Author + information
- Received March 30, 2018
- Revision received April 26, 2018
- Accepted May 17, 2018
- Published online September 3, 2018.
- Robert Zilberszac, MD, PhDa,∗ (, )
- Georg Heinze, PhDb,
- Thomas Binder, MDa,
- Günther Laufer, MDc,
- Harald Gabriel, MDa and
- Raphael Rosenhek, MDa,∗ ()
- aDepartment of Cardiology, Medical University of Vienna, Vienna, Austria
- bCenter for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
- cDepartment of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
- ↵∗Address for correspondence:
Dr. Raphael Rosenhek, OR Dr. Robert Zilberszac, Department of Cardiology, Vienna General Hospital, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Objectives This study sought to assess the long-term outcome of active surveillance in these patients.
Background The optimal timing of mitral valve surgery in asymptomatic primary mitral regurgitation (MR) remains controversial.
Methods Between 1997 and 2015, 280 consecutive patients with severe asymptomatic primary MR were enrolled in our heart valve clinic follow-up program. They were prospectively followed up every 6 months clinical and echocardiographical examinations until surgical criteria were reached. Event-free survival and overall survival as compared with the age- and gender-matched general population were assessed.
Results During a median potential follow-up of 93.4 (quartiles 55.3 to 152.9) months, 161 patients developed an indication for surgery and 13 patients died. Event-free survival rates were 78.0% (95% confidence interval [CI]: 73.2% to 83.2%) at 2 years, 52.2% (95% CI: 46.3% to 59.0%) at 6 years, 35.5% (95% CI: 29.3% to 43.1%) at 10 years, and 18.7% (95% CI: 12.3% to 28.5%) at 15 years. Overall survival rate was 99.6% (95% CI: 98.9% to 100%) at 2 years, 94.6% (95% CI: 91.7% to 97.6%) at 6 years, 85.6% (95% CI: 80.3% to 91.2%) at 10 years, and 74.5% (95% CI: 66.6% to 83.4%) at 15 years. Overall survival of patients managed according to an active surveillance strategy was comparable with the expected cumulative survival and early survival rates were even better in the study population (standardized mortality ratio: 0.667; 95% CI: 0.463 to 0.963; p = 0.013).
Conclusions Patients with severe asymptomatic primary MR may remain free of indications for surgery for extensive periods of time. In such patients, active surveillance performed in experienced centers is associated with a favorable prognosis, resulting in timely referral to surgery, excellent long-term survival, and good surgical outcomes.
Primary mitral regurgitation (MR) is the second most frequent valve disease requiring surgery (1). In these patients, mitral repair is associated with excellent outcomes in terms of perioperative mortality, post-operative left ventricular (LV) function, and long-term survival (2) with age- and gender matched life expectancy and good quality of life (3) when performed before the onset of severe symptoms, LV dysfunction or dilatation, pulmonary hypertension (PHT), and atrial fibrillation. Patients exhibiting these Class I or IIa indications for surgery should, thus, be referred to mitral repair without delay (4,5). However, the optimal timing of surgery in asymptomatic patients without any of these criteria remains controversial; the American College of Cardiology/American Heart Association guidelines (4) state that elective mitral valve repair should be considered if the operative risk is low and the likelihood of successful repair is >90% whereas the European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines (5) are more restrictive, recommending the consideration of surgery only when the LV is enlarged (left ventricular endsystolic diameter ≥40 mm) in the presence of either a flail leaflet or significant left atrial (LA) dilatation when a durable repair is likely, surgical risk is low, and the repair is performed in a heart valve center.
We previously found that asymptomatic patients with severe primary MR can be safely followed up in the setting of a dedicated heart valve clinic (HVC) until Class I or IIa indications for surgery are reached, resulting in excellent mid-term survival, not different from an age- and gender-matched population (6).
Nevertheless, some registries have suggested a potential survival benefit of early elective surgery (7,8). However, patients may remain asymptomatic for extended periods and surgical results may be inhomogeneous. Furthermore, particularly in the absence of LV or LA dilatation, the diagnosis of severe MR might be erroneous (9,10).
