Fig. 19.1
This figure demonstrates the subtle differences in ischemic mitral regurgitation (IMR) and functional mitral regurgitation (FMR) (Reprinted from Timek and Miller [7], © 2011, with permission from Elsevier)
Dynamic Nature of Mitral Regurgitation
IMR/FMR is also very dynamic in nature with variation in severity over time and level of activity. Inotropes will increase the dp/dt promoting more closing of the valve and reducing MR [23, 24]. Conditions (anesthesia, diuretic therapy) leading to a reduction in preload and left ventricular diastolic size will reduce MR [25]. Lancellotti et al. have demonstrated the importance of exercise echocardiography as a tool in unmasking MR in patients with congestive heart failure [26, 27]. A change in the effective regurgitant orifice area (EROA) is due to a systolic expansion of the mitral annulus; leading to increase in cooptation distance, increase in the tenting area (area between the mitral annulus and the leaflet cooptation line) and the sphericity index (both end-systolic and end-diastolic) [28]. A sudden increase in MR during daily activities can provoke flash pulmonary edema, acute systolic pulmonary hypertension and electromechanical dys-synchrony promoting further MR [27, 29, 30]. Any discrepancy between symptoms and resting echocardiographic findings should be investigated with exercise testing to unmask latent MR. Exercise induced MR is of great prognostic importance in these patients; a change in EROA >13 mm2 being a significant predictor of late mortality as demonstrated by Lancelotti and colleagues [31, 32] (Fig. 19.2).
Fig. 19.2
Lancellotti and colleagues demonstrated that survival was significantly different in patients stratified by effective regurgitant orifice (ERO); important cut-off values being ERO ≥20 mm2 at rest (a) and an increase in ERO ≥ 13 mm2 on exercise (b) (Reprinted with permission from Lancellotti et al. [31] by permission of Oxford University Press)
Quantification of Ischemic Mitral Regurgitation/ Functional Mitral Regurgitation
The following factors need to be considered for the quantification of IMR/FMR:
- (a)
Severity of MR; number and direction of the regurgitant jets &
- (b)
Degree of LV dilatation, dysfunction and remodeling.
Echocardiography needs to focus on both the mitral valve anatomy as well as the LV geometry: The important factors which need to be considered for evaluating a patient with mitral regurgitation are: LV indices: left ventricular volumes, ejection fraction, sphericity index, the diastolic function and wall motion abnormalities & MV indices: mitral annular dimensions, effective regurgitant orifice area (EROA), co-aptation depth, tenting area and tenting volume on 3-D Echo (Fig. 19.3) [16]. Table 19.1 denotes the measurements obtained with echocardiographic examination of 21 control subjects and 128 patients with left ventricular dysfunction (<50 %).
Fig. 19.3
A diagrammatic representation of the co-aptation depth (H), the tenting area (T) and Regurgitant volume; all are important in the quantification of mitral regurgitation (Reprinted with permission from Agricola et al. [16], by permission of Oxford University Press)
Table 19.1
denotes the measurements obtained with echocardiographic examination of 21 control subjects and 128 patients with left ventricular dysfunction (<50 %)
Variable | Comparison with controls | Comparison within LVD | Correlation with ERO | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
Control (n = 21) | LVD (n = 128) | p | No MR (n = 21) | ERO <10 mm2 | ERO 10 – <20 mm2 | ERO >20 mm2 | p for trend | r | p | |
Baseline characteristics | ||||||||||
