Aortic Valve Replacement In Asymptomatic Patients Research Articles

Do all patients with asymptomatic severe aortic stenosis need treatment?

Introduction Although guidelines recommend a watchful waiting strategy for patients with asymptomatic severe aortic stenosis, there have been considerable advancements in surgical and anaesthetic techniques along with the success of transcatheter aortic valve replacement (AVR) as a viable alternative to surgical AVR. Inevitably, these developments have raised questions as to whether or not there is still merit in waiting for symptoms to ensue before treatment may offered to these patients. Area covered The principal purpose of this paper is to review the data supporting earlier intervention in patients with asymptomatic severe aortic stenosis, and to project the implications these and other ongoing trials will have on indications for AVR in asymptomatic patients in the future. Expert opinion The threshold for intervention in certain subgroups of asymptomatic patients with severe AS has already been lowered. The next frontier will inevitably be determining whether all patients with severe AS should undergo AVR irrespective of their symptomatic status.

Timing of Intervention in Asymptomatic Aortic Stenosis

The decision to perform an intervention for asymptomatic severe aortic stenosis (AS) requires careful weighing of the risks of early intervention against those of watchful observation, and the optimal timing of intervention remains controversial. With improvements in surgical and postoperative care, long-term survival after surgical aortic valve (AV) replacement (AVR) is excellent in low-risk patients, and the emergence of transcatheter AVR may change the thresholds for early preemptive intervention, although a durability issue has to be resolved. A watchful observation strategy also has a risk of sudden death, irreversible myocardial damage, and increase in operative risk while waiting for symptoms to develop. We have been waiting for a prospective randomized trial to solve the intense debate between early AVR and watchful observation, and the RECOVERY (Randomized Comparison of Early Surgery versus Conventional Treatment in Very Severe Aortic Stenosis) trial provides the evidence to support early AVR for asymptomatic severe AS. Risk assessment with severity of AS and staging classification may help to facilitate the identification of patients who may benefit from early intervention. Based on the results of the RECOVERY trial, early surgical AVR is reasonable for asymptomatic patients with very severe AS (aortic jet velocity ≥4.5 m/s) and low surgical risk. Further evidence is required to extend the indications of surgical AVR and to consider transcatheter AVR in asymptomatic patients with severe AS.

Atrial fibrillation in severe aortic stenosis: Prognostic value and results of aortic valve replacement

ObjectivesAlthough atrial fibrillation (AF) is common, its impact on long-term mortality has not been reliably determined in patients with aortic stenosis (AS). We aimed to assess whether AF is associated with survival in patients with severe AS and to determine the impact of AF on the results of aortic valve replacement (AVR). MethodsThe study included 1838 consecutive patients with severe AS (77 ± 11 years, male 47%). Upon AS diagnosis, patients were screened for AF using a 12-lead electrocardiogram. The treatment strategy (conservative management or AVR) was selected by the heart team in accordance with current guidelines. The effect of AVR on survival was analyzed as a time-dependent covariate using the entire follow-up period. ResultsAF, diagnosed in 593 (32%) patients was associated with poor survival at 5 years (55 ± 2% vs 74 ± 1% for patients in sinus rhythm, P < .001), even after adjustment for established outcome predictors (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.33-1.84; P < .001). In patients with AF, AVR was associated with lower mortality (HR, 0.16; 95% CI, 0.12-0.22; P < .001) even in those with no or minimal symptoms (HR, 0.12; 95% CI, 0.08-0.20; P < .001). However, among patients who underwent AVR, those in AF had an excess mortality (HR, 1.59; 95% CI, 1.22-2.08; P < .001). ConclusionsIn severe AS, AF is a strong predictor of mortality even in asymptomatic or minimally symptomatic patients. After AVR, AF remains associated with poorer survival than sinus rhythm. In patients in AF, AVR is associated with lower mortality compared with conservative treatment. Further studies are needed to confirm the benefits of AVR in asymptomatic patients in AF with severe AS.

Exercise Testing and Stress Imaging in Aortic Valve Disease.

