HEART

ByMary Yvonnette C. Nerves, MD, FPSP

Once I had brains, and a heart also; so having tried them both, I should much rather have a heart.

--The Tin Woodsman of Oz

NORMAL

NORMALWeight: 250 to 300 g in females

300 to 350 g in males

Thickness of the free wall:

RV = 0.3 to 0.5 cm.

LV = 1.3 to 1.5 cm.

Hypertrophy: greater heart weight or ventricular thickness

Dilation: an enlarged chamber size

Cardiomegaly: an increase in cardiac weight or size (owing to hypertrophy and/or dilation)

Layers of the heart:

1. Epicardium

2. Myocardium

3. Endocardium

Pericardium: fibrous covering around the heart

Myocardiumcomposed primarily of a collection of specialized muscle cells called cardiac myocytes

Ventricular muscle contracts during systole and relaxes during diastole

Sarcomere: functional intracellular contractile unit of cardiac muscle

Specialized excitatory and conducting myocytes

BLOOD SUPPLY(3) Major Epicardial Coronary arteries:a. Left Anterior Descending Artery

- Anterior wall- Anterior two thirds of septum- Entire apex of heart, circumferentially

b. Left Circumflex Coronary Artery- posterior, lateral left aspect of heart.

c. Right Coronary Artery- posterior one third of septum, inferior

aspect, and posterior wall of heart.

VALVES1. Semilunar valves

a. Aortic valveb. Pulmonary valve

2. Atrioventricular valvesa. Mitral valveb. Tricuspid valve

PATHOLOGY

PATHOLOGY Failure of the pump

An obstruction to flow

Regurgitant flow

Disorders of cardiac conduction.

Disruption of the continuity of the circulatory system

Congestive Heart Failure (CHF)

pathophysiologic state resulting from impaired cardiac function that renders the heart muscle unable to maintain an output sufficient for the metabolic requirements of the tissues & organs of the body

Congestive Heart Failure (CHF)

the physiology of HF involves an interplay between 2 factors:

a) inability of the failing heart tomaintain sufficient cardiac output to support body functions

b) recruitment of compensatorymechanisms to maintain cardiacreserve

Cardiac output: amt of blood that the heart pumps each minute

- reflects how often the heart beats each minute (HR) and how much blood the heart pumps with each beat (SV)

CO = HR x SV

Causes of CHF Pump Failure: Failure that is intrinsic to

the myocardium. Two types:

Systolic Failure: Failure to pump blood out of heart.

Diastolic Failure: Failure to distend the heart to fill the ventricles, as in constrictive pericarditis.

Most common reason for pump failure is from myocardial hypertrophy, usually sec. to HPN.

Conduction System Failure: Secondary to

MI

Valvular Failure: Inflammatory (endocarditis), autoimmune, or congenital.

Cardiac Malformations: Congenital

Blood Loss / Obstruction of Blood Flow: Extracardiac causes. Pulmonary

emboli or bleeding.

Mechanisms that maintain arterial pressure and perfusion of vital organs in the presence of excessive hemodynamic burden or disturbance in myocardial contractility:

1. Frank-Starling mechanism- increased preload of dilation helps to

sustain cardiac performance by enhancing contractility

2. Myocardial structural changes - augmented muscle mass w/ or w/o cardiac chamber dilation, in whichthe mass of contractile tissue isaugmented

3. Activation of neurohumoral systems release of the neurotransmitter

norepinephrine by adrenergic cardiac nerves

activation of the renin-angiotensin-aldosterone system, and

release of atrial natriuretic peptide.

Heart’s compensatory changes Hypertrophy Ventricular dilatation Blood volume expansion by salt &

water retention Tachycardia

Extent of hypertrophy varies for different underlying causes: 350 – 600 gms: pulmonary HPN / IHD 400 – 800 gms: systemic HPN / aortic

stenosis / mitral regurgitation / dilated cardiomyopathy

600- 1000 gms: aortic regurgitation /hypertrophic

cardiomyopathy

The pattern of hypertrophy reflects the nature of the stimulus:1. Pressure-overload (concentric)

hypertrophy Pressure-overloaded ventricles (e.g., in

hypertension or aortic stenosis) develop pressure-overload hypertrophy of the LV, with an increased wall thickness

LV: the augmented muscle may reduce the cavity diameter

the predominant deposition of sarcomeres is parallel to the long axes of cells; cross-sectional area of myocytes is expanded (but cell length is not).

2. Volume-overload hypertrophy volume overload stimulates deposition

of new sarcomeres and cell length (as well as width) is increased

characterized by dilation with increased ventricular diameter

muscle mass and wall thickness are increased approximately in proportion to chamber diameter

Left-sided CHF

Failure of the left side of the heart to pump sufficient blood

Common causes of left-sided failure Ischemia (old or recent myocardial infarct,

ischemic muscle disease) Aortic or mitral valve disease Systemic hypertension Myocardial disease / cardiomyopathy

Clinical manifestations: Pulmonary congestion and edema Reduced cardiac output also causes reduced

renal perfusion, leading to Further salt & water retention Ischemic acute tubular necrosis Impairment of waste excretion, causing prerenal

azotemia

CNS perfusion is reduced, often resulting to hypoxic encephalopathy

Right-sided CHF

Failure of the right side of the heart to pump enough blood

Common causes of right-sided failure Pulmonary emboli (acute or chronic) Any disease interfering with lung ventilation

Emphysema / Cystic fibrosis Left-sided heart failure! Cardiac defects with left-to-right shunts

Clinical manifestations: Portal, systemic and dependent peripheral

congestion & edema & effusions (pleural & peritoneal)

Hepatomegaly w/ centrilobular congestion & atrophy of central hepatocytes nutmeg liver (chronic passive congestion)

Centrilobular necrosis Cardiac sclerosis

Congestive splenomegaly Renal congestion

HEART DISEASE

Congenital heart disease

Ischemic heart disease

Hypertensive heart disease (systemic & pulmonary)

Valvular heart disease

Nonischemic (primary) myocardial disease

Cardiac Neoplasms

CONGENITAL HEART

DISEASE

CONGENITAL HEART DISEASE Abnormalities of the heart andgreat vessels present at birth Most common type of heart disease among chldrenOccurs during 3rd to 8th week of gestation Incidence: 1% of livebirths Higher incidence among prematures

and stillborn

Heart at 18 to 22 days

22 days

Angioblasts (heart formingcells) first appear at 18 days

Two dorsal aortae developand subsequently fuse in themid-line to form a primitiveheart tube.

