1. The Aortic valve and Cardiac Failure Aortic stenosis
Scherman J
Chris Barnard Division of Cardio-Thoracic Surgery
U n i v e r s i t y o f C a p e T o w n
Hannes Meyer Symposium
12 April 2008

2. Aortic valve and Cardiac Failure
Tight AS and impaired LVEF - Options and outcomes • •
Prognostic indicators: Stenosis and pseudo-stenosis
Associated coronary artery disease • •
The role of MIBI scanning

3. Pathophysiology of AS¹
Afterload
LV wall stress
Concentric LVH
When discussing AS it is important to briefly revisit the pathophysiology:
In adults with AS, the obstruction develops gradually—usually over decades. During this time, the left ventricle adapts to the systolic pressure overload through a hypertrophic process. The resulting increase in relative wall thickness is usually enough to counter the high intracavitary systolic pressure, and as a result, LV systolic wall stress (afterload) remains within the range of normal; and as long as the wall stress is normal the ejection fraction is preserved.
However, if the hypertrophic process is inadequate and relative wall thickness does not increase in proportion to pressure, wall stress increases and the high afterload causes a decrease in ejection fraction. (This is referred to as afterload mismatch). Depressed contractile state of the myocardium may also be responsible for a low ejection fraction, and it is often difficult clinically to determine whether a low ejection fraction is due to depressed contractility or to excessive afterload. When low ejection fraction is caused by depressed contractility, corrective surgery will be less beneficial than in patients with a low ejection fraction caused by high afterload.
2. The average life expectancy in patients with symptomatic AS is about 2 years.*******************
Symptomatic patients: mortality rates up to 90% in a 2 year natural history of the disease² •
¹ Cardiac Surgery in the adult 2008: Mihaljevic T, Sayeed M, Stamou S et al
² Ann Thor Surg 2004; 78: Sharma UC, Barenbrug B, Pokharel S et al

4. What is tight/severe AS?¹ Why measure stenosis severity?
Aortic valve and Cardiac Failure
What is tight/severe AS?¹ •
Transvalvular gradient (TVG)
Aortic valve area (AVA)
Maximum Aortic velocity
> 40mm Hg
< 1cm²
> 4m/s
The ACC/AHA Practise guidelines for the management of patients with valvular heart disease, classify AS into three gradings according to these three parameters.
TVG: < 25mmHg, 25-40, >40. AVA: >1.5cm², 1-1.5, <1. Velocity: mild (2.6 to 3.0 m/s), moderate (3 to 4 m/s), or severe (4 m/s).
2. Why measure stenosis severity? The clinical utility of measuring stenosis severity is two-fold: to predict the optimal timing of valve replacement and to ensure that valve disease is the cause of the patient’s symptoms.
Despite our reliance on conventional measures of hemodynamic severity for clinical decision making, it is clear that there is no single value for velocity, gradient, or valve area that defines symptom onset in an individual patient.
Stenosis severity should be evaluated using all clinical and hemodynamic tools available to the clinician, including physical examination, pressure gradient, the amount of hypertrophy induced, and valve area.**************
Why measure stenosis severity? •
¹ Circulation 2006; 114; e84-e231. Bonow RO et al

5. Variation in long term outcomes¹
Surgery for severe AS and low LVEF
Historically: Impaired LVEF is considered a predictor of poor outcome after AVR •
Variation in long term outcomes¹ •
Patient Categories² •
2.The published long term outcomes after surgery for severe as has shown considerable variation. (due to patient selection, and changes in pre-, intra-, postoperative Mx)
Previous authors have prompted surgeons to try better to define which subgroups with AS and ventricular dysfunction might benefit from AVR.
3. It is now understood that patients with impaired ventricular function who undergo AVR for severe AS fall roughly into one of three groups.
High gradient – good outcomes.
The other two groups consist of patients who have low gradients. In these situations, the mean pressure gradient generated by the left ventricle may be low despite the presence of severe stenosis. Where the low gradient is because of ‘‘afterload mismatch’’, which limits myocardial fibre shortening and thereby apparently reduces left ventricular systolic function, AVR is associated with good outcomes. Other patients with severe AS and low transvalvular gradients will, however, respond poorly after AVR. These patients are assumed to have a coexisting cardiomyopathy in addition to the myocardial dysfunction which attends ‘‘afterload mismatch’’. It is in this last group that the effects of aortic valve surgery are least well established.
The next question obviously becomes – how do you distinguish?? Is there any prognostic indicators???************
High gradient
Low gradient (‘afterload mismatch’)
Low gradient (cardiomyopathy)
¹ Eur J Cardiothorac Surg 2006; 29: Chukwuemeka A, Rao V, Armstrong S et al
² Circulation 2007; 115; Carabello BA.