Aortic valve disease and especially aortic stenosis (AS) is a growing cardiac pathology. Aortic valve replacement (AVR) is still the only treatment with proven benefit on survival in symptomatic patients and in patients with a left ventricular ejection fraction (LVEF) <50%. The benefit of prophylactic AVR in asymptomatic patients is still unproven. Once symptoms develop, the prognosis worsens. Exercise testing has emerged as a tool to unmask the "pseudo-asymptomatic" patients with AS (those without self-reporting symptoms), to link "exercise induced dyspnea" more confidently and more objectively to aortic valve disease and to allow for a safe "watchful waiting strategy" in "pseudo-symptomatic" patients (those with dyspnea unrelated to aortic valve disease). In cases in which exercise testing is unable to link dyspnea to aortic valve disease, exercise stress echocardiography and cardiopulmonary exercise testing may be helpful. Whatever the results of exercise testing with regard to symptom development, an increase in mean aortic valve pressure gradient >18-20mmHg was associated with an increased risk of cardiac related events in severe AS patients (class IIb indication for AVR in the ESC guidelines). The decrease in LVEF during exercise as well as the development of exercise induced pulmonary hypertension, as revealed by exercise stress echocardiography, may be also useful in the risk stratification of these asymptomatic patients with severe AS. Data on the role of exercise echocardiography in asymptomatic severe aortic regurgitation patients is still scarce and further studies are needed. It seems that an exercise induced decrease in LVEF by 5% may be a better predictor of LV systolic dysfunction after AVR in asymptomatic patients or in patients with minimal symptoms. Exercise testing and exercise echocardiography are safe in the asymptomatic patients with aortic disease, provide useful clinical information that may help in risk assessment of these complicated patients and their use should be encouraged especially in heart valve clinics.

Meta-analysis of the impact of intervention versus symptom-driven management in asymptomatic severe aortic stenosis

ObjectiveThe management of patients with asymptomatic, severe aortic stenosis (AS) is controversial. We performed a meta-analysis to examine the impact on outcomes of aortic valve replacement (AVR) in patients with...

Rationale and design of the Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A randomized multicenter controlled event-driven trial

Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms. The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters. To the best of the authors' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients.

Basal longitudinal strain predicts future aortic valve replacement in asymptomatic patients with aortic stenosis.

To evaluate the prognostic value of global longitudinal strain (GLS) and basal longitudinal strain (BLS) with the knowledge of coexisting coronary pathology evaluated by multi-detector computed tomography (MDCT) coronary angiography. GLS and BLS are both sensitive markers of myocardial dysfunction and predictors of outcome in asymptomatic aortic stenosis. Aortic stenosis and ischaemic heart disease share risk factors and longitudinal function can be severely reduced in both conditions, why some of the previous findings of impaired regional longitudinal function in asymptomatic aortic stenosis could in fact be explained by silent ischaemic heart disease. Prospective follow-up of 104 asymptomatic patients with moderate-severe aortic stenosis defined as an aortic valve area <1.5 cm(2). Patients underwent a thorough clinical work-up, advanced echocardiographic analysis and coronary angiography by MDCT. The combined endpoint was indication for aortic valve replacement (AVR) and sudden cardiac death. During a median follow-up of 2.3 years (interquartile range 1.7-3.6) 43 patients (41%) met the endpoint of indication for AVR. The basal (13.4 ± 3.1% vs. 15.7 ± 3.1%) and mid-ventricular segments (14.9 ± 2.7% vs. 16.2 ± 2.9%) were significantly reduced, but with sparing of the apical segments, in patients who later underwent AVR. In various multivariable Cox regression models, including only BLS, but not GLS, remained an independent predictor of AVR. In contrast to GLS, reduced BLS is a significant predictor of future AVR in asymptomatic patients with aortic stenosis, independently of clinical characteristics, conventional echocardiographic measures, and coronary pathology.

