Atipical Chest Pain Normal Arteries

7/28/2019 Atipical Chest Pain Normal Arteries

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Profiles in Coronary Artery Disease

C. Michael Gibson

University of California San Francisco, School of Medicine, San Francisco, California 94118

Today's cardiologist is faced with a rapidly expanding selection of diagnostic and therapeutic modalities in themanagement of coronary artery disease. The purpose of this chapter is to place these evolving diagnostic andtherapeutic strategies into a clinical context through the use of case histories. The discussion of the cases is largelyevidence-based and draws on data from randomized, prospective trials.

ATYPICAL CHEST PAIN WITH NORMAL CORONARYARTERIES

The most common clinical manifestation of coronary artery disease is chest pain, but this symptom is nonspecific and

there is a broad differential diagnosis of the noncardiac causes of chest pain. An abbreviated list of the most commoncauses of noncardiac chest pain includes musculoskeletal disorders (costochondritis), neurologic disorders (cervicaldisc disease, thoracic outlet syndrome, zoster), mediastinal disorders (neoplastic and inflammatory), pulmonarydisorders (pneumonia, pleuritic processes, pulmonary embolism, neoplasia, and other parenchymal processes), andgastrointestinal disorders (esophageal spasm, esophagitis, peptic ulcer disease, cholecystitis, and pancreatitis). Thefairly common condition of esophageal spasm presents a particular diagnostic dilemma because both ischemiccoronary artery disease and esophageal spasm may respond to nitrates. Esophageal spasm may even result in radiationof the discomfort into the left arm.

A variety of cardiac conditions may also mimic the symptoms of obstructive coronary artery disease, includingmyocarditis, pericarditis, aortic and subaortic valvular disease, aortic dissection, thoracic aortic aneurysm,intramyocardial compression (bridging) of a coronary artery segment, primary pulmonary hypertension,cardiomyopathies, mitral valve prolapse, and a ruptured sinus of Valsalva aneurysm.

The frequency of finding normal or nonobstructive coronary anatomy at the time of cardiac catheterization isapproximately 20%, according to registry data from the Society of Cardiac Angiography . This frequency variesdepending on local practice patterns, including the use of noninvasive tests. Female gender is associated with a morethan four-fold higher incidence of false-positive exercise tolerance tests . The cause of atypical chest pain withdocumented ischemia, but in the absence of obstructive epicardial disease, is not clear. One potential cause isimpaired coronary vasodilator reserve. Data suggest that 50 mg of imipramine daily may reduce the frequency ofthese patients' symptoms by 52%, possibly through a visceral analgesic effect . The prognosis of patients withchest pain and angiographically normal coronary arteries is quite good .

(1)

(2)

(3)(4)

Another cause of ischemic chest pain in the presence of coronary arteries that appear normal or near-normal isepicardial coronary spasm. Although Prinzmetal originally described a syndrome of focal coronary spasm that

occurred at the site of fixed atherosclerotic narrowing , it has become appreciated that spasm can also occur at sitesthat are minimally diseased or are angiographically completely free of obstructive disease.(5)

Case 1

A 45-year-old man presented with chest discomfort. He had a 30 pack-year history of cigarette smoking and mildsystolic hypertension treated with an angiotensin-converting enzyme inhibitor. The chest discomfort occurred

predominantly at rest, often during emotional upset, but also on occasion with exertion. He exercised for 9 minuteson a standard Bruce protocol and had neither chest pain nor diagnostic electrocardiographic (ECG) changes. He wascompliant with a smoking cessation program and was prescribed aspirin. However, he continued to experiencesubsternal chest pain for the next 6 months, which prompted a diagnostic cardiac catheterization.

10/25/00 3:47 PSECTION VIII: SPECIFIC DISORDERS

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Example of coronary spasm. A diffuse mild lesion is present in the proximal circumflex on initial angiography.After several injections, the patient developed chest pain and the artery narrowed. The symptoms and narrowing

were relieved with sublingual nifedipine.