Age, y | 62 ± 10 | 65 ± 13 | 0.20 | 57 ± 16 | 68 ± 13 | 65 ± 14 | 68 ± 11 | 0.03 | 0.20 | 0.02 |
Sex, % males | 57 | 65 | 0.50 | 76 | 42 | 70 | 68 | 0.56 | −0.14 | 0.12 |
BSA, m2 | 1.9 ± 0.3 | 1.9 ± 0.2 | 0.52 | 2.0 ± 0.2 | 1.8 ± 0.3 | 1.9 ± 0.2 | 1.9 ± 0.2 | 0.61 | −0.04 | 0.70 |
SBP, mmHg | 134 ± 19 | 125 ± 21 | 0.05 | 126 ± 18 | 133 ± 21 | 127 ± 21 | 116 ± 19 | 0.003 | −0.37 | 0.0001 |
CI, L/min2/m2 | 2.9 ± 0.4 | 2.4 ± 0.5 | 0.0003 | 2.7 ± 0.5 | 2.6 ± 0.5 | 2.4 ± 0.5 | 2.3 ± 0.6 | 0.0005 | −0.34 | 0.0001 |
Global LV remodeling | ||||||||||
EDVI, ml/m2 | 65 ± 10 | 149 ± 46 | <0.0001 | 115 ± 28 | 150 ± 34 | 145 ± 52 | 169 ± 46 | 0.0001 | 0.49 | 0.0001 |
ESVI, ml/m2 | 24 ± 6 | 106 ± 43 | <0.0001 | 78 ± 29 | 108 ± 33 | 104 ± 51 | 119 ± 42 | 0.002 | −0.31 | 0.0005 |
Systolic L/D | 2.5 ± 0.5 | 1.5 ± 0.2 | <0.0001 | 1.6 ± 0.2 | 1.4 ± 0.2 | 1.5 ± 0.2 | 1.4 ± 0.2 | 0.012 | −0.31 | 0.0005 |
Diastolic L/D | 1.9 ± 0.2 | 1.4 ± 0.2 | 0.0001 | 1.5 ± 0.2 | 1.3 ± 0.2 | 1.4 ± 0.1 | 1.3 ± 0.2 | 0.007 | −0.29 | 0.001 |
EF, % | 64 ± 4 | 31 ± 9 | <0.0001 | 34 ± 10 | 28 ± 7 | 30 ± 10 | 31 ± 9 | 0.83 | −0.09 | 0.32 |
ESWS, g/cm2 | 158 ± 26 | 271 ± 67 | <0.0001 | 244 ± 56 | 284 ± 81 | 281 ± 65 | 267 ± 65 | 0.68 | 0.13 | 0.17 |
Secondary Changes in Leaflet Structure
Although this is primarily a condition of the left ventricle, the leaflets themselves are far from innocent by-standers in the disease process (Fig. 19.4 ). While the leaflets may appear grossly normal at surgery, significant biochemical changes have been identified in the leaflets in patients with long-standing cardiomyopathy. Grande-Allen and colleagues studied leaflet tissue obtained from recipient hearts explanted at the time of transplantation and tested them with tissue obtained from normal hearts at autopsy. Biochemically these leaflets had a higher cellular count (78 % more), higher collagen density (15 % more) and lower water content (7 % less). These changes made the leaflets thicker and less pliable compared to their normal counterparts. The chordae tendinae also had a smaller cross-sectional area compared to the normal cohort. The leaflets were 28–41 % longer than normal [34]. The leaflet length correlated with left atrial diameter, annular diameter while thickness correlated with annular size as well as left ventricular and left atrial dimensions [34].
Fig. 19.4
The flowchart by Gravnde-Allen et al. demonstrates changes in leaflet structure and composition in ischemic/functional mitral regurgitation (Reprinted from Grande-Allen et al. [34], © 2005, with permission from Elsevier)
Importance of Mitral Regurgitation on Survival with Heart Failure
The presence of IMR has a profound influence on survival. In 1988, Hickey et al. demonstrated a 34 % increase in mortality for patients with severe IMR compared to those with coronary artery disease and no MR. Even patients with mild IMR had a 4 % increase in mortality above baseline [35]. The Survival and Ventricular enlargement study (SAVE) demonstrated that even the presence of mild MR was an independent risk factor for cardiovascular mortality (Relative Risk = 2(1.28–3.04)) during a 3.5 years follow-up period [36]. Grigioni and colleagues compared 194 (IMR+) and 104 (IMR –ve) after matching them for age, gender and ejection fraction over a patient-year period of 817 years [37]. The IMR cohort experienced a much higher long-term mortality (62 +/− 5 % vs 39 +/− 6 %; p < 0.001) at the end of 5 years, with the presence of IMR independently affecting survival on a multi-variate analysis. The mean ejection fraction in this study was in the approximate range of 26–36 % for both cohorts (Fig. 19.5).
