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Coronary Heart Disease

We are going to be reviewing atherosclerosis, angina, ischemia, unstable angina, acute myocardial infarction. It is estimated that approximately 14 million Americans have some form of cardiovascular disease. Nearly a million died in 1995. This figure is about constant, comprised of about 41% of total deaths. This is not a disease solely of the elderly. One-sixth of the deaths were below age 65. Nearly one-third were below the age of 75. At least for men, there has been a very encouraging drop in the heart disease rating from the late 1970ís into the 1990ís. Interestingly, the same is not

Primary prevention and risk factors. There the so-called three modifiable risk factors: cigarette smoking, hypertension and hypolipoproteinemia. For instance, cigarette smoking current goal is complete cessation for every American and we do that by questioning the patient at every visit and intervening by encouraging cessation, utilizing nicotine replacement, counseling and now we have an antidepressant drug called Wellbutrin that is very helpful in breaking the habit. Itís necessary because both for men - shown in this panel - and women - shown in this panel - across all 

Screening for hypertension is another unambiguously valuable intervention, specifically looking for blood pressures of 140/90, screening every two years and of course intervening certainly with lifestyle, and medications for persistent elevation. Again, shown here from the Framingham study are the data both for men and for women in which utilizing blood pressure, low here and high here, there is a rise in atherosclerotic risk in both genders

Now hyperlipidemia is the last of the principle modifiable risk factors and the current National Cholesterol Education Project Standards asked us to screen patients at least every five years, with both dietary history total and HDL cholesterol. The goal is to keep the LDL cholesterol between 138-160 if you are minimal on the risks, but down this level is 100-130 _. Remember, this is primary prevention. Not secondary prevention. Among

Other primary prevention targets that have now been put forward by national bodies include: encouraging patients to get 30 minutes of exercise three to four times a week. Remember to take a walk at lunch time today at least, and being careful about weight. Weíve thrown out the weight charts and instead have introduced the concept of body mass index in which we compare the weight in kilograms to the height and _ squared, and we are

The most exciting news in the last five years in the management of patients in primary prevention has been the impact of lowering cholesterol substantially through the use of medications when diet fails, to get LDL levels down. The first of these studies was a study done with the drug pravastatin, Pravachol. The study was called the Western Scotland Coronary Prevention Study, WSCPS. It showed a 31% reduction in non-fatal MI or coronary heart disease death and a 32% reduction in all cardiovascular deaths. This started within six months of institution of therapy. As shown here, at least for the curve regarding non-fatal MI or coronary heart disease death, the population which was a rather high risk factor population with rather substantially elevated cholesterol, cigarette smoking, some even with coronary disease, were put on pravastatin up to 40 mg a day, and the curve started to divert in six months and continued out all the way to six years. So this was not an epi-phenomenon of an early phase, this was a persistent improvement that took place over time.

Confirming this more recently has been a trial done with the initial statin agent, lovastatin, Mevacor, that was done in Texas reported how Dr. Delgado and company, or I should say collaborators, 20-40 mg daily of lovastatin versus placebo, looking for the first major event and just not looking now at the life times but just in terms of the outcomes in five years, major events were reduced substantially. Revascularization need was reduced substantially, unstable angina reduced and coronary events all were reduced. Remember, these are patients with no known coronary disease just put on therapy.

What about other adjunctive therapies to these more potent impacts? Well, we have anti-platelet therapy with aspirin and we now still have the - the FDA recommended that aspirin should be given to patients at high risk for cardiovascular disease. In England, however, the British are in favor of it for all patients who do not have allergies. Doses between 75-325 a day. Other choices for intervention include hormone replacement therapy - a few words about that a little later - antioxidant vitamin therapy, and a new rage is looking for homocystine heterozygotic states and treating with vitamins for that.

Atherosclerosis can be stabilized and can regress. In a recent randomized controlled trial, you take over 2,700 women who had coronary artery disease, who had their uterus, and hence could be treated and treat them in this case with a combo product called Prempro that combines conjugated equine estrogen Premarin with hydroxyprogesterone, versus placebo. The expectation was that by taking such patients who had known coronary disease you would reduce event rates. So they took patients and looked for the development of MI or death, or secondary end points of hospitalization. Followed them out to 4.1 years. This was not expected. The secondary prevention was not demonstrated. There was not a reduction in overall coronary heart disease risk. In terms of primary events occurs paralleled each other, crossed over. There is a question of benefit only later on when patients went out 3-4 years. And there were a substantial number of side effects for wholesale administration of estrogen in this fashion. Gall bladder disease and most importantly the venous thrombi levels increased three fold in trials. Does this mean that you should never have a patient on estrogens or progesterone? Everyone is very cautious right now. There is clearly another larger scale trial ongoing looking at estrogen therapy alone, looking at natural estrogens - that is to say, not derived from pregnant mares urine - and then primary prevention. But if you have a postmenopausal woman who presents with a myocardial infarction, the take-home message is donít put her on Prempro.