Invited Commentary

This retrospective study by Khandhar and colleagues [1Khandhar S. Varadarajan P. Turk R. et al.Survival benefit of aortic valve replacement in patients with severe aortic regurgitation and pulmonary hypertension.Ann Thorac Surg. 2009; 88: 752-757Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar] evaluates the effect of aortic valve replacement (AVR) for severe aortic regurgitation (AR) in the setting of pulmonary hypertension (PHT). In this cohort of patients, AVR is safe and translates into a survival benefit at 5 years. Although the study is small, it offers a timely opportunity to reconsider indications for AVR and the underlying pathophysiology of left-heart causes of PHT. Current American College of Cardiology/American Heart Association recommendations for AVR do not include PHT. We know that untreated AR results in left ventricular dilation, dysfunction, and eventually, PHT [2Basu B. Cherian G. Krishnaswami S. Sukumar I.P. John S. Severe pulmonary hypertension in advanced aortic valve disease.Br Heart J. 1978; 40: 1310-1313Crossref PubMed Scopus (15) Google Scholar]. Severe AR also results in endothelial injury within the pulmonary vasculature, interstitial edema, and fibrosis, all of which contribute to increased pulmonary artery vascular tone. Furthermore, severe right ventricular dysfunction can result in chronic small emboli to the lungs and worsen the disease process, and likely blunt postoperative recovery. Indeed, these pulmonary insults are the consequences of prolonged disease. The reality of prolonged disease before surgical intervention raises two questions: whether PHT should be an indication for AVR and whether we are waiting too long to perform AVR in this population. At present, there is a class IIa recommendation to perform AVR in asymptomatic patients with evidence of severe left ventricular dysfunction, defined as end-diastolic dimension exceeding 75 mm or end-systolic dimension exceeding 55 mm. For women, in particular, this degree of left-heart dysfunction may be too severe to expect AVR to improve the clinical outcome. Further clarification of the effect of mitral valve function will also be helpful. Mitral stenosis and regurgitation both result in increased pulmonary vascular resistance and contribute to elevated pulmonary artery pressures. The mitral effective regurgitant orifice and mitral deceleration time have been shown to strongly correlate with elevated pulmonary artery pressures [3Enriquez-Sarano M. Rossi A. Seward J.B. Bailey K.R. Tajik A.J. Determinants of pulmonary hypertension in left ventricular dysfunction.J Am Coll Cardiol. 1997; 29: 153-159Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar]. Khandhar and associates [1Khandhar S. Varadarajan P. Turk R. et al.Survival benefit of aortic valve replacement in patients with severe aortic regurgitation and pulmonary hypertension.Ann Thorac Surg. 2009; 88: 752-757Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar] appropriately call our attention to mitral valve function in this cohort: 16 of the 32 patients receiving AVR had mitral valve repair (n = 8) or replacement (n = 8). Definitive aortic and mitral valve procedures may be necessary to restore left-sided hemodynamics and filling pressures. In fact, the lack of mitral regurgitation may suggest secondary causes of PHT at work. As we reconsider our indications for AVR in the setting of PHT, new screening variables and closer attention to mitral valve function will be essential. Survival Benefit of Aortic Valve Replacement in Patients With Severe Aortic Regurgitation and Pulmonary HypertensionThe Annals of Thoracic SurgeryVol. 88Issue 3PreviewSevere pulmonary hypertension occurs in approximately 10% of patients with severe aortic regurgitation (AR). The potential survival benefit of aortic valve replacement (AVR) in these patients is not known, and was analyzed in a large cohort of patients. Full-Text PDF

Nifedipine in Asymptomatic Patients with Severe Aortic Regurgitation and Normal Left Ventricular Function

Vasodilator therapy with nifedipine reduces left ventricular volume and mass and increases the ejection fraction in asymptomatic patients with severe aortic regurgitation. To assess whether vasodilator therapy reduces or delays the need for valve replacement, we randomly assigned 143 asymptomatic patients with isolated, severe aortic regurgitation and normal left ventricular systolic function to receive either nifedipine (20 mg twice daily, 69 patients) or digoxin (0.25 mg daily, 74 patients). By actuarial analysis, we determined that after six years a mean (+/- SD) of 34 +/- 6 percent of the patients in the digoxin group had undergone valve replacement, as compared with only 15 +/- 3 percent of those in the nifedipine group (P < 0.001). In the digoxin group, valve replacement (in a total of 20 patients) was performed because of left ventricular dysfunction (ejection fraction < 50 percent) in 75 percent, left ventricular dysfunction plus symptoms in 10 percent, and symptoms alone in 15 percent. In the nifedipine group, all six patients who underwent valve replacement did so because of the development of left ventricular dysfunction. In addition, all the patients in both groups who underwent aortic-valve replacement had an increase of 15 percent or more in the left ventricular end-diastolic volume index. After aortic-valve replacement, 12 of the 16 patients (75 percent) in the digoxin group and all six patients in the nifedipine group who had had an abnormal left ventricular ejection fraction before surgery had a normal ejection fraction. Long-term vasodilator therapy with nifedipine reduces or delays the need for aortic-valve replacement in asymptomatic patients with severe aortic regurgitation and normal left ventricular systolic function.