AIM Case Conference

1. AIM Case Conference Brandon E. Brown, M.D.

2. Case Presentation HPI: A 20 year old male presents for pre-op assessment prior to an elective left knee arthroscopy PastMedhx: Benign Monomelic Amyotrophy PastSurghx: none Meds: none Famhx: DM, “heart problems” Sochx: no EtOH, tob, drug abuse ROS: active and denies CP, SOB, DOE, orthopnea, edema, syncope, palpitations, etc. (all else reviewed and not pertinent)

3. Case Presentation (cont.) PE: VS: AF 61 142/55 100% RA 12 Gen: healthy appearing BM in NAD CV: inspection - prominent carotid upstroke visualized, nl. JVP; palpation - no LV/RV heave, no thrill palpated, PMI not displaced and approx. size of a quarter, palpable “knock” at RUSB, 3+ carotid upstroke; auscultation – nl. S1, S2; III/VI blowing diastolic murmur best heard at USB and radiating to apex Pulm: Lungs CTA w/ good excursion Neuro/MSK: left thenar muscle atrophy and weakened interosseous mm; strength otherwise WNL

4. Case Presentation (cont.)

5. LV End-Diastolic Diameter(LVEDD>65 = decompensated)

6. LV End-Systolic Diameter(LVESD>50mm = decompensated)

7. Aortic Root Diameter

8. Ejection Fraction Measurement(EF<50% = decompensated)

9. AV Pressure Half-Time Measurement(P1/2 <200ms = severe AI)

10. Parasternal Long Axis With Color Flow Doppler

11. Parasternal Long Axis With Color Flow Doppler

12. Parasternal Short Axis – Bicuspid Valve

13. Parasternal Short With Color Flow Doppler

14. Question #1 What pre-operative recommendations should we make regarding his cardiovascular status?

15. Peri-operative Management • Risk is determined by degree of LV dysfunction • Regurgitant volume determined by two factors: magnitude and duration of diastolic pressure gradient across valve and effective regurgitant orifice area. Gaasch, W. Vasodilator therapy in asymptomatic aortic regurgitation. UpToDate. 2001. Thus… • Avoid increases in peripheral vascular resistance (ie use of vasopressors) • Avoid bradycardia • Sensitivity to volume if marked LV dysfunction present • Avoid further reduction in diastolic blood pressure to prevent further decrease in coronary perfusion pressure

16. Question #2 Does vasodilator therapy delay need for aortic valve replacement surgery in patients such as this with asymptomatic aortic regurgitation?

17. Hydralazine Hydralazine vs. placebo 80 minimally symptomatic patients studied over two years. Avg. dose of 215 mg/day hydralazine given to 45 patients (35 placebo). No effect on BP or HR. Noted significant decrease in LVEDVI (primary endpoint), LVESVI, and an increase in EF. Greenberg, B; Massie, B; Bristow, D; et al. Long-term vasodilator therapy of chronic aortic insufficiency: A Randomized double-blinded, placebo-controlled trial. Circulation 1988; 78-91. Hydralazine vs. Enalapril 38 (of 76) asymptomatic patients treated with hydralazine at an avg. dose 177 mg/day over 12 months. In contrast, BP reduced, but no change in LV size or EF. Did note inc. in exercise duration, however. Lin, M; Chiang, HT; Lin, SL; et al. Vasodilator therapy in chronic asymptomatic aortic regurgitation: enalapril versus hydralazine therapy. J Am Coll Cardiol 1994; 24:1046.

18. ACE Inhibitors Hydralazine vs., Enalapril (cont.) 38 (of the 76 total) patients treated with avg. 31 mg/d of enalapril for 12 mths. Showed a decrease in BP, LV end-diastolic, and end-systolic volume indexes as well as mass index. Quinapril 12 asymptomatic patients treated with 10-20 mg/d of quinapril for one year. Noted a decrease in systemic arterial pressure, LV chamber volume, and improved exercise capacity. Schon, HR; Dorn, R; Barhtel, P; Schomig, A. Effect of 12 months quinapril therapy in asymptomatic patients with chronic aortic regurgitation. J Heart Valve Dis 1994; 3:500.

