Introduction
Traditionally, ischemic heart disease has been divided into several separate syndromes stable coronary artery disease, unstable angina UA 1,2 , non-Q wave myocardial infarction MI , and Q wave MI. However, the understanding of the conversion of a stable atherosclerotic lesion to a ruptured plaque with thrombosis has provided a unifying hypothesis for the etiology of acute coronary syndromes ACS 3-7 . The concept of myocardial ischemia as a spectrum provides a framework for understanding the...
CURRENT TECHNIQUES IN PCI Conventional Angioplasty
Although balloon catheters are used as adjunctive devices in most modern-era interventional therapies, they stand alone in conventional PTCA. The technical design of conventional PTCA equipment has evolved considerably in the last several years. Improvements include more supportive and flexible guiding catheters, more trackable and flexible guide wires, and improved crossing profiles of balloon catheters. These technical improvements have led to a 92 procedural success rate, and less than a 1...
Nuclear Imaging
The National Heart Attack Alert Program Working Group has recently published a summary and analysis of the published literature on the use of nuclear perfusion imaging in the ED for the evaluation of chest pain patients 39 . In general, the reported sensitivities and specificities of 99Tc sestamibi imaging for predicting acute MI in these studies was gt 90 and in the 80-90 range, respectively. Positive and negative predictive values in these studies were also high. In addition, their review of...
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a strong influence on epicardial hemodynamics, it is important to understand microvascular disorders that characterize coronary artery disease in its most active phases. One of the earliest events in acute myocardial ischemia is microvascular damage and dysfUnction 86 . Although injury may be the direct result of diminished nutritive blood flow, evidence also suggests that platelet micro-embolism, platelet-leukocyte aggregates, and inflammatory cytokines play important roles. The restoration of...
Conclusion 1
The current standard for adjunctive therapy with thrombolysis remains aspirin and heparin. Both of these medications came into use more than 50 yr ago when our understanding of the molecular biology underlying acute coronary syndromes was nonexistent. As we have deciphered the mechanisms underlying platelet activation and aggregation and thrombin generation and activity, we now stand at the thresh old of a new era in which exquisitely tailored pharmacotherapy can be used to inhibit the pathways...
Pathophysiologic Spectrum
Across the spectrum of myocardial ischemia, markers of inflammation, thrombosis, and platelet activation increase in frequency in parallel with the clinical severity of the ACS Fig. 3 . Markers of inflammation, such as C-reative protein CRP , are found in 13 of patients with stable coronary artery disease vs 65 of patients with UA and 76 of patients with acute MI 43 . Similarly, antibodies to C. pneumoniae are found in a higher percentage of patients with ACS than non-ACS patients 84 ....
Relationship Of Coronary Blood Flow To Clinical Outcomes
Several thrombolytic trials have demonstrated an important relationship between the different TFGs at 90 min after thrombolysis and clinical outcomes 50,75-78 . The GUSTO angiographic substudy involving 1431 patients provided important insight into the mechanism linking TIMI 3 flow with reduced mortality 50 . While the rate of TIMI grade 2 flow did not differ significantly among the thrombolytic regimens 25 with SK and subcutaneous heparin regimen, 28 with SK and intravenous IV heparin regimen,...
Transformation From Stable To Vulnerable Atherosclerotic Plaque
There is considerable heterogeneity in the structure of atherosclerotic plaques, and numerous investigations have attempted to identify special features of plaques that are involved in acute ischemic syndromes 5-12 . It has been observed in patients experiencing acute myocardial infarction, who have coincidentally undergone coronary arteriography at some point prior to the acute event, that the site of coronary occlusion is often not the site of the most stenotic lesion in the coronary tree...
Medical Treatment
An overview of the medical treatment of ACS is shown in Fig. 9. As discussed, aspirin has been shown in numerous studies to be beneficial across the entire spectrum of myocardial ischemia, from primary prevention of MI 103,104 to prevention of death or MI in all ACS 71-74,94,105 . Aspirin is also a very effective agent for secondary prevention of events 106,107 . Heparin has also been shown to be beneficial in reducing death or MI in non-STE ACS 73,75-77 . Low-molecular-weight heparin also...
