Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2704_Библиотеки_им_академика_М_И_Перельмана
.pdf
CHAPTER 7 Valvular Heart Disease
A
B
Chordae tendineae
AB
CD
Normal Acute MR
EDV=120
EDV=220
ESV=100
EF=0.75
EF=0.55
TABLE 7.9 Mechanisms of Mitral Regurgitation
Valvular Abnormality
Primary Mitral Regurgitation
Degenerative Mitral valve prolapse, thickening/calcification
Rheumatic Leaflet thickening/restriction
Infectious endocarditis Vegetations, tissue destruction, leaflet perforation
Systemic inflammatory conditions Libman-Sacks lesions
Malignancy associated Marantic endocarditis
Genetic connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome) Elongated, redundant leaflet tissue
Irradiation Diffuse leaflet thickening/calcification
Drug-induced (anorexigen, ergotamine) Diffuse leaflet thickening
Congenital Cleft/parachute mitral valve
73
Secondary Mitral Regurgitation
Modified from Otto C: Practice of Clinical Echocardiography, Fifth Edition. Philadelphia, Elsevier, 2017.
Anterolateral
papillary muscle
Type I
Posterolateral
papillary muscle
Type II
Type IIIb
Type IIIa
(ischemic)
Fig. 7.7 (A) Mitral apparatus. (B) Carpentier classification of mitral regur-
gitation. (From Interventional Cardiology Clinics, Volume 5, Issue 1, 2016.)
Ventricular distortion of mitral apparatus (coronary artery disease, cardiomyopathy)
Mitral annular dilation (usually with atrial fibrillation)
EDV=120
ESV=50
LAP
10
TSV=70
FSV=70
RSV=0
Chronic Compensated MR Chronic Decompensated MR
LAP
TSV=140
15
FSV=70
RSV=70
Fig. 7.8 Pathophysiology of mitral regurgitation. (From Otto C: Textbook
of Clinical Echocardiography, 5th ed., Elsevier, 2013.)
EF=0.58
EDV=200
ESV=60
EF=0.7
LAP 25
TSV=90
FSV=45
RSV=45
LAP 25
TSV=120
FSV=60
RSV=60
ESV=30
most commonly a blowing, high-pitched, holosystolic murmur best
heard at the apex. Depending on the direction of the MR jet, the murmur may radiate toward the axilla or the neck. In MR due to mitral
valve prolapse, a midsystolic click can be heard followed by a mid or
late systolic murmur.
Diagnosis
An electrocardiogram (ECG) and chest radiograph may have nonspecific findings such as left atrial enlargement or cardiomegaly, respectively. Pulmonary edema can be seen on chest radiograph in the setting
of CHF. However, the diagnosis of MR is ultimately made by TTE,
which can assess for the presence and severity of MR, the effect of MR
on the other cardiac chambers, the presence of concomitant valve disease, and possibly the etiology of MR. If TTE is inadequate, there are
other imaging modalities that are useful. CMR can be used to accurately
74 SECTION II Cardiovascular Disease
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
quantify the chamber sizes, LVEF, and the severity of MR. TEE can provide superior image quality to TTE, including three-dimensional imaging, and help to clarify the severity and anatomic mechanism of MR. In
the case of acute severe MR, if the level of suspicion is high and the TTE
does not show significant MR, a TEE can be performed. Alternatively, a
right heart catheterization can be considered. In the presence of significant MR, the pulmonary capillary wedge waveform would have prominent v waves from the regurgitant flow from the left atrium. Finally, in
patients who have symptoms that are out of proportion to the severity of MR, exercise echocardiography can be considered to assess for
changes in MR and pulmonary artery pressure with exercise.
Treatment
In acute severe MR, emergent or urgent surgical intervention is usually indicated. Until surgery can be performed, afterload reduction is
essential. This is achieved with an intra-aortic balloon pump which
not only reduces afterload but also improves cardiac output and coronary blood flow. Nitroprusside can also be given to reduce afterload
and ionotropic agents can be given for hemodynamic support. In the
absence of hypotension, diuretics can be given to treat pulmonary
edema.
There is no clear role for medical therapy in treating the primary process of chronic MR. The use of vasodilators in normotensive patients with normal LV systolic function is not recommended.
Hypertensive patients can be treated with standard antihypertensive
therapy which may limit worsening of MR. Patients with LV systolic
dysfunction can be given guideline-directed medical therapy (ACE
inhibitors/angiotensin-receptor blockers/angiotensin receptor–neprilysin inhibitor, β-blocker, aldosterone antagonist, and diuretics).
The indication for mitral valve intervention depends on several
factors. If a patient has severe symptomatic MR, mitral valve surgery
is recommended. If a patient has severe asymptomatic MR and LVEF
between 30% and 60%, LVESD 40 mm or greater, or if there is a progressive decrease in LVEF or increase in LVESD, then mitral valve surgery is also recommended. Also, in patients with severe asymptomatic
MR with new onset AF or pulmonary hypertension, mitral valve repair
can be considered if the likelihood of successful repair is greater than
95% and the expected mortality is less than 1%. In general, there is a
higher chance of successful repair in primary MR involving the posterior leaflet. Mitral valve repair is preferred over mitral valve replacement, when possible.
