Ischemic heart disease (IHD) is defined as lack of oxygen and decreased or no bloodflow to the myocardium resulting from coronary artery narrowing or obstruction.It may present as acute coronary syndrome (ACS), which includes unstable anginaand nonST-segment elevation (NSTE) or ST-segment elevation (STE) myocardialinfarction (MI), chronic stable exertional angina, ischemia without symptoms, orischemia due to coronary artery vasospasm (variant or Prinzmetal angina).PATHOPHYSIOLOGY Major determinants of myocardial oxygen demand (MVo2) are heart rate (HR), contractility,and intramyocardial wall tension during systole. Because the consequencesof IHD usually result from increased demand with a fixed oxygen supply, alterationsin MVo2 are important in producing ischemia and for interventions intended toalleviate it. The double product (DP) is the heart rate multiplied by the systolic blood pressure(DP = HR SBP) and serves as an indirect estimate of MVo2. The caliber of resistance vessels delivering blood to the myocardium and MVo2 arethe primary determinants in the occurrence of ischemia. Large epicardial or surface coronary vessels (R1) offer little resistance to myocardialflow and intramyocardial arteries and arterioles (R2), which branch into a densecapillary network to supply basal blood flow. Under normal circumstances, resistancein R2 is much greater than that in R1. Myocardial blood flow is inversely related toarteriolar resistance and directly related to coronary driving pressure. Atherosclerotic lesions occluding R1 increase arteriolar resistance, and R2 can vasodilateto maintain coronary blood flow. With greater degrees of obstruction, thisresponse is inadequate, and the coronary flow reserve afforded by R2 vasodilation isinsufficient to meet oxygen demand. The diameter and length of obstructing lesions and the influence of pressure dropacross an area of stenosis also affect coronary blood flow. Dynamic coronary obstructioncan occur in normal vessels and vessels with stenosis in which vasomotion or aspasm may be superimposed on a fixed stenosis. Persisting ischemia may promotegrowth of collateral blood flow. Relatively severe stenosis (>70%) may provoke ischemia and symptoms at rest.Lesions creating obstruction of 50% to 70% may reduce blood flow, but theseobstructions are not consistent, and vasospasm and thrombosis superimposed on anoncritical lesion may lead to clinical events such as MI. Regional loss of ventricular contractility may impose a burden on remaining myocardialtissue, resulting in heart failure (HF), increased MVo2, and rapid depletionof blood flow reserve. Zones of tissue with marginal blood flow may develop thatare at risk for more severe damage if the ischemic episode persists or becomes moresevere. Nonischemic areas of myocardium may compensate for severely ischemicand border zones of ischemia by developing more tension than usual in attempt tomaintain cardiac output. The left or right ventricular dysfunction that ensues may beassociated with an S3 gallop, dyspnea, orthopnea, tachycardia, fluctuating blood pressure,transient murmurs, and mitral or tricuspid regurgitation. Impaired diastolic andsystolic function leads to elevated left ventricular filling pressure.CLINICAL PRESENTATION Many ischemic episodes are asymptomatic (silent ischemia). Patients often have areproducible pattern of pain or other symptoms that appear after a specific amount ofexertion. Increased symptom frequency, severity, or duration, and symptoms at restsuggest an unstable pattern that requires immediate medical evaluation.Ischemic Heart Disease 11CHAPT ER103Ischemic Heart Disease | CHAPTER 11 Symptoms may include a sensation of pressure or burning over the sternum ornear it, which often radiates to the left jaw, shoulder, and arm. Chest tightness andshortness of breath may also occur. The sensation usually lasts from 30 seconds to30 minutes. Precipitating factors include exercise, cold environment, walking after a meal, emotionalupset, fright, anger, and coitus. Relief occurs with rest and within 45 secondsto 5 minutes of taking nitroglycerin. Patients with variant (Prinzmetal) angina secondary to coronary spasm are morelikely to experience pain at rest and in the early morning hours. Pain is not usuallybrought on by exertion or emotional stress or relieved by rest; the electrocardiogram(ECG) pattern demonstrates current injury with ST-segment elevation rather thandepression. Unstable angina is stratified into categories of low, intermediate, or high risk forshort-term death or nonfatal MI. Features of high-risk unstable angina include:(1) accelerating tempo of ischemic symptoms in the preceding 48 hours; (2) painat rest lasting more than 20 minutes; (3) age older than 75 years; (4) ST-segmentchanges; and (5) clinical findings of pulmonary edema, mitral regurgitation, S3, rales,hypotension, bradycardia, or tachycardia. Episodes of ischemia may also be painless, or silent, perhaps due to a higher thresholdand tolerance for pain than in patients who have pain more frequently.DIAGNOSIS Obtain medical history to identify the nature or quality of chest pain, precipitatingfactors, duration, pain radiation, and response to nitroglycerin or rest. Ischemic chestpain may resemble pain from noncardiac sources, and diagnosis of anginal pain maybe difficult based on history alone. Ask the patient about personal risk factors for coronary heart disease (CHD), includingsmoking, hypertension, and diabetes mellitus. Obtain family history that includes information about premature CHD, hypertension,lipid