19. ACE Inhibitors (cont.) Captopril Mildly symptomatic patients with severe AR treated with 25mg TID for 6 months. There was no change in BP or LV chamber size. This suggests that a reduction in arterial pressure is an important determinant of benefit with ACE-I. Wisenbaugh, T, etal. Six month pilot study of captopril for mildly symptomatic, severe isolated mitral and aortic regurgitation. J Heart Valve Dis 1994; 3:197.

20. ACE Inhibitors (cont.) Mori, Y, et al. Long-Term Effect of Angiotensin-Converting Enzyme Inhibitor in Volume Overloaded Heart During Growth: A Controlled Pilot Study. JACC. 2000. Objectives: to determine if long term therapy with ACE-I reduces inc. in LV mass in children with AR. Methods: 24 patients ages 0.3-16 years. 12 patients received ACE-I (cilazapril:0.03 to 0.04mg/d in 9 patients and enalapril:0.15-0.4mg/d in 3 patients). 12 placebo. Echo parameters again measured at avg. 3.4 years of follow-up.

21. ACE Inhibitors (cont.) Results: LV end-diastolic dimension decreased in the ACE-I group and increased in the placebo group. The mass normalized to growth also reduced in the ACE-I group and increased in the placebo group. Conclusions: Long-term treatment with ACE-I is effective in reducing LV volume and LV hypertrophy in growing children. Comments: Small patient numbers. Limited follow-up.

22. Nifedipine Nifedipine vs. Placebo 72 asymptomatic patients with chronic severe AR studied over 12 months. Randomized to 20 mg BID or placebo. Nifedipine resulted in a decrease in BP, decreased LV volume, and increased EF. All patients remained asymptomatic and none required AVR. Scognamigilio, et al. Long-term nifedipine unloading therapy in asymptomatic patients with chronic severe aortic regurgitation. J Am Coll Cardiol 1990; 16:424.

23. Nifedipine (cont.) Nifedipine vs. Digoxin Scognamigilio, et al. Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function. N Engl J Med 1994; 331:689. Objective: to determine if nifedipine reduced or delayed the need for AVR in patients with severe, isolated aortic regurgitation and normal left ventricular function. Design: RCT with 6 year follow-up Patients: 143 patients, mean age 35y, with severe AI and preserved EF

24. Nifedipine vs. Digoxin (cont.) Intervention: randomly allocated to digoxin, 0.25 mg/d or nifedipine, 20 mg BID Results:

25. Nifedipine vs. digoxin (cont.)

26. Nifedipine vs. Digoxin (cont.) Conclusions: Nifedipine was effective in delaying the need for AVR in asymptomatic patients with severe, chronic, isolated AR and normal LV systolic function. Comments: • Study was not blinded • Did digoxin have a deleterious effect?

27. Conclusions • Vasodilators reduce the hemodynamic burden on the volume-loaded LV in AR. • All studies except 1994 Nifedipine study had small patient numbers, short follow-up, and used suurrogate endpoints. • Among asymptomatic patients, those with severe AR and substantial LV enlargement (>65mm) are potential candidates for vasodilator therapy which may prolong the asymptomatic period and thus the need for AVR. • No published evidence to support use of vasodilators in asymptomatic patients with mild-moderate AR and mild LV enlargement. • RCT comparing nifedipine and ACE-I required before one may preferentially recommend ACE-I.

28. ACC/AHA Guidelines

29. Should My Patient Receive Vasodilator Therapy? According to the evidence, my patient does not technically meet criteria for afterload reduction therapy given his degree of LV dilation and severity of AR. However, given his degree of AI and expected development of progressive LV dilation, etc., I will recommend therapy.