For patients with prohibitive surgical risk, transcatheter mitral
valve repair (TMVR) can be considered (Figs. 7.9 and 7.10). Patients
with prohibitive surgical risk, at least moderate to severe primary MR
with NYHA class III or IV symptoms despite optimal medical therapy,
favorable anatomy, and reasonable life expectancy (≥2 years), should
be referred to a heart valve team for evaluation for TMVR. Trials
assessing the benefit of TMVR in secondary MR have yielded conflicting results. Nonetheless, TMVR has been approved for moderate to
severe or severe secondary MR.
Mitralclip device
Arm
Gripper
Mitralclip system
Steerable
guide
handle
Steerable guide, Steerable sleeve
and delivery catheter
Fig. 7.9 Mitralclip delivery system. (Modified from Abbott Vascular.)
Clip delivery system
Delivery
catheter
handle
Stabilizer
Mitralclip
device
PULMONIC REGURGITATION
Definition and Etiology
Pulmonic regurgitation (PR) is a result of inadequate coaptation of
the pulmonic leaflets resulting in diastolic flow from the pulmonary
artery to the right ventricle. Physiologic to mild PR is common in normal adults. Primary PR is due to an abnormality of the valve leaflets.
Causes of primary PR include iatrogenic, endocarditis, RHD, carcinoid
syndrome, and congenital. Secondary PR occurs in the setting of normal valve leaflets and can be seen in patients with pulmonary artery
dilation or severe pulmonary arterial hypertension. Severe PR is most
Fig. 7.10 Transcatheter mitral valve repair. (From Interventional Cardiol-
ogy Clinics, Volume 5, Issue 1, 2016.)
CHAPTER 7 Valvular Heart Disease
75
commonly seen in patients with of tetralogy of Fallot who underwent
surgical valvotomy or balloon valvuloplasty.
Pathophysiology
Regurgitant diastolic flow from the main pulmonary artery to the
right ventricle leads to RV volume overload. Eventually, patients may
develop RV dilation, RV dysfunction, and TR.
Natural History and Clinical Presentation
Patients with PR typically have a prolonged asymptomatic phase. As
RV systolic function declines, cardiac output decreases and patients
can develop fatigue or decreasing exercise tolerance. With RV dilation,
TR and elevated right-sided filling pressure may develop along with
signs and symptoms of right-sided heart failure such as ascites, peripheral edema, and hepatosplenomegaly.
Physical Examination
The murmur of PR is an early diastolic murmur best heard over the left
upper sternal border that increases in intensity with inspiration. A systolic
ejection murmur may also be heard with more significant amounts of PR
due to increased RV flow. With concomitant pulmonary hypertension,
a high frequency, blowing, diastolic murmur (Graham-Steell murmur)
may be present. On examination of the neck veins, a prominent a wave
can be seen in pulmonary hypertension and a prominent v wave in TR.
Diagnosis
ECG may have nonspecific findings such as RVH or arrhythmias. A
right bundle branch block with intraventricular conduction delay can
be observed in patients with a history of tetralogy of Fallot repair and
severe PR. RV dilation may be seen on chest radiograph.
TTE can confirm the diagnosis of PR and also evaluates the severity, etiology, and, hemodynamic effects of PR, as well as concomitant
valvular disease or pulmonary hypertension. CMR can also provide a
quantitative assessment of PR and RV size and function.
Treatment
Medical therapy of secondary PR should target the underlying cause.
Patients with right-sided heart failure can be given diuretics. However,
surgical intervention is recommended for severe symptomatic PR.
Surgery can also be considered for patients with severe asymptomatic PR with RV dilation or dysfunction, symptomatic arrhythmias,
or progressive TR. In general, patients with native PR undergo surgical valve replacement. Due to the risk of prosthesis regurgitation and
device embolization, a percutaneous approach is rarely recommended
for native PR. Alternatively, for those with prosthetic PR, percutaneous
valve replacement is an option.
TRICUSPID REGURGITATION
Definition and Etiology
TR is defined by the inadequate coaptation of the tricuspid leaflets
during systole resulting in regurgitant flow from the right ventricle to
the right atrium. Physiologic TR is present in about 70% of healthy
adults.
Primary TR, a result of an abnormality of the valve structure, is
rare. Possible causes include iatrogenic direct valve injury, chest wall
trauma or deceleration injury, endocarditis, RHD, carcinoid syndrome, ischemic heart disease (causing papillary muscle dysfunction),
myxomatous degeneration, Marfan syndrome, or drug-induced (fenfluramine, phentermine). The most common congenital heart disease
affecting the tricuspid valve is Ebstein’s anomaly.
Secondary TR occurs in the setting of normal valve anatomy and is
much more common. TR is most often a result of RV dilation, annular dilation, or leaflet tethering. This can occur in any condition with
increased right-sided filling pressures or pulmonary hypertension such
as left-sided heart failure, mitral valve disease, stenosis of the pulmonic
valve or pulmonary artery, primary pulmonary disease, left-to-right
shunting, and Eisenmenger syndrome.
Pathophysiology
With regurgitant systolic flow into the right atrium, there is a progressive increase in RAP and RV volume. This leads to signs and symptoms
of right-sided heart failure and low cardiac output due to RV systolic
dysfunction.
Natural History and Clinical Presentation
Since the right atrium is a compliant chamber, it is able to accommodate the regurgitant volume when TR is mild or moderate. Therefore,
patients are usually asymptomatic. Once severe, patients may have
symptoms of venous congestion and right-sided heart failure such as
hepatosplenomegaly, ascites, and peripheral edema. Patients with significant pulmonary hypertension may have signs of reduced cardiac
output such as fatigue and dyspnea on exertion.
