STEP 1

HyGuru Learn. Integrate. Apply.

USMLE Step 1 Notes

Created by: Rahul Damania, MD, David Shafran, MD & the HyGuru community

CONTACT US: 513 484 5819 [email protected] Cleveland, OH www.hyguru.com Cardiovascular (CV) QID Topic Educational Objective HyGuru: A Step Beyond System Subject Repeats 1623 Left atrial CV dysphagia can result from Left atrial dilation can cause dysphagia Cardiovascular (CV) Anatomy (Anat) 1 enlargement external compression of the • Rarely can compress left recurrent esophagus by a dilated and laryngeal nerve posteriorly displaced LA in pts w/ Anterior surface of heart RHD and MS/MR. • Right atrium superiorly • Right ventricle inferiorly 1805 Varicocele Pressure in the left renal vein may Right gonadal vein > IVC Cardiovascular (CV) Anatomy (Anat) 1 become ↑ due to compression •Left gondal vein > L renal vein > IVC where the vein crosses the aorta • L renal vein runs between SMA and beneath the SMA. This aorta (can be compressed) > varicocele "nutcracker effect" can cause hematuria and flank pain. Pressure can also be ↑ in the left gonadal vein, leading to formation of a varicocele.

1884 CT abdomen The IVC is formed by the union The Superior Mesenteric Vein joins the Cardiovascular (CV) Anatomy (Anat) 1 of the right and left common iliac Splenic vein to form the Portal vein veins at the lvl of L4-L5. The renal arteries and veins lie at the lvl of L1. The IVC returns venous blood to the heart from the ↓ extremities, portal system, and abdominal and pelvic viscera.

1943 Brachiocephalic The BCV drains the ipsilateral Brachiocephalic vein obstruction Cardiovascular (CV) Anatomy (Anat) 1 vein obstruction jugular and SCVs. The bilateral • Due to pancoast tumor or thrombotic BCVs combine to form the SVC. occlusion due to central line BCV obstruction causes SSx • R side from subclavian and internal similar to those seen in SVC carotid syndrome, but only on one side of • Ext carotid drains to subclavian the body. • R brachiocephalic vein drains R lymphatic duct • Right face and arm will be swollen R subclavian or axillary obstruction • R arm swelling only SVC compression • Bilaeral face, neck and arm swelling

1967 CABG The great saphenous vein is a LAD block Cardiovascular (CV) Anatomy (Anat) 1 superficial vein of the leg that • Left internal mammary artery is preferred originates on the medial side of vessel for bypass the foot, courses anterior to the • Great saphenous vein with multiple medial malleolus, and then travels bypasses up the medial aspect of the leg • Superficial vein of leg and thigh. It drains into the • Longest vein in body femoral vein w/i the region of the • Med foot > ant to med malleolus > femoral triangle, a few cm med aspect of leg/thigh (3• 4cm inferolateral to the pubic tubercle. Inferolateral to pubic tubercle) > femoral vein • Accessed surgically near femoral triangle (inguinal lig [sup], sartorius [lat], adductor longus [med]) Baker's cyst can compress popliteal art Small saphenous vein: lateral foot to popliteal vein 2130 Blunt aortic injury Traumatic aortic rupture is most Blunt aortic trauma (sudden Cardiovascular (CV) Anatomy (Anat) 1 often caused by the rapid deceleration) deceleration that occurs in MVCs. • Aortic isthmus (tethered by ligamentum The most common site of injury arteriosum) is more commonly ruptured is the aortic isthmus, which is • Can affect ascending aorta but is rare tethered by the ligamentum arteriosum and is relatively fixed and immobile compared to the adjacent descending aorta. 7646 Implantable LV leads in biventricular PMs Biventricular pacemaker 3 leads Cardiovascular (CV) Anatomy (Anat) 1 cardioverter course through the coronary • 1 in RA, 1 in RV defibrillator sinus, which resides in the AV • 1 in LV via the Ra > coronary sinus (via groove on the posterior aspect of atrioventricular groove on posterior heart) the heart. > lateral venous tributaries into LV

11730 Sinoatrial node The SA node consists of SA node Cardiovascular (CV) Anatomy (Anat) 1 specialized PM cells located at • Junction of right atrium and SVC the jxn of the RA and SVC. It is AV node the site of earliest electrical • Right atrium near septal cusp of tricupsid activation in pts w/ sinus rhythm. valve near coronary sinus

11832 Retinal artery RAO is a cause of acute, painless, Internal carotid > opthalmic artery > Cardiovascular (CV) Anatomy (Anat) 1 occlusion monocular vision loss. It is retinal artery usually caused by TE • Retinal artery occlusion: painless vision complications of atherosclerosis loss with cherry red spot on macula traveling from the ICA and through the ophthalmic artery. 11956 AV node The AV node is located on the AV node is located near the insertion of Cardiovascular (CV) Anatomy (Anat) 1 endocardial surface of the RA, the septal leaflet of the tricupsid valve near the insertion of the septal and the orifice of the coronary sinus leaflet of the TV and the orifice • Opening of the pulmonary vein is the of the coronary sinus. MC location of ectopic A Fib generation • Isthmus between the IVC and tricuspid annulus is site of ablation for A Flutter SA node is located in the upper right anterior portion near the opening for the SVC

12046 Subclavian steal Subclavian steal syndrome occurs Cardiovascular (CV) Anatomy (Anat) 1 syndrome due to severe stenosis of the proximal SCA, which leads to reversal in blood flow from the contralateral vertebral artery to the ipsilateral vertebral artery. Pts may have SSx related to arm ischemia in the affected extremity (eg, exercise-induced fatigue, pain, paresthesias) or vertebrobasilar insufficiency (eg, dizziness, vertigo).

654 Penetrating The LV forms the apex of the Stab in 5th intercostal space at the Cardiovascular (CV) Anatomy (Anat) 2 thoracic trauma heart and can reach as far as the midline in lateral direction will 5th ICS at the left MCL. All other penetrate the left lung chambers of the heart lie medial • Lung extend above 1st rib to the left MCL. The lungs • Stab wound more medial and deeper overlap much of the anterior could hit the left ventricle (anterior surface surface of the heart. covered by the lung) • Apex at midclavicular line Heart • Anterior surface: RV • Inferior surface: RV + LV touching central tendon • Posterior surface: LA Azygos vein • Posterior mediatinum immediately to the right of the midline 1699 Penetrating The RV composes most of the Stab wound to 4th intercostal left sternal Cardiovascular (CV) Anatomy (Anat) 2 thoracic trauma heart's anterior surface. A deep, body penetrating injury at the left • Skin sternal border in the 4th ICS • Pec major would puncture the RV. • Ext intercostal • Internal intercostal • Internal thoracic art and vein • Trasversus thoracis muscle • Parietl pleura • Pericardium • R ventricle Stab to the right of the vertebral body from behind could injury IVC Stab to 2nd intercostal left sternal border could injure pulmonary trunk L atrium: posteriod surface of heart L ventricle: lateral surface of heart

2023 Central venous The common cardinal veins of the Central line Cardiovascular (CV) Anatomy (Anat) 2 catheter developing embryo drain directly • Subclavian or internal jugular vein into the sinus venosus. These • SVC comes from common cardinal veins cardinal veins ultimately give rise which drain into the sinus venosus to the SVC and other constituents Embryonic veins of the systemic venous • Umbical > ligamentum teres hepatis circulation. • Vitellin > portal system • Cardinal >sinus venosus > SVC

8332 Echocardiography The LA forms the majority of the TEE Cardiovascular (CV) Anatomy (Anat) 2 posterior surface of the heart and • Pointed anteriorly: left atrium, atrial resides adjacent to the esophagus. septum and mitral valve Enlargement of the LA can compress the esophagus and cause dysphagia. 8333 Echocardiography The descending thoracic aorta lies TEE Cardiovascular (CV) Anatomy (Anat) 2 posterior to the esophagus and the • If pointed posteriorly: will see descending LA. This position permits clear aorta visualization of the descending RALS aorta by TEE, allowing for the • Right pulmonary artery is Anteriot to detection of abnormalities such as bronchi Left pulmonary artery is Superior dissection or aneurysm. to bronchi SVC • Formed behind right 1st costal cartilage • Compressed by pancoast tumor or mediastinal mass 11763 Central venous The femoral triangle (lateral to Femoral vein Cardiovascular (CV) Anatomy (Anat) 2 catheter medial) consists of the femoral • Just medial to femoral art (1 cm below nerve, femoral artery, femoral inguinal ligament, 0.5• 1 cm medial to vein, and deep inguinal femoral art) nodes/lymphatic vessels. • NAVEL from lat to med Cannulation of the femoral vein should occur approximately 1 cm below the inguinal ligament and just medial to the femoral artery pulsation.

11764 Cardiac The optimal site for obtaining Cardiac Cath Cardiovascular (CV) Anatomy (Anat) 2 catheterization vascular access in the lower • Cath into femoral or radial artery extremity during cardiac • Middle of hip below inguinal lig catheterization is the common • Arterial puncture ABOVE the inguinal femoral artery below the inguinal ligament increases risk for retroperitoneal ligament. Cannulation above the hemorrhage inguinal ligament can • Cannot be controlled by manual significantly ↑ the risk of pressure retroperitoneal hemorrhage. • Present with hemodynamic instaibility, hypotension Right paracolic gutter (between ascending colon and abdominal wall): fluid accumulation > think GI organ issue 11780 Pulmonary blood PAOP is measured at the distal tip Swan Ganz Catheter Cardiovascular (CV) Anatomy (Anat) 2 flow of the pulm artery catheter after • Catheter inserted into pulmonary artery > an inflated balloon occludes balloon infilated > measure P (PCWP = blood flow through a pulm artery LA and LV end diastolic pressure) branch. It closely corresponds to Pleural manometry LA and LV EDP. • Catheter placed into pleural space and measures pleural pressure 15197 Cardiac To access the left side of the Cardiovascular (CV) Anatomy (Anat) 2 catheterization heart, CVCs must cross the interatrial septum at the site of the foramen ovale. Entry into the LA allows for direct measurement of LA pressure and for access to arrhythmogenic foci on the LA myocardium or pulm veins.

8294 Tricuspid IE in IVDUs commonly affects Cardiovascular (CV) Anatomy (Anat) 3 regurgitation the TV, often leading to septic pulm emboli. Pts can have an early- or holo-systolic murmur of TR, which is best auscultated in the 4th or 5th ICS at the left lower sternal border.

1751 Patent ductus The ductus arteriosus is derived Aortic Arch Derivatives 1: maxillary art Cardiovascular (CV) Anatomy (Anat) 4 arteriosus from the sixth embryonic aortic • stapedius art, hyoid art arch. A patent ductus arteriosus • common carotid, prox part of internal (PDA) causes left-to-right carotid shunting of blood that can be • left > aortic arch; right > prox part of R heard as a continuous murmur subclavian art 6: left > ductus arteriosus; over the left infraclavicular right > prox pulmonary art region. Indomethacin (a PGE2 synthesis inhibitor) can be used to close a PDA in premature infants, but surgical ligation is often necessary in older patients.

11831 Coronary artery The inferior epigastric artery is 1 External iliac art Cardiovascular (CV) Anatomy (Anat) 4 disease of 2 branches of the external iliac • Gives off Inf Epigastric art (runs sup and artery and takes off immediately med into abdomen) proximal to the inguinal ligament. • Gives off Deep Circumflex Iliac artery It provides blood supply to the (also supplies lower abdominal wall) lower anterior abdominal wall as • Becomes common femoral artery once it it runs superiorly and medially up passes the inguinal ligament the abdomen. Medial circumflex femoral artery • Branch of Deep Femoral • Supplies femoral neck/head

11842 Atrial fibrillation AF is a/w ↑ risk of systemic TE. A fib Cardiovascular (CV) Anatomy (Anat) 5 The LA appendage is the most • Risk of systemic thromboembolism due common site of thrombus to stasis formation. • Left atrial appendage is MC site for clot Crista terminalis: separates smooth sinus venosus and pectinate muscles LV mural thrombus: systolic dysfunction > impaired apical wall movement

12151 Aortic dissection The intimal tear in Stanford type Cardiovascular (CV) Anatomy (Anat) 6 A AD (involving the ascending aorta) usually originates in the sinotubular jxn whereas the intimal flap in Stanford type B AD usually starts near the origin of the left SCA. Dissections can propagate distally to the thoracoabdominal aorta.

1871 Coronary blood The inferior wall of the LV forms RCA Cardiovascular (CV) Anatomy (Anat) 9 flow most of the inferior • Posterior descending art in 90% of pop (diaphragmatic) surface of the • PDA controls AV node heart and is supplied by the PDA. • Occlusion > inferior wall infarct In 85%-90% of individuals, the LAD PDA derives from the RCA (right • Give off diagonal branch dominant coronary circulation). • Supplies anterior papillary muscle Left circ • Lateral wall of LV Right marginal • From RCA • Supplies RV 11837 Coronary blood Coronary dominance is Coronary Dominance Cardiovascular (CV) Anatomy (Anat) 9 flow determined by the coronary artery • Determined by which artery supplies supplying the PDA. The PDA PDA originates from the RCA in • RCA 70% of time approximately 70%-80% of pts • Left circ 10% of time (right dominant), both the RCA • Codominant 20% of time and LCX in 10%-20% LAD: supply anterior 2/3 of septum and (codominant), and the LCX in 5%-ant wall of LV Left diagonal: branch of 10% (left dominant). The LAD and supplies lat wall of LV dominant coronary artery supplies Right marginal: branch of RCA and blood to the AV node via the AV supplies free wall of RV nodal artery.

1538 Pulmonary The IVC courses through the IVC filter: prevents the propagation of Cardiovascular (CV) Anatomy (Anat) 13 embolism abdomen and inferior thorax in a DVT from the legs to the lungs location anterior to the right half • Used in pt with contraindication to of the vertebral bodies. The renal anticoagulation Renal veins join IVC at veins join the IVC at the lvl of L1/L2 L1/L2, and the common iliac Common iliac veins becomes IVC at L4 veins merge to become the IVC at the lvl of L5. IVC filters are placed in pts w/ DVT who have c/i to anticoagulation Thx.

10467 Myocardial Leads I and aVL correspond to STEMI Cardiovascular (CV) Anatomy (Anat) 18 infarction the lateral limb leads on ECG. 1 and avL Therefore, ST elevation or Q • Lateral infarct > L circumflex waves in these leads are V1 V4 indicative of infarction involving • Anterior infart > LAD the lateral aspect of the left • Distal LAD in V3 and V4 ventricle, which is supplied by the V1 V6+1+avL left circumflex artery. • Left main coronary artery 2,3 and avF • Inferior infarct 12144 Myocardial Papillary muscle rupture is a life- Cardiovascular (CV) Anatomy (Anat) 18 infarction threatening complication that typically occurs 3-5 days after MI and presents w/ acute MR and pulm edema. The posteromedial papillary muscle is supplied solely by the PDA, making it susceptible to ischemic rupture.

1883 Community On posteroanterior chest x-ray, • RA: most of right side cardiac silhouette Cardiovascular (CV) Anatomy (Anat) 21 acquired the right middle lobe is seen IVC: most inferior edge of right border pneumonia adjacent to the right border of the • Pulmonary art: left side of silhouette just heart, which is primarily formed below aortic arch RV: anterior wall by the right atrium. Consolidation • SVC: flattened opacity parallel to in the right middle lobe can vertebral column that obscure the X-ray silhouette of terminates inferiorly at RA the right heart border.

788 Homocysteine ↑ lvls of plasma homocysteine are Homocysteine to Methionine Cardiovascular (CV) Biochemistry 2 an independent RFx for (Methionine synthase + methylene (Bioc) thrombotic events. Homocysteine tetrahydrofolate reductase + B9,12) can be metabolized to methionine Methionine to SAM via remethylation or to • Homocysteine to cystathionine cystathionine via transsulfuration. (cystathionine synthase + B6) Hyperhomocysteinemia is most Cystathionine to Cysteine (Cystathionase + commonly due to genetic B6) mutations in critical enzymes or Homocystinuria deficiencies of vitamin B12, • Increased risk for athero (damages vitamin B6, and folate. endothelial cells) B12 deficiency • Lethargy, seizures, paresthesias and hypotonia due to MMA 1047 Dilated Thiamine deficiency causes Thiamine def Cardiovascular (CV) Biochemistry 8 cardiomyopathy beriberi and Wernicke-Korsakoff • Beriberi: peripheral neuropathy and (Bioc) syndrome. Dry beriberi is dilated cardiomyopathy characterized by symmetrical • Can occur in less than 1 year of poor peripheral neuropathy; wet intake (help to differentiate between B12 beriberi includes the addition of def) high-output congestive heart • Infantile will present 2• 3months after failure. birth Riboflavin def • Angular cheilosis, stomatitis, glossitis • Normocytic anemia Vit A def • Increased risk for measels (explains why this is a tx) 2034 Southern blotting Southern blotting is a technique x linked recessive Cardiovascular (CV) Biochemistry 1 used to identify DNA mutations. • Father to son does not occur (Bioc) It involves restriction Southern blot for DNA endonuclease digestion of sample • DNA extracted DNA, gel electrophoresis, and • Restriction endonuclease gene identification w/ a labeled • Gel electrophoresis DNA probe. • DNA probe to identify target DNA 1229 Sensitivity and When undergoing Dx testing, pts • True positive = (sensitivity) x (# of pt Cardiovascular (CV) Biostatistics (Bios) 4 specificity w/ the disease can test (+) (true actually with dz) False negative = (1• (+), TP) or (-) (false (-), FN). The sensitivity) x (# of pt actually with dz) sensitivity of a test determines the proportion of pts that are correctly classified: TP = (Sensitivity) x (Number of pts w/ the disease) FN = (1 - Sensitivity) x (Number of pts w/ the disease)

1283 Comparing 2 The two-sample t test is a t test: comparing 2 means of populations Cardiovascular (CV) Biostatistics (Bios) 1 means statistical method commonly • Calculate p value employed to compare the means • P value < 0.05: reject null (the groups are of 2 groups of subjects. statistically significantly different) Linear regression • Model linear relationship between a dependent variable and an independent variable Correlation coefficient: measure of strenfth and direction of a linear relationship between 2 variables Chi squared: comparing 2 categorical data Meta analysis: used to increase power

1301 Bias The main purpose of blinding is Double blinding Cardiovascular (CV) Biostatistics (Bios) 4 to prevent pt or researcher • Prevents observer bias expectancy from interfering w/ an Beta error outcome. • Concludes no difference when there is one Recall bias • Inaccurate recall usually seen with dz • Seen in case control studies Selection bias • People are non randomly selection or from the selective loss of follow up

35 Transposition of An echocardiogram showing an Transposition of the Great Arteries Cardiovascular (CV) Embryology 1 the great vessels aorta lying anterior to the • Failure of aorticopulmonary septum to (Embr) pulmonary artery is diagnostic of spiral transposition of the great arteries • Will see anterior lying aorta (TGA). This life-threatening • Must have a shunt to live (ASD, PDA, cyanotic condition results from PFO, VSD) failure of the fetal • Associated with maternal diabetes aorticopulmonary septum to spiral Random normally during septation of the Syndactyly: failure of apoptosis truncus arteriosus. Hypospadias: failure of fusion Branchial cleft cyst: failure of obliteration VSD: failure of interventricular septum to proliferate Trunuc arteriosus: failure of septation 202 Atrial septal defect The foramen ovale is patent in Cryptogenic (paradoxical) Stroke Cardiovascular (CV) Embryology 2 approximately 25% of normal • DVT > PFo > stroke (Embr) adults. Although the foramen PFO ovale usually remains fxnally • Failure or septum primum and septum closed, transient ↑ of RA pressure secundum to fuse above LA pressure can produce a ASD right-to-left shunt, leading to • Absence of either septum primum or paradoxical embolism of venous secundum to develop clots into the arterial circulation. • Can cause HF, pulmonary HTN or Eisenmenger • Fixed S2 splitting Truncus arteriosus • Incomplete development of aorticopulmonary septum VSD • Incomplete closure of interventricular foramen 1705 Tetralogy of Fallot TOF results from anterior and TOF Cardiovascular (CV) Embryology 3 cephalad deviation of the • Abnormal neural crest cell migration > (Embr) infundibular septum during anterior and cephalad deviation of embryologic development, infundibular septum resulting in a malaligned VSD w/ • RV outflow tract obstruction can be an overriding aorta. As a result. subvalvular, intravalvular or supravalvular the pt has RV outflow obstruction TAPVR (resulting in a systolic murmur) • All blood back to Ra > must have ASD and squats to ↑ the peripheral or VSD SVR (afterload) and ↓ right-to- Failed Fusion of Sup and Inf endocardial left shunting across the VSD. cusion • Can lead to Eisenmenger syndrome

1750 Embryologic The 1st AA gives rise to a portion Pharyngeal Arch Cardiovascular (CV) Embryology 2 derivatives of the maxillary artery, and the • CN 5, maxillary art (Embr) 2nd AA gives rise to the stapedial • CN 7, stapedius art (typically regresses) artery, which typically regresses • CN 9, Common carotid art and prox in humans. The 5th AA internal carotid art 4: Superior laryngeal completely regresses, leaving no nerve, L aorta; r subclavian art 6: structures or vestiges in the adult. Recurrent laryngeal nerve. L ductus The 3rd AA forms the CCAs and arteriosus; r pulmonary art proximal ICAs. The 4th AA gives rise to part of the true AA and a portion of the SCAs. The 6th AA gives rise to the pulm arteries and the ductus arteriosus.

30 Turner syndrome Aortic coarctation in a Heart Dz Down Cardiovascular (CV) Genetics (Gene) 8 child/young adult presents with • Endocardial cushion (ostium primum, AV lower-extremity claudication (eg, regurg) pain and cramping with exercise), DiGeorge blood pressure discrepancy • TOF between the upper and lower • Truncus arteriosus extremities, and delayed or • Interrupted aortic arch: aortic arch is diminished femoral pulses. atretic or segment absent, low BP in legs, Turner syndrome (45,XO) is respiratory distress, CHF on 1 day of life associated with coarctation of the Freidreich aorta in up to 10% of cases. • HCM Kartagener • Situs inversus Marfan • Cystic medial necrosis (aortic dissection/aneurysm) • MVP TS • Ventricular rhabdomyoma Turner • Aortic coarc • Infantile: cyanosis of leg (patent PDA) • Adult: BP variable, rib notching • Bicuspid aortic 882 Down syndrome DS is most commonly caused by Down Syndrome Cardiovascular (CV) Genetics (Gene) 6 maternal meiotic nondisjxn, a • 95%: Meitotic nondisjunction process by which the fetus • 5%: Robertsonian translocation (14 and receives 3 full copies of 21) chromosome 21. Dysmorphic • 1% mosiascism features (eg, flat facial profile, • Flat face, epicanthal folds, upslanting protruding tongue, small ears, palpebral fissures, protruding tongue, small upslanting palpebral fissures) and ears, endocardial cushion heart defects cardiac defects (eg, endocardial Chromosomal deletions cushion defects) are Chx. • Cri du chat: 5p • DiGeorge: 22q11 Imprinting • Prader willi 8292 Turner syndrome TS is a/w congenital anomalies of Turner's Cardiovascular (CV) Genetics (Gene) 8 the aorta, and the most common • Short stature, webbed nick, broad chest, defect is a bicuspid AV. A shortened fourth metacarpal nonstenotic bicuspid AV can • Bicuspid aortic valve and pre ductal MFx as an early systolic, high- coarctation frequency click over the right 2nd • Early systolic, high frequency click interspace. Bicuspid AVs are at • Increased risk of stenosis, insufficienc risk for stenosis, insufficiency, and infection and infection. Downs • Complete atrioventricular canal, ASD and VSD Rheumatic heart disease • MR early, MS late Marfans, Ehlers Danlos, Fragile X • MVP PDA • Premature baby, rubella 13600 Dilated AD mutations in the TTN gene, Cardiovascular (CV) Genetics (Gene) 8 cardiomyopathy which encodes for the sarcomere protein titin, are the most common cause of familial DCM.

8711 Collagen types Type I collagen is the most Type 1 Collagen Cardiovascular (CV) Histology (Hist) 1 prevalent collagen in the human • Dermis, bone, tendon, ligaments, dentin, body and is the 1° collagen in cornea, scar tissue mature scars. Type 2 Collagen • Cartilage, vitreous humor, nucleus pulposus Type 3 Collagen • Skin, lungs, intestines, blood vessels, bone marrow, lymphatics and granulation tissue Type 4 Collagen • Basement membrane 568 Heart Acute cardiac transplant rejection Acute transplant rejection Cardiovascular (CV) Immunology 1 transplantation occurs wks following • Weeks after surgery (Immu) transplantation and is primarily a • Dense infiltrate of mononuclear cells cell-mediated process. On (mainly T cells) histopathologic analysis of an • T cell sensitization against graft MHC Ag endomyocardial Bx, a dense Hyperacute rejection mononuclear lymphocytic • Cessation of blood flow immediately infiltrate w/ cardiac myocyte dmg Hypersensitivity myocarditis will be visualized. Tx w/ • Perivascular infiltrate with abundant immunosuppressive Rx is aimed eosinophils primarily at preventing this form Chronic rejection of rejection. • Scant inflammatory cells with interstitial fibrosis

679 Endocarditis Staphylococcus epidermidis, a Cardiovascular (CV) Microbiology 15 Gram (+) coccus that grows in (Micr) clusters, is a skin commensal that is a common cause of infection in pts w/ prosthetic devices such as artificial joints or heart valves. Unlike S aureus, S epidermidis is coagulase (-). Unlike S saprophyticus (another coagulase (-) staphylococci species), S epidermidis is susceptible to novobiocin. 729 Endocarditis Staphylococcus aureus causes Staph Aureus Endocarditis (IV drug Cardiovascular (CV) Microbiology 15 acute BE w/ rapid onset of SSx, user) (Micr) including shaking chills (rigors), • Perforate heart valves, rupture chordae high fever, dyspnea on exertion, tendineae, send septic emboli to lung or and malaise. In IVDUs, it can brain cause right-sided endocarditis w/ Candida endocarditis septic embolization into the • 3rd MCC if IV drug user lungs. Culture negative endocarditis • HACEK • Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella Strep Gallolyticus (bovis) • Endocarditis + colon cancer 733 Endocarditis Enterococcus is a component of Enterococcus Cardiovascular (CV) Microbiology 15 the normal colonic and urogenital • Gram +, cat neg, grows in hypertonic (Micr) flora and is capable of growing in saline and bile, PYR positive, gamma hypertonic saline and bile. It is γ- hemolytic hemolytic, catalase (-), and • Can cause endocarditis after cytscopy, pyrrolidonyl arylamidase (+). GU colonoscopy, and obstetric procedures instrumentation or catheterization Viridans Strep has been a/w enterococcal • Dental procedures endocarditis. Corynebacterium, Haemophilus, Staph, Strep, Neisseria • Bactermia after nasal polyp removal

1001 Endocarditis Streptococcus gallolyticus Cardiovascular (CV) Microbiology 15 (formerly S bovis) endocarditis (Micr) and bacteremia are a/w GI lesions (colon ca) in ~25% of cases. When S gallolyticus is cultured in the blood, workup for colonic malignancy w/ colonoscopy is essential.