Examples of lesion regression taken from the Familial Atherosclerosis Treatment Study (FATS) study. The top row

On cardiac catheterization, coronary angiography initially showed a mild lesion in the proximal circumflex artery(Fig. 30.1 ). The left anterior descending (LAD) and the right coronary arteries were free of disease. However, afterthe initial injections contrast agent, the patient developed chest pain and a very brief episode of total occlusion of thecircumflex artery, which was followed by a marked and sustained reduction in the caliber of the circumflex artery(Fig. 30.1 ). His pulmonary capillary wedge (PCW) pressure rose to 30 mm Hg. He was treated with 10 mg ofsublingual nifedipine, with resolution of the chest pain and relief of coronary spasm on angiography. He was

prescribed a calcium channel blocker and experienced resolution of both his rest and exertional symptoms.

A

B

FIG. 30.1.

A:B:

Illustrative points

Coronary spasm can be observed during the performance of coronary angiography and is often caused by catheter-induced spasm at the ostium of the coronary artery (particularly the right coronary artery). The narrowing observed

here was not induced by the catheter tip, and the patient's presenting symptoms were reproduced. This patient mostlikely had . He may have also had exercise-induced coronary spasm. Although coronaryspasm occurred spontaneously during the course of cardiac catheterization in this patient, provocative testing withergonovine maleate is usually required to document this syndrome. Normal coronary arteries narrow diffusely inresponse to this agent, but patients with variant angina respond with focal spasm that totally occludes the coronaryartery. If coronary spasm is suspected based on the clinical history (nocturnal or temporally reproducible symptoms,intermittent ST-segment elevation), then calcium channel blockers and nitrates should be discontinued for at least 24hours before coronary angiography so that provocative maneuvers do not result in a false-negative study.

Prinzmetal's variant angina

The vast majority of patients respond well to nitrates plus a single calcium channel blocker, but approximately 10%require a combination of calcium channel blockers. Patients with drug-resistant coronary spasm often havemultivessel coronary spasm, which can be associated with fatal arrhythmias . If percutaneous transluminalcoronary angioplasty (PTCA) is performed in a patient with variant angina, the risk of restenosis is higher than in a

patient with a fixed obstruction (35% vs. 22%) .

(6)

(7)

STABLE ANGINA

Chronic ischemic heart disease is a common disorder in developed Western countries. Conventional medicalmanagement of this syndrome consists of -blockers, aspirin, and nitrates as needed to reduce symptoms. In patientswith hypercholesterolemia, there is clear evidence that the risk of cardiac events and all-cause mortality can bereduced with aggressive lipid lowering (810). Furthermore, prospective randomized data from angiographic trialshave shown that atherosclerotic disease progression can be halted or even reversed in patients with hyperlipidemia

. Examples of disease regression from the Familial Atherosclerosis Treatment Study (FATS), in which patientswith hyperlipoproteinemia were treated with lovastatin and cholestipol or niacin and cholestipol, are shown in Fig.

30.2 . Compared with control patients, percent stenosis in treated patients typically improved by approximately 1percentage point for each of the 2.5 years of follow-up in regression trials . Of interest, each of the arterialsegments has been shown to respond at an independent rate to lipid-lowering therapy , and it has beendemonstrated that, in addition to systemic risk factors, local mechanical factors such as shear stress may play a role inmediating disease progression .

(11)

(11) (11)(12)

(13)

FIG. 30.2.




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of images were obtained before lipid-lowering therapy, and the bottom row were obtained 2.5 years later. The leftanterior descending coronary artery (LAD) improved from 100% to 28% ( ), the left-panel obtusemarginal branch (OMB) from 39% to 18% (left-panel, lower arrows), the right coronary artery (RCA) from 48% to30%, a second OMB from 69% to 37%, and the left circumflex (LCx) from 44% to 30%. (From Brown BG, AlbersJJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men withhigh levels of apolipoprotein B. 1990;323:1289. Reprinted by permission of

. Copyright 1990, . All rights reserved.)

