Cardiovascular Pathology PDF

PATHOLOGY OF THE CARDIOVASCULAR SYSTEM Mervin Sam E. Econ DMD  OUTLINE I. Pathology of the Heart A. Ischemic Heart Disease B. Rheumatic fever & Infective Endocarditis C. Valvular Heart Disease D. Congenital Heart Dis...

PATHOLOGY OF THE CARDIOVASCULAR SYSTEM Mervin Sam E. Econ DMD  OUTLINE I. Pathology of the Heart A. Ischemic Heart Disease B. Rheumatic fever & Infective Endocarditis C. Valvular Heart Disease D. Congenital Heart Disease E. Diseases of the Myocardium and Pericardium F. Tumors of the Heart G. Congestive Heart Failure H. Hypertrophy of the Heart II. Pathology of the Blood Vessels A. Arterial disorders B. Venous disorders C. Tumors of blood vessels D. Vasculitides E. Functional Vascular disorders F. Hypertension  INTRODUCTION Cardiovascular dysfunction can be attributed to one (or more) of six principal mechanisms: Pump failure ○ when the myocardium contracts weakly during systole and there is inadequate cardiac output Flow obstruction ○ Lesions can obstruct blood flow through a vessel (e.g., atherosclerotic plaque) ○ In the case of a valvular blockage, the increased pressure overloads the chamber that pumps against the obstruction.  INTRODUCTION Regurgitant flow ○ A portion of the output from each contraction flows backward through an incompetent valve, adding a volume overload to the affected atria or ventricles Shunted flow ○ Blood can be diverted from one chamber of the heart to another through defects that can be congenital or acquired ○ can also occur between blood vessels  INTRODUCTION Disorders of cardiac conduction (Automaticity of the Pacemakers) ○ Conduction defects or arrhythmias due to uncoordinated generation or transmission of impulses lead to nonuniform and inefficient myocardial contractions Rupture of the heart or a major vessel ○ With subsequent exsanguination, either into body cavities or externally.  IA ISCHEMIC HEART DISEASE PATHOLOGY OF THE HEART  ISCHEMIC HEART DISEASE (IHD) broad term encompassing several closely related syndromes caused by myocardial ischemia ○ an imbalance between cardiac blood supply (perfusion) and myocardial oxygen and nutritional requirements accounts for 80-90% of all heart disease mortality Most common causes of IHD: ○ atherosclerosis (90-95% of cases) ○ vasospasm ○ thrombosis ○ stenosis ○ inflammatory arteritis  ISCHEMIC HEART DISEASE (IHD) Ischemia refers to reduction in blood supply to an organ. If ischemia is reversed rapidly there is no permanent damage to the organ. Prolonged ischemia can cause necrosis of the organ tissue which is called an infarct.  ISCHEMIC HEART DISEASE (IHD) SYNDROMES TO BE DISCUSSED UNDER IHD: Angina Pectoris (reversible) ○ Stable/Typical Angina (↑ demand) ○ Prinzmetal/Variant Angina (vasospasm) ○ Unstable/Crescendo Angina (preinfarction) Myocardial Infarction ○ Permanent myocardial damage ○ coagulative necrosis ○ Due to irreversible myocardial ischemia  ISCHEMIC HEART DISEASE ACUTE CORONARY SYNDROME (ACS) applied to any of the catastrophic manifestations of Ischemic Heart disease (IHD): ○ Myocardial infarction (MI), where ischemia causes frank cardiac necrosis ○ Angina pectoris (literally “chest pain”), where ischemia is not severe enough to cause infarction, but the symptoms nevertheless portend infarction risk ○ Chronic IHD with heart failure ○ Sudden cardiac death (SCD)  ISCHEMIC HEART DISEASE (IHD) FACTORS THAT LEAD TO ENDOTHELIAL DYSFUNCTION AND ACTIVATION IN ACS Vascular Endothelium Results of ↓ Nitric Oxide: Important role in atherosclerosis development Vicious Cycle: further endothelial cell Patients with atherosclerosis have a activation, cell attraction, and further dysfunctional endothelium decrease in nitric oxide Reduced Nitric Oxide production Interferes with adhesion molecule Superoxides enhance degradation of nitric oxide production Endothelial dysfunction is thought to be the early ↓ vascular relaxation manifestation of atherosclerosis ↑platelet aggregation ↑ smooth muscle cell (SMC) proliferation  ISCHEMIC HEART DISEASE (IHD) ROLE OF PLATELETS IN ACS Platelets are activated with thrombin, Activated Platelets serotonin (5HT), and collagen causing: Adheres to injured vascular wall Platelet secretion of adenosine Forms aggregates diphosphate (ADP) and thromboxane Accelerate thrombin generation A2 (TxA2) vWF also binds platelets Further amplifies activation and ○ Causes conformational change in platelet itself recruitment of other platelets Activated GP IIb/IIIa receptor site Platelets aggregate via binding of the Exposure allows binding of fibrinogen to cause glycoprotein (GP) IIb/IIIa receptors to platelet fibrinogen & von Willebrand factor aggregation by cross-linking of fibrin (vWF) further promotes platelet aggregation and growth of forms an occlusive thrombus the thrombus  ISCHEMIC HEART DISEASE (IHD) Vulnerable Plaques Plaques that contain large atheromatous cores or have thin overlying fibrous caps More likely to rupture Extrinsic Influences to the Plaque Adrenergic Stimulation Put physical stress on the plaque by causing hypertension or local vasospasm Factors for Plaque Disruption ↑ numbers of macrophages ↑ expression of tissue factor ↓ numbers of smooth muscle cells lipid core with high proportion of plaque volume Thin cap When all of these factors coincide, the plaque is at high Earliest Lesions isolated foam cells or fatty streaks in the vessel wall Lesion growth occurs mainly by lipid accumulation Intermediate Lesions may be associated with small extracellular lipid pools progresses to atheroma has a core of extracellular lipid Fibrous Plaque Stage characterized by accelerated increases in smooth muscle and collagen Complicated Lesions characterized by thrombosis, fissure, and hematoma formation Sequence of events of vessels that become stenotic due to atheroma formation  ISCHEMIC HEART DISEASE (IHD) MYOCARDIAL INFARCTION Death of cardiac muscle due to prolonged ischemia Loss of contractility: within 1-2 minutes of onset of severe ischemia ○ Irreversible injury: 20-30 minutes, in the setting of severe ischemia (blood flow ≤10% of normal) Earliest detectable feature of myocyte necrosis: sarcolemmal membrane disruption → myocardial proteins in blood ○ Basis for chemical tests in MI EPIDEMIOLOGY Age Peak 55-64 years (males) 80’s (females) Sex (3:1, Males:Females) Risk Factors HPN, hypercholesterolemia, cigarette smoking, DM, sedentary lifestyle, & Oral Contraceptive use ISCHEMIC HEART DISEASE (IHD) MYOCARDIAL INFARCTION  PATTERNS OF MYOCARDIAL INFARCTION Transmural Epicardial vessel occlusion (with no intervention) Subendocardial Regional: Acute plaque change → thrombosis → lysis of thrombus → blood flow restored Circumferential pattern: Shock in people with non-critical CA stenosis Multifocal Microinfarction Microembolization, vasculitis, vascular spasm  ISCHEMIC HEART DISEASE (IHD) MYOCARDIAL INFARCTION PATHOGENESIS Coronary Arterial Occlusion Sudden change in an atheromatous plaque Exposing these lesions (subendothelial collagen, necrotic tissue) to platelets, they adhere, become activated and aggregate to form microthrombi Vasospasm is also stimulated (due to mediators released from platelets) Tissue factor activates the coagulation cascade, adding to the bulk of thrombus Thrombus evolves and occludes the lumen of vessel  ISCHEMIC HEART DISEASE (IHD) MYOCARDIAL INFARCTION PATHOGENESIS In the absence of Evident Coronary Vascular Pathology, other mechanisms responsible for reduced coronary blood flow include: Vasospasm Emboli, Mural Thrombi and Vegetations Paradoxical emboli Vasculitis Sickle cell disease Amyloid deposition  MYOCARDIAL INFARCTION GROSS MORPHOLOGY (see next slide) Main vessel involved: left anterior descending (LAD) artery > right coronary artery (RCA), left circumflex artery (LCX) Myocardial infarction Aortic > Tricuspid > Pulmonic Cardinal changes: Leaflet thickening, commissural fusion and shortening, and thickening and fusion of the tendinous cords ○ Fish mouth deformity: Calcification and fibrous bridging of valvular commissures Verrucae Small (1-2 mm) vegetations overlying necrotic foci along the lines of closure MacCallum Plaques Subendocardial irregular thickenings (usually in left atrium), exacerbated by regurgitant jets  IMPORTANT! In ACUTE RHEUMATIC FEVER (ARF), the characteristic manifestation of carditis is Mitral regurgitation (MR). In RHEUMATIC HEART DISEASE (RHD), the characteristic finding is Mitral stenosis (MS).  