Heart first forms rostral tothe neural plate

As the brain grows, the heartmoves caudally into the neckand then into the chest

Origin of the Heart

Heart

Heart

Angioblasts

Latepresomiteembryo

18 days

EMBRYOLOGIC HEART DERIVATIVES:

Embryonic Structure Adult Structure

Bulbus Cordis Right Ventricle and Aortic Outflow Track

Primitive Ventricle Left Ventricle

Truncus Arteriosus Ascending Aorta, Pulmonary Trunk

Primitive Atria Auricular Appendages

Sinus Venosus Left Horn: Coronary Sinus Right Horn: Smooth part of the Right Atrium

Right Common and Anterior Cardinal Veins

Superior Vena Cava

Malformation

Incidence per Million Live

Births %

Ventricular septal defect 4482 42

Atrial septal defect 1043 10

Pulmonary stenosis 836 8

Patent ductus arteriosus 781 7

Tetralogy of Fallot 577 5

Coarctation of aorta 492 5

Atrioventricular septal defect 396 4

Aortic stenosis 388 4

Transposition of great arteries 388 4

Truncus arteriosus 136 1

Total anomalous pulmonary venous connection

120 1

Tricuspid atresia 118 1

TOTAL 9757

Etiology 1. Genetics - Trisomy 13, 15, 18 , 21, Turner

Syndrome

2. Environmental Factors- congenital rubella infection /

teratogens / alcohol / amphetamines / chemotx / anticonvulsants / thalidomide / retinoic acid

3. Multifactorial

Classification

1. Left to right shunt anomaly

2. Right to left shunt anomaly

3. Obstructive anomaly

SHUNT: an abnormal communication between chambers or blood vessels

LEFT TO RIGHT SHUNT

1. ASD –Atrial septal defect

2. VSD – ventricular septal defect

3. PDA – Patent ductus arteriosus

4. AVSD – Atrio-ventricular septal defect

ATRIAL SEPTAL DEFECT

direct communication between the atrial chambers

Abnormal opening in the atrial septum Most common CHD that is asymptomatic until adulthood Acyanotic at birth Symptoms may manifest in third decade

ATRIAL SEPTAL DEFECT

Major Types:1. Ostium secundum - 90% of ASD (most common)

- defect in the fossa ovale

- may be solitary or with other anomaly

ATRIAL SEPTAL DEFECT cont. Major Types:

2. Ostium primum - 5 % of ASD

- defect occurs near the AV valve

- assoc with a clefted anterior MV valve (partial ASD)

ATRIAL SEPTAL DEFECT cont. Major Types:

3. Sinus venosus defect- 5 % of ASD

- located near the entrance of SVC

- associated with TAPVR

Effects of ASD

RAH and enlargement RVH and enlargement Increase pulm blood flow pulm

HPN Murmur due to inc blood flow to pulm valve

VENTRICULAR SEPTAL DEFECT

direct communication between theventricular chambers

Incomplete closure of the ventricularseptum associated with other structural defects,such as tetralogy of Fallot 30% occur as isolated anomalies

VENTRICULAR SEPTAL DEFECT

Major Types:1. Membranous VSD

- 90 % of VSD

2. Infundibular VSD

- located below the PV or within the muscular septum (Muscular VSD)

ATRIOVENTRICULAR SEPTAL DEFECT

Complete AV canal defect Abn development of AV canal Incomplete closure of AV septum and inadequate formation of TV and MV Failure of fusion of sup and inf

endocardial cushions

AVSD: Types1. Partial AVSD - primum ASD, cleft ant mitral

leaflet2. Complete AVSD - large combined AVSD and a

large common AV valve - free communication of all 4

chambers

PATENT DUCTUS ARTERIOSUS

Persistence of communication between PA and aorta via ductusarteriosus 90 % as isolated anomaly 10 % assoc with VSD, coarctation, pulmonary or aortic stenosis “Machinery murmur “

RIGHT TO LEFT SHUNT

1. Tetralogy of Fallot (TOF)2. Transposition of the Great Vessels3. Truncus arteriosus4. Tricuspid atresia5. Total Anomalous Pulmonary Venous

Return

Components:

TETRALOGY OF FALLOT

cont. TOF: Morphology heart is often enlarged “ boot – shaped “ ("coeur en sabot“) RVH

Large VSD, overriding the aorta Subpulmonic valve stenosis obs to

RV outflow Assoc lesions: ASD, right aortic arch

TOF : clinical features

Right to left shunt “ Pink tetralogy “ – mild Pulm

Stenosis , LR shunt “ classic tetralogy “ severe PS ,

RL shunt Survival dependent on PS

TRANSPOSITION OF GREAT VESSELS

abnormal development of the truncoconal septum that results in inversion of the aorta and pulmonary arteries with respect to the ventricles (Ventriculo-arterial discordance) Aorta arises from RV, Pulm artery from LV Incompatible with life Assoc lesions: VSD (stable shunts); PDA (unstable shunts); RVH; LVhypoplasia

TRUNCUS ARTERIOSUS Failure to develop a dividing septum bet the aorta and pulmonary artery, resulting in a common trunk single great artery Failure of separation of truncus arteriosus into aorta and pulmonary

artery Assoc lesions: VSD Mixing of blood early cyanosis,

Pulm HPN

                                                                                                                                                                                      

TRICUSPID ATRESIA

absence of communication between the right atrium and ventricle due to developmental failure to form the tricuspid valve (complete absence of TV)