Example of a single-vessel intervention in a patient with stable angina. An 80% eccentric right coronary artery lesionwas treated with directional atherectomy with an excellent angiographic result .

arrowheads

N Engl J Med The New England Journalof Medicine Massachusetts Medical Society

Despite the small numbers of patients in these trials and the minimal changes in percent diameter narrowing of thearteries, a significant reduction in clinical events has been observed . Although lipid-lowering may not alter ormay only minimally alter the extent of structural lesions, it may instead improve the function ofarteries, such as stabilizing the plaque against plaque rupture or improving the vasomotor responsiveness of theartery to endothelial-derived relaxing factor . Statins may also reduce inflammation and thereby reducereperfusion injury .

(11)fixed dynamic

(14)(15)

(16)

Despite these preventive strategies and aggressive medical management, patients sometimes have persistent and/orintolerable symptoms that require cardiac catheterization to define coronary anatomy with an eye toward possibleintervention. The most appropriate intervention depends on the findings at coronary arteriography.

Case 2

A 55-year-old woman complained of chest discomfort that occurred with exertion in a stable pattern over the courseof 2 years. Her risk factors for coronary artery disease included a total cholesterol level of 280 mg/dL and a high-density lipoprotein (HDL) level of 30 mg/dL, giving a cholesterol/HDL ratio of 7.3. The family history was notablefor a myocardial infarction in her father at 50 years of age. The patient had been taking a -blocker for the past year,which helped but did not eliminate her symptoms of exertional angina. She was following an American HeartAssociation Diet and wanted to engage in an exercise program to improve her HDL level. An exercise tolerance testshowed 2 mm of ST depression in the inferior leads after 3 minutes. She was referred for cardiac catheterization,which showed normal LAD and circumflex arteries but an 80% eccentric right coronary artery lesion (Fig. 30.3 ).The patient was treated with directional atherectomy with excellent angiographic results (Fig. 30.3 ) and resolutionof exercise-induced ischemia.

AB

FIG. 30.3.

(A) (B)

Illustrative points

This woman had single-vessel disease, a clinical syndrome for which the benefits of PTCA have been compared withthose of medical therapy in a randomized, prospective fashion in the Veterans Affairs Angioplasty Compared toMedicine (ACME) trial . In that study of 212 patients with single-vessel disease, PTCA resulted in a reduction ofanginal symptoms compared with medical therapy at 1 month (50% vs. 24% angina free, respectively). However,although the benefit of PTCA was still significant at 6 months, the magnitude of this benefit was reduced (64% vs.45% angina free, respectively). Patients treated with PTCA also had an improvement of 2.1 3.1 minutes in exerciseduration, which was significantly greater than the 0.5 2.2 minutes observed in the medical therapy group. TheAtorvastatin Versus Revascularization Therapy (AVERT) study demonstrated that, among patients with stable anginaand minimal ischemia, aggressive lipid lowering to a low-density lipoprotein (LDL) level of 78 mg/dL can beassociated with a greater reduction in hospitalization for recurrent ischemia compared with PTCA . Despite thelower frequency of events in the medical therapy arm of AVERT, there was still a higher frequency of angina amongmedical therapy patients. This eccentric lesion was not treated with conventional PTCA but rather with atherectomy,which has been shown to result in a lower rate of restenosis at 6 months .

(17)

(18)

(19)

Case 3




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A 63-year-old man presented with 1 year of substernal chest pain with exertion. His risk factors for coronary arterydisease included a positive family history and a history of hypertension. He did not have diabetes. On exercisetolerance testing, he was found to have anterior ST-segment depression at 4 minutes on a standard Bruce protocol.His medications included a -blocker, aspirin, and nitrates, but he continued to experience chest pain withapproximately one block of exertion.