6. Severe AS and low LVEF: Prognostic indicators
Dobutamine stress echocardiography •
True aortic stenosis
Pseudo-stenosis
Preoperative LVESVI¹ ≤ 90ml/m² •
cardiac mortality & LV recovery
Preoperative LVESDI² ≤ 27.5mm/m²
1. Although not well proven, it is generally accepted that the best way to differentiate between these two types of patients is to increase cardiac output, usually with a positively inotropic agent, and then to remeasure the pressure gradient and valve area. Because area flow-dependence is most marked below flows of 5.0 l/min, this value seems a good target. If flow and gradient increase in parallel, there will be little increase in valve area, indicating true stenosis is present. If flow increases out of proportion to gradient, valve area will increase substantially, indicating that truly severe stenosis is not present (aortic pseudostenosis). - Pseudo-AS has been defined as a condition in which calculated aortic valve area falsely overestimates the severity of AS when aortic valve area is calculated at low flow.
2. Tarantini et al looked at prognostic indicators of cardiac mortalty and LV recovery in 52 patients with severe AS and depressed LVEF. They found LVESVI > 90ml/m² as indicator of better survival and LV function recovery.
3. In another study, pre-operative LVESD index < 27.5 mm/m2 was 85% sensitive and 72% specific in predicting intermediate-term recovery of LV function after AVR.
4. Wrt a specific valve choice, several authors have found improved LV mass regression during early follow up after stenless valves, homografts compared to stented bioprosthesis and mechanical valves. ***************** • •
Role of valve choice in LV mass reduction
¹ Eur J Cardiothorac Surg 2003; 24: Tarantini G, Bujo P, Scognanamiglio R et al
²Int J Cardiol Article in press Ding W, Lam Y, Kaya MG et al

7. Options for Aortic valve replacement
Mechanical AVR
Bioprosthesis
Homograft
Autograft
Aortic valve repair
Percutaneous balloon valvotomy
Apico-aortic valved conduit
Percutaneous transcatheter valve insertion
Transapical AVR
The literature is replete with nonrandomized studies comparing various valve types, and claims of survival superiority of one over the other.
Most of these data are not comparable as the study groups differ.************

8. Options for Aortic valve replacement•
Considerations
Durability and Structural valve deterioration (Age)
Risk of thromboembolism and haemorrhagic complications
Patient preference
Pregnancy
So the important aspects to consider when choosing a valve type for an individual includes:
The durability of the valve – which relates to age.
The risk of…………… - which relates to the use of anticoagulation.
*************

9. Major criteria for Aortic valve selection
Class I
1. A mechanical prosthesis is recommended for AVR in patients with a mechanical valve in the mitral or tricuspid position. (Level of Evidence: C)
2. A bioprosthesis is recommended for AVR in patients of any age who will not take warfarin or who have major medical contraindications to warfarin therapy. (Level of Evidence: C)
Class IIa
1. Patient preference is a reasonable consideration in the selection of aortic valve operation and valve prosthesis. A mechanical prosthesis is reasonable for AVR in patients under 65 years of age who do not have a contraindication to anticoagulation. A bioprosthesis is reasonable for AVR in patients under 65 years of age who elect to receive this valve for lifestyle considerations after detailed discussions of the risks of anticoagulation versus the likelihood that a second AVR may be necessary in the future. (Level of Evidence: C)
2. A bioprosthesis is reasonable for AVR in patients aged 65 years or older without risk factors for thromboembolism. (Level of Evidence: C)
3. Aortic valve re-replacement with a homograft is reasonable for patients with active prosthetic valve endocarditis. (Level of Evidence: C)
Class IIb
A bioprosthesis might be considered for AVR in a woman of childbearing age. (Level of Evidence: C)
ACC/AHA Guidelines for the management of patients with valvular heart disease, 2006

