Introduction part 1
The homo sapiens heart pumps over 5 liters of blood per minute to meet the body’s need. However, abnormal changes in their structure may lead to disturbing physiological consequences.
Cardiovascular disease reduces life expectancy and increases health cost, & is the number one cause of worldwide death. The overall weight of the heart averages about 325gm (0.5% of body weight), with much coming from the left ventricle. The left ventricle thickness is about 1.4cm, while the right ventricle thickness is about 0.4cm.
Hypertrophy results from an increase in heart’s weight or thickness, which is the cause of cardiomegaly. However, cardiomegaly may also result from both dilation and hypertrophy or either of them. Dilation is simply, the enlargement of the chamber size.
The myocardium composes of cardiac myocytes responsible for systole & diastole. Ventricular systole depends on the effective overlap of the actin & myosin filament, that causes the shortening of the sarcomere & eventually the myocyte.
In a normal ventricular dilation (diastole), heart filling stretches the cardiac muscle, increasing the degree of sarcomere shortening, & eventually the force of contraction. In excessive dilation, the actin-myosin overlap reduces, resulting in a decrease in the force of contraction and heart failure.
Atrial myocytes produce atrial natriuretic peptide, effective in vasodilation, natriuresis & diuresis, & beneficial in hypertension and congestive heart failure. The intercalated discs link up individual cardiac myocytes and contain specialized intercellular structures including gap junctions, for mechanical, electrical integration.
Gap junctions provide passage of ions across the membranes of adjoining cells. The abnormalities in their spatial distribution & respective proteins result in arrythmias & heart failure from ischemic & myocardial heart disease.
Introduction part 2
The heart valves enable a unidirectional flow of blood through the heart, & include mitral, tricuspid, aortic & pulmonary valves. The architecture of the valves from their outflow to inflow surface include: dense collagenous core> loose connective tissue> elastin layer> endothelial covering.
The function of the semilunar valves depends mainly on their structural integrity and movement. Therefore, in conditions of aortic root dilation, this can affect the semilunar valves, resulting in regurgitation. However, the function of the atrioventricular valves (AVV) depends on chordae tendineae, papillary muscles & the valves’ structural integrity. Conditions due to papillary muscle dysfunction, tendon rupture, & ventricular dilation may affect AVV closure, resulting in regurgitation.
In order to ensure a coordinated contraction of cardiac muscle, specialized excitatory and conducting myocytes- the cardiac conduction system is essential. They include: SA node> AV node> bundle of His> Right & left bundle branch> left anterior & posterior fascicles of the LBB> Purkinje fibers.
The three major coronary arteries include: left anterior descending (septal & diagonal branches); left circumflex artery (marginal branches); right coronary artery.
CARDIAC ORGANOGENESIS AND CAUSES OF CONGENITAL HEART DFECTS
By 15th day, earliest cardiac precursors from lateral mesoderm form 1st & 2nd heart field crescent cells> Progenitor cells of the 1st heart field form the LV, while that of 2nd heart field form the RV, atria, & conotruncus (outflow tract)> By 20th day, a beating tube forms that loops rightward> by 28th day, heart chambers begin to form>
neural crest cells migrate to divide the conotruncus into aortic arch & pulmonary trunk> endocardial cells invade ECM, to proliferate & differentiate into mesenchymal cells> ECM swells to form endocardial cushions that produce the atrioventricular valves (AVV) & outflow tract valves (OTV)> By the 50th day, further separation of ventricles, atria & AVV produce the four heart chambers.
Causes: partial loss of transcription factors following genetic abnormalities; congenital rubella infection; gestational diabetes; teratogenic therapeutic drugs; folate deficiency.
Next, we shall discuss the pathologies of cardiovascular system.
Congestive heart failure (heart failure)
Results from failure of the heart to pump blood sufficiently enough to meet metabolic demands of tissues. The two types are left & right sided heart failure.
Predisposing factors: chronic heart disease from chronic work overload, in valvular disease or hypertension; myocardial infarction; acute hemodynamic stresses from fluid overload or acute valvular dysfunction. These factors may cause systolic dysfunction.
Other predisposing factors: massive left ventricular hypertrophy, myocardial fibrosis, amyloid deposition, & constrictive pericarditis. These factors cause diastolic dysfunction.
How the heart responds: via the Frank-starling mechanism (increased filling volume to dilate the heard in order to enhance heart contraction); ventricular remodeling (hypertrophy); norepinephrine release by sympathetic nerves (increases HR, contraction, & vascular resistance); activation of ANP & renin-angiotensin-aldosterone system (to maintain filling volumes & pressure).