Physical Examination
TR leads to elevated RAP. This is demonstrated on physical examination by distended jugular veins. A prominent c-v wave due to
the regurgitant flow may be observed. Kussmaul sign, a paradoxical
rise in jugular venous pressure with inspiration, can be seen in the
setting of RV dysfunction. With right-sided heart failure, peripheral
edema, ascites, anasarca, and painful hepatosplenomegaly may be
present.
On cardiac exam, wide splitting of S2 and a loud P2 can be heard
with pulmonary hypertension. S3 or S4 may also be present in the
setting of RV dilation or hypertrophy. The murmur of TR is holosystolic and best heard at the mid left sternal border. The intensity
of the murmur will increase with maneuvers that increase venous
return such as inspiration, leg raise, and hepatic compression. An
RV heave may be appreciated on palpation in the setting of RV
dilation.
Diagnosis
TR is diagnosed by TTE. Echocardiography can help to determine
the severity and etiology of TR and RV size and function. In addition,
Doppler can be used to estimate the pulmonary artery systolic pressure. If the TTE is inconclusive, CMR can quantify TR, RV size, and
RV function. Right heart catheterization can provide direct measurements of right-sided pressures, pulmonary pressures, and pulmonary
vascular resistance.
Treatment
Medical therapy for severe TR and right-sided heart failure consists of diuretics to treat volume overload. If possible, the primary
disease process should be treated such as in ischemic heart disease,
left-sided heart failure, mitral valve disease, and pulmonary arterial
hypertension.
Isolated tricuspid valve surgery is only recommended in patients
with severe symptomatic primary TR or severe asymptomatic TR with
progressive RV dysfunction. If a patient is undergoing left-sided valve
surgery, tricuspid valve surgery is recommended for those with concomitant severe TR or at least mild functional TR with tricuspid annular dilation or right-sided heart failure.
76 SECTION II Cardiovascular Disease
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
SUGGESTED READINGS
Mack M, Leon M, et al: Transcatheter aortic-valve replacement with a balloon-
expandable valve in low risk patients, NEJM 380:1695–1705, 2019.
Nishimura R, Otto C, Bonow RO, et al.: 2014 AHA/ACC Guideline for the
management of patients with valvular heart disease, J Am Coll Cardiol
63:e57–e185, 2014.
Nishimura R, Otto C, Bonow RO, et al.: 2017 AHA/ACC focused update of the
2014 AHA/ACC Guideline for the management of patients with valvular
heart disease, J Am Coll Cardiol 70:252–289, 2017.
Nkomo V, Gardin J, et al.: Burden of valvular heart diseases: a population-
based study, Lancet 368:1005–1011, 2006.
Obadia J, Messika-Zeitoun D, et al.: Percutaneous repair or medical treatment
for secondary mitral regurgitation, NEJM 379:2297–2306, 2018.
8
David E. Lewandowski, Michael P. Cinquegrani
DEFINITION AND EPIDEMIOLOGY
The term coronary heart disease (CHD) describes a number of cardiac
conditions that result from the presence of atherosclerotic lesions in the
coronary arteries. The development of atherosclerotic plaque within
the coronary arteries can result in obstruction to blood flow, producing ischemia, which can be acute or chronic in nature. Atherosclerosis
is a disease process that starts at a young age and can be present for
years in an asymptomatic form until the degree of vessel obstruction
leads to ischemic symptoms. Obstructive atherosclerotic lesions can
cause chronic symptoms of exercise- or stress-related angina; or, in the
case of plaque rupture and acute thrombosis, sudden death, unstable
angina, or myocardial infarction (MI) may ensue.
In the United States, more than 18 million people experience some
form of CHD. Approximately 10 million suffer from symptoms of
angina, and at least 360,000 deaths occur each year from acute MI or
CHD-related sudden death. Despite progress in therapy and overall
reductions in CHD-related mortality, CHD remains the number one
cause of death in both men and women, accounting for 27% of deaths
in women (more than deaths due to cancer). The incidence of CHD
increases with age for both men and women. There are at least 1.3 million MIs per year in the United States and many more cases of unstable
angina. CHD frequently results in lifestyle-limiting symptoms due to
angina or impairment of left ventricular (LV) function. The cost of
care related directly to CHD and indirectly to lost productivity from
CHD is in the range of $156 billion per year. CHD remains a major
life-threatening disease process associated with significant economic
impact.
RISK FACTORS FOR ATHEROSCLEROSIS
There are a number of well-known risk factors for coronary artery
disease (CAD), some of which are modifiable (Table 8.1). Although
women ultimately also carry a significant atherosclerotic burden, men
develop CAD at younger ages, and the prevalence of the disease also
increases as men age. Another potent risk factor for the development
of CAD is a family history of premature CAD. This speaks to a nonmodifiable, genetically based risk. Commonly, multiple family members develop symptomatic CAD before the age of 55 years (65 years
for women). Risks are additive, making it very important to appreciate
the modifiable risk factors such as hyperlipidemia, hypertension, diabetes mellitus, metabolic syndrome, cigarette smoking, obesity, sedentary lifestyle, and heavy alcohol intake. Patients are risk-stratified
for the likelihood of developing clinically significant coronary artery
disease through the ASCVD (atherosclerotic cardiovascular disease)
score. Taking into account multiple patient-specific factors, the score
estimates the patient’s 10-year probability of experiencing an adverse
event such as nonfatal MI, cardiovascular death, or stroke. The score
can help guide blood pressure goals, the need for statin therapy, and
other key preventative measures against CAD.
