Plaque rupture, thrombosis, and healing. A. Arterial remodeling during atherogenesis. During the initial part of the life history of an atheroma, growth is often outward, preserving the caliber of lumen. This phenomenon of “compensatory enlargement” accounts in part for the tendency of coronary arteriography to underestimate the degree of atherosclerosis. B. Rupture of the plaque's fibrous cap causes thrombosis. Physical disruption of the atherosclerotic plaque commonly causes arterial thrombosis by allowing blood coagulant factors to contact thrombogenic collagen found in the arterial extracellular matrix and tissue factor produced by macrophage-derived foam cells in the lipid core of lesions. In this manner, sites of plaque rupture form the nidus for thrombi. The normal artery wall possesses several fibrinolytic or antithrombotic mechanisms that tend to resist thrombosis and lyse clots that begin to form in situ. Such antithrombotic or thrombolytic molecules include thrombomodulin, tissue and urokinase-type plasminogen activators, heparan sulfate proteoglycans, prostacyclin, and nitric oxide. C. When the clot overwhelms the endogenous fibrinolytic mechanisms, it may propagate and lead to arterial occlusion. The consequences of this occlusion depend on the degree of existing collateral vessels. In a patient with chronic multivessel, occlusive coronary artery disease, collateral channels have often formed. In such circumstances, even a total arterial occlusion may not lead to myocardial infarction, or it may produce an unexpectedly modest or a non-ST segment elevation infarct because of collateral flow. In the patient with less advanced disease and without substantial stenotic lesions to provide a stimulus to collateral vessel formation, sudden plaque rupture and arterial occlusion commonly produces ST-segment elevation infarction. These are the types of patients who may present with myocardial infarction or sudden death as a first manifestation of coronary atherosclerosis. In some cases, the thrombus may lyse or organize into a mural thrombus without occluding the vessel. Such instances may be clinically silent. D. The subsequent thrombin-induced fibrosis and healing causes a fibroproliferative response that can lead to a more fibrous lesion, one that can produce an eccentric plaque that causes a hemodynamically significant stenosis. In this way, a nonocclusive mural thrombus, even if clinically silent or causing unstable angina rather than infarction, can provoke a healing response that can promote lesion fibrosis and luminal encroachment. Such a sequence of events may convert a “vulnerable” atheroma with a thin fibrous cap prone to rupture into a more “stable” fibrous plaque with a reinforced cap. Angioplasty of unstable coronary lesions may “stabilize” the lesions by a similar mechanism, producing a wound followed by healing.
lipid lowering reduces coronary events, as reflected on this graph showing the reduction percentages for onset of the acute coronary syndromes achieved by participants in six major clinical studies. 4S, Scandinavian Simvastatin Survival Study (patients with coronary heart disease and elevated cholesterol); CARE, Cholesterol and Recurrent Events (patients with coronary heart disease and average cholesterol); LIPID, Long-Term Intervention with Pravastatin in Ischemic Disease (patients with coronary heart disease and average cholesterol); WOSCOPS, West of Scotland Coronary Prevention Study (normal patients with elevated cholesterol); AFCAPS/TexCAPS, Air Force Coronary Atherosclerosis Prevention Study/Texas Coronary Atherosclerosis Prevention Study (normal patients with average cholesterol); HPS, Heart Protection Study (patients with coronary heart disease, or at high risk, with a wide range of cholesterol).
Short- and long-term results in a long lesion in the right coronary artery. Left: A long (∼50 mm) area of disease (arrows) is present in the right coronary artery. Middle: Contrast injection after placement of two long second-generation stents (25 and 35 mm long) shows excellent patency throughout the proximal- and mid-portions of the vessel. Right: Follow-up angiogram 6 months after stent placement shows mild lumen reduction throughout the stented segment due to neointimal hyperplasia within the stent (note the separation between the stent shadows and the contrast-filled lumen). Mild degrees of proliferative narrowing are benign and common within stents (particularly long stents such as this one). Had the degree of lumen reduction been greater and associated with recurrent symptoms or an abnormal exercise test, however, re-intervention would have been performed, possibly followed by local radiation delivery (brachytherapy) to inhibit excessive subsequent tissue regrowth. Use of a drug-eluting stent would have virtually eliminated this in-stent neointimal hyperplasia.