Therefore, the present study sought to assess the 20-year outcome of an active surveillance strategy in a large population of patients with severe primary MR managed in a dedicated HVC.
All consecutive patients with severe primary mitral regurgitation (prolapse or flail leaflet) who were studied in our outpatient HVC between 1997 and 2015 were included in the study when they were asymptomatic, had an ejection fraction ≥60%, a left ventricular end-systolic diameter <45 mm, a Doppler sonographically estimated systolic pulmonary artery pressure ≤50 mm Hg, and presented with sinus rhythm. Exclusion criteria were previous cardiac surgery or additional hemodynamically significant valve lesions (moderate or severe) except for tricuspid regurgitation.
According to these criteria, 280 consecutive patients (88 females) were identified. The study protocol was approved by the ethics committee of the Medical University of Vienna and written informed consent was not demanded due to the observational study design.
At baseline, a comprehensive clinical assessment, including medical history, current medication, physical examination, electrocardiogram (ECG), blood tests, and transthoracic echocardiography, was performed.
The following data were collected: age, gender, body mass index, and body surface area; the patient’s symptomatic status; and presence of comorbidities (coronary artery disease [history of myocardial infarction, angioplasty, coronary artery bypass surgery, or angiographically documented coronary artery stenosis], arterial hypertension [blood pressure ≥140/90 mm Hg at repeated measurements or use of antihypertensive agents], hypercholesterolemia [total serum cholesterol ≥240 mg/dl or cholesterol-lowering medication], and diabetes [fasting blood glucose level >126 mg/dl or use of antidiabetic medication]).
All patients underwent a comprehensive echocardiographic examination by an experienced echocardiographer.
Apical 4- and 2-chamber views were used for calculation of ventricular volumes and ejection fraction using Simpson’s biplane formula. A left ventricular ejection fraction ≥60% was considered normal.
Quantification of MR severity was based on an integrated approach (11,12); valve morphology, cavity sizes, and LV function were assessed. Mitral valve prolapse was defined as displacement of 1 or both leaflets by at least 2 mm below the mitral annulus level into the LA during systole. Flail mitral leaflet was defined as a freely moving leaflet edge located in the LA. Systolic pulmonary artery pressure was derived from tricuspid regurgitant velocity.
HVC program and follow-up
Asymptomatic patients free of any Class I or IIa indications for surgery were followed up prospectively at every 6 months in the HVC until surgical criteria according to the prevailing guidelines (4,5) were reached. At each HVC visit, a thorough medical history was taken by a physician experienced in the management of patients with valvular heart disease with a specific focus on inquiring abut the presence of MR-related symptoms. In addition to echocardiography, patients underwent a physical examination, blood testing, blood pressure measurement, and 12-lead ECG. Patients were instructed to recognize symptoms related to MR and to report any symptom onset without delay. Exercise testing was performed in selected patients when doubt about whether they were truly asymptomatic existed. The decision to perform an exercise test was made on an individual basis according to clinical judgment. The only criterion used to refer a patient to surgery after an exercise test was the occurrence of symptoms during exercise.
Patients developing an indication for surgery were immediately referred to surgery and underwent a systematic pre-operative work-up (including coronary angiography).
For patients who underwent surgery, a postoperative follow-up visit was scheduled in the HVC to assess the surgical outcome. Further post-operative follow-up examinations in the HVC were scheduled at extended intervals, depending on surgical and clinical outcomes.
For the evaluation of outcome, events were defined as development of any criteria that indicated surgery or cardiac death related to MR. Furthermore, post-operative symptomatic status and LV function were assessed.
For the assessment of survival, the national mortality registry was queried and additional follow-up information was obtained from telephone interviews with the patients, their relatives, and their physicians.
Categorical baseline variables are described as counts and percentages and compared between groups using chi-square tests. Continuous baseline variables are described as median (quartiles) and compared between groups using Wilcoxon rank-sum tests and Kruskal-Wallis tests due to skewed distributions.
Median follow-up is calculated using the inverse Kaplan-Meier method. Survival rates (with 95% confidence intervals [CIs]) at clinically relevant time points and median survival (with quartiles) are deduced from Kaplan-Meier estimates.