Fig. 19.5
Patients with ischemic MR clearly have a poorer survival as demonstrated by this Kaplan-Meier curve (Reprinted from Grigioni et al. [37], © 2001, with permission from Wolters Kluwer Health Inc./American Heart Publications)
Trichon et al. evaluated 2057 pts with symptomatic systolic heart failure undergoing evaluation in the cardiac catheterization laboratory over a 14-year period. While 56 % had IMR of any grade, importantly almost half of these patients had moderate/severe IMR. They have demonstrated a 40 % survival at 5 years and have demonstrated that the presence of even moderate IMR is a risk factor for early mortality [38]. A study from the University of Michigan in 1421 patients with congestive heart failure (LV ejection fraction <35 %) demonstrated 50 % survival of 628 +/− 47 days for patients with severe IMR [39]. Importantly almost 50 % of the patients in this study had at least moderate MR, which demonstrates the important relationship between left ventricular systolic dysfunction and the presence of MR. Ellis et al. demonstrated an inferior outcomes in patients with IMR undergoing percutaneous intervention, especially in the subset of patients with LVEF <40 % [40].
Thus many retrospective studies have demonstrated poorer survival in patients with IMR with approximately 40 %–50 % survival at the end of 3–5 years.
What Degree of Ischemic Mitral Regurgitation Should Be Addressed?
All agree that moderate-severe IMR should be addressed at the time of coronary artery bypass grafting (CABG) [41, 42]. Correcting regurgitation at the time of CABG improves exercise capacity, symptoms and promotes reverse ventricular remodeling [43, 44]. The American College of Cardiology recommends concomitant mitral valve surgery in patients with LVEF <40 % with severe symptomatic mitral regurgitation. The committee prefers valve repair; but if that is not possible then replacement should be carried out with chordal preservation [45].
Results of Repair and Replacement with Ischemic/ Functional Mitral Regurgitation
David and colleagues were among the first to demonstrate good results with mitral valve replacement while preserving the subvalvar apparatus [46]. Bolling and Bach were the first to demonstrate successful mitral annuloplasty (MVA) in patients with cardiomyopathy. They were successful in operating on 16 patients (mean ejection fraction 16 +/− 5 %) without peri-operative mortality and demonstrated significant improvements in stroke volume, ejection fraction and cardiac output with concomitant reduction in regurgitant volume and fraction [2]. This landmark achievement disputed the theory of the “pop-off” effect of the mitral valve for a failing left ventricle. The Bolling hypothesis is that there is an “ annular solution for a ventricular problem… such that reconstruction of the mitral valve annulus` geometric abnormality by an undersized ring restores valvular competency, alleviates excessive ventricular workload, improves ventricular geometry and improves ventricular function”. This concept was validated by the Stanford group using animal models [47]. Mihaljevic and colleagues studied patients undergoing CABG + MVA (290) and CABG alone (100) and presented their results in a propensity-matched cohort [48]. A restrictive annuloplasty with the use of both rigid rings (22 %) (Carpentier-Edwards Classic Annuloplasty ring, Edward Lifesciences, Irvine, CA), partially flexible posterior annuloplasty bands (63 %) (Cosgrove-Edwards Annuloplasty system, Edward Lifesciences, Irvine, CA) and even posterior suture plication with autologous pericardium or Peri-Guard graft (6.9 %) (Baxter Healthcare Corp., Deerfield, IL) was performed. Their estimated survival for MVA + CABG (92 %, 74 % and 39 %) and CABG (88 %, 75 % and 47 % ) at the end of 1, 5 and 10 years was comparable (p = 0.3). In the early period of follow-up, renal insufficiency, severe wall motion abnormalities, and surgery in an earlier time period were the predictors of mortality. For the late constant hazard phase insulin dependent diabetes, renal insufficiency, older age, were significant predictors. The benefit of MVA was in abolishing early post-operative MR. Unfortunately this study