The Heart

1. The Heart

2. Cardiac Structure and Specializations • Myocardium • Valves • Conduction system • Blood supply

3. Effects of Aging on the Heart • Table 12-1

4. Heart disease: Overview of Pathophysiology • Failure of the pump • Obstruction to flow • Regurgitant flow • Shunted flow • Disorders of cardiac conduction • Rupture of the heart or a major vessel

5. Heart Failure • Heart is unable to pump blood as a rate sufficient to meet the metabolic demands of the tissues or can do so only at elevated filling pressures • Systolic dysfunction – progressive deterioration of myocardial contractile function • Diastolic dysfunction – inability of the chamber to expand and fill during diastole • Several physiologic mechanisms maintain arterial pressure and perfusion of vital organs • Frank-Starling mechanism • Myocardial adaptations, including hypertrophy with/without chamber dilation – ventricular remodeling • Activation of neurohumoral systems • Release of norepinephrine – increases HR, contractility, vascular resistance • Activation of the renin-angiotensin-aldosterone system • Release of atrial natriuretic peptide

6. Heart Failure • Cardiac Hypertrophy: Pathophysiology and Progression to Failure • Left-sided Heart Failure • Right-sided heart failure

7. Cardiac Hypertrophy • Increased mechanical work due to pressure or volume overload or trophic signals causes myocytes to increase in size • Increased protein synthesis, increased in DNA ploidy, increased number of mitochondria, increased size of nuclei • Pressure-overload hypertrophy – concentric increase in wall thickness, sarcomere in parallel • Volume-overload hypertrophy – ventricular dilation – sarcomeres in series • Oxygen supply to hypertrophied heart is tenuous, deposition of fibrous tissue, shift to fetal gene expression pattern, heightened metabolic demand • Vulnerable to decompensation • Physiologic vs pathologic hypertrophy • CHF – variable degrees of decreased cardiac output and tissue perfusion, as well as pooling of blood in the venous system

8. Left-sided Heart Failure • Causes • Ischemic heart disease • Aortic and mitral valvular disease • Myocardial diseases • Pulmonary edema – heart failure cells, Kerley B lines • Clinically – cough, dyspnea, orthopnea, PND, atrial fibrillation, increased vascular and extracellular volume, pre-renal azotemia, hypoxic encephalopathy

9. Rigth-sided Heart Failure • Causes • Most common is left-sided failure • Corpulmonale (pulmonary hypertension) • Congestion – liver and portal system, pleural, pericardial, peritoneal spaces, peripheral edema • Clinically – hepatosplenomegaly,peripheral edema, pleural effusions, ascites, hypoxia of CNS

10. Congenital Heart Disease • CHD = Abnormalities of the heart or great vessels present from birth • Most – faulty embryogenesis during the 3rd-8th week when the CVS form and begin functioning • Worst ones don’t survive to term • Those who do usually have only discrete regions of the heart affected e.g. septal defect or valvular defect

11. CHD • Dx • Some when change from fetal to postnatal circulation • 50% diagnosed by one year of life • Mild forms - adulthood

12. CHD • Incidence • 1% of all live births • CV defects among most common malformations and are the most common cause of heart disease in children • Higher in premies and stillborns • Table 12-2 VSD most common Tetralogy of Fallot most common cyanotic • Many survive into adulthood – repairs • Common problems Arrhythmias Additional surgery Ventricular dysfunction Use of prosthetics Risk of childbearing

13. CHD • ECM – swellings – endocardial cushions • Future valve development • Day 50 – 4 chambered heart • Signaling pathways regulating TFs Wnt VEgf bone morphogenetic factor TGF-beta FGF Notch • Heart – mechanical organ – exposed to flowing blood from earliest stages – hemodynamic forces play a role • Specific micro RNAs – critical role- patterns and levels of TF expression

