DISEASES OF THE HEART - content

• Cardiac hypertrophy and congestive • Cor pulmonale • Hypertensive heart disease

• Ischemic heart disease

• Valvular diseases • Myocardial diseases • Congenital heart diseases • Diseases of the • Cardiac neoplasms Normal values assessed by

• Free wall thickness: RV: 3-4 mm, LV: 10-11 mm

• End-diastolic volume (EDV) 120 ml • End-systolic volume (ESV) 50 ml • Stroke volume (SV) 70 ml

Weight: women: 300 gs, men: 350 gs

HYPERTROPHY OF THE HEART

• The cardiac myocytes are permanent cells (not able to enter the cell cycle) and, therefore, are not able to proliferate

• Increase in work load  increase in size and pumping capacity of ventricular myocytes

• Weight > 400 g

• Types: concentric dilative

Concentric hypertrophy

Pathogenesis An obstruction of outflow in systole (i.e., hypertension, stenosis)  the LV increases the end-systolic pressure  pressure overload   concentric remodeling and hypertrophy Morphologic features of concentric hypertrophy of LV: small lumen; markedly increased wall thickness (> 20 mm); increased mass (> 500 g) Clinical features of pressure-overloaded LV

- symptomless for a long period

- pump failure occurs lately

- risk of sudden cardiac death

Dilative hypertrophy

Pathogenesis Aortic/ incompetence leads to diastolic backflow  the regurgitated extra volume of blood is accepted with the dilation of the LV  an increased EDV is ejected into the circulation during the next systole (volume overload)  excentric remodeling and hypertrophy

Morphology of dilative hypertrophy of LV: enlarged lumen, enlarged size, slightly increased wall thickness, increased mass

Anterior wall

Septum

Posterior wall Clinical features of volume-overloaded LV

- pump failure occurs relatively early

- good response to drugs increasing contractility

- overall prognosis is better than that of pressure overload Cardiac hypertrophy  congestive heart failure

Pressure overload; Noncontracting areas in Volume overload; concentric HT: myocardial ; volume dilative HT: hypertension, overload: aortic incompetence, mitral incompetence

 cardiac work Heart failure Pump failure  wall stress Neurohumoral activation

 cell strech Neurohumoral activation Norepinephrin  Activation of the renin-angio- tensin-aldosteron system Progressive dilative hypertrophy Atrial natriuretic peptid 

 contractility; systolic dysfunction ARRHYTHMIAS

• Two types: tachyarrhythmia (>100 beats/minute) and bradyarrhythmia (<60 beats/minute)

• Dg.: upon ECG features

• Atrial and ventricular tachyarrhythmias have particular importance Pathogenesis •Most common arrythmia, due to atrial fibrosis resulting from atrial strech, atrial , neurohumoral activation, etc.. •The electrical signals don't begin in the SA node. Instead, they begin in another part of the atria (300- 600/minute) and spread a rapid, disorganized way; only a proportion of the impulses are conducted to the ventricles. •The atria and ventricles do not beat in a coordinated way; the ventricles usually beat 100 to 180 times a minute tachyarrhythmia Some risk factors of atrial fibrosis

• Coronary heart disease, hypertensive heart disease,

• Congestive heart failure per se

• Hyperthyroidism, alcohol toxicity, etc., Clinical features • Can be asymptomatic or symptomatic (palpitation [feeling that your heart is beating too hard or too fast, skipping a beat, or fluttering], tachyarrhythmia, dizziness, etc.,

• The pulse at wrist feels irregular and beats may be variable in strength

• Complications: atrial thrombi, embolism induced- , heart failure, and syncope [fainting; short loss of consciousness and muscle strength] Treatment

• Sinus rhythmus can be achieved with antiarrhythmic drugs or electrical cardioversion or catheter-based ablation technologies

• Anticoagulant therapy to prevent thrombus formation Life-threatening ventricular tachyarrhythmias

Sustained ventricular (>30 sec)

• Results in dizziness, syncope, hypotension and

• Pulse rate between 120 and 220 beats/minute

• Emergency electrical cardioversion is often necessary

• Very rapid and irregular ventricular activation with no mechanical effect

• The patient is pulseless and becomes rapidly unconscious, and respiration ceases (cardiac arrest)

• Treatment: electrical defibrillation CONGESTIVE HEART FAILURE (HF)