1002 Endocarditis Viridans streptococci produce Viridans Streptococci Cardiovascular (CV) Microbiology 15 dextrans that aid them in • Strep Mutans and Step Sanguinis (Micr) colonizing host surfaces, such as • Cause dental caries dental enamel and heart valves. • Cause subacute bacterial endocarditis, These organisms cause subacute deep wound infections, abdominal BE, classically in pts w/ pre- abscesses and septicemia existing cardiac valvular defects • Dextrans adhere to tooth enamel and after dental manipulation. fibrin platelet aggregates Anterior Uveitis • HSV, Syphilis, Lyme disease • HLa B27 Erythema nodosum • GAS, S Aureus, cocci, histo, blasto, chlamydia, crohns, sarcoid

1003 Endocarditis Viridans streptococci are normal Dental cleaning > bacterial endocarditis Cardiovascular (CV) Microbiology 15 inhabitants of the oral cavity and due to Viridans streptococci > dextrans (Micr) are a cause of transient bind to fibrin and platelets bacteremia after dental • MVP does not significantly increase procedures in healthy and your risk for subacte endocarditis diseased individuals. In pts w/ pre-Subendothelial collagen is important for existing valvular lesions, viridans platelet adhesion, not bacterial streptococci can adhere to fibrin- platelet aggregates and establish infection that leads to endocarditis.

8282 Catheter related The most important steps for Central Venous Catheter Cardiovascular (CV) Microbiology 3 bloodstream prevention of CVC infections are • S Aureus and S epi are common (Micr) infection as follows: infections Proper hand hygiene Reduction in CVC infection Full barrier precautions during • Hand watching insertion • Chlorhexidine skin disinfection Chlorhexidine skin disinfection • Sterile procedure Avoidance of the femoral • Subclavian or internal jegular insertion > insertion site femoral Removal of the catheter when it • Remove ASAP is no longer needed 31 Aortic coarctation Pts w/ adult-type coarctation of Spontaneous Intracranial Hemorrhage Cardiovascular (CV) Pathology (Path) 1 the aorta commonly die of HTN- • AVM, ruptured cerebral aneurysms, assoc complications, incl LV abuse of cocaine failure, ruptured dissecting AA, • Can also be due to coaractation of the and SICH. These pts are at ↑ risk aorta for ruptured intracranial aneurysms b/c of the ↑ incidence of congenital BAs of the COW as well as aortic arch HTN.

32 Patent ductus Digital clubbing and cyanosis w/o PDA Cardiovascular (CV) Pathology (Path) 4 arteriosus BP or pulse discrepancy are • Large PDA can lead to Eisenmenger pathognomonic for a large PDA syndrome > cyanosis and clubbing in lower complicated by Eisenmenger extremities WITHOUT pressure difference syndrome (reversal of shunt flow from upper to lower extremities from L-R to R-L). Severe Coarctation of aorta coarctation of the aorta can cause • Infant: cyanosis of lower extremities lower extremity cyanosis. R-L • Adults: pressure difference between shunting in pts w/ large septal upper and lower extremities, rib notching defects and TOF results in whole- ASD and VSD that become Eisenmenger body cyanosis. syndrome • Cyanosis of upper and lower body equally TOF • Whole body cyanosis

36 Atherosclerosis Stable angina pectoris results Stable Angina Cardiovascular (CV) Pathology (Path) 8 from myocardial O2 demand- • 75%+ occlusion of the coronary artery is supply mismatch and MFx as necessary chest pressure, tightness, or pain Unstable Angina or non STEMI that is reliably produced by • Ulcerated athero + partial thrombi exertion and relieved by rest. It occulsion most commonly occurs due to a Prinzmetal fixed atherosclerotic plaque • May occur at rest obstructing >70% of the coronary artery lumen that limits blood flow during exertion.

37 Myocardial STEMI involves transmural (full- Acute MI Cardiovascular (CV) Pathology (Path) 18 infarction thickness) infarction of the • typical chest pain not relieved by rest or myocardial wall, and usually nitroglycerin, diaphoresis, nause, results from acute atherosclerotic palpitation plaque rupture w/ the devel of • Peaked T waves (localized hyperK) overlying thrombus that fully • STEMI occludes the coronary artery • Q waves lumen. It classically presents w/ • MCC by plaque rupture with sudden-onset substernal chest superimposed thrombus completely pain that's not relieved by rest or occluding the coronary artery short-acting nitrates. ECG Random demonstrates STE in the affected Stable angina: 75% occlusiong of coronary leads w/ subseq devel of Q artery waves. Unstable angina: ulcerated atherosclerotic plaque with partially occluding thrombus Prinzmetal: coronary artery spasm (ST elevation) • Usually responds to nitro

39 Atherosclerosis Gradually developing myocardial Rate of arthero formation is most Cardiovascular (CV) Pathology (Path) 8 ischemia encourages the important in determining ischemic formation and maturation of damag collateral vessels and is most • Slowly progressing coronary artery athero likely to occur in the setting of a > arterial collateral circulation around slow-growing, stable occlusion atherosclerotic plaque. An • Fibrous cap over athero plaque thins > unstable atherosclerotic plaque risk of rupture Larger lipid rich core of (eg, that w/ active inflammation, athero > risk of rupture a lipid-rich core, a/o a thin fibrous • Macrophages secrete metalloproteinase cap) is more likely to rupture, which thin fibrous cap of athero resulting in the abrupt onset of Statins decrease inflammation of athero > ischemia/infarction that precludes stabilzes plaque the development of viable • More calcification of coronary artery > collateral vessels. the greater the risk of rupture 40 Myocardial After the onset of severe ischemia MI Cardiovascular (CV) Pathology (Path) 18 infarction leading to MI, early signs of coag 0 4hr: no change necrosis don't become apparent 4 12: early coag nec, edema, wavy fibers on LM until 4hrs after the onset • Cytoplasmic hypereosinophilia of MI. 12 24: coag nec, contraction band necrosis 15day: coag nec and neutrophils 510day: macrophage 10 14day: granulation tissue and neovascularization 2wk 2mnth: collagen deposition/scar

43 Myocardial Hibernating myocardium refers to • Myocardial hibernation: chronic Cardiovascular (CV) Pathology (Path) 18 infarction the presence of LV systolic myocardial ischemia that lowers dysfxn due to ↓ coronary blood myocardial metabolism and function to flow at rest that's partially or match blood flow preventing necrosis. completely reversible by coronary Disorganized contractile and revascularisation. cytoskeletal proteins, altered adrenergic contril and increased Ca2+ response > decreased contraction. Coronary revascularization and return of flow will improve contractility and LV function. • Ischemic preconditioning: repeated brief ischemic events protect myocardium from subseqent prolonged ischemia

72 Endocarditis Janeway lesions are nontender, Infective Endocarditis Vascular issue Cardiovascular (CV) Pathology (Path) 15 macular, and erythematous • Systemic emboli > cerebral, pulmonary or lesions typically located on the splenic palms and soles of pts w/ acute IE • Mycotic aneurysm and are the result of septic • Janeway (painless on palms and soles) embolization from valvular Immunologic issue vegetations. • Osler (painful on fingertips and toes) • Roth spots

73 SLE CV MFx of lupus include SLE Cardiovascular (CV) Pathology (Path) 7 accelerated atherosclerosis, small- • Hypercoag > likely to cause MI vessel necrotizing vasculitis, • Lidman Sacks (verrucous) endocarditis pericarditis, and Libman-Sacks • Sterile vegetations of both sides of the endocarditis (small, sterile valve > can cause regurg or stenosis vegetations on both sides of the Dermatomyositis valve). Renal involvement • Extramuscular: interstitial lung disease, classically MFx as DPGN, which vasculitis and myocarditis is Chx by diffuse thickening of the glomerular capillary walls w/ "wire-loop" structures on LM.

74 Carcinoid tumors Carcinoid syndrome typically Carcinoid Syndrome Cardiovascular (CV) Pathology (Path) 4 presents w/ episodic flushing, • Flushing, diarrhea and bronchospasm secretory diarrhoea, and • TIPS (Tricupsid Insufficiency, Pulmonary wheezing. It can lead to Stenosis) due to serotonin stimulating pathognomonic plaque-like fibroblast growth > plaque like fibrous deposits of fibrous tissue on the tissue deposits on endocardium right-sided endocardium, causing • High 5• HIAA TR and right-sided HF. ↑ 24-hr • CT/MRI to locate tumor urinary 5-HIAA can confirm the • Tx: octreotide and surgery Dx. Carcinoid tumor • Can secrete histamine, serotonin and VIP Hyperhomocysteinemia • Arterial or venous thrmbosis and atherosclerosis

76 Hypertrophic In pts w/ HCM, dynamic LVOT HCM Cardiovascular (CV) Pathology (Path) 9 cardiomyopathy obstr is due to abn systolic • LV outflow obstruction due to anterior anterior motion of the anterior motion of mitral valve toward the leaflet of the MV toward a interventricular septum during systole hypertrophied IV septum. • Harsh systolic crescendo decrescendo murmur > worsens with valsalva, standing up or nitro 82 Hypertrophic HCM is a common cause of SCD Endocardial thickening and Cardiovascular (CV) Pathology (Path) 9 cardiomyopathy in young adults. Histologic noncompliant ventricular walls: features incl cardiomyocyte restrictive cardiomyopathy hypertrophy and myofiber • Amyloid, sarcoid, endomyocardial disarray w/ ↑ interstitial fibrosis. fibrosis, Leoffler's The structural disarray creates a Patchy fibrosis in the mural endocardium: substrate for ventricular chronic ischemic heart disease arrhythmia (e.g. v-tach, VF) that can lead to SCD.

83 Hypertrophic HCM is Chx by asymmetric (eg, HCM Cardiovascular (CV) Pathology (Path) 9 cardiomyopathy septal) LVH that can result in • Missense mutation in beta myosin heavy SCD. AD mutations affecting the chain and myosin binding protein C cardiac sarcomere genes (eg, Marfans cardiac β-myosin heavy chain • fibrillin 1 mutation on chromosome 15 gene and myosin-binding protein K+ cardiac channel protein mutations: C gene) are responsible for the congenital long QT > increased risk of majority of cases. Torsades Mutated transthyretin: cardiac amyloidosis

84 Long QT Unprovoked syncope in a Congenital prolonged QT Cardiovascular (CV) Pathology (Path) 4 syndrome previously aSSx young person • Mutations in K channel (internal rectifier) may result from a congenital JervelL Lange Nielson LQTS. The 2 most important • AR congenital syndromes w/ QT • Neurosensory deafness prolongation — RWS and JLNS Romano Ward — are thought to result from muts • AD in a K+ channel protein that • No hearing issue contributes to the delayed rectifier Dilated CM current (IK) of the cardiac AP. • Mutation of cytoskeleton or mitochondria HCM • Mutatio in beta myosin heavy chain Arrhythmogenic Right Ventricular Cardiomyopathy • Mutation of Ca binding sarcoplasmic reticulum protein • Progressive fibrofatty change in myocardium

86 Long QT Congenital LQTS is most often Congenital long QT syndrome Cardiovascular (CV) Pathology (Path) 4 syndrome caused by genetic muts in a K+ • Decrease K efflux (internaL rectifier) > channel protein that contributes to long phase 3 > prolonged QT > torsades the outward-rectifying K+ HCM current. A ↓ in the outward K+ • Myosin binding protein C gene and Beta current leads to prolongation of myosin heavy chain gene mutations AP duration and QT interval. Scar from a previous MI increases risk for This prolongation predisposes to developing an arrhythmia the devel of life-threatening Dilated cardiomyopathy ventricular arrhythmias (e.g. TdP) • Sarcomere structural gene mutations that can cause palpitations, syncope, seizures, or SCD.

89 Acute pericarditis In contrast to angina, the chest Fibrinous pericarditis post MI Cardiovascular (CV) Pathology (Path) 5 pain of pericarditis is sharp and • 24 days after MI pleuritic and may be exacerbated • Sharp, pleuritic pain that is exacerbated by swallowing or coughing. PIP by swallowing (suggests posterior occurs b/w 2 and 4 days pericardium involvement) and radiating to following a transmural MI. PIP is neck (suggest inferior pericardium an inflammatory rxn to cardiac involvement) muscle necrosis that occurs in the • Must have transmural necrosis adjacent pericardium. • Tx: aspirin Dressler's • 4• 10 weeks after MI • Fever, pleuritis, leukocytosis, pericardial friction rub, new pericardial or pleural effusion • Autoimmune attack against heart • Tx: aspirin, NSAIDs or steroids 91 Long QT Jervell and Lange-Nielsen Congenital Prolonged QT Cardiovascular (CV) Pathology (Path) 4 syndrome syndrome is an AR disorder Chx Jervell Lange Nielsen by profound bilateral • K channel issue sensorineural hearing loss and • Neurosensory deafness congenital LQTS, which • AR predisposes to ventricular Romano ward arrhythmias and SCD. This • K channel issue condition occurs 2° to mutations • No deafness in genes that encode voltage- • AD gated K channels. Brugada • Na channel issue • Asians Syndactylyl • Failed separate of digits Hereditary Hemorrhagive Telangiectasia (Osler Weber Rendu) • AD • Vascular telangiectasias R t bl d 92 Dilated Dilation of the LV cavity Nonvalvular HF Ischemic and Dilated Cardiovascular (CV) Pathology (Path) 8 cardiomyopathy commonly occurs in response to • Normal of decreased wall thickness systolic dysfxn (eg, ischemic • Increased ventricular cavity size heart disease, DCM) or certain • Decreased contractile function types of valvular disease (ie, AR, • Normal diastolic function MR). Chronic volume overload Hypertensive or hypertrophic causes progressive eccentric • HTN: globally increased wall thickness hypertrophy that eventually leads • Hypertrophic: increased septal thickness to ↓ ventricular contractility and • Decreased ventricular cavity size DHF. • Normal contractile function • Decreased diastolic function

94 Amyloidosis RCM can be caused by Isolated Atrial Amyloidosis Cardiovascular (CV) Pathology (Path) 1 infiltrative diseases (e.g. • ANP localized to atria only amyloidosis, sarcoidosis, Medullary carcinoma of thyroid hemochromatosis) and often • Calcintonin in thyroid results in diastolic HF due to Pituitary gland amyloid ventricular hypertrophy w/ • Prolactin derived proteins impaired ventricular filling. Type 2 DM Cardiac amyloidosis is • Amylin (islet amyloid protein) characterised histologically by Alzheimer areas of myocardium infiltrated • Beta amyloid plaques by an amorphous and acellular MM pink material (amyloid). • Ig light chains (especially lambda) • Deposit in heart, skin, tongue, GI, kidney and peripheral nerves • Bence joint proteins in urine 95 Hypertrophic HCM is caused by genetic Hypertrophic Cardiomyopathy Cardiovascular (CV) Pathology (Path) 9 cardiomyopathy mutations affecting structural • AD with variable expression proteins of the cardiac sarcomere • Haphazard hypertrophied myocytes (eg, β-myosin heavy chain, Viral myocarditis myosin-binding protein C) and is • lymphocytic interstitial inflammatory one of the most common causes infilitrate of SCD in young adults. Hypersensitivity myocarditis Histologically, it is Chx by • Interstitial inflammatory infiltrate or cardiomyocyte hypertrophy w/ mononuclear inflammatory cells and haphazard cellular arrangement eosinophils and interstitial fibrosis.

98 Constrictive In constrictive pericarditis, Constrictive pericarditis Cardiovascular (CV) Pathology (Path) 2 pericarditis normal pericardium is replaced by • Viral, surgery, radiation or TB dense, rigid pericardial tissue that • JVD, kussmaul sign (rise in JVD with restricts ventricular filling, inspiration), pulsus paradoxus, pericardial leading to low CO and progr right-knock sided HF. PEx findings in such • Pericardial knock: sharp more pts incl ↑ JVP, pericardial knock, accentuate sound heard before S3 normally pulsus paradoxus, and a would be paradoxical ↑ in JVP w/ Pulmonary HTN inspiration (Kussmaul sign). • Loud P2 176 Myocardial Mitochondrial vacuolization is Irreversible Injury Cardiovascular (CV) Pathology (Path) 18 infarction typically a sign of irreversible cell • Mitochondrial vacuoles and phospholipid injury, signifying that the containing amorphous densities involved mitochondria are Reversible Injury permanently unable to generate • Myofibril relaxation ATP. • Disaggregation of polysomes • Disaggregatiuon of granular and fibrillar elements of the nucleus • Nuclear chromatin clumping • Triglyceride droplet accumulation (especially in hepatocytes) • Glycogen loss

179 Coronary blood In 90% of individuals, occlusion Inferior wall MI Cardiovascular (CV) Pathology (Path) 9 flow of the RCA can result in • aVF, 2 and 3 ST elevation transmural ischemia of the • RCA occlusion inferior wall of the LV, producing • Bradycardia due to SA nodal art block ST elevation in leads II, III, and LAD occlusion aVF as well as possible sinus • Can cause 2nd or 3rd degree HB node dysfxn. Occlusion of the proximal LAD would be expected to result in anteroseptal transmural ischemia, w/ ST elevations in leads V1-V4. Occlusion of the LCX would produce transmural ischemia of the lateral wall of the LV, w/ ST elevations mainly in V5 and V6, and possibly also in I and aVL.

180 Aging Normal morphological changes in Normal aging of heart Cardiovascular (CV) Pathology (Path) 8 the aging heart incl a ↓ in LV • Decreased LV size (apex base) > chamber apex-to-base dimension, sigmoid shape devel of a sigmoid-shaped • Increased interstitial CT +/ amyloid ventricular septum, myocardial • Lipofuscin: cytoplasmic brownish atrophy w/ ↑ collagen deposition, granules and accumulation of cytoplasmic Dilated cardiomyopathy lipofuscin pigment w/i • Increase risk of mural thrombi cardiomyocytes. Chronic hemolytic anemia • Can result in hemochromotosis of heart HCM • Septal wall hypertrophy Chronic ischemic heart • Diffuse subendocardial vacuolization and fibrosis

181 Primary Concentric hypertrophy is LVH Cardiovascular (CV) Pathology (Path) 14 hypertension characterised by uniform • Concentric: wall thickness thickening of the ventricular wall • Uniform thickening without change and narrowing of the ventricular outer dimensions of the heart cavity due to ↑ afterload (e.g. • MCC: long standing HTN followed by chronic HTN, AS). Eccentric AS hypertrophy is characterised by ↓ • Eccentric: cavity size ventricular wall thickness w/ an • Due to fluid overload (CHF or AR) assoc ↑ in chamber size due to ASD volume overload. • RA and RV eccentric dilation MR • Eccentric LVH MS • LA dilation, normal LV Normal aging • Decrease LV chamber size (shortening apex to base causing sigmoid septum)

185 Chronic heart Alveolar hemosiderin-laden HF due to LV dysfunction Cardiovascular (CV) Pathology (Path) 12 failure macrophages indicate alveolar • Pulmonary edema > RBC into alveoli > hemorrhage. They most phagocytosed by macrophages which commonly result from chronic ↑ convert Fe from Hb to hemosiderin (HF of pulm capillary hydrostatic cells > golden cytoplasmic granules that pressure in the setting of left- stains blue with Prussian blue) sided HF. COPD and asthma • Hyper reactive airway Granulomas in lung • TB, fungus, sarcoid, beryllium 188 Atrioventricular A complete AV canal defect is Complete atrioventricular canal septal Cardiovascular (CV) Pathology (Path) 1 canal defect comprised of an ASD, a VSD, defect and a common AV valve. It's the • MC cardiac defect in Down Syndrome most common congenital cardiac • ASD + VSD + single AV valve anomaly a/w Down syndrome. • Left to right shunting, AV valve regurg, excessive pulmonary blood flow, HF • Will hear AV valve regurg (best at apex) and increase pulmonary venous return (mid diastolic rumble) Tuberous Sclerosis • Tuberin and harmartin mutations • Cardiac rhabdomyomas in ventricles • Angiofibromas • CNS hamartomas

192 Myocardial VF is the most common mech of Acute MI Cardiovascular (CV) Pathology (Path) 18 infarction SCD due to AMI. It results from • Sudden Cardiac Death: Vfib or Vtach arrhythmogenic foci triggered by within 48hr of MI electrical instability in the • MCC of death within 2 days of MI ischemic myocardium. Wall rupture • 3• 7 days after MI Cardiogenic shock • From massive LAD MI 203 Ventricular septal VSD typically presents in the VSD Cardiovascular (CV) Pathology (Path) 2 defect neonatal period after pulm • Loud blowing holosystolic murmur at vascular resistance has declined. mid/lower left sternal border The clinical Px depends on the • Usually takes 4• 10days to present size of the defect, which ranges • Small: asymptomatic from an aSSx holosystolic • Large: HF, failure to thrive, murmur (small VSD) to HF (large diaphoresis with feeding (no murmur) > VSD). can lead to pulmonary HTN then RVH then eisenmenger Pulmonary stenosis: innocent murmur due to hypoplasia of branch pulmonary arteries • Low grade, mid systolic, high pitch blow murmur

228 Endocarditis Microemboli from the valvular Splinter hemorrhage in nails > think Cardiovascular (CV) Pathology (Path) 15 vegetations of BE are the most infective endocarditis FROM JANE common cause of subungual • Fever Roth spot Osler node Murmur splinter hemorrhages. The Janeway lesion Anemia presence of these lesions • Nailbed hemorrhage Emboli necessitates careful cardiac auscultation to detect a possible new-onset regurgitant murmur.

230 Endocarditis MVP w/ MR is the most common MVP Cardiovascular (CV) Pathology (Path) 15 predisposing condition for native • MC underlying valvular disease valve IE in developed nations. predisposing to infectious endocarditis in Rheumatic heart disease remains DEVELOPED countries a freq cause of IE in devel • Rheumatic HD is the MC underlying nations. cause in DEVELOPING countries • Bicuspid aortic valve, VSD, PDA and unrepaired TOF increase risk too CAD • Can cause ischemia of papillary muscle leading to MR

231 Endocarditis NBTE (marantic endocarditis) is Nonbacterial Thrombotic Endocarditis Cardiovascular (CV) Pathology (Path) 15 a form of non-infectious (marantic) endocarditis characterised by • Platelet rich thrombi attached to mitral valvular deposition of sterile valve leaflets platelet-rich thrombi. It likely • Common with advanced malignancy results from valvular dmg due to (associated with mucin producing cancer) inflammatory cytokines in the • Endothelial injury > platelet deposition setting of an underlying • Vegations consist of bland thrombus with hypercoagulable state, and it's strands of fibrin, immune complexes and most commonly seen w/ mononuclear cells advanced malignancy (esp. • Easily dislodged and embolize mucinous AC) or SLE. Systemic Sclerosis • Cor pulmonale, pericardial dz, myocardial fibrosis and conduction system disease 232 Mitral stenosis Rheumatic MS is characterised by Rheumatic Fever Cardiovascular (CV) Pathology (Path) 7 diffuse fibrous thickening and • Mitral regurg early then mitral stenosis distortion of the MV leaflets • Mitral stenosis: causes atrial dilation along w/ commissural fusion at resulting in a fib or atrial mural thrombus the leaflet edges. Pts often present • Will see fusion of the commisures of w/ a diastolic murmur, dyspnoea, the cusps and fatigue and are at ↑ risk of AF • Opening snap with mid diastolic murmur and TE (e.g. stroke). Mitral valve calcification is usually around the annulus, seen in women over 60, and asymptomatic Rheumatoid Arthritis • Can cause pericarditis or myocarditis

236 Mitral stenosis LA enlargement can sometimes Ortner Syndrome Cardiovascular (CV) Pathology (Path) 7 cause left recurrent laryngeal • MS > LA dilation > compresses L nerve impingement. Neurapraxia recurrent laryngeal nerve (neurapraxia) resulting in left vocal cord paresis leading to hoarseness and hoarseness may result. Reccurent laryngeal nerve • Innervates all laryngeal muscles except cricothyroid Other causes of hoarseness • Laryngeal edema • Vascular disease • Laryngeal mucosal disease (epi sloughing) • Vocal cord polyps 240 Rheumatic fever Interstitial myocardial Aschoff body: pathognomonic for ARF Cardiovascular (CV) Pathology (Path) 5 granulomas (Aschoff bodies) are • Anitschkow cells (caterpillar cells) found in carditis due to acute RF, • Hypersensitivity myocarditis: causes for which develops after an un-Tx loops, thiazides, ampicillin, azithromycin) GAS pharyngeal infection. • Viral myocarditis: adenovirus, coxsackie Aschoff bodies contain plump b, parvovirus b19 macrophages w/ abundant cytoplasm and central, slender ribbons of chromatin (Anitschkow, or caterpillar cells).

