Cardiology: Calcific Aortic Stenosis Quiz

Valvular Heart Diseases

• Valvular disease can be stenosis, insufficiency, or both.
• Sudden valvular disease can be caused by infection.
• Chronic rheumatic mitral stenosis develops over years.
• The failure of a valve to fully open obstructs blood flow.
• Acquired valvular stenosis is chronic.
• Valvular insufficiency occurs when the valve doesn't fully close, leading to backflow.
• Valvular insufficiency can be caused by intrinsic valve leaflet disease or disruption of supporting structures.
• Insufficiency can appear abruptly or insidiously
• The most common valvular abnormality is calcific aortic stenosis.
• Aortic stenosis is the calcification and sclerosis of normal or congenitally bicuspid aortic valves.
• Aortic insufficiency is often due to ascending aorta dilation, related to hypertension and aging.
• Rheumatic heart disease (RHD) is a cause of mitral stenosis.
• Myxomatous degeneration can cause mitral insufficiency.
• Left ventricular dilation can be a cause of mitral insufficiency.
• Ischemic or nonischemic heart failure can result in mitral insufficiency.

Etiology of Acquired Heart Valve Disease

• Mitral Valve Disease:
  • Mitral Stenosis: postinflammatory scarring, typically from rheumatic heart disease.
  • Mitral Insufficiency: abnormalities of leaflets, commissures, postinflammatory scarring, infective endocarditis, mitral valve prolapse, and "Fen-phen".
• Aortic Valve Disease:
  • Aortic Stenosis: postinflammatory scarring (rheumatic heart disease), senile calcific aortic stenosis, calcification.
  • Aortic insufficiency: intrinsic valvular disease, postinflammatory scarring, infective endocarditis, Aortic disease, degenerative aortic dilation, syphilitic aortitis, ankylosing spondylitis, rheumatoid arthritis, Marfan syndrome.

Calcific Aortic Stenosis

• The most common valvular abnormality, with prevalence of 2%.
• Common in the 7th to 9th decades
• In bicuspid valves, stenosis can appear much earlier (1-20 decades earlier).
• Bicuspid valves have more mechanical stress than normal valves.
• A common finding associated with bicuspid valves is dilation of the proximal ascending aorta.
• Age related wear and tear/ recurrent chronic injury (atherosclerosis, hyperlipidemia, and hypertension
• The abnormal valve cells resemble osteoblasts (synthesize bone matrix proteins) that promote calcium salt deposition.
• Statins or other measures do not prevent calcific degeneration of the valves.
• Calcified masses are on the outflow surfaces of the cusps.
• The layered valve architecture is preserved.
• Inflammation is variable, but metaplastic bone is often present.

Semilunar Valves

• Semilunar valves (aortic and pulmonary valves) have three layers: fibrosa, spongiosa, and ventricularis.

Calcific Aortic Stenosis, Morphology

• Calcium masses accumulate within the sinuses of Valsalva.
• Commissures aren't fused, unlike in post-rheumatic aortic stenosis.

Mitral Annular Calcification

• Calcification forms in the fibrous annulus.
• The calcification appears as irregular, hard nodules.
• The nodules are typically at the base of the leaflets.

Mitral Annular Calcification, Secondary Changes

• Fibrous thickening of leaflets, particularly where they rub against one another.
• Linear thickening on the LV endocardium, where abnormally long cords rub against the endocardium.
• Thickening of the LV mural endocardium or LA as a result of friction injury from prolapsing leaflets.
• Thrombi on atrial surfaces of leaflets or atrial walls.
• Focal calcification at the posterior mitral leaflet base.

Myxomatous Degeneration of the Mitral Valve

• Mitral valve leaflets are "floppy" and protrude into the atrium during systole.
• The afflicted leaflets are frequently enlarged, redundant, thick, and rubbery.
• The tendinous cords might be elongated, thinned, or ruptured.
• The annulus might be dilated.

Mitral Valve Prolapse, Pathogenesis

• Typically unknown but may be associated with heritable connective tissue disorders and Marfan syndrome

Mitral Valve Prolapse, Morphology

• The characteristic change in MVP is hooding of the mitral leaflets.
• The affected leaflets tend to be enlarged, redundant, thick, and rubbery
• The related chordae tendineae may be elongated, thinned, or ruptured.
• The annulus may be dilated.