His symptoms limited his lifestyle, and he elected to undergo cardiac catheterization, which showed an 80% proximalright coronary artery lesion and a 90% mid-LAD artery lesion. His PCW pressure was 10 mm Hg, and his left

ventricular ejection fraction (LVEF) was 55%. The patient had diffuse disease of the coronary arteries, with smallvessels that were less than 3.0 mm in diameter. He was treated with a multivessel PTCA, leaving a 10% to 20%residual stenosis at both sites. His chest discomfort resolved after the procedure.

Illustrative points

The role of percutaneous strategies in the patient with multivessel disease continues to evolve. It is difficult tointerpret nonrandomized data comparing the efficacy of multivessel PTCA with that of coronary artery bypassgrafting (CABG) because most multivessel PTCA series involve patients, such as this one, with two-vessel diseaseand a preserved LVEF. In contrast, many CABG series involve patients with three-vessel disease or left main diseaseand a higher proportion of patients with reduced LVEF . A number of randomized, prospective trials have now

been completed (e.g., EAST, RITA, GABI, ERACI) (2124) comparing percutaneous and surgical approaches tomultivessel disease. These studies have shown that the incidence of death and recurrent myocardial infarction issimilar after these two strategies. Although CABG has been associated with a higher incidence of myocardialinfarction and longer hospitalizations, patients treated with PTCA usually require more antianginal medications andrequire repeat revascularization more frequently (2124). This observation may be explained by two phenomena:first, patients treated with CABG have a higher incidence of postoperative infarction, and consequently they mayexperience less angina postoperatively in the infarcted territory on this basis; second, patients treated with PTCA mayhave been less completely revascularized. In many patients, chronic total occlusions limit the ability of a

percutaneous procedure to provide complete revascularization; indeed, approximately half the patients screened in theEAST trial were not deemed suitable for PTCA on this basis.

(20)

Although CABG surgery is a well established and characterized technique, new percutaneous techniques andadjunctive medical strategies to prevent restenosis continue to evolve. This difference renders comparisons betweenthese two strategies very difficult. It must also be realized that restenosis occurs relatively after PTCA, and that

vein graft degeneration occurs after CABG. Consequently, if the duration of follow-up is short, then angioplastywill appear less efficacious, whereas long-term follow-up over many years provides a more valuable comparison ofthese two strategies. The corollary is that PTCA patients may cross over to a strategy of CABG early on, but patientstreated with CABG may crossover to PTCA later in the course of a trial. A high rate of crossover in both directionscan confound the results of these trials if they are analyzed on a conventional intention-to-treat basis.

early

late

UNSTABLE ANGINA

The management of unstable angina continues to evolve rapidly. A variety of new adjunctive antiplatelet agents suchas clopidogrel and glycoprotein IIb/IIIa inhibitors , as well as low-molecular-weight heparin compounds

, have been demonstrated to be efficacious.(25) (26)

(27)

The term actually encompasses a variety of clinical syndromes that are of differing severity andcarry differing prognoses . Stable angina that has begun to increase in frequency or severity (Braunwald class IB[28]) has the most benign course and may respond in many cases to medical therapy alone. These patients have acomplication rate after PTCA which is comparable to that of patients with stable angina, but one that is lower thanthat of patients with angina at rest or postinfarction unstable angina . Patients with angina at rest associated withT-wave inversions or ST-segment depression (Braunwald class IIB and IIIB [28]), and particularly those with chest

pain that is refractory to medical therapy, have a poorer prognosis than do patients with progressive angina. Finally,patients with postinfarction angina (Braunwald class IIC and IIIC [28]) also have a poorer prognosis than patientswith progressive angina. The mainstay of medical therapy at this time remains aspirin, heparin, nitrates, and -

blockers. Thrombolytic agents were not shown to offer any clinical benefit in the Thrombolysis in Myocardial

unstable angina(28)

(28)




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Example of multivessel stenting in the setting of unstable angina. A 90% lesion in the midcourse of the saphenousvein graft to the posterior descending artery was treated with a 3.5-mm Palmaz-Schatz stent, leaving a 0% to10% residual stenosis . A 70% lesion at the origin of the saphenous vein graft to the obtuse marginal wastreated with a 3.0-mm Palmaz-Schatz stent, again leaving a 0% to 10% residual stenosis .