Results from unequal devision of AV canal

Assoc lesions: Large MV, underdeveloped RV, ASD, VSD or PDA

Early cyanosis with high MR

TOTAL ANOMALOUS PULM VENOUS CONNECTION (TAPVC)

No pulmonary veins in LA Pulm veins drain into the coronary

sinus or left innominate veins Assoc ASD or PDA

RAD, RVD, pulm trunk dilation, hypoplastic LA

Comparison of Left vs. Right Shunt Congenital Disease

Right Left Shunt Early cyanosis (blue

babies) Blood shunted past the

lungs

TOFTOGVTricuspid atresiaTruncus arteriosus

Left Right Shunt Late cyanosis (blue

kids) Pulmonary HPN

reversal of shunt (Eisenmenger syndrome)

VSD, ASD, PDA

OBSTRUCTIVE ANOMALIES

1. Coartation of aorta

2. Pulmonic stenosis / atresia

3. Aortic stenosis / atresia

COARTATION OF AORTA Types :

1. Infantile Coarctation

- tubular hypoplasia of aortic arch proximal to PDA

2. Adult Coarctation

- ridgelike coaptation of aorta at the level of ductus

arteriosus

Clinical manifestations depend almost entirely on the severity of the narrowing and the patency of the ductus arteriosus.

PULMONARY STENOSIS / ATRESIA

Common S/S dependent on size of PV May occur as isolated event or part of complex anomalyAssoc lesions: RVH; PA hypoplasia;

RV hypoplasia inPV atresia; ASD

                                                                                                                         

AORTIC STENOSIS / ATRESIA

Narrowing/ obstruction of AV

Three types:

a. Valvular AS

b. Subaortic stenosis

c. Supravalvular stenosis

                                                                                                                         

ISCHEMIC HEART

DISEASE

ISCHEMIC HEART DISEASE

Group of related cardiac diseases resulting from imbalance bet. blood supply to the heart and its demand for oxygen (myocardial ischemia)

Aka: Coronary artery disease or coronary heart disease

SYNDROMES OF IHD

1. Acute Myocardial Infarction

2. Angina Pectoris

3. Chronic Ischemic Heart Disease

4. Sudden Cardiac Death

IHD: Pathogenesis Decrease coronary perfusion relative

to blood demand Causes :

fixed stenosing atherosclerosis fissure, rupture, ulceration, hge

(acute plaque change) thrombosis vasoconstriction/ vasospasm

IHD : Role of fixed coronary obstruction

90 % of IHD with fixed CA atherosclerosis (fixed obstruction)

may affect single, dual or triple CA

Onset of symptoms depend on extent, severity of occlusion and acute plaque change

Associated with typical angina pectoris

Fixed coronary atherosclerosis

IHD: Role of acute plaque change

Assoc with acute coronary syndromes (unstable angina, AMI, sudden cardiac death) Acute change: rupture/fissuring,erosion/ulceration, hge into the atheroma Ischemia ppted by acute plaque change followed by thrombosis High in moderate stenosis and lipid rich atheroma

Acute plaque change

Acute Plaque Change: Fissuring, hemorrhage

ACUTE PLAQUE CHANGE : HGE Acute Plaque Change: Hemorrhage

IHD: Role of inflammation initial lesion: interaction bet.

endothelial cells & circulating leukocytes later stages: secretion of

metalloproteinases bymacrophages

IHD : role of thrombosis

Occlusive thrombi assoc with acute transmural MI

Partial occlusive thrombi assoc with unstable angina, subendocardial infarction and SCD

Acute Plaque Change Thrombosis

Role of vasoconstriction

Reduction of lumen size increases local mechanical forces increase risk of plaque rupture

ANGINA PECTORIS

paroxysmal, recurrent precordial orsubsternal chest pain, caused bytransient myocardial ischemia

which falls short of infarction 3 types :

a. Stable or typical AP b. Prinzmetal or variant AP c. Unstable or crescendo AP

Angina pectoris: Etiology Increased myocardial demand and decreased myocardial perfusion secondary to :

Chronic stenosing coronary atherosclerosis

Disrupted artherosclerotic plaques Vasospasm Thrombosis Coronary artery embolization

Stable Angina Pectoris

Most common form of AP Reduction of perfusion caused by chronic stenosing CA atherosclerosis Chest pain: transient, ppted by exertion, emotion, relieved by rest and vasodilators

Prinzmetal angina pectoris

Episodic pain at rest

Secondary to vasospasm

ECG changes suggestive of transmural ischemia (ST segment elevation)

Responds to nitroglycerin, Ca channel blockers and vasodilators

Unstable angina pectoris

Pain progressively increasing in frequency, duration, intensity, occurs at rest Assoc with acute plaque change,with

superimposed partial thrombosis or vasospasm Precursor to AMI (pre-infarction AP)

MYOCARDIAL INFARCTION

Localized area of cardiac muscle necrosis due to ischemia

Risk factors:

Major: HPN, Cigarette smoking, DM, Hyperlipidemia

Minor: obesity, sex, age, stress, physical inactivity

AMI: PathogenesisCoronary arterial occlusion: atherosclerosis with acute plaque change, thrombosis, vasospasm

Increase myocardial demand

Hemodynamic compromise

Emboli

unknown

Irreversible myocardial damage

After severe ischemia , lasting from 20 – 40 min or longer

Assoc with less than 10 % reduction of blood flow

Initial damage to sarcolemmal membrane

Myocardial changes in AMI:

Ischemic coagulation necrosis , initially at subendocardial region,

with wavefront progression

Morphologic changes evolve in time

Factors affecting severity of AMI

Location , severity of obstruction

Rate of development of occlusion

Duration of occlusion

Extent of collateral vessels

Metabolic demands of myocardium

Other factors : BP, HR, cardiacrhythm

TRANSMURAL INFARCTION

Transmural infarct necrosis involves the full or nearly the full

thickness of wall

Assoc with chronic atherosclerotic obstruction , acute plaque change and superimposed complete thrombosis

