1. Aortic Regurgitation: Old and New Andrew D. Ferguson UIC Cardiology February 7, 2008

2. Agenda Acute AR followed by Chronic Etiology Pathophysiology Natural History Diagnostic Evaluation Treatment Special Considerations

3. Acute AR: Etiology Endocarditis –Valve destruction and leaflet perforation –Paravalvular abscess rupture into LV, LA or RVOT Aortic dissection –Incomplete coaptation of leaflets –Flail leaflets from extension of dissection

4. Acute AR: Etiology Rupture of a congenital fenestration Traumatic rupture of leaflets after either deceleration injury or blunt trauma Iatrogenic –Aortic balloon valvotomy –Failed surgical repair or replacement

5. Pathophysiology Sudden, large regurgitant volume Normal-sized ventricle unable to fully accommodate volume overload Frank-Starling mechanism increases SV, but forward stroke volume markedly diminished (FSV=SV-Regurg volume)

6. Pathophysiology Tachycardia is compensatory –Increase or decrease CO? Increased LVEDP leads to: –Early closure of mitral valve –Increased LA pressures, which then lead to pulmonary edema –Myocardial ischemia Diminished myocardial perfusion pressure

7. Pathophysiology Pre-existing LVH (i.e. HTN, AS): –More susceptible to drastic hemodynamic consequences –Smaller, non-compliant LVs with a reduced preload reserve Examples: –Aortic dissection in longstanding HTN –IE in pre-existing AS –Iatrogenic (i.e. valvulotomy) for congenital AS

8. Acute AR: Hemodynamics

9. Natural History Severe acute AR generally presents with cardiovascular collapse: –Weakness –Severe Dyspnea –Hypotension Other sxs, if present, related to etiology: –For example, chest/back pain related to aortic dissection.

10. Evaluation: Physical Manifestations of cardiogenic shock: –Hypotension, pallor, diaphoresis, occasional cyanosis, peripheral vasoconstriction Soft or absent S1 due to early closure of MV (increased LVEDP) Soft A2, loud P2 Frequently an S3, no S4 Early diastolic, low-pitched murmur MAY be present after S2. Systolic flow murmur (increased SV)

11. Evaluation: Imaging CXR: CHF and pulmonary edema CT can be used in evaluation for aortic dissection Ultimately, echocardiography is the diagnostic procedure

12. Acute AR: Echo Color doppler demonstrates the regurgitant flow and aids grading Severe acute AR: –Vena contracta width >6mm –Diastolic pressure half-time <200ms –Holodiastolic flow reversal in desc. aorta TTE/TEE to diagnose IE, dissection

13. Treatment Death without tx is common, due to: –EMD, ventricular arrhythmias, pulmonary edema, or circulatory collapse. Any severity of acute AR: –Urgent aortic valve replacement –If surgery delayed, may stabilize in ICU: IV Vasodilators, i.e. nitroprusside Possibly inotropic agents, i.e. dopamine IABP contraindicated Exception: Mild acute AR due to endocarditis

14. Chronic AR: Etiology Leaflet Abnormalities: –Rheumatic fever –Endocarditis –Trauma –Bicuspid aortic valve –Rheumatoid arthritis –Myxomatous degeneration –Acromegaly –Fenfluramine-phentermine

15. Chronic AR: Etiology Ascending root or ascending aorta: –Systemic hypertension –Aortitis (e.g. syphilis) –Reiter’s syndrome –Ankylosing spondylitis –Trauma –Dissecting aneurysm –Marfan syndrome –Ehlers-Danlos syndrome –Pseudoxanthoma elasticum –Inflammatory bowel disease –Osteogenesis imperfecta –Annuloaortic ectasia

16. Chronic AR: Epidemiology Framingham Heart Study: –≥trace AI found in 13% men, 8.5% women –Rarely more than trace younger than 50 –Prevalence of ≥moderate AI: Age (range) MenWomen 50-593.70.2 60-6912.10.8 70-8312.22.3

17. Chronic AR: Pathophysiology Course of AR is insidious, often decades before clinically important Compensatory mechanisms aimed at: –Preservation of forward stroke volume and hence cardiac output –Maintenance of normal wall stress

18. Chronic AR: Wall Stress Large regurgitant volume leads to increase in LV end-diastolc volume Creates elevation in wall stress Laplace’s law: Compensate by increasing LV thickness, both eccentric and concentric Cavity Pressure x Radius LV Wall Stress = -------------------------------- Wall Thickness x 2

19. Chronic AR: Cardiac Output AR leads to diminshed forward stroke volume, and hence CO FSV = SV - ARV Increase SV to maintain FSV (CO) by: –Increase ventricular compliance (dilatation) –Maintain efficiency (hypertrophy)

20. Chronic AR: Hemodynamics

21. Clinical Manifestations May be asymptomatic for decades Symptoms due to enlarged LV: –Awareness of heartbeat, pounding –Atypical chest pain –Palpitations (ST, PACs, PVCs) Symptoms of LVH with LV dysfunction Angina

22. Chronic AR: Angina Uncommon in isolated AR due to dilation of coronary arteries Underlying CAD Subendocardial ischemia –Diminished perfusion pressure Nocturnal ischemia –Heart rate slows, arterial diastolic pressure falls. –Splanchnic ischemia may also occur, abd pain.