failed to demonstrate any incremental clinical benefit of concomitant MVA. In fact they caution that the longer ischemic time needed for MVA could be detrimental in the sick, old patient. They have projected a recurrence of 3 +/ 4 + MR in 9 % and 20 % in the CABG + MVA cohort at the end of 1 and 5 years respectively. Grossi et al. [42] studied a cohort of 223 patients over two decades, with 152 undergoing MVA (77 % ring and 23 % suture annuloplasty). As they have found the era of surgery to be an important predictor of outcome, we will concentrate on their results in patients operated after 1988. Analyzing their entire cohort, they report that type of surgery (repair vs replacement), papillary muscle rupture, congestive heart failure and acute MR impair long-term survival. In their contemporary series of patients (surgery after 1988) however, outcome are poorer for mitral valve replacement (hazard Ratio; 0.45(0.22–0.93)) and emergency surgery (hazard ratio 0.19(0.06–0.64)). Using complicated statistical models, they conclude that NYHA functional class and patient selection determine outcome rather than surgical procedure. Impressively almost 82 % from the MVA cohort were free of significant MR. They recommend restrictive MVA as the first strategy for patients with an annular pathology, while those with significant leaflet tethering or papillary muscle dysfunction would do better with posterior chordal preservation and MVR. Mayo Clinc recently presented their experience of 431 patients who underwent mitral valve repair/replacement for ischemic MR over a 14 year period [6]. Overall survival for the entire cohort was 82.7 %, 55.2 % and 24.3 % at the end of 1, 5 and 10 years respectively. All patients in the repair cohort underwent either an undersized band or rigid ring annuloplasty. Details of sub-annular apparatus preservation are unfortunately not available in individual patients due to the retrospective nature of the study, although institutional policy is to perform at least posterior chordal preservation. Prior CABG, emergency surgery and age were risk factors for early mortality (<1 year) while age, renal insufficiency and diabetes contributed to the late constant hazard phase. These results are similar to those at the Cleveland Clinic [48]. This underlines the importance of patient factors rather than procedure to late outcome.
Fukuda and colleagues [49] reported results of 126 patients with severe left ventricular dysfunction (≤30 %), who underwent mitral valve annuloplasty. They found that annuloplasty is not a predictor of improved survival. However they, as well as many others have demonstrated an improved quality of life and functional capacity after mitral valve surgery.
Two important issues regarding repair of ischemic mitral regurgitation are recurrent regurgitation and a more recently introduced concept of exercise induced mitral stenosis. The incidence of recurrent regurgitation after repair is not small. Gilinov et al. have reported a repair failure rate of 9 % over a 5-year period [41]. Chan and co-workers have demonstrated a recurrence rate of 23 % in their study evaluating 65 patients with mitral valve repair [50].
Exercise induced mitral stenosis is being increasingly reported with patients undergoing restrictive annuloplasty [51]. Magne and co-workers have reported increase in trans-valvular gradients with restrictive annuloplasty leading to pulmonary hypertension and increased clinical symptoms [51]. Some authors have implicated left ventricular dysfunction and pulmonary vascular disease rather than mitral valve gradients as the cause for pulmonary hypertension after ischemic mitral valve repair [52, 53].
Geometric Rings for Ischemic Mitral Regurgitation
The GeoformTM ring (Edwards Lifesciences, Irvine, CA) has a unique three dimensional shape designed to reduce the anteroposterior diameter and elevate P2 segment of the leaflet. DeBonis et al. demonstrated survival of 81.1 +/− 6.6 % at 3.5 years, while recurrent regurgitation was present in 16 %. Significant exercise induced mitral stenosis was not found in any of the survivors. Restricted motion of the posterior leaflet is an important predictor of recurrent regurgitation.