The myocardium is no longer able to pump sufficient blood to meet the need of the body, even at rest

Reduced systolic output (forward failure) is accompanied by inadequate emptying of the heart chambers (backward failure)  congestion in the venous circulation Classification

The pump failure may involve the left or right ventricle or both; and may be acute or chronic

Outcome: most frequent cause of death ACUTE LEFT-SIDED HF

Causes • Hypertensive crisis • Acute myocardial infarction • Others

Morphology Features of hypertensive heart disease or acute myocardial infarction + pulmonary edema

Pulmonary edema: lungs >1200 gs, congested and wet, airways contain bubbly fluid Clinical features

Forward failure (echocardiography: ejection fraction ≤ 40%) Hypoperfusion and dysfunction of major organs: Brain – somnolence  loss of concioussness Kidney - oliguria Liver - jaundice Gut - trophic erosions/ulcers  bleeding

Backward failure Pulmonary edema, cardiac dyspnea (shortness of breath) and tachypnea + right HF

Outcome Varies, frequently results in death CHRONIC LEFT-SIDED HF

Causes • Hypertensive heart disease • Chronic ischemic heart disease • Valvular heart disease: - aortic stenosis - aortic incompetence - mitral incompetence Morphology

1) Dilative hypertrophy of LV

2) Lateral dysplacement of the papillary muscles causing mitral regurgitation

3) Subsequent chronic dilation of the LA + thrombus in the left auricle

4) Brown induration of lungs Some interstitial fibrosis, alveolar microhemorrhages  hemosiderin-laden macrophages; sec. -induced atheromatous plaques in the pulmonary arteries Brown induration of lungs; atheromatous plaques in pulmonary arteries indicating sec. pulmonary hypertension Chronic congestion of lungs. Hemosiderin-laden macrophages in the alveoli Clinical features

Forward failure:  physical activity,  weakness

Backward failure: • Dyspnea during exercise than at rest • Fluid retention • Pulmonary edema, later systemic venous edema • Mitral regurgitation: systolic murmur

LA dilation  atrial strech  chronic atrial fibrillation  thrombus in the left auricle  danger of systemic thromboembolism

Prevention of thrombus formation: anticoagulation Outcome

The pump failure in the terminal phase is lethal (New York Heart Association grading for cardiac status; NYHA Grade IV)

Frequently, intercurrent upper airway or pulmonary infections (influenza, bronchopneumia) are the direct cause of death ACUTE RIGHT-SIDED HF

Cause • Massive pulmonary thromboembolism: obstruction of >50% of the pulmonary vascular bed

Morphology • Dilation of the RV plus • Acute systemic congestion: passive hyperemia of liver, spleen, kidneys, GI mucosa

Outcome • Fatal in significant number of cases

The liver in prolonged right-sided HF

• Hepatic congestion is complicated with necrosis in the centrilobular regions; the necrotic foci undergo sec. hemorrhage due to sinusoidal ruptures: central hemorrhagic necroses

• Necroenzymes AST (aspartate aminotransferase) and ALT (alanine aminotransferase) become elevated in the blood Hemorrhagic necrosis around the central vein (encircled) Portal tracts CHRONIC RIGHT-SIDED HF

Dilation and hypertrophy of the RV in response to chronic pulmonary hypertension

Causes 1. Chronic left-sided HF; mitral stenosis

2. Chronic diseases of the lung (chronic cor pulmonale) Obstructive diseases: chronic bronchitis, emphysema, bronchiectasis, + bronchial asthma Restrictive (interstitial) diseases, such as idiopathic pulmonary fibrosis, pneumoconiosis, Boeck sarcoidosis

3. Diseases of the pulmonary artery: recurrent pulmonary thromboembolism, primary pulmonary hypertension Causes

4. Deformities affecting chest movement: pectus carinatum (pigeon’s chest), pectus excavatum (funnel chest), kyphoscoliosis (abnormal curvature of the spine in both a coronal and sagittal plane)

5. Neuromuscular diseases affecting respiratory muscles Morphology RV hypertrophy (thickness › 6 mm) + dilation and manifestations of chronic systemic congestion Chronic systemic congestion

• Anasarca (pedal and pretibial edema; in bedridden patients: presacral) • Bilateral hydrothorax (500 - 1000 ml) • Hydropericardium (300 - 500 ml) • Ascites • Cyanotic induration of liver, spleen (congestive hepato- and splenomegaly) • Chronic congestion of the gut mucosa Chronic congestion of liver