241 Rheumatic fever Sydenham chorea presents w/ Rheumatic fever Cardiovascular (CV) Pathology (Path) 5 involuntary, rapid, irregular • Can develop 1 8 months after sore throat jerking movements involving the • Restlessness and purposeless jerking face, arms, and legs. It occurs movements (sydenham chorea) mos after group A streptococcal • Delayed autoimmune rxn to basal infection and is one of the major ganglia clinical MFx of acute RF. Pts w/ Parkinson this condition carry a high risk of • Only time you will see jerking chronic valvular disease. movements is with levodopa OD

242 Aortic stenosis Calcific degeneration of the AS Cardiovascular (CV) Pathology (Path) 8 trileaflet AV is the most common • Syncope, angina, dyspnea, fatigue cause of AS in developed nations. • In exercise, vasodilation without AS is Chx by progressive AV compensatory increased CO due to AS leaflet thickening and causes hypotension calcification, leading to restricted • Hard crescendo descrescendo systolic leaflet excursion and mobility. murmur @ 2nd R intercostal AS murmur is usually a harsh • Can lead to an S4 ejection-type systolic murmur • MCC: progressive valve leaflet heard best at the base of the heart thickening and calcification in the "aortic area" (2nd right • Biscupid valve will see AS in 50's or ICS) w/ radiation to the carotid 60's arteries. Rheumatic valve • Fusion of commissures HCM • Basal interventricular septum hypertrophy with subaortic obstruction MVP • Myxomatous degen AR • Infective endocard 300 Aging Lipofuscin is the product of lipid Lipofuscin Cardiovascular (CV) Pathology (Path) 8 peroxidation, accumulating in • Yellow brown, finely granular aging cells (esp. in pts w/ perinuclear pigment due to lipid malnutrition and cachexia). peroxidation • Commonly seen in heart and live of aging or cachectic, malnourish pt Hemosiderin • Fe overload Melanin • Oxidation product of tyrosine metabolism Glycogen • Clear vaculoes in cytoplasm Hyaline • Protein accumulation that is a glassy, homogeneous pink

442 Atherosclerosis Atherosclerosis is initiated by Atherosclerosis Cardiovascular (CV) Pathology (Path) 8 repetitive endothelial cell injury, • Endothelial injry (HTN, hyperlipidemia, which leads to a chronic smoking, diabetes, homocytseine, alcohol, inflammatory state in the virus) > subendo collagen exposed > underlying intima of large elastic monocytes adhere and platelets stick > arteries as well as in large- and monocytes stimulate medial smooth muscle medium-sized muscular arteries. migration and proliferation > foam cells accumulate > chronic inflammation continues to attract foam cells > SM form fibrous cap Pericytes are pluripotent cells in postcapillary venules

443 Coronary artery VSMCs are the only cells w/i the Atherosclerosis Cardiovascular (CV) Pathology (Path) 4 disease atherosclerotic plaque capable of • Endothelial damage increases expression synthesizing structurally of surface vascular celL adhesion important collagen isoforms and molecules allowing adhesion and migration other matrix components. of monocytes into the intima. Macrophages Progressive enlargement of the release PDGF, FGF, endothelin 1 and IL 1 plaque results in remodeling of causing migration/proliferation of the ECM and VSMC death, vascular smooth muscle cells within the promoting development of INTIMA. Smooth muscle cells synthesize vulnerable plaques w/ an ↑ collagen, elastin and proteoglycans propensity for rupture. forming the fibrous cap. • Macrophages release MMP that degrade the fibrous cap increasing vulnerability to rupture

444 Atherosclerosis Fatty streaks are the earliest Abdominal Aorta Cardiovascular (CV) Pathology (Path) 8 lesions of atherosclerosis and can • Fatty streak first appears in teens be seen as early as the 2nd decade Sequence of life. They appear as a • Endothelial damage collection of lipid-laden • LDL accumulated within vessel wall macrophages (foam cells) in the • Macrophages migration and become intima that can eventually foam cells progress to atherosclerotic • Growth factor released by platelets, plaques. macrophages and endothelial cells • Smooth muscles migrate, proliferation and form fibrous cap

446 Atherosclerosis During the development of Atheroma Cardiovascular (CV) Pathology (Path) 8 atherosclerotic plaque (atheroma), • Endothelial cell injury > altered gene activated macrophages, platelets, expression > platelet adhesion > platelets and endothelial cells release GFs release PDGF (also by dysfunction (eg, PDGF) that stimulate endothelial cells and macrophages > SM recruitment of SMCs from the migration into intima > SM proliferation arterial wall media and their • Platelets also release TGFbeta subsequent proliferation in the intima. 447 Atherosclerosis The likelihood of plaque rupture Athero Cardiovascular (CV) Pathology (Path) 8 is related to plaque stability rather • Symptoms at 70% occlusion than plaque size or the degree of • Plaque stability depends on fibrous cap luminal narrowing. Plaque production (smooth muscle cells) vs the stability largely depends on the breakdown of the cap by inflammation and mech strength of the fibrous cap. macrophages (that secrete Inflammatory macrophages in the metalloproteinase) intima may ↓ plaque stability by • Thinner the cap, the easier the rupture secreting metalloproteinases, HMG CoA reductase: cholesterol synth which degrade ECM proteins • Lysyl oxidase: covalently crosslinks (e.g. collagen). collagen • Needs Cu • High activity would increase cap thickness and make more stable Procollagen peptidase: cleaves terminal ends (def in Ehler Danlos)

448 Peripheral Intermittent claudication Peripheral Artery Disease Cardiovascular (CV) Pathology (Path) 4 vascular disease describes muscle pain that's • Claudication reproducibly caused by exercise • Lipid dille intimal plaques obstructing and relieved by rest; it occurs due arterial lumen to atherosclerotic stenoses (lipid- • Tx: cilostazol filled intimal plaques) in the large arteries that prevent sufficient blood flow to exercising muscle. The lower extremities are most commonly affected; however, proximal lesions (i.e. aortoiliac occlusion) can cause gluteal claudication a/o impotence.

449 Primary HTE is severely ↑ BP (typically Hyperplastic arteriolosclerosis Cardiovascular (CV) Pathology (Path) 14 hypertension >180/120 mm Hg) w/ evidence of • Diastolic over 130 end-organ dmg. In the kidneys, • Onion rings this can MFx as malignant • Renal art stenosis > HTN > nephrosclerosis, Chx by fibrinoid decreased blood to kideny > more RAAS necrosis and hyperplastic > vicious cycle arteriolosclerosis ("onion-skin" Accelerated malignant HTN appearance). A MAHA can occur • Retinal hemorrhage, exudates or due to erythrocyte fragmentation papilledema and platelet consumption at the narrowed arteriolar lumen.

451 Peripheral Thromboangiitis obliterans Buerger's Cardiovascular (CV) Pathology (Path) 4 vascular disease (Buerger disease) is a segmental, • Immune HSN to component of tobacco inflammatory vasculitis that smoke or direct endothelial cell toxicity affects the small- and medium- from tobacco smoke sized arteries and veins of the • Vascultiis of Radial and Tibial arteries distal extremities w/ • Thrombosing vasculitis that extends into inflammatory, intraluminal contiguous veins and nerves thrombi and sparing of the vessel • Isreal, Japan and India ethnicity wall. It is usually seen in young, Onion like concentric thicking heavy smokers, and can Px w/ • Malignant HTN (Diastolic > 120) digital ischemia and ulceration, Polyarteritis Nodosa extremity claudication, Raynaud • Transmural inflammation of arterial wall phenomenon, and superficial with fibrinoid necrosis thrombophlebitis.

452 Takayasu arteritis Takayasu arteritis is a chronic, Leukocytoclastic vasculitis Cardiovascular (CV) Pathology (Path) 1 large-artery vasculitis that 1arily • Microscopic polyangitis, microscoping involves the aorta and its polyarteritis, hypersensitivity vasculitis branches. It presents w/ (RA) constitutional (e.g. fever, weight • Segmental fibrinoin necrosis of small loss) and arterio-occlusive (e.g. vessels claudication, BP discrepancies, • Similar to PAN pulse deficits) findings in pts age Granulomatous inflammation of media <40. Histopathology shows • Takayasu and Temporal arteritis granulomatous inflammation of the vascular media. 453 Renal artery RAS is most often due to Renal Artery stenosis Cardiovascular (CV) Pathology (Path) 9 stenosis atherosclerosis. It can cause • MCC: atheromatous plaque severe, refractory HTN due to • Eventual renal atrophy due to lack of activation of the RAAS. Over oxygen and nutrients time, renal atrophy may occur due • Atrophich kidney: crowded glomeruli, to chronic O2 and nutrient tubulointerstitial atrophy and fibrosis deprivation. Histologic Ex may show crowded glomeruli, tubulointerstitial atrophy and fibrosis, and focal inflammatory infiltrates.

460 Polyarteritis PAN is segmental, transmural, Polyarteritis Nodosa Cardiovascular (CV) Pathology (Path) 2 nodosa necrotizing inflammation of • Segmental, transmural, necrotizing medium- to small-sized arteries. inflammation of medium size arteries Renal artery involvement is often • Kidney, heart, liver and GI commonly prominent. Vessels of the involved kidneys, heart, liver, and • Spares the lung gastrointestinal tract are most • Bears on a string appearance commonly involved in resulting • Can have palpable purpura or livedo ischemia, infarction, or reticularis hemorrhage. Cutaneous manifestations occur in up to one- third of patients, and include palpable purpura. The lung is very rarely involved.

462 Aortic aneurysm Myxomatous changes w/ pooling Myxomatous changes found in Cystic Cardiovascular (CV) Pathology (Path) 6 of proteoglycans in the media Medial Degeneration layer of large arteries are found in • Fragmentation of elastic tissue and CMD, which predisposes to the separation of elastic and fibromuscular devel of ADs and AAs. Medial components of tunic media, cleft like space degen is freq seen in younger filled with amorphous extracellar matrix individuals w/ Marfan syndrome. • Seen in Marfans • Lead to aortic aneurysms and dissections Beta aminopropionitrile (found in sweet peas) inhibits lysyl oxidase and will mimic Marfan syndrome False aneurysm • Leakage of blood causing hematoma outside of vascular wall

463 Aortic aneurysm AAA is a/w RFs (e.g. age >60, AAA Cardiovascular (CV) Pathology (Path) 6 smoking, HTN, male sex, FHx) • Over 60 that lead to chronic transmural • Smoking inflammation and ECM • HTN degradation w/i the wall of the • Male aorta. This leads to weakening Characterized by transmural inflammation and progr expansion of the aortic • > loss of elastin wall, resulting in aneurysm • > abnormal collagen remodeling formation, typically below the Cystic medial necrosis: loss of smooth renal arteries. muscle, collagen and elastic tissue (seen in Marfans) Vasa Vasorum Endarteritis (endarteritis obliterans) is seen in thoracic AA (infrarenal abdominal aorta lacks vasa 464 Aortic dissection AD classically presents w/ severe Aortic Dissection Cardiovascular (CV) Pathology (Path) 6 retrosternal pain that radiates to • Chest pain radiationg to the back the back. This condition develops • Tears through aortic intima when overwhelming • Type A: any portion of ascending aorta hemodynamic stress leads to involved (can also involve descending) tearing of the aortic intima w/ • Type B: only involved descending aorta blood subseq dissecting thru the • HTN is largest risk factor > vasa aortic media. The resulting vasorum occlusiong > decreased blood to intramural hematoma can extend media > degenerates SM in media + both proximally and distally and increased wall stiffness > tear can compress major arterial Aortitis branches and impair blood flow. • Takayasu and giant cell arteritis Aortic anuerysm • Syphilis > obliterative endarteritis 466 Hemangioma Cutaneous, strawberry-type Cardiovascular (CV) Pathology (Path) 6 capillary hemangiomas are common, benign, congenital tumors, which are composed of unencapsulated aggregates of closely packed, thin-walled capillaries. Initially, strawberry hemangiomas grow in proportion to the growth of the child, before eventually regressing. In 75-95% of cases, the vascular tumor will regress completely by age 7.

469 Hereditary Osler-Weber-Rendu syndrome Hereditary Hemorhagic Telangiectasia Cardiovascular (CV) Pathology (Path) 1 hemorrhagic (hereditary hemorrhagic (Osler Weber Rendu) telangiectasia telangiectasia) is an AD condition • Skin and mucosal telangiectasias marked by the presence of • Recurrent nosebleeds, GI bleeding and telangiectasias in the skin as well hematuria as the mucous membranes of the Sturge Weber lips, oronasopharynx, resp tract, • Facial angiomas GIT, and urinary tract. Rupture of • Leptomeningeal angiomas these telangiectasias may cause • Mental retardation epistaxis, GI bleeding, or • Seizures hematuria. • Hemiplegia • Skull radiopacities • Tram track calcifications • Pheo Tuberous Sclerosis • Hamartomas in CNS and skin • Angiofibroma • Renal angiomyolipoma • Cardia rhabodmyoma • Seizure 473 Aortic dissection HTN is the single most important Aortic dissection Cardiovascular (CV) Pathology (Path) 6 RF for the devel of intimal tears • "Septum" seen in aorta is tunica intima leading to AD. HTN, smoking, • HTN is the most important risk factor DM, and hypercholaemia are all • Cystic medial degeneration in Marfans major RFs for atherosclerosis, predisposes to young aortic dissection which predisposes more to AA For Step 1 formation than AD. • Diabetes = CAD Hypercholesterolemia • Predisposes to aortic aneurysm Smoking • Thromboangiitis obliterans of radial and tibial art Syphilis • Vasa vasorum obliterans > ascending aortic aneurysm

474 Chronic venous Varicose veins are dilated, Varicose veins Risk factors Cardiovascular (CV) Pathology (Path) 3 insufficiency tortuous veins most commonly • Prolonged standing, over 50, obesity, found in the superficial veins of multiple pregnancies Cause the leg. They're caused by • Incompetent valves Complication chronically ↑ intraluminal • Painful thromboses, stasis dermatitis, skin pressure a/o loss of tensile ulcerations (common over medial strength in the vessel wall, malleolus), poor wound healing and leading to incompetence to the superficial infections venous valves. Common Random complications incl oedema, stasis Peripheal artery disease = claudication dermatitis, skin ulcerations, poor Phlegmasia alba dolens: result of wound healing, and infections. iliofemoral venous thrombosis in peripartum women 475 Thrombophlebitis A PNPS of hypercoagulability Trousseau Syndrome Cardiovascular (CV) Pathology (Path) 1 may be seen in some pts w/ ca, • Migratory thrombophlebitis especially ACs of the pancreas, • Risk of visceral cancer (especially mucin colon, or lung. Superficial venous producing and pancreating) thromboses may therefore appear Celiac in one site and then resolve, only • Risk of hemorrhagic diathesis (vit k def) to recur in another site. This is Hyperthyroid known as Trousseau syndrome • Can cause hypercoag state (migratory superficial thrombophlebitis), an indication of visceral ca.

506 Subdural SDH occurs due to the rupture of Subdural hematoma Cardiovascular (CV) Pathology (Path) 1 hematoma cortical bridging veins. In young • Rupture of bridging cortical veins pts, it results from a fall or MVA • Gradual onset of symptoms and MFx w/ gradual onset of h/a • Crescent shaped mass that can cross and confusion. In elderly pts it suture lines may occur after a minor trauma • Elderly, shaken baby, and alcoholics and present w/ a variety of neuro Epidural SSx. You should know how to • Middle meningeal art recognise this on CT scan. • Biconvex mass Lateral striate art • Supply basal ganglia and internal capsule

809 Renal infarction Renal infarction presents w/ flank Renal infarction Cardiovascular (CV) Pathology (Path) 2 pain, hematuria, ↑ LDH, and a • Pale wedge shaped infarcts on CT, flank wedge-shaped kidney lesion on pain, hematuria, elevated LDH CT scan. The most common • MCC: thromboembolism (usually from cause of renal infarction is heart) systemic TE, often due to • Coagulative necrosis thrombus formation during AF. Lower Leg DVT The brain and kidneys are more • PE likely than other organs to suffer • Stroke due to PFO embolic infarctions b/c they are FSGS perfused at a higher rate. • Loss of antithrombin 3 causes hypercoaguable state Acute Interstitial nephritis • Fever, rash, eosinophilia/uria 878 Chronic venous Chronically ↑ venous pressure in Varicose veins Cardiovascular (CV) Pathology (Path) 3 insufficiency the ↓ extremities can lead to • Caused by incompetent valves incompetent venous valves and • Can result in venous stasis dermatitis venous dilation (varicose veins). • Risk factors: obesity and pregnancy Venous congestion and tissue Lymphedema ischemia can result in venous • Obstruction of lympoid capillaries stasis dermatitis. • Marked swelling of dorsum of distal limb • Initially soft and pitting but eventually becomes firm and nonpitting > leads to fibrosis of skin

939 Aortic stenosis The murmur of valvular AS is AS or PS Cardiovascular (CV) Pathology (Path) 8 typically an ejection or • Crescendo descrescendo systolic murmur midsystolic murmur of crescendo- peaking at midsystole radiating to carotids decrescendo configuration w/ • MCC: calcification max intensity over the right 2nd Ankylosing spondylitis ICS and radiation to neck and • Aortitis > AR carotid arteries. The most MR common cause of AS in elderly • Chordal rupture pts (age >70) is degen Thoracic aortic aneurysms and AR calcification of the AV leaflets. • Cystic medial necrosis 947 Mitral valve MVP is most often caused by MVP with MR Cardiovascular (CV) Pathology (Path) 1 prolapse defects in connective tissue • Midsystolic click with late systolic murmr proteins that predispose to best heard at the apex myxomatous degen of the mitral • Disappears with squatting (increased VR leaflets and chordae tendineae. > leaflets don't snap as hard) Cardiac auscultation typically • Myxomatous degeneration (pathologic reveals a MC f/b a MR murmur; degen of connective tissue) the click and murmur occur later • Seen in Marfans and Ehlers danlos in systole or disappear completely and OI w/ manoeuvres (e.g. squatting) • Proliferation of spongiosa in leaflets, that ↑ LV EDV. fragmentation of elastin fibers with increase mucopolysaccharides and type 3 collagen deposition

1040 Acute pericarditis Pericarditis is the most common Acute pericarditis Cardiovascular (CV) Pathology (Path) 5 CV MFx a/w SLE. It presents w/ • SLE sharp pleuritic chest pain that is • Middle or left chest pain that radiates to relieved by sitting up and leaning neck shoulder (trapezius ridge) > worsens forward. with inspiration and relieved by leaning forward • Can hear pericardial friction rub Aortic dissection • Long standing HTN, Marfan and Ehlers danlos Cardiac tamponade • Beck's triad: Hypotension, distant heart sounds and JVD • Also pulsus paradoxus Non bacterial endocarditis (Libman Sacks) • Both sides of valves

1439 Cardiac The combo of JVD, hypotension, Cardiac Tamponade Cardiovascular (CV) Pathology (Path) 2 tamponade and muffled heart sounds is • Pulsus parasoxus highly suggestive of cardiac • Beck's: JVD, hypotension and muffled tamponade. Tachycardia and heart sounds pulsus paradoxus are also freq • Tachycardia seen w/ tamponade. Lung Ex is Tension pneumothorax normal, which can help • Hypotension distinguish cardiac tamponade • Tachycarida from tension PTX. • Tachypnea • JVD • Absent breath sounds and hyperresonance Epidural hematoma • Cushing's triad: HTN, bradycardia, decreased RR 1852 Kawasaki disease Kawasaki disease is a vasculitis Kawasaki Cardiovascular (CV) Pathology (Path) 1 of medium-sized arteries that • Asian children under 5 presents w/ persistent fever for • Fever for 5 or more day >5days, bilateral conjunctivitis, • Bilateral non exudative conjunctival cervical LAD, and injection mucocutaneous involvement. • Cervical lymphadenopathy Coronary artery aneurysms are a • Erythema of palatine mucosa, fissure serious complication of Kawasaki erythematous lip and strawberry tongue disease. • Edema of hands and feet, erythema of palms and soles, desquamation of the fingertips • Rash on extremities that spreads centripetally to trunk • Development of coronary artery aneurysm Marfan or HTN • Dissecting aneurysm Temporal arteritis M l bli d 1882 Myocardial Ion pump failure due to ATP Myocardial swelling due to ischemia Cardiovascular (CV) Pathology (Path) 18 infarction defic during cardiac ischemia • Low ATP > low Na/K pump and Ca causes intracellular accumulation SERCA pump > high Na and Ca inside of Na+ and Ca2+. The ↑ cell causes swelling (also in mitochondria) intracellular solute conc draws • Intracellular K will be low free water into the cell, causing the cellular and mitochondrial swelling that's observed histologically. 2074 Endocarditis Chronic valvular inflammation Infective endocarditis Cardiovascular (CV) Pathology (Path) 15 and scarring a/w RHD predispose • Predisposed by RF, MVP, prosthetic to an ↑ risk of IE, which is Chx valves by valvular vegetations w/ RF destruction of the underlying • Mitral valve inflammation and scarring cardiac tissue. Myocardial hypertrophy • HTN, AS and HCM Myocardial fibrosis • Sarcoid, amyloid, Chagas, myocarditis, prior MI 2075 Endocarditis Vegetations are caused by Infective Endocarditis Cardiovascular (CV) Pathology (Path) 15 bacterial colonization and growth • Initially due to disruption of normal on a sterile fibrin-platelet nidus endocardial surface that forms on the • Typical atrial surface of AV valve or damaged/disrupted endothelial ventricular surface of semilunar valve surface of the valvular apparatus. • Fibrin and platelets allow for adherance Endomyocardial fibrosis: restrictive cardiomyopathy characterized by thickening and fibrosis of apical endocardial surface (tropical regions) Myxomatous degeneration of mitral valve: thickened and redundant mitral leaflet with elongated chordae > prolapse

7568 Renal artery In unilateral RAS, the narrowed Cardiovascular (CV) Pathology (Path) 9 stenosis renal artery causes hypoperfusion of the affected kidney w/ subseq ischemic dmg (e.g. tubular atrophy, interstitial ischemia, glomerular crowding). In contrast, the contralateral kidney is exposed to high BP and typically shows changes of HTN nephrosclerosis (e.g. arteriolar wall thickening due to hyaline or hyperplastic arteriolosclerosis).

7616 Acute heart failure Acute cardiogenic pulm oedema Cardiovascular (CV) Pathology (Path) 7 results from ↑ pulm venous pressure. The alveolar capillaries become engorged w/ blood and there's a transudation of fluid plasma across the alveolar- capillary membrane, appearing as pink, acellular material w/i the alveoli.

7666 Myocardial RV infarction (right-sided HF) Cardiovascular (CV) Pathology (Path) 18 infarction can lead to shock via impaired forward blood flow to the left heart, which ↓ left-sided preload (↓ PCWP) and ↓ CO. The ↓ RV output also ↑ RA and CVP.

7667 Myocardial Severe systemic hypotension (eg, Cardiovascular (CV) Pathology (Path) 18 infarction shock) is most likely to cause ischemia 1st in areas of high metabolic demand (eg, hippocampus) or watershed zones, which are areas that are supplied by the distal branches of two different major arteries. Commonly affected areas in the colon include the splenic flexure and RSJ. 8296 Atrial myxoma Myxomas are the most common Cardiac myxoma Cardiovascular (CV) Pathology (Path) 3 1° cardiac neoplasm and usually • Mid diastolic rumbling murmur best arise w/i the LA. The tumours heard at apex typically cause position- • Positional cardiovascular symptoms dependent obstr of the MV, • Mucopolysaccharide stroma, abnormal leading to a mid-diastolic murmur blood vessels, and hemorrhaging and SSx of ↓ CO (e.g. dyspnoea, • Produce IL 6 causing constitutional syncope). Constitutional SSx (e.g. symptoms fever, weight loss) may also be Acute Myeloid Leukemia present. Histologically, the • Can met to the heart tumours demonstrate scattered • Will see pancytopenia, weakness, fatigue, cells w/i a mucopolysaccharide ecchymoses stroma and abn blood vessels w/ hemorrhaging.

8458 Electrical injury Although lightning injuries are Lightning related complications Cardiovascular (CV) Pathology (Path) 1 rare, they are a/w a 25% fatality Cardiac: arrhythmia rate. Two-3rds of lightning- • Neuro: seizure, peripheral nerve damage, related deaths occur w/i the 1st hr respiratory failure Derm: lichtenberg after injury, w/ fatal arrhythmias figures (fern lead pattern) and superficial and resp failure as the most burns common causes. Pts w/ minor • MSK: rhabdomyolysis, bone fx, cutaneous involvement may still compartment syndrome Other: cataracts have major internal injury after (late), ruptured tympanic membrane, lightning strikes and high-voltage curling electrical contact. ulcer

8610 Acute heart failure The CXR in ADHF typically Sudden onset of SOB with orthopnea, Cardiovascular (CV) Pathology (Path) 7 shows prominent pulm vessels; pulmonary edema, dilated heart > this patchy, bilateral airspace Acute Decompensated HF opacification; and blunting of the • Kerley B line: short horizontal lines costophrenic angles due to pleural situated perpendicularly to the pleural effusions. surface that represent edema of the interlobular septa Idiopathic Interstitiual Fibrosis: reticular opacities and decreased long volume. Present with progressive dyspnea and nonproductive cough. • COPD: flattened diaphragm Pulmonary HTN: look for RVH and enlarged pulmonary arteries

11636 Atherosclerosis Atherosclerosis is a PPx process Athero Cardiovascular (CV) Pathology (Path) 8 involving endothelial cell dysfxn, • Abdominal aorta and it develops most rapidly in • Coronary artery areas w/ bends and branch points • Politeal artery that encourage turbulent blood • Carotid artery flow. The lower abdo aorta and • Diabetes = coronary artery athero coronary arteries are the vascular beds most susceptible to atherosclerosis; they tend to develop atherosclerosis earliest in life and have the highest overall atherosclerotic burden.