disorders, and diabetes mellitus. Findings on cardiac examination may include abnormal precordial systolic bulge,decreased intensity of S1, paradoxical splitting of S2, presence of S3 or S4, apical systolicmurmur, and diastolic murmur. Laboratory tests: hemoglobin, fasting glucose (to exclude diabetes), and fasting lipidpanel. High-sensitivity C-reactive protein (hsCRP); homocysteine level; evidence ofChlamydia infection; and elevations in lipoprotein (a), fibrinogen, and plasminogenactivator inhibitor may be helpful. Cardiac enzymes are normal in stable angina.Troponin T or I, myoglobin, and creatinine kinase myocardial band (CK-MB) maybe elevated in unstable angina. Resting ECG is normal in about half of patients with angina who are not experiencingacute ischemia. Typical STT-wave changes include depression, T-wave inversion,and ST-segment elevation. Variant angina is associated with ST-segment elevation,whereas silent ischemia may produce elevation or depression. Significant ischemia isassociated with ST-segment depression greater than 2 mm, exertional hypotension,and reduced exercise tolerance. Exercise tolerance (stress) testing (ETT), thallium myocardial perfusion scintigraphy,radionuclide angiocardiography, ultrarapid computed tomography, and coronaryangiography may be performed in certain circumstances. Obtain a chest radiographif the patient has HF symptoms.TREATMENT Goals of Treatment: Short-term goals are to reduce or prevent anginal symptoms thatlimit exercise capability and impair quality of life. Long-term goals are to preventCHD events such as MI, arrhythmias, and HF and to extend the patients life.104SECTION 2 | Cardiovascular DisordersNONPHARMACOLOGIC THERAPY Primary prevention through modification of risk factors should reduce prevalence ofIHD. Secondary intervention is effective in reducing subsequent morbidity and mortality. Risk factors for IHD are additive and can be classified as alterable or unalterable.Unalterable risk factors include gender, age, family history or genetic composition,environmental influences, and, to some extent, diabetes mellitus. Alterable riskfactors include smoking, hypertension, hyperlipidemia, obesity, sedentary lifestyle,hyperuricemia, psychosocial factors such as stress, and use of drugs that may bedetrimental (eg, progestins, corticosteroids, calcineurin inhibitors).PHARMACOLOGIC THERAPY-Adrenergic Blockers Decreased HR, contractility, and blood pressure reduce MVo2 and oxygen demandin patients with effort-induced angina. -Blockers do not improve oxygen supply,and, in certain instances, unopposed -adrenergic stimulation may lead to coronaryvasoconstriction. -Blockers improve symptoms in approximately 80% of patients with chronic exertionalstable angina, and objective measures of efficacy demonstrate improved exercise durationand delay in the time at which ST-segment changes and initial or limiting symptomsoccur. -Blockade may allow angina patients previously limited by symptoms to performmore exercise and improve cardiovascular performance through a training effect. Ideal candidates for -blockers include patients in whom physical activity is a prominentcause of attacks; those with coexisting hypertension, supraventricular arrhythmias,or post-MI angina; and those with anxiety associated with anginal episodes.-Blockers may be used safely in angina and HF. -Blockade is effective in chronic exertional angina as monotherapy and in combinationwith nitrates and/or calcium channel blockers (CCBs). -Blockers are first line inchronic angina requiring daily maintenance therapy because they are more effectivein reducing episodes of silent ischemia and early-morning peak of ischemic activityand improving mortality after Q-wave MI than nitrates or CCBs. If -blockers are ineffective or not tolerated, monotherapy with a CCB or combinationtherapy may be instituted. Reflex tachycardia from nitrates can be blunted with-blocker therapy, making this a useful combination. Initial doses of -blockers should be at the lower end of the usual dosing range andtitrated to response. Treatment objectives include lowering the resting HR to 50 to 60beats/min and limiting maximal exercise HR to approximately 100 beats/min or less.HR with modest exercise should be no more than approximately 20 beats/min aboveresting HR (or a 10% increment over resting HR). There is little evidence to suggest superiority of any particular -blocker. Those withlonger half-lives may be administered less frequently, but even propranolol may be giventwice daily in most patients. Membrane-stabilizing activity is irrelevant in angina treatment.Intrinsic sympathomimetic activity appears to be detrimental in patients with restor severe angina because the reduction in HR would be minimized, limiting reductionin MVo2. Cardioselective -blockers may minimize adverse effects such as bronchospasm,intermittent claudication, and sexual dysfunction. Combined nonselective - and-blockade with labetalol may be useful in patients with marginal left ventricular (LV)reserve. Adverse effects of -blockade include hypotension, decompensated HF, bradycardia,heart block, bronchospasm, altered glucose metabolism, fatigue, malaise, and depression.Abrupt withdrawal has been associated with increased severity and number ofanginal episodes and MI. Tapering of therapy over several days should minimize riskof withdrawal reactions if therapy is to be discontinued.Nitrates Nitrates reduce MVo2 secondary to venodilation and arterial-arteriolar dilation,leading to a reduction in wall stress from reduced ventricular volume and pressure