Cumulative all-cause survival probabilities of the patient group were estimated using the Kaplan-Meier method and compared with the hypothetical survival of an age- and gender-matched reference population. The reference population was taken from the 2012 life tables published by Statistics Austria. Mortality of the patient group was compared with that of the reference population using the standardized mortality ratio (SMR) and associated 95% CI. The SMR is computed as the observed divided by the expected number of deaths.
The reported p values are the results of 2-sided tests. Values of p ≤ 0.05 are considered to be statistically significant. The R software (R Core Team, Vienna, Austria) was used for statistical analysis.
Two hundred eighty consecutive patients were included in the study and the baseline patient characteristics are given in Table 1. Of note, the majority of patients was male and presented with flail mitral leaflets.
During a median potential follow-up of 93.4 (quartiles: 55.3 to 152.9) months, 161 patients developed an indication for surgery and 13 patients died. Event-free survival rates were 78.0% (95% CI: 73.2% to 83.2%) at 2 years, 52.2% (95% CI: 46.3% to 59.0%) at 6 years, 35.5% (95% CI: 29.3% to 43.1%) at 10 years, and 18.7% (95% CI: 12.3% to 28.5%) at 15 years (Figure 1).
Event-free survival did not differ between patients with mitral prolapse and flail leaflet with respective event-free survival rates of 78.5% (95% CI: 67.0% to 87.0%) at 2 years, 65.0% (95% CI: 43.0% to 67.8%) at 6 years, 39.8% (95% CI: 26.3% to 55.0%) at 10 years, and 14.1% (95% CI: 4.2% to 38.9%) at 15 years for patients with prolapse and 77.7% (95% CI: 71.5% to 83.0%) at 2 years, 51.1% (95% CI: 43.9% to 58.3%) at 6 years, 34.0% (95% CI: 26.9% to 42.1%) at 10 years, and 19.0% (95% CI: 11.9% to 29.3%) at 15 years for patients with flail leaflets (p = 0.95).
Deaths in previously asymptomatic patients
Reasons of death were as follows: liver cirrhosis (n = 2), Parkinson’s disease (n = 1), lung cancer (n = 1), pancreatic cancer (n = 1), thyroid cancer (n = 1), chronic obstructive pulmonary disease (n = 1), leukemia (n = 1), acute anterior ST-segment elevation myocardial infarction (n = 1), heart failure (n = 2), and sudden death (n = 2). The 2 patients who died due to heart failure were both elderly (91 and 84 years of age, respectively), were asymptomatic, and had had a preserved left ventricular systolic function (LVSF) at their last examination in the HVC but opted not to attend further follow-up visits. The 2 sudden deaths occurred in the 50-year-old and 78-year old men who were free from any Class I or IIa indications for surgery at their last examinations that took place 105 and 38 days before death, respectively.
Although the 78-year-old did not undergo autopsy, the 50-year-old patient was examined post-mortem and a dilated heart was described, but no other direct cause of death could be identified. This particular patient had severe MR based on a flail posterior leaflet and attended all 6 of his scheduled follow-up visits every 6 months since inclusion. At his last visit, he was still asymptomatic, the LV function was preserved (ejection fraction 70%; global longitudinal strain −22.5%), his LV was mildly enlarged (left ventricular end-diastolic diameter 54 mm, left ventricular end-systolic diameter 38 mm, indexed left ventricular end-diastolic volume 61 ml/m2), and there was no evidence of atrial fibrillation or PHT. No annular disjunction was found upon review of his ECGs; his ECG showed left anterior hemiblock but no repolarization abnormalities and no premature ectopic complexes. No magnetic resonance imaging (MRI) was performed to evaluate myocardial fibrosis. The patient suddenly collapsed at work and cardiopulmonary resuscitation (CPR) was promptly initiated, including the use of an automated external defibrillator until paramedics arrived. After prolonged CPR (including transfer of the patient to our center during ongoing CPR), spontaneous circulation could not be achieved at any time and after having received 10 futile shocks for ventricular fibrillation, the patient finally went into asystole and CPR was terminated after 90 min.
