Acquired Heart Disease: Coronary Insufficiency

Anatomic Considerations

The coronary arteries, the predominant blood supply to the heart, arise from the sinuses of Valsalva. They are the first arterial branches of the aorta, and two are usually present. The coronary arteries are designated right and left according to the embryologic chamber that they predominantly supply. The left coronary artery (LCA) arises from the left coronary sinus, which is located posterior; the right coronary artery (RCA) arises from the right coronary sinus, which is located anterior. The LCA, also called the left main coronary artery, averages approximately 2 to 3 cm in length and courses in a left posterolateral direction, winding behind the main pulmonary artery trunk and then splitting into the left anterior descending (LAD) and left circumflex arteries. The LAD courses in an anterolateral direction to the left of the pulmonary trunk and runs anteriorly over the interventricular septum. The diagonal branches of the LAD supply the anterolateral wall of the left ventricle (LV). The LAD is considered the most important surgical vessel because it supplies more than 50% of the LV mass and most of the interventricular septum. The LAD has several septal perforating branches that supply the interventricular septum from its anterior aspect. The LAD extends over the interventricular septum up to the apex of the heart, where it may form an anastomosis with the posterior descending artery (PDA), which is typically a branch of the right coronary system ( Fig. 60.1 ).

The circumflex artery passes in the atrioventricular (AV) groove and gives off the obtuse marginal branches that extend toward but do not quite reach the apex of the heart. The obtuse marginal branches are designated numerically from proximal to distal. The circumflex coronary artery usually terminates as the left posterolateral branch after taking a perpendicular turn toward the apex.

The term ramus intermedius is used to designate a dominant coronary vessel that arises from the occasional trifurcation of the LCA. This branch can be intramyocardial and difficult to locate at times.

The RCA supplies most of the right ventricle as well as the posterior part of the LV. The RCA emerges from its ostium in the right coronary sinus and passes deep in the right AV groove. At the superior end of the acute margin of the heart, the RCA turns posteriorly toward the crux and usually bifurcates into the PDA over the posterior interventricular sulcus and right posterolateral artery. The RCA also supplies multiple right ventricular branches (i.e., the acute marginal branches). On occasion, the PDA arises from both the RCA and LCA, and the circulation is considered to be codominant. The AV node artery arises from the RCA in approximately 90% of patients. The sinoatrial node artery arises from the proximal RCA in 50% of patients. Although the source of the PDA is often used clinically to define dominance of circulation in the heart, anatomists define it according to where the sinoatrial node artery arises. Table 60.1 summarizes the hierarchy of the coronary artery anatomy.

All the epicardial conductance vessels and septal perforators from the LAD give rise to a multitude of branches, termed resistance vessels, that penetrate into the ventricular wall. These vessels play a crucial role in oxygen and nutrient exchange with the myocardium by forming a rich capillary plexus. This plexus offers a low-resistance sink that allows arterial blood flow to increase unimpeded when oxygen demand rises. This is important because the myocardial vascular bed extracts oxygen at its full capacity, even in low-demand circumstances, thereby allowing no margin for further oxygen extraction when demand is high.

An intricate network of veins drains the coronary circulation, and the venous circulation can be divided into three systems: the coronary sinus and its tributaries, the anterior right ventricular veins, and the thebesian veins. The coronary sinus predominantly drains the LV and receives 85% of coronary venous blood. It lies within the posterior AV groove and empties into the right atrium. The anterior right ventricular veins travel across the right ventricular surface to the right AV groove, where they enter directly into the right atrium or form the small cardiac vein, which enters into the right atrium directly or joins the coronary sinus just proximal to its orifice. The thebesian veins are small venous tributaries that drain directly into the cardiac chambers and exit primarily into the right atrium and right ventricle. Understanding of the anatomy of the coronary sinus is essential for placement of the retrograde cardioplegia cannula during cardiopulmonary bypass (CPB).

Physiology and Regulation of Coronary Blood Flow

Aortic pressure is a driving force in the maintenance of myocardial perfusion. During resting conditions, coronary blood flow is maintained at a fairly constant level over a wide range of aortic perfusion pressures (70–180 mm Hg) through the process of autoregulation.

Because the myocardium has a high rate of energy use, normal coronary blood flow averages 225 mL/min (0.7–0.9 mL per gram of myocardium per minute) and delivers 0.1 mL/g/min of oxygen to the myocardium. Under normal conditions, more than 75% of the delivered oxygen is extracted in the coronary capillary bed, so any additional oxygen demand can be met only by increasing the flow rate. This highlights the importance of unobstructed coronary blood flow for proper myocardial function. Box 60.1 summarizes the unique features of coronary blood flow.