Transcript of "Heart"
A. Schematic representation of electrocardiogram, aortic pressure pulse (AOP), phonocardiogram recorded at the apex, and apex cardiogram (ACG). On the phonocardiogram, S1, S2, S3, and S4 represent the first through fourth heart sounds; OS represents the opening snap of the mitral valve, which occurs coincident with the O point of the apex cardiogram. S3 occurs coincident with the termination of the rapid-filling wave (RFW) of the ACG, while S4 occurs coincident with the a wave of the ACG. B. Simultaneous recording of electrocardiogram, indirect carotid pulse (CP), phonocardiogram along the left sternal border (LSB), and indirect jugular venous pulse (JVP). ES, ejection sound; SC, systolic click.
A. Schematic representation of ECG, aortic pressure (AOP), left ventricular pressure (LVP), and left atrial pressure (LAP). The shaded areas indicate a transvalvular pressure difference during systole. HSM, holosystolic murmur; MSM, midsystolic murmur. B. Graphic representation of ECG, aortic pressure (AOP), left ventricular pressure (LVP), and left atrial pressure (LAP) with shaded areas indicating transvalvular diastolic pressure difference. EDM, early diastolic murmur; PSM, presystolic murmur; MDM, middiastolic murmur.
The six frontal plane (A) and six horizontal plane (B) leads provide a three-dimensional representation of cardiac electrical activity.
The horizontal plane (chest or precordial) leads are obtained with electrodes in the locations shown.
Left ventricular hypertrophy (LVH) increases the amplitude of electrical forces directed to the left and posteriorly. In addition, repolarization abnormalities may cause ST-segment depression and T-wave inversion in leads with a prominent R wave (“strain” pattern). Right ventricular hypertrophy (RVH) may shift the QRS vector to the right; this effect usually is associated with an R, RS, or qR complex in lead V1. T-wave inversions may be present in right precordial leads (“strain” pattern).
Acute ischemia causes a current of injury. With predominant subendocardial ischemia (A), the resultant ST vector will be directed toward the inner layer of the affected ventricle and the ventricular cavity. Overlying leads therefore will record ST depression. With ischemia involving the outer ventricular layer (B) (transmural or epicardial injury), the ST vector will be directed outward. Overlying leads will record ST elevation.
A variety of metabolic derangements, drug effects, and other factors may prolong ventricular repolarization with QT prolongation or prominent U waves. Repolarization prolongation, particularly if due to hypokalemia or pharmacologic agents, indicates increased susceptibility to torsades de pointes type ventricular tachycardia. Hypothermia is associated with a distinctive convex “hump” at the J point (Osborn wave, arrow). Note QRS and QT prolongation along with sinus tachycardia in the case of tricyclic antidepressant overdose.
Two-dimensional echocardiographic still-frame images from a normal patient with a normal heart. Upper: Parasternal long axis view during systole and diastole (left) and systole (right). During systole, there is thickening of the myocardium and reduction in the size of the left ventricle (LV). The valve leaflets are thin and open widely. Lower: Parasternal short axis view during diastole (left) and systole (right) demonstrating a decrease in the left ventricular cavity size during systole as well as an increase in wall thickening. LA, left atrium; RV, right ventricle; Ao, aorta.
Left: Transesophageal echocardiographic view of a patient with severe mitral regurgitation due to a flail posterior leaflet. The arrow points to the portion of the posterior leaflet that is unsupported and moves into the left atrium during systole. Right: Color-flow imaging demonstrating a large mosaic jet of mitral regurgitation during systole. LA, left atrium; LV, left ventricle; AV, aortic valve.