Now there are some, if you will, health food approaches. Alternative therapies for the management of angina.. The concept that this fellow Dirk thinks angina is a dirty word, and really canít give you a good idea about what natural remedy to take. But if you go to the Internet at this location you will pick them up. There are a lot of concepts out there that patients may utilize in terms of vitamin E, which we still utilize because of the antioxidant benefit. Garlic therapy, Ginkgo and so forth. Iím not trying to recommend any of these instead of looking at the more safe approach, which are in the ACCH, ADCP guidelines that Iíve alluded to that are mnemonically put forth as ABCD and E. And Iíd like to review them. Aspirin and the anti-anginals, beta-blocker blood pressure control, cholesterol and cigarettes, diet and diabetes, and education and exercise. So letís take a look at whatís standard, not whatís on the fringe.

Nitrates are the sine qua non therapy for the acute ischemic episode. They relax smooth muscle by releasing nitric oxide and as a consequence can cause dilatation, if the artery is in spasm. But interestingly thatís not the mechanism by which nitrates usually relieve angina. They relieve it by the central venous pooling that takes place, resulting in a reduced pre-load and hence less myocardial oxygen demand. The concept behind nitrates is that tachyphylaxis with continuous administration vitiates their benefits so give them intermittently. They are contraindicated in patients, or relatively contraindicated, with aortic stenosis, or low blood pressure. In any of these circumstances patients may have coexisting angina from coronary disease and one has to carefully assess whether they will be helped by a reduction in pre-load and an increase in blood flow, as shown in this graphic over here.

The chronic therapy that is most advisable but is underutilized is that therapy provided by beta-blockers. Beta-blockers hit all levels of myocardial oxygen demand. They do nothing for supply but they sure do with demand. They reduce heart rate, they reduce blood pressure and hence reduce wall tension. And finally, they reduce contractility. With the exception of decompensated heart failure, bronchospasm requiring steroids is severe, and heart plaque without a pacemaker, they can utilize in those patients. Of course, some patients canít tolerate them. They get into trouble for a variety of reasons, such as CNS depression, lipid abnormalities, sexual dysfunction, intolerance of exercise and impairment, but except for these they are very helpful. The one pitfall in the use of beta-blockers is being very leery about advancing the dose. All too often the rule of 60 is employed. If the pulse rate is 60 you can increase the dose. Thatís fallacious. The sinus node will not slow progressively in usual patients even if you raise the dose, and you may get additional benefits from going to higher and higher doses. This is particularly true in the elderly who often cannot tolerate beta-blockers if you apply the rule of 60. But if you push the dose higher, particularly in an elderly patient who does not want to look at an intervention, it may be very helpful to them. We sometimes even put pacemakers into patients to allow us to push the dose of beta-blockers higher and so get the benefit on blood pressure and contractility.

Now calcium channel blockers became a vogue in the 1980ís and to the 1990ís but there is a withdrawal in excitement about the use in the management of chronic stable angina as a first line agent. That loss of enchantment comes because of observations about increased risk with only one sub-group of calcium channel blockers, and those are the so-called dihydropyridines, reflected by the classic drug Procardia, nifedipine, given in the short-acting form. There appeared to be an increased risk of coronary mortality in those patients, particularly if patients were in a state of unstable angina. I will tell you my own line and that is that these drugs have been beautifully demonstrated to affect symptoms and so are very helpful for patients who cannot tolerate beta-blockers at all. Or in whom beta-blockers and nitrates have not been effective, these can be added as additional agents. They are very good for reducing blood pressure. They are coronary dilators and they reduce myocardial oxygen demand. They are contraindicated, as with beta-blockers, in heart failure and heart block but in unstable angina, if itís a dihydropyridine, you should be very very cautious. Long-acting dihydropyridines such as Norvasc and amlodipine and similar drugs to it seem to be safe and can be utilized with a great deal of confidence.

Letís turn from the medical to the intervention. We now have several techniques available to us, or so-called percutaneous coronary interventions or percutaneous revascularization. So much so that I changed the slide from angioplasty to percutaneous procedures. The approach is to a particular patient, depends upon the lesion that the operator sees and then the operatorís own choice. No longer do we refer a patient, " I want you to put in and do an angioplasty or this or this." You refer the patient and the operator decides whether the patient is appropriate for balloon angioplasty and stent placement or not. And the choices include standard angioplasty, arthrectomy and stent placement. There are risks associated with these.