Infarction (TIMI III) trial, possibly because of the exposure of fibrin-bound thrombin and the procoagulant effectsafter thrombolysis, as well as the platelet-rich composition of thrombi in patients with unstable angina, which aremore resistant to thrombolytics .(29)

In patients with acute coronary syndromes, glycoprotein IIb/IIIa inhibitors have been shown to reduce the compositeend point of death, recurrent myocardial infarction, and urgent revascularization by approximately 30% . Themetaanalysis of Kong and coworkers did show an early mortality benefit for this class of agents, and a mortality

benefit was observed when abciximab was combined with intracoronary stenting in the EPISTENT trial . The

subgroups of patients who derive the greatest benefits appear to be those with ST-segment depression (not justflipped T waves), those with elevated serum troponin levels, and those for whom aspirin has failed . Themajority of the benefit occurs in the first days after the intervention.

(26)

(30)

(31)

Case 4

A 72-year-old man had undergone CABG surgery 13 years previously, with saphenous vein grafts placed to the twoobtuse marginals and the LAD artery. He underwent reoperation 8 years ago, with a left internal mammary arterygraft being placed to the LAD artery and saphenous vein grafts being placed to the obtuse marginal and to the

posterior descending artery. He now presented with chest pain at rest and associated inferolateral ST-segmentdepression. Myocardial infarction was ruled out by creatine kinase enzymes, but troponin was positive. Hismedications on admission included oral nitrates, a -blocker, a calcium channel blocker, aspirin, and furosemide.Despite heparinization, intravenous nitroglycerin, and maximal medical therapy for 4 days, he continued to havechest pain at rest with inferolateral ST-segment depression.

FIG. 30.4.

(A)(B) (C)

(D)

Example of primary angioplasty for acute myocardial infarction. The patient developed chest pain andST-segment elevation and was found to have a totally occluded obtuse marginal branch . The patient underwent

primary percutaneous transluminal coronary angioplasty, with restoration of TIMI grade 3 flow and a minimalresidual stenosis .

FIG. 30.5.(A)

(B)

He was prescribed a glycoprotein IIb/IIIa inhibitor and was later brought to the cardiac catheterization laboratory,where he was found to have total occlusion of all his native vessels proximally, a patent left internal mammary arterygraft to his LAD artery, a 90% lesion in the midcourse of the saphenous vein graft to the posterior descending artery(Fig. 30.4), and a proximal 70% lesion of the saphenous vein graft to the first obtuse marginal artery. The LVEFwas moderately reduced at 40%.

The patient had a 3.5-mm Palmaz-Schatz stent placed in the saphenous vein graft to the posterior descending artery,leaving a 0% to 10% residual stenosis (Fig. 30.4 , ). He was given a loading dose of clopidogrel. An exercisetolerance test with thallium imaging performed 10 days after the procedure showed persistent lateral wall ischemia.

Therefore, a second 3.0-mm Palmaz-Schatz stent was placed in the saphenous vein graft to the obtuse marginal, againleaving a 0% to 10% residual stenosis (Fig. 30.4 , ). He continued to receive clopidogrel for 1 month after theprocedure and experienced full resolution of his symptoms.