Indications for surgery
Indications for surgery included the following: symptoms (n = 115), asymptomatic mild LV dysfunction (n = 11), asymptomatic LV dilatation (n = 7), asymptomatic de novo atrial fibrillation (n = 10), asymptomatic PHT (n = 9), endocarditis (n = 7), before major noncardiac surgery (n = 1), and patient’s request (n = 1). Figure 2 shows survival free of symptoms, survival free of asymptomatic LV dysfunction, endocarditis, and survival free of asymptomatic PHT or atrial fibrillation to indicate surgery.
Surgery and surgical outcomes
During follow-up, 147 patients underwent surgery, whereas surgery was not performed despite guideline-based indications being present in 14 patients for the following reasons: refusal by the patient (n = 11) and denial by the heart team due to advanced age and comorbidities (n = 3).
Mitral repair was performed in 127 patients (86%), 9 patients received a mechanical and 11 a biological valve prosthesis and 1 patient was treated with percutaneous edge-to edge repair. Additional tricuspid repair was performed in 23 patients, concomitant coronary artery bypass surgery in 27 patients, and a maze procedure was performed in 18 patients. Major operative complications occurred in 10 patients (7%): bleeding events necessitating operative revision or pericardiocentesis in 7 patients and sternal infections requiring surgical intervention in 3 patients. Postoperative permanent pacemaker implantation occurred in 6 patients.
There were no deaths in the perioperative (within 30 days of surgery) or early postoperative (1 to 3 months after surgery) phase; however, 1 patient died 94 days after mechanical mitral valve replacement and tricuspid repair surgery while still in the intensive care unit, following a postoperative phase complicated by bacterial and fungal pneumonia, as well as gastrointestinal bleeding and pericardial tamponade.
At least mild residual MR was present in 67 patients (46%), whereas at least moderate residual MR was found in 22 patients (15%). Reoperation was necessary in 8 patients due to failed mitral repair after a median of 8 (quartiles 2 to 49) months. Re-repair was possible in 4 patients (50%), whereas mitral replacement was performed in the remaining patients. Four of the 8 patients undergoing reoperation died after a period of 34 (quartiles 3 to 66) months including 1 perioperative death 29 days after mechanical valve replacement and 1 death 296 days after mechanical replacement caused by a spontaneous retroperitoneal hematoma.
Postoperative changes of LV diameters and ejection fractions are presented in Figure 3. Postoperative LVSF was impaired in 22 patients (15%). Four of these patients underwent mitral replacement and 7 concomitant aortocoronary bypass surgery Preoperatively, 15 of these patients had had a preserved LVSF (68%), 6 patients a mildly impaired LVSF (27%), and 1 patient a moderately impaired LVSF (5%). This latter patient had refused to undergo regular follow-up examinations and returned 12 years after her initial visit to the HVC with decompensated congestive heart failure and underwent urgent biological mitral replacement.
Regarding postoperative functional outcome, 119 patients (81%) were asymptomatic, 24 patients (16%) had mild symptoms (New York Heart Association [NYHA] functional class II), and 4 patients (3%) had severe symptoms (NYHA functional class ≥III). Preoperatively, 2 of these patients were in NYHA functional class II, 1 in NYHA functional class IV, and 1 patient was asymptomatic and referred to surgery because of new-onset atrial fibrillation and PHT.
Overall survival including perioperative and late deaths after surgery was 99.6% (95% CI: 98.9% to 100%) at 2 years, 94.6% (95% CI: 91.7% to 97.6%) at 6 years, 85.6% (95% CI: 80.3% to 91.2%) at 10 years, and 74.5% (95% CI: 66.6% to 83.4%) at 15 years. Survival of the patients managed according to an active surveillance strategy was comparable with the expected cumulative survival and early survival rates were even better in the study population (SMR, 0.667; 95% CI: 0.463 to 0.963; p = 0.013) (Figure 4).
