CARDIOVASCULAR PATHOLOGY 3

HYPERTROPHY

HYPERTENSIVE HEART DISEASE

common cause of secondary ventricular hypertrophy

a long-term condition that develops over many years in people who have high blood pressure

hypertension leads to remodelling of the heart shape, in particular of the left ventricle

types of LV hypertropy

concentric

  • due to pressure overload
  • hyperfunction of isometric tyoe due to an increase in downstream resistance
  • new sarcomeres are formed in parallel

eccentric

  • due to volume overload
  • hyperfunction of isotonic type with increased residual volume
  • new sarcomeres are formed in series

other causes are:

  • diabetes
  • obesity
  • congenital heart disease
  • drug consumption

factors influencing LV geometry

  1. severity, duration
  2. volume load
  3. age
  4. race/ethnicity
  5. sex
  6. comorbidities
  7. genetic factors

complications

  • infarction (starting from the endocardium)
  • blood clots forming in the lumen and fibrillations
  • heart failure

also the RV can be involved

due to increased pulmonary circulation resistance or obstacles to the outflow

caused by

  • diseases of pulmonary parenchyma
  • diseases of pulmonary vessels
  • disorders affecting chest movement
  • disorders inducing pulmonary arterial constriction

complications

  • chronic pulmonary heart, e.g. cystic fibrosis, extensive emphysema --> pulmonary hypertension
  • acute pulmonary heart, due to thromboembolic events in the pulmonary arteries

triangular infarction is observed in the case small emboli manage to pass these vessels

MYOCARDIAL NON-ISCHEMIC DISEASES

cardiomyopathies

classification

MOGES classification

  • Multi-functional phenotype
  • Organ involved
  • Genetic inheritance
  • Etiological derivation
  • functional Status

pathological classification

primary

  • only involve the myocardium
  • acquired, genetic or mixed

secondary

  • other organs can be involved
  • autoimmune or secondary to endocrine pathology, e.g. diabetes mellitus, infiltrative diseases, neuromuscular storage disorders, nutritional deficiencies and toxic alcohol CT

MYOCARDITIS

  • one of the main causes of sudden cardiac death
  • pathological pattern: inflammation + necrosis
  • quite frequent and indolent
  • likely to cause DILATED CARDIOMYOPATHY
  • gold standard for diagnosis: biopsy of myocardium

very heterogeneous in clinical presentation
on the basis of the first cause of myocarditis

Dallas criteria on myocardial biopsy:

  1. inflammation
  2. necrosis of myocytes

in a biopsy, remember to look for:

  1. weight (generally, the heart is heavier)
  2. flabby heart (viral infections)
  3. abscesses (bacterial infection)
  4. sclerosis (sign of infection healing)

when evaluating the histology

look for signs of necrosis, phlogosis
and inflammatory cells

  • viral infections --> lymphocytes (roundish nucleus)
  • bacterial infections --> granulocytes (lobulated nucleus)
  • hypersensitivity --> eosinophils, perivascular interstitial inflammatory infiltrates, sometimes heterogeneous
  • sarcoidosis --> non-necrotizing granulomas with giant cells, epithelioid cells, fibroblasts
  • parasites --> eosinophils

VIRAL MYOCARDITIS

at autopsy, FLABBY HEART

one of the most common causes of unexpected sudden cardiac death (developing into dilated cardiomyopaty if the patient survives)

no specific histologic alterations, thus we should rely on IHC, PCR molecular analysis and immunophenotyping of lymphocytes by using CD3 for T cells, CD20 for B cells and CD68 for macrophages

acute myocarditis

if it evolves towards healing, there may be a scar causing myocardial sclerosis and some CD3+ lymphocytes may be present in the scar

commonly associated with COVID19 infection

BACTERIAL MYOCARDITIS

autopsies show yellow and soft areas (abscesses), concentric hypertrophy of the left side of myocardium

at microscopy, abscesses are observed and they are full of granulocytes, myocardial cells are fragmented and lots of macrophages try to clean the area

TRYPANOSOMA MYOCARDITIS

  • uncommon
  • associated with acute or chronic forms
  • in chronic form, there is the presence of branch blocks, death from arrhythmias and decompensation due to dilated cardiomyopathy
  • trypanosoma can be identified at the microscopic level

GIANT CELL MYOCARDITIS

  • unknown etiology
  • affecting cells with several nuclei
  • associated with tumors like thymoma, AID, ventricular tachycardia
  • not benign, as it may progress to fibrosis