11640 Costochondritis Costosternal syndrome Costosternal syndrome (costochonditis) Cardiovascular (CV) Pathology (Path) 1 (costochondritis) usually occurs • Pain is reproducable with palpation and after repetitive activity and is worsens with movement characterised by pain that is Pleural or pericardial pain reproducible w/ palpation and • Worsens with inspiration worsened w/ movement or Aortic dissection changes in position. • Usually a difference of > 10 in each arm 14789 Myocarditis Acute myocarditis is most Cardiovascular (CV) Pathology (Path) 1 commonly caused by a viral infection (e.g. coxsackievirus, adenovirus, influenza). It often resolves w/o noticeable SSx, but pts can develop serious complications, incl decompensated HF due to DCM or SCD due to ventricular arrhythmia. Histopathology typically demonstrates myofibrillary necrosis w/ inflammatory mononuclear infiltrate.

14964 Aortic stenosis AS most commonly results from Cardiovascular (CV) Pathology (Path) 8 age-related CAVD. The early pathogenesis of CAVD closely mimics that of arterial atherosclerosis. In the later stages, fibroblasts diffiate into osteoblast-like cells and deposit bone matrix, leading to progr valvular calcification and stenosis. 14978 Myocardial MI that causes ischemia of the Cardiovascular (CV) Pathology (Path) 18 infarction papillary muscle or nearby LV wall can result in acute MR w/ development of a new systolic murmur. Timely restoration of blood flow can improve papillary muscle dysfxn and lead to resolution of the regurgitation.

14980 Lymphedema Chronic lymphedema is most Cardiovascular (CV) Pathology (Path) 1 commonly caused by an acquired disruption of lymphatic drainage (eg, due to malignancy or lymphadenectomy), and typically presents with swelling and thickened skin in one or more extremities. Treatment is usually conservative and involves compression bandages and physiotherapy; diuretics are ineffective and contraindicated.

14989 Stress Stress-induced (takotsubo) Cardiovascular (CV) Pathology (Path) 1 cardiomyopathy cardiomyopathy is characterised by hypokinesis of the mid and apical segments and hyperkinesis of the basal segments of the LV, resulting in systolic dysfxn. The condition is likely caused by a surge of catecholamines in the setting of physical or emotional stress. It usually affects postmenopausal women and resolves on its own w/i several wks.

14992 Dilated Peripartum cardiomyopathy is a Cardiovascular (CV) Pathology (Path) 8 cardiomyopathy relatively uncommon cause of DCM that may be related to impaired fxn of angiogenic GFs. DCM involves compensatory eccentric hypertrophy, which ↑ ventricular compliance and also allows for temporary maintenance of CO. Over time, ovewhelming wall stress leads to LV failure w/ ↓ EF and SSx HF. 14993 Dilated DCM results from 1° myocardial Cardiovascular (CV) Pathology (Path) 8 cardiomyopathy dysfxn leading to eccentric remodelling of the LV. Pts can develop LV mural thrombus and are at risk for SCD due to ventricular arrhythmia. Familial DCM is typically inherited in an AD pattern, and most commonly results from truncating muts of the TTN gene that codes for the sarcomere protein titin.

14997 Atrial myxoma Myxomas are the most common Cardiovascular (CV) Pathology (Path) 3 1° cardiac neoplasm and approx. 80% originate in the LA. Pts may present w/ SSx MV obstr that may worsen w/ certain body positions, constitutional findings (e.g. fever, weight loss), or systemic embolisation (e.g. stroke, mesenteric ischemia, acute limb ischemia).

14998 Atrial myxoma Myxomas are the most common Cardiovascular (CV) Pathology (Path) 3 1° cardiac neoplasm, and approx. 80% originate in the LA. Pts may have systemic embolisation (e.g. stroke) or SSx MV obstr that may be worse w/ certain body positions. Histopathologic Ex reveals amorphous ECM w/ scattered stellate or globular myxoma cells w/i abundant mucopolysaccharide ground substance.

14999 Acute pericarditis Fibrinous pericarditis is the most Cardiovascular (CV) Pathology (Path) 5 common type of pericarditis and is Chx by pericardial inflammation w/ a serous, fibrin- containing exudate in the pericardial space. Pleuritic chest pain and a triphasic friction rub are frequently seen. Common causes include viral infection, MI, uremia, and rheumatologic disease (eg, SLE, RA).

15000 Acute pericarditis Viral infection is thought to be Cardiovascular (CV) Pathology (Path) 5 the most common cause of acute pericarditis. It causes a fibrinous or serofibrinous pericarditis that is often Chx by pleuritic chest pain, a friction rub on cardiac auscultation, diffuse ST elevation on ECG, and mild to moderate- sized pericardial effusion.

15195 Aortic Eccentric ventricular hypertrophy Cardiovascular (CV) Pathology (Path) 8 regurgitation results in a dilated cavity w/ relatively thin ventricular walls due to the addition of myocardial contractile fibers in series in response to chronic volume overload. Chronic AR can result from aortic root dilation and is a common cause of eccentric hypertrophy. 15196 Aortic stenosis Concentric LVH involves Cardiovascular (CV) Pathology (Path) 8 thickening of the ventricular walls and ↓ in the ventricular cavity size. It occurs via the addition of myocardial contractile fibers in parallel in response to chronic pressure overload. AS and prolonged systemic HTN are common causes of concentric LVH.

15198 Pulmonary PV stenosis causes a crescendo- Cardiovascular (CV) Pathology (Path) 1 stenosis decrescendo systolic murmur (best heard at the left upper sternal border) and delays closure of the PV, resulting in widened splitting of S2. Inspiration ↑ blood flow to the right side of the heart, causing ↑ intensity of the murmur and even later closure of the PV.

15542 Primary Concentric LVH involves Cardiovascular (CV) Pathology (Path) 14 hypertension uniform thickening of the LV walls w/ ↓ in LV cavity size and most commonly results from prolonged systemic HTN. It can progress to HTN heart disease w/ impaired diastolic filling and HF w/ preserved EF. Histopathology demonstrates transverse thickening of cardiomyocytes w/ prominent hyperchromatic nuclei and interstitial fibrosis.

15554 Pulmonary Transcatheter aortic valve Cardiovascular (CV) Pathology (Path) 13 embolism implantation (TAVI) allows for minimally invasive management of severe aortic stenosis in elderly patients who are unable to tolerate open surgical valve replacement. Paravalvular aortic regurgitation is a common complication of TAVI, resulting from improper sealing of the prosthetic valve to the native aortic valve annulus.

15555 Heart block 3rd-degree (complete) AV block Cardiovascular (CV) Pathology (Path) 2 involves dysfxn of the AV node, resulting in total lack of communication b/w the atria and ventricles. On ECG, there's dissociation of P waves and QRS complexes, w/ P waves marching out at the intrinsic rate of the SA node and QRS complexes at the intrinsic rate of the His bundle or ventricles (escape rhythm).

15559 Lyme disease Early disseminated Lyme disease Cardiovascular (CV) Pathology (Path) 3 can have cardiac involvement (Lyme carditis) that most commonly MFx w/ varying degrees of AV conduction block. Pts may be aSSx, but those w/ complete AV conduction block are likely to have dyspnea, lightheadedness, or syncope. 15839 Aortic aneurysm TAAs are usually aSSx until they Cardiovascular (CV) Pathology (Path) 6 grow large enough to compress surrounding structures or cause rupture. The most common SSx presentation is chest or back pain, but compression of nearby structures can cause dysphagia, hoarseness, cough, or dyspnoea.

15840 Aortic aneurysm Ruptured AAA is a Sx emergency Cardiovascular (CV) Pathology (Path) 6 that usually Px w/ the acute onset of severe abdominal and back pain in pts w/ appropriate RFx (eg, advanced age, smoking, atherosclerosis). Accompanying syncope, hypotension, and shock may occur quickly (intraperitoneal rupture) or may be delayed (retroperitoneal rupture).

15885 Aortic dissection The most common SSx of acute Cardiovascular (CV) Pathology (Path) 6 AD is sudden onset of severe, sharp or tearing chest and back pain. Complications include stroke, AR, and myocardial ischemia. In addition, a dissection can extend into the pericardium, resulting in tamponade w/ ↓ CO and shock.

15886 Aortic dissection Marfan syndrome involves a Cardiovascular (CV) Pathology (Path) 6 deleterious mut in fibrillin that mainly affects the structural integrity of the CV and MSK systems. Aortic root disease predisposes to AD, which can present w/ sudden-onset chest or back pain, acute AR, and HF. Common histologic findings in aortic disease incl fragmentation and loss of the elastic lamellae w/ fibrosis and CMD.

15891 Aortic dissection CMD (necrosis) is the classic Cardiovascular (CV) Pathology (Path) 6 histologic finding in AD, as it weakens the aortic wall and allows a small intimal tear to readily propagate. Collagen, elastin, and smooth muscle are replaced by a basophilic mucoid ECM w/ elastic tissue fragmentation and cystic collections of mucopolysaccharide.

33 Bicuspid aortic AS is the most common Bicuspid aortic valve Cardiovascular (CV) Pathophysiology 1 valve complication of bicuspid AVs. • Shape causes increased hemodynamic (Patp) Pts w/ bicuspid AVs develop stress causing premature atherosclerosis clinically significant AS on and calcification by mid 50's average around age 50. In (symptomatic) comparison, senile calcific • Less than 1% increased risk of aortic stenosis of normal AVs generally dissection becomes SSx age >65. • 23% increased risk for infective endocarditis • MCC of vfib in pt under 30 is hypertrophic cardiomyopathy 42 Myocardial Loss of cardiomyocyte Total myocardial ischemia Cardiovascular (CV) Pathophysiology 18 infarction contractility occurs w/i 60 2nds • Heart will stop beating in 60 seconds (Patp) after the onset of total ischemia. • Although there is still ATP around, ATP When ischemia lasts less than 30 in locations of high metabolic demand is min, restoration of blood flow rapidly depleted and causes heart to stop leads to reversible contractile Ischemia less than 30 min > reversible dysfxn (myocardial stunning), w/ damage contractility gradually returning • Myocardial stunning: prolonged to normal over the next several dysfunction of myocardium, function hrs to days. However, after about returns within days 30 min of total ischemia, Adenosine is potent vasodilator in coronary ischemic injury becomes arteries (persistent ischemia depletes irreversible. adenosine

75 Dilated DCM results from direct dmg to Decompensated HF Cardiovascular (CV) Pathophysiology 8 cardiomyopathy cardiomyocytes leading to • Systemic and Pulmonary edema (Patp) myocardial contractile dysfxn • This viral origin in young pt with previos (systolic dysfxn), volume URI like symtpoms overload, and ventricular dilation. • Direct viral injury and autoimmune Viral myocarditis is a common rxn > inflammation > dialtion and systolic cause of DCM and should be dysfunction suspected in young pts who • Also familial, alcohol, cocaine, develop HF following a SSx viral pregnancy, hemochromatosis prodrome. HTN • Concentric LVH AS • High systolic pressure gradient across aortic valve MI • Regional wall motion abnormality HCM • Asymmetric septal hypertrophy and systolic anterior motion of mitral valce 85 Hypertrophic HCM is characterised by HOCM Cardiovascular (CV) Pathophysiology 9 cardiomyopathy asymmetric ventricular septal • Harsh crescendo decrescendo systoil (Patp) hypertrophy and dynamic LVOT murmur at lower left sternal border obstr. ↓ in LV blood volume, via • Decreased preload or decreased manoeuvres or conditions that ↓ afterload increase obstruction and murmur preload (e.g. abrupt standing, > standing up would make murmur louder Valsalva strain phase) or • Increaed preload or afterload will afterload, worsen LVOT obstr make murmur quieter > and ↑ the intensity of the HCM squatting murmur.

90 Wolff-Parkinson- Wolff-Parkinson-White syndrome WPW triad Cardiovascular (CV) Pathophysiology 2 White syndrome is characterized by symptomatic • Shortened PR interval (under 0.12) (Patp) paroxysmal supraventricular • Wide QRS tachycardia (eg, atrioventricular • Delta wave reentrant tachycardia) due to the presence of an accessory conduction pathway. During normal sinus rhythm, the presence of this accessory pathway causes ventricular preexcitation, which can be identified on ECG by the triad of a shortened PR interval, early upslope of the QRS complex (delta Wave), and a widened QRS interval.

93 Restrictive Diastolic HF is caused by ↓ Decompensated CHF Cardiovascular (CV) Pathophysiology 1 cardiomyopathy ventricular compliance and is • Orthopnea, bibasilar crackles, JVD, (Patp) characterised by normal LV EF, edema normal LV EDV, and ↑ LV filling Restrictive cardiomyopathy pressures. HTN, obesity, and • Reduced LV compliance infiltrative disorders (e.g. • Idiopathic, amyloidosis, sarcoidosis, transthyretin-related amyloidosis, hemochromatosis sarcoidosis) are important causes • Transthyretin: carrier of thyroxine > of DHF. mutation in TTR gene cause misfolding and amyloid in the heart Dilated CM • Alcohol, doxorubicin, selenium, viral myocarditis • Increased LV compliance 96 Cardiac CT typically presents w/ Cardiac Tamponase Cardiovascular (CV) Pathophysiology 2 tamponade hypotension w/ PP, ↑ JVP, and • Maliginancy, radiation (Patp) muffled heart sounds (HS; Beck's • Infection triad). PP refers to an abn • Hydralazing, isoniazid exaggerated ↓ in SBP >10mmHg • CT diseases on inspiration, and is a common • Beck triad: hypotension, JVD and finding in pts w/ pericardial muffled heart sounds effusion w/ CT. • Pulsus paradoxus • Enlarged water bottle shaped heart Constrictive pericarditis • Takes months to develop • Usually after radiation Viral myocarditis • Pulsus alternans: pulse amplitude changes

97 Acute pericarditis Acute-onset, sharp, and pleuritic Acute Pericarditis Cardiovascular (CV) Pathophysiology 5 chest pain that ↓ w/ leaning • Sharp, pleuritic chest pain that decreases (Patp) forward is char of acute when leaning forward pericarditis. • High pitched, leathery and scratch Fibrinous/serofibrinous friction rub pericarditis is the most common • Commonly caused by MI, RF or uremia form of pericarditis and a • Viral fibrinous exudate can occur pericardial friction rub is the most Kussmaul Sign specific physical finding. Viral • Increased JVD with inspiration pericarditis is often preceded by a • Constrictive pericarditis, restrictive URI. cardiomyopathy, right HF, tricupsid stenosis and rarely cardiac tamponase Pulsus Paradoxus • Cor pulmonale, constrictive pericarditis, cardiac tamponade, COPD and asthma

186 Diastolic HF w/ preserved EF is Chx by Diastolic HF Cardiovascular (CV) Pathophysiology 4 dysfunction diastolic dysfunctlon, which • Normal EF (Patp) frequently occurs in the setting of • Normal end diastolic volume prolonged systemic HTN due to • Increased LV filling pressure concentric LVH. Pts w/ • Decreaed LV compliance longstanding HTN have ↑ SVR. Systolic HF • Decreased EF • Increaed end diastolic volume 187 Congenital cardiac Increased blood oxygen VSD: loud holosystolic murmur best Cardiovascular (CV) Pathophysiology 2 defects saturation between 2 right-sided heard over the left sternal border (Patp) vessels or chambers indicates the • Increased RA and RV SpO2 but RV > presence of a left-to-right shunt. RA SpO2 If the abnormal oxygen increase • ASD: fixed S2 splitting occurs between the right atrium • SpO2 of RA and RV would be and the right ventricle, a identical ventricular septal defect (VSD) is Bifid carotid pulse with brisk upstroke likely present. Small VSDs indicated HOCM produce a holosystolic murmur that is loudest over the lower left sternal border.

189 Embolic stroke Paradoxical embolism occurs Paradoxical emboli Cardiovascular (CV) Pathophysiology 1 when a thrombus from the venous • DVT through PFO, VSD, ASD or (Patp) system crosses into the arterial pulmonary arteriovenous malformation to circulation via an abnormal brain connection b/w the right and left • ASD: wide and fixed splitting of S2 cardiac chambers (eg, PFO, ASD, Random AR or VSD). Atrial left-to-right • Early diastolic decrescendo murmur shunts cause wide and fixed HCM splitting of S2 and can facilitate • Systolic mumur that gets quieter with paradoxical embolism due to standing MS or TS periods of transient shunt reversal • Diastolic murmur with presystolic (eg, during straining or accentuation due to atrial contraction coughing). • A fib causes murmur to disappear TS or RBBB • Wide split S1 that is accentuated by inspiration 193 Myocardial LV free-wall rupture is an Post MI Cardiovascular (CV) Pathophysiology 18 infarction uncommon but devastating mech • Witin 24hr: Fibrinolytic therapy causing (Patp) complication of transmural MI intracranial or GI bleeding that occurs w/i 5 days or up to • First 48/72hr: V fib then V tach 2wks following the event. • Days 5 14: wall/septum/papillary rupture Rupture leads to cardiac tamponade that causes hypotension and shock w/ rapid progr to cardiac arrest. Autopsy typically reveals a slit-like tear at the site of infarction in the LV wall.

194 Marfan syndrome CV lesions are the most life- Marfan Cardiovascular (CV) Pathophysiology 2 threatening complications a/w • Fibrillin 1 on chromosome 15 (Patp) MFS. Early-onset CMD of the • MVP and cystic medial degeneration of aorta predisposes to AD, the most aorta common COD in these pts. • MCC of death: aortic dissection • 2nd MCC of death: cardiac failure due to MVP or aortic regurg Homocystinuria • Marfan habitus • Increased risk for athero and thrombotic events 195 Myocardial Rupture of the LV free wall is a Post MI Issues Cardiovascular (CV) Pathophysiology 18 infarction catastrophic mechanical • 514 days: macrophage rupture structure (Patp) complication of anterior wall MI in order from most to least common (free that usually occurs w/i the 1st 5- wall leading to tamponade, septum leading 14 days after MI. Rupture leads to to VSD, papillary muscle leads to regurg) hemopericardium and CT, • 1 month+: true aneurysm leades to mural causing profound hypotension thrombus, arrhythmias, HF or rarely and shock w/ rapid progression to rupture PEA and death.

196 Pulmonary arterial PAH should be suspected in Pulmonary HTN Cardiovascular (CV) Pathophysiology 8 hypertension young and otherwise healthy pts • RV hypertrophy (cor pulmonale) (Patp) w/ fatigue, progr dyspnoea, • Progressive dyspnea atypical chest pain, or • Primary: mid aged females unexplained syncope. Long- • Characteristic intimal hyperplasia and standing PAH leads to fibrosis, medial hypertrophy and plexiform hypertrophy a/o dilation of the lesions RV (cor pulmonale). Random AS and HTN • LV hypertrophy WPW • Sudden cardiac death in young pt • Delta wave

198 Pulmonary arterial Left-sided HF can cause 2° PAH LHF Cardiovascular (CV) Pathophysiology 8 hypertension via ↑ left-sided diastolic filling • MCC: HTN (Patp) pressures transmitting backward • High LV pressure > high LA pressure > to the pulm veins, resulting in pulmonary venous congestion > damages pulm venous congestion. Over pulmonary endotheium > low NO and high time, pulm arterial remodelling endothelin produced > high resistance > (medial hypertrophy and intimal pulmonary art SM proliferation (medial thickening w/ fibrosis) can occur, hypertrophy) and intimal thickening and but not to the extent that occurs in fibrosis > plexiform lesions (1°) PAH. Other causes of Pulmonary HTN • COPD • Hypoxia • Congenital left to right shunt • Pulmonary fibrosis • Recurrent PE

200 Mitral DHF is a common cause of 2° Functional MR Cardiovascular (CV) Pathophysiology 6 regurgitation (fxnal) MV regurgitation. ↑ LV • Holosystolic murmur heard in CHF pt (Patp) EDV causes dilation of the MV when fluid overloaded that disappears once annulus and restricted movement treatment is initiated and fluid is decreased of the chordae tendineae w/ Mitral Valve calcification subsequent regurgitation. Tx w/ • Calcification of annulus in pt over 60 diuretics and vasodilators can • Asymptomatic improve HF-induced MR. 201 Atrial septal defect Wide, fixed splitting of the 2nd ASD Cardiovascular (CV) Pathophysiology 2 heart sound is a Chx auscultatory • Wide fixed splitting S2 (Patp) finding in pts w/ ASD. A • Increased pressure on right side of the hemodynamically significant heart ASD can produce chronic pulm • Needs to be fixed in order to prevent HTN as a result of left-to-right pulmonary artery change intracardiac shunting. • High pressure in pulmonary arteries > Eisenmenger syndrome is the late- medial hyperthropy that can become severe onset reversal of a left-to-right enough its pressure is great than systemic > shunt due to pulm vascular right to left shunt (Eisenmenger) sclerosis resulting from chronic • Changes in pulmonary arteries are pulm HTN. Closure of the ASD irreversible may be required to prevent Eisenmenger syndrome irreversible pulm vascular • Will see cyanosis, polycythemia and sclerosis and a permanent clubbing Eisenmenger syndrome. Hypertrophy of RA and RV are reversible

204 Tetralogy of Fallot In pts w/ TOF, the degree of TOF Cardiovascular (CV) Pathophysiology 3 RVOT obstr is the major • Right ventricular outflow tract (RVOT) (Patp) determinant of the degree of R-L obstruction is most important factor for intracardiac shunting and severity resulting cyanosis. • Increases Right >Left shunting of blood through VSD • Degree is RVOT can change > tet spells • Associated with DiGeorge, Down and 227 Aortic AR causes a decrescendo AR Cardiovascular (CV) Pathophysiology 8 regurgitation diastolic murmur w/ maximal • Wide PP (Patp) intensity occurring just after • High pitched blowing descrescendo closure of the AV, when the diastolic murmur beginning immedaitely pressure gradient b/w the aorta after A2 and LV is the highest. The pressure tracing for AR is Chx by loss of the aortic dicrotic notch, steep diastolic decline in aortic pressure, and high-peaking systolic pressures.

233 Mitral stenosis The best and most reliable Mitral Stenosis Cardiovascular (CV) Pathophysiology 7 auscultatory indicator of the • Best indicator of intensity is length of (Patp) degree of MS is the A2-OS time between S2 (technically A2) and interval. A shorter interval Opening Snap indicates more severe stenosis. • The worse the stenosis, the higher the Other auscultatory findings can residual pressure in the L atrium causes a incl a diastolic rumbling murmur louder and earlier opening snap w/ presystolic accentuation due to • Can lead to pulmonary HTN and right LA contraction. sided HF • When MS becomes sever enough to precipitate A Fib, presystolic accentuation of the MS murmur disappears

234 Mitral stenosis Isolated MS causes ↑ upstream Mitral stenosis Cardiovascular (CV) Pathophysiology 7 pressures in the LA and pulm • High P difference between LA and LV (Patp) veins and arteries. LV EDP is • High LA P > a fib and mural thrombus normal or ↓ due to obstr of blood • High pulmonary P > pulmonary flow thru the stenotic valve. An ↑ edema/hemorrhage LV EDP suggests addnal • High RV P > tricuspid regurg, JVD and downstream pathology (e.g. AV peripheral edema disease, LV failure). Rheumatic fever • MR early then MS late • AS (primarily) and some AR: both increase LV diastolic P • Cusp fusion (fish mouth) Chronic pulmonary HTN (due to MS) • Decrease pulmonary vessel compliance, reactive hypertrophy and partial obliteration of pulmonary capillaries 235 Mitral stenosis Cardiac auscultation in pts w/ MS Presystolic accentuation Cardiovascular (CV) Pathophysiology 7 reveals a loud 1st heart sound, an • Increase in diatolic murmur with atrial (Patp) early diastolic OS after the 2nd kick heart sound, and a low-pitched diastolic rumble best heard at the cardiac apex. The OS is caused by the sudden opening of the MV leaflets when the LV pressure falls below the LA pressure at the beginning of diastole.

237 Aortic In chronic AR, persistent LV Chronic AR Cardiovascular (CV) Pathophysiology 8 regurgitation volume overload triggers • Complication of infective endocarditis (Patp) eccentric hypertrophy, which • Increased preload > increase SV causes a compensatory ↑ in SV to • Eccentric hypertrophy (sarcomeres added maintain CO. This compensatory in series) mech allows for a relatively long • Maintained CO aSSx in most pts; however, LV • Decreased aortic pressure in diastole dysfxn eventually occurs, leading (afterload) > wide PP to HF. Acute AR • Small LV cavity • Increased LV end diastolic P > pulmonary edema • Declined CO • Reflex tach AS • Concentric hypertrophy 238 Aortic Chronic aortic regurgitation (AR) Aortic regurg Cardiovascular (CV) Pathophysiology 8 regurgitation causes a reduction in diastolic • Head bobbing (hyperdynamic pulse with (Patp) blood pressure and a wide PP) compensatory increase in left LV Restriction ventricular stroke volume. These • Small SV changes create a high-amplitude, LV Dilation rapid rise-rapid fall pulsation (ie, • Small SV and low PP widened pulse pressure) and the other characteristic findings of AR (eg, head bobbing. "pistol- shot" femoral pulses).