Overall survival did not differ between patients with mitral prolapse and flail leaflet with respective survival rates of 100% at 2 years, 91.7% (95% CI: 79.9% to 97.1%) at 6 years, 86.0% (95% CI: 71.8% to 93.7%) at 10 years, and 67.7% (95% CI: 41.0% to 86.4%) at 15 years for patients with prolapse and 98.6% (95% CI: 95.6% to 99.5%) at 2 years, 94.7% (95% CI: 91.0% to 97.1%) at 6 years, 84.9% (95% CI: 77.7% to 90.3%) at 10 years, and 75.4% (95% CI: 65.8% to 83.3%) at 15 years for patients with flail leaflets (p = 0.94).
Early elective surgery in asymptomatic severe primary MR?
The optimal management strategy for patients with asymptomatic severe primary MR is controversial. Although some studies describe a potential advantage of early elective surgery (7,8,13), they need to be interpreted carefully (14).
Data from MIDA (Mitral Regurgitation International Database) suggested that early surgery was associated with a survival benefit in patients with flail leaflets when compared with “watchful waiting” (7). However, this was not a randomized study, having the limitations of a registry. It was based on an arbitrary definition of watchful waiting characterized by “medical management during the first 3 months of follow-up” and did not involve systematic structured follow-up in the reference centers. More importantly, in the “medical management” group, a “minimal subjective manifestation” (i.e., symptoms) was present in 32% of the patients, and 19% of the patients had a class II indication for surgery. In the registry reported by Kang et al. (8), early surgery was associated with lower event-rates and mortality but follow-up was not very strict because it included telephone interviews besides annual visits in the outpatient clinic. Interestingly, 17 patients in the early surgery group were lost to follow-up; 3 deaths that included 2 strokes and 1 infection were not taken into consideration because they were judged to be of “noncardiac” origin. However, events in the “conventional group” included heart failure as an indication for surgery in 22 patients and cardiac deaths in 6 patients who had already developed symptoms. In a more recent analysis with larger patient numbers, Kang et al. (15) reported no difference in overall mortality between early surgery and watchful waiting. Thus, the reported registries do not provide conclusive evidence in favor of early surgery.
Several additional caveats have to be considered in the context of early elective mitral valve surgery in asymptomatic patients.
Quantification of MR severity requires experience and may be challenging. Although the use of quantitative parameters such as the effective orifice area is recommended, it has been shown that interobserver agreement of quantitative parameters for the grading of MR is only close to 50% (16). Furthermore, even when using an integrative and quantitative approach, agreement between echo and cardiac MRI was only modest (10). Consequently, MR quantification in asymptomatic patients without signs of LV or LA dilatation may be overestimated. In a prospective study of patients with MR that were referred to mitral surgery, severe MR was confirmed using MRI in only 12 of 38 of patients who underwent surgery (9).
The outcomes of mitral valve surgery may be inhomogeneous. Experienced groups may achieve excellent repair rates >90% with a very low operative mortality <1% (17). However, in real world practice, up to 50% of the patients receive a mitral replacement, resulting in higher operative mortality (18) and exposure to prosthetic valve associated risks. Importantly, repair rates, operative mortality, and morbidity depend on hospital procedural volumes (19). Operative mortality may be <1% for high-volume centers and as high as 3% for low-volume centers (19). In addition, the combined risk of mortality and major morbidity is close to 10% even in high-volume centers (19). A high hospital volume alone was found not to guarantee successful mitral repair, denoting the “lottery of mitral valve repair surgery” (20). Ultimately, apart from hospital volume, individual surgeon-specific volume is essential; in an Society of Thoracic Surgeons database analysis of patients undergoing isolated mitral valve surgery, a strong correlation between surgeon-specific annual mitral valve volume with a probability of mitral repair was found with a predicted repair rate of 80% for 50 annual procedures (18). Strikingly, the median number of annual mitral valve operations performed per surgeon was only 5. In addition, the overall experience (and learning curve) of an individual surgeon needs to be considered, optimal outcomes being reliably achieved only after more than 300 procedures (21). Other aspects that need to be considered include the durability of repair with a rate of recurrence of at least moderate MR of 1.5% to 4% per year (22,23) and an annual reoperation rate of 0.5% to 2% (24,25). Thus, a more liberal approach to surgery may be valid for experienced surgeons in high-volume centers after careful evaluation. On the other hand, these considerations do not warrant a general recommendation of early elective surgery in asymptomatic patients with preserved LV function who are in sinus rhythm.
