* HEART DISEASE THE predominant cause of morbidity and mortality in the Western Hemisphere 40% of all deaths Vast

majority of heart disease is ischemic heart disease (80%) Remainder of heart disease is due to: Hypertensive heart disease and cor pulmonale Congenital heart disease Valvular heart disease (multiple etiologies): Sterile and infective endocarditis Aortic stenosis Mitral valve prolapse Rheumatic heart disease with valvular derangements *Congestive Heart Failure Definition: Multisystem derangement that occurs when the heart is no longer able to eject blood delivered to it by the venous system in a manner sufficient to meet the metabolic demands of the body *Systolic vs. Diastolic Heart Failure Systolic Failure- heart is unable to adequately contract and propel blood Diastolic Failure- heart is unable to adequately relax allowing for proper filling of cardiac chambers *Types of Heart Failure Left Heart Failure Inability to pump blood due to HTN, mitral/aortic valve disease, ischemia or primary disease. (Systolic failure) Right Heart Failure Inability to meet the demands of venous return due to left heart failure, pulmonary disease, valvular disease or left-to-right shunts High Output Failure Elevated CO due to increased tissue demand which is often secondary to sepsis & vasodilatation *Response to Heart Failure Short-term Increased sympathetic stimulation (positive inotropy & chronotropy). Includes stimulation of renin-angiotensin system secondary to decrease in renal perfusion. Long term Heart muscle remodeling in order to maximize cardiac output (FrankStarling law) Hypertrophy Dilatation *Clinical Findings (Heart Failure Lungs Dyspnea, SOB, crackles, orthopnea, PND Heart Tachycardia, S3, murmurs, PMI changes, fibrillation Systemic Hepatic congestion, lower extremity edema, JVD, splenomegaly, pulmonary congestion/pleural effusions I*ischemic Heart Disease Definition: Syndromes causing an imbalance between myocardial oxygen demand and supply Most common cause of death in developed world (1/3) Peak incidence between 60 to 70 y/o Men > Women (until 80s) *Risk Factors (IHD) HTN Sedentary life-style DM Smoking LDL Hypertriglyceridemia

Family history *Ischemic Heart Disease Pathogenesis Closely associated with atherosclerosis Pathways: 75% narrowing is considered critical stenosis Acute plaque changes which usually occur between 50-75% stenotic range ACUTE CORONARY SYNDROME ATHEROSCLEROSIS Disease of the muscular arteries (not veins) coronary cerebral vessels Progressive deposition of cholesterol esters Accounts indirectly for half of annual mortality Ischemic heart disease MI Cerebrovascular disease Stroke Lesions start as fatty streaks subendothelial accumulation of large foam cells (derived from macrophages plus SM cells) filled with lipid Fibrous Plaque More advanced and the cause of disease Develop from fatty streaks Projects into arterial lumen Reduced blood flow Most of the changes are in the intimal layer Risk factors cause: Endothelial Dysfunction Injury to the endothelium is the primary event Mechanical, tissue hypoxia, Impair endothelial protection decrease in plasminogen activators, heparan sulphate, prostacyclin If the endothelium is damaged it no longer serves as a barrier LDL cholesterol passes into the intima and accumulates and modified (oxidized) by free radicals Attracts monocytes and is ingested by macrophages Key step is attraction of monocytes and T lymphocytes by TNF (tumor necrosing factor) and MCP (monocyte chemoattractant protein) released by injured endothelium and expression of VCAM-1 (vascular cell adhesion molecule), ICAM (intercellular adhesion molecule) Monocytes migrate to subendothelial space where they become macrophages Foam Cells Foam cells secrete PDGF(platelet-derived growth factor), IL-1 (interleukin), TGF (transforming growth factor), TNF which activate SM cells to migrate and proliferate and deposit connective tissue Foam cells also release tissue factor which is highly thrombogenic *Results of Ischemic Heart Disease Angina Pectoris Acute Myocardial Infarction Sudden Cardiac Death Chronic Ischemic Heart Disease *Angina Pectoris Stable (or classic) angina Intermittent substernal chest pain Represents reversible myocardial ischemia 75% fixed coronary lesion Treat with nitroglycerin causing vasodilatation and decreased cardiac work Unstable (or preinfarction) angina Crescendo chest angina increasing in frequency with progressively less work Due to acute plaque changes Associated with thrombosis, embolism and/or vasospasm