The Carpentier-McCarty-Adams ETLogixringTM is the first ring specifically designed to treat asymmetrical restriction of the posterior leaflet. Initial results are favorable with a low residual grade of regurgitation and improvement in echocardiographic parameters early after surgery [54]. A recent study demonstrates significant reduction (p < 0.0006) in the mitral annular diameter, tenting area as well as tenting height after use of the ETLogixringTM. They conclude that the ring is useful for selective patients with ischemic mitral regurgitation. While functional mitral stenosis has not been reported with the GeoformTM ring, Martin and colleagues have recently reported their results on 40 patients with the ETLogixringTM [55].
The choice of ring for the repair of ischemic regurgitation is a very complex issue, and an exhaustive discussion regarding this issue is beyond the purview of this article. However while energy and dollars are being spent on devising and marketing new rings, reports are also available demonstrating comparable changes in the geometry of the mitral valve [56].
Percutaneous Techniques to Deal with Mitral Regurgitation
As discussed in the earlier part of the chapter, mortality and morbidity associated with the surgical treatment of mitral regurgitation may be significant. Patients may be denied surgery on the grounds that it is too high risk [57]. Various techniques are present attempting to correct mitral regurgitation in a minimally invasive manner. A detailed classification (based on functional anatomy) is provided by Chiam and Ruiz in their comprehensive review [58].
Among the many experimental methods, the MitraClipTM (Abbott Vascular, Santa Clara, CA) based on the Alfieri edge-to-edge repair is the only method having entered and completed clinical trials. The technique is based on the open surgical technique of Alfieri where the anterior and posterior leaflets are approximated together to create a double mitral orifice. A steeable catheter is utilized to deploy the clip. The approach is antegrade via a trans-septal puncture. In 2009, Feldman and colleagues reported the mid-term results of the EVEREST (Endovascular Valve Edge-to-edge Repair trial) trial, the first randomized controlled single arm study aimed at assessing feasibility of percutaneous mitral valve repair [59]. A total of 107 patients underwent MitraClipTM repair with <1 % in-hospital mortality. Overall, 74 % had procedural success, defined as residual mitral regurgitation ≤2 + at the end of the procedure. At the end of 1 year, 66 % were free of ≥2 + MR, surgery or death. During surgery, repair was still possible in the majority of patients. Although clip embolization was not an issue, partial clip dislodgement occurred in 9 %. The EVEREST II trial (NCT 00209274) was undertaken comparing surgical repair and MitraClipTM in a 2:1 randomized manner. The non-inferiority end-point of the study was met, demonstrating that device therapy was comparable to surgical repair at the end of 1 year of follow-up. In another sub-study of EVEREST II, high-risk patients (STS score >12 %) undergoing MitraClipTM repair were compared to similar patients electing for optimal medical therapy. This study demonstrated a significant improvement in clinical symptoms and left ventricular reverse remodeling after 12 months in the device cohort. A large clinical study from Germany has also demonstrated the benefit of device therapy, however it is important to note that the follow-up duration of these patients is still limited [60]. Given the relatively high incidence of recurrence of regurgitation in the EVEREST study, careful thought is needed before opting for this procedure and an open discussion with the patient regarding this aspect is important.
Devices can be implanted in the coronary sinus to reduce the septo-anterior dimensions of the mitral valve. The Monarc device® (Edwards Lifesciences, Irvine, CA) consists of proximal self-expandable anchors with a spring-like bridge with shortening forces. The EVOLUTION trial reported a reduction in MR garde in 85.7 % patients with severe regurgitation pre-operatively. The main concern is compression of the circumflex coronary artery, which was present angiographically in 30 % at the end of 6 months. Among these patients, 13.3 % had myocardial infarction. The TITAN trial reported results with the Carillon device (Cardiac Dimension Inc., Kirkland, WA), a fixed-length double anchor implant to be positioned in the coronary sinus. Among 53 patients enrolled in the study, 32 % devices were recaptured after implant, the main reason being circumflex coronary artery compression.
