AIM Case Conference

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AIM Case Conference

• Brandon E. Brown, M.D.

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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)

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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

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Case Presentation (cont.)
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LV End-Diastolic Diameter(LVEDDgt65
decompensated)
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LV End-Systolic Diameter(LVESDgt50mm
decompensated)
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Aortic Root Diameter
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Ejection Fraction Measurement(EFlt50
decompensated)
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AV Pressure Half-Time Measurement(P1/2 lt200ms
severe AI)
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Parasternal Long Axis With Color Flow Doppler
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Parasternal Long Axis With Color Flow Doppler
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Parasternal Short Axis Bicuspid Valve
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Parasternal Short With Color Flow Doppler
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Question 1

• What pre-operative recommendations should we
  make regarding his cardiovascular status?

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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

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Question 2

• Does vasodilator therapy delay need for aortic
  valve replacement surgery in patients such as
  this with asymptomatic aortic regurgitation?

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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 241046.

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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 3500.

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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 3197.

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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 (cilazapril0.03 to
  0.04mg/d in 9 patients and enalapril0.15-0.4mg/d
  in 3 patients). 12 placebo. Echo parameters again
  measured at avg. 3.4 years of follow-up.

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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.

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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 16424.

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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 331689.
• 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

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Nifedipine vs. Digoxin (cont.)

• Intervention randomly allocated to digoxin,
  0.25 mg/d or nifedipine, 20 mg BID
• Results

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Nifedipine vs. digoxin (cont.)
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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?

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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 (gt65mm) 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.

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ACC/AHA Guidelines
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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.