243 Aortic stenosis The murmur of AS is a systolic AS Cardiovascular (CV) Pathophysiology 8 ejection-type, crescendo- • Large difference in pressure between LV (Patp) decrescendo murmur that starts and aortic pressure after the 1st heart sound and • Crescendo decrescendo murmur (loudest typically ends before the A2 mid systole > large difference in pressure) component of the 2nd heart sound. The intensity of the murmur is proportional to the magnitude of the LV to aorta pressure gradient during systole.

244 Aortic stenosis In pts w/ chronic AS and Severe aortic stenosis Cardiovascular (CV) Pathophysiology 8 concentric LVH, atrial • Pt with chronic AS and concentric LVH, (Patp) contraction contributes atrial contraction contributes significantly significantly to LV filling. Loss to LV filling of atrial contraction due to AF • 10% of pt develop a fib >sudden decrease can ↓ LV preload and CO in left ventricular sufficiently to cause systemic filling due to loss of atrial contraction > hypotension. ↓ forward filling of acute pulmonary edema and hypotension the LV can also result in backup of blood in the LA and pulm veins, leading to acute pulm edema. 246 Diastolic A low-freq, late diastolic sound Gallops Cardiovascular (CV) Pathophysiology 4 dysfunction on cardiac auscultation that •S3 (Patp) immediately precedes S1 is most • Immediately after S2 often S4. An abn S4 can be heard • Rapid ventricular filling in pts w/ ↓ ventricular compliance • Turbulent blood flow due to high volume (e.g. HTN heart disease, AS, • Normal in children, young adults and HCM) due to a sudden rise in pregnancy EDP w/ atrial contraction. • Abnormal: over 40, HF, restrictive cardiomyopathy, high output states S4 (best heard with bell in lat decub at apex) • Just before S1 • Atrial contraction forcing blood into stiff ventricle (HTN, AS, HCM) • Normal in healthy older adults • Abnormal: younger adults, children, ventricular hypertrophy, acute MI

293 Peripheral Phenotypically mixing refers to Reperfusion injury Cardiovascular (CV) Pathophysiology 4 vascular disease coinfection of a host cell by 2 • High ROS generation by parenchymal (Patp) viral strains, resulting in progeny cells, endothelial cells, and leukocytes virions that contain nucleocapsid • Irreversible mitochondrial damage proteins from 1 strain and the • Inflammation that attracts neutrophils unchanged parental genome of causing additional injury the other strain. B/c there's no • Activation of complement causing cell change in underlying viral injury genomes (no genetic exchange), Random the next gen of virions revert to • Cellular swelling: reversible injury their original, unmixed • Glutathione peroxidase decreases ROS phenotypes. • Mitochondrial vacuolization: irreversible injury but not directly associated with increased creatine kinase

296 Aging Dystrophic calcification occurs in Dystrophic calcification of aortic valve Cardiovascular (CV) Pathophysiology 8 dmgd or necrotic tissue in the • Occurs with cell injury and death (Patp) setting of normal Ca lvls; (necrosis) with normal Ca levels metastatic calcification occurs in • Stains dark purple on H&E normal tissue in the setting of Random hypercalcemia. Amyloidosis: restrictive cardiomyopathy Hypercalcemia: metastatic calcification of normal tissue (especially in alkaline environement of kidneys, lungs, arteries and gastric mucosa)

726 Rheumatic fever Acute RF is a complication of Acute Rheumatic Fever Cardiovascular (CV) Pathophysiology 5 untreated group A streptococcal • Anti GAS Ab attach host cardiac and (Patp) pharyngitis. RHD is the most neuronal tissue common cause of acquired • JONES valvular heart disease and CV • Tx: penicillin (prevents RF) death in developing countries. • Empiric tx: decrease RF related heart The incidence of acute RF and disease RHD has been ↓ in industrialized • Penicillin does not prevent PSGN nations w/ prompt Tx of Serum sickness streptococcal pharyngitis w/ • Associated with Hep B and penicillin penicillin. 751 Prostacyclins Prostacyclin (prostaglandin I2) is Prostacyclins (PGI2 from PGH2) Cardiovascular (CV) Pathophysiology 1 synthesized from prostaglandin • Synthesized in endothelium (Patp) H2 by prostacyclin synthase in • Inhibits platelet aggregation and vascular endothelial cells. Once adhesion, vasodilation, increased secreted, it inhibits platelet permeability and stimulates leukocyte aggregation and causes chemotaxis (all oppose TXA2) vasodilation to oppose the fxns of • Damaged endothelium decreased thromboxane A2 and help PGI2 synthesis and TXA2 predominates > maintain vascular homeostasis. occlusion Serotonin • Produced by platelets • Vasodilation and increased premeability Kallikrein • Converts kininogen > bradykinin Protein C • Inactivated Factor 5a and 8a

843 Chronic heart ↓ CO in HF triggers neuroendo CHF Cardiovascular (CV) Pathophysiology 12 failure compensatory mechanisms to • Decreased Co > RAAS stimulated (Patp) maintain organ perfusion; (vasoconstriction, Na retention, high however, the compensatory aldosterone) and increased sympathetic mechanisms are maladaptive over output the long term. ↑ sympathetic output and activation of the RAAS stimulate vasoconstriction and volume retention, compounding the hemodynamic stress on an already failing heart and creating a vicious cycle of decompensation.

943 Mitral In pts w/ MR, LV afterload is Mitral regurg Cardiovascular (CV) Pathophysiology 6 regurgitation determined by the balance of • Forward SV: blood in aorta (Patp) resistance b/w forward flow • Backward SV: blood into LA (aortic pressure) and regurgitant • Amount of backward SV is related to flow (LA pressure). A ↓ in SVR ↑ afterload (decreased afterload will decrease the ratio of forward to regurgltant backward SV) blood flow and improves CO. Decreased HR > higher EDLVV > worse backward SV • Same as increase preload (if MR is volume dependent) • Increase contractility will wrosen backward SV 944 Mitral Pts w/ severe MR develop left- MR Cardiovascular (CV) Pathophysiology 6 regurgitation sided volume overload w/ an S3 • The best indicator of MR severity is the (Patp) gallop due to the large volume of presence of an S3 gallop (larger amout of regurgitant flow re-entering the regurg leads to S3) ventricle during mid-diastole. The MPV absence of an S3 gallop excludes • Mid systolic click with occur earlier in severe chronic MR. systole with decrease LV volume

945 Mitral LV systole corresponds to the Mitral regurg Cardiovascular (CV) Pathophysiology 6 regurgitation time of passive filling of the LA • Elevation of the V Wave pressure (Patp) (atrial diastole). MR leads to Aortic regurg markedly ↑ LA pressure during • Elevated LV diastolic pressure and this period, creating the char early decrease aortic diastolic pressure and large V wave on LA pressure Aortic stenosis tracing. • Abnormal pressure gradient across aortic valve (LV systolic pressure >> aortic systolic pressure)

952 Coronary blood ↑ in resting blood flow to Coronary steal disease Cardiovascular (CV) Pathophysiology 9 flow ischemic myocardium are • Coronary arteries distal to atheroma are (Patp) primarily mediated by locally- maximally dilated acting substances (eg, adenosine, • With adenosine or dipyridamole NO) that trigger coronary (vasodilators) are given it will actually arteriolar vasodilation. Rx shunt blood away from the ischemic areas arteriolar vasodilators (eg, • Theory behind pharm stress test adenosine, dipyridamole) mimic Epicardial vessels the vasodilation that occurs w/ • RCA, LCA, LAD, Left circ exercise and may cause redistribution of blood flow from ischemic to nonischemic areas of myocardium, so-called coronary steal. 1532 Chronic heart The ↓ CO in HF leads to ↓ renal CHF Cardiovascular (CV) Pathophysiology 12 failure perfusion and conseq stim of the • Increase Renin from JG cells (Patp) RAAS in a maladaptive effort to • Angiotensin (made by liver) > ang 1 maintain effective BV. Inactive (renin) in sysemic circulation AT-I is converted into active AT- • Ang 1 > ang 2 (angiotensin converting II by endothelial-bound ACE in enzyme) in the lung the lungs. • This means higher ang 2 than ang 1 in the pulmonary vein 1578 Cor pulmonale Peripheral edema results from the Transudate causes Cardiovascular (CV) Pathophysiology 1 accumulation of fluid in the • Elevated capillary hydrostatic pressure (Patp) interstitial spaces. Factors that • Abnormal arteriolar dilation or promote edema include elevated imparied venous return capillary hydrostatic pressure, • Decreased plasma oncotic pressure decreased plasma oncotic • Nephrotic, liver dz, malnutrition pressure, sodium and water • Sodium and water retention retention, and impaired lymphatic • Increase intravascular volume drainage. In chronic heart failure, (increased capillary hydrostatic P) increased lymphatic drainage • Lymphatic obstruction initially offsets factors favoring • Causes by filariasis, malignancies, and edema, whereas acute changes surgery/radiation (eg, venous thrombosis, heart Moderate transudate can be offset by failure decompensation) are more compensatory increase in lymph drainage likely to produce edema. preventing edema

2070 Jugular venous On JVP tracings, the 1st peak is Jugular Venous Tracing A: right atrial Cardiovascular (CV) Pathophysiology 1 pulse the a wave, which is generated by contraction (Patp) atrial contraction. This is notably • C: right ventricular contraction X: right absent in pts w/ AF. atrial relaxation • V: right atrial filling • Y: Right atrial emptying 2071 Constrictive Calcification and thickening of Constrictive Pericarditis Cardiovascular (CV) Pathophysiology 2 pericarditis the pericardium are common • Thickened and calcified pericardium (Patp) features of constrictive • Slowly progressive dyspnea, chronic pericarditis on CT. CFx include edema and ascites slowly progressive dyspnea, • Rapid y descent peripheral edema, and ascites. • Causes: radiation of chest, cardiac surgery and TB Aortic dissection • Sudden chest pain radiating to the back HCM • Prominent a wave • Thickened interventricular septum Ischemic heart • Looks for calcification of coronary art or aorta

2096 Mitral MR results in a blowing, Rheumatic Fever Cardiovascular (CV) Pathophysiology 6 regurgitation holosystolic murmur heard best • MR for the first few decades > then MS (Patp) over the cardiac apex w/ radiation Ascending Aortic Aneurysm to the axilla. RHD is a very • Aortic regurg common cause of MR in underdeveloped countries. 2099 Pulsus paradoxus PP is defined by a ↓ in SBP of Pulsus Paradoxus Cardiovascular (CV) Pathophysiology 2 >10 mm Hg w/ inspiration. It is • Inspiration > more preload > RV expands (Patp) most commonly seen in pts w/ CT into LV (normally LV can move in but can also occur in severe pericardal space) > but if can't then lower asthma, COPD, and constrictive LVEDV > small SV pericarditis. • See with cardiac tamponade, COPD, asthma, constrictive pericarditis AS • Pulsus parvus et tardus MR • Bound pulses with brisk uptroke (increase LV ejection volumes) 2100 Pulsus paradoxus Asthma and COPD exacerbation Asthma or COPD causing pulsus Cardiovascular (CV) Pathophysiology 2 are the most frequent causes of paradoxus (Patp) PP in the absence of significant • MCC of pulses paradoxus in absence pericardial disease. β-adrenergic of pericardial disease agonists control acute asthma and • Give B2 agonist > Gs > increased cAMP COPD exacerbations by causing Cromolyn bronchial smooth muscle • Stabilized mast cells preventing relaxation via ↑ intracellular degranulation cAMP. Corticosteroids • Prevent eosinophil degranulation

2105 Aortic AR causes a high-pitched, Aortic regurg Cardiovascular (CV) Pathophysiology 8 regurgitation blowing, diastolic murmur w/ a • Early descendo diastolic murmur (Patp) decrescendo intensity pattern. The • Can present with palpitations, atypical murmur of AR due to aortic root chest pain, left HF dilation is best heard at the right • The duration of the murmur gives upper sternal border, whereas the insight into severity (holodiastolic is murmur of AR due to valvular severe) pathology is best heard at the left HCM 3rd ICS. • Mitral regurg (systolic murmur) MVP • Midsystolic click 2106 Aortic stenosis A bicuspid AV is a common AS Cardiovascular (CV) Pathophysiology 8 cause of AS in the United States. • Harsh, crescendo decrescendo systolic (Patp) The classic auscultatory finding murmur @ R sternal border that radiates to in pts w/ AS is a harsh, crescendo- carotids decrescendo systolic ejection • Syncope, angina and dyspnea murmur heard best in the right • Under 60 > think bicuspid aortic valve or 2nd ICS w/ radiation to the rheumatic heart disease carotids. • Over 60 > calcification due to wear and tear Marfans • Aortic dilation > AR • Aortic dissection MVP • Mid systolic click @ cardiac apex 2107 S4 The 4th heart sound (S4) is a low • S4 = hypertrophy S3 = dilation Cardiovascular (CV) Pathophysiology 1 frequency sound heard at the end • Children: S3 is normal, S4 is pathologic (Patp) of diastole just before S1. It is due to ↓ LV compliance and is often a/w RCM and LVH.

2108 Chronic heart S3 is a low-freq sound occurring S3 gallop Cardiovascular (CV) Pathophysiology 12 failure immediately after S2 that's • Bell over apex in left lat decubitus (Patp) commonly a/w ↑ ventricular ESV. position Due to S3 freq occurs in the setting of • Forceful, rapid filling of a ventricle that MR and systolic HF (e.g. DCM). has normal compliance • Normal or even decreased filling rates when ventricular compliance is low • Blood flowing into an overfilled ventricle with high end systolic volume Tamponade • Bulging of intraventricular septum into LV > pulsus parasdoxus

2109 Patent ductus PDA is characterised by a PDA Cardiovascular (CV) Pathophysiology 4 arteriosus continuous murmur heard best in • Continuous murmur with S2 splitting (Patp) the left infraclavicular region w/ during inspiration (physiologic) max intensity at S2. A small PDA • Max intensity at S2 is often aSSx and is usually Aortic regurg detected incidentally during • Associated with ascending aortic routine cardiac auscultation. It aneurysm occurs most commonly in pts Lutembacher Syndrome born prematurely and those w/ • Continuous ASD murmur when coupled cyanotic congenital heart disease. with mitral valve obstruction 2117 Ventricular septal A VSD is a/w a low-pitched, VSD Cardiovascular (CV) Pathophysiology 2 defect holosystolic murmur at the mid to • Low pitched holosystolic murmur best (Patp) ↓ left sternal border. It heart at left sternal border accentuates during maneuvers • Accentuated with handgrip (increased that ↑ afterload (eg, handgrip afterload shunts blood through VSD more) maneuver). A small VSD is ASD usually aSSx and produces a • Mid systolic pulmonary ejection murmur louder murmur due to higher HCM interventricular pressure gradient. • Murmur will get quieter with increased afterload or preload (decrease obstruction) • Would with valsalva due to decreased preload AR • Early diastolic murmur • Increased with increased afterload

2124 Coronary blood The coronary sinus communicates Right sided heart pressure will cause Cardiovascular (CV) Pathophysiology 9 flow freely w/ the RA and will become coronary sinus dilation (Patp) dilated 2° to any factor that • R heart HTN can be caused by pulmonary causes ↑ RA pressure. The most HTN (especially in a midaged female) common cause is pulm HTN, Severe HTN leading to ↑ right heart pressures. • Can cause aortic dissection Pericardial effusion can cause coronary sinus compression

11797 Wolff-Parkinson- WPW pattern is characterised by Cardiovascular (CV) Pathophysiology 2 White syndrome a shortened PR interval, widening (Patp) of the QRS complex, and slurred initial upstroke of the QRS complex (δ wave). It's caused by an accessory pathway that bypasses the AV node, causing preexcitation of the ventricles. Pts w/ WPW pattern can develop SSx arrhythmia (e.g. AV re-entrant tachycardia) due to re-entry of electrical impulses thru the accessory conduction pathway.

11833 Myocardial The dominant RCA perfuses both RV MI Cardiovascular (CV) Pathophysiology 18 infarction the inferior wall of the LV and • Due to RCA infarct > inferior wall (Patp) the majority of the RV. Proximal • Hypotension, JVD occlusion can cause RV MI, • Clear lungs which Px w/ hypotension (↓ CO) • High central venous P, normal or low and distended jugular veins (↑ PCWP, low CO CVPs). The lungs will be clear on LV MI auscultation and XR (lack of • High central venous P, high PCWP, low pulm edema) unless concomitant CO left-sided HF is also present.

11849 Primary PRA is a measure of the amount • Low Na diet > increased RAAS Cardiovascular (CV) Pathophysiology 14 hypertension of ATI generated per unit of time. • Renal art stenosis > increased RAAS (Patp) It provides a useful Ax of the RAA axis. Factors that ↑ PRA incl low Na+ intake and anti- HTN Rx such as diuretics (e.g. hydrochlorothiazide), ACEIs, and ARBs (e.g. valsartan).

11851 Mitral Regurg flow into the LA in acute Mitral Regurg Cardiovascular (CV) Pathophysiology 6 regurgitation MR leads to ↑ LA pressure and ↑ • Acute: Increased preload, decreased (Patp) LV EDV (preload). The low- afterload, normal resistance pathway also ↓ LV contractile function, increased EF, afterload w/ a resulting ↑ in EF increased SV, pulmonary edema but overall ↓ in forward SV. ↑ LA • Compensated: increased preload, normal pressure and ↓ CO result in pulm afterload, normal contractile function, oedema and severe hypotension, increaed EF, normal SV, no pulmonary respectively. edema • Decompensated: increased preload and afterload, decrease contrile function, EF and SV, pulmonary 13979 Septic shock Septic shock causes widespread Cardiovascular (CV) Pathophysiology 6 arteriolar vasodilation, which (Patp) leads to a decrease in systemic vascular resistance and a compensatory increase in cardiac output. Central venous pressure and pulmonary capillary wedge pressure are also decreased due to pooling of blood in the dilated veins Increased flow rates through the peripheral capillaries lead to incomplete oxygen extraction by the tissues and high mixed venous oxygen saturation.

14959 Pulmonary arterial Pulmonary arterial hypertension Cardiovascular (CV) Pathophysiology 8 hypertension results from endothelial (Patp) dysfunction that leads to an increase in vasoconstrictive, proproliferative mediators (eg, endothelin, thromboxane A2) and a decrease in vasodilative, antiproliferative mediators (eg, nitric oxide, prostacyclin). The relative imbalance in these mediators leads to vasoconstriction and intimal-wall thickening with a consequent increase in pulmonary vascular resistance.

14966 Aortic stenosis Angina often occurs in AS even Cardiovascular (CV) Pathophysiology 8 in the absence of obstr CAD. It (Patp) results from ↑ myocardial O2 demand due to an ↑ in LV mass (i.e. concentric hypertrophy) and ventricular wall stress.

15001 Vasospastic Vasospastic angina involves Cardiovascular (CV) Pathophysiology 2 angina hyperreactivity of coronary artery (Patp) smooth muscle. Pts are usually young (age <50) and w/o significant RFx for CAD; they experience recurrent episodes of chest discomfort that typically occur during rest or sleep and resolve w/i 15 min.

15180 Coronary artery Stable angina results from fixed Cardiovascular (CV) Pathophysiology 4 disease coronary artery stenosis that (Patp) limits blood flow to downstream myocardium, preventing the myocardial O2 supply from ↑ during exertion. Dobutamine mimics the effects of exercise and ↑ myocardial O2 demand; it can be used during stress testing to provoke areas of ischemic myocardium, which can be recognized on imaging by a localized and transient ↓ in contractility (ie, wall motion defect).

15199 Pulmonary arterial Pulm HTN can be recognized on Cardiovascular (CV) Pathophysiology 8 hypertension PEx by a loud pulmonic (Patp) component of S2 and an accentuated, palpable impulse at the left stemal border (left parasternal lift due to RV heave). 15241 Septic shock Septic shock can Px w/ either Cardiovascular (CV) Pathophysiology 6 hyper- or hypothermia. The initial (Patp) disturbance is peripheral vasodilation leading to ↓ SVR, ↓ CVP and ↓ PCWP. A compensatory ↑ in sympathetic drive causes an ↑ in CO; the resulting high flow rates lead to incomplete O2 extraction in the tissues, resulting in high mixed venous O2 saturation.

15269 Athlete's heart Athlete's heart refers to Cardiovascular (CV) Pathophysiology 1 physiologic cardiac adaptations (Patp) that improve cardiac fxn in response to high-lvl endurance training. There's predominant eccentric hypertrophy w/ a smaller component of concentric hypertrophy, leading to an overall ↑ in LV mass, enlarged LV cavity size, ↑ LV wall thickness, and ↓ resting HR.

15310 Hypertrophic Pts w/ HCM may be aSSx and Cardiovascular (CV) Pathophysiology 9 cardiomyopathy often have a FHx of HCM or (Patp) SCD. Findings consistent w/ HCM incl an overall ↑ in LV mass, ↓ LV cavity size w/ impaired diastolic fxn, LVH predominantly affecting the septum, and normal or ↑ LV EF.

15354 Aortic aneurysm AAA is focal dilation of the Cardiovascular (CV) Pathophysiology 6 abdominal aorta above normal (or (Patp) >3 cm in diameter). It is generally aSSx until aneurysm rupture, which is frequently fatal. RFx include age >65, smoking, and male sex.

15528 Sick sinus aSSx LV systolic dysfxn is a Cardiovascular (CV) Pathophysiology 2 syndrome common stage in the progr of HF. (Patp) Neurohormonal mechs, incl the SNS and RAAS, help maintain the aSSx period by ↑ volume retention and peri resistance to maintain organ perfusion. Although these mechs are beneficial in the short term, they're ultimately deleterious, ↑ hemodynamic stress and cardiac remodelling that eventually lead to DHF.

15574 Sick sinus SSS results from degeneration Cardiovascular (CV) Pathophysiology 2 syndrome (usually age-related) of the SA (Patp) node, leading to impaired conduction and ↓ CO w/ SSx of dyspnea, fatigue, lightheadedness, presyncope, and syncope. ECG typically demonstrates bradycardia w/ sinus pauses (delayed P waves), sinus arrest (dropped P waves), and jxnal escape beats.

15650 Acute heart failure Pts w/ DHF have ↑ LV EDP and ↓ Cardiovascular (CV) Pathophysiology 7 CO that's most often 1arily due to (Patp) LV dysfxn. RA pressure (i.e. CVP) is also ↑ in advanced HF due to volume overload; RHF (most often occurring 2° to LHF) can also contribute to ↑ RA pressure. 15651 Chronic heart The ventricular myocardium Cardiovascular (CV) Pathophysiology 12 failure secretes BNP in response to the (Patp) ventricular stretch and strain that typically occurs w/ volume overload. BNP, along w/ ANP secreted by the atrial myocardium, stimulates vasodilation and salt and water excretion to help relieve volume overload.

15693 Long QT Congenital LQTS is commonly Cardiovascular (CV) Pathophysiology 4 syndrome caused by a mutation that slows (Patp) the delayed rectifier K current that repolarizes the cardiomyocyte AP. Certain Rx (eg, macrolide Abx, antipsychotics, antiemetics) also slow the K repolarization current and prolong the QT interval. Excessive QT prolongation can trigger serious cardiac arrhythmia (ie, TdP), resulting in syncope or SCD.

15729 Tricuspid Severe TR can lead to right-sided Cardiovascular (CV) Pathophysiology 3 regurgitation HF, evidenced by JVD, (Patp) hepatomegaly, lower extremity edema, and the absence of pulm edema. Permanent PM placement can cause TR b/c the RV lead passes through the TV orifice and can disrupt valve closure.

16596 Aortic A large, acute pulmonary Cardiovascular (CV) Pathophysiology 8 regurgitation embolism causes a rapid increase (Patp) in right ventricular (RV) pressure that leads to RV cavity enlargement and RV dysfunction. Thickening of the RV wall is not seen in acute pulmonary embolism, as there is no time for compensatory hypertrophy to occur in response to the increased pressure load.

38 Vasospastic Prinzmetal (variant) angina is Prinzmetal angina Cardiovascular (CV) Pharmacology 2 angina Chx by episodic, transient atks of • Angina at rest or at night not related to (Phar) coronary vasospasm (at rest and excursion at night), producing temporary • Transient ST elevation transmural myocardial ischemia • Due to coronary vasospasm w/ ST-segment elevation. • Dihydroergotamine: ergot alkaloid used Possible triggers are cigarette for migraines can precipitate smoking, cocaine/amphetamines, • Stimulates both alpha receptors and and dihydroergotamine/triptans. serotonin receptor Tx includes tobacco/Rx cessation • Prinzmetal can also be triggered by and vasodilator Thx (eg, nitrates, cigarettes, cocaine/amphetamine, and CCBs). triptans • Tx: CCB

136 Nitrates Nitrates (via conversion to NO) Hypertensive emergency Cardiovascular (CV) Pharmacology 7 activate guanylate cyclase and ↑ • Tx: ntiroglycerine, nitroprusside Nitrates (Phar) intracellular lvls of cGMP. ↑ lvls • Becomes NO by SM cells of vasculature of cGMP lead to myosin light- > activated GC > increased cGMP > chain dephosphorylation, decreased intracellular Ca > decreaed resulting in vascular smooth activity of MLCK and dephosphorylation muscle relaxation. of myosin light chain > relaxation 137 Angina Pharmacologic nitrates (e.g. Nitroglycerine Cardiovascular (CV) Pharmacology 1 nitroglycerin, isosorbide • Venodilater (especially large veins) (Phar) mononitrate, isosorbide dinitrate) Precapillary sphincters are meta to NO and S-nitrothiols • Respond to NE and epi in vascular smooth muscle cells, • Dilate with histamine, hypoxia, high leading to an ↑ in cGMP that CO2, and acidosis stims vasodilation. Large veins Arterioles: dilate with alpha1 blockers and are predominantly affected, CCB leading to ↑ venous capacitance and ↓ venous return (preload), which ↓ LV wall stress and myocardial O2 demand to relieve anginal SSx.