Devices based on these two principles: the edge-to-edge repair and reducing the septo-anterior dimensions are the most promising at the moment. Many other methods are in various stages of experimental trials. Surgical therapy will always remain the gold standard of care for these patients, and the use of alternative therapies needs to be done with an informed discussion with the patient regarding the possibility of recurrent regurgitation. However, open surgical approach is not without significant morbidity and postoperative recovery. A careful balance needs to be achieved between attaining a better clinical end-point and the patient’s quality of life.
To summarize, mitral regurgitation is definitely a predictor of mortality in patients with poor ventricular function. Significant mitral regurgitation (moderate or more) warrants surgical intervention, even more so if done concomitantly with coronary artery surgery. Surgery in the form of a restrictive annuloplasty can be performed with an early mortality of 5–10 %. While late survival will not be favorably altered with mitral valve surgery, quality of life and functional capacity is definitely superior. Mitral valve replacement is comparable to repair with regards outcome, especially if performed using the chordal sparing approach. Patient factors like renal dysfunction, age, diabetes, and era of surgery are important predictors of survival. Important concerns with repair like the risk of recurrence and the risk of inducing functional mitral stenosis have to be considered while making the decision to repair or replace the valve. Geometrically altered rings are available for the repair of ischemic mitral regurgitation; however experience with them is limited when compared to the use of conventional rings and bands for degenerative mitral valve repair. Hence further data is necessary to allow us to make an informed decision regarding choosing any one ring over the other.
Percutaneous techniques are still to find a niche in the armamentarium of available procedures. While they may be beneficial for a select population of very high risk patients, much more data needs to be obtained to determine their place amongst various options already at hand.
Tricuspid Regurgitation
Tricuspid valve disease may occur in patients with congestive heart failure. It is primarily due to two mechanisms: (a) Tricuspid regurgitation (TR) develops secondary to pulmonary hypertension and right ventricular dysfunction (b) Primary tricuspid valve disease can occur due to isolated right ventricular dysfunction or more commonly due to pacemaker lead induced damage.
Secondary TR is the most common tricuspid valve pathology associated with congestive heart failure. Right ventricular dysfunction results in a gradual increase in the annular diameter of the tricuspid valve. This enlargement occurs at the anterior aspect of the annulus corresponding to the right ventricular free wall. Its shape changes from a saddle to a more planar dimension [61]. An enlarged annulus leads to improper cooptation of the leaflets and a predominantly central jet of regurgitation. They may suffer from ascites, pedal edema and hepatomegaly, the classical features of right-sided failure. Additionally they also demonstrate reduced functional capacity, fatigue and dyspnea on exertion.
Dreyfus et al. have demonstrated that TR may fail to resolve after correction of the left sided-pathology [62]. The presence of severe TR is also an independent predictor of mortality [39]. Hence severe TR is best corrected surgically at the time of mitral valve surgery (Class I indication) [63]. Data regarding tricuspid valve surgery in isolated TR or TR after prior correction of left sided pathology is less clear (Class IIA indication) [63]. In patients with ischemic/functional mitral regurgitation, TR is a more important issue. Matsunaga et al. demonstrated a 30 % prevalence of 2+TR in patients undergoing mitral valve surgery. In spite of adopting a very liberal policy towards surgical correction of the tricuspid valve, almost 2/3rd of the patients developed moderate TR at the end of 3 years [64].
Tricuspid valve repair consists of various procedures like (1) autologous procedures viz. bicuspidalization [65] or De Vega annuloplasty & (2) annuloplasty procedures using rigid or flexible bands/rings. A large series of 790 patients demonstrates the use of four different techniques: DeVega repair, Peri-Guard® pericardial strip annuloplasty, Edwards-Cosgrove flexible band and Carpentier-Edwards semi-rigid ring.
Tricuspid valve replacement can be performed using either a mechanical or bioprosthesis. As a general rule, tissue valves are preferred unless specifically contra-indicated for other reasons. Readers are encouraged to pursue the article by Chikwe et al. for a detailed description of the available surgical procedures [66].