Prinzmetal (or variant) angina Substernal chest pain occurring at rest Due to vasospasm with or without a fixed atherosclerotic lesion Pathogenesis is unknown Treated with calcium channel blockers resulting in vasodilatation *MYOCARDIAL INFARCTION Necrosis due to local ischemia which is primarily caused by thrombi Can lead to vasospasm and/or emboli Site, size and effect of an MI depends on location of event Location: Left Anterior Descending (40 to 50%) Right Coronary Artery (30 to 40%) Left Coronary Artery (15 to 20%) Vascular obstruction leads to myocardial ischemia Within 30 min the subendocardium becomes infarcted Within 3 to 6 hours the lesion becomes transmural and reaches its full size Treatment within 3 hours reduces morbidity and mortality dramatically *DIAGNOSIS OF MI H&P EKG Labs Myoglobin- earliest rise CK-MB- 2 to 4 hours after MI (not specific) TROPONIN-I- highly sensitive and specific Show around 4 hrs after MIpeak at 48 hrs C-reactive protein *COMPLICATIONS OF MI Contractile dysfunction (pump failure) -In 10%- 15% of patients -70% mortality with cardiogenic shock Arrhythmias- major cause of sudden death in MI -Type of arrhythmia is secondary to location and size of infarct Mural thrombus- due to lack of motility of ventricular wall and thrombogenic nature of damaged myocytes Papillary muscle dysfunction/rupture: Mitral valve regurgitation Rupture around day three s/p AMI 50% mortality rate with rupture Ventricular rupture: Occurs around day 4 to 7 s/p AMI Results in cardiac tamponade 1 to 3% involve septum resulting in a left to right shunt Fibrinous pericarditis: Occurs on day 2 to 4 Associated with transmural neutrophilic infiltrate Leads to restrictive pathology Ventricular aneurysm: Late complication of large transmural infarcts Results in bulging during systole Often contains mural thrombi Can disrupt conduction pathways *SUDDEN CARDIAC DEATH Definition: Death within 24 hours of initial symptomatology -Most deaths occur within 1 hour Most commonly related with ischemic heart disease 50% of all patients with ischemic heart disease suffer this fate Ultimate cause of death is usually arrhythmia- electrical irritability of myocardium Seen in 300,000 to 400,000/yr Causes of sudden cardiac death Coronary Artery Diseases Coronary Atherosclerosis

Developmental Disorders Coronary Artery Embolism Myocardial Diseases Cardiomyopathies Myocarditis Right Ventricular dysplasia Valvular Diseases Mitral Valve Prolapse Left Ventricular Outflow Obstruction Endocarditis Conduction Abnormalities *HYPERTENSIVE HEART DISEASE Results in LV hypertrophy in patients with poorly controlled HTN Differentiated from LV hypertrophy secondary to aortic stenosis or primary hypertrophic cardiomopathy Some regression possible with adequate treatment Leads to heart failure due to decreased efficiency *COR PULMONALE Definition: Right-sided heart failure secondary to pulmonary hypertension Causes of pulmonary hypertension are diverse and extensive Intrinsic Lung Diseases Chronic Obstructive Lung Disease Diffuse Pulmonary Interstitial Fibrosis Cystic Fibrosis Diseases of the Pulmonary Vasculature Pulmonary Embolism Primary Pulmonary Vascular Sclerosis Extensive Pulmonary Arteritis (e.g. Wegeners Granulomatosis) Drug-, Toxin-, Radiation- induced vascular sclerosis Disorders Affecting Chest Movement Kyphoscoliosis Marked Obesity (Pickwickian Syndrome) Neuromuscular Diseases Disorders inducing Pulmonary Arteriolar Constriction Metabolic Acidosis Hypoxemia Chronic Altitude Sickness Obstruction to Major Airways Idiopathic Alveolar Hypoventilation * CARDIAC VALVES (valvular heart diseases) Valves help each heart chamber perform its work without being affected by adjacent chambers Valves perform their responsibilities passively or passively and actively Pathologies include regurgitation and stenosis Acquired stenosis (2/3) of valve disease *Rheumatic Heart Disease Immune mediated disorder secondary to pharyngitis caused by GA HS (Strep. pyogenes) Presents 2-3 weeks following infection Possibly due to cross reactivity of anti-M capsular Abs Slight familial predisposition 3% of infections progress to RF 70% have mitral valve involvement 25% have combined mitral & aortic valve involvement Mitral valve involvement > women Aortic valve involvement > men

