Acute
management of myocardial infarction in a diabetic patient
Ajay Jain, Jonathan Hill
London Chest Hospital, and St Bartholomew’s Hospital, London,
UK
Correspondence: Dr Jonathan Hill, London Chest Hospital, London,
UK.
A case is presented of a male patient with multiple
risk factors for coronary artery disease, including type 2 diabetes.
The acute management of myocardial infarction including thrombolysis
and intervention is discussed with special reference to management
in diabetes. Emphasis is placed on the requirements for precise
glycemic control and the additional metabolic risks of diabetes
in acute coronary syndromes.
Case report
A 58-year-old Asian man presented to our institution within 2
h of spontaneous onset of severe central chest pain. A history
of CCS grade 2 angina for several months was described, in addition
to type 2 diabetes mellitus, which had been diagnosed at the age
of 50. Initial therapy had been with dietary restriction only;
however, persistent hyperglycemia had required the initiation
of metformin tablets 6 months after the initial diagnosis. The
patient was taking no other medication. Other than a neuropathic
diabetic foot ulcer no other complications of diabetes were known
to be present. He was also known to have hyperlipidemia, with
plasma cholesterol 6.1 mmol/L, but no history of smoking, hypertension,
or family history of coronary artery disease.
Initial examination was unrevealing. The ECG obtained in the emergency
room revealed planar anterior ST-segment elevation, consistent
with acute anterior myocardial infarction. Echocardiogram showed
hypokinesis of the anterior wall of the left ventricle, with moderate
left ventricular function. Laboratory data showed an elevated
creatinine kinase and elevated cardiac troponin I. The blood glucose
was 19 mmol/L.
Tissue plasminogen activator was given intravenously according
to the standard regimen. Intravenous heparin was commenced, and
in addition a glucose, insulin, and potassium (GIK) infusion was
initiated. Partial resolution of acute ECG changes was seen with
resolution of the chest pain. However, 2 h following completion
of thrombolysis, severe pain returned, associated with further
ST-segment elevation in the anterior chest leads.
Abciximab infusion was commenced and the patient was immediately
transferred to the cardiac catheterization laboratory. Coronary
angiography revealed a severe proximal stenosis in the left anterior
descending coronary artery. Direct stenting was performed using
a 3.5 X 18 mm slotted tube stent. TIMI 3 perfusion was restored
with no residual stenosis in the LAD. Intravascular ultrasound
revealed satisfactory stent deployment.
The patient made an uneventful recovery and was discharged on
day 5 post-procedure, free of chest pain; a twice-daily regimen
of subcutaneous insulin was commenced to improve his glycemic
control.
 Figure
1. Severe proximal stenosis in left anterior descending artery.
Discussion
Despite the presence of type 2 diabetes and the increased risk
of restenosis, acute intervention was the best option to preserve
left ventricular function in this case. The use of adjunctive
insulin (GIK) to improve outcome in the setting of acute coronary
syndromes is well described. These studies have examined both
diabetic and nondiabetic populations. However, the Diabetes Mellitus
Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI)[1]
trial has investigated the role of GIK therapy in acute myocardial
infarction. This trial looked solely at diabetic patients, and
showed a significant reduction in mortality in those who were
treated with glucose and insulin. A metaanalysis[2]
of GIK trials in mainly nondiabetic patients suffering myocardial
infarction (which excluded the DIGAMI study) suggested a mortality
reduction of 28% with the use of GIK treatment.
Several mechanisms for this beneficial effect have been offered.
Myocardial ischemia has been shown to provoke increased levels
of free fatty acids (FFA) via a mechanism mediated by increased
sympathetic activity. These FFA lead to increased myocardial oxygen
requirements and depression of myocardial contraction.[3,4]
Delivery of exogenous glucose has been shown to provide a
fuel that is more efficiently utilized than either FFA or glycogen,
and is thus more likely to prevent ischemic myocardial injury.[5]
Electrical instability and, consequently, ventricular arrhythmias
may also be increased via the detrimental effect of FFA on calcium
homeostasis and free radical production. Insulin lowers the plasma
concentration of FFA by inhibiting lipolysis.