14. CHD • Cardiac Development – figure 12-3 • First heart field • TFs: TBX5, Hand1 • Mainly LV • Second heart field • TF: Hand2, FGF=10 • Outflow tract, RV, most of atria • Cardiac neural crest • Septation of outflow tract, aortic arches

15. CHD • AD mutations – partial loss of function in one or more required factors, TFs usually • “The main known cause of CHD consist of sporadic genetic abnormalities.” • single gene mutations • small chromosome deletions • additions or deletions of whole chromosomes • Table 12-3

16. CHD • Heterozygotes = 50% reduction in activity = deranged cardiac development • Factors work together- large protein complexes – different single gene mutations produce similar defects • Signaling pathways or structural roles NOTCH1 – bicuspid AV NOTCH2, JAGGED1 – TOF Fibrillin – Marfan’s

17. CHD • DiGeorge Syndrome Small deletion of 22q11.2 in 50% 4thbranchial arch and 3rd and 4th pharyngeal pouches Thymus, parathyroids, heart TBX1 • Chromosomal aneuploidies Turner Syndrome Trisomies 13,18, 21 21- most common genetic cause of CHD endocardial cushion defects

18. CHD • First-degree relatives of affected patients are at increased of CHD – subtle forms of genetic variation • Environmental factors? +/- genetic factors congenital rubella infection gestational diabetes exposure to teratogens nutritional factors? transient environmental stresses during 1st trimester?

19. CHD • Clinical features • Left-to-right shunts • Right-to-left shunts • Obstructive lesions • Shunt= abnormal communication between chambers or vessels • Obstruction = narrowing (if complete- atresia)

20. CHD • R to L Hypoxemia Cyanosis Emboli bypass lungs – brain infarction, abscess ( paradoxical embolism) Clubbing (hypertrophic osteoarthropathy) Polycythemia

21. CHD • L to R • Normally low-pressure, low-resistance pulmonary circulation now sees high flow volumes and pressures • RVH • Atherosclerosis of pulmonary vessels • medial hypertrophy • vasoconstriction • irreversible obstructive intimal lesions • Pulm pressures reach systemic levels • R to L shunt • Eisenmenger Syndrome • Altered hemodynamics of CHD • Dilation, hypetrophy or both • Decreased volume and muscle mass – hypoplasia – before birth, atrophy – postnatally

22. CHD • L to R ASD VSD PDA AV septal defects

23. CHD • ASD abnormal, fixed opening in the atrial septum usually asymptomatic until adulthood 3 types Secundum(90%) – center of the septum Primum (5%) –adjacent to the AV valves Sinus venosus ( 5%) – SVC, associated with APVR Clinical L to R Pulmonary blood flow -2-4 times normal murmur from increased pulmonic valve blood flow Surgical or catheter correction – low mortality, normal long-term survival • PVO –oval fossa, 80% closed permanently, 20% potential opening that can become clinically important r-to-l

24. CHD • VSD Most common congenital anomaly 20-30% isolated finding Most are associated with other cardiac anomalies Classified by size and location 90% membranous Rest are infundibular ( below the PV) or muscular Muscular can be multiple ( “Swiss-cheese”) Clinical Large – problems from birth, RVH, pulmonary hypertension, correct before irreversible changes Smaller – well-tolerated

25. CHD • PDA DA stays open, allowing L to R shunt from aorta to pulmonary artery 90% isolated anomaly “machinery-like” murmur close as soon as possible to prevent irreversible PH Some congenital lesions are ductus dependent and there by need to keep the DA open- e.g. aortic atresia, use prostaglandin E

26. CHD • AV septal defect Complete atrioventricular canal defect Partial – primum ASD with mitral insufficiency Complete – large combined AV septal defect and a common AV valve – all 4 chambers communicate, all have hypertrophy 1/3 have Down syndrome Surgically correctible

27. CHD • R to L Tetralogy of Fallot Transposition of the Great Arteries Truncusarteriosus Tricupsid Atresia Total Anomalous Venous Connection