Stenosis > regurgitation Incidence on decline- abxtx, socioeconomics, decreased virulence *Diagnosis of Rheumatic Fever Jones criteria- 2 major manifestations or 1 major and 2 minor manifestations Major manifestations: (1) migratory polyarthritis (2) carditis (3) subcutaneous nodules (4) erythema marginatum (5) Sydenham chorea Minor- non-specific 1% mortality rate *Calcific Aortic Stenosis Degenerative valvular changes with age (repeated mechanical stress) and/or atherosclerosis Common with congenitally unicuspid (rare) or bicuspid valves (1%) Frequently asymptomatic Sclerotic with calcifications at line of closure Left heart failure and crescendo-decrescendo systolic murmur Stenosis causes increased pressures across valve and increase in proximal chamber *Mitral Valve Prolapse Floppy valve syndrome 3 to 5% of the population with 97% being asymptomatic Presents between 20 to 40 y/o More common in women Associated with Marfans Syndrome or ruptured papillary m./chordae tendinae Intercordal hooding with thick, rubbery valves Concomitant involvement of tricuspid (20-40%) Harsh holosystolic murmur with possible infective endocarditis, arrhythmias, or thrombi Unknown cause ENDOCARDITIS *Nonbacterial Thrombotic Endocarditis Also known as marantic endocarditis Sterile deposition of fibrin, platelets, and blood components Associated with debilitated patients Often resolve spontaneously (Lamble excrescences) Commonly affects mitral valve (50%) Unknown etiology, possible due to subtle endothelial abnormalities Embolic events are main concern * Libman-Sacks Endocarditis Sterile vegetations associated with SLE Found on undersurface of tricuspid and mitral valves, cords, or endocardium Embolic events and valve fibrosis are of concern *Infective Endocarditis Heart valve infection commonly due to bacteria Commonly affects aortic and mitral valves Bulky friable, necrotizing vegetations Types: Acute Organisms of high virulence, destructive, 50% mortality even with tx (i.e. Staph. aureus) Subacute Organisms of low virulence with previous valvular damage, less destructive (i.e. Strep. viridans) Diagnosis by culture and/or histology Treatment requires six months of antibiotics Organism (native valves): Strep. viridans (50 to 60%) Staph. aureus (20%), most common in IV drug users HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)