ID CONGENITAL HEART DISEASE PATHOLOGY OF THE HEART  CONGENITAL HEART DISEASE Diseases of heart and great vessels present at birth Most arise at 3-8 weeks AOG Most common genetic cause: Trisomy 21 (Down syndrome) Clinical categories: ○ Left-to-right shunts ○ Right-to-left shunts ○ Obstructive lesions  CONGENITAL HEART DISEASE LEFT TO RIGHT SHUNTS Clinically, acyanotic (initially) Characterized by increased pulmonary blood flow ○ Causes pulmonary vascular remodeling → pulmonary pressure = systemic pressure → right-to-left shunt (Eisenmenger mechanism) → clinically cyanotic ○ Pulmonary hypertension: marks irreversibility of CHD lesions  CONGENITAL HEART DISEASE LEFT TO RIGHT SHUNTS ATRIAL SEPTAL DEFECT (ASD) Defect in interatrial septum Types: ○ Secundum (90%) ○ Primum (adjacent to AV valves) (5%) ○ Sinus venosus (near entrance of SVC) (5%) Secundum ASDs generally well-tolerated (symptoms appear late in life (~30 years old) Diagnostic clues: ○ Fixed widely split S2: prolonged ejection of RV, increased BF across PV ○ Murmur: pulmonary stenosis-like, due to increased blood flow across PV  CONGENITAL HEART DISEASE LEFT TO RIGHT SHUNTS VENTRICULAR SEPTAL DEFECT (VSD) Most common congenital heart disease Types: ○ Membranous (90%): membranous interventricular septum ○ Infundibular: Below pulmonary valve ○ Muscular: Within muscular septum Size: ○ 10mm: non-restrictive VSDs: clinically, failure to thrive and repeated infections; if uncorrected, would lead to Eisenmengerization Closure of defect (Dictum: size matters) ○ Small defects usually (30-50% of cases) close spontaneously; most common: 1st 2 years of life ○ Small muscular VSDs are more likely to close (80%) than membranous (35%) ○ Vast majority of lesions that close do so before age 4 ○ Moderate to large VSDs are less likely to close  CONGENITAL HEART DISEASE LEFT TO RIGHT SHUNTS PATENT DUCTUS ARTERIOSUS (PDA) Ductus arteriosus: mechanism to bypass unoxygenated lungs and direct blood flow from pulmonary artery to aorta Functional closure occurs soon after birth ○ Increased oxygen tension, ↓PVR, ↓PGE2 Anatomic closure occurs few months after birth → ligamentum arteriosum Diagnostic clue: continuous machinery-like murmur Duct-dependent lesions: CHDs that rely on PDA for blood flow (e.g. TGA) Administration of PGE2 in infants for survival (to maintain patency of DA)  CONGENITAL HEART DISEASE RIGHT TO LEFT SHUNTS Clinically, cyanotic CHDs Other clinical findings: paradoxical embolism, clubbing (hypertrophic osteoarthropathy), polycythemia Can either have increased or decreased pulmonary blood flow (lesions with PS or atresia in the pulmonary circulation → ↓ pulmonary blood flow)  CONGENITAL HEART DISEASE RIGHT TO LEFT SHUNTS TETRALOGY OF FALLOT Most common cyanotic CHD Defect: anterosuperior displacement of the infundibular septum Boot shaped heart on CXR Clinical features: ○ Pulmonic stenosis, hypoxic tet spells (paroxysmal worsening of cough) Components: Vestricular septal defect Right ventricular outflow tract obstruction (RVOT) sec to subpulmonary stenosis Aorta overriding the VSD Right ventricular hypertrophy  CONGENITAL HEART DISEASE RIGHT TO LEFT SHUNTS TRANSPOSITION OF THE GREAT ARTERIES (TGA) Distinguishing feature: ventriculoarterial discordance The conotruncal septum fails to develop in a spiral fashion Most common type: dextro TGA/d-TGA RV → Aorta, LV → Pulmonary trunk Seen in infants of diabetic mothers, male “egg on a string appearance” on CXR  CONGENITAL HEART DISEASE OBSTRUCTIVE LESIONS Usually acyanotic (isolated) Obstruction offers resistance and therefore pressure overload on the chamber prior to the obstruction Aortic stenosis → LVH Pulmonic stenosis → RVH  CONGENITAL HEART DISEASE OBSTRUCTIVE LESIONS COARCTATION OF THE AORTA INFANTILE Hypoplasia of the aortic arch proximal to the PDA Associated with TURNER SYNDROME (+) lower extremity cyanosis RVH ADULT Coarctation oposite the ligamentum arteriosum distal to the arch vessels Upper extremity hypertension Rib notching on CXR sec to increased blood flow to intercostal vessels LVH SUMMARY CONGENITAL HEART DISEASE Congenital heart disease represents defects of cardiac chambers or the great vessels; these either result in shunting of blood between the right and left-sided circulation or cause outflow obstructions. Lesions range from relatively asymptomatic to rapidly fatal. Environmental (toxic or infectious) and genetic causes both contribute. Malformations associated with Left-to-right shunts are the most common and include ASDs, VSDs, and PDA. Shunting results in Right sided volume overload that eventually causes pulmonary hypertension and, with reversal of flow and right-to-left shunting, cyanosis (Eisenmenger syndrome) SUMMARY Malformations associated with Right-to-left shunts include tetralogy of Fallot and transposition of the great arteries. These lesions cause early-onset cyanosis and are associated with polycythemia, hypertrophic osteoarthropathy, and paradoxical embolization. Obstructive lesions include forms of aortic coarctation; the clinical severity of these lesions depends on the degree of stenosis and the patency of the ductus arteriosus  ISCHEMIC HEART DISEASE ISCHEMIC HEART DISEASE Ischemic heart disease (IHD) - is a broad term encompassing several closely related syndromes caused by myocardial ischemia which is an imbalance between cardiac blood supply (perfusion) and myocardial oxygen an nutritional requirements. It is also known as “Coronary Artery Disease” Most common cause of death in developed countries. In most cases, syndromes of IHD are consequences of coronary atherosclerosis. Cardiac ischemia may be the result of: Increased demand (increased heart rate or hypertension) Diminished blood volume (hypotension or shock) Diminished oxygen (pneumonia) Diminished oxygen carrying capacity (anemia or carbon monoxide poisoning) The manifestations of IHD are a direct consequence of the insufficient blood supply to the heart. The clinical pre-sensation may include one or more of the following cardiac syndromes: 1. ANGINA PECTORIS- ischemia induces pain but is insufficient to cause myocyte death. It has three types: stable, prinzmetal and unstable. 2. MYOCARDIAL INFARCTION- this occurs when the severity or duration of ischemia is sufficient to cause cardiomyocyte death. 3. CHRONIC IHD with CHF- this progressive cardiac decompensation, which occurs after acute MI or secondary to accumulated small ischemic insults, eventually precipitates mechanical pump failure. 4. SUDDEN CARDIAC DEATH- this occurs as a consequence of tissue damage from MI, but most commonly results from a lethal arrhythmia without myocyte necrosis. PATHOGENESIS Atherosclerosis of the coronary artery. Narrowing of the lumen. Changes in atheromatous plaque: Acute plaque change Coronary artery thrombosis Coronary artery vasospasm Atherosclerotic narrowing can affect any of the coronary arteries. The following elements that contributes to the development of coronary atherosclerosis: 1. Inflammation plays an essential role at all stages of atherosclerosis. from inception to plaque rupture. 2. Thrombosis associated with an eroded or ruptured plaque that triggers the acute coronary syndromes. 3. Vasoconstriction. In most patients, unstable angina, infarction and sudden cardiac death occurs because of abrupt plaque change followed by thrombosis. ACUTE CORONARY SYNDROMES - refers to any of the three catastrophic manifestations of IHD such as unstable angina, myocardial infarction and sudden cardiac death. ANGINA PECTORIS (chest pain) It is an intermittent chest pain caused by transient, reversible myocardial ischemia. The pain is a consequence of ischemia-induced release of adenosine, bradykinin, and other molecules that stimulates autonomic nerves. Three types of angina: 1. TYPICAL/STABLE ANGINA- it is a predictable episodic chest pain associated with particular levels of extortions or some increased demand. The pain is describe as “crushing” or “squeezing” substernal sensation that often radiates down the left arm or to the left jaw. It can be relieved by rest or by drug such as nitroglycerin. 2. PRINZMETAL/VARIANT ANGINA- it occurs at rest and pain is caused by coronary artery spasm. 