A B

C D

Illustrative points

This patient had an uncomplicated postintervention course, as has 140,300,410]become common since theintroduction of glycoprotein IIb/IIIa inhibitors, intracoronary stenting, and clopidogrel. Glycoprotein IIb/IIIainhibitors have been shown to reduce the incidence of myocardial infarction before intervention, and this patient wasgiven a glycoprotein IIb/IIIa inhibitor before the intervention. As discussed previously for patients with stable




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Example of a lesion with a high risk of reocclusion after thrombolysis. The lesion is an ulcerated, eccentric plaque inthe right coronary artery with TIMI grade 2 flow that was collateralized by the left anterior descending coronaryartery.

angina, the choice of revascularization strategies in the patient with unstable angina and multivessel disease iscomplex. This patient would have required a third CABG operation, which carries a mortality rate two to three timesgreater than that of the second operation and much higher than that of the initial operation . Some authors haveadvocated dilating only the culprit lesion in the setting of unstable angina . However, this patient demonstratesthat multiple lesions may require dilation to eliminate exercise-induced ischemia. There are conflicting results in theliterature as to whether patients with unstable angina have a higher restenosis rate than those with stable angina.Although conventional angioplasty of bypass grafts has been associated with a high rate of restenosis, the results ofstent placement in bypass grafts have been more favorable . In addition, intracoronary stenting of native coronary

vessels larger than 3.0 mm has been shown to reduce restenosis rates at 6 months when compared with conventionalangioplasty in randomized trials , .

(32)(33)

(34)

(35) (36)

ACUTE MYOCARDIAL INFARCTION

Although thrombolysis has been the primary mode of therapy for acute myocardial infarction, thrombolytic strategieshave been limited by the fact that approximately 20% of patients fail to achieve reperfusion, 10% to 15% experiencereocclusion, and approximately 1% have a risk of intracranial bleeding . Since the last edition of this textbook,more potent and fibrin-specific thrombolytic agents have been evaluated , , and they have now beencombined with glycoprotein IIb/IIIa inhibitors to accelerate the rate of thrombolysis . At the same time thatimprovements have been developed for thrombolytic strategies, newer interventional techniques have been introducedthat present a formidable challenge to thrombolytic agents because they may achieve a higher incidence of TIMIgrade 3 flow and a lower rate of reocclusion and are associated with a low rate of intracranial hemorrhage , .

(37)(38) (39)

(40)

(37) (41)

Case 5

A 70-year-old woman was admitted to the hospital with chest pain at rest and nonspecific ECG changes. Her riskfactors for coronary artery disease included hypercholesterolemia and hypertension. After admission, she was treatedwith aspirin and heparin, and the dosing of her -blocker was increased. On the second day of hospitalization, shedeveloped chest pain that was refractory to intravenous nitrates, heparin, aspirin, and -blockers. An ECG showed 1to 2 mm of new ST-segment elevation in leads I, L, and V6, as well as 1 to 2 mm of ST depression in leads V1-V2.She received an additional bolus of heparin for a subtherapeutic partial thromboplastin time and was given 5 mg ofmetoprolol intravenously.

The patient developed chest pain in the afternoon, at a time when the cardiac catheterization laboratory staff waspresent in the hospital and a cardiac catheterization suite was immediately accessible. She was rushed to the cardiaccatheterization suite, where she was found to have single-vessel disease with a totally occluded circumflex obtusemarginal branch (Fig. 30.5 ). The patient underwent primary PTCA with restoration of normal TIMI grade 3 flowand a minimal residual stenosis (Fig. 30.5 ). She was discharged to home 3 days later, after a negative submaximalexercise tolerance test.

AB

FIG. 30.6.

Illustrative points

There are several prospective randomized trials comparing the efficacy of primary PTCA with that of thrombolytictherapy . This patient was in many ways an ideal candidate for primary PTCA, both because immediate access tocardiac catheterization was available and because she was an elderly woman, a subgroup that has been shown toderive particular benefit from primary PTCA . In the Primary Angioplasty in Myocardial Infarction trial(PAMI), primary PTCA was associated with a lower rate of intracranial hemorrhage and a lower rate of reinfarctionor death compared with thrombolytic therapy . This patient is part of a small subgroup of patients with acircumflex lesion, the natural history of which is not well characterized in thrombolytic trials because such lesionsrepresent less than 15% of lesions in these trials.