Mitral Valve Prolapse, Histology

• The key histologic change is marked myxomatous degeneration of the spongiosa layer.
• Collagenous fibrosa layer attenuates, affecting structural integrity

Mitral Valve Prolapse, Secondary changes

• Fibrous thickening of the valve leaflets as they rub against one another.
• Linear fibrous thickening along the LV endocardium where abnormally long cords rub against it.
• Thickening of the LV or LA mural endocardium, caused by friction-induced injury from prolapsing leaflets.
• Thrombi on the atrial surfaces of the leaflets or walls.
• Focal calcification at the base of the posterior mitral leaflet.

Rheumatic Fever and Rheumatic Heart Disease

• Rheumatic fever is an acute, immunologically mediated, multisystem inflammatory disease that typically follows group A streptococcal pharyngitis.
• Active Rheumatic fever is often accompanied by a few weeks of group A streptococcal infections in other sites , like the skin
• Acute rheumatic carditis manifests prominently, frequently progressing into chronic rheumatic heart disease (RHD)

Rheumatic Heart Disease (RHD)

• Characterized by deforming fibrotic valvular disease, especially the mitral valve.
• The only known cause of mitral stenosis
• A significant public health problem in low-income countries.

Acute Rheumatic Fever, Pathogenesis

• Cause: host immune responses to group A streptococcal antigens that cross-react with host proteins.
• A 2- to 3-week delay in symptoms is common, reflecting the time for an immune response.
• Heart tissue damage is due to a combination of antibody- and T-cell-mediated reactions.
• Streptococci are absent in the lesions.

Acute Rheumatic Fever, Morphology

• During acute RF, focal inflammation is seen in various tissues.
• Distinctive lesions in the heart (Aschoff bodies) are comprised of T lymphocytes, occasional plasma cells, and plump activated macrophages (Anitschkow cells).
• Macrophages exhibit abundant cytoplasm and central nuclei with chromatin condensed into a centrally located slender wavy ribbon. These are referred to as "caterpillar cells"
• Inflammation is widespread throughout the heart layers.
• Necrotic foci and small vegetations (verrucae) are present along lines of closure.
• Subendocardial lesions may develop, often exacerbated by regurgitant jets.
• Thickened areas are known as MacCallum plaques.

RHD Morphology

• Chronic RHD is characterized by thickened mitral leaflets, commissural fusion, and shortening.
• The mitral valve is always involved in chronic RHD, sometimes in isolation in about two-thirds of cases.
• Mitral valves are more commonly affected, often in conjunction with the aortic valve about 25% of the time.
• Tricuspid valve involvement is less frequent.

RHD, Micro

• Valves show acute inflammatory organization, neovascularization and transmural fibrosis.
• Aschoff bodies are seldom identified in tissue specimen from patients with chronic RHD, due to the interval between the initial insult and deformities.

RHD, Morphology of acute mitral valvulitis

• Acute rheumatic mitral valvulitis superimposed upon chronic rheumatic heart disease.
• Small vegetations (verrucae) are visible along the line of closure of the mitral valve leaflet.

Acute Rheumatic Carditis, Micro

• Myocardium exhibits a circumscribed nodule of mixed mononuclear inflammatory cells with associated necrosis
• Large activated macrophages have prominent nucleoli, and chromatin condensed into long, wavy ribbons (caterpillar cells).

RHD, Morphology of mitral stenosis/thickning

• Mitral stenosis shows diffuse thickening and distortion of the mitral valve leaflets and commissural fusion
• Chordae tendineae thickening.

Rheumatic Aortic Stenosis

• Surgical specimens show thickening and distortion of the cusps, as well as commissural fusion.

Rheumatic Fever, Clinical Features

• Migratory polyarthritis of large joints
• Subcutaneous nodules (typically on extensor surfaces of extremities)
• Erythema marginatum (occurs in 5% of patients), the skin manifestation.
• Sydenham chorea (neurologic disorder, characterized by involuntary movements)

Rheumatic Fever, Diagnosis

• Evidence of preceding group A streptococcal infection, and two or more of the following :
  • Two major manifestations or a combination of one major and two minor manifestations.
• Criteria for minor manifestations are less specific and include fever, arthralgia, elevated acute-phase reactants.

Rheumatic Fever, Diagnosis (Acute RF)

• Acute RF typically appears 10 days-6 weeks after group A streptococcal infection about 3% of patients and predominantly affects 5-15 year olds.
• Pharyngeal cultures are typically negative by the time the illness begins, but antibodies to streptococcal enzymes (e.g., streptolysin O, Dnase B).
• Predominant clinical symptoms are often carditis and arthritis in both adults and children, though arthritis is more commonly found in adults.
• Polyarthritis, accompanied by fever, is common; one joint after another becomes painful and swollen, and subsides spontaneously without residual disability.

