Joel Boudreaux MD, Mohammad Bashir MBBS
University of Iowa
7/5/2024
Abbreviations & Definitions
AR – Aortic regurgitation; used interchangeably with aortic insufficiency (AI)
AV – Aortic valve
AVR – Aortic valve replacement
EF – Ejection fraction
LV – Left ventricle
LVEDD – Left ventricular end diastolic diameter
LVESD – Left ventricular end systolic diameter
Indications & Guidelines for Management by Grade/Stage of Disease
Aortic valve regurgitation (AR) can be broadly categorized into acute and chronic phenotypes. While intervention for acute AR is typically indicated, intervention for chronic AR is dependent on stage. In addition to symptoms, each stage is characterized by valve anatomy, valve hemodynamics, and the function and dimensions of the left ventricle (LV).
Surgical indications and timing of intervention for AR are outlined in the ACC/AHA guidelines published in 2020.1 Indications referencedare derived from this publication unless otherwise noted.
Stages of Chronic AR
A: At risk (Normal valve hemodynamics in the setting of a bicuspid or sclerotic AV)
B: Progressive (mild to moderate AR with normal EF and normal to mildly dilated LV dimensions)
C: Asymptomatic severe
C1: Normal EF (>55%) and mild to moderate LV dilation (LVESD <50 mm)
C2: Reduced EF (<55%) or severe LV dilation (LVESD >50 mm)
D: Symptomatic severe
Indications for Surgical Intervention in Chronic AR
Class I
Symptomatic severe AR
Asymptomatic severe AR with LV dysfunction (LVEF 55%)
Asymptomatic severe AR undergoing cardiac surgery for other indications
Class IIa
Asymptomatic severe AR with LV enlargement (LVESD >50mm) and EF >55%
Asymptomatic moderate AR undergoing cardiac surgery for other indications
Class IIb
Asymptomatic severe AR with EF >55% and low surgical risk with progressive LV dysfunction or LV enlargement on 3 serial studies
Valve Choice
Note that the recommendations below apply to both stenotic and regurgitant aortic valves.
For patients who require AVR, the choice of a prosthetic valve should be based on a shared decision-making process that accounts for the patient’s values and preferences and includes a discussion of the indications for and risks of anticoagulant therapy and the potential need for and risks associated with valve reintervention. (Class I)
For patients of any age requiring AVR for whom anticoagulant therapy is contraindicated, cannot be managed appropriately, or is not desired, a bioprosthetic valve is recommended. (Class I)
For patients <50 years of age who do not have a contraindication to anticoagulation and require AVR, it is reasonable to choose a mechanical over a bioprosthetic valve. (Class IIa)
For patients 50 to 65 years of age who require AVR and do not have a contraindication to anticoagulation, it is reasonable to individualize the choice of either a mechanical or bioprosthetic AVR, with consideration of individual patient factors and after informed shared decision-making. (Class IIa)
In patients >65 years of age who require AVR, it is reasonable to choose a bioprosthetic over a mechanical valve. (Class IIa)
Special Situations
Bicuspid Aortic Valve:
In patients with BAV and severe AR who meet the criteria for AVR, aortic valve repair may be considered in selected patients if the surgery is performed at a comprehensive valve center. (Class IIb)
Concomitant Stenosis and Regurgitation
In symptomatic patients with combined AS and AR and a peak transvalvular jet velocity of ≥4.0 m/s or a mean transvalvular gradient of ≥40 mmHg, AVR is recommended. (Class I)
In asymptomatic patients with combined AS and AR who have a jet velocity of ≥4.0 m/s with an LVEF <50%, SAVR is recommended. (Class 1)
Prosthetic Valve Regurgitation
In patients with intractable hemolysis or HF attributable to prosthetic transvalvular or paravalvular leak, surgery is recommended unless surgical risk is high or prohibitive. (Class I)
In asymptomatic patients with severe prosthetic regurgitation and low operative risk, surgery is reasonable. (Class IIa)
In patients with prosthetic paravalvular regurgitation with the following: 1) either intractable hemolysis or NYHA class III or IV symptoms, 2) who are at high or prohibitive surgical risk, and 3) have anatomic features suitable for catheter-based therapy, percutaneous repair of paravalvular leak is reasonable when performed at a comprehensive valve center. (Class IIa)