3. UNSTABLE/CRESCENDO ANGINA- it is characterized by increasingly frequent pain, precipitated by progressively less exertion or even occurring at rest. MYOCARDIAL INFARCTION MYOCARDIAL- referring to muscle of the heart. INFARCTION-refers to lack of oxygen causing death of the tissue. Commonly known as the “heart attack”. It is the necrosis of the heart muscle resulting from ischemia. ATHEROSCLEROSIS- is the major underlying cause of IHD. While MI occurs virtually at any age. Men are at greater risk than women. The vast majority of myocardial infarctions are caused by ACUTE THROMBOSIS WITH CORONARY ARTERIES. (formation of blood clot inside a blood vessel of the heart) In most instances, disruption or erosion or pre-existing atherosclerotic plaque may serve as nidus for thrombus generation, vascular occlusion, and subsequent infarction of the perfused myocardium. CORONARY ARTERY OCCLUSION In a typical MI, the following sequence of events takes place: An atheromatous plaque is eroded. Platelets adhere, aggregate and activated- releasing thromboxane A2, adenosine diphosphate, and serotonin which causes platelet aggregation and vasospasm. Activation of coagulation- exposure of tissue factor and other mechanism that adds to the growing thrombus. ANGIOGRAPHY- it is performed within 4 hours of the onset of MI demonstrates coronary thrombosis in almost 90% of cases. ANGIOGRAMS- are the images generated during an angiography procedure. MYOCARDIAL RESPONSE TO ISCHEMIA Coronary artery obstruction blocks the myocardial block supply. Within seconds of vascular obstruction, aerobic glycolysis ceases in cardiac myocyte leading to accumulation of LACTIC ACID. The functional consequence is a rapid loss of contractility occurring within a minute of or so of the onset of ischemia. Ultrastructural changes including myofibrillar relaxation, glycogen depletion & mitochondrial swelling. These changes are reversible and cell death is not immediate. Severe ischemia lasting 20-40 mins will lead to irreversible necrosis and damage of myocytes. REPERFUSION- happens in infarction but not in necrosis. Progression of the myocardial necrosis after coronary occlusion. Myocardial ischemia also contributes to arrhythmias probably by causing electrical instability (irritability) of ischemic regions of the heart. SUBENDOCARDIAL ZONE-this is where there the irreversible injury of ischemic myocytes first occurs. INFARCTION-tissue death or necrosis caused by a lack of oxygen due to an obstruction of tissue’s blood supply. Patterns of Infarction: Size and distribution. Rate of development. Metabolic demands. Extent of collateral supply. Three types of infarction: 1. TRANSMURAL INFARCTION (STEMIs)- it involves the thickness of the ventricle (from endocardium to epicardium) and caused by epicardial vessel occlusion through a combination of chronic atherosclerosis and acute thrombosis. 2. SUBENDOCARDIAL INFARCTION (NSTEMIs)- MI’s are limited to the inner third of the myocardium. 3. MICROSCOPIC INFARCTS- it occurs in the setting of small-vessel occlusions and may not show any diagnostic ECG changes. Myocardial infarcts that are less than 12 hrs. old usually are not grossly apparent. TRIPHENYLTETRAZOLIUM CHLORIDE- a substrate for lactate dehydrogenase. By 12-24 hours after MI an infarct usually can be grossed by a red-blue discoloration caused by stagnated trapped blood. The therapeutic goal of in acute myocardial infarction is the restoration of tissue perfusion as quickly as possible. Such reperfusion is achieved by thrombolysis, angioplasty, or coronary arterial bypass graft. Late restoration of blood flow into ischemic tissues can incite greater local damage and that is called the “reperfusion injury”. Factors involved in reperfusion injury: 1. MITOCHONDRIAL DYSFUNCTION- ischemia alters the mitochondrial membrane permeability, which allows protein to move into the mitochondria. 2. MYOCYTE HYPERCONTRACTURE- intracellular levels of calcium are increased as a result of impaired calcium cycling and sarcolemma damage. 3. FREE RADICALS- these are produced within minutes after reperfusion and causes damage to the myocytes by altering membrane proteins and phospholipids. 4. LUEKOCYTE AGGREGATION- it may occlude the microvasculature and contribute to the “noreflow” phenomenon. 5. PLATELET & COMPLEMENT ACTIVATION- it also contributes to the microvascular injury. Repercussed myocardial infarction CLINICAL MANIFESTATIONS Chest pain (neck, jaw, epigastrium & left arm) Pain typically last for several minutes to hours. Fatigue. Dyspnea. Vomiting. Anxiety. diaphoretic. Pulse is rapid and weak. SILENT INFARCTS- are common with patients with underlying diabetes mellitus and in older adults. ELECTROCARDIOGRAPHIC ABNORMALITIES- are important for the diagnosis of the myocardial infarctions. LABORATORY EVALUTION: It is based on measuring the blood levels of intracellular macromolecules that leak out of injured myocardial cells through damaged cell membranes. These molecules include: myoglobin. cardiac troponins T and I (TnT, TnI) creatine kinase (CK, and more specifically the myocardial-specific isoform, CK- MB) lactate dehydrogenase. CARDIAC ENZYMES IN MI: CARDIAC TROPONINS T and I (TnT, TnI)- are the best markers for acute MI. CREATINE KINASE (CK-MB)- is the second best marker after the cardia specific troponins. Various forms of creatine kinase (CK) are found in the brain, myocardium and skeletal muscle. However, the CK-MB isoform is principally derived from myocardium is the more specific indicator of heart damage. CK-MB activity begins to rise within 2 to 4 hours of MI, peaks at 24 to 48 hours, and it returns to normal with approximately 72 hours. CONSEQUENCES AND COMPLICATIONS OF MI: ▪ DEATH 50% of deaths are associated with acute MI occur in individuals who never reach the hospital. ▪ CARDIOGENIC SHOCK (10% to 15%) of patients after acute MI. with a large infarct ( 40% of the Left ventricle). ▪ MYOCARDIAL RUPTURE RUPTURE OF THE VENTRICULAR FREE WALL- hemopericardium and cardiac tamponade. (usually fatal) RUPTURE OF THE VENTRICULAR SEPTUM- VSD and left-to-right shunt PAPILLARY MUSCLE RUPTURE- severe mitral regurgitation ▪ PERICARDITIS Fibrinous or hemorrhagic pericarditis Appears 2 to 3 days after infarction. Spontaneously resolves with time. ▪ INFARCT EXPANSION Because of the weakening of necrotic muscle, there may be disproportionate stretching, thinning, and dilation of the infarct region (especially with anteroseptal infarcts). ▪ VENTRICULAR ANEURSYM A late complication. Most commonly results from a large transmural anteroseptal infarct that heals with the formation of thinned wall of a scar tissue. ▪ PROGRESSIVE HEART FAILURE CHRONIC ISCHEMIC HEART DISEASE A.K.A “ischemic cardiomyopathy” It is a progressive heart failure secondary to ischemic myocardial damage. Sudden cardiac death. Arrythmias are common along with CHF. Morphologic features: Left ventricular dilation and hypertrophy. Coronary artery disease Evidence of prior MI (scarring) Mural thrombi may be present. SUMMARY: Vast majority of cases, cardiac ischemia is due to coronary artery atherosclerosis, vasospasm, vasculitis and embolism are less common causes. Cardiac ischemia results from a mismatch between coronary supply and myocardial demand and manifest as different syndromes including: Angina pectoris Unstable angina Acute myocardial infarction Sudden cardiac death Ischemic cardiomyopathy Myocardial ischemia leads to loss of myocyte function within 1-2 mins but causes death after only 30-40 minutes. It is diagnosed based on the symptoms, electrocardiographic changes and measurements of serum-biomarkers such as: cardiac specific troponins. Complications of infarction includes: ventricular rupture, papillary muscle rupture, aneurysm formation, mural thrombus, arrythmia, pericarditis and CHF. ARRHYTHMIAS Aberrant rhythms can be initiated anywhere in the conduction system, from the sinoatrial (SA) node down to the level of an individual myocyte; they are typically designated as originating from the atrium (supraventricular) or within the ventricular myocardium. Abnormalities in myocardial conduction can be sustained or sporadic (paroxysmal) ARRHYTHMIAS Myocardial Infarction associated arrhythmias include: ○ tachycardia - fast heartrate ○ bradycardia - slow heart rate ○ an irregular rhythm with normal ventricular contraction, ○ ventricular fibrillation - chaotic depolarization without functional ventricular contraction or no electrical activity at all (asystole). ARRHYTHMIAS Patients may be unaware of a rhythm disorder, or may note a “racing heart” or palpitations (irregular rhythm); loss of adequate cardiac output due to sustained arrhythmia can produce lightheadedness (near syncope), loss of consciousness (syncope), or sudden cardiac death. Ischemic injury is the most common cause of rhythm disorders, either through direct damage or through the dilation of heart chambers that alters signal conduction. ○ If the SA node is damaged other fibers or even the atrioventricular (AV) node can take over pacemaker function, albeit at a much slower intrinsic rate (causing bradycardia). ○ If the atrial myocytes become “irritable” and depolarize independently and sporadically (as occurs with atrial dilation), the signals are variably transmitted through the AV node leading to the random “irregularly irregular” heart rate of atrial fibrillation. ○ If