The possible effects of insulin upon coagulation may also play
a role in the improved outcome in acute coronary syndromes.[6]
Diabetes is associated with coagulation abnormalities including
increased platelet activation and aggregation, increased fibrinogen
concentration, and increased circulating von Willebrand factor.
Recent reports of the complementary role of GIK and reperfusion
therapy are encouraging. Animal models suggest that GIK has the
ability to protect ischemic myocardium for 10 h or longer.[7]
This potentially may offer a longer period for optimal revascularization.
GIK may reduce reperfusion injury after successful revascularization,
again via suppression of FFA and limitation of the extent of ischemic
myocardial injury. Reperfusion in turn may increase the effectiveness
of GIK therapy, since GIK alone can only delay the onset of myocardial
necrosis, and restoration of blood flow is required to prevent
lactic acidosis and hydrogen ion accumulation.
The BARI (Bypass Angioplasty Revascularization Investigation)
and EAST (Emory Angioplasty versus Surgery Trial) trials[8,9]
compared multivessel PTCA with multivessel CABG in a mixed
population of diabetic and nondiabetic patients. However, subgroup
analysis in both studies tended towards a worse long-term outcome
for the diabetic compared with the nondiabetic patient. With improvements
in stent technology and deployment,[10,11] and
the advent of IIb/IIIa platelet inhibitors such as abciximab,
the immediate and long-term outcomes for diabetics continue to
improve.[12]
Conclusions
This case illustrates that in addition to conventional revascularization
methods, close attention should also be paid to the metabolic
consequences of myocardial infarction, especially in patients
with diabetes. An understanding of glucose and FFA metabolism,
and their interaction with the coagulation cascade, will enhance
reperfusion therapy in this high-risk group of patients.
REFERENCES
Comment in:
- ACP J Club. 1996 Jan-Feb;124(1):1
Randomized trial of insulin-glucose infusion
followed by subcutaneous insulin treatment in diabetic patients
with acute myocardial infarction (DIGAMI study): effects on
mortality at 1 year.
Malmberg K, Ryden L, Efendic S, Herlitz J, Nicol P, Waldenstrom
A, Wedel H, Welin L.
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
OBJECTIVES. We tested how insulin-glucose infusion followed by
multidose insulin treatment in diabetic patients with acute
myocardial infarction affected mortality during the subsequent 12
months of follow-up. BACKGROUND. Despite significant improvements
in acute coronary care, diabetic patients with acute myocardial
infarction still have a high mortality rate. METHODS. A total of
620 patients were studied: 306 randomized to treatment with
insulin-glucose infusion followed by multidose subcutaneous
insulin for > or = 3 months and 314 to conventional therapy.
RESULTS. The two groups were well matched for baseline
characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6
+/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the
1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control
patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the
infusion group and 82 (26.1%) in the control group had died
(relative mortality reduction 29%, p = 0.027). The mortality
reduction was particularly evident in patients who had a low
cardiovascular risk profile and no previous insulin treatment
(3-month mortality rate 6.5% in the infusion group vs. 13.5% in
the control group [relative reduction 52%, p = 0.046]; 1-year
mortality rate 8.6% in the infusion group vs. 18.0% in the control
group [relative reduction 52%, p = 0.020]). CONCLUSIONS.
Insulin-glucose infusion followed by a multidose insulin regimen
improved long-term prognosis in diabetic patients with acute
myocardial infarction.
Publication Types:
- Clinical Trial
- Randomized Controlled Trial
PMID: 7797776 [PubMed - indexed for MEDLINE]
Comment in:
Glucose-insulin-potassium therapy for treatment
of acute myocardial infarction: an overview of randomized
placebo-controlled trials.
Fath-Ordoubadi F, Beatt KJ.
Medical Research Council Clinical Sciences Centre, Postgraduate
Medical School, and Department of Cardiology, Hammersmith
Hospital, London, UK. 100412.3302@compuserve.com
BACKGROUND: Glucose-insulin-potassium (GIK) therapy has been
advocated for the treatment of acute myocardial infarction.