Coronary bypass. This has been around since the late 1960ís. Itís 30 years that weíve been doing this and we have fairly clear indications. Of course, any patient refractory to medical therapy, left vein stenosis greater than 50% even if the patient is relatively asymptomatic, thatís an indication. This is the data versus medical therapy of effects on prognosis from the 1970ís showing that survival in surgical groups in several studies was superior to medical therapy in this era. Now there havenít been many advances in terms of medical therapy since the 1970ís. Some but not

What about newer approaches to ischemia management? First is the question of medical therapy versus angioplasty. Just reported a week ago in the New England Journal, in the Evert Trial the atorvastatin, Lipitor at a dose of 80 mg a day was given to patients one to two vessel disease, were being considered for percutaneous revascularization. And the outcome, fascinating. Ischemic events were reduced 36% with atorvastatin. This just began to approach statistical significance in the small number in the trial of 341, was not powered enough to make an unambiguous statement but it shows the feasibility of medically treating patients who are stable. And I emphasize that stable. Patients who are unstable should not be given this period of time to get into trouble.

What are some of the other approaches? We used enhanced, extracorporeal _. Dr. _ speaking this afternoon is a lead author on the paper on that in the Journal of the American College of Cardiology showing its value. We have transmyocardial laser revascularization, and finally, our surgeons have come up with some new ideas, including minimally invasive coronary bypass graft surgery, which to my mind still represents a technique in development.

In the few remaining minutes I would like to just quickly go through issues regarding silent ischemia, unstable angina Q-MI. The concept of silent ischemia has been introduced already from the notion that before chest pain develops there can be ischemia changes and so if we monitor the patients we can pick up silent episodes of SD depression indicative of ischemia. The therapeutics of this are still up in the air. And the value of

Unstable angina is defined as angina occurring out of the usual pattern. It can be at rest, new onset, and most commonly increasing angina in terms of more frequent episodes and prolonged episodes compared to a baseline. There are now clear concepts pathophysiologically that this also represents an unstable plaque with thrombosis. This tends to be a more complex anatomy than stable angina, and this is very important: angiography where we cannot separate unstable anginaís anatomy form that of non-QMI. In both cases they are often non-obstructive but severe thrombi at the site of

What are some of the newer notions in the management of unstable angina? Itís the introduction first in the unstable patient of the 2B3A inhibitors. These are a summation of the trials and outcomes for the use of these agents, such as ReoPro, abciximab and Integrilin and other agents in combined trials. There has been a definite advantage, as far as the going on to myocardial infarction for such patients. These are the several trials that have been reported recently. At this time, however, the use of 2B3A inhibitors though being pushed, there is still to my mind looking for clear consensus. But for the patient who is about to undergo an intervention, it seems very reasonable to use the agents.

Another new agent is fractionated heparin. Instead of using unfractionated standard heparin, this trial called Essence reported two years ago looked at the value of enoxaparin, and this has also been reproduced with dalteparin in the so-called _ trial, in looking at the value of using this agents. Itís much easier to use because you donít have to wait Ö you donít have to dose it according to blood tests. You just give it. You donít even have to have an IV. You can give it subcutaneously. The risk of major hemorrhage is comparable, the risk of minor bleeding was increased, and in terms of end-points there was some superiority compared to unfractionated heparin.

A few final words about myocardial infarction, and those are as follows: we are talking about the complications of complete obstruction for the coronary artery resulting in electrical, mechanical and structural impairments. Modern therapies focus on, A: the use of medical re-perfusion utilizing aspirin. This was shown in the ISIS II trial where aspirin alone was as good as streptokinase alone in reducing mortality in the early stages. When

Which agent is the best to use? Thatís still, to my mind not such a clear cut issue. There are some definite advantages to rapidly acting agents such as TPA, particularly when TPA has been combined with a front-loading protocol giving more up front. Patients however, who don't work out, tend to be considered for an angioplasty and we have two kinds of angioplasty, primary and rescue. The primary circumstance today there is increasing interest in giving, doing angioplasty even if the patient does not have a contraindication to lytic therapy. Rescue angioplasty is utilized for failure of

Concluding now, heparin in acute MI is standard. Nitrates are used for the management of ischemia but have no benefit for long term protection. Beta-blockers are definitely valuable but are underutilized in the United States. The IV loading protocol in the early stages with metoprolol and atenolol should be considered, but more importantly for chronic use, metoprolol, atenolol, propranolol, atenolol all have been demonstrated to be valuable long term. Iíll point out that beta-blockers with intrinsic sympathomimetic activity should not be used, and thatís limited to the agent called pindolol. ACE-inhibitors are currently a standard of care for patients who have anterior wall myocardial infarction, significant inferior and lateral wall MIís. Captopril is very safe for early use. Enalapril in early use is not safe but for longer use, that is at discharge, is very valuable. There are other ACE -inhibitors that can be used chronically. 