the AV node is dysfunctional, varying degrees of heart block occur, ranging from simple prolongation of the P-R interval on the ECG (first-degree heart block), to intermittent transmission of the signal (second-degree heart block), to complete failure (third-degree heart block). ARRHYTHMIAS Certain heritable conditions (fortunately rare) can also cause arrhythmias. They are important to recognize because they may alert physicians to the need for intervention to prevent sudden cardiac death in the proband and their family members. Some of these disorders are associated with recognizable anatomic abnormalities (e.g., congenital anomalies, hypertrophic cardiomyopathy, mitral valve prolapse). Primary electrical disorders - other heritable disorders precipitate arrythmias and sudden death in the absence of structural cardiac pathology Channelopathies – most important channel; caused by mutations in genes that are require for normal function of Na+ K+ and C+ channels ARRHYTHMIAS Sudden Cardiac Death (SCD) ○ defined as unexpected death due to a lethal arrhythmia such as asystole or sustained ventricular fibrillation. Roughly 400,000 individuals are victims of SCD each year in the United States. Coronary artery disease is the leading cause of SCD, being responsible for 80% to 90% of cases. Unfortunately, SCD may be the first manifestation of IHD. Younger victims of SCD, nonatherosclerotic causes are more common, including the following: ○ Congenital coronary arterial abnormalities ○ Mitral valve prolapse ○ Myocarditis or sarcoidosis ○ Dilated or hypertrophic cardiomyopathy ○ Pulmonary hypertension ○ Myocardial hypertrophy. Increased cardiac mass is an independent risk factor for SCD; thus, in some young individuals who die suddenly, including athletes, hypertensive hypertrophy or unexplained increased cardiac mass is the only pathologic finding. ARRHYTHMIAS SUMMARY Arrhythmias can be caused by ischemic or structural changes in the conduction system or by myocyte electrical instability. In structurally normal hearts, arrhythmias more often are due to mutations in ion channels that cause aberrant repolarization or depolarization. SCD most frequently is due to coronary artery disease leading to ischemia. Myocardial irritability typically results from nonlethal ischemia or from preexisting fibrosis from previous myocardial injury. SCD less often is due to acute plaque rupture with thrombosis that induces a rapidly fatal arrhythmia  VALVULAR HEART DISEASE VALVULAR HEART DISEASE Valvular disease may result in stenosis, insufficiency (regurgitation or incompetence), or both. ○ Stenosis is the failure of a valve to open completely, obstructing forward blood flow. Valvular stenosis is almost always due to a primary cuspal abnormality stemming from a chronic process (e.g., calcification or valve scarring). ○ Regurgitation results from failure of a valve to close completely, thereby allowing backflow of blood insufficiency can result from either intrinsic disease of the valve cusps (e.g., endocarditis) or disruption of the supporting structures It can appear abruptly, as with chordal rupture, or insidiously as a consequence of leaflet scarring and retraction. Turbulent flow through diseased valves typically produces abnormal heart sounds called murmurs; best heard at different locations on the chest wall Valvular abnormalities can be congenital or acquired congenital valvular lesion is a bicuspid aortic valve, containing only two functional cusps instead of the normal three; ○ this malformation occurs with a frequency of 1% to 2% of all live births, and has been associated with a number of mutations ○ The two cusps are of unequal size, with the larger cusp exhibiting a midline raphe resulting from incomplete cuspal separation The most important causes of acquired valvular diseases Degenerative Valve Disease Degenerative valve disease is a term used to describe changes that affect the integrity of valvular ECM. Degenerative changes include the following: ○ Calcifications, which can be cuspal (typically in the aortic valve) or annular (in the mitral valve) Mitral annular calcification is usually asymptomatic unless it encroaches on the adjacent conduction system. Alterations in the ECM. In some cases, changes consist of increased proteoglycan and diminished fibrillary collagen and elastin (myxomatous degeneration); in other cases, the valve becomes fibrotic and scarred. Degenerative Valve Disease ○ Changes in the production of matrix metalloproteinases or their inhibitors ○ Degenerative changes in the cardiac valves are probably an inevitable aspect of aging related to the repetitive mechanical stresses to which valves are subjected—40 million beats per year, with each normal opening and closing requiring substantial valve deformation. Calcific Aortic Stenosis Calcific aortic degeneration is the most common cause of aortic stenosis. In most cases, calcific degeneration is asymptomatic and is discovered only incidentally by viewing calcifications on a routine chest radiograph or autopsy The incidence of calcific aortic stenosis is increasing in pace with longevity. In anatomically normal valves, it typically begins to manifest when patients reach their 70s and 80s; onset with bicuspid aortic valves is at a much earlier age (often 40 to 50 years of age) Although simple progressive age-associated “wear and tear” is often invoked to explain the process, cuspal fibrosis and calcification also can be viewed as the valvular counterparts to age-related arteriosclerosis. Thus, chronic injury due to hyperlipidemia, hypertension, inflammation, and other factors implicated in atherosclerosis have been proposed as contributors to valvular degenerative changes, but firm evidence is lacking MORPHOLOGY ○ The hallmark of calcific aortic stenosis is heaped-up calcified masses on the outflow side of the cusps; these protrude into the sinuses of Valsalva and mechanically impede valve opening commissural fusion (usually a sign of previous inflammation) is not a typical feature of degenerative aortic stenosis, although the cusps may become secondarily fibrosed and thickened. An earlier, hemodynamically inconsequential stage of the calcification process is called aortic valve sclerosis. Clinical Features In severe disease, valve orifices can be compromised by as much as 70% to 80% Cardiac output is maintained only by virtue of concentric left ventricular hypertrophy; the chronic outflow obstruction can drive left ventricular pressures to 200 mm Hg or more. The hypertrophied myocardium is prone to ischemia, and angina may develop. Systolic and diastolic dysfunction collude to cause CHF, and cardiac decompensation eventually ensues. The development of angina, CHF, or syncope in aortic stenosis heralds the exhaustion of compensatory cardiac hyperfunction and carries a poor prognosis; without surgical intervention, 50% to 80% of patients die within 2 to 3 years Myxomatous Mitral Valve In myxomatous degeneration of the mitral valve, one or both mitral leaflets are “floppy” and prolapse—they balloon back into the left atrium during systole. Primary mitral valve prolapse is a form of myxomatous mitral degeneration affecting some 0.5% to 2.4% of adults; thus, it is one of the most common forms of valvular heart disease, with women affected almost 7-fold more often than men. Conversely, secondary myxomatous mitral degeneration affects men and women equally, and can occur in any one of a number of settings in which mitral regurgitation is caused by some other underlying cause (e.g., IHD) MORPHOLOGY Myxomatous degeneration of the mitral valve is characterized by ballooning (hooding) of the mitral leaflets. The affected leaflets are enlarged, redundant, thick, and rubbery; the tendinous cords also tend to be elongated, thinned, and occasionally rupture. In those with primary mitral disease, concomitant tricuspid valve involvement is frequent (20% to 40% of cases); less commonly, aortic and pulmonic valves also may be affected. ○ On histologic examination, the essential change is thinning of the valve layer known as the fibrosa layer of the valve, on which the structural integrity of the leaflet depends, accompanied by expansion of the middle spongiosa layer owing to increased deposition of myxomatous (mucoid) material. The same changes occur whether the myxomatous degeneration is due to an intrinsic ECM defect (primary), or is caused by regurgitation secondary to another etiologic process (e.g., ischemic dysfunction) Clinical Features In a minority of cases, patients complain of palpitations, dyspnea, or atypical chest pain. Auscultation discloses a mid systolic click, caused by abrupt tension