28. CHD • Tetralogy of Fallot 4 cardinal features VSD Obstruction of the right ventricular outflow tract (subpulmonary stenosis) An aorta that overrides the VSD RVH Embryoloigcally – anterosuperior displacement of the infundibular septum “Boot-shaped” heart – marked apical RVH Sometimes PVS, PV atresia Sometines AV insufficiency, ASD 25% right aortic arch Clinical – Classic TOF – r-to-l shunt Pink TOF – l to r shunt because of mild subpulmonary stenosis As child grows obstruction becomes worse Stenosis protects pulmonary arteries from overload and RV failure rare because RV decompressed by the VSD

29. CHD • TGA Ventriculoarterialdiscord Aorta from RV PA from LV Separation of the systemic and pulmonary circulations – incompatible with life unless a shunt exists VSD or PFO or PDA or artificial shunt –balloon atrial septostomy Surgical repair

30. CHD • TA Failure of separation into the aorta and PA Single vessel giving rise to the systemic, pulmonary and coronary circulation • Associated VSD

31. CHD • TAPC Pulmonary veins fail to join the left atrium PFO or ASD Aplastic Left atrium LV normal size

32. CHD • Obstructive Congenital Anomalies Coartation of the aorta PS and atresia AS and atresia

33. CHD • Coarctation of the Aorta Males 2x females Associated with Turner syndrome 2 classic types “Infantile” – hypoplasia of the arch proximal to a PDA, symptomatic in early childhood, cyanosis over lower half of body, surgical correction needed early “Adult” – discrete ridgelikeinfolding of the aorta, just opposite a closed DA (ligamentumarteriosus) distal to the arch vessels, hypertension in upper extremities, signs of arterial insufficiency in lower, notching of the ribs due to collateral circulation Clinical – murmur with thrill LVH

34. CHD • PS and atresia Obstruction of the PV Isolated or part of a more complex anomaly RVH Poststenotic dilation of PA Complete obstruction- need shunt to survive Mild – asymptomatic Symptomatic – surgical correction

35. CHD • AS and atresia Vavular-hypoplastic, dysplastic, decreased number Subvalular-dense fibrous tissue below the cusps Supravavular- aortic dysplasia, thickened and constricted, deletion on chromosome 7, elastin gene, Williams- Beurensyndrome, hypercalcemia, cognitive abnormalities, facial anomalies Hypoplasticleft heart syndrome – severe stenosis of atresia – underdevelopment of LV and aorta – endocardialfibroelastosis Clinical – systolic murmur, thrill, LVH, antibiotic prophylaxis for SBE, avoid strenuous activity, sudden death

36. Ischemic Heart Disease • Leading cause of death worldwide for both men and woman. • Ischemia = oxygen and nutrients insufficiency • 90% cause is atherosclerotic lesions in the coronary arteries, thus “coronary artery disease” • Other causes – emboli, blockage of small myocardiql blood vessels, shock

37. Ischemic Heart Disease • Angina Pectoris • Myocardial Infarction • Chronic IHD – ischemic cardiomyopathy • Sudden cardiac death

38. Ischemic Heart Disease • Peak in mortality in 1963, fallen by 50% since then due to prevention, diagnostic and therapeutic advances • The dominant cause of the IHD syndromes is insufficient coronary perfusion relative to myocardial demand, due to chronic, progressive atherosclerotic narrowing of the epicardial coronary arteries, and variable degrees of superimposed acute plaque change, thrombosis, and vasospasm

39. Ischemic Heart Disease • Fixed lesion obstructing > 75% of the lumen leads to Symptomatic ischemia precipitated by exercise • Obstruction of 90% leads to symptoms even at rest • May lead to formation of collateral vessels over time • Clinically significant stenotic lesions tend to predominate in the first several centimeters of the LAD and LCX and along the entire length of the RCA