(41)

(42)

(42)




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Case 6

A 56-year-old man presented with chest discomfort that awoke him from sleep 1 hour before admission. Onpresentation to the emergency room, he had a blood pressure of 92/54 mm Hg. His ECG showed sinus bradycardia ata rate of 52 beats per minute (bpm), with 2 mm of ST-segment elevation in leads II, III and avF. He was given a

bolus of heparin intravenously and treated with 100 mg of tissue-type plasminogen activator (tPA) over 90 minutes.Initially, he was treated with intravenous nitroglycerin, which resulted in a further drop in blood pressure. Right-

sided leads were obtained, which showed 1 mm of ST-segment elevation in the right precordial leads. He was treatedaggressively with intravenous fluids, resulting in a rise in his blood pressure, but he also began to develop rales onexamination. His chest pain persisted for the first 60 minutes after thrombolysis.

Given the patient's hemodynamic instability and persistent chest pain, he was taken to the cardiac catheterizationlaboratory. Shortly after vascular access was obtained, his chest pain resolved and his ST-segment elevationimproved. On angiography, he was found to have an ulcerated eccentric 90% stenosis in the mid-right coronaryartery (Fig. 30.6), with TIMI grade 2 flow that was collateralized by the LAD artery. Given that the vessel was openand the patient's pain had resolved, it was elected not to intervene. However, 6 hours later the patient developedrecurrent chest pain, and repeat cardiac catheterization showed a total occlusion of the right coronary artery, whichwas treated with PTCA, resulting in restoration of TIMI grade 3 flow and a 30% residual stenosis.

Illustrative points

This patient had several angiographic features on early catheterization that have been associated with reocclusion 1day later . In descending order of importance, these angiographic features are the presence of an ulceration, the

presence of TIMI grade 2 (slow) flow, the presence of thrombus, the presence of an eccentric lesion, increased lesionseverity, and the presence of collaterals. The management of a patent artery with slow flow is poorly defined. Despitean intuitive belief that adjunctive angioplasty should improve clinical outcomes in patients with a patent(normal and slow flow combined) but narrowed artery after successful thrombolysis, several large trials have shownno benefit for PTCA in this setting .

(43)

routine

(44)

Currently, there is an impetus toward improving the flow in patent arteries after thrombolysis based on the findingthat better TIMI flow grades and better TIMI frame counts are associated with improved outcomes , .However, it remains unclear whether TIMI grade 2 flow is just a of larger infarcts or a of more

extensive necrosis. Indeed, it has been shown that the magnitude of slow flow is proportional to the extent ofmyocardial necrosis , and Kloner et al. demonstrated repeatedly that this may be mediated by themicrovasculature . Furthermore, we showed that perfusion at the level of the myocardium (the myocardial

perfusion grade or blush) is a predictor of mortality in acute myocardial infarction, independent of flow in theepicardial artery . It appears that flow in all three arteries (not just the culprit artery) may be abnormal, andthat global flow abnormalities are related to a higher mortality rate in acute myocardial infarction . Therefore,there is an increased emphasis on treating the microvasculature in addition to treating the stenosis in patients withTIMI 2 flow. Treatment of the stenosis may confer benefits above and beyond those of improved flow, such as

potential reduction in the risk of reocclusion.

(45) (46)marker cause

(47)(48)

(49)(50)

Case 7

A 69-year-old woman presented to the emergency room of a local community hospital with 5 hours of substernal

chest discomfort radiating to the left arm, and 2 mm of ST-segment elevation in the anterior precordial leads. Shehad a blood pressure of 90/60 mm Hg, a pulse rate of 90 bpm, and rales one-half way up her lung fields bilaterally.She was treated immediately with aspirin, intravenous heparin, and 1.5 million units of streptokinase. After 60minutes of persistent chest pain and ST-segment elevation, she was transferred for cardiac catheterization. She wasfound to have a totally occluded LAD artery, which was treated with rescue PTCA, resulting in restoration of TIMIgrade 3 flow and a minimal residual stenosis.