Cyanotic induration  fibrotic replacement of the hepatocytes  cardiac fibrosis  fibrotic septa form pseudolobules  cardiac cirrhosis (rare) HYPERTENSIVE HEART DISEASE

LV hypertrophy as a response to long-standing systemic arteriolar vasospasm

Early phase: concentric hypertrophy of LV: wall thickness > 20 mm; weight > 500 g Late phase: LV hypertrophy + dilation: wall thickness < 20 mm; weight > 550 g Clinical features

• Asymptomatic for a long time

• Atrial fibrillation is common (results from left and strech)

• Cause of death in 1/3 of hypertensive patients (congestive HF, sudden death)

• Since hypertension aggravates atherosclerosis, patients with hypertensive heart disease also suffer from coexisting ischemic heart disease ISCHEMIC HEART DISEASE (IHD)

• The most common cause of death in industrialized countries

• Pathogenesis: reduced coronary blood flow commonly due to coronary atherosclerosis

• Atherosclerosis causes chronic progressive narrowing of the coronary lumina, a process that can be punctuated by acute disruption of vulnerable plaques and thrombosis Atheromatous plaque- induced stenoses (arrows)

Prof. Rudas László, Kör-ITO IHD manifests clinically in four overlapping syndromes, differing in severity and tempo:

1. Sudden cardiac death

2. pectoris

3. Myocardial infarction (MI)

4. Chronic IHD 1. SUDDEN CARDIAC DEATH

Victims have stenosing plaques, often with occlusive thrombus on the left anterior descending (LAD) artery (artery of ‘sudden death’)

Cause of death: Fatal (ventricular fibrillation  ) Sudden death of a 48-year-old heavy smoker man Autopsy: LAD artery thrombosis on a stenosing plaque 2. ANGINA PECTORIS

• Substernal paroxysmal pain or discomfort precipitated by exercise or excitement and relieved by rest

• The pain radiates to the shoulder and left arm  sign of myocardial ischemia Main forms of angina

Stable • Most common • Precipitated by exercise or excitement • Associated with 70% or greater chronic stable stenosis

Unstable • Pain is becoming increasingly more severe and is precipitated by increasingly less effort • Acute plaque disruption  partial thrombosis or hemorrhage  complete occlusion within 0.2-4 hours

Prinzmetal’s • Occurs at rest • Related to the spasm of coronary arteries • Responds well to nitroglycerin 3. CORONARY OCCLUSION AND MYOCARDIAL INFARCTION (MI)

Pathogenesis • Plaque rupture with superimposed thrombosis • Intraplaque hemorrhage • Rarely: vasospasm, embolisation in the coronary circulation Consequence

• Ischemia of supplied myocytes  contractile dysfunction  necrosis of supplied myocytes  contractions cease

• Necrosis is complete within 4 to 6 hours  anemic infarction within 24-48 hours

• Types of MI: transmural or subendocardial

TRANSMURAL INFARCTION

Occurs within the distribution of a single coronary artery and the full thickness of the ventricular wall is involved

• 50% of cases: LAD artery obstruction  anteroseptal infarction

• 20%: circumflex (Cx) artery obstruction  lateral infarction

• 30%: right coronary (RC) artery obstruction inferior infarction; may clinically be silent Anatomic distribution of transmural MI

JCE Underwood: General and Systemic Pathology, 2004 Occlusive thrombus (dissected with the scissor) on atheromatous plaque (arrow) Morphologic changes after coronary occlusion

Time frame Grossly Microscopically after occlusion 0-18 hours None None 18-48 hours Dark mottling or pale Early myocyte necrosis, neutrophils , edema 2-7 days Anemic infarction Complete Mural thrombus on coagulative necrosis Focal fibrinous 1-3 weeks Grayish, depressed Granulation tissue >1 month Firm, gray Scar tissue (fibrosis) MI: yellowish area of necrosis, hyperemic border Fibrosis of myocardium: dense collagenous scar at site of previous infarction ST-elevation (arrow) in coronary occlusion

Prof. Rudas László, Kör-ITO Clinical features of coronary occlusion (see pathophysiology lectures)

• Substernal pain persisting for > 20 min and not relieved by nitroglycerin

• Rapid, weak pulse, sweating, dyspnea, etc.