Atherosclerotic Coronary Heart Disease

A. Epidemiology

Although the death rate from coronary disease decreased 28.7% in the past decade, atherosclerotic coronary heart disease remains the leading cause of death in the United States. The prevalence of disease is 13.9 million. Every year, approximately 600,000 Americans die of coronary heart disease. The number of myocardial infarctions annually is 1.1 million, of whom 1/3 die (includes pre hospital phase). 5% of myocardial infarcts occur below the age of 40; 45% occur in people below 65. Overall more women die than men.


Current research has also identified a likely association with homocysteine levels.

A cardiac history should include information regarding all risk factors. Particular attention should be directed to the modifiable risk factors which include:



Hyperlipoproteinemia - coronary heart disease risk rises directly with both total cholesterol and LDL cholesterol and inversely with HDL cholesterol. Credible trials utilizing HMG Co A reductase inhibitors have demonstrated both lesion regression and event reduction in both primary and secondary prevention. Routine screening for lipid disorders is advised by the National Cholesterol Education Project, although the American College of Physicians have questioned this approach. Current guidelines suggest that all adults 20 years of age and over should have total cholesterol (and HDL cholesterol if accurate results are available) measured at least every 5 years. These screening measurements may be made in a non fasting state.

<200 mg/dL Desirable

200-239 mg/dL Borderline high

>240 mgldL High

HDL-Cholesterol <35 mgldL Low HDL - Cholesterol

If levels are above 240, then HDL and triglyceride studies should be obtained. LDL can be calculated by the formula:

LDL = Total Cholesterol - HDL-C - Triglycerides/5

Goals include: Total cholesterol below 200, Total C/HDL-C below 4, LDL-C below 100.. In primary prevention, therapy of patients with several risk factors appears justified. Dietary management is cornerstone of therapy. Recent trials of HMG Co A Reductase inhibitors for primary prevention document substantial reduction in primary events (West of Scotland Trial, AFCAPS/TEXCAPS trial).

Primary prevention has also identified the role of antithrombotic therapy. The Physicians' Aspirin Trial demonstrated that a 324 mg aspirin every other day could reduce the risk of myocardial infarction in middle aged men; however, total cardiovascular death rate was not reduced due to increased strokes. Aspirin prophylaxis appears warranted. Data for women are not as well established.. Use of antioxidant therapy has been proposed as benefiting prevention.

The epidemiologic case for estrogen replacement in post menopausal women has been argued persuasively; this may reduce the risk by 50%. This should be considered in individuals with premature menopause (surgical or spontaneous), strong family history of premature atherosclerosis, and multiple risk factors in whom malignancy risks (breast, endometrial) are acceptable and can be monitored.

B. Pathophysiology

The pathogenesis of atherosclerosis spans decades. Injury to the intima and its repair yield the early lesion of fatty streak - over time in the setting of risk factors a productive lesion may result. Recently, the concept of the destabilization of the atherosclerotic plaque has become a focus of research. The plaques which are likely to rupture and produce acute coronary syndromes tend to be those with a high proportion of lipid, those in which LDL may be oxidized, and those which have greater infiltration of activated monocytes. Risk factors may play a role in facilitating abnormal reparative processes and destabilizing plaques.

A long latent phase precedes the clinical manifestations: angina, unstable angina, myocardial infarction, and sudden death. The timing of acute clinical events cannot be predicted even from angiography. Atherosclerotic lesions leading to clinical events may thus change abruptly, suggesting that an acute event on a non obstructing plaque underlies the occurrence of myocardial infarction or unstable angina. Epidemiologic studies of onset of myocardial infarction have identified arousal from sleep and vigorous exercise as potent inducers of obstruction. The role of inflammation has been highlighted in recent studies showing the presence of activated macrophages in lesions and epidemiological association with such infective agents as chlamydia pneumoniae. The pathogenesis of acute ischemic syndromes is dependent on thrombotic mechanisms.

Ischemia of the myocardium is the substrate for angina. Ischemia may occur in the absence of definable symptoms. This can be identified by electrical, biochemical, hemodynamic, or transport parameters.

Ischemia has continued to be defined as insufficient coronary blood flow for myocardial oxygen demands. Factors determining oxygen delivery include:

Coronary resistance is the most important factor. It is changed by the atherosclerotic lesions leading to flow limiting stenoses (usually greater than 75% stenosis).

Factors determining myocardial oxygen demand include:

Changes in demand have been used to account for episodes of classic angina. Wall tension reflects the intravascular volume status (preload - radius) and the systemic resistance and flow (blood pressure - afterload). Changes in supply to due to changing stenoses (vasoconstriction) account for vasospastic angina, silent ischemia, and may occur during stable angina as well. Changes in supply have been invoked to account for episodes of variant (vasospastic) angina.