Combinations of Thrombolytics with Platelet Glycoprotein IIBIIIA Inhibitors and
With the failure of new thrombolytic monotherapies to improve early coronary patency and clinical outcomes compared with tPA, interest has shifted toward combina tion pharmacotherapies 135 . Theoretical arguments have been made for combining fibrinolytics with augmented antiplatelet therapies 136 . The platelet membrane glycoprotein GP Ilb IIIa, a specific fibrinogen receptor, is the final common pathway in platelet activation and an attractive therapeutic target. Antibodies, peptides, and...
Risk Stratification In Acute Coronary Syndromes
A possible explanation of the conflicting results in the above trials is the fact that patients with unstable angina and non-ST-elevation wave MI present with a wide spectrum of clinical risk for death and cardiac ischemic events. Ideally, one ought to be able to identify high risk patients who might benefit mostly from an aggressive invasive approach, and those with lower risk where conservative management might be more appropriate. Several analyses have been performed attempting to identify...
References Hzm
1. Tigerstedt R, Bergman PG. The kidneys and the circulation. Scand Arch Physiol 1898 8 223-227-. as translated by Ruskin A., in classics in arterial hypertension. Charles C. Thomas, Springfield, IL, 1956, pp. 273. 2. Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on experimental hypertension. The production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med 1937 59 347-378. 3. Yamazaki T, Komuro I, Kudoh S, et al. Angiotensin II partly mediates...
Tfg Classification Scheme
The original definition of the TFGs from the TIMI 1 study in 1986 are as follows 1 Grade 0 No perfusion. No antegrade flow beyond the point of occlusion. Grade 1 Penetration without perfusion. Contrast material passes beyond the area of obstruction but fails to opacify the entire coronary bed distal to the obstruction for the duration of the cineangiographic filming sequence. Grade 2 Partial perfusion. Contrast material passes across the obstruction and opacifies the coronary distal to the...
Use of Calcium Blockers in Patients with Unstable Angina
Several small randomized trials have examined the use of nifedipine and diltiazem in unstable angina. A meta-analysis of these trials 37 showed no reduction in MI or death rates in patients given calcium antagonists 110 of 561 patients 20 treated with calcium antagonists developed MI, compared to 104 of 548 19 in the control group death rates were 2.4 and 1.6 for the calcium antagonist and control groups, respectively Fig. 5 . The largest trial, the Holland University Nifedipine Metoprolol...
References Vkl
1. American Heart Association. 2001 Heart and Stroke Statistical Update. American Heart Association, Dallas, 2001. 2. Hu FB, Stampfer MJ, Manson JE, et al. Trends in the incidence of coronary heart disease and changes in diet and lifestyle in women. N Engl J Med 2000 343 530-537. 3. Castelli WP. Cardiovascular disease in women. Am J Obstet Gynecol 1988 158 1553-1567. 4. Kannel WB. Hypertension, hypertrophy, and the occurrence of cardiovascular disease. Am J Med Sci 1991 302 199-204. 5. Komanoff...
Pci Xas
In the Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis RESTORE trial 164 of 2139 patients, there was a 38 relative reduction 5.4 vs 8.7 in the placebo group, p 0.005 of the composite end point death, acute MI, repeat revascularization, or stent placement at 2 d, and a 27 relative reduction at 7 d p 0.02 in patients treated with tirofiban, with no significant increase in bleeding complications. At 30 d and 6 mo, the 3 difference in absolute event rates was unchanged, and the...
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Ejection fraction lt 40 PPA 69 Exercise time lt 6 METS, PPA 58 for D, RI, UA, CHF, VA. aAbbreviations D, death RI, reinfarction UA, unstable angina CHF, congestive heart failure VA, ventricular arrhythmia PPA, positive predictive accuracy R, revascularization METS, metabolic equivalents BP, blood pressure RR, relative risk W, Watts DST DHR, change in ST-segment depression vs change in heart rate. b490 out of 981 received thrombolytics. aAbbreviations D, death RI, reinfarction UA, unstable...