SUBENDOCARDIAL INFARCTION

Necrosis limited to inner 1/3 or ½ ofventricle

Assoc with diffuse stenosing coronaryatherosclerosis w/o thrombosis

and acute plaque change

AMI: MorphologyGROSS Early recognition: Triphenyl tetrazolium

chloride (unstained area) Coagulation necrosis of myocardium Gross changes evident after 4-12

hours 18-24 hrs: pale to cyanotic 7-10 days: circumferential rim of

granulation tissue 6 weeks: fibrous scar

AMI : morphology Microscopic: within 1 hr: intercellular edema, wavy fibers

at periphery, coagulation necrosis not yetevident

12-72 hrs: neutrophilic infiltration into necrotictx, myocyte coag necrosis, dead myocytes hypereosinophilic w/ loss of nuclei

between 3-7 days: disintegration of dead myofibers

After 7-10 days: granulation tx replaces necrotic tx fibrous scar

TimeGross

Features Light Microscope Electron Microscope

Reversible Injury

0-½ hr

None None Relaxation of myofibrils; glycogen loss; mitochondrial swelling

Irreversible Injury

½-4 hr

None Usually none; variable waviness of fibers at border

Sarcolemmal disruption; mitochondrial amorphous densities

4-12 hr

Occasionally dark mottling

Beginning coagulation necrosis; edema; hemorrhage

 

12-24 hr

Dark mottling Ongoing coagulation necrosis; pyknosis of nuclei; myocyte hypereosinophilia; marginal contraction band necrosis; beginning neutrophilic infiltrate

 

Time Gross Features Light Microscope EM

 

 

1-3 days Mottling with yellow-tan infarct center

Coagulation necrosis, with loss of nuclei and striations; interstitial infiltrate of neutrophils

 

3-7 days Hyperemic border; central yellow-tan softening

Beginning disintegration of dead myofibers, with dying neutrophils; early phagocytosis of dead cells by macrophages at infarct border

 

7-10 days

Maximally yellow-tan and soft, with depressed red-tan margins

Well-developed phagocytosis of dead cells; early formation of fibrovascular granulation tissue at margins

 

Time Gross Features Light Microscope EM

10-14 days

Red-gray depressed infarct borders

Well-established granulation tissue with new blood vessels and collagen deposition

 

2-8 wk Gray-white scar, progressive from border toward core of infarct

Increased collagen deposition, with decreased cellularity

 

>2 mo Scarring complete Dense collagenous scar

 

CA Atherosclerosis with Thrombosis

Acute Plaque Change: Fissures /

Ulceration

AMI : Wavy fibers

AMI : ½ to 4 hrs

AMI : Coagulation necrosis, hge, edema at 4-12 hrs

AMI : 12-24 hrs

AMI at 12-24 hrs: Contraction band necrosis

Contraction band necrosis

AMI at 12-24 hrs: Myocyte hypereosinophilia, contraction band, leukocytes

AMI : 1-3 days

AMI at 1-3 days: Coagulation necrosis, loss of striations,

leukocytes

AMI at 1-3 days: Necrosis, loss of nuclei/striations, leukocytic infiltration

AMI at 3-7 days

AMI at 3-7 days: Disintegration of myocyte, PMNs, phagocytosis

AMI at 3-7 days: Disintegration of myocytes, neutrophils, early

phagocytosis

AMI at 7-10 days: Well developed phagocytosis, fibrovascular granulation tissue

AMI at 10-14 days: Well developed granulation tissue

AMI at 2-4 weeks: Well developed fibrosis

Fibrosis

Clinical Features Symptoms: rapid weak pulse &

diaphoretic; dyspnea

ECG: new Q waves

Labs: myoglobin, cardiac troponins I & T (TnI, TnT), creatine kinase, LDH, CRP, etc.

Absence of a change in the levels of CK and CK-MB during the 1st 2 days of chest pain & of troponin in the days ff essentially excludes the diagnosis of MI

Serum Markers Used to Diagnose MI

Elevated by

Peak Returns to Normal by

CK-MB 4-8 hrs 18 hrs 2-3 days

Troponin I & T 3-6 hrs 16 hrs 7-10 days

LDH 24 hrs 3-6 hrs 8-14 days

Complications Contractile dysfunction

Arrhythmias

Myocardial rupture

Pericarditis

RV infarction

Infarct extension

Infarct expansion

Complications Mural thrombus

Ventricular aneurysm

Papillary muscle dysfunction

Progressive late heart failure

Complications The propensity towards specific complications & the prognosis after MI depend primarily on infarct size, site & fractional thickness of the myocardial wall that is damaged.

Large transmural infarcts: cardiogenic shock, arrhythmias, & late CHF

Anterior transmural: free wall rupture, expansion, mural thrombi, & aneurysm

Posterior transmural infarcts: conduction blocks, RV involvement

CHRONIC ISCHEMIC HEART DISEASE

Cardiac findings in patients, often but not exclusively elderly, who develop progressive heart failure as a consequence of ischemic myocardial damage

Aka: ischemic cardiomyopathy

Morphology:Heart is enlarged & heavy, sec. to LVH & dilation

Discrete gray white scars of healed infarcts

Micro: myocardial hypertrophy, diffuse subendocardial vacuolization, scars of previous healed infarcts

SUDDEN CARDIAC DEATHUnexpected death from cardiac causes early after symptom onset (usually within 1 hr) or without the onset of symptoms

Nonatherosclerotic causes of SCD:Congenital structural or coronary arterial abnormalities

Aortic valve stenosis

Mitral valve prolapse

Dilated or hypertrophic cardiomyopathy

Myocarditis

Pulm HPN

Hereditary or acquired abn of the cardiac conduction system

Isolated hypertrophy

The ultimate mechanism of SCD is most often a lethal arrythmia (eg. asystole, ventricular fibrillation)