For patients with severe HF symptoms caused by bioprosthetic valve regurgitation who are at high to prohibitive surgical risk, a transcatheter valve-in-valve procedure is reasonable when performed at a comprehensive valve center. (Class IIa)
Transcatheter Valve Intervention
Due to the annular and root dilation often present in chronic AR, as well as the lack of significant valvular calcification, transcatheter AVR (TAVR) has a limited role in the management of these patients. In patients with isolated severe AR with surgical indications and who are candidates for surgery, TAVR should not be performed. (Class III)
Summary Table: Surgical Indications for Aortic Regurgitation
| Stage | Criteria | Indication | Evidence |
|---|---|---|---|
| Acute | 2 Evidence of elevated LV end diastolic pressure including a pressure halftime of less than 300ms on the AR velocity curve Evidence of pulmonary congestion | Surgical repair indicated in most cases | 1 |
| Chronic | |||
| A (At Risk) | Bicuspid aortic valve; aortic valve sclerosis; aortic root or ascending aorta pathology; infective endocarditis; rheumatic heart disease | There is no indication for surgical intervention | |
| B (Progressive) | Mild AR: Jet width <25% of LVOT Vena contracta <0.3 cm Regurgitant volume <30 mL/beat Regurgitant fraction <30% ERO <0.10 cm2 Angiography grade 1 Moderate AR: Jet width 25–64% of LVOT Vena contracta 0.3–0.6 cm Regurgitant volume 30–59 mL/beat Regurgitant fraction 30-49% ERO 0.10–0.29 cm2 Angiography grade 2 |
Class 2a indication for SAVR if undergoing cardiac surgery for other indications | 1 |
| C (Asymptomatic Severe) | 2 OR Angiography grade 3 to 4 AND Evidence of left ventricular dilatation | Class 1 indication for AVR if undergoing cardiac surgery for other indications | 1 |
| Stage C1 | As above, with normal LVEF (>55%) and mild to moderate LV dilation (LVESD <50 mm) | Class IIb indication for AVR if low surgical risk when there is progressive decline in EF on 3 or more serial studies to low normal range (55-60%) or progressive increase in LV dilation into the severe range (LVEDD >65mm) | 1,4,6 |
| Stage C2 | 2) | Class I indication for AVR if EF no other cause for systolic dysfunction is identified Class 2a recommendation if EF is >55% and LV is severely enlarged (LVESD >50 mm or indexed LVESD >25 mm/m2) | 1,4,5,7 1,4,6,8 |
| D (Symptomatic Severe) | 2 OR Angiography grade 3 to 4 AND Evidence of left ventricular dilatation | Class I indication for AVR | 1,2,7 |
Supporting Evidence for Current Indications & Guidelines
The three key parameters defining the need for intervention in chronic AR are symptoms, LV systolic dysfunction, and LV enlargement. Patients with moderate to severe AR left untreated have a mortality above 34%.2 Both survival and functional status are related to the development of symptoms, and even mild symptoms are predictive of excess mortality. 2,6
LV systolic dysfunction is an important predictor of outcomes in chronic AR with or without symptoms. Dujardin and colleagues identified an LVEF <55% as a significant predictor of mortality.2 Other studies have similarly found systolic dysfunction predictive of mortality following intervention.8 When compared to mild systolic dysfunction, those with severe systolic dysfunction (LVEF <35%) are at greater risk of mortality following intervention.7 While postoperative EF improves in both groups, both early and late mortality, as well as heart failure events, are greater in those with severe dysfunction.5 These data are reflected in the 2020 guidelines, where the systolic dysfunction cutoff for intervention decreased from 60 to 55%.1
LV dimensions are also pertinent predictors of outcomes in chronic AR. LV enlargement, as defined by an LVESD >40mm, has been shown predictive of post-operative LV dysfunction.8 Other studies have implicated the LVESD indexed for body surface area (LVESDi) >25mm2 as predictive of excess mortality in patients with chronic AR. Newer data goes further in showing an LVESDi >20mm2 as predictive of mortality after AVR.4 Though the 2014 guideline updates decreased the LV size cutoff for intervention to an LVESD of 50mm, no subsequent changes were made in the 2020 guidelines. This remains a controversial subject, and we can expect further debate in future guideline revisions.