23. Chronic AR: Examination Physical examination remains important both for initial diagnosis and following progression of disease Many characteristic attributes which help grade severity/progression: –Surface exam –Auscultation –Peripheral exam

24. Chronic AR: Surface Exam Consistent with LV enlargement and forceful systolic function Apical impulse: –Displaced laterally and inferiorly –Diffuse and hyperdynamic Dilatation of ascending aorta: –Sternal notch pulsation and possibly thrill

25. Chronic AR: Auscultation Heart Sounds: –S1 soft, ?reflecting long PR interval –S2 variable; soft, absent, or single A2 often soft or absent P2 may be normal, increased or obscured by the diastolic murmur –S3 occasionally present due to volume overload –S4 usually absent

26. Chronic AR: Auscultation Murmurs: –Diastolic regurgitant murmur: Good positive and negative predictive values Begins immediately after A2 High-pitched, blowing, sustained or decrescendo Best appreciated with patient sitting up, leaning forward, and holding breath in expiration Guage severity –Intensity does not correlate to severity (may be absent) –Murmur in early diastole and blowing ---> mild AI –As lesion becomes more severe, murmur extends through more of diastole, become holodiastolic and rougher **Beware of transient murmur of AR: –E.g. HD patients in volume overload, resolves with HD

27. Chronic AR: Auscultation Murmurs, cont.: –Regurgitant murmur varies with squatting/Valsalva –Austin Flint murmur Mid to late diastolic apical rumble Results from competing flows of the mitral inflow and the regurgitant lesion Distinguish from MS by lack of loud S1 & OS –Systolic murmur Mainly a result of functional stenosis (  SV and  rate) Cresc-decresc harsh murmur beginning after S1

28. Chronic AR: Peripheral Exam Wide pulse pressure –Increased stroke volume Abrupt distention of peripheral arteries Elevation of systolic pressure –Regurgitation into LV Quick collapse of arteries Low diastolic pressure Many non-specific peripheral signs

29. Peripheral Signs of Severe AR Quincke’s sign: capillary pulsation Corrigan’s sign: water hammer pulse Bisferiens pulse (AS/AR > AR) De Musset’s sign: systolic head bobbing Mueller’s sign: systolic pulsation of uvula Durosier’s sign: femoral retrograde bruits Traube’s sign: pistol shot femorals (auscultation) Hill’s sign:BP Lower extremity >BP Upper extremity by –> 20 mm Hg - mild AR –> 40 mm Hg – mod AR –> 60 mm Hg – severe AR

30. Chronic AR: ECG LVH Evidence of LA hypertrophy Leftward axis ST segment depression –One study showed 83% of patients with rest or exercise ST abnl had enlarged ventricle (>55mm) or low EF (<45%) Arrhythmias/conduction abnl uncommon

31. Chronic AR: Echo

32. Characteristic Findings: –If primary valvular, can see leaflet thickening, vegetations, calcification, and prolapsed or flail leaflets –Aortic root dilatation or evidence of aneurysm (either dissecting or saccular) –High frequency, diastolic fluttering of anterior mitral leaflet from AR jet –Doppler is highly sensitive for detecting AR jet –Increased LVESV and LVEDV

33. Chronic AR: Severity Assessment Severe AR present by echo with at least one of the following findings: –Regurgitant fraction ≥50% –Vena contracta width >6mm –Regurgitant volume ≥60mL –Central jet width ≥65% OF LVOT –ERO area ≥0.30cm 2

34. Chronic AR: Echo Severity Other indirect measures: –Rate of decline in regurgitant slope The sharper the decline, the more severe –Degree of reversal in pulse wave velocity in the descending aorta –Magnitude of LV outflow tract velocity

35. Chronic AR: Severity

36. Chronic AR: Cath Goals: LV size and function, aortic root dimensions/disorders, quantitation of AR

37. Chronic AR: CT/MRI Especially important with suspected aortic disease AR due to bicuspid aortic valve may have concommitant aortic dilatation

38. Chronic AR: Natural History Asymptomatic %/Y Normal LV function (Good prognosis) –Progression to symptoms &/or LV dysfunction < 6 –Progression to asymptomatic LV dysfunction < 3.5 –75% 5-year survival –Sudden death < 0.2 Abnormal LV function –Progression to cardiac symptoms 25 Symptomatic (Poor prognosis) –Mortality > 10 Bonow RO, et al, JACC. 1998;32:1486. (593 patients, mean 6.6yrs)