However, the results from the clinical trials have been
inconclusive, largely because of the small number of patients
recruited and discrepancies between protocols used in these
studies. METHOD AND RESULTS: A systematic MEDLINE search for all
the randomized placebo-controlled studies of GIK therapy in acute
myocardial infarction was made, and a meta-analysis of the
mortality data was performed. Fifteen trials were identified, 5
were excluded because of poor randomization, and 1 was excluded
because recruitment was limited to diabetic patients. The 9
remaining trials with a total of 1932 patients were included in
the analysis. Hospital mortality was reduced from 21% (205 of 972
patients) in the placebo group to 16.1% (154 of 956) in the GIK
group (P=.004; odds ratio, 0.72; 95% confidence interval [CI],
0.57 to 0.90). The proportional mortality reduction was 28% (CI,
10% to 43%). The number of lives saved per 1000 patients treated
was 49 (95% CI, 14 to 83). CONCLUSIONS: The findings indicate that
GIK therapy may have an important role in reducing the in-hospital
mortality after acute myocardial infarction. The value of this
therapy in the era of thrombolysis and acute revascularization by
primary angioplasty can be fully resolved only by conducting a
large randomized mortality study.
Publication Types:
PMID: 9286943 [PubMed - indexed for MEDLINE]
3. Opie L, Lamp S. Glycolysis preferentially
inhibits ATP-sensitive K+ channels in isolated guinea pig cardiac
myocytes. Science. 1987;238:67–69.
Effects of glucose and fatty acids on
myocardial ischaemia and arrhythmias.
Oliver MF, Opie LH.
National Heart and Lung Institute, London, UK.
Evidence for the utilisation of substrates by the ischaemic
myocardium and its dependence for viability on a critical supply
of glucose was established many years ago. It was recognised that
an excess of free fatty acids (FFA) could increase the severity of
ischaemic damage and possibly be arrhythmogenic. But metabolic
intervention to improve survival during acute myocardial
infarction was not regarded as a priority, perhaps because of
uncertainty about its value and the advent of trials of
beta-blocker and antiarrhythmic drugs. There has never been an
adequate trial of the benefit to the ischaemic or infarcting
myocardium of increasing local glucose concentrations or reducing
the availability of FFA. We have taken into account new knowledge
of the effects of fatty acids on cation channels and brought up to
date the arguments for metabolic intervention with glucose-insulin
solutions or antilipolytic drugs sustained ischaemia.
Publication Types:
PMID: 7904009 [PubMed - indexed for MEDLINE]
5. Runnman E, Weiss J. Exogenous
glucose utilization is superior to glycogenolysis at preserving
cardiac function during hypoxia [abstract]. Circulation. 1988;78(suppl
II):261.
Thromboxane biosynthesis and platelet function
in type II diabetes mellitus.
Davi G, Catalano I, Averna M, Notarbartolo A, Strano A,
Ciabattoni G, Patrono C.
Department of Medicine, University of Chieti, Rome, Italy.
It has been suggested that platelet hyperreactivity in patients
with diabetes mellitus is associated with increased platelet
production of thromboxane. We therefore compared the excretion of
a thromboxane metabolite and platelet function in 50 patients with
Type II diabetes mellitus who had normal renal function and
clinical evidence of macrovascular disease and in 32 healthy
controls. The mean (+/- SD) excretion rate of urinary
11-dehydro-thromboxane B2 was significantly higher in the patients
than in the controls (5.94 +/- 3.68 vs. 1.50 +/- 0.79 nmol per
day; P less than 0.001), irrespective of the type of macrovascular
complication. Tight metabolic control achieved with insulin
therapy reduced the levels of 11-dehydro-thromboxane B2 by
approximately 50 percent. The fractional conversion of exogenous
thromboxane B2 (infused at a rate of 4.5, 45.3, or 226.4 fmol per
kilogram of body weight per second) to urinary
11-dehydro-thromboxane B2 was assessed in four patients, in whom
it averaged 5.4 +/- 0.1 percent; this value did not differ from
that measured in healthy subjects. Aspirin in low doses (50 mg per
day for seven days) reduced urinary excretion of the metabolite by
approximately 80 percent in four patients. The fact that
thromboxane biosynthesis recovered over the following 10 days was
consistent with a platelet origin of the urinary
metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 2345567 [PubMed - indexed for MEDLINE]
Protective effect of increased glycolytic
substrate against systolic and diastolic dysfunction and increased
coronary resistance from prolonged global underperfusion and
reperfusion in isolated rabbit hearts perfused with erythrocyte
suspensions.