138 Nitrates Sublingual nitroglycerin is used Nitroglycerin Cardiovascular (CV) Pharmacology 7 for rapid SSx relief in pts w/ • Venodatiol (Phar) stable angina. The 1° anti- • Decreased preload (decrease LV end ischaemic effect of nitrates is diastolic volume and pressure) mediated by venodilation w/ a ↓ • Modest reduction in afterload in LV EDV and wall stress, • Mild coronary artery dilation and reduced resulting in ↓ myocardial O2 coronary vasospasm demand and relief of angina SSx. Beta blockers and CCB • Decrease HR and contractility Dihydropyridine CCB • Coronary artery vasodilation > can cause cornoary steal syndrome

139 Nitrates Isosorbide dinitrate has a low Sublingual nitro Cardiovascular (CV) Pharmacology 7 bioavailability due to extensive • No first pass metabolism by liver (Phar) 1st-pass hepatic metabolism prior Isosorbide dinitrate to release in systemic circulation. • Extensive first pass metabolism by liver > Sublingual NG is absorbed low bioavailability > needs much high directly from oral mucosa into the doses than sublingual venous circulation and has a higher bioavailability.

140 Nitrates The main AEx seen w/ nitrate Nitrates Cardiovascular (CV) Pharmacology 7 Thx include h/a and cutaneous • Venodilation primarily (Phar) flushing along w/ lightheadedness • Adverse: HA, flushing, hypotension, and hypotension due to systemic reflex tach vasodilation. • Avoid in hypertophic cardiomyopathy, RV infarct, and with Sildenafil CCB and BB • Delay AV node Raynauds • Amphetamines, ergotamine, chemo Constipation • Opioids, Fe supp, CCB, and anticholinergics Thiazide • Gout Nocturnal wheezing • GERD or BB with pulmonary disease Urinary retention • TCA and antihistamines

141 Hypertrophic The dynamic LVOT obstruction HCM Cardiovascular (CV) Pharmacology 9 cardiomyopathy that occurs in HCM worsens w/ ↓ • Systolic murmur that accentuates with (Phar) LV volume, which can be caused standing from supine by ↓ in cardiac preload a/o • Avoid: vasodilators (nifedipine, nitro, afterload. Therefore, Rx that ↓ ACE inhibitor) > decreased afterload venous return or SVR (DHP causing lower LV volumes; diuretics > CCBs, NG) should generally be decrease LV preload avoided. • Both causes increased outflow obstruction 142 Nitrates Pts taking daily maintenance Nitrate Cardiovascular (CV) Pharmacology 7 nitrates need to have a nitrate-free • Rapid tolerance (Phar) period every day to avoid • Thought to be due to decreased tolerance to the Rx. vascular sensitivity to nitrates and increased sensitivity to endogenous vasoconstrictors • Pharmacokinetic drug interaction • P450 inhibition or stimulation Pharmacodynamic drug antagonism • Ability of one drug (due to MOA) to antagonize effect of another drug Effect potentiation • One drug's ability to increase the effect of another drug

143 Nitrates Using nitrates together w/ PDEIs Nitrates cre converted to NO by Cardiovascular (CV) Pharmacology 7 used for ED and pulm HTN vascular smooth muscles > NO (Phar) causes a profound systemic stimulates guanylyl cyclase to hypotension b/c they both ↑ production cGMP intracellular cGMP which causes • cGMP is degraded by vascular smooth muscle phosphodiesterase relaxation. Their use together is • Nitrate + sildenafil = severe absolutely c/i. hypotension •Tachyphylaxis: tolerance causing 145 Calcium channel CCBs inhib the L-type Ca2+ CCB Cardiovascular (CV) Pharmacology 3 blocker channel on vascular smooth • Dihydropyridine: nifedipine (Phar) muscle and cardiac cells. DHPs • Arterial (e.g. nifedipine, amlodipine) • Nondihydropyridine: verapamil primarily affect peripheral • Myocardium arteries and cause vasodilation. • Give nifedipine if pt in heart block or Non-DHPs (e.g. verapamil, bradycardia diltiazem) affect the myocardium and can cause bradycardia and slowed AV conduction.

147 Digoxin Digoxin toxicity typically Digoxin toxicity Cardiovascular (CV) Pharmacology 4 presents with cardiac arrhythmias • Arrhythmias (Phar) and nonspecific gastrointestinal • Anorexia (nausea, vomiting), neurological • Nause and vomiting (confusion, weakness), and visual • Abdominal pain symptoms. Elevated potassium is • Fatigue another sign of digoxin toxicity • Confusion and weakness and is caused by inhibition of Na- • Color vision alterations K-ATPase pumps. • Hyperkalemia

148 Digoxin Digoxin directly inhibs the Na-K- Digoxin Cardiovascular (CV) Pharmacology 4 ATPase pump in myocardial • Increases parasympathetic tone of AV (Phar) cells, leading to a ↓ in Na+ efflux node and an ↑ in intracellular Na+ lvls. • Inhibits Na/K pump: decreases Na efflux This ↓ the forward activity of the and K influx > decreased Ca efflux NCX, causing ↑ intracellular (normally Na enters and Ca exits) Ca2+ concentration and improved cAMP is the 2 messenger for excitation myocyte contractility. contraction coupling

149 Chronic heart Milrinone is a PDE-3 inhib that ↓ Milrinone and inamrinone Cardiovascular (CV) Pharmacology 12 failure the degradation of cAMP to • PDE3 inhibitor > increased cAMP > (Phar) provide 2 beneficial effects for vasodilation and increased cardiac treating systolic HF. Ca2+ influx contractility into cardiomyocytes is ↑, which ↑ ACE inhib cardiac contractility. In addn, • Angioedema Ca2+-myosin light chain kinase Digoxin, beta blocker, CCB interaction is ↓, which causes • AV block vasodilation and ↓ cardiac preload and afterload. 150 Primary α1-blockers such as doxazosin, Alpha1 Blockers Cardiovascular (CV) Pharmacology 14 hypertension prazosin, and terazosin are useful • Adverse: orthostatic hypotension and (Phar) for the Tx of both BPH and HTN. vertigo Pts w/ CAD and HF along w/ • First dose is the wrost HTN will benefit from Thiazides cardioselective β-blockers. • Adverse: hyponatremia Hydrochlorothiazide is presently Eplerenone the 1st-line Rx for the Tx of • Less anti androgenic (decreased risk of essential HTN in the gen pop. gynecomastia compared to spironolactone)

153 Heart block Common AEx of non-DHP CCBs Beta blockers and CCB can cause heart Cardiovascular (CV) Pharmacology 2 (eg, diltiazem, verapamil) include block and bradycardia (Phar) constipation, bradycardia, AV Veramapil and Diltiazem conduction block ((-) • L type CCB > works on phase 4 in SA chronotropic effect), and and AV worsening of HF in pts w/ ↓ LV • Adverse: constipation (verapamil > fxn ((-) inotropic effect). diltiazem Nifedipine • Adverse: HA, dizziness, flushing and peripheral edema Indapamide: thiazide Terazosin • Adverse: lightheaded and orthostasis • Prazosin: PTSD

154 Calcium channel Amlodipine is a DHP CCB Adverse HTN drugs Cardiovascular (CV) Pharmacology 3 blocker commonly used as monoThx or in • Thiazide (Phar) combination w/ other agents for • AKI, hyponatremia, hypoK, Tx of HTN. Major AEx include hyperuricemia, high glucose and lipids h/a, flushing, dizziness, and Nifedipine peripheral edema. • Peripheral edema (arteriolar dilation > increase cap hydrostatic P) • Decrease risk with ACE inhibitor • Dizziness Beta blockers • Bronchospasm • Bradycardia • Fatigue • Impotence Eplerenone • Less risk of gynecomastia

155 Digoxin Digoxin is used for ventricular Digoxin Cardiovascular (CV) Pharmacology 4 rate control in AF as it ↓ AV • Rate control by enhancing vagal tone (Phar) nodal conduction by ↑ inhibiting AV node conduction parasympathetic vagal tone. • Great for A fib, A flutter with rapid Digoxin is also used in HF due to ventricular rate its (+) inotropic effect. These Random effects are accomplished via inhib • Decreased AP duration > decreaed of the Na-K-ATPase pump. refractory period > allow increased HR • Delayed afterdepolarization: complete repolarization but hyperexcitable due to high intracellular Ca > proarrhythmic

156 Digoxin Digoxin tox presents w/ Digoxin OD Cardiovascular (CV) Pharmacology 4 nonspecific GI (e.g. anorexia, • GI issues first (Phar) nausea, vomiting) and neuro (e.g. • Confusion, weakness, fatigue fatigue, confusion, weakness) • Yellow color change SSx. Changes in colour vision are • Cardiac arrhythmias a more specific, but rarer, finding. • Risk of toxicity with hypokalemia, Life-threatening ventricular hypovolemia, and renal failure arrhythmias are the most serious • Tx: Anti digoxin Ab complication. 159 Antiarrhythmic For class I antiarrhythmics, Na+- Class 1 Antiarrhythmics exhibit use Cardiovascular (CV) Pharmacology 12 drugs channel-binding strength is IC > dependence (Phar) IA > IB. Use dependence • 1C > 1A > 1B describes the phenomenon in • The more they are used, the longer the which higher HRs lead to ↑ Na+ drug binds channel blockade due to 1B (Lidocaine, mexiletine, tocainide) cumulative blocking effects over • Bind less avidly to Na channels than multiple cardiac cycles. Class IC other class 1 drugs antiarrhythmics demonstrate the • Fastest dissociation meaning very little most use dependence due to their use dependence slow dissociation from the • More selective for ischemic myocardium receptor, and class IB drugs have do to reduced RMP delaying Na channel the least use dependence as they transition from inactive to resting (1B rapidly dissociate. binds longer) 1C (Propafenone and flecainide) 1A (Disopyramide, quinidine, and procainamide) 160 Dyslipidemia Niacin is used in the Tx of Niacin Cardiovascular (CV) Pharmacology 11 hyperlipidemia. It ↑ HDL lvls and • Increases HDL (Phar) ↓ LDL lvls and triglycerides. • Causes cutaneous flushing, warmth and Niacin causes cutaneous flushing, itching > mediated by PGE2 and PGD2 which is mediated by • Prophylaxis with aspirin 30min before prostaglandins and can be • Can also cause hyperglycemia and diminished by preTx w/ aspirin. hyperuricemia Vancomycin • Red man syndrome due to NOn IgE mediated mast cell degranulation Serotonin syndrome • AMS, autonomic hyperactivity, hyperreflexia and myoclonus Substance P • Mediated pain > topical capsaicin can cause depletion of Substance P

161 Drug induced Most statins are metabolized by CYP inducers Cardiovascular (CV) Pharmacology 3 myopathy cytochrome P450 3A4, w/ the • Carbamazepine (Phar) exception of pravastatin. • Phenobarbital Concomitant administration of Rx • Phenytoin that inhibit statin metabolism (eg, • Rifampin macrolides) is a/w ↑ incidence of • Griseofulvin statin-induced myopathy and CYP inhibitors rhabdomyolysis. ARF is a • Cimetidine possible sequela of • Ciprofloxacin rhabdomyolysis. • Erythromycin (not azithromycin) • Cyclosporine • Azoles • Grapefruit juice • INH • Ritonavir All statin drugs (except pravastatin) are metabolized by CYP3A4 • CYP inhibitor increases risk of hdh ii 315 Patent ductus PDA is common in preterm PDA Cardiovascular (CV) Pharmacology 4 arteriosus infants and presents w/ a • Placental production of PGE2 (Phar) continuous murmur, widened • Continuous murmur PPs, and SSx of CV strain. • Wide PP and bounding pulses Indomethacin or ibuprofen • Metabolic acidosis therapy can inhib PGE2 synthesis • Tachy, cardiomegaly and eisenmenger and accelerate closure. • Indomethacin closes PDA IL 1: produced by macrophages 551 Dose response Cortisol exerts a permissive effect Permissiveness Cardiovascular (CV) Pharmacology 4 curves on many hormones to help • When 1 hormone allows another to exert (Phar) improve the response to a variety its maximal effect of stressors. For example, cortisol • Cortisol and NE are permissive increases vascular and bronchial (cortisol upregualted alpha1 receptors) smooth muscle reactivity to • If you ever see cortisol in this type of catecholamines and increases question, go permissive regardless of other glucose release by the liver in drug response to glucagon. Additive • When the the combined effect of 2 drugs is equal to the sum of the individual drug effects Synergistic • When the combined effect excessed the sum of the individual drug effects Tachyphylaxis • Rapid development of tolerance 577 Contraception The absolute c/i to the use of OCP Cardiovascular (CV) Pharmacology 3 OCPs are: prior Hx of TE event • Estrogen: suppresses GnRH (Phar) or stroke, Hx of an oestrogen- • Progesterone: decreases risk of dependent tumour, women over endometrial cancer and thickens cervical age 35yrs who smoke heavily, mucus hypertriglyceridaemia, • Adverse: breakthrough menstrual decompensated or active liver bleeding, breast tenderness, weight gain, disease (would impair steroid DVT, PE, stroke and MI meta), preg. Never give to women • Over 35 that smokes • Previous thromboembolic event • Hx of estrogen dependent tumor • Hypertriglyceridemia • Decompensated/active liver dz (impaired steroid metabolism) • Pregnancy 625 Amiodarone Amiodarone is 40% iodine by Amio Cardiovascular (CV) Pharmacology 1 weight. It can cause • Corneal micro deposits (Phar) hypothyroidism due to ↓ • Optic neuropathy production of thyroid hormone. • Peripheral neuropathy Amiodarone can also cause • Check LFT, PTF, TFT hyperthyroidism due to ↑ thyroid • Can cause ED hormone synthesis or destructive thyroiditis w/ release of preformed thyroid hormone.

645 Endocarditis Initial empiric Tx of coagulase (-) Mitral Valve replacement Cardiovascular (CV) Pharmacology 15 staphylococcal infection should • Infected with Staph epi (Phar) include vancomycin due to • 80% of Staph Epi is MRSA widespread methicillin resistance, • Tx: vancomycin esp. in nosocomial infections. If • Can add gentamicin or rifampin for susceptibility results indicate a severe case methicillin-susceptible isolate, Native valve endocarditis vancomycin can be switched to • If methicillin sensitive nafcillin or oxacillin. • Tx: nafcillin Random mecA gene codes for methicillin resistance > altered PBP

686 Aldosterone MRBs (e.g. spironolactone, Spironolactone and Eplerenone Cardiovascular (CV) Pharmacology 3 antagonists eplerenone) improve survival in • Block deleterious effect of aldosterone on (Phar) pts w/ CHF and ↓ LV EF. They heart > regression of fibrosis and improved shouldn't be used in pts w/ ventricular remodeling hyperkalaemia or renal failure. • Improves survival in CHF with low EF • Adverse: gynecomastia spironolactone > eplerenone Mannitol • Used for high ICP and acute glaucoma • Can cause pulmonary edema 689 Primary Fenoldopam is a selective Malignant HTN Cardiovascular (CV) Pharmacology 14 hypertension peripheral dopamine-1 receptor • End organ damage: encephalopathy, (Phar) agonist. It is given IV to ↓ BP in papilledema, AKI HTE, especially in pts w/ renal Fenoldopam insufficiency. Fenoldopam causes • D1 agaonist arteriolar dilation, ↑ renal • D1 > Gs > arterial vasodilator (especially perfusion, and promotes diuresis renal vasodilation causing diuresis and and natriuresis. antriuresis) • Great for pt with AKI Hydralazine • Direct arteriolar vasodilator • Can cause reflex tach along with sodium and fluid retention Nitroglycerin • Large vein dilator Phenylephrine: alpha agonist 691 Angiotensin ARBs work by blocking ATII-1 RAAS Release Cardiovascular (CV) Pharmacology 1 receptor blockers receptors, inhib the effects of • Low Na to macula densa (Phar) ATII. This results in arterial • Beta1 sympathetic input vasodilation and ↓ aldosterone • Low BP secretion. The resulting fall in BP Ang 2 stimulates type 1 angiotensin 2 ↑ renin, ATI, and ATII lvls. ARBs receptors to vasoconstrict and to don't affect the activity of ACE, make/release aldosterone and therefore they don't affect ARBs (losartan) bradykinin degradation and don't • High renin, ang 1, ang 2, low aldo normal cause cough. bradykinin • Blocks vasoconstriction Beta1 Blocker • Low everything (decreases renin release) Aliskirin • High renin, low everything else Spironolactone • High everything 693 ACE inhibitors ACEIs can cause significant 1st- ACE inhibitor Cardiovascular (CV) Pharmacology 7 dose hypotension in pts w/ • First dose hypotension, especially those (Phar) volume depletion (eg, from who are volume depleted (on a diuretic) or diuretic use) or HF. To ↓ the risk have HF of 1st-dose hypotension, ACEI • Due to abrupt decrease in Ang 2 Thx should be initiated at low dosages.

697 Hyperkalemia ACEIs block the conversion of Drugs that cause hyperK Cardiovascular (CV) Pharmacology 1 AT-I to AT-Il, thereby ↓ • Non selective Beta blockers: no K into (Phar) vasoconstriction and aldosterone cells secretion. ↓ aldosterone leads to • ACE inhibitors: no aldosterone K retention, which can cause • ARBs: no aldosterone hyperkalemia, especially in pts w/ • K sparing diuretics renal insufficiency and in those • Digoxin: inhibit Na/K pump taking other Rx that ↑ K lvls (eg, • NSAIDs: reduced renin and aldosterone ARBs, MRBs). secretion Random Verpamil • Adverse: constipation, peripheral edema and bradycardia Indapamide (thiazide) • hyperGLUC Amlodipine • Reflex tachycardia and peripheral edema

711 Dyslipidemia Tx w/ statins causes hepatocytes Statins Cardiovascular (CV) Pharmacology 11 to ↑ their LDL receptor density, • Decreased production of cholesterol (Phar) leading to ↑ uptake of circulating causes upregulation of LDL receptor LDL. • Reduce risk of acute coronary event • Anti inflammatory property, improves endothelial dysfunction and stabilizes atherosclerotic plaques • Decrease TAG and minimal change of FFA • Biliary excretion of cholesterol decreases in pt on statin (decrease cholesterol production in liver) Fibrates decrease VLDL production 713 Antiplatelet GI mucosal injury and bleeding TIA Cardiovascular (CV) Pharmacology 1 therapy are the most common side effects • Must treat BP, hypercholesterolemia (Phar) of aspirin. These are due (statin) and anticoagulate (aspirin) primarily to COX-1 inhib, which • Aspirin can cause GI bleeding (PPI results in impaired PG-dependent will reduce the risk of ulcer formation) GI mucosal defence and ↓ platelet Sexual dysfunction aggregation. • SSRI, TCA, thiazide, spironolactone, clonidine Pioglitazone • PPARgamma activater • Increease risk of bladder cancer

778 Drug induced The 1° side effects of statins • Statin + fibrate = myopathy Cardiovascular (CV) Pharmacology 3 myopathy include myopathy and hepatitis. • Statin + ezetimibe = myopathy (less of a (Phar) Fibrates such as gemfibrozil can chance than when a statin is given with a impair hepatic clearance of fibrate) statins, ↑ the risk of severe • Bile acid sequestrant decrease statin GI myopathy. absorption Niacin • Hepatotoxic, flushing, hyperglycemia, 780 Drug induced liver Common AEs of HMG-CoA hiiStatin Cardiovascular (CV) Pharmacology 2 injury reductase inhibs (statins) include • Hepatotoxic and myopathy (Phar) muscle and liver tox. Hepatic • Test LFT transaminases should be checked Ezetimibe prior to initiating therapy and • Hepatotoxic with statin repeated if SSx of hepatic injury Niacin occur. • Decrease FA release, VLDL synthesis and HDL clearance • Flushing, hyperuricemia Fibrate • Activate PPARalpha and decrease VLDL synthesis • Myopathy and gallstones Omega 3 FA • Decreased VLDL and ApoB synthesis 781 Dyslipidemia Although low HDL concentration Main lipid lowering drug effect Cardiovascular (CV) Pharmacology 11 is a/w ↑ CV risk, the use of Rx to Statins (Phar) ↑ HDL lvls does not improve CV • Lowers LDL outcomes. HMG-CoA reductase • Best at decreasing risk of CAD inhibitors (statins) ↓ total Fibrates (activated PPARalpha > cholesterol and LDL lvls. Statins transcription factor for LPL) are the most effective lipid-↓ing • Lowers TAG Rx for 1° and 2° prevention of Bile acid sequesterants CV events, regardless of baseline • Lowers LDL but increases TAG lipid lvls. Niacin • Increases HDL • Ideally men over 40, women over 50 • Delivers cholesterol to liver via SRB1 Ezetimibe • Lowers LDL Omega 3 FA • Lowers TAG Exercise and weight loss • Lowers TAG

823 Myocardial Fibrinolytic Thx for acute STEMI MI Cardiovascular (CV) Pharmacology 18 infarction is a reasonable reperfusion • PCI and fibrinolysis (Phar) technique for pts w/ no c/i to • Tenecteplase, alteplase thrombolysis. Fibrinolytic agents • Risk of intrecerebral hemorrhage such as alteplase bind to fibrin in • Alteplase converts plasminogen to the thrombus (clot) and activate plasmin which hydrolyzes key bonds in the plasmin, which leads to fibrin matrix causing clot lysis thrombolysis. The most common Reperfusion of ischemic myocardium AEx of thrombolysis is • Arrhythmias, myocardial stunning hemorrhage (eg, GI, (prolonged but reversible contractile intracerebral). dysfunction) and myocyte death 898 Antiarrhythmic Adenosine causes SVT Cardiovascular (CV) Pharmacology 12 drugs hyperpolarization of the nodal • Adenosine is DOC (Phar) PM to briefly block conduction • Adverse: flushing, bronchospasm, AV through the AV node, and it is block and sense of death effective in the initial Tx of Amio PSVT. Common AEx include • SVT and V Tach flushing, chest burning (due to • Adverse: photodermatitis, blue/grey skin, bronchospasm), hypotension, and pulmonary fibrosis, hypo or hyperthyroid high-grade AV block. Verapamil • Constipation and gingivial hyperplasia

899 Antiarrhythmic Amiodarone (and other class III Antiarrhymthmics 1A Cardiovascular (CV) Pharmacology 12 drugs and class IA antiarrhythmic • Slows AP and prolongs APD 1B (Phar) agents) causes lengthening of the • No effect on AP cardiac AP, which MFx as QT • Shortens APD 1C interval prolongation on ECG. • Slows AP QT prolongation caused by • No change on APD amiodarone, in contrast to other 2 Rx, is a/w a very low risk of TdP. • Slows SA and AV node > prolong refractoriness 3 • No effect on AP • Prolongs APD • Amio: very low risk of torsades 4 • Slows SN and AV node > prolong refractoriness Adenosine • Increase K efflux > delays AV conduction Dig 900 Antiarrhythmic Lidocaine is a class IB MI Cardiovascular (CV) Pharmacology 12 drugs antiarrhythmic Rx that tends to • Arrhythmias within first 48hr (Phar) bind to inactivated Na channels • Amio is DOC and rapidly dissociates. As a • Lidocaine is 2nd line result, it is effective in Class 1b suppressing ventricular • Weakest Na channel blockers (fastest to tachyarrhythmias induced by dissociated) rapidly depolarizing and ischemic • Binds to inactivated Na channels (already myocardium. depol but not yet repol) • Ischemic myocardium has higher than normal RMP, dealying recovering (longer time in inactivate state) Digoxin • Increase parasympathetic on AV node Ibutilide • Class 3 • Prolonged QT Class 1a • Binds to active Na channels • Blocks K channels > prolonged QT

901 Antiarrhythmic Class III antiarrhythmic drugs Cardiomyocyte Cardiovascular (CV) Pharmacology 12 drugs (e.g. amiodarone, sotalol, • 0: Na (Phar) dofetilide) predominantly block • 1: K (some inward Na) K+ channels and inhib the • 2: Ca + K outward K+ currents during phase • 3: K 3 of the cardiac AP, thereby • 4: Na/K pump prolonging repol and total AP Class 3 duration. • Amiodarone, sotalol, dofetilide) inhibits K efflux Adenosine: binds A1 receptor, increased K efflux and decreased Ca influx 1A: quinidine, procainamide, dysopryramide 1B: lidocaine 1C: flecainide 948 Chronic cough Cough is a very well recognized ACE inhibitor Cardiovascular (CV) Pharmacology 1 AEx of ACEI Thx. Cough 2° to • Increased bradykinin, substance P and (Phar) ACEI Thx is Chx as dry, prostaglandins nonproductive, and persistent. • Bradykinin or substance P could The mechanism behind ACEI irritate the lung causing cough induced cough is accumulation of bradykinin, substance P, or prostaglandins. b/c ARBs do not affect ACE activity, they theoretically should not cause cough.

949 ACE inhibitors Angioedema is a rare and serious Angioedema Cardiovascular (CV) Pharmacology 7 AE of ACEI therapy. ACEI ↑ • C1 esterase inhibitor deficiency (Phar) bradykinin lvls, which ↑ vascular • ACE inhibitor permeability and lead to • High bradykinin for both angioedema. SSx include tongue, Ige dependent mast cell degranulation lips, or eyelid swelling and, less • Urticaria and pruritus frequently, laryngeal oedema and Ige INdependent mast cell degranulation difficulty breathing. ACEI should • Opiates, vancomycin be discontinued in affected pts.