Illustrative points

There has been only one randomized, prospective trial assessing the efficacy of rescue angioplasty for failed




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thrombolysis. There is an inherent belief among angioplasty operators that restoring perfusion would certainly bebeneficial, and this bias is reflected by the fact that almost 80% of operators approached to participate in theRandomized Evaluation of Salvage Angioplasty with Combined Utilization of Endpoints (RESCUE) studydeclined, because they believed that it would be unethical to withhold attempted revascularization for an occludedvessel immediately after failed thrombolysis.

(51)

The RESCUE trial involved 150 patients from 20 centers with TIMI grade 0 or 1 flow 1.5 to 8 hours aftermyocardial infarction. Generalization of results from this trial are limited because enrollment was restricted to

patients with their first myocardial infarction and to those patients with an anterior infarction. There was nodifference in outcome for the prespecified primary end point of the trial, the resting LVEF at 30 days aftermyocardial infarction (40% with PTCA vs. 39% without PTCA). The incidence of death in patients treated withrescue angioplasty was 5.2%, which did not differ significantly from the 9.9% for those not treated with rescueangioplasty. As a secondary end point, death and congestive heart failure were analyzed together, and there was atrend for a reduced incidence in the group treated with rescue PTCA (6.5% vs. 16.4%, = .055). The magnitude of

benefit in this trial and in others may be small because thrombolysis must first fail over the course of the first 90minutes, and time must then be taken to bring the patient to the cardiac catheterization suite. Because of the inherenttime delays in performing rescue angioplasty, the benefits of restoration of patency may not be realized.

p

early

Several other trials have evaluated the strategy of rescue PTCA in a nonrandomized, retrospective fashion . Inkeeping with the fact that the reperfusion paradigm of thrombolytic success is only partially fulfilled in

cases of successful rescue PTCA, the and often reperfusion achieved in these patients in the TIMI 4 trialresulted in an overall rate of adverse events (death, severe congestive heart failure, cardiogenic shock, or LVEF lessthan 40%), 28.8%, that was intermediate between that of patients with immediate thrombolytic success (22.8%) andthat of patients treated with no rescue PTCA for an occluded vessel (35.1%), who frequently achieved reperfusioneven later . Overall success rates have varied (71% to 100%) and on the whole have been lower than thosereported for primary PTCA, probably because of either a larger or a more pharmacologically resistant thrombus

burden . Similarly, mortality rates have been high (10% to 17%), and in particular the mortality rates of patientswith a failed procedure have been very high (33% to 39%) . Pooled data have shown no improvement in leftventricular function between the time of the rescue procedure and 7 days later and suggest that the rate of reocclusionis higher in patients treated with tPA (24%) compared with nonspecific plasminogen activators (14%) . A

potential problem with a strategy of rescue PTCA lies in identifying patients who would be appropriate candidatesfor intervention, because reliable clinical and noninvasive markers of reperfusion have not been validated forwidespread use. The utility of new device interventions in this setting has not been evaluated.

(52)early and full

delayed full

(52)

(53)(53)

(53)

The management of acute myocardial infarction continues to evolve rapidly. Throughout all of the clinical trial data,one paradigm that consistently emerges is the importance of early restoration of patency regardless of thethrombolytic agent or mechanical strategy used to open the artery. In keeping with the time-dependent nature of theopen-vessel hypothesis, the choice of a revascularization strategy should be guided by the clinician's assessment of themost expeditious method by which patency can be achieved in a given patient, at a given time of the day, at a giveninstitution, by a given operator .(37)



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Atipical Chest Pain Normal Arteries