Metabolic syndrome deserves particular attention given that up to
25% of the adult US population may satisfy the definition of the disorder as laid out by the National Cholesterol Education Program Adult
Treatment Panel. The definition of metabolic syndrome requires the
presence of at least three of the following five criteria: waist circumference greater than 102 cm in men or 88 cm in women, triglyceride level
150 mg/dL or higher, high-density lipoprotein (HDL) cholesterol level
lower than 40 mg/dL in men or 50 mg/dL in women, blood pressure
130/85 mm Hg or higher, and fasting serum glucose level 110 mg/dL
or higher. The features of metabolic syndrome are largely modifiable
risk factors for CAD.
Hyperlipidemia, in particular elevated levels of low-density lipoprotein (LDL) cholesterol, plays a pivotal role in the development and
evolution of atherosclerosis. HDL-cholesterol is believed to be protective, likely due to its role in transporting cholesterol from the vessel wall
to the liver for degradation. Increased levels of HDL are inversely proportional to the risk of CAD-related problems. The interplay among
circulating lipids is complex. Elevated levels of triglycerides are a risk
factor for CAD and are frequently associated with reduced levels of
protective HDL. Hyperlipidemia is highly modifiable, and clinical trials
have shown that drug treatment directed at lowering LDL-cholesterol
significantly reduces the risk of CAD-related complications or death.
As with hyperlipidemia, hypertension contributes to the risk of
CAD-related complications. Hypertension, probably through sheer
stress, causes vessel injury that supports the development of atherosclerotic plaque. Increasing severity of hypertension is associated
with greater risk of CAD. Control of hypertension is associated with a
reduced risk of CAD. Recent guidelines advise more aggressive blood
pressure goals for patients at high risk for coronary artery disease.
Antihypertensive medications are advised for patients with a blood
pressure greater than 130/80 and diabetes, chronic kidney disease, or
an ASCVD 10-year risk of greater than 10%.
Diabetes mellitus is a prominent risk factor for CAD, and the disease is becoming epidemic. Diabetes mellitus typically is associated
with other risk factors, such as elevated triglycerides, reduced HDL, and
hypertension, which accounts for the enhanced risk of CAD-related
problems in diabetic patients. It is not clear that control of hyperglycemia in diabetic patients translates into a reduced risk of CAD, but the
presence of diabetes mellitus drives the need to ensure good treatment
77
78 SECTION II Cardiovascular Disease
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
TABLE 8.1 Risk Factors and Markers for
Coronary Artery Disease
Nonmodifiable Risk Factors
Age
Male sex
Family history of premature coronary artery disease
Modifiable Independent Risk Factors
Hyperlipidemia
Hypertension
Diabetes mellitus
Metabolic syndrome
Cigarette smoking
Obesity
Sedentary lifestyle
Heavy alcohol intake
Markers
Elevated lipoprotein(a)
Hyperhomocysteinemia
Elevated high-sensitivity C-reactive protein (hsCRP)
Coronary arterial calcification detected by EBCT or MDCT
EBCT, Electron beam computed tomography; MDCT, multidetector
of other modifiable risk factors. Although metformin remains the
first-line agent for glycemic control, the new sodium-glucose cotransporter-2 (SGLT-2) inhibitors and the glucagon-like peptide-1 (GLP-1)
receptor agonists have shown improvements in ASCVD outcomes in
patients with diabetes and established CAD.
Chronic kidney disease (CKD) is increasingly being recognized as
a unique risk factor in the development of CAD. Although not recognized as a CAD risk equivalent to diabetes, patients with CKD, particularly end-stage renal disease (ESRD) on dialysis, have dramatically
elevated risks of CAD compared to the general population. In addition, outcomes of acute coronary syndrome (ACS) in CKD patients are
worse compared to the general population.
Cigarette smoking has long been known as a significant risk factor for
both CAD and lung cancer. Cigarette smoking is associated with increased
platelet reactivity and increased risk of thrombosis, as well as lipid abnormalities. This addictive habit is modifiable, and smoking cessation can lead
to a decrease in CAD event rates by 50% in the first 2 years of cessation.
Similar to diabetes mellitus, obesity (body mass index >30 kg/m2)
is associated with risk factors such as hypertension, hyperlipidemia,
and glucose intolerance. Although multiple risk factors are frequently
present in obese people, obesity itself carries some independent risk
for CAD. The location and type of adipose tissue appear to influence
CAD risk, with abdominal obesity posing a greater risk for CAD in
men and women.
Numerous clinical studies have shown the benefit of regular aerobic
exercise in decreasing the risk for CAD-related problems, both in the
people without known CAD and in those with the disease. Sedentary
lifestyles carry an increased risk that is modifiable through exercise.
Another common attribute of life, alcohol consumption, can influence the risk of CAD in both directions. One to two ounces of alcohol
per day may reduce the risk for CAD-related events, but more than 2
ounces of alcohol per day is associated with an increased risk of events.
Lower levels of alcohol consumption can increase HDL levels, although
it is not clear that this is the mechanism of benefit. In contrast, excessive
alcohol consumption is associated with hypertension, a definite risk for
CAD, although other effects of high-dose alcohol may also be at play.
Additional factors that may have some role in adding CAD
risk include lipoprotein(a) and homocysteine. Lipoprotein(a) is
structurally similar to plasminogen and may interfere with the
activity of plasmin, thus contributing to a prothrombotic state.