on the redundant valve leaflets and chordae tendineae as the valve attempts to close; there is sometimes an associated regurgitant murmur. Although in most instances the natural history and clinical course are benign, approximately 3% of patients develop complications such as hemodynamically significant mitral regurgitation and CHF, particularly if the chordae or valve leaflets rupture. Patients with primary myxomatous degeneration also are at increased risk for the development of infective endocarditis, as well as SCD due to ventricular arrhythmias. Stroke or other systemic infarctions may rarely occur from embolism of thrombi formed in the left atrium. Rheumatic Valvular Disease Rheumatic fever is an acute, immunologically mediated, multisystem inflammatory disease that occurs after group A β-hemolytic streptococcal infections (usually pharyngitis, but also occasionally infections at other sites, such as skin). Rheumatic heart disease is the cardiac manifestation of rheumatic fever. It is associated with inflammation of all parts of the heart, but valvular inflammation and scarring produce the most important clinical features. Rheumatic Valvular Disease The valvular disease principally takes the form of deforming fibrotic mitral stenosis; indeed rheumatic heart disease is essentially the only cause of acquired mitral stenosis. The incidence of rheumatic fever (and thus rheumatic heart disease) has declined remarkably in many parts of the Western world over the past several decades due to a combination of improved socioeconomic conditions, rapid diagnosis and treatment of streptococcal pharyngitis, and a fortuitous (and unexplained) decline in the virulence of many strains of group A streptococci. Nevertheless, in developing countries and economically depressed urban areas in the United States, rheumatic fever and rheumatic heart disease remain important public health problems Pathogenesis Acute rheumatic fever is a hypersensitivity reaction classically attributed to antibodies directed against group A streptococcal molecules that cross-react with host myocardial antigens (see also Chapter 5). In particular, antibodies against M proteins of certain streptococcal strains bind to proteins in the myocardium and cardiac valves and cause injury through the activation of complement and Fc receptor–bearing cells (including macrophages). CD4+ T cells that recognize streptococcal peptides can cross-react with host antigens and elicit cyt Okine mediated inflammatory responses. The characteristic 2- to 3-week delay in symptom onset after infection is explained by the time needed to generate an immune response; streptococci are completely absent from the lesions. Since only a small minority of infected patients develop rheumatic fever (estimated at 3%), genetic susceptibility to the development of the cross-reactive immune responses is likely in those affected. The deforming fibrotic lesions are the predictable consequence of healing and scarring associated with the resolution of the acute inflammation MORPHOLOGY Acute rheumatic fever is characterized by discrete inflammatory foci within a variety of tissues. The myocardial inflammatory lesions—called Asc hoff bodies—are pathognomonic for rheumatic fever. these are collections of lymphocytes (primarily T cells), scattered plasma cells, and plump activated macrophages called Anitschkow cells associated with zones of fibrinoid necrosis. The Anitschkow cells have abundant cytoplasm and nuclei with chromatin that is centrally condensed into a slender, wavy ribbon (so-called “caterpillar cells”). MORPHOLOGY salient features: The pericardium may exhibit a fibrinous exudate, which generally resolves without sequelae. The myocardial involvement—myocarditis—takes the form of scattered Asc hoff bodies within the interstitial connective tissue. Valve involvement results in fibrinoid necrosis and fibrin deposition along the lines of closure forming 1- to 2- mm vegetations—verrucae—that cause little disturbance in cardiac function MORPHOLOGY ○ Chronic rheumatic heart disease is characterized by organization of acute inflammation and subsequent scarring. Asch off bodies are replaced by fibrous scar so that these lesions are rarely seen in chronic disease. Classically, the mitral valves exhibit leaflet thickening, commissural fusion and shortening, and thickening and fusion of the chordae tendineae (Fig. 11.19C to E). Fibrous bridging across the valvular commissures and calcification create “fish mouth” or “buttonhole” stenosis. (Fig. 11.19C). Microscopic examination shows neovascularization (visibly evident in Fig. 11.19D) and diffuse fibrosis that obliterates the normal leaflet architecture. Clinical Features Acute rheumatic fever occurs most often in children; the principal clinical manifestation is carditis. Nevertheless, about 20% of first attacks occur in adults, with arthritis being the predominant feature. Symptoms in all age groups typically begin 2 to 3 weeks after streptococcal infection and are heralded by fever and migratory polyarthritis— one large joint after another becomes painful and swollen for a period of days, followed by spontaneous resolution with no residual disability. The clinical signs of carditis include pericardial friction rubs and arrhythmias; myocarditis may be sufficiently severe to cause cardiac dilation and resultant functional mitral insufficiency and CHF. Nevertheless, less than 1% of patients die of acute rheumatic fever Clinical Features The diagnosis of acute rheumatic fever is made based on serologic evidence of previous streptococcal infection in conjunction with two or more of the Jones criteria: (1) carditis; (2) migratory polyarthritis of large joints; (3) subcutaneous nodules; (4) erythematous annular rash (erythema marginatum) in the skin; and (5) Sydenham chorea, a neurologic disorder characterized by involuntary purposeless, rapid movements (also called St. Vitus dance). Minor criteria such as fever, arthralgias, EKG changes, or elevated acute phase reactants also can help support the diagnosis. Infective Endocarditis Infective endocarditis (IE) is a microbial infection of the heart valves or the mural endocardium that leads to the formation of vegetations composed of thrombotic debris and organisms, often associated with destruction of the underlying cardiac tissues. The aorta, aneurysmal sacs, other blood vessels, and prosthetic devices also may become infected. Although fungi, rickettsia (agents of Q fever), and chlamydial species can cause endocarditis, the vast majority of cases are caused by extracellular bacteria Infective Endocarditis Infective endocarditis is classified into acute and subacute forms based on the tempo and severity of the clinical course; the distinctions are related to the virulence of the responsible microbe and whether underlying cardiac disease is present. Acute endocarditis refers to tumultuous, destructive infections, frequently involving a highly virulent organism attacking a previously normal valve. It is associated with of substantial morbidity and mortality, even with appropriate antibiotic therapy and/or surgery. Subacute endocarditis refers to infections by organisms of low virulence affecting a previously abnormal heart, especially scarred or deformed valves. The disease typically appears insidiously and—even if untreated— follows a protracted course of weeks to months; most patients recover after appropriate antibiotic therapy. Pathogenesis Infective endocarditis can develop on previously normal valves, but cardiac abnormalities predispose to such infections; rheumatic heart disease, mitral valve prolapse, bicuspid aortic valves, and calcific valvular stenosis are all common substrates. Prosthetic heart valves now account for 10% to 20% of all cases of IE. Sterile platelet-fibrin deposits at sites of pacemaker lines, indwelling vascular catheters, or endocardium damage by flow “jets” stemming from preexisting cardiac disease all can be foci for bacterial seeding and development of endocarditis. Host factors such as neutropenia, immunodeficiency, malignancy, diabetes mellitus, and alcohol or intravenous drug abuse also increase the risk for IE and adversely affect outcomes. The causative organisms differ depending on the underlying risk factors; 50% to 60% of cases occurring on damaged or deformed valves are caused by Streptococcus viridians, a relatively banal group of normal oral flora. Additional bacterial agents include enterococci and the so-called “HACEK group” (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella), all commensal in the oral cavity. More rarely, gram-negative bacilli and fungi are involved. Foremost