Transesophageal echocardiographic view of a patient with a dilated aorta, aortic dissection, and severe aortic regurgitation. The arrow points to the intimal flap that is seen in the dilated ascending aorta. Left: The long axis apex down view of the black and white two-dimensional image in diastole. Right: Color-flow imaging that demonstrates a large mosaic jet of aortic regurgitation. Ao, aorta; RV, right ventricle; AR, aortic regurgitation.
A. Exercise sestamibi study on a 71-year-old, white female with atypical angina. Left: Stress images; right: rest images. The images are normal. There is even sestamibi update throughout the myocardium at rest and during stress. B. Exercise sestamibi study on a 75-year-old male with a history of typical angina. Left: Stress images; right: rest images. The stress images show a large defect involving the apex, lateral, and inferior walls (thick arrows), which improves at rest (thin arrows). Subsequent coronary angiography demonstrates severe three-vessel coronary artery disease. SA, short axis; Mid, middle of the left ventricle; VLA, vertical long axis; HLA, horizontal long axis.
Left ventricular (LV), radial artery, and pulmonary capillary wedge (PCW) pressures in a patient with normal cardiovascular function. Note the absence of a pressure gradient between the LV and radial artery in systole and between the LV and PCW in diastole.
Left ventricular (LV), right ventricular (RV), and pulmonary capillary wedge (PCW) pressure tracings in a patient with severe constrictive pericarditis. Note the diastolic dip and plateau (“square root sign”) pattern for left and right ventricular diastolic pressures (left). The wedge pressure (right) shows early systolic and early diastolic dips.
ECG lead II showing spontaneous cessation of supraventricular tachycardia followed by a 6-s pause prior to resumption of sinus activity. The patient was asymptomatic during supraventricular tachycardia, but the sinus pause caused severe light-headedness.
Example of marked His-Purkinje system disease with a relatively normal PR interval. Surface leads I, aVF, and V1 are shown with electrograms from the high right atrium (HRA), His bundle electrogram (HBE), and time lines (T). The QRS shows right bundle branch block and left anterior hemiblock; the PR interval is minimally elevated at 205 ms, but the HV interval exceeds 100 ms. Such a prolonged HV interval mandates a pacemaker.
ECG in Wolff-Parkinson-White syndrome. There is a short PR interval (0.11 s), a wide QRS complex (0.12 s), and slurring on the upstroke of the QRS produced by early ventricular activation over the bypass tract (delta wave, d in lead I). The negative delta waves in V1 are diagnostic of a right-sided bypass tract. Note the Q wave (negative delta wave) in lead III, mimicking myocardial infarction.
Normally functioning implantable defibrillators. A continuous Holter monitoring tracing is shown. On the top strip, a rapid polymorphic tachycardia is initiated which beats more uniformly. The automatic implantable cardioverter/defibrillator (ICD) senses the rhythm and delivers a shock which restores sinus rhythm.
Schema of reentry. Y branching of the Purkinje system to ventricular muscle is shown in panels A through C. The right limb (blue) of the Purkinje system has a longer refractory period than the left. A. During a slow stimulated rate (S1), conduction proceeds normally over both Purkinje fibers, resulting in collision in the ventricular muscle. B. An early premature stimulus (S2) results in block in the Purkinje fiber on the right and slow conduction down the left. The impulse conducts through the ventricle and attempts to reenter the initial site of block but fails because this site has not fully recovered excitability. C. An earlier stimulus (S3) again results in block on the left. The resulting slower propagation down the left fiber provides enough time for the initial site of block to recur and allows the impulse to conduct through it to produce a reentrant circuit.
Ventricular parasystole. At varying sinus cycle lengths during exercise, interectopic intervals remain constant at 1620 to 1640 ms. However, the coupling intervals between sinus and ectopic complexes vary between 510 and 310 ms.
Examples of supraventricular tachycardia (SVT). Arrows indicate P waves. A. AV nodal reentry. Upright P waves are visible at the end of the QRS complex. B. AV reentry using a concealed bypass tract. Inverted retrograde P waves are superimposed on the T waves. C. Automatic atrial tachycardia. Inverted P waves follow the T waves and precede the QRS complex.