In response to increased load, such as that caused by strenuous exercise, the healthy heart can increase myocardial blood flow four- to sevenfold. Blood flow is increased through several mechanisms. Local metabolic neurohumoral factors cause coronary vasodilation when stress and metabolic demand increase, thereby lowering the coronary vascular resistance. This results in increased delivery of oxygen-rich blood, mimicking the phenomenon of reactive hyperemia. When a transient occlusion to the coronary artery is released (e.g., during the performance of a beating-heart operation), blood flow immediately rises to exceed the normal baseline flow and then gradually returns to its baseline level. The autoregulatory mechanism responsible is guided by several metabolic factors, including carbon dioxide, oxygen tension, hydrogen ions, lactate, potassium ions, and adenosine. Adenosine, a potent vasodilator and a degradation product of adenosine triphosphate, accumulates in the interstitial space and relaxes vascular smooth muscle. This results in vasomotor relaxation, coronary vasodilation, and increased blood flow. Another substance that plays an important role is nitric oxide, which is produced by the endothelium. Without the endothelium, coronary arteries do not autoregulate, suggesting that the mechanism for vasodilation and reactive hyperemia is endothelium dependent.

Extravascular compression of the coronaries during systole also plays an important role in the regulation of blood flow. During systole, the intracavitary pressures generated in the LV wall exceed intracoronary pressure, and blood flow is impeded. Hence, approximately 60% of coronary blood flow occurs during diastole. During exercise, increased heart rate and reduced diastolic time can compromise flow time, but this can be offset by vasodilatory mechanisms of the coronary vessels. Buildup of atherosclerotic plaques and fixed coronary occlusion significantly impair coronary arterial compensatory mechanisms while heart rate is elevated. This forms the basis for exercise-induced stress tests, in which abnormal physiologic responses to increased physical activity unmask underlying CAD.

Pathogenesis

The primary cause of CAD is endothelial injury induced by an inflammatory wall response and lipid deposition. There is evidence that an inflammatory response is involved in all stages of the disease, from early lipid deposition to plaque formation, plaque rupture, and coronary artery thrombosis. Vulnerable or high-risk plaques that are prone to rupture have the following characteristics: a large, eccentric, soft lipid core; a thin fibrous cap; inflammation within the cap and adventitia; increased plaque neovascularity; and evidence of outward or positive vessel remodeling.

Thinner fibrous caps are at a higher risk for rupture, probably because of an imbalance between the synthesis and the degradation of the extracellular matrix in the fibrous cap that results in an overall decrease in the collagen and matrix components ( Fig. 60.2 ). Increased matrix breakdown caused by matrix degradation by an inflammatory cell-mediated metalloproteinase or reduced production of extracellular matrix results in thinner fibrous caps. Not all plaque ruptures are symptomatic; whether they are depends on the thrombogenicity of the plaque’s components. Tissue factor within the lipid core of the plaque, secreted by activated macrophages, is one of the most potent thrombogenic stimuli. Rupture of a vulnerable plaque may be spontaneous or caused by extreme physical activity, severe emotional distress, exposure to drugs, cold exposure, or acute infection.

Fixed Coronary Obstructions

More than 90% of patients with stable IHD (SIHD) have advanced coronary atherosclerosis caused by a fixed obstruction. Atherosclerotic plaques of the coronary arteries are concentric (25%) or eccentric (75%). Eccentric lesions compromise only a portion of the lumen; through vascular remodeling, the arterial lumen may remain patent until late in the disease process. The impact of an arterial stenosis on coronary blood flow can be appreciated in the context of the Poiseuille law. Reductions in luminal diameter up to 60% have minimal impact on flow, but when the cross-sectional area of the vessel has decreased by 75% or more, coronary blood flow is significantly compromised. Clinically, this loss of flow often coincides with the onset of exertional angina. A 90% reduction in luminal diameter results in resting angina.

Clinical Presentation

Clinically, IHD has two predominant modes of presentation:

• Stable angina

• Acute coronary syndrome: ST-segment elevation myocardial infarction (STEMI) and its complications, non-STEMI (NSTEMI), and unstable angina (UA)

Anginal pain is the main presenting symptom of IHD. It typically lasts minutes. The location is usually substernal, and pain can radiate to the neck, jaw, epigastrium, or arms. Anginal pain is precipitated by exertion or emotional stress and relieved by rest. Sublingual nitroglycerin also usually relieves angina within 30 seconds to several minutes.

On presentation, angina must be classified as stable or unstable. Patients are said to be having UA if the pain is increasing (in frequency, intensity, or duration) or occurring at rest. Such patients should be transferred promptly to an emergency department.

Patients, especially female and elderly patients, sometimes present with atypical symptoms, such as nausea, vomiting, midepigastric discomfort, or sharp (atypical) chest pain. In the Women’s Ischemic Syndrome Evaluation (WISE) study, 65% of women with ischemia presented with atypical symptoms.