The Ideal Marker
An ideal marker of cardiac injury should be both cardiac-specific and have zero blood concentration in the absence of myocardial injury. It should become elevated in the serum soon after the onset of an episode of chest pain to allow the detection of high-risk patients as early as possible and should remain elevated for many hours to allow detection in patients who delay in seeking evaluation. Persistent elevation of a marker for several days could aid in diagnosis and risk stratification of...
References Gpj
1. Boden WE, O'Rourke RA, Crawford MH, et al. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital VANQWISH Trial Investigators. N Engl J Med 1998 338 1785-1792. 2. Fragmin and Fast Revascularisation during Instability in Coronary artery disease Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery...
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Fig. 2. Shown here is a histogram displaying the percent of patients with a given CTFC grouped by bins of 5 frames following thrombolysis in the TIMI 4, TIMI 10A, and TIMI 10B trials. Note that very few patients have a CTFC gt 100. Fig. 2. Shown here is a histogram displaying the percent of patients with a given CTFC grouped by bins of 5 frames following thrombolysis in the TIMI 4, TIMI 10A, and TIMI 10B trials. Note that very few patients have a CTFC gt 100. Fig. 3. Cumulative distribution...
Comparative Trials of Thrombolytic Regimens
There are three large mortality trials comparing tPA with SK. These trials are summarized in Table 3 and discussed below 115 . GISSI-2 International Study Group Trial. The GISSI-2 International Study was the first adequately powered mortality study to compare tPA with SK and also to explore the Comparative Mortality Trials of tPA vs SK or APSAC GISSI-2 End Drug SK 3h tPA SK 3h tPA APSAC SK Accel. tPA SK tPA n patients 10,396 20,173 10,344 10,328 Death Reinfarction Any stroke Hemorrhagic stroke...
Platelet Pathophysiology In Arterial Thrombosis
Platelets are the smallest of blood cells, with an average diameter of 1-2 im and a mean cell volume of 5-6 fL, and have a life span of approx 7-10 d 9 , which apparently is not reduced in activated platelets 10 . The average platelet count is quite high, ranging from 140-440 X 109 L 11 . Therefore, even seemingly subtle changes related to the function and activation status of platelets may have a significant impact on physiologic or pathologic processes. Platelets play a central role in the...
The Troponins
The troponins T, I, and C are a group of three distinct proteins that are part of the contractile apparatus of all striated muscle. TnT 33 kDa provides the structural component that links the troponin complex with tropomyosin to the actin filament. TnI 23.5 kDa is the regulatory subunit involved in the contraction-relaxation process and TnC 18 kDa is a calcium-binding subunit. TnI and TnT each exist in three isoforms skeletal slow- and fast-twitch and cardiac that are readily identified as...
Arrythmogenesis
Since activation of the renin-angiotensin system, along with other neurohormones, occurs during the acute and convalescent phases of MI, this system may play an important role in arrhythmogenesis, which is mediated by direct and in direct effects of angiotensin II 69-71 . At least five mechanisms are postulated through which angiotensin II may promote cardiac arrhythmias during MI i angiotensin II mediates increases in cardiac filling pressures, thereby abnormally increasing wall stress 72 ii...
Echocardiogram
Resting echocardiography is examined in the Systematic Review's report 5 . Its theoretical appeal for the diagnosis of ACI in the ED is based on the relationship between regional myocardial wall motion abnormalities and cardiac ischemia. When the myocardium becomes ischemic, there is a nearly immediate alteration in wall motion, and the wall becomes hypokinetic or dyskinetic 93 . However, there are some caveats regarding its use in the ED. When looking for ACI, it still has a high enough...
New Paradigm Of Clinical Syndromes
The extent of local thrombosis at the site of coronary plaque rupture is largely responsible for the severity of the clinical syndrome Fig. 1 . If the thrombosis causes total occlusion of the coronary artery, persistent ischemic pain and STE develop, which usually evolves into a Q-wave MI 11,12 . In some patients, the amount of local thrombosis is extensive, but the obstruction is subtotal, resulting in a flow-limiting coronary stenosis and myocardial ischemia e.g., UA sometimes associated with...