The responses of the left ventricle to increased afterload, increased preload, and increased and reduced contractility are shown in the pressure-volume plane. ESPVR, end-systolic pressure-volume relation; EES, the slope of the end-systolic pressure-volume relation. Left. Effects of increases in preload and afterload on the pressure-volume loop. Since there has been no change in contractility, ESPVR is unchanged. With an increase in afterload, stroke volume falls (1 -> 2); with an increase in preload, stroke volume rises (1 -> 3). Right. With increased myocardial contractility, the normal ESPVR moves to the left of the normal line (lower end-systolic volume at any end-systolic pressure) and stroke volume rises (1 -> 3). With reduced myocardial contractility, the ESPVR moves to the right; end-systolic volume is increased and stroke volume falls (1 -> 2).
Interplay between cardiac function and neurohumoral and cytokine systems. Myocardial injury, of many etiologies, can depress cardiac function, which in turn causes activation of the sympathoadrenal system (SAS) and the renin-angiotensin-aldosterone system (RAAS) and the elaboration of endothelin, arginine vasopressin (AVP), and cytokines such as tumor necrosis factor (TNF) &agr;. In acute heart failure (left), these are adaptive and tend to maintain arterial pressure and cardiac function. In chronic heart failure (right) they cause maladaptive hypertrophic remodeling and apoptosis, which cause further myocardial injury and impairment of cardiac function. The horizontal line on the right (*) shows that chronic maladaptive influences can be inhibited by angiotensin converting enzyme inhibitors, &bgr;-adrenergic blockers, angiotensin type I receptor blockers, and aldosterone antagonists.
Complete transposition of the great arteries is depicted in the left panel. The aorta arises from the right ventricle and the pulmonary artery from the left ventricle. The only mixing between the two circulations occurs across a patent foramen ovale. In the right panel, the tetralogy of Fallot drawing illustrates the two most important anatomic findings, a large ventricular septal defect and RV outflow tract obstruction. A right-to-left shunt is shown across the ventricular septum.
Transesophageal echocardiographic view of a patient with a dilated aorta, aortic dissection, and severe aortic regurgitation. The arrow points to the intimal flap that is seen in the dilated ascending aorta. Left: the long axis apex down view of the black and white two-dimensional image in diastole. Right: color flow imaging that demonstrates a large mosaic jet of aortic regurgitation. AO, aorta; RV, right ventricle; AR, aortic regurgitation.
Once adherent, some white blood cells will migrate into the intima. The directed migration of leukocytes probably depends on chemoattractant factors including modified lipoprotein particles themselves and chemoattractant cytokines depicted by the smaller spheres, such as the chemokine macrophage chemoattractant protein 1 produced by vascular wall cells in response to modified lipoproteins. Leukocytes in the evolving fatty streak can divide and exhibit augmented expression of receptors for modified lipoproteins (scavenger receptors). These mononuclear phagocytes ingest lipids and become foam cells, represented by a cytoplasm filled with lipid droplets. As the fatty streak evolves into a more complicated atherosclerotic lesion, smooth-muscle cells migrate from the media (bottom of lower panel), through the internal elastic membrane (solid wavy line), and accumulate within the expanding intima where they lay down extracellular matrix that forms the bulk of the advanced lesion (bottom panel, right-hand side).
PTCA balloon catheter. The lesion is typical of the straightforward lesion anatomy treated by early (pre-1985) coronary angioplasty
PTCA (lower left panel), there is restored antegrade flow with residual stenosis. After stent placement (lower right panel), there is no residual stenosis and brisk flow. This improvement was associated with reversal of shock hemodynamics, including normalization of severe lactic acidosis.
Stent placement in a diseased saphenous vein graft. Left: Severe eccentric stenosis in an 8-year-old saphenous vein graft to the left anterior descending coronary artery. Middle: After balloon angioplasty, the lumen remains stenotic due to elastic recoil of the vessel wall and disruption (dissection) of the plaque. Right: After placement of a coronary stent, both recoil and dissection have been overcome, providing a large smooth lumen.