Signs & symptoms: low cardiac output & tissue perfusion; pooling of blood in the venous system; pulmonary edema; peripheral edema.
Decompensated cardiac hypertrophy
This condition results from cumulative changes that occur during cardiac hypertrophy. Clinical manifestations include: cardiomegaly, cardiac failure, & sudden death.
Two forms of hypertrophy: pressure, & volume overload hypertrophy.
Causes of pressure overload hypertrophy: systemic hypertension; aortic stenosis; mitral stenosis. Causes of volume-overload hypertrophy include: mitral regurgitation; aortic regurgitation; & myocardial infarction
Other causes of cardiac hypertrophy include: dilated cardiomyopathy; hypertrophic cardiomyopathy; mitral regurgitation; aortic regurgitation; activation of β-adrenergic receptors; ischemic heart disease.
Pathogenesis: increase in myocyte size> disproportionate capillary number> low oxygen & nutrient delivery to hypertrophied heart> fibrous tissue deposition> expression of immediate-early genes (c-fos, c-myc, c-jun, EGR1)> genetic expressions of fetal/embryonic forms of β-myosin, collagen, ANP> high metabolic demands> increased oxygen consumption>
abnormal myocardial metabolism> alterations in intracellular handlings of calcium ions> myocytes apoptosis> down-regulation of miR-208 (protective when over-expressed)> heart failure.
Left-sided heart failure
This is the failure of left ventricular wall contraction, resulting in pulmonary congestion, tissue hypoperfusion, & organ dysfunction. Macroscopically, there is left ventricular hypertrophy & dilation. Two forms: systolic & diastolic failure.
Systolic failure results from factors that damage the contractile function of the left ventricle, leading to insufficient cardiac output. Diastolic failure arises from the abnormal stiffness of left ventricle & restricted ability to relax during diastole. In diastolic failure, cardiac output is preserved at rest, but affected during strenuous exercises due to rises in left ventricular filling pressure.
Common causes include: hypertension; ischemic heart disease; myocardial diseases; aortic and mitral valvular diseases.
Predisposing factors for diastolic failure: age >65; female gender; hypertension (most common); diabetes mellitus; bilateral renal artery stenosis; obesity; myocardial fibrosis in cardiomyopathies & IHD; cardiac amyloidosis; restrictive pericarditis.
Clinical manifestations: left atrial dilation & stasis; atrial fibrillation; thrombosis & thromboembolic stroke; pulmonary congestion, & edema; cough & dyspnea; orthopnea; paroxysmal nocturnal dyspnea; hypoxic encephalopathy; irritability; restlessness.
Other clinical manifestations: reduction in renal perfusion & activation of renin-angiotensin-aldosterone system> salt & water retention> expansion of extracellular fluid volume> exacerbation of pulmonary edema> prerenal azotemia in severe renal hypoperfusion. It is complicated by right-sided heart failure.
Diagnosis: Kerly B-lines on X-ray images, which signifies perivascular and interstitial edema in the interlobular septa.
Cor pulmonale
This is an isolated right-sided heart failure that results from various disorders affecting the lungs. Causes of Cor pulmonale are: hypoxia; chronic sleep apnea; high altitude; parenchymal diseases of the lungs; primary pulmonary hypertension; recurrent lung thromboembolism.
Pathogenesis: increased pulmonary hypertension> hypertrophy & dilation of the right ventricle & atrium.
Clinical manifestations: congestive hepatic central vein & hepatomegaly: portal hypertension, splenomegaly (≥150gm), & bowel edema; pericardial & peritoneal effusions; ascites; ankle & pretibial edema; presacral edema; anasarca; mental deficits.
Other clinical manifestations: congestive kidney, peripheral edema with azotemia; left ventricular dysfunction, lung edema, & pleural effusion; biventricular CHF.
Treatment and management: ACE inhibitors; β-1 adrenergic blockers; diuretics.
Right to left shunt
This arises from abnormal channels between heart chambers or blood vessels, resulting in blood flow from pulmonary to systemic circulation.
Causes include: tetralogy of Fallot; transposition of great arteries; persistent truncus arteriosus.
Clinical manifestations: hypoxemia; cyanosis; paradoxical embolism; brain infarction & abscess; hypertrophic osteoarthropathy (clubbing of the tips of fingers & toes from prolonged cyanosis).
Left to right shunt
This arises from abnormal channels between heart chambers or blood vessels, resulting in blood flow from systemic to pulmonary circulation. The causes are: patent ductus arteriosus; atrial septal defect (ASD); ventricular septal defect (VSD).