The cellular responses to ischemia are time dependent. Initial response is a reduction in relaxation followed by reduction in contraction with subsequent rise in filling pressure. During ischemia, the auscultatory correlates will be an S4 (reduced relaxation) and later an S3, murmur, or paradoxical second heart sound (reduced contractility). ECG changes (ST depressions, arrhythmias) can occur at this point. Angina follows the development of these steps. Cellular integrity can be maintained up to 20 minutes of ischemia, although repeated shorter bouts of ischemia result in myocardial dysfunction ("stunning"). Prolonged but reversible systolic dysfunction can be seen in circumstances of chronic underperfusion ("hibernation").. Organ integrity can be maintained up to 1-2 hours (accounting for the ability to utilize thrombolytic drugs). Beyond this period, cell death occurs with resultant organ response (infarction).

Stable ischemic syndromes can be accounted for by fixed flow states (atherosclerotic plaque, collateral circulation) with variable demands (increases in heart rate, blood pressure). Variant angina ("Prinzmetars") can occur with spasm at an atherosclerotic lesion or in a morphologically normal artery without demands changing. UNSTABLE ischemic syndromes reflect abrupt and variable flow reductions. Rupture of an atherosclerotic plaque which was not flow limiting may lead to thrombosis which can either occlude or severely narrow the artery. Vasospasm or platelet aggregation at the site of such an active plaque can produce angina at rest. 

Angina Pectoris

A. Diagnosis

A typical history of stable angina pectoris has a specificity of 95% for atherosclerotic disease in a population of high prevalence. The history permits classification according to the Canadian Cardiovascular Society (I-IV). Issues of concern include identifying stability, non painful anginal equivalents, and identifying high risk subsets of patients.

Physical examination can identify factors increasing demand (heart rate, blood pressure, fever) or reducing blood flow (cyanosis, pallor). Examination of the asymptomatic patient is helpful to identify other manifestations of atherosclerosis - bruits, absent pulses. Examination during symptoms may reveal transient signs of left ventricular dysfunction (S4, S3, murmur, rales) or dysrhythmia.

Laboratory evaluation should include complete blood count, thyroid function if appropriate, electrocardiogram, and chest X Ray. STRESS TESTING is useful when appropriately ordered. An optimal test will raise the heart rate to 80-85% of the age determined maximum heart rate (220 - age). Ischemic responses are reflected in ST segment depressions, fiat or downsloping, below baseline, at least 0.5 mm.

Sensitivity for detection of disease in men is 65-75%; specificity is 75-85%. False positives are considerably increased in populations with low incidence of disease - young women. Specificity is reduced in patients with resting EKG abnormalities, including left ventricular strain pattern, bundle branch block, Wolf Parkinson White, pacemaker. Therapy with beta blockers, digoxin, or in the setting of an electrolyte abnormality reduces the value of testing. No patient should be referred for testing without a prior examination and review of the electrocardiogram.

Interpretation of test findings involves not only the electrocardiographic response. The following characteristics suggest high risk coronary disease:

Indications for testing depend on the clinical circumstance. Contraindications to stress testing include:

Stress testing in the presence of such contraindications considerably increases the risks of mortality and myocardial infarction from the standard 0.01%. All patients must be evaluated prior to referral for stress testing.

Radionuclide Stress Testing has been utilized for evaluating ischemic disease in specific circumstances. Thallium 201 isotope scanning with exercise is employed in place of standard stress testing in the face of resting ECG abnormalities (e.g. left bundle branch block, pacemaker) or with impaired exercise capacity. A new radiopharmaceutical introduced for scanning which is comparable is Technetium SESTAMIBI (Cardiolyte). Patients unable to exercise adequately can be tested effectively with pharmacologic stressors: dipyridamolel adenosine and dobutamine. Gated blood pool studies (MUGA) have demonstrated reversible regional wall motion abnormalities with exercise.

Echocardiography can show regional wall motion abnormalities indicative of ischemic disease. Echo is useful in excluding other conditions producing angina - hypertrophic cardiomyopathy, severe aortic stenosis. Stress echocardiography can demonstrate reversible wall motion defects with stress indicative of ischemia. The standardization and reproducibility of the technique is operator dependent; it has been improved and can be equivalent to thallium or sestamibi imaging. Pharmaceutical stress echo with dipyridamole, adenosine, or dobutamine can also be performed. This modality has been clearly increasing by virtue of its ease and lower cost.

Coronary Arteriography is the definitive means for detecting, localizing, and assessing the extent of anatomically important coronary stenoses. Location and extent of stenoses correlates with prognosis. There is lower survival with left main and three vessel disease than with one or two vessel disease. Anatomy does guide the choice of therapy: left main disease is better treated surgically than medically in all groups. Risks of the procedure are acceptable in most patients - 0.5% or less for mortality, serious morbidity but rise in the elderly, women, diabetes, renal insufficiency, peripheral vascular disease. Patients should be referred if there is clinical evidence for unstable angina, non invasive evidence for high risk lesions and impaired left ventricular function, as well as failure of standard medical therapy to control symptoms and improve function.