TAKOSUBO STRESS-INDUCED MYOCARDITIS

  • it simulates octopus fishing trap
  • aka broken heart syndrome
  • defined by temporary and reversible systolic abnormality of LV in the apical area resembling MI
  • coronary arteries are not affected
  • MRI can be used to diagnose dilated CMP
  • in women, emotional and physical stress can cause it

primary cardiomyopathies

ARRHYTHMOGENIC RV DYSPLASIA

  • adult prevalence 1:2000-5000
  • one of the most important cause of sudden cardiac death in young people
  • genetic form (adhesion molecules alteration)
  • deletion and thinning of the RV since muscle is substituted by adipose tissue
  • at biopsy: yellow areas and thinning of the remaining myocardium and papillary muscles

symptoms

  • fainting
  • heart palpitations
  • dizziness
  • shortness of breath
  • fatigue
  • legs swelling
  • persistent cough
  • sudden death

major criteria of diagnosis (biopsy)

  1. extensive fibrofatty tissue replacement
  2. with myocardial atrophy (residual myocytes, 60% by morphometric analysis or 50% if estimated)

3 samples must be taken from different regions of the RV free wall

HYPERTROPHIC

  • genetic, autosomal alteration
  • prevalence 1:5000
  • symptoms: shortness of breath, chest pain, changes in heart electrical system, arrhythmia and sudden cardiac death
  • hypercontractility associated with altered systolic and diastolic activity
  • diagnosis: echocardiography showing a small heart cavity with hypertrophy of the walls
  • at biopsy: hypertrophy of muscle which is not regular as cells acquire a Y shape (+fibrosis)

a LV hypertrophy which is not secondary to other physiological causes like hypertension

heart weight is >500 g, interventricular septum is >4 cm, asymmetrical hypertrophy involving the anteroseptal part

RV maybe compressed, looking like a banana

three different types defined on the basis of the area interventricular septum more severely affected by hypertrophy

  1. basal type
  2. mid-ventricular type
  3. apical type

the mitral valve may get thicker, continuously protruding towards the septum; fibrosis of the subendocardium affected by continuous contact with hypertrophic valve

mitral valve lesion may cause reflux, causing an increase in the LA size, eventually leading to atrial fibrillation (--> flogosis of the auricles)

consequences

  • atrial fibrillation
  • ischemia, fibrosis
  • secondary dilation
  • fainting
  • sudden cardiac death

in the case od end-stage failur, heart transplantation is an option

LV COMPACTION

  • spongy form involving the apex of the LV
  • arrest of the normal embryological development
  • association with systolic dysfunction and sudden death
  • typical and non typical

DILATED

  • no signs or symptoms in the early stage of the disease
  • prevalence 1:2500
  • linked to peripartum pregnancy and association with a genetic background occurring after pregnancy
  • systolic dysfunction, reduced LV ejection fraction, enlarged LV
  • only therapy: hear transplantation

primary dilated CMP

associated with genetic forms (specific mutations of proteins involved in proper functionality of myocardium and also in musculo-degenerative disorders)

secondary dilated CMP

associated with infective, autoimmune causes, toxicity, drug-induced (CT. e.g. anthracycline)

more than 50 genes encoding for cytoskeletal myocardial proteins can be involved

gross findings

  • heart can be 2-3 times heavier
  • main hallmarks: LV dilation and flabby heart
  • concomitant RV dilation of the heart, resulting in a more roundish shape
  • mitral insufficiency, resulting in papillary
    muscle dysfunction
  • tricuspid regurgitation associated
    with annular dilation
  • damaged endocardium by blood flow
  • endothelial cell disruption associated with clots
  • eventually, ventricular endocardial fibrosis

microscopic
appearance

  • hypertrophic nuclei
  • myocytes may not be hypertrophic
  • staining alterations
  • eosinophilic areas indicate skeletal muscle cells suffering