among the factors predisposing to endocarditis is seeding of the blood with microbes. The mechanism or portal of entry of the agent into the bloodstream may be an obvious infection elsewhere, a dental or surgical procedure that causes a transient bacteremia, injection of contaminated material directly into the bloodstream by intravenous drug abusers, an occult source from the gut, or oral cavity, or trivial injuries. Recognition of predisposing anatomic substrates and clinical conditions causing bacteremia allows appropriate antibiotic prophylaxis. MORPHOLOGY In both acute and subacute forms of the disease, friable, bulky, and potentially destructive vegetations containing fibrin, inflammatory cells, and microorganisms are present on the heart valves The aortic and mitral valves are the most common sites of infection, although the tricuspid valve is a frequent target in the setting of intravenous drug abuse. Vegetations may be single or multiple and may involve more than one valve; they can sometimes erode into the underlying myocardium to produce an abscess cavity (ring abscess) MORPHOLOGY myocardium to produce an abscess cavity (ring abscess) (Fig. 11.21B). Shedding of emboli is common because of the friable nature of the vegetations. Since the fragmented vegetations contain large numbers of organisms, abscesses often develop at the sites where emboli lodge, leading to development of septic infarcts and aneurysms resulting from bacterial infection of the arterial wall (mycotic aneurysms). Subacute endocarditis typically causes less valvular destruction than acute endocarditis. On microscopic examination, the vegetations of subacute endocarditis often have granulation tissue at their bases (suggesting chronicity), promoting development of chronic inflammatory infiltrates, fibrosis, and calcification Clinical Features Fever is the most consistent sign of infective endocarditis. However, in subacute disease (particularly in older adults), fever may be absent, and the only manifestations may be nonspecific fatigue, weight loss, and a flulike syndrome; splenomegaly also is common in subacute cases. By contrast, acute endocarditis often manifests with rapidly developing fever, chills, weakness, and lassitude. Murmurs are present in 90% of patients with left-sided lesions. In those who are not treated promptly, micro emboli are formed, which can give rise to petechia, nail bed (splinter) hemorrhages, retinal hemorrhages (Roth spots), painless palm or sole erythematous lesions (Janeway lesions), or painful fingertip nodules (Osler nodes); diagnosis is confirmed by positive blood cultures and echocardiographic findings Clinical Features Prognosis depends on the infecting organism and the development of complications. Adverse sequelae generally begin within the first weeks after onset of the infectious process and can include glomerulonephritis due to glomerular trapping of antigen- antibody complexes, with hematuria, albuminuria, or renal failure. Clinical features of septicemia, arrhythmias (suggesting extension to underlying myocardium and conduction system), and systemic embolization bode ill for the patient. Left untreated, IE generally is fatal. However, with appropriate long-term (6 weeks or more) antibiotic therapy and/or valve replacement, mortality is reduced. For infections with low-virulence organisms (e.g., Streptococcus viridians or Streptococcus bovis), the cure rate is 98%, and for enterococci and Staphylococcus aureus infections, cure rates range from 60% to 90%; however, infections with aerobic gram negative bacilli or fungi are associated with fatality rate of approximately 50% Noninfected Vegetations Nonbacterial Thrombotic Endocarditis Nonbacterial thrombotic endocarditis (NBTE) is characterized by the deposition of sterile thrombi on cardiac valves, typically in those with an underlying hypercoagulable state. Although NBTE can occur in otherwise healthy individuals, a wide variety of diseases associated with general debility or wasting are associated with an increased risk for NBTE—hence the alternate term marantic endocarditis. In contrast to infective endocarditis, the sterile valvular lesions of NBTE are nondestructive Nonbacterial Thrombotic Endocarditis The vegetations in NBTE are typically small (1 to 5 mm in diameter) and valvular damage is not a prerequisite. Indeed, the condition usually occurs on previously normal valves. Rather, hypercoagulable states are the usual precursor to NBTE; such conditions include chronic disseminated intravascular coagulation, hyperestrogenic states, and those associated with underlying malignancy, particularly mucinous adenocarcinomas. Noninfected Vegetations Nonbacterial Thrombotic Endocarditis Nonbacterial thrombotic endocarditis (NBTE) is characterized by the deposition of sterile thrombi on cardiac valves, typically in those with an underlying hypercoagulable state. Although NBTE can occur in otherwise healthy individuals, a wide variety of diseases associated with general debility or wasting are associated with an increased risk for NBTE—hence the alternate term marantic endocarditis. In contrast to infective endocarditis, the sterile valvular lesions of NBTE are nondestructive Nonbacterial Thrombotic Endocarditis Although the local effect on the valve usually is trivial, NBTE lesions can become clinically significant by giving rise to emboli that can cause infarcts in the brain, heart, and other organs. NBTE also can serve as a potential nidus for bacterial colonization and the consequent development of infective endocarditis. Noninfected Vegetations Endocarditis in Systemic Lupus Erythematosus: Libman-Sacks Endocarditis Libman-Sacks endocarditis is characterized by the presence of sterile vegetations on the valves of patients with systemic lupus erythematosus It occurs in about 10% of patients with SLE. ○ The lesions probably develop as a consequence of immune complex deposition and thus exhibit associated inflammation, often with fibrinoid necrosis of the valve adjacent to the vegetation; subsequent fibrosis and serious deformity can result in lesions that resemble chronic rheumatic heart disease. these can occur anywhere on the valve surface, on the cords, or even on the atrial or ventricular endocardium Similar lesions can occur in the setting of anti-phospholipid antibody syndrome CARDIOMYOPATHIES AND MYOCARDITIS CARDIOMYOPATHY Cardiac diseases due to intrinsic myocardial dysfunction It constitutes a group of diseases that directly affect the structural and functional ability of myocardium. Diseases of the heart muscle in which the heart loses it’s ability to pump blood effectively. During cardiomyopathy the heart muscle becomes enlarged or abnormally thick or rigid CAUSES OF CARDIOMYOPATHY: PRIMARY ▪ Refers to those conditions in which the etiology of the heart disease in unknown. SECONDARY Refers to the cause of myocardial disease that are known. CLASSIFICATION OF CARDIOMYOPATHY ISCHEMIC CARDIOMYOPATHY - Is a condition when your heart muscle is weakened as a result of inadequate oxygen supply due to heart attack or coronary artery disease. NON ISCHEMIC CARDIOMYOPATHY - These forms of cardiomyopathy are not related to known coronary artery disease. TYPES OF NON ISCHEMIC ✓ DILATED CARDIOMYOPATHY (DCM) ARRYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY ✓ HYPERTHROPHIC CARDIOMYOPTHY ✓ RESTRICTIVE CARDIOMYOPATHY DILATED CARDIOMYOPATHY Characterized by progressive cardiac dilation and contractile dysfunction. It is a disease of the heart muscle usually starting in heart’s main pumping chamber ETIOLOGY OF DILATED MYOCARDITIS – Inflammatory disorder that precedes the development of cardiomyopathy and sometimes caused by viral infections. TOXICITIES – Cardiotoxic agents due to cocaine, amphetamines and some chemotherapy drugs MUSCULAR DYSTROPHY – Weakening of muscles PREGNANCY – “PERIPARTUM CARDIOMYOPATHY” ALCOHOL ABUSE HYPERTENSION ISCHEMIA ANOREXIA VALVE DISEASE ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPTHY (ARVC) Is a disease of the heart muscle that replaces the normal heart muscle into fatty fibrous tissue which makes the right ventricle dilated and contracts poorly. SYMPTOMS: VENTRICULAR ARRYTHMIAS – Irregular heart rhythms originating in the ventricles or lower chambers of the heart. PALPITATIONS – Fluttering in the chest due to abnormal heart rhythms. DIZZINESS OR FAINTING - caused by irregular heart rhythms. SUDDEN CARDIAC DEATH – It is the first sign of ARVD HEART FAILURE – Shortness of breath with activity, inability to carry out normal activities without fatigue and swelling in the legs, ankles and feet HYPERTROPHIC CARDIOMYOPATHY Caused by