Hyperhomocysteinemia has been associated with increased vascular
risks, including coronary, cerebral, and peripheral vascular disease. It
is not clear that a causal link exists, and the use of folic acid supplementation to lower homocysteine levels has not been shown to reduce
the risk of MI or stroke.
C-reactive protein (CRP) is a marker of systemic inflammation,
and it indicates an increased risk for coronary plaque rupture. Highsensitivity assays for CRP (hsCRP) have measured elevated levels that
correlate with risk for MI, stroke, peripheral vascular disease, and sudden cardiac death. Another marker for the presence of CAD is coronary calcification. The process of atherosclerosis is often associated
with deposition of calcium within the plaque.
Coronary artery calcification can be detected by fluoroscopy
during cardiac catheterization as well as by computed tomography (CT) scanning using multidetector computed tomography
(MDCT). CT technology allows for a quantitative measure of coronary calcium deposits that correlates with the probability of having
significant obstructive lesions. Advantages to this method include
low cost and relatively low radiation exposure. This technology can
be used in conjunction with ASCVD score stratification to identify
patients at elevated risk for MI. Patients in whom coronary calcification is identified should be approached with aggressive risk-factor
modification.
Historically, low-dose aspirin therapy (75-162 mg daily) has been
recommended for patients deemed “high-risk” for CAD for the prevention of CAD-related adverse events. More recently, several trials
looking at aspirin use for patients without CAD (primary prevention)
failed to find a mortality benefit. Furthermore, in patients over age
70 there was a significantly increased risk of bleeding associated with
aspirin use that outweighed any small reduction in ASCVD events.
Given these findings, the use of aspirin for patients without established CAD is no longer routinely recommended. Aspirin use in
patients with established CAD (secondary prevention) is still highly
recommended.
PATHOLOGY
The process of atherosclerosis is known to begin at a young age.
Autopsies of teenagers frequently demonstrate the presence of atherosclerotic changes in coronary arteries. Atherosclerosis is a process
linked to the subintimal accumulation of small lipoprotein particles
that are rich in LDL. Subintimal deposits of LDL are oxidized, setting
off a cascade of events that culminate in not only the development
of atherosclerotic plaque but also vascular inflammation. Vascular
inflammation drives progression of atherosclerosis as well as the
potential rupture of plaque leading to vessel occlusion. The process of
lipoprotein uptake by the vessel wall is enhanced by vascular endothelial injury, which may be triggered by hypercholesterolemia, the toxic
effects of cigarette smoking, sheer stresses associated with hypertension, or vascular effects of diabetes mellitus.
Oxidized LDL aggregates trigger the expression of endothelial cell
surface adhesion molecules, including vascular adhesion molecule-1,
intracellular adhesion molecule-1, and selectins, which results in the
binding of circulating macrophages to the endothelium. In response
to cytokines and chemokines released by endothelial and smooth
muscle cells, macrophages migrate into the subintimal region, where
they ingest oxidized LDL aggregates. These LDL-laden macrophages
are also called foam cells (based on the microscopic appearance),
CHAPTER 8 Coronary Heart Disease
79
and the accumulation of foam cells represents the development of
atherosclerosis.
Foam cells break down, releasing pro-inflammatory substances
that promote ongoing accumulation of both macrophages and T lymphocytes. This process potentiates the development of atherosclerotic
plaque. Growth factors are also released that promote smooth muscle
cell and fibroblast proliferation. The net result is the development of a
fibrous cap, which covers a lipid-rich core.
Important contributors to the pathologic evolution of atherosclerotic plaque include impaired endothelial synthesis of nitric oxide
and prostacyclin, both of which play major roles in vascular homeostasis. The loss of these vasodilators leads to abnormal regulation of
vascular tone and also plays a role in evolving a local prothrombotic
state. Platelets adhere to areas of vascular injury and are not only prothrombotic but also release growth factors that help drive the aforementioned proliferation of smooth muscle cells and fibroblasts. A key
structural constituent of the fibrous cap is collagen, and its synthesis
by fibroblasts is inhibited by cytokines elaborated by accumulating T
lymphocytes. Foam cell degradation also releases matrix metalloproteinases that break down collagen, leading to weakening of the fibrous
core and making it prone to rupture. T lymphocytes tend to accumulate at the border of plaque, which is the frequent site of plaque
rupture.
As the fibrous cap thins through collagen degradation and eventually ruptures, blood is exposed to the thrombogenic triggers of collagen
and lipid. In this setting, platelets are activated and begin to aggregate at
the site of rupture. Platelets release vasoconstrictor substances thromboxane and serotonin, but more importantly, they serve as the trigger
for thrombin formation, which leads to local thrombosis. Thrombin
accumulation along with ongoing platelet activation can lead to rapid
accumulation of thrombus in the vessel lumen. The combination of
platelet-mediated thrombus accumulation and vasoconstriction can
significantly limit blood flow, leading to myocardial ischemia. The
degree of ischemia and its duration can culminate in MI. Complete
vessel occlusion by thrombus leads to the greatest degree of myocardial
ischemia and infarction, typically resulting in an ST elevation myocardial infarction (STEMI). Incomplete vessel occlusion limits blood flow
enough to cause symptomatic myocardial ischemia and lesser degrees
of MI, resulting in the syndromes of unstable angina or non–ST segment elevation myocardial infarction (NSTEMI).