B. Medical Therapy of Stable Angina

Atherosclerotic risk factor intervention has direct benefit in reducing myocardial ischemia Cessation of smoking reduces systemic vasoconstriction and eliminates carbon monoxide. Blood pressure control reduces afterload. Alteration of coronary prone behavior eliminates destructive responses to stress. Most risk factor changes do not yield short term benefits in preventing myocardial infarction or mortality. Lipid control is notable: The "4S" - Scandinavian Simvistatin - study showed reduction in risk by as early as 6 months.

Goals of medical therapy of stable angina include relief for individual symptomatic episodes, prophylaxis to enhance regular function, prevention of myocardial infarction and sudden death. Principal agents include:

Nitrates reduce demand by decreasing venous return through visceral venous pooling, leading to decreased wall tension (decreased preload). They increase flow by dilating collaterals. They may cause changes in coronary vasomotor tone reducing spasm. They may improve flow in diseased arteries by small increments in vessel diameter. They may interfere with platelet adhesiveness. Nitrate action appears to depend upon the ability to generate nitric oxide at the site of smooth muscle in the vessel walls.

Intermittent administration has been the mainstay of symptomatic therapy for attacks with sublingual tablets or oral spray. Interval administration of longer acting preparations (Isosorbide dinitrate, Isosorbide mononitrate) can provide some prophylaxis for attack. Continuous administration of short or long acting agents leads to tachyphylaxis, attenuation of clinical effect. Topical delivery can only be effective if nitrate free intervals are used (patch off for 6-8 hours). Contraindications to use include severe aortic stenosis and idiopathic hypertrophic subaortic stenosis, hypotension.

Beta Blockers remain a mainstay of prophylactic treatment. Demand is reduced by lowering of heart rate, blood pressure (afterload), and contractility. Membrane stabilization may account for the "cardioprotective" effect which has been posited as the mechanism for the protection against sudden death. Beta blockers do not improve oxygen supply. Contraindications to use include

Decompensated congestive heart failure due to ventricular systolic dysfunction. Bronchospastic disorders with severe obstruction Heart block - 2nd or complete without a pacemaker

Calcium Channel Blockers had assumed a major role in prophylactic therapy. Mechanisms for effect include reduction in demand by decrease in contractility, heart rate, blood pressure (afterload). They are all potent vasodilators capable of preventing spontaneous spasm and reducing coronary resistance. They are a mainstay of therapy for vasospastic angina. They are effective monotherapy for angina, particularly in patients intolerant of beta blockers due to bronchospasm, diabetes, peripheral vascular disease, Contraindications include decompensated congestive heart failure, heart block - 2nd or third degree without a pacemaker. The agents have different profiles of activity. Recent retrospective reviews have raised questions regarding safety of their use as primary agents.

Aspirin at low doses (75 mg daily) has been demonstrated efficacious in reducing risk after unstable angina and following myocardial infarction

C. Catheter Based Revascularization

Revascularization by percutaneous catheter has become a principal means of revascularization. Tools available include balloon angioplasty to disrupt and stretch the vessel at the lesion; atherectomy devices to to shave or cut through lesions; and expandible metallic stents may be placed to keep the vessel from recoiling and reducing lumenal diameter. The utility of these technique have expanded to include multiple vessels, multiple lesions within the same artery, and bypass grafts. Initial successes can be as great as 90%, with a risk for emergency surgery of 1-3% and mortality of 1-2%. Long term success is not as good - 30-40% restenosis of a single vessel at 3-6 months. Stents may reduce this risk by 1/2. Extensive use of stents have been undertaken without substantial long term data. Once the initial period of restenosis is passed, the long term patency appears excellent. Long term studies have shown efficacy in anginal control.

Efficacy trials comparing medical therapy, PTCA, and coronary bypass graft surgery are becoming available. In 2 vessel disease, the strategy of angioplasty had a lower initial mortality, but subsequently had the same survival as a surgical approach and cost as much (Emory Angioplasty Surgery Trial). The BARI trial showed that diabetic patients were distinctly better treated with surgery than with angioplasty. Whom to refer once catheterization has demonstrated significant disease remains a clinical judgment.

Patients with recurrent angina after PTCA usually warrant repeat catheterization. If this has occurred within 6 months of PTCA then repeat dilatation should be considered.

D. Coronary Bypass Graft Surgery

Coronary bypass graft surgery can be performed with a mortality of less than 1.7% in suitable patients with stable angina. The rate increases with female sex, impaired left ventricular function, age, and emergency status. Indications include:

Angina relief is greater than 85% initially. At 10 years, nearly 50% of patients have noted recurrent angina. Recurrent angina may be related to both progression of native disease as well as occlusion of bypass grafts.