Morphology:Marked coronary atherosclerosis with critical (> 75%) stenosis involving one or more of the 3 major vessels is present in 80-90% of SCD

Healed MI is present in 40%

Subendocardial myocyte vacuolization indicative of severe chronic ischemia is common

HYPERTENSIVE HEART DISEASE

HYPERTENSIVE HEART DISEASE

Systemic (left-sided) hypertensiveheart disease

Pulmonary (right-sided) hypertensive heart disease (Cor pulmonale)

Systemic HHD

Diagnostic Criteria: LVH, concentric

- Absence of other lesions that might induce cardiac hypertrophy

Hx or pathologic evidence of HPN

Morphology: GROSS: thickened LV wall w/

increased heart wt MICRO:

- earliest change: increase in transverse diameter of

the myocytes

- myocytes & nuclei enlarged

- diffuse interstitial fibrosis

Pulmonary HHDconsists of RVH, dilation, & potentially failure secondary to pulmonary HPN caused by dso of the lungs or pulmonary vasculature

Pulmonary HHD Acute cor pulmonale:

- RV dilation after massive pulmonary embolization

Chronic cor pulmonale

- Result of chronic RV pressure overload

Table 12-6. Disorders Predisposing to Cor Pulmonale

Diseases of the Pulmonary Parenchyma

Chronic obstructive pulmonary disease

Diffuse pulmonary interstitial fibrosis

Pneumoconioses

Cystic fibrosis

Bronchiectasis

Diseases of the Pulmonary Vessels

Recurrent pulmonary thromboembolism

Primary pulmonary hypertension

Extensive pulmonary arteritis (e.g., Wegener granulomatosis)

Drug-, toxin-, or radiation-induced vascular obstruction

Extensive pulmonary tumor microembolism

Disorders Affecting Chest Movement

Kyphoscoliosis

Marked obesity (pickwickian syndrome)

Neuromuscular diseases

Disorders Inducing Pulmonary Arterial Constriction

Metabolic acidosis

Hypoxemia

Chronic altitude sickness

Obstruction to major airways

Idiopathic alveolar hypoventilation

Table 12-6. Disorders Predisposing to Cor Pulmonale

Morphology: GROSS:

- Acute: marked RV dilation w/o hypertrophy

- Chronic: RV wall thickens RV dilation may lead to tricuspid

regurgitation

VALVULAR HEART DISEASE

valvular involvement by dse causingstenosis, insufficiency, or both

STENOSIS: failure of a valve toopen completely, impeding forward flow INSUFFICIENCY: failure of a valve to close completely, allowing reversed flow

Valvular Heart Disease

Mitral Valve Disease Aortic Valve Disease

Mitral Stenosis Aortic Stenosis

Postinflammatory scarring (rheumatic heart disease)

Postinflammatory scarring (rheumatic heart disease)

  Senile calcific aortic stenosis

  Calcification of congenitally deformed valve

Mitral Regurgitation Aortic Regurgitation

Abnormalities of Leaflets and Commissures

Intrinsic Valvular Disease

Postinflammatory scarring Postinflammatory scarring (rheumatic heart disease)

Infective endocarditis Infective endocarditis

Mitral valve prolapse  

Fen-phen-induced valvular fibrosis  

MAJOR ETIOLOGIES OF ACQUIRED HEART VALVE DISEASE

Abnormalities of Tensor Apparatus Aortic Disease

Rupture of papillary muscle Degenerative aortic dilation

Papillary muscle dysfunction (fibrosis) Syphilitic aortitis

Rupture of chordae tendineae Ankylosing spondylitis

  Rheumatoid arthritis

  Marfan syndrome

Abnormalities of Left Ventricular Cavity and/or Annulus

 

LV enlargement (myocarditis, dilated cardiomyopathy)

 

Calcification of mitral ring  

Mitral Valve Disease Aortic Valve Disease

Most frequent causes of major functional valvular lesions:

Aortic stenosis: calcification ofanatomically normal & congenitally bicuspid aortic valve

Aortic insufficiency: dilation of theascending aorta

Mitral stenosis: RHD

Mitral insufficiency: myxomatous degeneration (MVP)

Valvular Degeneration caused by Calcification

Calcific Aortic Stenosis

Calcific Stenosis of Congenitally Bicuspid Aortic Valve

Mitral Annular Calcification

Calcific Aortic Stenosis most common of all valvular

abnormalities

age-related dystrophic calcification, degeneration & stenosis of the AV

Acquired aortic stenosis: calcif owing to progressive & advanced age-assoc “wear & tear” of either previously anatomically normal AV or congenitally bicuspid valves

Morphology:

- Hallmark: heaped-up calcified masses w/in the aortic

cusps

- commissural fusion is NOT a usual feature

- MV generally normal

- concentric LVH from chronicpressure overload

Calcific Stenosis of Congenitally Bicuspid Aortic Valve

Frequency: 1.4% of live births neither stenotic nor symptomatic atbirth or throughout early life Congenitally Bicuspid Aortic Valve: only 2 functional cusps of unequal size, the larger having a median raphe

MV is normal

Mitral Annular Calcification

degenerative, noninflammatory, calcific deposits w/in the mitral annulus, usually in the elderly GROSS: irreg, stony hard, occlly

ulcerated nodules behind the leaflets

Regurgitation occur owing to inadeq systolic contraction of the MV ring

Mitral Annular Calcification

stenosis by impairing opening of the mitral leaflets

Calcific nodules may provide a site for thrombi that can embolize

Nodular calcific deposits may cause arrythmias by impinging on the conduction pathways

rare focus of infective endocarditis

Calcific valvular degeneration. C and D, Mitral annular calcification, with calcific nodules at the base. C, Left atrial view. D, Cut section of myocardium.