MI is the most profound consequence of atherosclerotic plaque
pathology, but significant disability can also develop when atherosclerotic plaques expand in size, leading to obstruction of blood flow
and resultant myocardial ischemia. Plaque growth, driven by smooth
muscle cell proliferation, initially causes the vessel to expand toward
the adventitia (Glagov remodeling). Once a limit of lateral expansion is reached, the enlarging plaque encroaches on the vessel lumen.
Typically, when the diameter of the lumen is decreased by at least 70%,
myocardial ischemia and symptoms of angina can develop under conditions of increasing demand for blood flow. In the case of exercise,
increases in heart rate and blood pressure lead to increasing myocardial oxygen demand; when flow-limiting atherosclerotic lesions are
present, oxygen demand may not be met by supply and myocardial
ischemia ensues. The greater the degree of vessel obstruction, the
more likely it is that myocardial ischemia and angina will occur at
low workloads, even to the point of angina at rest. Fig. 8.1 shows an
angiogram demonstrating a coronary artery obstruction before and
after angioplasty. Other forms of stress, such as emotional stress or
cold exposure, can also cause symptoms of angina in patients with significant obstructive plaque through mechanisms such as hypertension
(increased myocardial oxygen demand) or sympathetically mediated
vasoconstriction and tachycardia.
CLINICAL PRESENTATIONS OF CORONARY ARTERY
DISEASE
The clinical syndromes that patients experience due to the presence
of CAD principally relate to the occurrence of myocardial ischemia.
Myocardial ischemia develops when there is a mismatch of oxygen
delivery and oxygen demand. Given that extraction of oxygen by the
myocardium is very high, any increase in oxygen demand must be met
with an increase in coronary blood flow. Oxygen demand is directly
related to increases in heart rate, myocardial contractility, and wall
stress (which are related to blood pressure and cardiac dimensions).
There is a reflex increase in myocardial oxygen demand driven by these
factors as the heart is required to deliver more systemic blood flow in
the face of various stresses, the most common of which is increased
exertion. Coronary blood flow also depends on the vascular tone of
arterioles that are under the control of vasodilators derived from normal functioning endothelium and autonomic tone.
Coronary blood flow increases to meet an increase in myocardial
oxygen demand through endothelium-mediated vasodilation. In the
face of atherosclerosis, endothelial dysfunction may develop, resulting in reduced endothelium-mediated vasodilation. Endothelial dysfunction coupled with a flow-limiting stenosis sets the stage for the
development of myocardial ischemia. The coronary vessel distal to a
flow-limiting stenosis tends to be maximally dilated. As myocardial
oxygen demand increases, the myocardium distal to a flow-limiting
stenosis is no longer able to augment flow by additional dilation. An
overall limitation in the ability to increase coronary blood flow due to
flow-limiting stenosis and endothelial dysfunction results in supply/
demand mismatch and myocardial ischemia.
The major clinical manifestation of myocardial ischemia is chest
discomfort (angina pectoris), which is usually described as a pressure
or sensation of midsternal tightness. It may be quite pronounced in
intensity or relatively subtle. Myocardial ischemia produces not only
the sensation of angina pectoris but also a number of derangements in
myocyte function. As in any tissue, inadequate oxygen delivery leads
to a transition to anaerobic glycolysis, increased lactate production
causing cellular acidosis, and abnormal calcium homeostasis. The net
consequences of these cellular abnormalities include reductions in
myocardial contractility and relaxation. Decreased myocardial contractility results in systolic wall motion abnormalities in the area of
ischemia, and the abnormality of relaxation causes reduced ventricular compliance. These changes cause an increase in LV filling pressures above the normal range. The cellular abnormalities related to
myocardial ischemia also translate into changes in cellular electrical
activity that appear as abnormalities in the electrocardiogram (ECG).
Myocardial ischemia may result in either ST depression or ST elevation, depending on the duration, severity, and location of the ischemia.
The cellular, mechanical, and electrical abnormalities caused by ischemia typically precede the patient’s perception of angina.
Myocardial dysfunction due to ischemia may recover quickly to
normal if the duration of ischemia is brief. Prolonged myocardial
ischemia can lead to conditions of myocardial stunning or myocardial hibernation. In the case of stunning, the mechanical dysfunction induced by prolonged ischemia persists for hours or days until
function returns to normal. In the face of chronic ischemia, myocyte
viability may be maintained, but because of ischemia, mechanical dysfunction persists; in this condition, known as hibernation, restoration
of blood flow can result in recovery of myocardial function.
The heart’s conduction system is less prone to ischemic injury,
but ischemia can lead to impaired conduction. Ischemic disruption
of myocyte electrical homeostasis also sets the stage for potentially
life-threatening arrhythmias.
80 SECTION II Cardiovascular Disease
AB
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Fig. 8.1 Angiograms of the right coronary artery. (A) Discrete stenosis is observed in the middle segment
Angina Pectoris and Stable Ischemic Heart Disease
Definition
Angina pectoris is a clinical manifestation of obstructive CAD, which
in turn is usually the result of atherosclerotic plaque formation over
a number of years. The term angina pectoris refers to the symptom of
chest discomfort that may be described by the patient as a sensation
of chest tightness or burning. Of the 18,000,000 adults in the United
States with heart disease, as many as 9,400,00 have angina pectoris. It
is estimated that 785,000 people experience a new ischemic episode
annually, and recurrent events occur in at least 470,000 Americans
each year.