S. epidermidis (prosthetic valves) Variable clinical signs and symptoms Acute- rapid onset, fever, chills, weakness, lassitude Sub-acute- highly variable, with FEVER, fatigue, flu like symptoms New murmurs are consistently found Vegetations on echocardiogram, (+) blood cultures- major criteria Preventative antibiotic therapy is crucial in patients with hx of valve replacement MYOCARDITIS Mononuclear inflammation/infiltration of the myocardium Causes are idiopathic to infectious to autoimmune in nature Most commonly associated with viral agents (parasitic most common in 3rd world) PCR (polymerase chain reaction) can be used to determine organism Pts. can be asymptomatic. Many have fever, fatigue, chest discomfort, SOB, palpitations Acute sequelae- arrhythmia, dilated cardiomyopathy (chronic also) , mitral regurgitation Causes Viruses (e.g. Coxsackie virus, Echovirus, Influenza virus, HIV, Cytomegalovirus) Chlamydia Rickettsia Bacteria (e.g. Corynebacterium diphtheria, Neisseria meningitides, Borrelia burgdorferi) Fungus (e.g. Candida sp.) Protozoa (e.g. Trypansoma cruzi, Toxoplasmosis) Helminths (e.g. Trichinosis) Immune-Mediated Reactions Post viral Post streptococcal (Rheumatic Fever) Systemic Lupus Erythematosus Drug hypersensitivity (e.g. methyldopa, sulfonamides) Transplant Rejection Unknown Sarcoidosis Giant Cell Myocarditis (poor prognosis) CARDIOMYOPATHIES Definition: Primary myocardial abnormalities (intrinsic disease) Types: Dilated (i.e. Flabby) Progressive hypertrophy, dilation, and contractile dysfunction due to cytoskeletal protein dysfunction Most common cardiomyopathy (90%) Four chamber dilatation with mild hypertrophy Causes include viral, Ethanol, toxins, pregnancy, inherited (muscular dystrophies) Hypertrophic Marked septal hypertrophy Intermittent outflow obstruction Interventricular septum is disproportionately thickened Abnormal sarcomeric proteins with haphazard myocyte arrangement Restrictive Decreased compliance due to idiopathic fibrosis, Lofflers syndrome, etc PERICARDITIS Inflammation of the pericardium most commonly due by viral agents Types: Acute -- Fibrinous exudate which resolves or progresses to chronic form Chronic Varies from delicate fibrous adhesions to fibrotic scarring Sequelae: Constrictive pericarditis Pericardial Effusions

Serous Due to decreased protein (cirrhosis) or increased pressure (CHF) Serosanguinous Due to decreased protein with blood (trauma or cancer) Chylous Due to lymphatic obstruction (cancer) Sanguinous Due to trauma or acute events (dissections or rupture) Heart Tumors Types: Metastatic (#1 overall) Myxomas Lipomas Rhabdomyomas (#1 in children) Angiosarcomas Rhabdomyosarcomas CONGENITAL HEART DISEASES Three shunts of fetal circulation 1. Ductus Arteriosus Protects lungs against circulatory overload Allows RV to strengthen High pulmonary vascular resistance, low pulmonary blood flow Carries moderately saturated blood 2. Ductus Venosus Connects umbilical vein to IVC Flow regulated via sphincter Conducts highly oxygenated blood 3.Foramen Ovale Shunts highly oxygenated blood from RA to LA FATE OF THE SHUNTS 1. Foramen Ovale: Closes at birth due to decreased flow from placenta and IVC Pulmonary venous return causes pressure in LA to be higher than that in RA 2. Ductus Arteriosus: Due to decreased pulmonary vascular resistance, PA pressure falls belowsystemic pressure and blood flow through DA is diminished Closure mediated by bradykinin Prostaglandin E2 may reopen DA 3. Umbilical Vessels Constrict at birth and are then tied and cut CYANOSIS IN THE NEW BORN Arterial oxygen saturation less than 90% PO2 less than 60 torr Common Causes: Intrinsic pulmonary disease Congenital heart lesions Central nervous system depression with hypoventilation CYANOTIC HEAR DISEASES The 5 Ts Tetralogy of Fallot 4 lesions Overriding aorta Right ventricular hypertrophy Ventricular septal defect Right ventricular outflow tract obstruction Cyanosis is caused by Right to Left shunting through the VSD Correction Early repair, unless patient is premature or low birth weight VSD is closed with patch Obstructing RV muscle is removed All other outflow tract abnormalities are addressed Transposition of the Great Arteries