Myxomatous Degeneration of the Mitral Valve (MV Prolapse)

one or both MV leaflets are “floppy” & prolapse, or balloon back into the LA during systole

Mitral Valve Prolapse: affect 3% or more of adults, most often women

Myxomatous degeneration of the MV: pathologic

MORPHOLOGY

Gross: interchordal ballooning (> 4mm) of the MV leaflets & elongated, attenuated, or occlly ruptured chordae tendinae

Myxomatous degeneration of the mitral valve. A, Long axis of left ventricle demonstrating hooding with prolapse of the posterior mitral leaflet into the left atrium (arrow).

Myxomatous degeneration of the mitral valve.

MORPHOLOGY

Micro: thinning & degeneration ofthe fibrosa layer w/ myxomatous thickening of the spongiosa

- Secondary changes:

a. fibrous thickening of the valve leaflets

b. thickened LV endocardium

c. atrial thrombosis

d. calcification of the mitral annulus

Pathogenesis

underlying developmental defect of CT

common feature of Marfan syndrome (caused by mutations inthe gene encoding fibrillin-1 – formation of elastic fiber)

Clinical Features

MVP: asymptomatic; midsystolic click on auscultation

- Complications:

a. infective endocarditis

b. mitral insufficiency

c. atrial & ventricular arrhythmias

d. stroke or other systemic infarcts

Rheumatic Fever & RHD

RF: an acute, immunologicallymediated, multisystem, inflamm

dse triggered by pharyngeal infection w/ Group A beta- hemolytic strep

Most important consequence: chronic valvular deformities

MORPHOLOGY

Micro: Myocarditis: Aschoff bodies foci of swollen

eosinophilic collagen surrounded by lymphos, occasional plasma cells, and plump macrophages called Anitschkow cells (pathognomonic for RF); some of the larger macrophages become

multinucleated to form Aschoff giant cells Found in muscle layer

Fibrinous pericarditis – “bread & butter” Endocarditis

MORPHOLOGY

Micro: Subendocardial collections of Aschoff

nodules, usually in the LA, induce thickenings called MacCallum plaques

Chronic RHD: Cardinal anatomic changes

1. Fibrous thickening of the leaflets

2. Commissural fusion & shortening

3. Thickening and fusion of the tendinous cords

Pathogenesis ARF is a hypersensitivity reaction induced by group A streptococci

Abs directed against the M proteins of certain strains of streptococci cross-react with glycoprotein Ags in the heart, joints, & other tissues

Clinical Features Diagnosis rests on the clinical hx & the presence of 2 of 5 major (Jones) criteria:

(1) migratory polyarthritis of the large joints

(2) carditis

(3) subcutaneous nodules

(4) erythema marginatum of the skin,

(5) Sydenham chorea: neurologic dso w/ involuntary purposeless, rapidmovements.

Infective Endocarditis

colonization of the heart valves w/ microbiologic organisms that leads to

fotn of friable, infected vegetations & freq valve injury

most cases are bacterial

Classification:1. Acute Infective Endocarditis

2. Subacute Infective Endocarditis

Acute Endocarditis caused by highly virulent organisms,

often seeding a previously normal valve & producing a necrotizing, ulcerative & invasive infection

Subacute Endocarditis caused by an organism of mod to low

virulence seeding previously injured valve, causing less valvular destruction

Etiology & Pathogenesis

bacteremia are prerequisites

Risk factors:

- Cardiac congenital anomalies

- Chronic RHD

- MVP, degenerative calcific stenosis, Bicuspid aortic valve, Prosthetic

valves

- Host factors: neutropenia, malignancy

- sterile platelet-fibrin deposits

Etiology & Pathogenesis Causative organisms: S. viridans: endocarditis of native but

previously damaged or otherwise abn valves

S. aureus: attack either healthy or deformed valves; IV drug users

Enterococci & HACEK grp (Haemophilus, Actinobacillus,Cardiobacterium, Eikenella, Kingella)

S. epidermidis: prosthetic valve endocarditis

MORPHOLOGY Gross: friable, bulky, & destructive vegetations containing fibrin, inflam cells & bacteria or other organisms present

Most common sites of infection: AV & MV

Vegetations sometimes erode into theunderlying myocardium to produce an abscess cavity (ring abscess)

MORPHOLOGY Systemic emboli may occur at any time because of the friable nature of the vegetations

Subacute endocarditis: less valvular destruction; granulation tx at their bases suggesting chronicity

Clinical Features

fever is the most consistent sign

Subacute: fever is slight or absent

Acute: fever, chills, weakness & lassitude

Duke’s Criteria: stdized assessment of pts w/ IE

Pathologic Criteria

Microorganisms, demonstrated by culture or histologic examination, in a vegetation, embolus from a vegetation, or intracardiac abscess

Histologic confirmation of active endocarditis in vegetation or intracardiac abscess

Clinical Criteria

Major

Positive blood culture(s) indicating characteristic organism or persistence of unusual organism

Echocardiographic findings, including valve-related or implant-related mass or abscess, or partial separation of artificial valve

New valvular regurgitation

Minor

Predisposing heart lesion or intravenous drug use

Fever

Vascular lesions, including arterial petechiae, subungual/splinter hemorrhages, emboli, septic infarcts, mycotic aneurysm, intracranial hemorrhage, Janeway lesions†

Immunologic phenomena, including glomerulonephritis, Osler nodes,‡ Roth spots,§ rheumatoid factor

Microbiologic evidence, including single culture showing uncharacteristic organism

Echocardiographic findings consistent with but not diagnostic of endocarditis, including new valvular regurgitation, pericarditis

Non-infected Vegetations

Nonbacterial ThromboticEndocarditis (NBTE)

Endocarditis of SLE (Libman-Sacks Disease

marantic endocarditis char by deposition of small masses of

fibrin, platelets, & other bld components on the leaflets of the cardiac valves Valve lesions are sterile & do not contain microorg

Nonbacterial ThromboticEndocarditis (NBTE)

Gross: vegetations are sterile, nondestructive and small & occur singly or multiply along the line of closure of the leaflets Micro: bland thrombus w/o accompanying inflam reaction or induced valve damage

Morphology

hypercoagulable state w/ systemic activation of blood coagulation

such as DIC related to some underlying dse eg. CA

Pathogenesis

mitral amd tricuspid valvulitis w/ small, sterile vegetations Micro: verrucae consists of a finely

granular, fibrinous eosinophilic material that may contain

hematoxylin bodies

Endocarditis of SLE (Libman-Sacks Dse.)