Concomitant tricuspid valve surgery with mitral procedures can be done very safely (1–2 % early mortality). A comparison of the various available procedures demonstrates more durable results with prosthetic annuloplasty compared to autologous procedures [67].
Results after the surgical repair of isolated tricuspid valve repair are less satisfactory. Severe underlying right ventricular failure has been implicated as an important causative factor. Predictors of poor outcome after isolated tricuspid surgery are poor NYHA functional class, pre-operative hemoglobin and right ventricular end-systolic area [68].
A study reviewing the Mayo Clinic experience with isolated tricuspid valve replacement demonstrated that NYHA class IV and a higher Charlson index were independent predictors for late mortality [69]. The only echocardiographic predictor identified was right index of myocardial performance (RIMP) ratio [69]. Among survivors, almost a quarter needed re-admission for congestive heart failure during the follow-up period. Hence intensive surveillance is important even after surgery to ensure good functional status and quality of life.
The poor results are partly due to a reluctance of surgeons to operate on the tricuspid valve. Analysis of the Society of Thoracic Surgeons cardiac database from 2004–2007 demonstrates that tricuspid valve surgery is conducted in very small numbers [70]. Authors at the Mayo clinic demonstrate that surgery can be done with a reasonable outcome if patients are operated before the onset of severe right ventricular failure [69].
In conclusion, we recommend that patients with 2+TR should undergo concomitant repair at the time of left-sided procedures. Patients with isolated TR have a higher mortality; it is important in these patients to proceed with surgery before the onset of severe right ventricular failure. Attention to diuretic therapy and fluid balance are important even after surgery to ensure a good functional status and quality of life.
Aortic Regurgitation
Aortic regurgitation produces predominantly a volume overload on the left ventricle. The lesion is well tolerated initially and symptoms are minimal. However a left ventricular end-systolic diameter >50 mmHg is associated with increased mortality, and is an indication for aortic valve replacement. Guidelines recommend surgery even for asymptomatic patients with left ventricular dysfunction (LVEF <50 %), however studies have demonstrated a significant reluctance to conduct surgery in these high-risk patients [63]. The Euro Heart Survey has demonstrated that only 22 % with LVEF in the range of 30–50 % underwent surgery while only 3 % with severe LV dysfunction (LVEF <30 %) received operative intervention [71]. A retrospective single center study demonstrated that only a third of the patients with severe AR and LV dysfunction actually underwent surgery. The pre-operative factors cited for non-intervention were an older age, female gender, presence of diabetes and renal dysfunction, and the need for concomitant procedures. Operative mortality is in the range of 7–10 % [72]. Kamath and co-workers have demonstrated that in severe AR patients with severe LV dysfunction, AVR is an independent predictor of improved survival [73]. AVR had significant survival benefit with 1-year, 2-year, and 5-year survival rates of 88 %, 82 %, and 70 %, respectively, compared to 65 %, 50 %, and 37 %, respectively, in the population who did not receive AVR surgery (p < 0.001). Patients with severe LV dysfunction (LVEF <35 %) and (LVEF <20 %) demonstrated a 5-year survival of 70 % and 60 % respectively. Although survival cannot match the age-matched normal population, we have still demonstrated a benefit for surgical intervention. Propensity matched results have also demonstrated the advantage of surgical therapy [72].
A study from the Mayo Clinic demonstrated that preoperative ejection fraction, left ventricular end-systolic dimension, indexed end-systolic dimension, end-diastolic dimension, and indexed end-diastolic dimension were univariate predictors of late ejection fraction. In a multivariate model, the only predictor of late normal ejection fraction was a higher preoperative ejection fraction (odds ratio, 2.85; p < 0.001) [74].
Thankfully, regression in left ventricular dimensions has been demonstrated after aortic valve replacement. Bonow et al. monitored changes in left ventricular dimensions and ejection fraction after aortic valve replacement in 61 patients [75]. They utilized echocardiography and radionuclide scanning to assess them over a 7-year period. Between preoperative and early postoperative studies, left ventricular end-diastolic dimension decreased (from 75 ± 6 to 56 ± 9 mm, p < 0.001), peak systolic wall stress decreased (from 247 ± 50 to 163 ± 42 dynes), and ejection fraction increased (from 43 ± 9 % to 51 ± 16 %, p < 0.001). However patients without early increase in the ejection fraction failed to demonstrate any improvement long-term. They further demonstrate a significant improvement in ejection fraction even in patients with severe LV dysfunction [72].