Pathology
As a symptom, angina pectoris is experienced when myocardial ischemia develops. Myocardial ischemia and angina pectoris may occur in
the face of obstructive atherosclerotic plaque that limits blood flow in
the face of increased demand such as exertion or emotional excitement.
Myocardial oxygen demand is directly related to increases in heart rate
and blood pressure; these variables, in turn, can be manipulated with
medical therapy to reduce the demand. Restricted oxygen supply, in
the form of reduced blood flow, can also induce myocardial ischemia.
Blood flow reduction is a prominent feature of acute presentations of
CAD such as NSTEMI and STEMI, but atherosclerosis-mediated coronary vasoconstriction, or coronary vasospasm, is also a potential cause
of flow limitation leading to myocardial ischemia. Another example of
supply limitation is anemia, whereby reduced oxygen-carrying capacity coupled with obstructive lesions leads to myocardial ischemia and
symptoms of angina pectoris. The term stable angina pectoris refers
to myocardial ischemia caused by either plaque-mediated flow limitation in the face of excess demand or supply limitation due to coronary
vasospasm.
Clinical Presentation
Angina pectoris may manifest in either stable or unstable patterns
(Table 8.2), but the symptom expression is similar. Typically, patients
complain of retrosternal discomfort that they may describe as pressure,
tightness, or heaviness. The symptom can be subtle in its presentation,
and inquiry as to the presence of “chest pain” may lead to a negative
response in a patient experiencing angina pectoris. When taking a history aimed at discerning angina pectoris, one needs to seek answers
to these more nuanced descriptions of symptoms. In addition to
chest discomfort, patients may have associated discomfort in the arm,
throat, back, or jaw. They also may experience dyspnea, diaphoresis, or
nausea associated with angina pectoris.
There is a good deal of variability in the expression of symptoms
related to myocardial ischemia, although each person tends to have
a unique signature of symptoms. Some have no chest discomfort but
only radiated arm, throat, or back symptoms; dyspnea; or abdominal
discomfort. Myocardial ischemia can also manifest in a “silent” form,
particularly in the elderly and in patients with long-standing diabetes
mellitus. The duration of angina pectoris varies, probably depending
on the magnitude of the underlying myocardial ischemia. Exertionrelated angina pectoris, the hallmark of stable obstructive CAD, typically resolves with rest or with decreased intensity of exercise. In stable
angina pectoris, the duration of events is usually in the range of 1 to 3
minutes. Prolonged symptoms in the 20- to 30-minute range are indicative of a more serious problem such as NSTEMI or STEMI.
The physical examination of patients with CAD is typically normal. However, if the patient is physically examined during an episode
of myocardial ischemia, either at rest or after exertion, significant
changes may be present. As with any form of discomfort, there may
be a reflex increase in heart rate and blood pressure. Elevated heart
rate and blood pressure may act to sustain the duration of angina
by increasing myocardial oxygen demand in the face of supply-limiting coronary stenosis. Acute mitral regurgitation can develop if the
distribution of myocardial ischemia includes a papillary muscle, the
supporting structure of the mitral valve. The physical examination in
such cases would demonstrate a new systolic murmur consistent with
mitral regurgitation. If severe enough in degree, this mitral regurgitation will cause decreased LV compliance and, consequently, an
acute elevation in left atrial and pulmonary vein pressure leading to
pulmonary congestion. In this setting, the patient will have not only
CHAPTER 8 Coronary Heart Disease
TABLE 8.2 Angina Pectoris
Type Pattern ECG Abnormality Medical Therapy
Stable Stable pattern, induced by physical exertion,
exposure to cold, eating, emotional stress
Lasts 5-10 min
Relieved by rest or nitroglycerin
Unstable Increase in anginal frequency, severity, or
duration
Angina of new onset or now occurring at
low level of activity or at rest
May be less responsive to sublingual
nitroglycerin
Prinzmetal or
variant angina
AV, Atrioventricular; ECG, electrocardiography; LMWH, low-molecular-weight heparin; MI, myocardial infarction.
Angina without provocation, typically
occurring at rest
Baseline often normal or non-
specific ST-T changes
Signs of previous MI
ST-segment depression during
angina
Same as stable angina,
although changes during
discomfort may be more
pronounced
Occasional ST-segment eleva-
tion during discomfort
Transient ST-segment elevation
during pain
Often with associated AV block
or ventricular arrhythmias
≥70% Luminal narrowing of
one or more coronary arteries
from atherosclerosis
Plaque rupture with plate-
let and fibrin thrombus,
causing worsening coronary
obstruction
Coronary artery spasm Calcium-channel blockers
Aspirin
Sublingual nitroglycerin
Anti-ischemic medications
Statin
Aspirin and clopidogrel
Anti-ischemic medications
Heparin or LMWH
Glycoprotein IIb/IIIa inhibitors
Nitrates
81
the symptom of angina pectoris but also the symptom of dyspnea and
the physical finding of rales. Ischemia-induced increases in LV filling
pressure due to diminished compliance also can occur independently
of ischemia-induced mitral regurgitation. Decreased LV compliance
can produce the abnormal heart sound S4; in the case of severe diffuse
myocardial ischemia causing LV systolic dysfunction, an S3 may also
be perceived. Resolution of myocardial ischemia results in not only a
cessation of angina pectoris but also a return to the patient’s baseline
physical examination status.