Diagrammatic comparison of the lesions in the four major forms of vegetative endocarditis.

CARDIOMYOPATHIES

Inflammatory disorders (myocarditis) Immunologic & systemic metabolic

disorders Genetic abnormalities in cardiac muscle cells

Myocardial Diseases

Cardiomyopathy: heart disease resulting from a primary abnormality in the myocardium

(3) Categories of cardiomyopathy:a. Dilated – most commonb. Hypertrophicc. Restrictive

Dx: Endomyocardial biopsy

char by progressive cardiac dilation & contractile (systolic)

dysfunction Aka: Congestive cardiomyopathy 25-35% have familial form

Dilated Cardiomyopathy

Gross: heart is heavy & flabby, w/ dilation of all chambers

Micro: histologic abnormalities arenonspecific & usually do not

reflect a specific etiologic agent Most muscle cells are hypertrophied

with enlarged nuclei, but many are attenuated, stretched, and irregular

Interstitial and endocardial fibrosis of variable degree

Morphology

Myocarditis: viral nucleic acids (coxsackievirus B & other enterovirus) Alcohol or other toxicity Pregnancy-associated: peripartum CM Genetic influences: autosomal dominant/autosomal recessive/x-linked recessive/mitchondrial defect affects the cytoskeleton

Pathogenesis

commonly affects individuals between ages 20-50 slowly progressive signs & symptoms of CHF

Clinical Features

Aka: idiopathic hypertrophicsubaortic stenosis / hypertrophic obstructive cardiomyopthy

char by myocardial hypertrophy,abnormal diastolic filling, &

intermittent ventricular outflow obstruction heart is thick-walled, heavy, &

hypercontracting

Hypertrophic Cardiomyopathy

Gross: massive myocardial hypertrophy without ventricular dilation- classic pattern: disproportionate thickening of the ventricular septum as compared with the free wall of the LV (assymetrical septal hypertrophy)- C/S: ventricular cavity compressed

Morphology

Micro: most impt histologic features- extensive myocyte hypertrophy w/

transverse myocyte diameters > 40um

- myofiber disarray- interstitial & replacement fibrosis

Morphology

caused by a mutation in any one of several genes that encode proteins that are part of the sarcomere, the contractile unit of cardiac & skeletal muscle most cases are familial, transmitted as autosomal dominant 12 sarcomeric genes: B-MHC gene

Pathogenesis

impaired diastolic filling of the massivelyhypertrophied LV reduced chambersize & poor compliance with reduced stroke volume decreased CO & increase in pulm venous

pressure exertional dyspnea harsh systolic ejection murmur

Clinical Features

anginal pain Major clinical problems:

- atrial fibrillation w/ mural thrombus fotn

- infective endocarditis of MV- intractable cardiac failure

- ventricular arrythmias- sudden death

char by primary decrease in ventricular compliance, resulting inimpaired ventricular filling during diastole contractile (systolic) function of the

LV is not affected

Restrictive Cardiomyopathy

Gross: ventricles of normal size or sl enlarged, cavities are no dilated & the myocardium is firm

biatrial dilation commonly observed

Micro: patchy or diffuse interstitial fibrosis

Morphology

idiopathic or associated with distinct diseases that affect the myocardium:

- radiation fibrosis- amyloidosis- sarcoidosis- metastatic tumor- products of inborn errors of metabolism

Pathogenesis

other restrictive conditions:- endomyocardial fibrosis- Loeffler endomyocarditis- endocardial fibroelastosis

Pathogenesis

Functional Pattern

LV Ejection Fraction*

Mechanisms of Heart Failure Causes

Indirect Myocardial Dysfunction (Not Cardiomyopathy)

Dilated <40% Impairment of contractility (systolic dysfunction)

Idiopathic; alcohol; peripartum; genetic; myocarditis; hemochromatosis; chronic anemia; doxorubicin (Adriamycin); sarcoidosis

Ischemic heart disease; valvular heart disease; hypertensive heart disease; congenital heart disease

Cardiomyopathy and Indirect Myocardial Dysfunction: Functional Patterns and Causes

Hypertrophic 50-80% Impairment of compliance (diastolic dysfunction)

Genetic; Friedreich ataxia; storage diseases; infants of diabetic mothers

Hypertensive heart disease; aortic stenosis

Restrictive 45-90% Impairment of compliance (diastolic dysfunction)

Idiopathic; amyloidosis; radiation-induced fibrosis

Pericardial constriction

Cardiomyopathy and Indirect Myocardial Dysfunction: Functional Patterns and Causes

Cardiac Infections

Viruses

Chlamydia

Rickettsia

Bacteria

Fungi

Protozoa

Toxins

Alcohol

Cobalt

Catecholamines

Carbon monoxide

Lithium

Hydrocarbons

Arsenic

Cyclophosphamide  

Doxorubicin (Adriamycin) and daunorubicin

Conditions Associated with Heart Muscle Diseases

Metabolic

Hyperthroidism

Hypothyroidism

Hyperkalemia

Hypokalemia

Nutritional deficiency (protein, thiamine, other avitaminoses)

Hemochromatosis

Neuromuscular Disease

Friedreich ataxia

Muscular dystrophy

Congenital atrophies

Storage Disorders and Other Depositions

Hunter-Hurler syndrome

Glycogen storage disease

Fabry disease

Amyloidosis

Conditions Associated with Heart Muscle Diseases

include inflammatory diseases of the myocardium that result in injury to cardiac myocytes the inflammatory process is thecause rather than a response

to myocardial injury

Myocarditis

Major Causes of Myocarditis

Infections

Viruses (coxsackievirus, ECHO, influenza, HIV, CMV)

