ISCHEMIC HEART DISEASES ( IHD ) Resulting from myocardial ischemia [ imbalancebetween supply (perfusion), and demand of heartfor oxygenated blood] In 90% of cases, the cause is reduction in coronaryblood flow due to atherosclerotic coronary arterialobstruction. Thus, IHD is often termed coronary artery disease(CAD) or coronary heart disease (CHD).
IHD divided into:-o Angina pectoris: ( stable, Prinzmetal , unstable ):ischemia is less severe and does not cause deathof cardiac muscle.o Myocardial infarction (MI) : duration and severity ofischemia is sufficient to cause death of heart muscle.o Chronic IHD with heart failure.o Sudden cardiac death. Acute myocardial infarction, unstable angina,and sudden cardiac death are referred toacute coronary syndrome.
ANGINA PECTORIS: Three patterns :( 1 ) Stable ( typical ) angina: most common form. caused by chronic stenosing coronary atherosclerosis. Occur whenever there is increased heart demand(by physical activity, or emotional excitement). relieved by rest or nitroglycerin (strong vasodilator).
( 2 ) Prinzmetal ( variant ) angina: uncommon pattern. occurs at rest and is due to coronary artery spasm. there is elevated ST segment on electrocardiogram(ECG) indicative of transmural ischemia. anginal attacks are unrelated to physical activity,but responds to vasodilators such as nitroglycerin.
( 3 ) Unstable ( crescendo ) angina: precipitated with less effort, often occurs at rest,and tends to be of more prolonged duration. induced by disruption of an atherosclerotic plaquewith superimposed partial thrombosis and possiblyembolization or vasospasm (or both). is often the prodrome of subsequent acute MI. Thus sometimes referred to preinfarction angina.
MYOCARDIAL INFARCTION (MI): Is the death of cardiac muscle resulting fromischemia. Transmural versus Subendocardial Infarction: Transmural:o Most MI are transmural.o ischemic necrosis involves full or nearly fullthickness of ventricular wall in distribution ofa single coronary artery.o usually associated with coronary atherosclerosis,acute plaque change, and superimposed thrombosis.
Subendocardial (non-transmural) infarct:o limited to inner one third or one half ofventricular wall.o occur as a result of plaque disruption followed bycoronary thrombus that becomes lysed beforemyocardial necrosis extends across the majorthickness of the wall.o can also result from prolonged and severe reductionin systemic blood pressure (as in shock)superimposed on chronic, otherwise noncritical,coronary stenoses.
Incidence and Risk Factors: MI may occur at any age. Frequency rises with increasing age. Predispositions to atherosclerosis are :hypertension, cigarette smoking, diabetes mellitus,and hypercholesterolemia Blacks and whites are equally affected. Men are at greater risk of MI than women. The decrease of estrogen following menopausecan permit rapid development of CAD.
Pathogenesis: Coronary arterial occlusion: sequence of events:-o disruption in atheromatous plaque, manifest asintraplaque hemorrhage, erosion or ulceration, orrupture or fissuring.o Platelets, which exposed to subendothelial collagenand necrotic plaque contents, undergo adhesion,aggregation, activation, and release of potentaggregators ( thromboxane A2, serotonin, andplatelet factors 3 and 4).o Vasospasm is stimulated by platelet aggregation.o Frequently within minutes, the thrombus evolves tocompletely occlude the lumen of coronary vessel.
In 10% of cases, transmural acute MI is notassociated with atherosclerotic plaque thrombosis.other mechanisms may be involved:• Vasospasm: isolated, intense, perhaps in associationwith platelet aggregation (cocaine abuse).• Emboli: from:- left atrium in atrial fibrillation;vegetative endocarditis; paradoxical emboli fromright side of heart or peripheral veins .• Unexplained: caused by coronary vasculitis,hemoglobinopathies, amyloid deposition in vascularwalls.