The Pathophysiology Of Cardiogenic Shock From Myocardial Infarction
A comprehensive understanding of the pathophysiologic characteristics and events of cardiogenic shock must be attained to impact the discouraging outcome of patients with this entity. The assiduous hemodynamic decline involves several interactive processes. Early initial 60 min in the course of infarction autonomic disturbances have a predominant influence on a patient's hemodynamic status. As reported by Webb et al. 8 sympathetic overactivity tachycardia and hypertension occurred in 36 of...
Primary Pci Is The Treatment Of Choice For Patients With Ami At Qualified
In a well-known meta-analysis of 10 randomized trials of acute STEMI, primary PCI lowered the rates of death, stroke, and the combined end point of death or reinfarction compared to fibrinolytic therapy 2 . The trials in this meta-analysis were performed before the advent of newer fibrinolytic agents and glycoprotein GP Ilb IIIa platelet inhibitors and before the widespread use of coronary stenting. More recent randomized studies utilizing these newer modalities continue to demonstrate an even...
Atypical Presentations
Few studies address what proportion of ED patients with ACI present with atypical symptoms, a group for whom the diagnostic triage decision is often most problematic. Among hospitalized patients with AMI, 13-26 had no chest pain or had chief complaints other than chest pain i.e., dyspnea, extreme fatigue, abdominal discomfort, nausea, or syncope 23,24 . In our ED study of 10,689 patients 2 presenting with a wide range of clinical symptoms, we found that 31 of patients with suspected ACI...
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left-sided leads i.e., midclavicular line, fifth intercostal space for V4R, anterior axillary line for V5R, and midaxillary line for V6R . Posterior leads continue in the same horizontal plane as the precordial leads i.e., fifth intercostal space, but continue on to the posterior axillary line for V7, midscapular line for V8, and paraspinal for V9 44 . A plethora of articles assess the diagnostic value of V4R and other right-sided leads to detect RVI 8,47-51 . There is a consensus that within...
Sorin J Brener MD and Eric J Topol MD
Fibrinolytic Therapy Vs Mechanical Reperfusion Key Concepts and Differences Primary Angioplasty Advances in Primary Angioplasty Devices and Pharmacology Epicardial and Myocardial Reperfusion Rescue and Facilitated Angioplasty Targeted Subgroups for Primary Angioplasty Technical Aspects of Primary Angioplasty Economic Aspects of Primary Angioplasty Limitations of Primary Angioplasty Current Guidelines for Primary Angioplasty Summary and Recommendations References
How To Reduce Your Chance of a Heart Attack
To find your risk for a heart attack, check the boxes that apply to you A family history of early heart disease Father or brother diagnosed before age 55 Mother or sister diagnosed before age 65 Age Men 45 years or older Women 55 years or older One or more previous heart attacks, angina, bypass surgery or angioplasty, stroke, or blockages in neck or leg arteries The more risk factors you have, the greater your risk for a heart attack Reduce Your Risk of a Heart Attack by Taking Steps To Prevent...
References Yvr
1. Mehta RH, Stalhandske EJ, McCargar PA, et al. Elderly patients at highest risk with acute myocardial infarction are more frequently transferred from community hospitals to tertiary centers reality or myth Am Heart J 1999 138 688-695. 2. Weaver WD, Simes J, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction. JAMA 1997 278 2093-2098. 3. Schomig A, Kastrati A, Dirschinger J, et al. Coronary stenting plus platelet...
Direct Thrombin Inhibitors
Unlike UFH, direct thrombin inhibitors such as hirudin and bivalirudin do not require a cofactor to inhibit thrombin 66,67 . The class prototype, hirudin, is a 65-amino-acid polypeptide derived from the medicinal leech Hirudo medicinalis , that binds selectively to thrombin in a 1 1 fashion at 2 sites. The 72-amino-acid carboxy terminus binds to the fibrinogen recognition site of thrombin. The amino terminus binds to thrombin's catalytic site. This binding is not covalent but the dissociation...