Rheumatic Fever, Diagnosis (Clinical Features of Acute Carditis)

• Clinical features related to acute carditis include pericardial friction rubs, tachycardia, and arrhythmias.
• Myocarditis can cause cardiac dilation, leading to functional mitral valve insufficiency.
• 1% of those affected die from fulminant cardiac involvement.

Rheumatic Fever, Diagnosis (Clinical Features)

• Cardiac murmurs
• Cardiac hypertrophy
• Cardiac dilation,
• Heart failure
• Arrhythmias (particularly atrial fibrillation associated with mitral stenosis)
• Thromboembolic complications

RHD, Prognosis & Treatment

• RHD outcomes are variable.
• Surgical valve repair or replacement greatly improves survival outlook

Infective Endocarditis (IE)

• Microbial infection of the heart valves or mural endocardium, leading to vegetation formation.
• Vegetations are comprised of thrombotic debris and microorganisms, often causing underlying cardiac tissue destruction.
• Prompt diagnosis, pathogen identification, and effective treatment are critical.

Infective Endocarditis, Classic Classification

• Acute IE, caused by highly virulent organisms like S. aureus, rapidly produces destructive lesions and is often difficult to treat with antibiotics alone
• Subacute IE, caused by less virulent organisms like viridans streptococci, is characterized by insidious infections of deformed valves with less destruction.

Infective Endocarditis, Pathogenesis

• RHD, MVP, degenerative calcific valvular stenosis, bicuspid aortic valves (or not), artificial heart valves and congenital cardiac defects increase risk of IE.
• Common pathogens for IE include Streptococcus viridans (normal oral flora), Staphylococcus aureus (often associated with IV drug users), enterococci, HACEK group ((Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella).
• In 10% of IE cases, no organism is isolated, often due to prior antibiotic therapy, difficulties isolating the agent, and organisms being deeply embedded in the vegetation.

Infective Endocarditis, Pathogenesis (Source of bacteremia/fungemia).

• Infections elsewhere.
• Dental or surgical procedure.
• Contaminated IV drug needles and usage
• Breaks in epithelial barriers ( gut, oral cavity, skin).
• Patients with valvular abnormalities or ongoing bacteremia may benefit from antibiotic prophylaxis.

Infective Endocarditis, Morphology

• Vegetations on heart valves are often friable, bulky, potentially destructive, and contain fibrin, inflammatory cells, and bacteria.
• Aortic and mitral valves are most frequently involved, but valve involvement of the right side of the heart is particularly frequent in intravenous drug abusers.
• Vegetations can be single or multiple, may involve more than 1 valve, and can erode into the underlying myocardium forming abscesses (abscess rings)
• Vegetations can cause embolization, leading to septic infarcts or mycotic aneurysms.

Infective Endocarditis, Morphology (Subacute IE)

• Subacute IE vegetations have less valvular destruction compared to acute IE; this distinction is often subtle microscopically.
• Granulation tissue is often present in the bases of the vegetations, indicative of healing.
• Fibrosis, calcification, and a chronic inflammatory infiltrate may occur with time

Infective Endocarditis. Clinical Features

• Acute IE is rapid onset with fever, chills, weakness, and lassitude.
• Fever can be mild or absent, while manifestations may include nonspecific fatigue, weight loss, and flu-like symptoms in older adults.
• Many patients with left-sided IE present with a murmur.

Modified Duke criteria for Infective Endocarditis

• Diagnosis utilizing either clinical or pathological criteria. Clinically, 2 major criteria, 1 major + 3 minor or 5 minor criteria are needed for definitive IE diagnosis
• Possible IE is defined as 1 major criterion + 1 minor criterion or 3 minor criteria

Nonbacterial Thrombotic Endocarditis (NBTE)

• Deposition of sterile thrombi on the leaflets of the cardiac valves.
• Histologically, these thrombi are bland, nondestructive, and loosely attached to the valve; no inflammatory reaction is evident.
• Thrombi can be a source for systemic embolization leading to infarction of the brain, heart, or other tissues.
• NBTE is often found in debilitated patients with conditions like sepsis, cancer, hypercoagulability (chronic disseminated intravascular coagulation, hyperestrogenic states, and malignancy), or conditions like an indwelling catheter.

Endocarditis of Systemic Lupus Erythematosus (Libman-Sacks Disease)

• Small (1-4 mm) sterile vegetations, typically seen in the context of SLE & antiphospholipid syndrome.
• Immune complex deposition that involves activation of complement and recruitment of Fc-receptor cells cause damage
• These vegetations might occur anywhere on the valve leaflets, chordae or endocardium (atrial or ventricular)
• Ultimately valvular scarring and leaflet fusion result from persistent injury.