Diagnosis and Differential Diagnosis
Three basic forms of testing have played major roles in assessing
patients with chest discomfort possibly due to CAD. All of these tests
capitalize on the effect of myocardial ischemia on various aspects of
cardiac physiology. First, myocardial ischemia induced by exercise or
by spontaneous coronary occlusion results in subendocardial ischemia, which appears on an ECG as diffuse ST depression (Fig. 8.2).
Once ischemia resolves, the ECG returns to normal. Second, myocardial ischemia typically affects a segment of heart muscle, and that
territory develops a wall motion abnormality that can be detected by
either echocardiography or nuclear scintigraphy. Third, the basis for
myocardial ischemia is a decrease in coronary and myocardial blood
flow. This abnormality can be detected by assessing the distribution of
radioactive tracers such as thallium 201 or technetium sestamibi using
specialized detectors for imaging myocardial perfusion. All stress test
techniques used in diagnosing patients with possible CAD rely on these
means of detecting the impact of myocardial ischemia on cardiac electrical activity, mechanical function, or myocardial perfusion.
Stress testing in its various forms frequently plays a pivotal role in
the assessment of patients with possible CAD. In using stress testing, it
is important to understand the significance of pretest probability of CAD
in interpreting the results of any stress test method. For a patient with
a high pretest probability of CAD, a positive test is highly predictive of
underlying CAD, and a negative test carries the weight of being falsely
negative. The opposite is true in a patient with a low pretest probability of
CAD: A negative test is associated with a high negative predicative value
for the presence of CAD, but a positive test is likely to be falsely positive.
Stress testing is useful not only as a diagnostic tool but also in
the long-term management of established CAD. Exercise stress testing, through its ability to quantify exercise capacity, can monitor the
effectiveness of medical therapy directed at reducing myocardial ischemia. The findings of an exercise stress test also have predictive value
in that patients with ischemia induced at low workloads are more likely
to have extensive multivessel disease, whereas those who achieve high
workloads are less prone to ischemic complications of CAD. A higher
risk for poor outcomes related to CAD is implied by (1) ECG changes
of ST depression early during exercise and persisting late into recovery;
(2) exercise-induced reduction in systolic blood pressure; and (3) poor
exercise tolerance (<6 minutes on the Bruce stress test protocol).
Patients with a normal resting ECG can reliably be assessed by standard exercise stress testing with ECG monitoring (Fig. 8.3). The specificity of ST changes with exertion is significantly reduced in the face
of baseline ECG abnormalities related to LV hypertrophy, left bundle
branch block (LBBB), preexcitation, or use of digoxin. Various imaging techniques (echocardiography, nuclear scintigraphy, magnetic
resonance imaging) have been developed to overcome the impact of
baseline ECG abnormalities on the validity of stress testing. Because
women also have lower specificity for ECG changes during exercise
testing than men, an imaging technique is frequently used in the
assessment of women. Overall, the addition of an imaging technique
to stress testing significantly improves the sensitivity, specificity, and
predictive value of the stress test but also greatly increases its cost.
Radionuclide stress testing is a common form of imaging-based
stress test. Near peak exertion, a radionuclide tracer (thallium-201,
technetium-99, or tetrofosmin) is administered intravenously. The
tracer is distributed to the myocardium in a quantity directly proportional to blood flow. This type of image testing relies on a disparity of
tracer uptake to detect an area of ischemia. Thallium-201 redistributes over 4 hours to viable myocardium, allowing for comparison of
stress-induced ischemia to a baseline state. The other tracers do not
share this redistribution feature, and tests using technetium-99 or
tetrofosmin require both “rest” and “stress” injections of tracer to
differentiate ischemic myocardium. Patients with normal perfusion
studies have a low risk of coronary events (<1%/year). The presence
of a positive perfusion study confers a risk of about 7%/year for coronary events, with the risk increasing relative to the extent of perfusion
abnormality.
An alternative means of imaging for exercise testing is the use of
echocardiography to detect ischemia-induced wall motion abnormalities. This form of testing is increasingly favored because there is no
82 SECTION II Cardiovascular Disease
Boston University Hospital 1 MAR 1999
B
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
I
II
III
aVR
aVL
aVF
V1
V2
V3
V4
V5
V6
A
I
aVR
V1
V4
II
III
Fig. 8.2 Electrocardiogram obtained during angina (A) and after the administration of sublingual nitroglycerin
aVL
aVF
radiation associated with its use, whereas radionuclide tracers expose
the patient to a significant dose of radiation. Stress echocardiography
carries with it the same enhancement in sensitivity, specificity, and predictive value as radionuclide imaging. An additional benefit of echocardiography imaging is more discrete anatomic data on valve function. If
it is coupled with Doppler flow imaging, information regarding exercise-induced mitral regurgitation can be obtained.
Another means of assessing for exercise-induced wall motion
abnormalities is the use of radionuclide ventriculography or multigated acquisition scanning (MUGA). This technique is usually
included as part of the interpretation of an exercise stress radionuclide
V2
V3
V5
V6
study. This imaging technique does not provide the anatomic detail
associated with echocardiography, and it has the negative feature of
significant radiation exposure.
An additional imaging technique for stress testing is the use of magnetic resonance imaging. Radiation is not a concern, and cardiac structural imaging can match echocardiography (or exceed it in patients
with poor images on echocardiography). The technique is not as easy
to execute as echocardiography and is not as frequently utilized.
Not all patients who require noninvasive testing for CAD are able
to exercise to a degree sufficient to induce ischemia, and for some
patients exercise testing is not an option at all. For these patients,
Соседние файлы в папке Библиотека им академика М.И. Перельмана