Goldman Chest Pain Protocol
The Goldman Chest Pain Protocol 7 is based on a computer-derived model using recursive partitioning analysis to predict myocardial infarction in patients with chest pain Tables 11 and 12 . It has good sensitivity about 90 for AMI, but it was not developed to detect UAP as well. In a clinical impact study of low-intensity, nonintru-sive intervention performed at a teaching hospital ED 16 , no differences in hospital-ization rate, length of stay, or estimated costs was demonstrated between the...
Timi Myocardial Perfusion Grade
It has recently become apparent that epicardial flow does not necessarily imply tissue level or microvascular perfusion 21,22 . This led to the recent development of a new angiographic measure of tissue level perfusion, the TIMI myocardial perfusion grade TMPG 4 , as follows TMPG 3 Normal entry and exit of dye from the microvasculature. There is the ground glass appearance blush or opacification of the myocardium in the distribution of the culprit lesion that clears normally, and is either gone...
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Fig. 5. Diabetic women benefit from glycoprotein Ilb IIIa antagonism. Women with diabetes in the EPISTENT trial who were treated with abciximab and coronary stent placement demonstrated a significant reduction in adverse outcomes at 1 yr compared to women treated with placebo or the combination of balloon angioplasty and abciximab. MI, myocardial infarction TVR, target vessel revascularization 48 . batide was associated with a significant reduction in the incidence of death or myocardial...
WARFARIN Mechanism of Action
Vitamin K, a cofactor required for the conversion of precursor proteins into active coagulation factors II, VII, IX, and X, is disrupted by warfarin. As a consequence, the vitamin K-dependent proteins exposed to warfarin during their synthesis are rendered dysfunctional. Where coagulation factors have already been completely synthesized prior to warfarin treatment, the drug has no effect. As a result, the coagulation factors that are fully established have to be depleted by way of normal...
Allergy Hypotension Fever
SK and APSAC are antigenic and potentially allergenic although serious anaphylaxis and bronchoconstriction are rare incidence lt 0.2-0.5 96,103,104,110,118,160 . In ISIS-2, any allergic reaction was observed in 4.4 receiving SK compared to 0.9 receiving placebo, an absolute excess of 3.5 103 . In the comparative study ISIS-3 118 , any allergic-type reaction was reported after SK in 3.6 , APSAC in 5.1 , and tPA duteplase in 0.8 p lt 0.00001, SK vs tPA . Most of these reactions were minor only...
De Novo Lesions
Coronary stent implantation was originally assessed in the treatment of focal de novo lesions in large native coronary arteries. Early trials such as Belgium and Netherlands Stent Trial BENESTENT 55 and Stress Restenosis Study Investigation STRESS 56 measured the safety and efficacy of stents vs PTCA for stable CAD. These trials both demonstrated that stents conferred significant advantages in angiographic restenosis rates, and trends towards decreased target vessel revascularization TVR , and...
Interaction of the ReninAngiotensin System with the Fibrinolytic System and
Another important proposed mechanism of the renin-angiotensin system in acute coronary syndromes concerns the ability to modulate the plasma fibrinolytic system, which is based on the balance between plasminogen activator inhibitor-1 PAI-1 and tissue-type plasminogen activator tPA . tPA is released from endothelial cells and is present in small amounts in plasma where it catalyzes the conversion of plasminogen to plasmin. Plasmin proteolytically degrades fibrin, hence its antithrombotic...
Angioplasty Of Ccx
aShort- and medium-term clinical outcomes from 5 major randomized trials of GP IIb IIIa antagonists in the treatment of patients with non-ST-elevation ACS. MI, myocardial infarction. Modified from ref. 91. aShort- and medium-term clinical outcomes from 5 major randomized trials of GP IIb IIIa antagonists in the treatment of patients with non-ST-elevation ACS. MI, myocardial infarction. Modified from ref. 91. Fig. 8. Thirty-day event-rate curves mortality or myocardial infarction for patients...