39. Chronic AR: Treatment Management depends upon: –Severity Based on clinical and echo criteria –Symptoms If equivocal, consider exercise testing –LV function (>50% or ≤50%) If equivocal, consider RVG or MRI –LV dimensions (LVSD, LVDD)

40. Chronic AR: Treatment Mild to moderate AR –Do not require treatment –Serial monitoring (symptoms, echo) Symptomatic with mild to moderate AR –Consider other etiologies of symptoms E.g. mitral stenosis

41. Severe AR: Management Asymptomatic with normal LV function –First question if truly asymptomatic??? –Consider exercise testing if sedentary or equivocal symptoms Medical therapy (i.e. vasodilators) –Not recommended Serial monitoring –Symptoms and LV dimensions and function

42. Severe AR: Medical Therapy Treat systemic arterial diastolic HTN –Cautious use of BB Treat afib and bradyarrhythmias –Poorly tolerated Treat LV dysfunction prior to surgery –Digoxin, salt restriction, diuretics, ACE/ARB Treat angina –Nitrates not as helpful than in +CAD Vasodilators - next slide

43. Severe AR: Theory of Vasodilators Improve stroke volume and reduce regurgitant volume hopefully reducing: –LVEDV –Wall stress –Afterload Results in preserved LVEF and reduction in LV mass

44. Severe AR: Vasodilators Conflicting results of efficacy in controlled randomized trials Most recent and only placebo-controlled –95 consecutive patients, followed 7 years –Placebo, long-acting nifedipine, enalapril –No reduction in symptoms or LV dysfunction –No sig dif in LV dimension, EF, or mass If used, goal is to reduce systolic BP Not indicated in normal BP or normal LV size

45. Severe AR: Vasodilators

46. Physical Activity Reduction in regurgitant volume from: –Decrease in PVR and resultant diastolic blood pressure –Decreased diastolic filling period which accompanies tachycardia Failure of increased EF Uncertain ultimate consequences

47. Physical Activity Also recommend Holter monitoring in those who wish to perform competitive athletics to detect ventricular arrhythmias 36th Bethesda Conference, JACC 2005

48. Chronic AR: Serial Testing Initial Presentation (mod to severe AR) –Establish stability and chronicity –If unknown, repeat exam and TTE in 2-3mos Once stability and chronicity established, frequency of reevaluation depends on: –Severity of AR –Degree of LV dilatation –Level of systolic function –The level of progression of dilatation and/or dysfxn Repeat eval with any hint of progression

49. Chronic AR: Surgery

50. Chronic AR: Surgical Caveats Symptomatic severe AR with Normal LVSF: –Surgery indicated for NYHA class III-IV and Canadian class II-IV angina –NYHA class II, question etiology of symptoms (deconditioning or aging?) Consider exercise testing

51. Chronic AR: Surgical Caveats Symptomatic severe AR with  LVSF: –AVR for 25%<EF<50%, NYHA II-IV NYHA IV have worse post-op survival and lower rates of recovery of systolic function –EF 60mm NYHA IV - surgical mortality nears 10% –Cannot predict who may recover LV function NYHA II-III - AVR likely, especially if: –Recent onset of symptoms and evidence of LV dysfunction –Intensive short-term vasodilators result in sx improvement –IV inotropy improves hemodynamics or systoic function

52. Long-term AVR survival

53. Copyright ©2006 American College of Cardiology Foundation. Restrictions may apply. Bonow, R. O. et al. J Am Coll Cardiol 2006;48:e1-e148 Management strategy for patients with chronic severe aortic regurgitation

54. Special Considerations Endocarditis Prophylaxis –No longer recommended in this population Elderly –Pure AR is uncommon (combined AS/AR) –Age >75 more likely to: Develop symptoms or  LVSF earlier Have persistent  LVSF and CHF sxs post-operatively Have worse post-operative survival rate –Goal of therapy is to improve QOL Therefore, symptoms guide therapy after risks are balanced against expected long-term improvement

55. Special Considerations Pregnancy –AR with NYHA III-IV sxs or EF<40% Considered high maternal and/or fetal risk Should receive AVR before surgery –AR with NYHA I-II sxs and normal EF Considered low maternal and/or fetal risk Generally tolerate pregnancy without problems –Symptoms can be treated with diuretics and vasodilators (nifedipine), if necessary –Termination if presents with high risk as above –If refuse, only operate for refractory class III-IV

56. Advice Please read the guidelines if: –You feel my talk was incomplete –I didn’t make any sense –You fell asleep, or –If you’re like me and need to hear/read things many times to ingrain the info.

57. Thank You