abnormal genes in the heart muscle that makes the walls of the heart chamber to contract harder and become thicker than normal TYPES OF HYPERTHROPHIC CARDIOMYOPATHY OBSTRUCTIVE TYPE - The septum thickens & bulges only into the left ventricle 24% -NON OBSTRUCTIVE 20% Entire ventricle may become thicker or it may happen only at 10% the bottom of the heart CLINICAL FEATURES Shortness of breath during mild exercise Decrease cardiac output Easy fatigue Angina Syncope Hypertension PHYSICAL EXAMINATION AND TREATMENT TRANSTHORACIC ECHOCARDIOGRAPHY Transducer is pressed firmly against the skin. The transducer aims an ultrasound beam through your chest to your heart, producing moving images of how the heart is currently work. ELECTROCARDIOGRAM (ECG) Uses magnetic fields and radio waves to create images of the heart. CARDIAC MRI - Uses magnetic fields & radio waves to create images of the heart. CARDIAC CATHERIZATION Is a procedure used to diagnose and treat certain cardiovascular conditions RESTRICTIVE CARDIOMYOPATHY Disease of the heart muscle that impairs diastolic filling, sketch and the systolic function remains unaffected. CAUSES: Radiation, treatment, scarring after surgery HEMOCHROMATOSIS – Too much iron is deposited into tissue, including heart tissue AMYLYOIDOSIS – Abnormal proteins are deposited into heart tissue ENDOMYOCARDIAL FIBROSIS – Principally disease of children & young adult in Africa and tropical areas. It is characterized by fibrosis of the left & right ventricular endocardium. CAUSES: LOEFFLER ENDOMYOCARDITIS – Characterized by a stiffened, poorly functioning heart caused by infiltration of the heart by eosinophils. Family history of cardiomyopathy Heart failure Long term alcoholism Long term high blood pressure Diabetes & other metabolic disease  SIGNS & SYMTOMS Shortness of breath ✓ Swelling of the abdomen, legs, ankles and feet ✓ Other signs: dizziness, lightheadedness, fainting during mild exercises, abnormal heart rhythms and murmurs. MYOCARDITIS MYOCARDITIS Is an inflammatory disease of the myocardium caused by different infectious and noninfectious triggers. It can also affect the function of the heart, the normal electrical signaling of the heart. TYPES OF MYOCARDITIS According to Lieberman’s clinic pathological classification: Fulminant Myocarditis – Severe disease following viral infection, leading to sudden compromise of organ systems. Acute Myocarditis – Patient’s condition wherein heart dysfunction is present which may respond to treatment. Chronic Active Myocarditis – These patients initially respond to treatment but then relapse and finally develop heart dysfunction. Chronic Persistent Myocarditis – Persistent inflammation, but minimal to no heart dysfunction. TYPES OF MYOCARDITIS ACCORDING TO PATHOLOGICAL CLASSIFICATION LYMPHOCYTIC – Viral, autoimmune EOSINOPHILIC – Hypersensitivity myocarditis GRANULOMATOUS – Giant cell myocarditis NEUTROPHILIC – Bacterial fungal myocarditis CAUSES: Viral infections –Viruses that cause the common cold, flu, chickenpox & glandular fever, German measles, gastrointestinal infections and adenovirus. Bacterial infections – staphylococcus, streptococcus Parasitic infections – toxoplasma Chagas disease Fungal infections – molds, yeasts and fungi. Allergic reactions – medication Reactions to chemicals, radiation or radiotherapy Immune conditions PHYSICAL EXAMINATIONS: Physical exam and Medical history ✓Blood Tests ✓Electrocardiogram (ECG ✓Chest X-ray ✓Echocardiogram ✓Magnetic Resonance Imaging (MRI) ✓Positron Emission Tomography (PET) ✓Endomyocardial Biopsy PERICARDIAL DISEASE PERICARDIAL DISORDER Include effusion and inflammatory conditions, sometimes resulting in fibrous constriction. Isolated pericardial disease is unusual and pericardial lesions. PERICARDITIS PRIMARY PERICARDITIS is uncommon. It most often due to viral infection. Although bacteria, fungi, or parasite may also involved. Pericarditis is secondary to - Acute myocardial infarction - Cardiac surgery -Radiation to the mediastinum or processes involving other thoracic structures UREMIA - is the most common systemic disorder associated with pericarditis. FLUID ACCUMULATION ACUTE PERICARDITIS can cause cardiac TAMPONADE, with declining cardiac output and consequent shock. CHRONIC CONSTRICTIVE PERICARDITIS produces a combination of right sided venous distention and low cardiac output, similar to the clinical picture in restrictive cardiomyopathy. ACUTE SUPPURATIVE (PURULENT, EXUDATE ) PERICARDITIS PERICARDIAL EFFUSION The pericardial sac contains at most 30 to 50 ml of clear, serous fluid. Serous or fibrinous effusions in excess of this amount occur most commonly in the setting of pericardial inflammation. Other types of pericardial effusions and their causes include : SEROUS : Congestive heart failure, hypoalbuminemia of any cause SEROSANGUINEOUS blunt chest trauma, malignancy, ruptured myocardial infarction or aortic dissection. CHYLOUS mediastinal lymphatic obstruction THE CONSEQUENCES OF PERICARDIAL ACCUMULATIONS : Depend on the volume of fluid and the ability of the parietal pericardium to stretch; the latter depends largely on how fast the effusion accumulates. Slowly accumulating effusion even as large as 1000ml can be well tolerated. By contrast rapidly developing collections of as little as 250 ml CARDIAC TUMORS Metastatic Neoplasm Tumor metastases constitute the most common malignancy of the heart. Metastatic cardiac lesions occur in about 5% of pxs dying of cancer In descending order these are lung cancer, lymphoma, breast cancer, leukemia, melanoma, hepatocellular carcinoma and colon cancer Primary neoplasm Uncommon Mostly benign The five most common have no malignant potential and account for 80% to 90% of all primary heart tumors. In descending order of frequency, these are myxomas, fibromas, lipomas, papillary fibroelastomas', and rhabdomyomas. Angiosarcomas constitute the most common primary malignant tumor of the heart Myxomas Most common primary tumors of the adult heart. Mostly single and classically arising in the region of the fossa ovalis (atrial septum). They can be small (less than 1cm in diameter) to massive (up to 10cm across), sessile or pedunculated masses. 90%are atrial, with the left atrium accounting for 80% Rhabdomyomas It is a gray-white masses up to several centimeters in diameter that protrude into the ventricular chambers. Most frequent primary tumors of the heart in infants and children. Frequently are discovered owing to valvular or outflow obstruction. Occurs with high frequency in patients with tuberous sclerosis caused by mutations in the TSC1. Histologic examination shows a mixed population of cells; most characteristics are large, rounded, or polygonal cells containing numerous glycogen-laden vacuoles separated by strands of cytoplasm running from the plasma membrane to the centrally located nucleus, so called spider cells Clinical Features The major clinical manifestations are due to valvular “ball-valve” obstruction, embolization, or a syndrome of constitutional signs and symptoms including fever and malaise. This syndrome is attributable to tumor elaboration of the cytokine interleukin-6, a major mediator of the acute-phase response. Echocardiography is the diagnostic modality of choice, and surgical resection is almost uniformly curative. LIPOMAS Lipomas are localized, poorly incapsulated masses of adipose tissue; these can be asymptomatic, create ball-valve obstruction (as with myxomas), or produce arrhythmias. Papillary Fibroelastomas Usually are only incidentally identified lesions, although they can embolize. Generally located on valves, they form distinctive clusters (up to 1cm in diameter) of hairlike projections that grossly resemble sea anemones. Histologic examination shows myxoid connective tissue containing abundant mucopolysaccharide matrix and laminated elastic fibers, all surrounded by endothelium. Cardiac Angiosarcomas Not clinically or morphologically distinctive from their counter-parts in other locations Also the other sarcomas  CARDIAC TRANSPLANTATION A heart transplant, or a cardiac transplant, is a surgical transplant procedure performed on patients with end-stage heart failure or severe coronary artery disease when other medical or surgical treatments have failed. Indications The general indications for cardiac transplantation include deteriorating cardiac function and a prognosis of less than 1 year to live. Specific indications include the following: Dilated cardiomyopathy - Dilated cardiomyopathy (DCM) is a medical condition in which the heart's ability to pump blood is lessened because its main pumping chamber, the left ventricle, is enlarged and