In patients with an indication for AVR, the choice of prosthetic valve type, either mechanical or bioprosthetic, depends largely upon age, ability to tolerate anticoagulation, and patient preference. A large retrospective review of patients undergoing AVR with either a biological or mechanical prosthesis found a significant improvement in 15-year survival in those receiving a mechanical prosthesis in patients between 45 and 54 years of age.3 This mortality benefit was not appreciated above 55 years of age. Mechanical valves were associated with a lower need for reoperation but a higher risk of bleeding.
Ongoing Trials/Recent Publications
Though TAVR presently plays a limited role in AR due to the annular and root dilation often present in chronic AR, as well as the lack of significant valvular calcification needed to hold the prosthesis in place, use of a self-expanding valve in select patients deemed high-risk for surgery has been shown feasible. However, mortality in these patients (13%) greatly exceeds that of TAVR used for aortic stenosis.9 A novel transcatheter valve designed for use in pure AR has shown promising early results.10 We can expect further investigation in the coming years.
Expert Commentary
When presented with acute AI, it is important to note the etiology. Many times, this is associated with infective endocarditis or acute type A aortic dissection. In these instances, AVR or surgery may be indicated for those etiologies rather than the degree of AI. Always look for endocarditis or aortic dissection when presented with a patient with acute AI. However, when chronic AI is associated with root dilatation, surgery might be indicated for the aneurysm according to its size rather than the degree of AI, EF, or size of the LV. In those instances, a valve-sparing root operation might be indicated if done at a comprehensive valve center. AVR may be indicated in patients with mild AI or greater in the setting of LV assist device placement. This is to prevent re-circulation in the ventricular assist device circuit.
Sources
- Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Circulation. 2021;143(5):e72-e227.
- Dujardin KS, Enriquez-Sarano M, Schaff HV, et al. Mortality and morbidity of aortic regurgitation in clinical practice. A long-term follow-up study. Circulation. 1999;99:1851–7.
- Goldstone AB, Chiu P, Baiocchi M, et al. Mechanical or biologic prostheses for aortic-valve and mitral-valve replacement. N Engl J Med. 2017;377:1847–57.
- Yang LT, Michelena HI, Scott CG, et al. Outcomes in Chronic Hemodynamically Significant Aortic Regurgitation and Limitations of Current Guidelines. J Am Coll Cardiol. 2019;73(14):1741-1752.
- Chaliki HP, Mohty D, Avierinos J-F, et al. Outcomes after aortic valve replacement in patients with severe aortic regurgitation and markedly reduced left ventricular function. Circulation. 2002;106:2687–93.
- Bonow RO, Picone AL, McIntosh CL, et al. Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function. Circulation. 1985;72(6):1244-1256.
- Bhudia SK, McCarthy PM, Kumpati GS, et al. Improved outcomes after aortic valve surgery for chronic aortic regurgitation with severe left ventricular dysfunction. J Am Coll Cardiol. 2007;49:1465–71.
- Murashita T, Schaff HV, Suri RM, et al. Impact of left ventricular systolic function on outcome of correction of chronic severe aortic valve regurgitation: implications for timing of surgical intervention. Ann Thorac Surg. 2017;103:1222–8.
- Anwaruddin S, Desai ND, Szeto WY, et al. Self-Expanding Valve System for Treatment of Native Aortic Regurgitation by Transcatheter Aortic Valve Implantation (from the STS/ACC TVT Registry). Am J Cardiol. 2019;124(5):781-788.
- Vahl TP, Thourani VH, Makkar RR, et al. Transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation (ALIGN-AR): a prospective, multicentre, single-arm study. Lancet. 2024;403(10435):1451-1459.
