10. Arterosclerose and the Heart

Question 1

Hypertension

Answer 1

• common disorder affecting 25% of the population; it is a risk for atherosclerosis, congestive heart failure, and renal failure.
• may be primary (idiopathic) or less commonly secondary to an indentifiable underlying condition. In 95% of cases it is idiopathic or “essential”. The remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing (renovascular hypertension), or adrenal disorders.
• Essential hypertension represents 95% of cases and is a complex, multifactorial disorder, involving environmental influences and genetic polymorphisms that influence sodium resorption, aldosterone pathways, the adrenergic nervous system, and the renin-angiotensin system.
• occasionally is caused by single-gene disorders or is secondary to diseases of the renal arteries, kidneys, adrenal glands, or other endocrine organs.

Question 2

Atherosclerosis

Answer 2

• Atherosclerosis is an intima-based lesion composed of a fibrous cap and an atheromatous (literally, “gruel-like”) core; the constituents of the plaque include SMCs, ECM, inflammatory cells, lipids, and necrotic debris.
• Atherogenesis is driven by an interplay of vessel wall injury and inflammation. The multiple risk factors for atherosclerosis all cause EC dysfunction and influence SMC recruitment and stimulation.
• Major modifiable risk factors for atherosclerosis are hypercholesterolemia, hypertension, cigarette smoking, and diabetes mellitus.
• Atherosclerotic plaques develop and grow slowly over decades. Stable plaques can produce symptoms related to chronic ischemia by narrowing vessels, whereas unstable plaques can cause dramatic and potentially fatal ischemic complications related to acute plaque rupture, thrombosis, or embolization.
• Stable plaques tend to have a dense fibrous cap, minimal lipid accumulation, and little inflammation, whereas “vulnerable” unstable plaques have thin caps, large lipid cores, and relatively dense inflammatory infiltrates.

Question 3

Congenital Heart Disease

Answer 3

• represents defects of cardiac chambers or the great vessels; these either result in shunting of blood between the right- and left-sided circulation or cause outflow obstructions. Lesions range from relatively asymptomatic to rapidly fatal. Environmental and genetic causes.
• Malformations associated with left-to-right shunts are the most common and include ASDs, VSDs, and PDA. Shunting results in right-sided volume overload that eventually causes pulmonary hypertenstion and, with reversal of flow and right-to-left shunting, cyanosis (Eisenmenger syndrome).
• Malformations associated with Right-to-left shunts include tetralogy of Fallot and transposition of hte great arteries. These lesions cause early-onset cyanosis and are associated with polycythemia, hypertrophic osteoarthropathy, and paradoxical embolization.
• Obstructive lesions include forms of aortic coarctation; the clinical severity of these lesions depends on the degree of stenosis and the patency of the ductus arteriosus.

Question 4

Ischemic Heart Disease

Answer 4

• In the vast majority of cases, cardiac ischemia is due to coronary artery atherosclerosis; vasospasm, vasculitis, and embolism are less common causes.
• Myocardial ischemia leads to loss of myocyte function within 1 to 2 minutes but causes death after only 30 to 40 minutes. Myocardial infarction is diagnosed on the basis of symptoms, electrocardiographic changes, and measurements of serum biomarkers such as cardiac-specific troponins. Gross and histologic changes of infarction require hors to days to develop.
• Infarction can be modified by therapeutic intervention (e.g., thrombolysis or stenting), which salvages myocardium at risk but may also induce reperfusion-related injury.
• Complications of infarction include ventricular rupture, papillary muscle rupture, aneurysm formation, mural thrombus, arrhythmia, pericarditis, and CHF.

Question 5

Cardiac ischemia results from a mismatch between coronary supply and myocardial demand and manifests as different, albeit overlapping syndromes:

Answer 5

• Angina pectoris is exertional chest pain due to inadequate perfusion, and is typically due to atherosclerotic disease causing greater than 70% fixed stenosis (so-called “critical stenosis”)
• Unstable angina is characterized by increasingly frequent pain, precipitated by progressively less exertion or even occurring at rest. It results from an erosion or rupture of atherosclerotic plaque triggering platelet aggregation, vasoconstriction, and formation of a mural thrombus that need not necessarily be occlusive.
• Acute myocardial infaction typically results from acute thrombosis after plaque disruption; a majority occur in plaques that did not previously exhibit critical stenosis.
• Sudden cardiac death usually results from a fatal arrhythmia, typically without significant acute myocardial damage.
• Ischemic cardiomyopathy is progressive heart failure due to ischemic injury, either from previous infarction(s) or chronic ischemia.

Question 6

Hypertensive Heart Disease

Answer 6

• can affect either the left ventricle or the right ventricle; in the latter case, due to primary pulmonary disease (cor pulmonale). Elevated pressures induce myocyte hypertrophy and interstitial fibrosis that increases wall thickness and stiffness.
• The chronic pressure overload of systemic hypertension causes left ventricular concentric hypertrophy, often associated with left atrial dilation due to impaired diastolic filling of the ventricle. Persistently elevated pressure overload can cause ventricular failure with dilation.
• Cor pulmonale results from pulmonary hypertenstion due to primary lung parenchymal or vascular disorders. Hypertrophy the right ventricle and atrium is characteristic; dilation also may be seen when failure supervenes.

Question 7

Valvular Heart Disease

Answer 7

• Valve pathology can lead to occlusion (stenosis) and/or regurgitation (insufficiency); acquired aortic or mitral valve stenosis accounts for approximately two thirds of all valve disease.
• Valve calcification typically results in stenosis; abnormal matrix synthesis and turnover leads to myxomatous degeneration and insufficiency.
• Inflammatory valve diseases cause postinflammatory neovascularization and sccarring. Rheumatic heart disease results from anti-streptococcal antibodies that cross-react with cardiac tissues; it most commonly affects the mitral valve and is responsible for almost all cases of acquired mitral stenosis.
• Infective endocarditis can rapidly destroy normal valves, or can be indolent and minimally destructive of previously abnormal valves. Systemic embolization can produce sceptic infarcts.
• Nonbacterial thrombotic endocarditis occurs on previously normal valves as a result of hypercoagulable states; embolization is an important complication.

Question 8

Cardiomyopathies and myocarditis

Answer 8

• Cardiomyopathy refers to intrinsic cardiac muscle disease; there may be specific causes, or it may be idiopathic.
• The three general pathophysiologic categories of cardiomyopathy are dilated (accounting for 90% of the causes), hypertrophic, and restrictive (least common).
• DCM results in systolic (contractile) dysfunction. Causes include myocarditis, toxic exposures (e.g., alcohol), and pregnancy. In 20% to 50% of cases, mutations affecting cytoskeletal proteins are responsible.
• HCM results in diastolic (relaxation) dysfunction. Virtually all cases are due to autosomal dominant mutations in the proteins that make up the contractile apparatus, in particular B-myosin heavy chain.
• Restrictive cardiomyopathy results in a stiff, noncompliant myocardium and can be due to depositions (e.g., amyloid), increased interstitial fibrosis (e.g., due to radiation), or endomyocardial scarring.
• Arrhythmogenic right ventricular cardiomyopathy is an autosomal dominant disorder of cardiac muscle that manifests with right-sided heart failure and rhythm disturbances that can cause sudden cardiac death in athletes.
• Myocarditis is an inflammatory disorder caused by infections or immune reactions. Coxsackieviruses A and B are the most common pathogens in the United States. Clinically, myocarditis may be asymptomatic, give rise to acute heart failure, or evolve to DCM.