weakened. Ischemic cardiomyopathy - Ischemic cardiomyopathy (IC) is a condition when your heart muscle is weakened as a result of a heart attack or coronary artery disease. Congenital heart disease for which no conventional therapy exists or for which conventional therapy has failed. Intractable angina or malignant cardiac arrhythmias for which conventional therapy has been exhausted. Age younger than 65 years Ability to comply with medical follow-up care Contraindications Contraindications for heart transplantation include the following: Age older than 65 years - This is a relative contraindication; patients who are older than 65 years are evaluated on an individual basis Active systemic infection Active systemic disease such as collagen-vascular disease or sickle cell disease Active malignancy - Patients with prior malignancies who have demonstrated a 3- to 5-year disease-free interval may be considered, depending on the tumor type and the evaluating program An ongoing history of substance abuse (eg, alcohol, drugs, tobacco) Psychosocial instability Inability to comply with medical follow-up care Outcome Hypertension, diabetes mellitus, and obesity are associated with exponential increases in postoperative mortality rates. Heart transplant recipients with all three of these metabolic risk factors were found to have a 63% increased mortality compared to patients without any of the risk factors. What is heart transplant rejection? Your immune system’s job is to seek out and destroy foreign substances in the body. It destroys bacteria and viruses to help keep you healthy. Normally, this is a good thing. But sometimes the immune system’s response can lead to problems. During a heart transplant, a surgeon removes your badly working heart and replaces it with a healthy heart from a donor. The immune system sees the new heart as a foreign object and can start to attack it. This is known as transplant rejection. When you have a heart transplant, you will need to take certain medicines for the rest of your life. These help to prevent rejection of the new heart by your immune system. Transplant rejection is very common. It’s common even in people who take all their medicines as prescribed. What is heart transplant rejection? The most common type of heart transplant rejection is called acute cellular rejection. This happens when your T-cells (part of your immune system) attack the cells of your new heart. It happens most often in the first 3 to 6 months after transplant. Humoral rejection is a less common type. It’s also known as acute antibody rejection. It can develop during the first month after transplantation. Or it can happen as late as months to years after transplant. With humoral rejection, antibodies injure the blood vessels in your body, including your coronary arteries. This can cause problems with blood flow to the heart. Heart transplant rejection can also be long-term (chronic). Coronary artery vasculopathy is a form of chronic rejection. It affects the coronary arteries. These supply the heart muscle with oxygen and nutrients. In coronary artery vasculopathy, the inner lining of the blood vessel thickens. This can lead to less blood going to the heart muscle. Your healthcare provider may prescribe certain medicines to prevent and treat this type of rejection. What causes heart transplant rejection? Heart transplant rejection can happen in a normally functioning immune system. Failing to take anti-rejection medicines as prescribed can cause transplant rejection. But many people who take their medicines as prescribed still have rejection. No one knows for sure why this happens. Who is at risk for heart transplant rejection? Certain things increase the chances of both short-term (acute) and chronic heart transplant rejection. One of the most important factors is a genetic mismatch between the heart donor and heart recipient. Younger heart recipients are also at greater risk for both kinds of rejection. Other things that specifically increase the chances of acute transplant rejection include: Time after transplantation. Rejection risk is highest several weeks after the transplant and then starts to decrease. Being a female heart recipient or female heart donor Some factors that specifically increase the chances of chronic rejection include: High cholesterol Cytomegalovirus infection Older heart donor Male donor Younger recipient History of acute heart rejection Coronary heart disease in the donor or the recipient Insulin resistance What are the symptoms of heart transplant rejection? Some of the symptoms of acute heart transplant rejection include: - Feeling tired or weak - Fever or chills - Shortness of breath - Fast or irregular heartbeat - Drop in blood pressure - Swelling of your feet, hands, or ankles - Sudden weight gain - Flu-like aches and pains - Reduced amounts of urine - Dizziness or fainting - Nausea or loss of appetite It's common for rejection to happen without any symptoms at all. Because of very intense rules for screening after transplant, many cases are found before symptoms develop. This is one reason why it is so important to make all your follow-up visits. Chronic heart transplant rejection often has no symptoms at all. The first symptom might be a heart attack. How is heart transplant rejection diagnosed? Electrocardiogram (ECG) to monitor the heart rhythm Echocardiogram to evaluate heart function Other tests are sometimes needed for the diagnosis of chronic rejection. These tests help provide a better look at the blood vessels. These may include: Coronary angiography Intravascular ultrasound Cardiac stress testing How is heart transplant rejection treated? Treatment depends on a number of factors. These include the severity of the rejection, symptoms, current medicines, and the type of rejection. Some options for treating acute cellular transplant rejection include: Increasing the dose of or how often you take a current anti- rejection medicine Changing to a different anti-rejection medicine Adding other medicines that suppress the immune system. This might be prednisone or a similar steroid. For more severe cases, you may need treatment with medicines given by IV (intravenous) Plasmapheresis is the main treatment for rejection caused by antibodies. This is called acute humoral rejection. Plasmapheresis filters the blood and removes the harmful antibodies. Sometimes light therapy to treat the white cells in removed blood is used (photopheresis). The treated blood is then returned to you. Increasing the dose of anti-rejection medicines is another way to treat chronic rejection. If the damage is more severe, you may have a lot of blockages in the coronary arteries. For this, you may need angioplasty or open heart surgery. These procedures help blood flow better in the coronary arteries. Rarely, chronic rejection needs another transplant. Living a heart-healthy lifestyle can decrease the risk of developing chronic rejection in the form of coronary artery vasculopathy. After you get treatment for rejection, you will need to be closely monitored. You might need follow-up tests to see how you respond. Medicines used to prevent rejection do suppress the immune system. This increases the risk for infection. Your risk of heart failure also increases with rejection. Because of these possible complications, your healthcare provider may: Give you antibiotic and antiviral medicines. These are needed if you are using certain anti-rejection medicines. They don’t treat the rejection itself, but they may help to prevent infection. Give you medicines to treat heart failure, such as beta-blockers. You may need these if the rejection is severely affecting your new heart Allograft arteriopathy - single most important long term limitation of cardiac transplantation - it is a condition of late, progressive, diffusely stenosing intimal proliferation in the coronary arteries leading to ischemic injury - immunosuppression required for allograft survival increases the risk of opportunistic infections and certain malignancies (eg. Epstein-Barr virus-associated lymphoma) Pathogenesis -immunologic responses that include local production of growth factors, which in turn promote intimal smooth muscle cell recruitment and proliferation with ECM(extra cellular matrix) synthesis Allograft arteriopathy is a vexing problem because it can lead to: silent Myocardial Infarction Congestive heart failure - occurs when your heart muscle doesn't pump blood as well as it should. narrowed arteries in your heart (coronary artery disease) or high blood pressure, gradually leave your heart too weak or stiff to fill and pump efficiently. Sudden death THANK YOU !