Chlamydiae (eg. C. psittaci)

Rickettsiae (eg. R. typhi, typhus fever)

Bacteria (eg. C. diphtheriae, N. meningitidis, Borrelia)

Fungi (eg. Candida)

Protozoa (eg. T. cruzi, toxoplasmosis)

Helminths (eg. Trichinosis)

Immune-mediated reactions

Postviral

Poststreptococcal (rheumatic fever)

SLE

Drug hypersensitivity

Transplant rejection

Unknown

Sarcoidosis

Giant cell myocarditis

Gross: normal or dilated;lesions diffuse or patchy

ventricular myocardium flabby & mottled by either pale foci or minute hemorrhagic lesions

mural thrombi present in any chamber

Micro: interstitial inflam infiltrate &focal necrosis of myocytes adjacent to the inflam cells

Morphology

PERICARDIAL DISEASE

Normal: 30-50 ml; thin, clear, straw-colored fluid in the pericardial sac

parietal pericardium undergoes distention by

- fluid: pericardial effusion- blood: hemopericardium- pus: purulent pericarditis

Pericardial Effusion & Hemopericardium

Types of Pericardial effusion Serous: most common form

- Causes: CHF, hypoproteinemia Serosanguinous: usually the result

of blunt chest trauma (eg. CPR) Chylous: lymphatic obstruction

Hemopericardium: accum of pure,often clooted blood in the pericardium w/o an inflam component

Cause: traumatic perforation myocardial rupture after a transmural

MI rupture of the intrapericardial aorta, hge from an abscess or tumor

metastasis

PericarditisInfectious Agents

Viruses

Pyogenic bacteria

Tuberculosis

Fungi

Other parasites

Presumably Immunologically Mediated

Rheumatic fever

Systemic lupus erythematosus

Scleroderma

Postcardiotomy

Postmyocardial infarction (Dressler) syndrome

Drug hypersensitivity reaction

Miscellaneous

Myocardial infarction

Uremia

Following cardiac surgery

Neoplasia

Trauma

Radiation

usually secondary to a variety of cardiac diseases, thoracic or systemic dso, metastases from neoplasms arising in remote site or a surgical procedure in the heart most often of viral origin

Pericarditis

Serous pericarditis: RF, SLE,scleroderma, tumors & uremia

Morph: inflam reaction in the epicardial &pericardial surfaces w/

scant numbers of PMNs, lymphocytes, & macrophages

Acute Pericarditis

Fibrinous / Serofibrinous pericarditis: - most frequent type of pericarditis

composed of serous fluid mixed w/ a fibrinous exudate

Causes: AMI, Dressler syndrome, uremia, chest radiation, RF,

SLE,trauma Clinical: pericardial friction rub

Morph:

Fibrinous: surface is dry w/ a fine granular roughening

Serofibrinous: increased inflam process induces more & thicker fluid (yellow & cloudy) & often fibrin

Purulent or Suppurative pericarditis: denotes invasion of the pericardial

space by infective organisms Routes:

a) direct extension fr neighboring inflam

b) seeding from the blood c) lymphatic extension d) direct extension during cardiotomy

Purulent pericarditis: Exudate ranges from a thin to

creamy pus of up to 400 to 500ml- serosal surfaces are

reddened, granular, & coated w/ the exudate

Micro: acute inflam reaction- organization is the usual

outcome

Hemorrhagic pericarditis: composed of blood mixed w/ a fibrinous

or suppurative effusion most commonly caused by malignant

neoplastic involvement of the pericardial space

Other causes: bacterial infections, patients w/ an underlying bleeding diathesis, TB, cardiac surgery

Caseous pericarditis

Healing of acute lesions resolution or pericardial fibrosis ranging from a thick, pearly, nonadherent epicardial plaque (soldier’s plaque), to thin delicate adhesions to massive adhesionsAdhesive mediastinopericarditis:

pericardial sac is obliterated & the parietal layer is tethered to mediastinal tissue

Chronic or Healed Pericarditis

Constrictive pericarditis: marked by thick, dense, fibrousobliteration, often w/ calcification of the pericardial sac that encases the heart, limiting diastolic expansion & restricting cardiac output

- most common cause: TB

Chronic or Healed Pericarditis

Adhesive Mediastinopericarditis - follow a suppurative or caseous pericarditis, previous cardiac surgery, or irradiation to the mediastinum. - pericardial sac is obliterated, and adherence of the external aspect

of the parietal layer to surr structures produces a great strain on cardiac function.

CARDIAC NEOPLASMS

CARDIAC NEOPLASMS

Rare

Metastatic tumors: 5%

Benign tumors: 80-90% of primary tumors of the heart

Myxoma

Most common primary cardiac tumor in adults

90 % located in the left atrium Complication :

ball-valve obstruction embolization

Myxoma Gross: almost always single

- favored site of origin: region ofthe fossa ovalis in the atrial septum

- Size: small to large (up to 10 cm.)- sessile or pedunculated masses that vary from globular hard masses mottled w/ hge to soft, translucent, papillary,or villous lesions having a gelatinous appearance

Micro: stellate or globular myxoma (“lepidic”) cells, endothelial cells, smooth muscle cells and undifferentiated cells embedded within an abundant acid mucopolysaccharide ground substance & covered on the surface by endothelium Carney’s syndrome: autosomal dominant

transmission, multiple cardiac & extracardiac myxomas, spotty pigmentation, & endocrine overactivity

Rhabdomyoma

Most frequent primary cardiac tumor in children

Most arise from ventricular chamber

cause valvular or outflow tract obstruction

Rhabdomyoma Gross: small, gray-white myocardial

masses up to several cm located on either the left or the right side of the heart & protruding into the ventricular chambers

Micro: large, rounded, or polygonal cells containing numerous glycogen-laden vacuoles separated by strands of

cytoplasm running from the plasma membrane to the more or less centrally located nucleus (spider cells)

Metastases to the heart

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