reviewed. (Am Heart J
proteins, structural proteins, and signaling molecules as key players in 2001;141:e1.)
disease pathogenesis, and they have opened up new mechanism- 4/90/112080
based approaches to therapy.
Direct thrombin inhibitors in acute coronary syndromes and during
percutaneous coronary intervention: Design of a meta-analysis
based on individual patient data
Direct Thrombin Inhibitor Trialists’ Collaborative Group*
Background More than 30 randomized trials involving more We examined these outcomes at the completion of active treatment
than 40,000 patients with acute coronary syndrome and undergoing and during long-term follow-up, as well as in clinically important
percutaneous coronary intervention have evaluated the efficacy and subgroups.
safety of direct thrombin inhibitors relative to unfractionated heparin. Methods Individual patient data, including baseline demograph-
However, few trials have been large enough to provide reliable esti- ics, previous history of vascular disease, conventional vascular risk
mates of treatment effects on major cardiovascular outcomes. There- factors, qualifying diagnosis, prognostic markers including biochemi-
fore uncertainty remains regarding the benefits of direct thrombin cal markers of extent of myocardial injury, cointerventions, and fatal
inhibitors on major cardiovascular outcomes such as death or and nonfatal cardiovascular outcomes, have been obtained from 14
myocardial infarction and the balance of any such benefits against randomized studies, constituting more than 95% of the available ran-
the risk of major bleeding. domized evidence. These data will undergo exhaustive data check-
Objectives By combining data on individual patients from all ing for completeness and consistency and will then be merged into a
the major studies, we sought to obtain reliable estimates of the master database for analysis. Analyses will undergo extensive
treatment effects of direct thrombin inhibitors on death, myocardial scrutiny by trialists of the direct thrombin inhibitor studies before incor-
infarction, major bleeding, and secondary outcomes including poration into a manuscript. (Am Heart J 2001;141:e2.)
refractory or recurrent ischemia and need for revascularization. 4/90/111954