RESTRICTIVE

  • unknown prevalence
  • either genetic or acquired
  • likely to be associated with infiltrative diseases, like amyloidosis, or with abnormal storage diseases
  • endocardium and myocardium are generally involved
  • the heart is not heavy
  • LV is rigid and noncompliant
  • impaired diastolic filling, causing pressure increase
  • diastolic hypertension can involve pulmonary circulation causing pulmonary hypertension and involvement of the RV with right heart failure
  • usually there is jugular dilation
  • complete disarray of the structure

amyloidosis is the most common cause and it can be associated with myeloma; also neuroendocrine tumors seem to be involved with amyloid deposition

infiltration of the ventricle wall
produces a pseudohypertrophy

variants

tropical endomyocardial fibrosis

  • initiated by fever and gradually leading to heart failure
  • typical of tropical and subtropical regions
  • macro: fibrosis of endocardium, appearing wide and opaque; LV fibrosis extends from apex to mitral valve, sometimes involving papillary muscles
  • micro: trichrome staining with red colour representing muscle and blue colour representing fibrosis

non-tropical endomyocardial fibrosis

  • children <3 y
  • incompatible with survival of the newborn
  • secondary forms are associated with congenital heart abnormalities
  • micro: endocardial fibroelastic thickening

hypereosinophilic syndrome

  • aka Loeffler endocardial fibrosis
  • lots of eosinophilic cells and granulocytes in sub-endocardium
  • frequently associated with thrombosis

ENDOCARDITIS

non-rheumatic
endocarditis

abacterial thrombotic

  • aka "marantic" or "terminal"
  • non-infected vegetations
  • frequent in cachetic patients
  • due to deposition of clots on axial surface of mitral, aortic and tricuspid valve
  • clots are friable and soluble, leading to CNS, lung and coronary embolism

SLE-related

  • ex-verrucosa atypical of Libman-Sacks
  • more likely to involve th tricuspid valve
  • macro: located on the edge of the valve, on tendon cords and in surrounding parietal endocardium
  • micro: edema, lymphocytes, plasma cells, monocytes, core debris (hematoxynophilic bodies)

infected bacterial vegetation

in acute forms

involvement of healthy valves, due to virulent agents, e.g. Staph., Strep. beta, HACEK

in subacute forms

involvement of alrady altered/prolapsed valves (more commonly aortic and mitral valves), less virulent, caused by Strep. alpha hemolytic

prolonged course, death of the patient due to embolism

in advanced lesions

permanent damage of the valve, associated with valcular insufficiency and heart failure

carcinoid heart disease

septic emboli are the most common complication; in cases of CHD, right-to-left shunt may be present and may lead to paradoxical embolism (treatment leads to restitutio ad integrum, sometimes fibrosis)

  • likely to produce hormones, e.g. tryptophan, affecting the right endocardium
  • more frequent in patients with neuroendocrine tumor of the intestine and liver metastases
  • sometimes, also the lung is involved (thus, the left endocardium)
    • skin redness, cramps, nausea, vomiting
  • macro: intimal fibrous thickening of internal surfaces of heart chambers and right valves
  • micro: smooth muscle cells, collagen and mucopolysaccharide matrix

rheumatic
endocarditis

etiology

  • group A beta Streptococcus
  • onset: tonsillitis and angina, fever
  • 3% of pts have damage due to cross immunity protein M Streptococcus and heart glycoproteins
  • sites: endocardium, myocardium and pericardium
    (more commonly, mitral and aortic valves)

acute phase

  • at the beginning, serous valvulitis
  • fibroinoid material deposition around the vessels or on the valve surface
  • micro: Anitschkow-type cells (aka "caterpillar" cells), characterized by an ovoid nucleus; they may coalesce to form multinucleated Aschoff Giant cells; also, granulomas (PATHOGNOMONIC) may be observed

chronic phase

  • associated with fibrosis
  • calcifications and pericarditis, fibrinous material deposits
  • there may be adhesions between 2 layers of pericardium, with the involvement of also the endocardium around the vessels and of the valve

DEGENERATIVE VALVE DISEASE

  • associated with vegetations formation
  • it is a degenerative process of valves due to repeated mechanical stress
  • more likely to involve mitral and aortic valves
  • the main alteration is fibrosis, associated with calcification and it canbe completely asymptomatic

three types

calcification / stenosis of the aorta:
valsava sinuses are completely filled by carcinoid material --> dystrophic process with progressive accumulation of salts and the valve is stiff; commissures are not fused (as in rheumatoid/infiltrative endocarditis)
--> myocardial hypertrophy, LV hypertrophy and dilation, calcium deposits
--> angina of coronal artery, syncope for cerebral oxygenation

calcification of mitral valve:
due to degenerative lesion, calcification of the annulus may take place, sometimes in a setting of Marfan syndrome; prolapse is seen at microscopy

mitral valve prolapse:
due to mucopolysaccharides within the valve; at microscopy, the valve is thickened and transparent due to the presence of this material

evolution

completely asymptomatic or complicated by heart failure