Eberli FR, Weinberg EO, Grice WN, Horowitz GL, Apstein CS.
Whitaker Cardiovascular Institute of Boston University School of
Medicine, MA 02118.
Current therapy of myocardial infarction may include early
reperfusion. We simulated myocardial perfusion conditions during
evolving myocardial infarction in isolated, normothermic,
isovolumic rabbit hearts perfused with buffer containing bovine
red blood cells (hematocrit of 40%), and we assessed the effects
of high levels of glucose and insulin as "therapy" during
prolonged (150-minute) severe underperfusion and reperfusion.
Protocol 1 consisted of underperfusion at a constant coronary
perfusion pressure of 8 mm Hg. The control group (n = 8) received
5.5 mmol/l glucose and 15 microunits/ml insulin; the group treated
with high levels of glucose and insulin (G + I) (n = 8) received
19.5 mmol/l glucose and 250 microunits/ml insulin during both
underperfusion and reperfusion. Relative to the control group, the
G + I group experienced 1) greater developed pressure during
underperfusion and increased recovery during reperfusion, 2)
preserved diastolic function during underperfusion and
reperfusion, 3) lower coronary resistance and greater coronary
flow during the underperfusion period, 4) increased glycolytic
flux and preserved glycogen stores and high energy phosphate
levels, and 5) less loss of myocyte enzymes (creatine kinase and
alanine aminotransferase). In protocol 2, coronary flow was kept
identical in control (n = 8) and G + I hearts (n = 8) during the
underperfusion period, and left ventricular end-diastolic pressure
was kept below 10 mm Hg in both groups to minimize subendocardial
damage and vascular compression. In this protocol, the effect of
the G + I intervention in the prevention of an increase in
coronary resistance during the underperfusion period was
distinguished from its myocellular metabolic effects; the high G +
I substrate had protective effects on mechanical and metabolic
function that were less marked than, but similar to, those in
protocol 1, indicating that its mechanisms of protection during
underperfusion affected both cardiac function and coronary
resistance. We conclude that the G + I intervention, in clinically
relevant concentrations, markedly protected severely underperfused
myocardium for 150 minutes and may be a beneficial intervention in
combination with reperfusion therapy in acute myocardial
infarction.
PMID: 1991351 [PubMed - indexed for MEDLINE]
Erratum in:
- N Engl J Med 1997 Jan 9;336(2):147
Comment in:
Comparison of coronary bypass surgery with
angioplasty in patients with multivessel disease. The Bypass
Angioplasty Revascularization Investigation (BARI) Investigators.
BACKGROUND: Coronary-artery bypass grafting (CABG) and
percutaneous transluminal coronary angioplasty (PTCA) are
alternative methods of revascularization in patients with coronary
artery disease. We tested the hypothesis that in selected patients
with multivessel disease suitable for treatment with either
procedure, an initial strategy of PTCA does not result in a poorer
five-year clinical outcome than CABG. METHODS: Patients with
multivessel disease were randomly assigned to an initial treatment
strategy of CABG (n = 914) or PTCA (n = 915) and were followed for
an average of 5.4 years. Analysis of outcome events was performed
according to the intention to treat. RESULTS: The respective
in-hospital event rates for CABG and PTCA were 1.3 percent and 1.1
percent for mortality, 4.6 percent and 2.1 percent for Q-wave
myocardial infarction (P < 0.01), and 0.8 percent and 0.2 percent
for stroke. The five-year survival rate was 89.3 percent for those
assigned to CABG and 86.3 percent for those assigned to PTCA (P =
0.19; 95 percent confidence interval of the difference in
survival, -0.2 percent to 6.0 percent). The respective five-year
survival rates free from Q-wave myocardial infarction were 80.4
percent and 78.7 percent. By five years after study entry, 8
percent of the patients assigned to CABG had undergone additional
revascularization procedures, as compared with 54 percent of those
assigned to PTCA; 69 percent of those assigned to PTCA did not
subsequently undergo CABG. Among diabetic patients who were being
treated with insulin or oral hypoglycemic agents at base line, a
subgroup not specified by the protocol, five-year survival was
80.6 percent for the CABG group as compared with 65.5 percent for
the PTCA group (P = 0.003). CONCLUSIONS: As compared with CABG, an
initial strategy of PTCA did not significantly compromise
five-year survival in patients with multivessel disease, although
subsequent revascularization was required more often with this
strategy. For treated diabetics, five-year survival was
significantly better after CABG than after PTCA.