Morphology:Time Gross Features Light Microscope Electron MicroscopeReversible Injury0–½ hr None NoneRelaxation of myofibrils; glycogenloss; mitochondrial swellingIrreversible Injury½–4 hr NoneUsually none; variable wavinessof fibers at borderSarcolemmal disruption;mitochondrial amorphousdensities4–12 hr Occasionally dark mottlingBeginning coagulation necrosis;edema; hemorrhage12–24 hr Dark mottlingOngoing coagulation necrosis;pyknosis of nuclei; myocytehypereosinophilia; marginalcontraction band necrosis;beginning neutrophilic infiltrate1–3 daysMottling with yellow-tan infarctcenterCoagulation necrosis, with loss ofnuclei and striations; interstitialinfiltrate of neutrophils3–7 daysHyperemic border; centralyellow-tan softeningBeginning disintegration of deadmyofibers, early phagocytosis ofdead cells by macrophages atinfarct border7–10 daysMaximally yellow-tan and soft,with depressed red-tan marginsWell-developed phagocytosis ofdead cells; early formation offibrovascular granulation tissue atmargins10–14 daysRed-gray depressed infarctbordersWell-established granulationtissue with new blood vessels andcollagen deposition2–8 wkGray-white scar, progressivefrom border toward core of infarctIncreased collagen deposition,with decreased cellularity>2 mo Scarring complete Dense collagenous scar
Healed myocardial infarct. The necrotic fibers have been replaced by densecollagenous scar (pink areas filling the right lower quadrant of the image).This healed area will have decreased contractility compared to the adjacentpreserved myocardium.
Clinical Features: MI is diagnosed by typical symptoms, biochemicalevidence, and ECG pattern. Patients have rapid weak pulse and sweatingprofusely (diaphoretic). Dyspnea due to impaired contractility of ischemicmyocardium and the resultant pulmonary congestionand edema. In 10% to 15% of MI patients: asymptomatic and discovered only later by ECGchanges(new Q waves). Such "silent" MIs are common in patients withdiabetes mellitus and in elderly patients.
Lab. evaluation: Based on measuring blood levels of intracellularmacromolecules that leak out of injured myocardialcells. These include myoglobin, cardiac troponins T and I(TnT, TnI), creatine kinase (CK), and lactatedehydrogenase. TnI and TnT : are not normally detectable incirculation, after acute MI levels of both rise at2 to 4 hours and peak at 48 hours ,remain elevatedfor 7 to 10 days after acute event.
Creatine kinase:o Enzyme that is highly concentrated in brain,myocardium, and skeletal muscle.o Composed of two dimers "M" and "B “.o Isoenzyme CK-MM is derived from skeletal muscleand heart ; CK-BB from brain, lung, and many othertissues ; and CK-MB principally from myocardium.o Total CK activity is sensitive but not specific.o CK-MB rise within 2 to 4 hours of onset of MI, peaksat 24 hours, and returns to normal within 72 hours. Absence of change in levels of CK and CK-MB duringfirst 2 days of chest pain , and of troponin in daysfollowing essentially excludes diagnosis of MI.
C-reactive protein (CRP) : predict the risk of (M.I)in patients with angina, and the risk of new infarctsin patients who recover from infarcts.Other diagnostic modalities : Echocardiography (for visualization of abnormalitiesof regional wall motion). Radioisotope studies such as radionuclideangiography (for chamber configuration). Perfusion scintigraphy (for regional perfusion). Magnetic resonance imaging- M.R.I (for structuralcharacterization).
Consequences and Complications of MI: Half of deaths occur within 1 hour of onset. Factors associated with poor prognosis includeadvanced age, female gender, diabetes mellitus ,and previous MI. Three-fourths of patients have one or morecomplications which include:o Left ventricular failure.o Severe pump failure (cardiogenic shock).o Arrhythmias :- sinus bradycardia, heart block ,sinus tachycardia, ventricular tachycardia, andventricular fibrillation.
o Myocardial rupture:-(1) rupture of ventricular free wall.(2) rupture of ventricular septum.(3) papillary muscle rupture.o Pericarditis.o Mural thrombus.o Ventricular aneurysm.
CHRONIC ISCHEMIC HEART DISEASE : Describe cardiac findings in patients, often elderly,who develop progressive heart failure asa consequence of ischemic myocardial damage.Morphology:o Hearts are usually enlarged and heavy secondaryto left ventricular hypertrophy and dilation.o Moderate to severe stenosing atherosclerosis ofcoronary arteries .o Microscopic findings: myocardial hypertrophy,diffuse subendocardial vacuolization, andscars of previously healed infarcts.
SUDDEN CARDIAC DEATH: Unexpected death from cardiac causes. A complication and often the first clinicalmanifestation of IHD. With decreasing age of victims, the followingnon- atherosclerotic causes become probable:o Congenital structural or coronary arterialabnormalities.o Aortic valve stenosis.o Mitral valve prolapse.o Myocarditis.o Dilated or hypertrophic cardiomyopathy.o Pulmonary hypertension.o Hereditary or acquired abnormalities of cardiacconduction system.