Clinical manifestations: increased volume and pressure in pulmonary circulation; right ventricular hypertrophy & pulmonary artery atherosclerosis; pulmonary arterial vasoconstriction; pulmonary vascular resistance & hypertension; right to left shunt; late cyanosis.
Atrial septal defect
This is an abnormal, fixed opening in the atrial septum arising from incomplete tissue formation resulting in left to right shunt. Symptoms are usually evident after age 30.
Clinical manifestations: murmur around the pulmonary valve; right-sided volume overload. Complications are: heart failure; paradoxical embolism; irreversible pulmonary hypertension.
Patent foramen ovale
A small opening created by an unsealed open flap of tissue in the atrial septum at the oval fossa after birth. The unsealed flap may open due to factors that add more pressure on the right side of the heart.
Predisposing factors: sustained pulmonary hypertension; sneezing; bowel movement; coughing.
Clinical manifestations: brief right to left shunt; paradoxical embolism.
Ventricular septal defect
An incomplete closure of the ventricular septum that allows free flow of blood between the right and left ventricles.
Clinical manifestations: left to right shunting; right ventricular hypertrophy; pulmonary hypertension; irreversible pulmonary vascular disease; new right to left shunting; cyanosis; & death.
Patent ductus arteriosus
This occurs when the ductus arteriosus, which spontaneously closes, remains open after birth. Newborns are usually asymptomatic at birth.
Clinical manifestations: left to right shunting> harsh murmur> (machinery-like)> volume or pressure overload> pulmonary hypertension> pulmonary vascular disease; (in case of any VSD), new right to left shunt.
Complete atrioventricular septal defect
A large hole in the heart, in which all four heart chambers freely communicate, resulting in volume hypertrophy of each. It occurs often among Down syndrome patients.
Causes: It arises from embryologic failure of the superior and inferior endocardial cushions to adequately fuse. Hence, leading to incomplete closure of the AV septum, & malformation of tricuspid and mitral valves.
Tetralogy of Fallot
A disorder with four features including VSD, overriding aorta; right ventricular hypertrophy & subpulmonic stenosis/pulmonary valvular stenosis. They all arise embryologically from anterior superior displacement of the infundibular septum.
Clinical manifestations: right to left shunting; cyanosis at birth.
Transposition of great vessels
A condition in which the aorta arises from the right ventricle, and the pulmonary artery from the left ventricle. The embryologic defect is due to abnormal separation of truncal and aortopulmonary septa.
It may occur in association with VSD (creates a stable shunt) or patent foramen ovale/PDA (they create an unstable shunt).
Clinical manifestations: right to left shunt; right ventricular hypertrophy; left ventricular atrophy.
Persistent truncus arteriosus
This arises from a developmental failure of the embryologic truncus arteriosus to separate into aorta and pulmonary artery. Hence, truncus arteriosus gives rise to systemic, pulmonary, and coronary branches, while also receiving blood from both ventricles. It occurs in association with VSD.
Clinical manifestation: pulmonary hypertension> right to left shunting> cyanosis> irreversible pulmonary hypertension.
Stable angina, Prinzmetal angina, Unstable angina
They are forms of angina pectoris, a clinical syndrome of IHD/CAD that feature sudden, recurrent attacks of precordial or substernal chest discomfort. The discomfort may be choking, squeezing, constricting, or knifelike. These conditions arise from a short-term duration (15sec-15min) of myocardial ischemia, without myocyte necrosis.
Stable angina is the most common form of angina pectoris, resulting from an imbalance in myocardial perfusion and demand. The cause includes a chronic stenosing coronary atherosclerosis. Predisposing factors include physical activity, emotional excitement, or any other cause of increased cardiac work load. Alleviating factors include rest and nitroglycerin.
Prinzmetal variant angina arises from coronary artery spasm with a possibly underlying significant coronary atherosclerosis. It has no relation with exercise, heart rate, or blood pressure. Alleviating factors are nitroglycerin, and calcium channel blockers.
Unstable angina is an increasingly frequent pain with longer duration, that occurs at rest or lower levels of physical activity. The cause includes disruption of atherosclerotic plaque, partial mural thrombosis formation; embolization and vasospasm.
Acute myocardial infarction
An IHD syndrome presenting as the death of cardiac muscle fiber following a longer duration of severe tissue ischemia. Heart muscle necrosis initially occurs in the subendocardial zone, before spreading across the entire wall (transmural).
Causes: coronary artery pathology (90% of cases); vasospasm from cocaine abuse; ischemia from (vasculitis, sickle cell disease, shock, amyloid deposition in vascular walls, vascular dissection, inadequate myocardial protection during heart surgery); emboli from (left atrium, left-sided mural thrombosis, paradoxical emboli, intracardiac prosthetics, valve vegetations).