40. Angina Pectoris • Paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort cause by transient myocardial ischemia that fall short of inducing myocyte necrosis • Three overlapping patterns • Stable or typical angina • Prinzmetal variant angina • Unstable or crescendo angina

41. Myocardial Infarction • Death of cardiac muscle due to prolonged severe ischemia • Sequence of events in typical MI • Sudden change in an atheromatous plaque • Platelets adhere, become activated, release their granule contents, and aggregate to form microthrombi when exposed to subendothelial collagen and necrotic plaque contents • Vasospasm is stimulated by mediators released by platelets • Tissue factor activates the coagulation pathway, adding to the bulk of the thrombus • Frequently within minutes, the thrombus evolves to completely occlude the lumen

42. Myocardial Infarction • Myocardial response • Cessation of aerobic metabolism within seconds leading to inadequate high-energy phosphates and accumulation of lactic acid • Severe ischemia induces loss of contractility within 60 seconds • Ultrastructural changes – potentially reversible, develop within a few minutes • Myofibrillar relaxation • Glycogen depletion • Cell and mitochondrial swelling

43. Myocardial Infarction • Table 12-4 Approximate time of onset of key events in ischemic cardiac myocytes • Key feature in the early phases of myocyte necrosis – disruption of the integrity of the sarcolemmal membrane allowing intracellular macromolecules to leak out of cells into the cardiac interstitium and ultimately into the microvasculature and lymphatics in the region of the infarct

44. Myocardial Infarction • In most cases of acute MI, permanent damage to the heart occurs when the perfusion of the myocardium is severely reduced for an extended interval (usually at least 2-4 hours). This delay in the onset of permanent myocardial injury provides the rationale for rapid diagnosis in acute MI – to permit early coronary intervention, the purpose of which is to establish reperfusion and salvage as much “at risk” myocardium as possible.

45. Myocardial Infarction • Precise location, size, and specific morphologic features of an acute MI depend on: • Location, severity, and rate of development of coronary obstruction • Size of the vascular bed perfused by the obstructed vessels • Duration of the occlusion • Metabolic/oxygen needs of the myocardium at risk • Extent of collateral vessels • Presence, site, severity of coronary arterial spasm • Other factors – HR, rhythm, blood oxygenation

46. Myocardial Infarction • Typically • LAD – apex, anterior wall of LV, anterior 2/3 of ventricular septum • The coronary artery that perfuses the posterior third of the septum is called dominant ( either the LCX or RCA) • Right dominant circulation (4/5 of population) • LCX – lateral wall of the LV • RCA – entire RV free wall, posterobasal wall of the LV, posterior third of the septum

47. Myocardial Infarction • Transmuralvssubendocardial infarction • Most MIs are transmural – full thickness in the distribution of a single artery, ST elevation • Subendocardial – area of necrosis limited to inner 1/3 to1/2 of ventricular wall, non-ST elevation, normally the least perfused area of the myocardium, most vulnerable to ischemia

48. Myocardial Infarction • Infarct modification by reperfusion • Reperfusion – most effective way to “rescue” ischemic myocardium • May trigger deleterious complications • Arrhythmias • Myocardial hemorrhage with contraction bands • Irreversible cell damage superimposed on the original ischemic injury (reperfusion injury) • Microvascular injury • Prolonged ischemic dysfunction (myocardial stunning)

49. Myocardial Infarction • Appearance of reperfused myocardium • Hemorrahagic • Irreversibly injured myocytes – contraction bands • Reperfusion not only salvages reversible injured cells but alters the morphology of lethally injured cells

50. Myocardial Infarction • Consequences and Complications • Contractile dysfunction • Arrhythmias • Myocardial rupture • Pericarditis • Right ventricular infarction • Infarct extension • Infarct expansion • Mural thrombus • Ventricular aneurysm • Papillary muscle dysfunction • Progressive late heart failure