Most common cyanotic condition that requires hospitalization in first 2 weeks of life Aorta arises from RV and carries oxygenated blood to the lungs Truncus Arteriosus Single artery arises from the heart, supplying both aorta and pulmonary artery. VSD below the truncal valve allows mixing of right and left ventricular blood Tricuspid Atresia Tricuspid valve fails to develop, therefore leaving no connection between RA and RV (which is hypoplastic) Desaturated blood from RA must cross through PFO to LA and LV Total Anomalous Pulmonary Venous Return Pulmonary veins are not connected to the LA, but rather converge into a confluence just post to the LA Confluence drains into a systemic vein, which may be obstructed Causes symptomatic pulmonary edema and cyanosis

Ebsteins Anomaly Defect that mainly affects the tricuspid valve. The tricuspid valve is located lower than normal The upper part of the right ventricle is part of the right atrium, making the right ventricle is too small and the right atrium is too large. Abnormal leaflets may let blood leak back into the atrium after it has flowed into the ventricle. The backward flow of blood makes the atrium even larger and the ventricle even smaller. Often Associated with other heart lesions ASD Pulmonary Stenosis Pulmonary Atresia ACYANOTIC HEART DISEASE a group of cardiac diseases with a Left TO Right shunt or left heart abnormality Acyanotic lesions make up about one third of congenital heart disease. ASD Most commonly occurs in the ostium secundum- covering the central portion of the inter-atrial septum. Generally asymptomatic for the first 3 decades of life. Symptoms may include exercise intolerance, dyspnea on exertion, and fatigue cause by right heart failure and pulmonary hypertension VSD May be anywhere in intra-ventricular septum Approx of all VSDs are small, and more than close spontaneously. Highest closure rates in the first decade of life. Eisenmengers complex: Left TO Right shunt causes pulmonary hypertension with resulting reversal of the direction of the shunt. Reversal of the shunt leads to cyanosis, dyspnea, hemoptysis, reduced exercise tolerance, syncope, palpitations, and atrial fibrillation PDA Small PDA does not increase risk for heart failure- but does carry a risk for bacterial endocarditis. Without ligation- there is an ongoing risk for bacterial endocarditis, heart failure, and development of Eisenmengers complex. COARCTATION OF AORTA Coarctation usually occurs just distal to the left subclavian artery at the ligamentum arteriosum Causes systemic hypertension and secondary LVH with heart failure. Young adults may be asymptomatic except for hypertension and decreased lower extremity pulses.

May be seen on CXR- characterized by the 3 sign- coarct segment between dilated left subclavian above and convexity of descending aorta below. HYPERTENSION Classification of Blood Pressure (JNC VII) Normal and Prehypertension or Stage 1 hypertension or Stage 2 hypertension or Peripheral vascular disorders: Disorders affecting the arteries, veins, and lymphatics of the extremities. Occlusive arterial disease includes peripheral arterial occlusion thromboangiitis obliterans . Venous diseases include venous thrombosis and varicose veins, combined arteriovenous disorders include arteriovenous fistula, and lymphatic disorders include lymphedema and lipedema. Systolic BP, mm Hg <120 120-139 140-159 >160 Diastolic BP, mm Hg <80 80-89 90-99 >100