Long-term success is related to graft patency and complete revascularization. ASPIRIN 324 mg daily can improve saphenous vein graft patency. Use of the internal mammary artery leads to longer patency rates than with saphenous veins. Newer techniques to minimize the trauma of surgery include a mini CABG which involves the anastomosis of the mammary to the LAD without bypass and the Heart Port, which leads to a smaller incision.

Recurrent angina post coronary bypass warrants reassessment as for stable angina. Catheterization is often advised. Reoperation can be performed at a higher, but often quite acceptable, risk of mortality and morbidity.

E. Refractory Angina

Novel approaches to patients with medically intractable angina who are unsuitable to revascularization

are being explored. Extracorporeal External Counterpulsation (EECP) has shown efficacy in a clinical trial. Transmyocardial Laser Revascularization (TMR) has shown efficacy in an initial study.

 Silent Ischemia

Ambulatory monitoring procedures can demonstrate ST segment depression without symptoms during the day in up to 70% of patients with symptomatic angina. The demonstration of a greater risk in patients with unstable angina who manifest silent ischemia has led to interest in detecting silent ischemia in patients with stable angina. Techniques include exercise treadmill testing and monitoring. A circadian variation is found, with more episodes during the early morning hours. Whether suppression of silent ischemia itself will improve prognosis remains unproven. However, therapy does appear warranted for the individual whose stress testing suggests higher risk anatomy or in individuals following unstable angina or non transmural MI. 

Unstable Angina

This syndrome comprises angina which no longer occurs predictably - rest angina, new onset of angina, and increasing angina. Its pathoanatomy is that of a coronary circulation impaired by a recently ruptured atherosclerotic plaque, usually platelet rich. It is indistinguishable from the lesion which produces non Q MI. Other mechanisms include occlusion of an artrery which has collateral circulation, vasospastic angina, cocaine or anaphylaxis induced spasm. Differential also includes new anemia, thyrotoxicosis, hypertension in patient with stable angina.

Diagnosis should be performed rapidly (30 minutes) to exclude acute myocardial ischemia requiring reperfusion therapy. History, ECG, and physical should be reviewed to identify high risk features:

Patients judged to be of low risk, might be managed as outpatients with an accelerated evaluation, but most patients will be admitted. High risk patients should enter a CCU. Initial therapies have as a goal the stabilization of the process as reflected by reduced frequency of episodes. Overall goals are prevention of progression to myocardial infarction or death. Methods include:

a. Antithrombotic therapy - Intravenous heparin bolus then infusion to APTT 2.5 times control for 3-5 days, followed by Aspirin. Thrombolytic therapy is contraindicated. There is no role for warfarin.

b. Nitrates - intravenous nitroglycerine followed by intermittent nitrates

c. Beta blockers - intravenous if patient is very high risk

d. Calcium channel blockers - second line therapy if intolerant or unreponsive to beta blockers and nitrates. Dihydropyridines should not be used alone without beta blockers.

e. Intra aortic balloon counterpulsation - for recurrent episodes.

Diagnostic measures are directed toward specific goals. Initially, myocardial infarction should be ruled out by serial cardiac specific enzymes and serial electrocardiograms. Chest X Ray, Lipids, and LV function can be determined. Cardiac catheterization should be performed for patients with high risk features or failure to respond to therapy within 48 hours. The TIMI III B study showed that there was no difference in mortality or MI if all stabilized patients had cath or if they were evaluated by stress testing first. Stress testing should be performed once the patient is stabilized. On the other hand, a Veterans Hospital cooperative study indicated that a noninvasive approach was superior.

Non Q MI should be considered in the spectrum of unstable syndromes. Generally, extent of myocardial infarction is less, short term prognosis better, and issues of management initially more directed to stabilization, detection of risk for further events, and protection against such events. 

Acute Myocardial Infarction

The pathophysiology of myocardial infarction extends from the issue of ischemia to that of injury to cardiac muscle and structures. 90% of transmural myocardial infarctions are associated with thrombotic occlusion of the infarct related arteries at the site of an atherosclerotic plaque. The occluding thrombus is fibrin and red cell rich, different from the "white" platelet thrombi of unstable angina and/or non Q MI. Unless reperfusion can be effected in a timely fashion, this thrombus creates ischemic injury to tissues with consequent electrical, mechanical, and structural changes. The current discussion will focus on the acute management of myocardial infarction as an ischemic syndrome, with emphasis on those arenas that have been illuminated by clinical studies.