Pathogenesis in (90% of cases): atheromatous plaque rupture> platelet aggregation & microthrombi> formation> vasospasm> tissue factor activation> thrombosis and coronary artery occlusion.
Reversible myocyte injury for ischemia lasting <20min. presents with features such as: low ATP; lactic acid accumulation> cell swelling> loss of contractility> acute heart failure. Irreversible myocyte necrosis occurs when prolonged perfusion loss is ≥20min. Permanent heart damage takes place when duration of myocardial ischemia is ≥2hrs. Relatively significant number of healthy myocytes at risk are salvageable <2hrs. of ischemia.
Diagnosis: coronary angiography; ECG; cardiac troponin T & I- “the gold standard” (rises at 2-4hrs., peaks at 48hrs, & persists up to 10 days after MI); CK-MB (rises within 2-4hrs. peaks at 24hrs., & returns to normal within 72hrs.).
Coronary intervention techniques enable reperfusion to restore blood flow and rescue ischemic heart muscle. They include: thrombolysis; percutaneous transluminal coronary angioplasty with stenting; coronary artery bypass graft surgery.
Clinical manifestations: rapid, weak pulse; dyspnea; sweating; it may be asymptomatic in about 1/10th of patients.
Complications: contractile dysfunction and cardiogenic shock; arrhythmias; myocardial rupture (occurs 3-7 days after MI); cardiac tamponade; acute VSD; true and false ventricular aneurysms; Dressler syndrome (occurs 2-3 days after MI); acute right-sided HF; mural thrombosis; mitral valve regurgitation; chronic IHD.
Note: posterior transmural infarcts may produce conduction blocks or right ventricular dysfunction; large transmural infarcts produce arrhythmias, cardiogenic shock, & CHF; anterior transmural infarcts produce myocardial rupture, aneurysm, and mural thrombi.
Transmural infarction and Subendocardial infarction
These are forms of myocardial infarction differentiated by the distribution of necrotic tissues across the ischemic zone on a ventricular wall. Their causes include coronary atherosclerotic plaque rupture and thrombosis.
Transmural infarction involves the full thickness of the ventricular wall, leaving about 0.1mm of subendocardial myocardium. They produce ST-elevation infarcts on ECG. Subendocardial infarction affects one third to one half of the ventricular wall. They give rise to non-St elevation infarcts on an ECG. In addition, they can result from global hypotension due to noncritical coronary stenosis.
Myocardial reperfusion injury
An irreversible cell death on a vulnerable ischemic myocardium following the restoration of blood flow.
Pathogenesis: oxidative stress> calcium overload> potential inflammation, microvascular injury, & hemorrhage> capillary endothelial swelling and occlusion.
Predisposing factors: thrombolysis; angioplasty; stenting; coronary artery bypass graft surgery.
Chronic ischemic heart disease (ischemic cardiomyopathy)
An IHD syndrome, in which there is progressive heart failure, due to decompensated noninfarcted myocardium, following an ischemic myocardial damage. Medical history may include past MI, previous coronary arterial interventions; and angina attacks.
Predisposing factors: severe obstructive coronary artery disease. Macroscopically, left ventricular hypertrophy and dilation, with discrete scar tissues.
Sudden cardiac death
An unexpected death from heart diseases in persons without symptoms, or death within an hour of symptoms onset. This is also an IHD syndrome.
Predisposing factors: fatal arrhythmias; acute myocardial ischemia; myocarditis; heritable primary electrical disorders; dilated and hypertrophic cardiomyopathy; cardiac hypertrophy; cocaine, methamphetamine, and catecholamines; pulmonary hypertension; aortic valve stenosis; mitral valve prolapse.
The heritable primary electrical disorders include: long QT syndrome; short QT syndrome Brugada syndrome; Wolff-Parkinson White syndrome; catecholaminergic polymorphic ventricular tachycardia; congenital sick-sinus syndrome; isolated cardiac conduction disease.
Systemic hypertensive heart disease
This results from a hypertrophic adaptive response of the heart to pressure overload by hypertension, and leads to adverse effects. These effects include: myocardial infarction; cardiac dysfunction; cardiac dilation; CHF; sudden death.
Predisposing factors: chronic hypertension >140/90mmHg (Framingham study).
Criteria for diagnosis: left ventricular hypertrophy (without cardiovascular pathology) + history of hypertension.
Clinical manifestations: left ventricular hypertrophy; atrial enlargement; atrial fibrillation; CHF; IHD; cerebrovascular stroke; sudden cardiac death.