• ECG: ST-elevation

• Blood chemistry: 2 to 4 hours after coronary occlusion, troponin I and creatine kinaseMB become detectable as myocardial cells start to undergo necrosis; the titers are increasing; peak at 48 hours Clinical consequences of coronary occlusion and MI

0-18 hr - anemic infarct: not present yet

• Sudden death

• ”Malignant” arrhythmias, such as , ventricular fibrillation  lethal without treatment (half of coronary occlusion-associated deaths occur within the first hour!!!)

• In survivors: acute left-sided HF; if half of the LV does not contract  cardiogenic shock  mostly lethal

2-7 days – consequences of anemic infarct

Rupture of the infarcted area (lethal):

• Free wall:

• Septum: left-to-right shunt

• Papillary muscle  mitral incompetence

Embolism from mural thrombi

Hemopericardium due to rupture of the free wall of the LV

61 Rupture of the interventricular septum

62 Months after – consequences of healed infarct (fibrosis)

• Chronic aneurysm (does not rupture!)

• Embolism from thrombi in aneurysm

• Scar in the posterior wall: mitral regurgitation

• Compensatory hypertrophy and dilation of the LV  chronic left-sided HF, and death within years

Anteroseptal chronic aneurysm Apical chronic aneurysm, with mural thrombus MI, late phase Q-wave

Prof. Rudas László, Kör-ITO Modification of infarct size by restoration of coronary flow (reperfusion)

Life expectancy without reperfusion therapy:

Myocardial necrosis

• in > 50% of the LV  cardiogenic shock  death

• in 30% of the LV  if the patient survives the first 3 weeks  myocardial fibrosis  congestive HF years later Coronary arteries function as end arteries  collateral circulation does not exist in healthy individuals

Good news

• In response to gradually developing stenosing plaques  collaterals progressively open

• Repeated angina pectoris or silent ischemia induce myocytes to tolerate a greater subsequent ischemic insult (phenomenon of preconditioning)

• After preconditioning, the loss of myocardial viability in infarction is progressive, occurring over a period of several hours

Aim of medical treatment To restore blood flow in the area at risk for infarction and thereby to rescue the ischemic (but not yet necrotic) heart muscle

Tool for reperfusion Percutaneous transluminal coronary angioplasty followed by stent implantation

Results of reperfusion

• < 20 min: necrosis does not develop

• 2-4 hr: partial salvage: small-sized infarction (reperfusion injury)  small area of scar tissue

• > 6 hr: does not decrease myocardial infarct size; if patients survive, large scar  later congestive HF

Reperfusion injury

• Complex pathogenesis

• Grossly:

• Microscopically: necrobiotic muscle fibers with hypereosinophilic contraction bands + disrupted capillaries + interstitial hemorrhage

• Healing: by fibrosis Reperfusion injury: hemorrhage in the septum, and the anterior and posterior wall; angioplasty 12 hours after the onset of symptoms

Anterior Septum

LV

RV

Posterior Contraction bands: intensely eo transverse bands composed of hypercontracted sarcomers (irreversible) SUBENDOCARDIAL MI

Pathogenesis • The subendocardial region is most vulnerable to hypoperfusion and hypoxia

• In patients with several stenosing plaques in the coronaries, transient decreases in O2 delivery as from hypotension (i.e., polytraumatisation, GI hemorrhage), anemia or pneumonia or increases in O2 demand as with tachycardia or hypertension can cause subendocardial MI

Morphology

• Multifocal; smaller areas are involved

• Coagulative necrosis of cells and/or myocyte vacuolization (myocytolysis)

• Heals with fibrosis

ECG: non-ST elevation MI

Outcome: better prognosis than transmural MI, if the initiating injury responds to appropriate therapy

Myocytolysis: loss of staining of nuclei (irreversible) 4. CHRONIC IHD

Pathogenesis • Progressive HF in elderly patients • Exhaustion of the hypertrophied viable myocytes • History of angina pectoris and/or recognized MI

Morphology

• Plaques with severe stenosis in LAD, CX, RCA • Dilated hypertrophy; all chambers are dilated • Cut surface: small (2-3 mm) fibrotic foci + larger transmural scars • + Mural thrombi in ventricles or atria Chronic IHD: dilative hypertrophy, apical fibrosis (arrow), dilated atrium, thrombus in the left auricle

79 Causes of death • Congestive HF • Re-infarction • Arrhythmia