and

Peripheral Arterial Occlusion Occlusion of blood supply to the extremities by atherosclerotic plaques (atheromas), a thrombus, or an embolism. Clinical syndromes of arterial occlusion depend on the vessel involved, the extent of obstruction, how rapidly occlusion progresses, and whether collateral flow is adequate. Acute occlusion: The history includes sudden onset of severe pain, coldness, numbness, and pallor in an extremity. Chronic occlusion: The initial symptom is intermittent claudication. Symptoms of claudication--a pain, ache, cramp, or tired feeling that occurs on walking--are most common in the calf but may occur in the foot, thigh, hip, or buttocks. Thromboangiitis Obliterans (Buerger's Disease) An obliterative disease characterized by inflammatory changes in small and mediumsized arteries and veins.; may be a reaction to tobacco by persons with a specific phenotype. . The patient may complain of coldness, numbness, tingling, or burning before there is objective evidence of disease. Pulsations in one or more pedal arteries and often at the wrist are impaired or absent. The disease progresses proximally. The acute stage will progress unremittingly if the patient continues to smoke; tissue may be damaged sufficiently to necessitate amputation. Raynaud's Disease and Phenomenon Spasm of arterioles, usually in the digits and occasionally in other acral parts (eg, nose, tongue), with intermittent pallor or cyanosis. Raynaud's disease, most common in young women , is idiopathic. Raynaud's phenomenon is secondary to other conditions, such as connective tissue disorders (scleroderma, RA, SLE), obstructive arterial diseases (arteriosclerosis obliterans, thromboangiitis obliterans, thoracic outlet syndrome), neurogenic lesions, drug intoxications, dysproteinemias, myxedema, primary pulmonary hypertension, and trauma. Intermittent blanching or cyanosis of the digits is precipitated by exposure to cold or by emotional upset. Color changes may be triphasic (pallor, cyanosis, redness--reactive hyperemia) or biphasic (cyanosis, redness); do not occur above the metacarpophalangeal joints. Vasospasm of the digital arteries and arterioles may last minutes to hours but is rarely severe enough to cause gross tissue loss; Rewarming the hands restores normal color and sensation. Raynaud's disease is differentiated from Raynaud's phenomenon by bilateral involvement and no evidence of an underlying cause. Venous Thrombosis The presence of a thrombus in a vein. Thrombosis may affect superficial veins (superficial thrombophlebitis) or deep veins (deep vein thrombosis). Thrombosis is virtually always accompanied by phlebitis, thus the terms thrombosis and thrombophlebitis are used interchangeably Prolonged venous thrombosis may lead to chronic venous insufficiency, in which there is edema, pain, stasis pigmentation, stasis dermatitis, and stasis ulceration. Many factors may contribute to venous thrombosis: injury to the endothelium of the vein, indwelling catheters,

 injection of irritating substances, thromboangiitis obliterans, septic phlebitis; hypercoagulability associated with malignant tumors, blood dyscrasias, oral contraceptives, idiopathic thrombophlebitis stasis in postoperative and postpartum states, prolonged bed rest of any chronic illness, heart failure, stroke, and trauma. Prolonged immobilization with the legs dependent while traveling (especially on long flights) is a risk factor, even in normal persons. Strenuous exercise of muscles in the affected extremity (eg, arm) is also a risk factor. Anticoagulant drugs (eg, heparin, the coumadin compounds) can prevent thrombi from forming or extending. Symptoms of acute thrombophlebitis arise over hours to 1 or 2 days. The disease is usually self-limited and lasts 1 to 2 wk, after which the acute process subsides and painful symptoms disappear. DVT is usually benign but can cause lethal pulmonary emboli or chronic venous insufficiency. Superficial thrombophlebitis alone, even when recurrent, causes neither of these serious complications Superficial thrombophlebitis requires no specific therapy other than relief of discomfort. Warm compresses over involved veins and NSAIDs are helpful. For DVT, the objectives of therapy are to prevent pulmonary embolism and chronic venous insufficiency. When edema subsides, the patient should be measured for a firm below-knee elastic stocking (providing 30 to 40 mm Hg pressure) to control the edema that will occur with ambulation. Varicose Veins Elongated, dilated, tortuous superficial veins (usually in the legs) with incompetent valves, permitting reversed flow. Varicose veins are associated with valvular dysfunction. Secondary factors include hormonal changes during early pregnancy, pressure on the pelvic veins during later pregnancy, and an abdominal tumor. Prolonged standing (eg, in some occupations) aggravates but does not cause varicose veins. Varicose veins may be associated with aching, fatigue, or heat that is relieved by elevating the leg or by wearing compression hosiery. Probably the most significant feature about the history of pain of varicose veins is that the pain is relieved when the leg is elevated. Treatment is primarily to relieve symptoms and manage complications. Patients with asymptomatic varicosities often seek cosmetic treatment. Lightweight compression hosiery for small, mildly symptomatic varicose veins is helpful and often adequate. Heavier elastic (support) stockings, knee-length or thigh-length, may be worn by patients with advanced varicose veins who prefer not to have active therapy or in whom active therapy is contraindicated.