Hence, aortic valve replacement is beneficial even in patients with advanced left ventricular dysfunction. Compared to metical therapy, benefit in terms of quality of life and functional capacity is observed after surgery. Associated preoperative factors and a higher operative mortality rate have to be considered when considering surgical intervention in patients with severe aortic regurgitation and left ventricular dysfunction.
Aortic valve replacement is one of the most common adult cardiac procedures performed in the USA. Patients with a poor ejection fraction typically develop a subset of aortic stenosis (AS): a low gradient, low flow (LF-LG) severe AS.
Definition
LF-LG severe AS is defined as a combination of an EOA ≤1.0 cm2 (or EOA index <0.6 cm2/m2) with a low mean trans-valvular gradient (less than 40 mmHg). Low-flow mean either a cardiac index <3 l/m2/min or an ejection fraction (less than 40 or 35 %).
Pseudo-Severe Aortic Stenosis
Patients with primarily left ventricular dysfunction may have a small aortic valve area with low trans-valvular gradient due to their sub-normal stroke volume. The small effective orifice area of the aortic valve in these patients is secondary to incomplete opening during systole.
This stratification has a significant clinical consequence as aortic valve replacement fails to improve the symptomatology in the latter cohort and may actually be detrimental.
Role of Dobutamine Stress Echocardiography
Dobutamine stress echocardiography [76] is implemented as a confirmatory test for assessing LF-LG AS. While true aortic stenosis will present with a significant increase in gradient (mean transvalvular gradient >40 mmHg) with minimally increase flow and aortic valve orifice area (change <0.3 cm2, valve area <1 cms2) pseudo-severe aortic stenosis will demonstrate an increased flow without much change in the gradient [63]. The European Committee for guidelines on valvular heart disease recommends this test for all patients with LF-LG AS. Apart from being a diagnostic test, the increase in ejection fraction helps to assess contractile reserve of the left ventricle, an important prognostic indicator [77]. Contractile reserve is defined as an increase in ejection fraction >20 % with dobutamine infusion compared to the baseline [78].
Momin et al. studied the changes in stroke volume, left ventricular ejection fraction, aortic valve area and mean pressure gradient in patients with and without contractile reserve on DSE. Patients with an intact contractile reserve demonstrated an increase in stroke volume (33 %), LVEF (12 %), aortic valve area (0.1 cm2) and MPG (47 %). Those devoid of contractile reserve demonstrated minimal increase in values on Dobutamine stress echocardiography.
TOPAS Study
The TOPAS (Truly or Pseudo-Severe Aortic Stenosis) is a prospective study conducted to improve the accuracy of differentiating true from pseudo-aortic stenosis. While authors agree that DSE is a reliable test, stenotic indices obtained from the DSE depend upon the magnitude of flow increase achieved. Blais and co-workers have developed a new stenotic index, the EOAprojwhich determines the orifice area at a standardized flow rate of 250 ml/s, a constant which they have derived using hydraulic models in the laboratory. Hence they have presented their equation as: EOAproj=EOArest+ VC*(250-Qrest). The authors have further indexed this obtained value to the patient’s body surface area to derive the indexed projected EOA. Using a cut-off of ≤ 0.55 cm2/m2, the sensitivity of this score increased from 93 to 100 % (Fig. 19.6) [79].
Fig. 19.6
The technique of indexed projected effective orifice area is a reliable test to differentiate true and pseudo-severe aortic stenosis. The panels D-F demonstrate the change of this parameter in patients with true (red triangles) and pseudo-severe (blue triangles) aortic stenosis (Reprinted with permission Blais et al. [79]. © 2006, with permission from Wolters Kluwer Health Inc)
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