1014 Dilated Anthracycline CTx agents (e.g. Doxorubicin (any rubicin) Cardiovascular (CV) Pharmacology 8 cardiomyopathy doxorubicin, daunorubicin) cause • Generate ROS for chemo > also (Phar) cardiotox mainly thru the cardiotoxic formation of anthracycline- • Swelling of sarcoplasmic reticulum is topoisomerase II DNA cleavage early sign > loss of cardiomyocytes complexes that affect healthy (myofibrillar dropout) cardiomyocytes. The cardiotox is • Dexrazoxane prevents DCM dependent on the cumulative dose Cor Pulmonale of anthracycline received, and it • Accentuation and splitting of S2, JVD, manifests as DCM. hepatomegaly Restrictive CM • Hemochromatosis, amyloidosis, sarcoidosis, radiation, Loefflers, endocardial fibroelastosis HCM • Beta myosin heavy chain mutation Pericardial fibrosis • Cardiac surgery, radiation theryapy or virus 1080 Peripheral SSx Mx PVD includes a graded Cilostazol Cardiovascular (CV) Pharmacology 4 vascular disease exercise program and cilostazol. • Used for peripheral claudication (Phar) Cilostazol is a PDEI that inhibs • PDE3 inhibitor > high cAMP and PKA platelet aggregation and acts as a • PKA inhibits platelet aggregation direct arterial vasodilator. Pts w/ (preventing plately shape PVD should also receive an change and degranulation) and causes antiplatelet agent (aspirin or vasodilation (preventing MLCK from clopidogrel) for 2° prevention of working) CAD and stroke. Abciximab • Ab against GP2b,3a Heparin • Potentiates antithrombin 3, inhibits thrombin and Xa Argatroban • Direct thrombin inhibitor • Use with HIT

1082 Myocardial In the fibrinolytic pathway, tPA • tPA, reteplase, tenecteplase are fibrin Cardiovascular (CV) Pharmacology 18 infarction converts plasminogen to plasmin, specific fibrinolytics Contraindications: (Phar) which then breaks down fibrin hemorrhagic stroke, ischemic strong within clot. The administration of a tPA 1 year, active internal bleeding, 180/100 or analogue (eg, alteplase, suspected dissecting aneurysm tenecteplase, streptokinase) Reperfusion can like to arrhythmias triggers fibrinolysis and can (usually benign) restore myocardial perfusion in pts w/ STEMI who cannot undergo timely PCI. 1118 Phosphodiesterase ANP, BNP, and NO activate ANP and BNP Cardiovascular (CV) Pharmacology 1 inhibitors guanylyl cyclase and ↑ conversion • Activate guanylyl cyclase > cGMP > (Phar) of GTP to cGMP. PDEIs (e.g. PKG > vasodilation sildenafil) ↓ the degradation of • NO activates cytosolic guanylyl cGMP. ↑ intracellular cGMP lvls cyclase lead to relaxation of vascular Silfenafil smooth muscle and vasodilation. • PDE 5 inhibitor > more cGMP • Severe hypotension if given with nitrates GABA • Ligant gated ion channel Vit D • Intracellular receptor that translocated to nucleus Insulin • Tyrosine kinase IL 2 • JAK/STAT, also MAPK and phosphoinositide 3• kinase 1164 Sympathomimetic Blanching of a vein into which • NE drip for septic shock cause can Cardiovascular (CV) Pharmacology 5 agents NE is being infused together w/ necrosis of skin (Phar) induration and pallor of the surrounding the IV site (vasoconstriction) tissues surrounding the IV site are so give an alpha1 blocker (phentolamine) signs of NE extravasation and Random resulting vasoconstriction. Tissue • Isoproterenol: beta2 agonist necrosis is best prevented by local injection of an α1 blocking drug, such as phentolamine.

1166 ACE inhibitors ACEIs and ARBs ↓ the risk of Cardiovascular (CV) Pharmacology 7 CKD in pts w/ HTN and DM. (Phar) ACEIs ↑ lvls of bradykinin and can cause nonproductive cough, an effect not see w/ ARBs.

1196 Myocardial β blockers are used in AMI to ↓ B1 blockade Cardiovascular (CV) Pharmacology 18 infarction morbidity and mortality by ↓ CO • Decreased HR, contractility, O2 (Phar) and myocardial O2 demand. Non- consumption, renin release cardioselective β blockers (e.g. • Adverse: worsen HF, brachycardia or propranolol, nadolol) can trigger heart block bronchospasm in pts w/ • Use in acute MI (improves long term underlying asthma and COPD. survival) Cardioselective β blockers (e.g. B2 blockade metoprolol) predominantly affect • Vasospasm, bronchoconstriction, β1 receptors and are preferred in decreased glycogenolysis and such pts. gluconeogenesis, decreased K into cells • Adverse: exacerbate COPD, worrse peripheral artery disease, hypoglycemia and hyperkalemia Carvedilol and labetalol • Combined alpha and beta blockers • Safe in COPD

1200 Anticoagulants Warfarin is an oral anticoagulant Warfarin Cardiovascular (CV) Pharmacology 8 that inhibits the carboxylation of • Monitor PT/INR (Phar) vitamin K-dependent coagulation • Use for A Fib, DVT, PE factors II, VII, IX, and X. It is • OD Tx: Vit K + FFP used in AF, DVT, and pulm TE. • Adverse: skin necrosis (especially with PT/INR should be monitored Protein C deficiency) regularly during Tx w/ warfarin. Hep aPTT is used for monitoring • Monitor PTT UFH. • OD Tx: protamine

1252 Primary Direct arteriolar vasodilators ↓ BP Hydralazine, Minoxidil Cardiovascular (CV) Pharmacology 14 hypertension but trigger reflex sympathetic • Arteriolar vasodilation (Phar) activation and stimulate the RAA • Activates sympathetic nerve system > axis. This results in tachycardia tachycardia, increased contractility, CO and edema. To counteract such and RAAS release (retain water and salt) compensatory effects, these • Usually given with sympatholytics and agents are often given in diuretics combination w/ sympatholytics Beta blockers and diuretics. • Cold feet and hands 1342 Orthostatic Orthostatic hypotension is a Orthostatic hypotension Cardiovascular (CV) Pharmacology 1 hypotension frequent cause of light- • Decrease in systolic > 20 or diastolic > 10 (Phar) headedness and syncope and is with standing defined as a ↓ in SBP Normal sequence upon standing (>20mmHg) or DBP (>10mmHg) • Low VR on standing from the supine • Low CO position. Rx (α1-adrenergic • Drop in BP cause baroreceptor reflex antagonists, diuretics), volume • Sympathetic response > alpha1 causing depletion, and autonomic dysfxn vasoconstriction and beta1 causing are common causes of orthostatic increased HR and contractility hypotension. Orthostatic hypotension causes • Alpha1 blockers • Diuretics • Diabetes • Parkinsons • Hyperglycemia

1343 Alpha agonists α-adrenergic agonists ↑ SBP and Alpha1 Agonist Cardiovascular (CV) Pharmacology 1 DBP by stimulating α1- • Vasoconstriction (Phar) adrenoreceptors in the vascular • Mydriasis walls, causing vasoconstriction. • Initial increased contractility (countered The ↑ systemic BP then causes a by increased reflex vagal tone > inhibit SA reflexive ↑ in vagal tone, node, decrease AV node conduction, and resulting in ↓ HR and slowed AV decreased contractility) node conduction. • Increase internal urethral sphincter tone Alpha2 Agonist • Decreased BP • Decreaesd IOP • Decreased lipolysis • Decreased NE release • Increased platelet aggregation

1344 Cardiogenic shock Dobutamine is a β adrenergic Dobutamine Cardiovascular (CV) Pharmacology 1 agonist w/ predominant activity • B1 agonist (Phar) on β1 receptors. It causes an ↑ in • Used in refractory HF with severe LV HR and cardiac contractility, dysfunction and cardiogenic shock leading to an ↑ in myocardial O2 • B1: Gs > positive ionotropy, positive consumption. chronotropy, mild vasodilation • Increase myocardial oxygen consumption • Will actually decrease PCWP due to increased CO Caught between a rock and a hard place > stressing the heart is bad but the pt is in cardiogenic shock

1364 Sympathomimetic EPI ↑ SBP (α1 + β1) and HR Phentolamine Cardiovascular (CV) Pharmacology 5 agents (β1), and either ↑ or ↓ DBP • Non specific Alpha blocker (Phar) depending on the dose (either α1 Phenylephrine or β2 predominates). PreTx w/ • Selective alpha agonist propranolol eliminates the β Isoproterenol effects of EPI (vasodilation and • Non selective Beta agonist tachycardia), leaving only the α Atropine effect (vasoconstriction). • Muscarinic antagonist

1367 Sympathomimetic NE stim cardiac β1 Norepi Cardiovascular (CV) Pharmacology 5 agents adrenoceptors, which ↑ cAMP • Alpha1 > Alpha2 > Beta1 (Phar) concentration w/i cardiac • Vasoconstrction via Alpha1 (Gq) myocytes and leads to ↑ • Increase HR and contractility via Beta1 contractility, conduction, and HR. (Gs) Peripheral vasoconstriction • HR usually goes down due to occurs via stim of α1 baroreceptor reflex in response in increase adrenoreceptors in vascular BP smooth muscle cells and Random activation of an IP3 signalling B2 in vascular SM: Gs resulting in pathway. vasodilation 1444 Beta blocker Pts who have OD'd on β blockers Beta Blocker OD Cardiovascular (CV) Pharmacology 1 poisoning should be Tx w/ glucagon, which • Decreased myocardial contractility, (Phar) ↑ HR and contractility bradycardia, AV block independent of adrenergic • Tx: glucoagon > increase cAMP > receptors. Glucagon activates increase intracellular Ca > increase HR GPCRs on cardiac myocytes, and contractility causing activation of adenylate cyclase and ↑ intracellular cAMP. The result is Ca2+ release from intracellular stores and ↑ SA node firing.

1505 SLE Procainamide and hydralazine DILE Cardiovascular (CV) Pharmacology 7 have the highest risk of causing • Hydralazine (Phar) DILE, which is Chx by the • Procainamide development of lupus-like SSx in • Isoniazid addition to (+) ANA and anti- • Minocycline histone Abs. Unlike w/ SLE, anti- • Quinidine dsDNA Abs are rarely seen. • Slow acetylators are at a greater risk for DILE Amio adverse • Thyroid dysfunction, lung fibrosis, liver toxic, blue/grey discoloration, photosensitivity Lidocaine adverse • tremor, drowsiness, change in mental status, rarely seizures Verapamil adverse • Heart block, constipation, gingival hyperplasia Adenosine adverse 1506 Antiarrhythmic Sotalol has both β adrenergic- Paroxysmal A Fib Cardiovascular (CV) Pharmacology 12 drugs blocking and class III • Rate control: class 2 and 4 (Phar) antiarrhythmic (K+ channel- • Rhythm control: class 1 and 3 blocking) properties and is • Prolonged QT: class 1a and 3 occasionally used in Tx of AF. Diltiazem Major AEs of sotalol include • Prolonged PR interval bradycardia, proarrhythmia, and Metoprolol most commonly TdP due to QT • Decreased HR and contractility interval prolongation. Ranolazine • Inhibts late phase inward Na flow • Does not change HR or contractility, decrease O2 demand 1507 Antiarrhythmic Class III antiarrhythmic Rx • Dofetilide: Class 3 antiarrhythmic Cardiovascular (CV) Pharmacology 12 drugs (amiodarone, sotalol, dofetilide) • K channel > internal reflectifer (Phar) predominantly block K channels Verapamil and inhibit the outward K • L type Ca channels currents during phase 3 of the cardiac AP, thereby prolonging repolarization and total AP duration. 1508 Antiarrhythmic Class IC antiarrhythmic agents • QRS complex = Ventricular Cardiovascular (CV) Pharmacology 12 drugs (flecainide) block the fast Na+ depolarization (phase 0) = Na entering cell (Phar) channels responsible for = Class 1 antiarrhythmics ventricular depol (phase 0), Clase 1 prolonging QRS duration w/ little • 1a: prolong QRS and QT effect on the QT interval. Class • 1b: no change in QRS or QT IA and class III agents cause the • 1c: prolongs QRS and no change in QT most QT prolongation.

1509 Antiarrhythmic The class IA antiarrhythmics Class 1 Na blockers Cardiovascular (CV) Pharmacology 12 drugs (quinidine, procainamide, and • Moderate K channel blocking (Phar) disopyramide) are Na+ channel- 1A blocking agents that depress • Quinidine, Procainamide, Disopyramide phase 0 depol. They also prolong • Prolong AP, ERP, and QT repol due to moderate K+ channel-1B blocking activity, ↑ AP duration • Lidocaine, mexiletine in cardiac myocytes. • Shortens AP 1C • Flecainide, propafenome • No change on AP but prolongs ERP Use dependence C > A > B Adenosine • Increase K efflux Dig • Increa PNS at AV node 1565 Chronic heart Neurohormones (e.g. NE, ATII, CHF Cardiovascular (CV) Pharmacology 12 failure and aldosterone) play a large role • ACE inhibitor, ARBs, Beta blockers and (Phar) in the deleterious cardiac Spironolactone are only drugs to decrease remodelling that occurs in HF w/ mortality rate ↓ EF. ACEIs, ARBs, MRBs, and β • Prevent deleterious cardiac blockers ↓ mortality in these pts remodeling by ↓ neurohormonal-mediated cardiac remodelling.

1780 Aging Digoxin is a cardiac glycoside Digoxin toxicity Cardiovascular (CV) Pharmacology 8 that's predominantly cleared by • GI issues, visual changes (Phar) the kidneys. Elderly pts typically • Increse risk with age due to decreased exhibit age-related renal renal function (will see rise in Cr) insufficiency, even in the • Lean muscle mass is also important presence of normal creatinine consideration (not as important as renal lvls. The dose of digoxin must be function) ↓ in these pts to prevent tox.

1828 Coronary artery Clopidogrel irreversibly blocks Stable angina Cardiovascular (CV) Pharmacology 4 disease the P2Y12 component of ADP • Tx: aspirin or clopidogrel for aspirin (Phar) receptors on the platelet surface intolerant pt and prevents platelet aggregation. Apixaban Clopidogrel is as effective as • Direct Xa inhibitor aspirin in the prevention of CV • Prophylaxis for DVT, not CAD events in pts w/ coronary heart Cilostazol disease. • Phosphodiesterase inhibitor • Use: claudication Eptifibatide • Gp2b/3a inhibitor NSAIDs and Celecoxib 1836 Beta 2 agonists Isoproterenol is a β1 and β2 Adrenergic agonist Cardiovascular (CV) Pharmacology 1 adrenergic receptor agonist that Alpha1 (Phar) causes ↑ myocardial contractility • Epi, NE, phenylephrine and ↓ SVR. Beta1 • Epi, Dopamine, Dobutamine, Isoproterenol Beta2 • Isoproterenol, terbutaline Isoproterenol • Non selective Beta agonist • Increase cradiac contractility and HR, vasodilate, uterine relaxation Random Adenosine 1944 Chronic heart Rx that have been shown to HF Cardiovascular (CV) Pharmacology 12 failure improve long-term survival in pts • Carvedilol, metoprolol, ACE inhibitors, (Phar) w/ HF due to LV systolic dysfxn ARBs, and aldosterone antagonists only include β blockers, ACEIs, medications to prove decreased mortality ARBs, and aldosterone Amio antagonists. • SVT and ventricular arrhythmias 1947 Dose response Phenoxybenzamine is an Irreversible Competitive Antagonist or Cardiovascular (CV) Pharmacology 4 curves irreversible α1 and α2 adrenergic Noncompetitive Antagonist (Phar) antagonist that effectively ↓ the • Same Km arterial vasoconstriction induced • Lower Vmax by NE. B/c phenoxybenzamine is • Phenoxybenzamine: irreversible an irreversible antagonist, even Atropine, labetalol, phentolamine and very high concentrations of NE, propanolol such as those seen in • All reversible pheochromocytoma, can't overcome its effects.

1948 Primary β blockers inhibit release of renin B1 blockers Cardiovascular (CV) Pharmacology 14 hypertension from renal juxtaglomerular cells • Decrease mycardial contractility and HR (Phar) through antagonism of β1 • Decrease renin release receptors on these cells. • Do not effect circulating level of Inhibition of renin release catecholamines prevents activation of the RAA pathway, which results in ↓ vasoconstriction and ↓ renal Na and water retention. 2002 Primary TZDs ↑ serum Ca, uric acid, Glc, Thiazide adverse and mechanism Cardiovascular (CV) Pharmacology 14 hypertension cholesterol, and triglyceride lvls. • HypoNa: inhibits Na/Cl in DCT (Phar) They ↓ serum Na, K, and Mg lvls. • HypoK: compensatory rise in renin and aldo • HyperCa: increased reabsorption in DCT • HypoMg: decreased reabsorption in DCT • Hyperglycemia and hypercholesterolemia: decreased insulin release and increased insulin resistance • Hyperuricemia: increase reabsoprtion in PCT

2005 Aldosterone All diuretics except for the K- Pt with HF and hypokalemia Cardiovascular (CV) Pharmacology 3 antagonists sparing class cause K loss by ↑ • Add spironolactone to spare K in late (Phar) Na delivery to the late distal DCT and early collecting duct tubule and cortical collecting • Causes downregulation of ENaC and duct, where aldosterone-induced Na/K pumps Na reabsorption occurs at the • Amiloride and triamterene block ENaC expense of K. K-sparing diuretics on principal cells (eg, spironolactone, amiloride) act on the late distal tubule and cortical collecting duct to antagonize the effects of aldosterone.

2006 Antiarrhythmic β blockers ↓ AV nodal Beta Blockers and non DHP CCB Cardiovascular (CV) Pharmacology 12 drugs conduction, leading to an ↑ AV • Prolong PR interval (Phar) nodal refractory period. This T wave inversion correlates to PR interval • Myocardial ischemia prolongation on an ECG. Prlonged QT • Class 1a and 3 • Macrolide and fluorquinolones • Typical and Atypical antipsychotics • TCA • Ondonsetron

6811 Septic shock Phenylephrine is a selective α1 Cardiovascular (CV) Pharmacology 6 adrenergic receptor agonist that ↑ (Phar) PVR and SBP and ↓ PP and HR.

7640 Torsades de TdP refers to polymorphic Prolonged QT Cardiovascular (CV) Pharmacology 1 pointes ventricular tachycardia that • Hypokalemia, hypomagnesemia (Phar) occurs in the setting of a • Class 1A and 3 antiarrhythmics congenital or acquired prolonged • Macrolides and fluoroquinolones QT interval. TdP is most • Methadone commonly precipitated by Rx that • Antipsychotics prolong the QT interval such as Class 2 and 4 antiarrhythmics certain antiarrhythmics (sotalol, • Prolong PR interval quinidine), antipsychotics (haloperidol), and Abx (macrolides, fluoroquinolones).

8289 Beta blockers β1 adrenergic receptors are found Beta1 antagonist Cardiovascular (CV) Pharmacology 3 in cardiac tissue and on renal • Decreaed cardiac cAMP (Phar) JGA cells, but not in vascular • Decreased JG cell cAMP smooth muscle. Selective • No change is vascular smooth muscle blockade of the β1 receptor (e.g. cAMP w/ atenolol) leads to ↓ cAMP lvls • If Beta2 antagonist: decreased in cardiac and renal tissue w/o vascular SM cAMP significantly affecting cAMP lvls in vascular smooth muscle.

8291 Pharmacokinetics Clearance (CL) determines the Pharmacokinetics Cardiovascular (CV) Pharmacology 1 dose rate required to maintain a • Half life = Vd x 0.7/ CL (Phar) steady-state plasma concentration • Maintenance dose = Steady state x CL x (Cpss): #6nov dose interveral/ Bioavailability Maintenance dose = Cpss x CL / • Loading dose = Vd x Steady state/ [Bioavailability fraction] Bioavailability The bioavailability fraction = 1 if administered IV. 8869 Antiarrhythmic Class 10 antiarrhythmics such as QRS typically slightly decreaes with Cardiovascular (CV) Pharmacology 12 drugs flecainide are potent sodium exercise (Phar) channel blockers that have Flecainide (1C) increased effect at faster heart • Acvidly binds to Na channels responsible rates (use-dependence). This for phase 0 > causing QRS prolongation makes them more effective at (especially with use) treating tachyarrhythmias, but can Use dependence C>A>B also cause prolonged QRS Dofetilide duration (a proarrhythmic effect) • Class 3 at higher heart rates. • Prolongs QT • Reverse dose dependence > slower the HR the longer the QT 11836 Nitrates Nitrates are primarily Nitrates Cardiovascular (CV) Pharmacology 7 venodilators and increase • Venous dilation (increased capacitance) (Phar) peripheral venous capacitance, • Decreased LV end diastolic pressure thereby reducing cardiac preload (decreased preload) and left ventricular end-diastolic • Decreased systemic vascular resistance volume and pressure. Nitrates (modest arteriolar dilator) also have a modest effect on arteriolar dilation and cause a decrease in systemic vascular resistance and cardiac afterload.

11844 Dyslipidemia Fibrates lower TG lvls by • TAG > 500: use fibrates Fibrates Cardiovascular (CV) Pharmacology 11 activating PPAR-α, which leads • Activate PPARalpha causes decresed (Phar) to ↓ hepatic VLDL production VLDL production and upregulates LPL and ↑ LPL activity. Fish oil • Omega 3 FA: decrease VLDL supplements containing high production, inhibits apolipoprotein B concentrations of ω-3 FAs ↓ TGs synthesis by ↓ production of VLDL and • Proprotein convertase subtilisin kexin 9 apoB. (PCSK9) inhibitor: Ab that reduces LDL receptor degradation 11925 Sympathomimetic Dobutamine is a β-adrenergic Dobutamine Cardiovascular (CV) Pharmacology 5 agents agonist w/ predominant activity • Predominant Beta1 agonist, weak Beta2 (Phar) on β1 receptors and weak activity and Alpha1 agonist on β2 and α receptors. • Weak vasodilation Stimulation of β2 receptors leads Milrinone to an ↑ production of cAMP and ↑ • Phosphodiesterase inhibitor cytosolic Ca concentration. This Ranolazine facilitates the interaction b/w • Inhibits late phase inward Na channels in actin and myosin, resulting in ↑ ischemic myocardium > reduced Na/Ca myocardial contractility. exchange > decrease O2 myocardial demand

14780 Bradycardia Conduction impairment is Cardiovascular (CV) Pharmacology 1 common w/ acute inferior wall (Phar) MI. Sinus bradycardia often occurs due to nodal ischaemia and an ↑ in vagal tone triggered by infarction of myocardial tissue; the ↑ vagal tone can be counteracted by the antichol effects of atropine.

14844 Dilated Trastuzumab is a mAb that blocks Cardiovascular (CV) Pharmacology 8 cardiomyopathy HER2 to disrupt malignant cell (Phar) signalling and encourage apoptosis. B/c HER2 helps preserve cardiomyocyte fxn, trastuzumab can cause cardiotox that manifests as a ↓ in myocardial contractility w/o cardiomyocyte destruction or myocardial fibrosis.

15515 Hypertrophic Many pts w/ HCM have poor Cardiovascular (CV) Pharmacology 9 cardiomyopathy cardiac reserve (e.g. exercise (Phar) intolerance) due to LVOT obstruction. This outflow obstruction is worsened by ↓ LV blood volume. β blockers ↓ HR and LV contractility to ↑ LV blood volume, ↓ LVOT obstruction, and improve SSx. 144 Calcium channel Contraction initiation in cardiac Cardiac myocyte Cardiovascular (CV) Physiology (Phys) 3 blocker and SMCs is dependent on • Depolarization of L type Ca channel on extracellular Ca influx through L- plasma membrane allows Ca influx > Ca type Ca channels, which can be binds to RyR2 on SR > Ca released prevented by CCBs (eg, • Vascular SM have similar squence verapamil). Skeletal muscle is after initial depolarization; Ca Calmodulin resistant to CCBs, as Ca release facilitate actin myosin interaction by the SR is triggered by a Skeletal muscle mechanical interaction b/w L-type • L type Ca channel directly interact with and RyR Ca channels. RyR1 of SR > there is no influx of Ca (physical interaction triggers Ca from SR to be released) • This explains why verapamil has no effect of skeletal muscles

157 Natriuretic ANP and BNP are released from Nesiritide Cardiovascular (CV) Physiology (Phys) 1 peptides the atria and ventricles, • Recombinant BNP respectively, in response to • Used in decompensated CHF myocardial wall stretch due to • Activated GC > cGMP > vasodilation and intravascular volume expansion. decreaed Na reabsorption in kidneys > These endogenous hormones diuresis promote ↑ GFR, natriuresis. and TGFbeta diuresis. • Cell cycle arrest (used as tumor suppressor), angiogenesis, and fibroblast stimulation Bradykinin • Vasodilation of art, venodilation of veins and pain • Metabolized by ACE Endothelin and Ang 2 • Vasoconstrictors • Endothelin possibly released by Ang 2 183 Coronary blood During ventricular systole, the • Right ventricle: relatively constant blood Cardiovascular (CV) Physiology (Phys) 9 flow coronary vessels supplying the flow rate throughout cardiac cycle LV are compressed by the surrounding muscle. As a result, the majority of LV blood flow occurs during diastole. The systolic ↓ in coronary blood flow is greatest in the subendocardial region, making this portion of the LV most prone to ischemia and infarction.