10. Mechanical Aortic valve prosthesis
Caged ball
Durable
Easy insertion, redo
Anticoagulation
Tilting disk
Bileaflet

11. Stented and Non-stented bioprosthesis•
Low thromboembolism rates without Warfarin •
Freedom from structural valve deterioration is age-specific •
Stented bioprosthesis vs
Compared to mech valves, the risk of thromboembolism is lower with bioprosthesis.
2. With bioprosthesis, SVD is the concern and is age-spesific. Above 65yrs – 90% freedom at 15 yrs. Below 40yrs – 50% reintervention required at 10 yrs.
3. In general: stented bovine pericardial valves seem to be doing better than stented procine valves, wrt freedom from SVD and lower TVG’s relating to greater LV mass reduction post operatively.
4. The argument favoring the use of stentless valves is that stented valves of any kind are at least partially stenotic (particularly in small sizes) and that even small postoperative gradients may lead to incomplete LV mass regression postoperatively, which will, in turn, lead to impaired long-term survival and symptom status.
Porcine
Pericardial •
Stentless bioprosthesis
Enhanced hemodynamic efficiency
Less TVG

12. Impact of age on structural valve dysfunction
Stented and Non-stented bioprosthesis •
Low thromboembolism rates without Warfarin •
Freedom from structural valve deterioration is age-specific
The graft shows that at increasing age there is a lower rate of structural valve deterioration.
Impact of age on structural valve dysfunction
¹ Ann Thorac Surg 2001: 72; , Banbury MK, Cosgrove DM, White JA et al.

13. Stented and Non-stented bioprosthesis•
Low thromboembolism rates without Warfarin •
Freedom from structural valve deterioration is age-specific •
Stented bioprosthesis vs
Advantage of bioprosthesis over mech valves. This also relates to outcomes wrt thromboembolic and hemoragic complications.
2. With bioprosthesis, SVD is the concern and is age-spesific. Above 65yrs – 90% freedom at 15 yrs. Below 40yrs – 50% reintervention required at 10 yrs.
3. There is some evidence suggesting that stented bovine pericardial valves seem to be doing better than stented procine valves, wrt freedom from SVD and lower TVG’s relating to greater LV mass reduction post operatively.
4. The argument favoring the use of stentless valves is that stented valves of any kind are at least partially stenotic (particularly in small sizes) and that even small postoperative gradients may lead to incomplete LV mass regression postoperatively, which will, in turn, lead to impaired long-term survival and symptom status.
Porcine
Pericardial •
Stentless bioprosthesis
Enhanced haemodynamic efficiency
Less TVG

14. Aortic valve Homografts
Excellent haemodynamic efficiency
Low risk of thromboembolism
Structural valve deterioration
Potential difficult redo surgery
Despite early enthusiasm for homograft aortic valves, it appears that their durability is no better than that of bioprosthetic aortic valves.
Except for the setting of active endocarditis requiring emergent surgery, we rarely use homografts in adults with aortic stenosis.

15. Pulmonary valve autotransplantation•
Advantages
Excellent hemodynamic efficiency
Low risk of thrombo-embolism
Growth potential
Low risk of endocarditis •
Disadvantages
Potential aortic root dilatation: 10% has AR after 10 yrs.
2 Valves at risk
More complex surgery
Potential aortic root dilatation
Homograft – Structural valve deterioration

16. Aortic valve repair Limited expertise•
Limited expertise •
High rates of restenosis and recalcification

17. Percutaneous balloon aortic valvotomy
Class IIb
1. Aortic balloon valvotomy might be reasonable as a
bridge to surgery in hemodynamically unstable adult
patients with AS who are at high risk for AVR. (Level
of Evidence: C)
2. Aortic balloon valvotomy might be reasonable for
palliation in adult patients with AS in whom AVR
cannot be performed because of serious comorbid
conditions. (Level of Evidence: C)
Class III
Aortic balloon valvotomy is not recommended as an
alternative to AVR in adult patients with AS; certain
younger adults without valve calcification may be an
exception. (Level of Evidence: B)
Bridge to surgery
Comorbidities
….. So it therefor only has a palliative role.
Not a alternative to AVR
ACC/AHA Guidelines for the management of patients with valvular heart disease, 2006

18. LV-to-Descending Aortic shunt•
Favourable short term outcomes •
Unknown long term hemodynamics and complication rates
In situations involving pathologies that make standard AVR operations particularly risky, such as multiple previous operations, severe aortic calcification, and previous radiation therapy, a left ventricle–to– descending thoracic aortic shunt using a Dacron graft containing a valve can be an effective alternative treatment.
No long term data is available on their performance.