The term acute coronary syndrome has evolved to refer to a constellation of clinical symptoms that represent myocardial ischemia. It encompasses both STEMI and NSTEMI. Myocardial infarction (MI) often is manifested as crushing chest pain that may be associated with nausea, diaphoresis, anxiety, and dyspnea. Symptoms of the hypoperfusion that follows MI may include dizziness, fatigue, and vomiting. Heart rate and blood pressure may be initially normal, but both increase in response to the duration and severity of pain. Loss of blood pressure is indicative of cardiogenic shock and indicates a poorer prognosis. At least 40% of the ventricular mass must be involved for cardiogenic shock to occur.

Mechanical complications of MI include acute ventricular septal defect (VSD), papillary muscle rupture, and free ventricular rupture. They usually occur approximately 7 to 10 days after the initial MI.

Physical Examination

Some clinical findings are generic and are related to the systemic manifestations of atherosclerosis. Eye examination may reveal a copper wire sign, retinal hematoma or thrombosis secondary to vascular occlusive disease, and hypertension. Corneal arcus and xanthelasma are features noticed in cases of hypercholesterolemia. Other clinical manifestations are caused by sequelae of CAD ( Box 60.2 ).

A thorough vascular evaluation is essential for any patient who presents with CAD because atherosclerosis is a systemic process. In addition, if surgery is being planned, the extremities should be evaluated for any previous surgical scars or fractures that could potentially preclude conduit harvest.

Diagnostic Testing

Cardiac Catheterization and Intervention

Coronary catheterization is the “gold standard” for diagnosis of CAD. Coronary angiography defines coronary anatomy, including the location, length, diameter, and contour of the epicardial coronary arteries; the presence and severity of coronary luminal obstructions; the nature of the obstruction; the presence and extent of angiographically visible collateral flow; and coronary blood flow.

The classification for defining coronary anatomy that is still used today was developed for the Coronary Artery Surgery Study (CASS) and further modified by the Balloon Angioplasty Revascularization Investigation (BARI) study group. This scheme assumes that there are three major coronary arteries: the LAD, the circumflex, and the RCA, with a right-dominant, left-dominant, or codominant circulation. The extent of disease is defined as one-vessel, two-vessel, three-vessel, or left main disease; a luminal diameter reduction of at least 70% is considered to be significant stenosis ( Figs. 60.3 and 60.4 ). Left main disease, however, is defined as stenosis of at least 50% ( Fig. 60.5 ). Despite being recognized as the traditional gold standard for clinical assessment of coronary atherosclerosis, this test is not without limitations. There is marked variation in interobserver reliability, and investigators have found only 70% overall agreement among readers with regard to the severity of stenosis; this was reduced to 51% when restricted to coronary vessels rated as having some stenosis by any reader. Also, angiography provides only anatomic data and is not a reliable indicator of the functional significance of a given coronary stenosis unless a technique such as fractional flow reserve (FFR) is used to provide information about the physiologic effects of the stenosis. FFR is measured by passing a sensor guidewire into the LAD or circumflex vessels for LCA lesions. Thereafter, the flow reserve in the artery is checked by using adenosine to induce hyperemia in the coronary system, which is discussed in the next section on FFR. In addition, angiography cannot distinguish between vulnerable and stable plaques. In angiographic studies performed before and after acute events and early after MI, plaques causing UA and MI commonly were found to be 50% obstructive before the acute event and were therefore angiographically “silent.” ^, Diagnostic testing methods to identify vulnerable plaque and, therefore, the patient’s risk of MI are being intensely studied, but no gold standard has yet emerged. Despite these limitations of coronary angiography, the extent and severity of CAD as revealed angiographically remain important predictors of long-term patient outcomes. ^,

In the CASS registry of medically treated patients, the 12-year survival rate of patients with normal coronary arteries was 91% compared with 74% for those with one-vessel disease, 59% for those with two-vessel disease, and 40% for those with three-vessel disease.

Importantly, besides informing the decision whether to intervene surgically or with percutaneous coronary intervention (PCI), the salient characteristics of coronary lesions (e.g., stenosis severity, length, and complexity and presence of thrombus), the number of lesions threatening regions of contracting myocardium, the effect of collaterals, and the volume of jeopardized viable myocardium also can afford some insight into the potential consequences of subsequent vessel occlusion and therefore the haste with which surgery should be scheduled.

PCI techniques in current use include balloon dilation, stent-supported dilation, atherectomy and plaque ablation with a variety of devices, thrombectomy with aspiration devices, specialized imaging, and physiologic assessment with intracoronary devices.

Coronary artery stents were the first substantial breakthrough in the prevention of restenosis after angioplasty. Although stent recoil and compression are not completely insignificant problems, the greatest cause of lumen loss in stented coronary arteries is neointimal hyperplasia. This is the principal mechanism of in-stent stenosis and results from inappropriate cell proliferation—hence, the advent of cytotoxic drug-eluting stents (DESs).