205 Tetralogy of Fallot In pts w/ TOF, squatting during a TOF Cardiovascular (CV) Physiology (Phys) 3 Tet spell ↑ SVR and ↓ right-to- • Right to left shunt > cyanosis (tet spell) > left shunting, thereby ↑ pulm squating increases afterload (SVR) blood flow and improving reversing the shunt making it left to right O2ation status. improving cyanosis

456 Primary Isolated systolic HTN (ISH; SBP Isolated Systolic HTN Cardiovascular (CV) Physiology (Phys) 14 hypertension >140mmHg w/ DBP <90mmHg) • Systolic > 140 is due to age-related stiffness and • Diastolic < 90 ↓ in compliance of the aorta and • Caused by increased arterial stiffness, major peri arteries. increase CO due to AR, anemia or hyperthyroid Decreased CO • Low systolic, diastolic and MAP Decreased pulmonary residue volume • Due to destruction of alveolar walls Increased sympathetic tone or renal art stenosis • All BP variables go up

951 Coronary blood The high systolic intraventricular Myocardial perfusion during diastole Cardiovascular (CV) Physiology (Phys) 9 flow pressure and wall stress of the LV (decreased during exercise) prevent myocardial perfusion • Adenosine and NO are primary during systole; therefore, the vasodilators Contraction during systole majority of LV myocardial increase vornary pressure preventing blood perfusion occurs during diastole. flow > highest at subendocardial region Shorter duration of diastole is the • Diastolic pressure does not change during major limiting factor for coronary exercise (TPR blood supply to the LV decreases) myocardium during periods of tachycardia (e.g. exercise). 1510 Cardiac An ↑ in effective SV or EF is Cardiovascular (CV) Physiology (Phys) 6 physiology depicted on the LV pressure- volume relationship by widening of the loop w/ a shift in the isovolumic relaxation line to the left (indicating less residual blood volume in the ventricle at end- systole).

1511 Cardiac Pressure-volume loops represent Cardiac loop Cardiovascular (CV) Physiology (Phys) 6 physiology the relationship b/w pressure and • Moving R verticle line of graph to the R volume in the LV during systole means increased preload and diastole. An ↑ in the • Moving arc up means increased afterload circulating volume ↑ preload (LV (decreases SV) EDV) and causes a rightward • Moving R ventricle line of graph to the L widening of the pressure-volume means decreaed preload loop. • Moving L verticle line of graph to the L means increased contractility (dobutamine) • Moving L verticle line of graph to the R means decreased contractility (MI)

1512 Hypovolemic Intravenous fluids increase the RAAS Cardiovascular (CV) Physiology (Phys) 1 shock intravascular and left ventricular • Increases HR and contractility end-diastolic volumes. The • Arteriolar bed constriction (maintains end increase in preload stretches the organ perfusion + shunts blood to vital myocardium and increases the organs) end-diastolic sarcomere length, • Venous constriction to increase preload leading to an increase in stroke • Water retention volume and cardiac output by the Giving saline in hypovolemic shock Frank-Starling mechanism. • Increase end diastolic sarcomere length > increase contractility • Decreae sympathetic NS > decrease HR • Decrease RAAS • Decrease TPR and cardiac contractility VELOCITY

1513 Cardiac The cardiac AP conduction speed Cardiac Conduction Cardiovascular (CV) Physiology (Phys) 6 physiology is slowest in the AV node and • Purkinje > atrial muscle > ventricular fastest in the Purkinje system. muscle > AV node Conduction speed of the atrial muscle is faster than that of the ventricular muscle.

1515 Carotid Carotid sinus massage leads to an SVT Cardiovascular (CV) Physiology (Phys) 1 baroreceptors ↑ in PSNS tone causing • Vagal maneuver: carotid massage, temporary inhib of SA node valsalva, cold water immersion activity, slowing of conduction Carotid massage thru the AV node, and • Increased pressure > increased firing prolongation of the AV node carried by CN 9 > increased refractory period. It's a useful parasympathetic via CN 10 and decreased vagal manoeuvre for termination sympathetics (decrease SA node firing, of PSVT. slows AV conduction and prolongs refractory period) • As pressure goes up, firing goes up

1516 Coronary blood Coronary autoregulation allows Heart extractions 70+% of O2 from the Cardiovascular (CV) Physiology (Phys) 9 flow coronary blood flow to be 1arily blood. In times of increased O2 demand, driven by myocardial O2 demand vasodialtion is the only way to increase over a wide range of perfusion O2 to the heart (mostly by local pressures (60-140mmHg). It's metabolites mostly accomplished by • Adenosine and NO are the most imporant alterations in vascular resistance • eNOS makes NO from Arg via release of adenosine and NO • NO release is stimulated by ACh, NE, 5• in response to myocardial HT, ADP, thrombin, histamine, bradykinin hypoxia. and endothelin • NO is also released in response to pulsatile stretch and flow shear stress (major regulator of flow mediated vasodilation) Beta2: NOT stimulated by NE 1517 Mitral stenosis The classic cardiac auscultation MS Cardiovascular (CV) Physiology (Phys) 7 findings in MV stenosis include • Opening snap with diastolic rumble an OS f/b a diastolic rumbling • Being shortly after S2 murmur that is heard best over the • Opening snap due to abrupt halt of leaflet apex of the heart. On the motion during mitral valve opening due to ventricular pressure-volume loop, fusion of the mitral valve leaflet tips MV opening occurs at the point • The more severe the stenosis the b/w isovolumetric relaxation and closer to S2 diastolic filling.

1518 AV fistula and AV shunts can be congenital or AV fistula Cardiovascular (CV) Physiology (Phys) 1 P/V curves acquired; acquired forms can • Pulsatile mass with thrill on palpation result from medical interventions (constant bruit) or penetrating injuries. AV shunts • Increase preload, increase CO, decrease ↑ preload and ↓ afterload by afterload routing blood directly from the arterial system to the venous system, bypassing the arterioles. High-volume AV shunts can eventually result in high-output cardiac failure.

1528 Pulmonary blood The circulatory system is a The pulmonary and systemic Cardiovascular (CV) Physiology (Phys) 2 flow continuous circuit, and therefore circulations have the same blood flow the volume output of the left per minutes ventricle must closely match the • The only exception is the bronchial output of the right ventricle. This circuit, which supplies that lungs and balance is necessary to maintain drains to the left atrium (technically continuous blood flow through increasing the body and exists both at rest systemic output more than pulmonary but and during exercise. less than 5%)

1529 Cardiac The Fick principle can be applied • CO = SV x HR Cardiovascular (CV) Physiology (Phys) 6 physiology to calculate CO using the rate of • CO = rate of O2 consumption/ Art O2 consumption and the AV O2 Venous O2 difference MAP = CO x TPR content difference: • Blood O2 content = (O2 bind capacity x CO = rate of O2 consumption / % sat) + dissolved O2 AV O2 content difference

1530 LV volume and Ventricular pressure and volume Cardiovascular (CV) Physiology (Phys) 1 pressure curves allow 1 to ID the phases of the cardiac cycle and to determine the exact time of opening and closure of the cardiac valves. The AV opens when LVP exceeds the central aortic pressure at the end of isovolumetric contraction.

1531 Cardiac In cardiac pacemaker cells, phase Cardiovascular (CV) Physiology (Phys) 6 physiology 0 depol is mediated by an inward flux of Ca2+. This differs from phase 0 of cardiomyocytes and Purkinje cells, which results from an inward Na+ current.

1557 Heart sounds The 3rd heart sound (S3) is a low- CHF Cardiovascular (CV) Physiology (Phys) 1 frequency sound occurring during • S3 due to big floppy heart early diastole after S2. LV gallops • S3 is the due to blood hitting ventricular (S3 a/o S4) are best heard w/ the walls bell of the stethoscope over the • Normal is kids and young adults cardiac apex while the pt is in the • If heard over 40, this ventricualr dilation left lateral decubitus position at • Best heard with bell of stethoscope over end expiration. cardiac apex with pt in L lat decubitus position at END EXPIRATION Random Amily nitrite: decreased VR Furosemide: decreased end systolic ventricular volume Valsalva and abrupt standing: decreased VR 1589 Physical exercise The cardioresp response to With exercise Cardiovascular (CV) Physiology (Phys) 2 exercise includes ↑ HR, CO, and • Normal arterial O2 and CO2 RR in order to balance the ↑ total • Decreased venous O2 and increased CO2 tissue O2 consumption and CO2 production. These coordinated adaptations result in relatively constant ABG values whereas venous O2 is ↓ and venous CO2 is ↑.

1591 Mitral stenosis Under normal circumstances, • Swan Ganz catheter: PCWP = LA Cardiovascular (CV) Physiology (Phys) 7 PCWP closely reflects LA and pressure LV EDP. MS leads to an ↑ in the MS LA pressure that is reflected as ↑ • High LA pressure PCWP during pulm artery • Normal ventricular pressure catheterization. LV filling may be AS normal, resulting in an ↑ pressure • High LVEDP and PCWP gradient b/w the LA and LV Tamponade during diastole. • Equalization of pressure in all chambers (elevated) Dilated cardiomyopathy • Systolic dysfunction > high LVEDP and PCWP Restrictive cardiomyopathy • Diastolic dysfunction > high LVEDP and 1609 Carotid sinus The carotid sinus is a dilation of Carotid Body Baroreceptor Cardiovascular (CV) Physiology (Phys) 1 hypersensitivity the ICA located just above the • Decreased BP > decreased firing via CN bifurcation of the CCA. The 9 (Hering nerve which synapses on carotid sinus reflex has an medulla) > increased sympathetic stim afferent limb that arises from the • High BP > high firing via CN 9 > baroreceptors in the carotid sinus increase parasympathetic stim via CN 10 and travels to the vagal nucleus Aortic Arch Baroreceptor and medullary centers via the • CN 10 is afferent limb glossopharyngeal nerve (CN IX); • More responsive to high BP than low BP the efferent limb carries (high pressure system) parasympathetic impulses via the vagus nerve (CN X).

1621 Renal artery Blood flow is directly • Flow = (P1 P2/ viscosity x L) x r^4 Cardiovascular (CV) Physiology (Phys) 9 stenosis proportional to the vessel radius • If you decrease the radius by 2 > flow raised to the fourth power. will increase by 16 Resistance to blood flow is inversely proportional to the vessel radius raised to the fourth power. 1622 Physical exercise Exercising muscles can receive Exercise Cardiovascular (CV) Physiology (Phys) 2 up to 85% of the total CO during • Increased sympathetic stimulation > periods of strenuous activity. increase HR, SV, CO, LV diastolic Although sympathetic discharge volume, LV diastolic P, pulmonary artery during exercise causes ↑ CO and systolic P, contraction of all arterioles splanchnic vasoconstriction, besides the working muscles there's only a modest ↑ in mean causing increase systolic BP, BP as vasodilation w/i active DECREASED systemic vascular resistance skeletal muscles significantly ↓ • Muscles release adenosine, K, ATP, the total SVR. CO2 and lactate that cause vasodilation

1624 Cardiac output and MI causes a sharp ↓ in CO due to CO vs VR grpah Cardiovascular (CV) Physiology (Phys) 2 venous return loss of fxn of a zone of • When VR crosses x axis: mean systemic myocardium. On a cardiac fxn filling pressure (measure of degree of curve, MI would ↓ both the slope filling of the circulatory system relative to and the maximal height of the the circulatory capacity) line. • Change in blood volume to move x axis intercept • Increase TPR will shift VR curve down and decrease CO • Decreased TPR will shift VR curve up and increase CO • Decreased contractility will only shift CO down • Chronic anemia will in contractility and thus CO • Anaphylaxis: increase contractility but decrease VR 1625 Cardiac output and A chronic AV shunt would ↑ CO • Cardiovascular (CV) Physiology (Phys) 2 venous return b/c of ↑ sympathetic stimulation • Will see an increase in cardiac out and to the heart, ↓ TPR, and ↑ venous decreased TPR return. It would also cause the • On graph > Increased contractility, venous return curve to shift to the increased venous return, increased CO and right b/c the circulating blood same right atrial pressure (end diastolic volume is ↑ through renal volume) retention of fluids and b/c venous • Acute would be the same but venous pooling is ↓ by the ↑ sympathetic return would cross x axis at same place as tone. normal Phenylephrine • Increased TPR > decreased CO (higher afterload and less preload) Anaphylaxis • Significant drop in venous return

1652 Diastolic Na nitroprusside is a short-acting • Cardiovascular (CV) Physiology (Phys) 4 dysfunction agent that causes balanced • Arterial and Venous dilation > will see vasodilation of the veins and drop in afterload and preload arteries to ↓ both LV preload and Increase contractility afterload. The balanced • Larger SV > less LV end systolic vol vasodilation allows for Nitroglycerin maintenance of SV and CO at a ↓ • Venous dilation > decreased preload LV pressure (↓ cardiac work).

1653 Cardiac pressure Right-sided pressures in the heart Pressure readings Cardiovascular (CV) Physiology (Phys) 1 range are lower than left-sided • SVC and RA: 1 6mmHg RV: 25/2 pressures due to lower resistance • Pulmonary artery: 25/10 in the pulm vasculature. RV • Pulmonary artery wedge and LA: 812 diastolic pressure is similar to LV: 120/10 RA/CVP (1-6 mm Hg), whereas pulm artery diastolic pressure is slightly higher (6-12 mm Hg) due to resistance to flow in the pulm circulation.

1661 Aortic AR causes an ↑ in total SV w/ Aortic Regurg Cardiovascular (CV) Physiology (Phys) 8 regurgitation abrupt distension and rapid falloff • Eccentric hypertrophy with increeased of peripheral arterial pulses, LV end diastolic volumes resulting in a wide PP. This leads • Blowing decrescendo diastolic murmur to bounding peripheral pulses and • Hyperdynamic pulses (wide PP, bound head bobbing w/ each heartbeat. femoral and carotid pulses, head bobbing) AS • Pulsus parvus et tardus Coarctation • HTN in upper, diminshed and delayed pulses in lower

1782 Pericardial PP refers to an exaggerated drop Cardiac tamponase Cardiovascular (CV) Physiology (Phys) 1 effusion (>10 mm Hg) in SBP during • Hypotension, JVD, muffled heart sounds inspiration. It is most commonly • Electical alternans seen in pts w/ CT but can also • Pulsus paradoxus (pericardial fluid limits occur in severe asthma, COPD, RV expansion exacerbated by inspiration, hypovolemic shock, and pushes septum into LV decreaed SV) constrictive pericarditis. Pulsus alternans: variation in pulse amplitude due to LV dysfunction Dicrotic pulse: severe systolic dysfunction and high TPR Hyperkinetic pulse: aortic regurg, AV fistula or thyrotoxicosis Pulsus parvus et tardus: fixed LV outflow tract obstruction (AS) 1931 Muscle structure Ca efflux from cardiac cells prior Cardiac contraction Cardiovascular (CV) Physiology (Phys) 1 and physiology to relaxation is primarily • Voltage dependent (L type) Ca2+ mediated via an Na/Ca exchange channels open during phase 2 > Ca enters pump and SR Ca-ATPase pump. > Ryanodine receptor release Ca from SR > positive feedback Cardiac relaxation • 3 Na/1 Ca exchange pump and SERCA (ATP pump) remove Ca from cytoplasm and return it to the SR Calmodulin • Excitation contraction coupling in smooth muscles

1973 Antiarrhythmic Class IV antiarrhythmics (eg, Cardiac Node AP Cardiovascular (CV) Physiology (Phys) 12 drugs verapamil, diltiazem) are • Phase 4: Na enters during diastolic commonly used to prevent depolarization > later transient inward Ca recurrent nodal arrhythmias (eg, current PSVT). They work by blocking • Phase 0: threshold met > more Ca influx Ca channels in slow-response • Verapamil is a non DHP CCB that cardiac tissues, slowing phase 4 slows diastolic depolarization during late (spontaneous depolarization) and phase 4 and all of phase 0 phase 0 (upstroke). This ↓ Class 1 and Class 4 impulse conduction velocity in • Raise threshold potential of cardiac fast the SA and AV nodes. and slow response tissues, respectively Class 1B • Shorts AP Class 1A, 3 and 4 • Increase refractory period Class 4 • Decrease intracellular Ca in cardiac MYOCYTE

1974 Cardiac AP The cardiac myocyte AP consists Mycocardial depolarization Cardiovascular (CV) Physiology (Phys) 1 of rapid depolarization (phase 0), • Phase 2: L type DHP Ca channels open initial rapid repolarization (phase 1), plateau (phase 2), late rapid repolarization (phase 3), and resting potential (phase 4). The AP is a/w ↑ membrane permeability to Na and Ca and ↓ permeability to K.

1975 Cardiac The phase 4 slow depolarization Cardiac Nodes Cardiovascular (CV) Physiology (Phys) 6 physiology in cardiac PM cells occurs due to • Phase 4: Na influx and little K efflux the closure of repolarizing K through funny channel > channels, the slow influx of Na • 50 opens t type Ca channels open > 40 L through funny channels, and the type Ca channels open opening of T-type Ca channels. •Phase 0: begins at 40, Ca depolarizes cell ACh and adenosine ↓ the rate of fully Phase 3: L type Ca channels close, K spontaneous depolarization in channels open Adenosine cardiac PM cells by prolonging • Binds A1 receptors increasing K efflux phase 4. during phase 4 slowing HR • Also inhibits L type Ca channels further prolonging depolarization • ACh slows phase 4 NE • Facilitates L type Ca channel opening increasing depolarization 1976 Pacemaker Cardiac pacemaker impulse • SA node: 60 100 bpm AV node: 45 55 Cardiovascular (CV) Physiology (Phys) 1 potential generation normally occurs in the bpm Bundle of His: 20 bpm Purkinje: 10 SA node, which has the fastest bpm firing rate of all conductive cells. • In 3rd degree heart block: AV node is The cells in other areas of the responsible for ventricular heart rate conduction system (eg, AV node, bundle of His, and Purkinje fibers) may serve as pacemakers if normal impulse conduction is impaired. 1977 Atrial fibrillation AF occurs due to irregular, A Fib Cardiovascular (CV) Physiology (Phys) 5 chaotic electrical activity w/i the • Absent P waves atria and Px w/ absent P waves, • Irregularly irregular r R interval irregularly irregular R-R • Narrow QRS intervals, and narrow QRS • AF leads to electrical remodeling of the complexes. The AV node atria with the development of shortened refractory period regulates the refractory periods and increased number of atrial impulses that conductivity (A fib begets A fib) reach the ventricle and determines • Ventricular rate is determined by AV the ventricular contraction rate in node refractory period conditions where the atria Brundle branch conductivity: determine undergo rapid depolarization. QRS complex • If wide QRS, look at lead 1: if positive then RBBB, if negative then LBBB

1978 Chronic heart Atrial natriuretic peptide (ANP) Neprilysin (Sacubitril) Cardiovascular (CV) Physiology (Phys) 12 failure and brain natriuretic peptide • Metalloprotease that inactivates ANP, (BNP) are secreted by atrial and glucagon, bradykinin ventricular cardiomyocytes in ANP response to myocardial stretching • Activates guanylate cyclase induced by hypervolemia. These • Kidney: dilates afferent art, inhibits Na natriuretic peptides inhibit the reabsorption in PCT and inner medullary renin-angiotensin-aldosterone collecting duct, inhibits renin release system and stimulate peripheral • Adrenal: decreased aldo release vasodilation and increased • Blood vessel: vasodilation and increase urinary excretion of sodium and permeability water. Neprilysin inhibitors (eg. Duodenal mucosa sacubitril) prevent the • Gastrin, secretin and CCK degradation of ANP and BNP, enhancing their beneficial effects in heart failure.

1983 Tricuspid A holosystolic murmur that ↑ in Ho Cardiovascular (CV) Physiology (Phys) 3 regurgitation intensity on inspiration most • Tri regurg: loudens on inspiration likely represents TR. The other • Mitral regurg and VSD: do not get louder holosystolic murmurs (which are on inspiration (no change) 2° to MR or a VSD) do not typically ↑ in intensity during inspiration.

2009 Coronary blood Myocardial oxygen extraction Myocardial muscles extract the largest Cardiovascular (CV) Physiology (Phys) 9 flow exceeds that of any other tissue or amount of O2 of any tissue organ; therefore, the cardiac • Thus O2 demand is tightly coupled venous blood in the coronary with coronary blood flow (Adenosine and sinus is the most deoxygenated NO are predominant vasodialtors) blood in the body. Due to the high degree of oxygen extraction, increases in myocardial oxygen demand can only be met by an increase in coronary blood flow.

2055 Atrial fibrillation Palpitations refer to a subjective A fib Cardiovascular (CV) Physiology (Phys) 5 sensation/awareness of the • Absent P waves heartbeat due to rapid arrhythmias • Varying r R interval or forceful ventricular • Irregularly irregular contractions. AF is the most • Can be seen with excessive alcohol common cause of an irregularly consumption irregular rhythm and is detected Ventricular hypertrophy on ECG by an absence of • High QRS voltage in precordial leads organized P waves and varying R- R intervals. 8293 Supine Pregnant women > 20 wks Supine hypotension Cardiovascular (CV) Physiology (Phys) 1 hypotension gestation can experience • Usually in late pregnancy due to compression of the IVC by the compression of IVC decreasing venous gravid uterus while in the supine return position. This ↓ venous return and • Peripheral neuropathy can cause CO, which can result in orthostatic hypotension due to decreased hypotension and syncope. autonomic function (diabetes) • Hypotension in early pregnancy due to reduced TPR Vasovagal syncope caused by concomitant withdrawal of sympathetic efferent and enhanced parasympathetic activity (bradycardia, vasodilation and orthostasis)

8546 Chronic heart The ↓ CO in HF triggers Acute decompensated HF Cardiovascular (CV) Physiology (Phys) 12 failure compensatory activation of the • Reduced CO and high ventricular SNS and RAAS, resulting in pressure vasoconstriction (↑ afterload), • Increase sympathetic (increased HR and fluid retention (↑ preload), and contractility, RAAS, release of ADH) deleterious cardiac remodelling. Adverse These mechs perpetuate a • Increased afterload worsens CO downward spiral of cardiac • High RAAS leads to volume overload deterioration, leading to SSx • Deleterious cardiac remodeling due to DHF. hemodynamic stress and neurohumoral stimulation

8563 Arginine in NO Nitric oxide is synthesized from Endothelium dependent vasodilation Cardiovascular (CV) Physiology (Phys) 1 production arginine by nitric oxide synthase. • ACh, bradykinin or shear stress increases As a precursor of nitric oxide, endothelial Ca > increased eNOS (take arginine supplementation may Arg + O2 + NADPH > NO + citrullin) > play an adjunct role in the NO activates GC > high cGMP > activated treatment of conditions that PKG which decreased Ca > vasodilation improve with vasodilation, such as stable angina.

11745 Chronic heart Neprilysin is responsible for the BNP Cardiovascular (CV) Physiology (Phys) 12 failure breakdown of the natriuretic • Released by ventricles peptides and AT-II; therefore, • Cause diuretic, natriuretic and inhibition of neprilysin ↑ the vasodilatory effect activity of these peptides. For Tx • Neprilysin: metalloportease that cleaves of HF, neprilysin inhibition is and inactivated peptide combined w/ AT-II receptor • If inhibits, increased natriuretic blockade to optimize the (+) peptides (helpful for HF) effects of the natriuretic peptides (eg, vasodilation, diuresis) while blocking the (-) effects of AT-II (eg, vasoconstriction, fluid retention).

12187 Endocarditis During the normal cardiac cycle, Cardiovascular (CV) Physiology (Phys) 15 central aortic pressure is higher than RV pressure during systole and diastole. Consequently, an intracardiac fistula b/w the aortic root and RV will most likely demonstrate a left-to-right cardiac shunt as blood continuously flows from the aortic root (high pressure) to the RV (low pressure).

14743 Atrial fibrillation AF is recognized by an irregularly Cardiovascular (CV) Physiology (Phys) 5 irregular rhythm w/ variable R-R intervals and absence of P waves on ECG. The development of AF most commonly involves ectopic electrical foci in the pulm veins that trigger fibrillatory conduction in abnormal (remodeled) atrial tissue. 14745 Atrial flutter Atrial flutter demonstrates rapid Cardiovascular (CV) Physiology (Phys) 1 and regular atrial activity in a saw- toothed pattern (flutter or F waves) on ECG. Typical atrial flutter is caused by a large re- entrant circuit that traverses the cavotricuspid isthmus of the RA, which is the target site for radiofrequency ablation.

14976 Aortic AR causes a rapid fall in aortic Cardiovascular (CV) Physiology (Phys) 8 regurgitation pressure during diastole w/ an ↑ in LV EDV and a compensatory ↑ in SV. These hemodynamic changes create Chx pressure changes, including ↓ aortic diastolic pressure, ↑ aortic systolic pressure, and ↑ LV diastolic and systolic pressures.

15391 Diastolic Prolonged systemic HTN leads to Cardiovascular (CV) Physiology (Phys) 4 dysfunction concentric LVH via the addition of myocardial contractile fibers in parallel. The thickening of the LV walls ↓ LV compliance, leading to impaired diastolic filling and HF w/ preserved EF. In response to ↓ CO, the kidneys activate the RAAS, stimulating Na retention and vasoconstriction that worsens volume overload and can lead to DHF.

15516 Hypertrophic HCM typically involves Cardiovascular (CV) Physiology (Phys) 9 cardiomyopathy interventricular septal hypertrophy that obstructs LV outflow and creates a systolic murmur that ↓ in intensity w/ maneuvers that ↑ LV blood volume (eg, hand grip, passive leg elevation). HCM is Chx by ↑ LV muscle mass w/ a small LV cavity, preserved EF, and impaired LV relaxation leading to diastolic dysfxn.

15526 Acute heart failure SV is the absolute volume of Cardiovascular (CV) Physiology (Phys) 7 blood ejected from the LV w/ each contraction and is calculated by subtracting LV ESV from LV EDV. EF is the relative volume of blood ejected from the LV w/ each contraction; it is calculated by dividing SV by LV EDV. CO, the volume of blood ejected into the aorta per unit time, is estimated by multiplying SV by HR.

15534 Chronic heart LHF leads to chronically ↑ pulm Cardiovascular (CV) Physiology (Phys) 12 failure venous and capillary pressures, w/ resulting pulm oedema and extravasation of RBCs into the alveolar parenchyma. The Fe from RBCs is taken up by alveolar macrophages and stored as hemosiderin, appearing as brown pigment on histopathology.