Publication Types:
- Clinical Trial
- Multicenter Study
- Randomized Controlled Trial
PMID: 8657237 [PubMed - indexed for MEDLINE]
Comment in:
Outcome of coronary bypass surgery versus
coronary angioplasty in diabetic patients with multivessel
coronary artery disease.
Weintraub WS, Stein B, Kosinski A, Douglas JS Jr, Ghazzal ZM,
Jones EL, Morris DC, Guyton RA, Craver JM, King SB 3rd.
Division of Cardiology, Emory University School of Medicine,
Atlanta, Georgia 30322, USA. bill@hp3.eushc.org
OBJECTIVES: This study sought to compare the outcome of
percutaneous transluminal coronary angioplasty (PTCA) (n = 834)
and coronary artery bypass graft surgery (CABG) (n = 1805) in
diabetic patients with multivessel coronary disease from an
observational database. BACKGROUND: There is concern about
selection of revascularization in diabetic patients with
multivessel coronary artery disease. METHODS: Data were collected
prospectively and entered into a computerized database. Follow-up
was by letter or telephone or additional events resulting in
readmission. RESULTS: After CABG there were more in-hospital
deaths (0.36% vs. 4.99%, p < 0.0001) and a trend toward more Q
wave myocardial infarctions than after PTCA. Five- and 10-year
survival rates were 78% and 45% after PTCA and 76% and 48% after
CABG, respectively (p = 0.47). At 5 and 10 years,
insulin-requiring patients had lower survival rates of 72% and 31%
after PTCA and 70% and 48% after CABG, respectively (p = 0.54).
Multivariate correlates of long-term mortality were older age, low
left ventricular ejection fraction, heart failure and
hypertension. In the total group, insulin requirement was a
correlate of long-term mortality. For the total group, choice of
therapy had a multivariate hazard ratio close to 1. In the
insulin-requiring subgroup, the multivariate hazard ratio was 1.35
(95% confidence interval 1.01 to 1.79) for PTCA versus CABG.
Corrected for baseline differences, 5- and 10-year survival rates
were 68% and 36% after PTCA and 75% and 47% after CABG,
respectively, in the insulin-requiring subgroup. Nonfatal events
were more common after PTCA, especially additional
revascularization. CONCLUSIONS: This study reveals a high
incidence of events in diabetic patients and raises further
questions about angioplasty in insulin-requiring diabetic patients
with multivessel disease.
PMID: 9426011 [PubMed - indexed for MEDLINE]
10. Savage M, Fischman D, Slata
P, et al. Coronary intervention in the diabetic patient: improved
outcome following stent implantation versus balloon angioplasty.
J Am Coll Cardiol. 1997;29(suppl A):188A.
11. Thierry J, Fajadet J, Jordan C, et al. Coronary
stenting in diabetics: immediate and mid-term clinical outcome.
Catheter Cardiovasc Intervent. 1999;47:279–284.
12. Lincoff A, Tcheng J, Cabot C, et al. Marked
benefit in diabetic patients treated with stent and abciximab
combination: 6 month outcome of the EPISTENT trial. J Am Coll
Cardiol. 1999;33(suppl A):82–84.
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