Cardiogenic Shock
Cardiogenic shock is the result of substantial loss of myocardial function gt 40 of left ventricular mass in 80 , or the development of mechanical complications in 20 of those in whom it occurs 93,94 . Historically, cardiogenic shock was associated with an exceedingly poor prognosis, with mortality averaging 70 94-96 . Temporizing measures, such as intra-aortic counterpulsation and inotropic support do not affect survival in the absence of reperfusion. Overall, fibrinolytic agents have not...
Subacute Thrombosis after Coronary Stenting
A major limitation of coronary stenting in early trials was the risk of subacute thrombosis, which occurred in up to 8 of cases, and generally eventuated in MI or death 55,56,79,80 . Because subacute thrombosis generally occurs late, at 2-14 d postintervention, it is a more feared complication than abrupt closure immediately following conventional PTCA, which generally occurs while the patient is still in the cardiac catheterization laboratory. Initial efforts involving intensive...
VANQWISH Trial
The VANQWISH trial 34,35 was designed to compare outcomes of patients with a non-Q wave MI who were randomized prospectively to an early invasive strategy vs an early conservative strategy. The primary end point of the trial was all-cause mortality or nonfatal infarction during at least 1 yr of follow-up. A total of 920 patients mean age 61 10 yr were randomized and followed for a mean duration of 23 mo range 12-44 mo . In the invasive arm, 462 patients underwent early coronary angiography...
References Nui
1. The TIMI Study Group. The Thrombolysis in Myocardial Infarction TIMI trial. Phase I findings. N Engl J Med 1985 312 932-936. 2. Gibson CM, Cannon CP, Daley WL, et al. The TIMI frame count a quantitative method of assessing coronary artery flow. Circulation 1996 93 879-888. 3. Ross AM, Neuhaus KL, Ellis SG. Frequent lack of concordance among core laboratories in assessing TIMI flow grade after reperfusion therapy. Circulation 1995 92 I-345. 4. Gibson CM, Cannon CP, Murphy SA, et al....
ANTICOAGULATION Coagulation Cascade
Thrombin is a glycosylated serine protease that plays a fundamental role in thrombosis 117 . Thrombin is generated from prothrombin by the prothrombinase complex, which includes factors Xa, Va, calcium, and phospholipids Fig. 7 . Its main action is to transform fibrinogen into fibrin. Thrombin is one of the most potent endogenous platelet activator 110-112 . The active catalytic site lies within a relatively narrow canyon on the molecule's surface Fig. 8 118 . Adjacent to this site is the...
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aEnd points measured at 21 d included patients without STE. bEnd points measured at 35 d death vascular mortality included patients without STE. Study also included a factorial randomization to aspirin. cEndpoints measured at 30 d included patients without STE. dMajor bleeds and stroke attributed by investigator to SK. Nonfatal stroke at 6 mo was 0.7 in each group 102 . NR not reported. SK Streptokinase. aEnd points measured at 21 d included patients without STE. bEnd points measured at 35 d...
Laser Angioplasty
Light amplification by stimulated emission of radiation LASER angioplasty utilizes highly organized light emitted from optical fibers at the catheter tip to destroy obstructing atherosclerotic tissue. The two types of systems currently available are the excimer laser coronary angioplasty ELCA , which emits light with wavelength 308 nm, and the holmium yttrium-aluminum-garnet Ho YAG , which emits light with wavelength 2100 nm. The specific effects on atherosclerotic tissue vaporization, direct...
Myoglobin 1
Myoglobin is a 17.8-kDa heme protein common to all striated muscle therefore, it is not cardiac-specific. Owing to its small size, it may be detected in the serum within 1-3 h after the onset of ischemic symptoms. Despite a lack of specificity, myoglobin has high diagnostic sensitivity thus, a negative myoglobin during this time frame has excellent negative predictive value 51,52 . Because of rapid renal clearance, myoglobin remains elevated above the reference range for only 12-18 h. This...