19. Percutaneous transcatheter valve insertion
¹J Am Coll Cardiol. 2004; 43: Cribier A, Eltchaninoff H, Tron C et al.

20. Transapical Aortic valve implantation
Via left minithoracotomy on beating heart during rapid ventricular pacing, via 33Fr sheath.
The current biggest series has been published by the University of Leipzig-50 patients.
Transapical vs Transfemoral – has increased stroke rates, probably due to more aortic manipulation.*****************
Cribier Edwards prosthesis: Balloon expandible pericardial xenograft
Transapical aortic valve implantation
Eur J Card Surg Article in press. Walther T, Falk V, Kempfert J et al

21. Management strategy for severe AS
Figure 3. Management strategy for patients with severe aortic stenosis. Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is discordance between clinical findings and echocardiography. Modified from CM Otto. Valvular aortic stenosis: disease severity and timing of intervention. J Am Coll Cardiol 2006;47:2141–51
In symptomatic patients with AS, AVR improves symptoms and improves survival. These salutary results of surgery are partly dependent on LV function. The outcome is similar in patients with normal LV function and in those with moderate depression of contractile function. The depressed ejection fraction in many patients in this latter group is caused by excessive afterload (afterload mismatch), and LV function improves after AVR in such patients. If LV dysfunction is not caused by afterload mismatch, survival is still improved, but improvement in LV function and resolution of symptoms might not be complete after AVR. Therefore, in the absence of serious comorbid conditions, AVR is indicated in virtually all symptomatic patients with severe AS.
¹ Circulation 2006; 114; e84-e231. Bonow RO et al

22. AS associated with coronary artery disease
In patients with AS, prevalence of CAD is 40-50% in those with typical angina, 25% in those with atypical chest pain, and 20% in those without chest pain¹ •
In patients with severe AS, angina is a common symptom in young patients with normal coronaries.
CAD is a common finding in older symptomatic men with AS •
1. The probability of developing CAD in the general population and the prevalence of CAD in patients who come to medical attention can be estimated on the basis of age, sex, and clinical risk factors. The prevalence of CAD in patients with valvular heart disease is determined by these same variables
2. In patients with severe AS, angina is a common symptom in young patients with normal coronary arteries and congenital or rheumatic AS. On the other hand, CAD is a common finding in older symptomatic men with AS.
3……. In contrast, ischemic symptoms in patients with valvular heart disease may have multiple causes, such as LV chamber enlargement, increased wall stress or wall thickening with subendocardial ischemia, and RV hypertrophy.
Angina is a less specific indicator of CAD in patients with valvular heart disease than in the general population •
¹ Circulation 2006; 114; e84-e231. Bonow RO et al

23. Outcomes: AS associated with CAD
Coexisting CAD is a complex risk factor for premature death after operation •
Concomitant CABG carries a higher earlier mortality (6.3%) than either AVR alone (3.9%) or CABG alone (2.8%) •
Patients with both aortic valve and CAD who undergo only AVR have lower survival than patients who undergo concomitant CABG •
2. Numbers from STS database.**************
The number of bypass grafts does not adversely affect survival. The patient’s preoperative risk factors is a better predictor of outcome¹ •
¹ Ann Thorac Surg 2007; 83: Kobayashi KJ, Williams JA, Nwakanma L et al

24. AS associated with coronary artery disease
Indications for catheterization •
Class I
1. Coronary angiography is indicated before valve surgery (including infective endocarditis) or mitral balloon commissurotomy in patients with chest pain, other objective evidence of ischemia, decreased LV systolic function, history of CAD, or coronary risk factors (including age). Patients undergoing mitral balloon valvotomy need not undergo coronary angiography solely on the basis of coronary risk factors. (Level of Evidence: C)
2. Coronary angiography is indicated in patients with apparently mild to moderate valvular heart disease but with progressive angina (Canadian Heart Association functional class II or greater), objective evidence of ischemia, decreased LV systolic function, or overt congestive heart failure. (Level of Evidence: C)
3. Coronary angiography should be performed before valve surgery in men aged 35 years or older, premenopausal women aged 35 years or older who have coronary risk factors, and postmenopausal women. (Level of Evidence: C)
History
Symptoms
Risk Factors
Age
ACC/AHA Guidelines for the management of patients with valvular heart disease, 2006