Early diagnosis has become essential to enable rapid utilization of revascularization strategies. The longest interval in delay is the prehospital phase - public education focuses on identifying the symptoms which-would prompt patients to call for emergency help. Actual transport time and response of an emergency medical system is not as significant as thought. In the emergency department, "Door to Needle" times appear to be dependent on rapid diagnosis and decision making. Emergency department evaluation includes history of pain syndrome, evidence of prior ischemic disease, and physical findings of heart rate, blood pressure, perfusion, congestion. ECG is essential and should be considered definitive in appropriate settings with ST elevations in 2 or more consecutive leads. Adjuncts for rapid diagnosis in ER include echocardiography and rapid assays for myosin and troponin T. Definitive diagnosis can be extended with serial observations of cardiac specific enzymes and EKG.

Initial management is directed to Aspirin administration - chew 324 mg of soluble aspirin based on the mortality benefit demonstrated by the first ISIS trial. Adjunctive measures include rest, pain management, oxygen ,and rhythm monitoring. Lidocaine administration is no longer considered to have a prophylactic benefit and is thus no longer standard unless monitoring is not available.

Eligibility for reperfusion therapy has expanded: patients at all ages, patients without qualifying ST elevations if they have LBBB and ST depressions in true posterior MI, and in patients who have received brief periods of CPR. Time since onset of pain may be as long as 12 hours, although the greatest benefit is seen if lytic therapy is administered within 2 hours. Contraindications are unchanged; patients anticipated to have major benefit from lytic therapy should be considered for primary angioplasty. The GUSTO trial showed unequivocal but clinically small benefits for tissue plasminogen activator (TPA) vs. Streptokinase (SK). SK is preferred for general use and for greater time since onset of pain. TPA is favored for early presentations, hypotensive patients, and individuals who have received SK within a year (blocking antibodies. "Front Loading" TPA - administering a higher initial dose - has been favored. All patients receive aspirin and subsequent heparin. Recently the introduction of Reteplase has simplified management due to bolus administration.

Angioplasty for acute myocardial infarction has been evaluated in several strategies. PRIMARY Angioplasty entails dilation of the infarct related artery during the acute phase of MI without prior lyric therapy. Its benefit, suggested by non randomized studies, has now been validated by several prospective studies. Its general use in place of lytic therapy is still being debated. Current indications would include: contraindications to lytic therapy; prior CABG, advanced age, and EKG limited diagnosis. Other strategies for angioplasty have not been validated as effective. One circumstance that does seem to benefit patients is dilatation in the setting of cardiogenic shock.

Coronary bypass has been demonstrated as effective in acute MI as primary therapy if the health care system is geared to immediate management. It is otherwise reserved for mechanical complications, such as mitral insufficiency, VSD, and rupture, as well as recurrent ischemia and cardiogenic shock.

Subsequent management following admission includes adjunctive therapies which have revealed benefit for survival or LV function as well as specific therapies for complications.

Coronary care units for monitoring of life threatening arrhythmias reduced the in hospital mortality 50% after their introduction. A lower incidence of primary ventricular fibrillation, use of lytic therapies, have led to shorter CCU stays.

Aspirin is continued through the hospital stay. Heparin is employed for all patients receiving lytic therapy for up to 5 days. Heparin is also utilized for patients with anterior wall myocardial infarction with conversion to warfarin therapy to prevent systemic embolization. Prolonged bed rest patients should receive subcutaneous heparin for pulmonary embolus protection.

Nitrates have not been validated (ISIS 4) as protective for mortality and LV function. They remain a mainstay of therapy for symptomatic ischemia and congestion.

Beta blockers do have clear indication for prophylaxis in the initial (and post hospital) phase. Intravenous loading with metoprolol or atenolol in patients without contraindications can reduce early death and LV dysfunction.

Calcium channel blockers have a small role in acute MI management. There is a mortality risk for use of dihydrophyridines. Diltiazem increases mortality in patients with LV dysfunction. They should be considered only when beta blockers are contraindicated or not tolerated in patients being treated for symptomatic ischemia.

Converting enzyme inhibitors have very clear long term benefit in patients with LV dysfunction, hypertension, and anterior wall myocardial infarction. Early administration Captopril, a short acting agent, has survival benefit. Hypotension is a limiting parameter. Initiation of therapy after the initial period of instability permits wider use. Several agents have been shown to have benefit (Class benefit).

Magnesium does not appear to confer a survival benefit in a population with high use of thrombolytics (ISIS 4), although smaller studies with patients who were not lytic eligible suggested benefit (LIMIT 2). It may be appropriate for non lytic patients, certainly for those with hypomagnesemia and arrhythmias.

Prophylactic anti arrhythmic therapy has been abandoned. Lidocaine is employed for symptomatic arrhythmias. The CAST trial demonstrated a negative benefit for prophylactic antiarrhythmics. Amiodarone is being investigated as a potential agent for long term prophylaxis for patients with impaired LV function.