25. When to do CABG in patients undergoing AVR
Treatment of CAD at the time of AVR •
Class I
Patients undergoing AVR with significant stenoses
(greater than or equal to 70% reduction in luminal
diameter) in major coronary arteries should be
treated with bypass grafting. (Level of Evidence: C)
Class IIa
1. In patients undergoing AVR and coronary bypass
grafting, use of the left internal thoracic artery is
reasonable for bypass of stenoses of the left anterior
descending coronary artery greater than or equal to
50% to 70%. (Level of Evidence: C)
2. For patients undergoing AVR with moderate stenosis
(50% to 70% reduction in luminal diameter), it is
reasonable to perform coronary bypass grafting in
major coronary arteries. (Level of Evidence: C)
Significant stenosis
The reverse also holds true:
Patients with severe as and important cad should have avr at the time of cabg. The approach is less clear if as is moderate or mild, because it is difficult to predict when these patients will develop severe as after coronary revascularization.
Moderate stensosis
ACC/AHA Guidelines for the management of patients with valvular heart disease, 2006

26. When to do AVR in patients undergoing CABG
Class I
AVR is indicated in patients undergoing CABG who
have severe AS who meet the criteria for valve
replacement. (Level of Evidence: C)
Class IIa
AVR is reasonable in patients undergoing CABG
who have moderate AS (mean gradient 30 to 50 mm
Hg or Doppler velocity 3 to 4 m per second). (Level
of Evidence: B)
Class IIb
AVR may be considered in patients undergoing
CABG who have mild AS (mean gradient less than
30 mm Hg or Doppler velocity less than 3 m per
second) when there is evidence, such as moderate severe
valve calcification, that progression may be
rapid. (Level of Evidence: C)
Severe aortic stenosis
Moderate stensosis
The reverse also holds true:
Patients with severe as and important cad should have avr at the time of cabg. The approach is less clear if as is moderate or mild, because it is difficult to predict when these patients will develop severe as after coronary revascularization.
Mild stensosis
ACC/AHA Guidelines for the management of patients with valvular heart disease, 2006

27. Cardiac Radionuclide Imaging•
Assessment of LV Function
Assessment of CAD (MIBI)
Assessment of myocardial viability
Screening for CAD in patients with severe aortic stenosis with angina • •
Coronary angiography remains the gold standard in the preoperative work-up of patients with aortic stenosis presenting with angina¹
Due to their non-invasive nature the use of cardiac radionuclide imaging have been investigated in the assessment of LV Fx, CAD, myocardial viability.
Assessment of CAD – MIBI: The amount of radioactive exposure you will receive is less than from an angiogram. The radioactive tracer we use is called Technetium-99m-NUBI. For those patients with a background in Chemistry, MIBI is an acronym for 2-methoxy isobutyl isonitrile. Once injected, MIBI travels to your heart via the blood supply and then becomes trapped within healthy, active muscle cells in the heart.
....and much interest has been in patients with severe aortic stenosis who presents with angina, to rule out associated cad. The sensitivity and specificity of these test are such that angiography has remained the goldstandard for the assessment of associated cad.
Assessment of miocardial viability- Most studies evaluating the radionuclide techniques for assessing viability have focused on analysis of resting tracer uptake. The uptake of 201Tl is an energy-dependent process requiring intact cell membrane integrity, and he presence of 201Tl implies preserved myocyte cellular viability.
Because of the lack of specificity and sensitivity of angina for the concomitant presence of coronary disease in aortic stenosis, there has been much interest in the use of myocardial perfusion imaging in preoperative evaluation. The sensitivity and specificity of stress perfusion are relatively good but probably not adequate for patients about to undergo valve surgery. Thus, in practice, perfusion imaging has not supplanted coronary angiography in the preoperative work-up of patients with aortic stenosis.*******
¹Circulation. 2006; 108; 1404 – Klocke FJ, Baird MJ, Lorell BH et al

28. Conclusion •
Most patients with AS and depressed LVEF will benefit from AVR
Favourable Prognostic factors: •
True aortic stenosis
LVESVI ≤ 90ml/m²
LVESDI ≤ 27.5mm/m²
Replacement valves with low TVG’s •
Severe AS with associated mod-severe CAD: Ø for both
CAD with associated severe AS: Ø for both
CAD with associated mild-mod AS: Ø for CAD, Ø for AS reasonable
Cardiac radionuclide imaging – some use in screening, but not the gold standard •

29. thank you