Excellent outcomes with active surveillance
Careful monitoring and follow-up until established indications for surgery, as defined in current guidelines are reached, is thus a valuable strategy. We have previously reported the safety of such a strategy, regarding perioperative and mid-term outcomes (6). The present study confirms that also the long-term outcomes of such an active surveillance strategy assessed in a large patient population are excellent. In comparison with the general population, no inferior long-term survival was found at 20 years and early survival was even better in the study population. This might be explained on the one hand by referral bias that potentially excludes patients with multiple comorbidities, especially those with advanced malignant disease, and the fact that vascular risk factors such as hypertension, hypercholesterolemia, and diabetes are promptly addressed in the course of the systematic patient workup in the HVC on the other hand. Furthermore, coronary artery disease was systematically screened and treated in patients who eventually developed an indication for surgery.
Importantly, the rates of asymptomatic LV dysfunction were low (7% of indications for surgery) and surgical outcomes were good, as expressed by a repair rate of 86%, a rate of residual MR comparing well with previous studies (26), a low surgical complication rate, and a low incidence of post-operative functional impairment. Post-operative LV dysfunction occurred in 15% of operated patients, a rate markedly lower than reported in previous series of patients who underwent surgical correction of MR (27).
In the setting of severe symptomatic MR (NYHA functional classes III and IV), sudden death is frequent with a reported rate of 7.8% per year (28). However, in the present study, only 2 cases of sudden death occurred in asymptomatic patients with preserved LV function, resulting in a sudden death rate of 0.1% per year, thus being comparable with the expected sudden death rate in the general population (29).
The concept of active surveillance in the setting of a HVC
In the present study, a strategy of watchful waiting was evaluated. It involved clinical and echocardiographic follow-up examinations performed in the setting of a HVC at a tertiary reference center every 6 months. Given the nature of this strategy, the term of active surveillance seems more appropriate. Although it is true that it may involve an initial conservative management phase, it is not a “conservative management” strategy because indications for surgery are strictly assessed and applied.
Providing a dedicated setting to deliver the required specialized care is thus essential for asymptomatic patients with MR. Active surveillance indeed involves a structured approach with scheduled follow-up visits in an experienced setting that also allows for further work-up, if required. Of note, one quarter of the patients had an indication for surgery based on echocardiographic or ECG findings, despite being asymptomatic, highlighting the importance of comprehensive follow-up.
Indeed, both the recent American College of Cardiology/American Heart Association (4) and the recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines (5) on valvular heart disease now recognize the importance of heart valve centers of excellence. In this context, active surveillance of patients with MR in a dedicated HVC allows one to achieve an improved quality of care by optimal follow-up and timely referral to surgery.
Only patients with chronic severe primary MR were included in the study and, therefore, the results cannot be extrapolated to other forms of MR.
Surgical indications for asymptomatic primary MR have evolved mildly over the course of the study with the addition of surgical indications in selected low-risk asymptomatic patients in the more recent guideline updates. However, in the current analysis none of the patients were operated on for those latter reasons.
It might be viewed as a limitation that the assessment of the symptomatic status may be challenging and exercise testing, which was shown to be a predictor of outcome (30), was not performed in all patients. At the same time, the physician-based assessment of the functional status with the use of exercise testing in selected patients according to clinical judgment yielded excellent long-term survival.
Exercise echocardiography (31) was not routinely performed because its predictive value is unclear and neither the European nor the American guidelines base a surgical indication on that test.
The concept of LV global longitudinal strain in patients with primary MR has only been introduced long after the study initiation and this parameter was not part of the study protocol.
As mentioned previously, quantitation of MR severity may be challenging, however, in the present study, an integrated approach was used to quantify MR as recommended by current recommendations (11,12) and, furthermore, the majority of the patients had flail leaflets, which is highly characteristic of the presence of severe MR (11,12).
Mitral annular dysjunction has been described to occur in patients with mitral valve prolapse (32) and a recent article sought to address this issue with a three-dimensional echo study (33). In the present study we focused on the established analysis of mitral valve morphology only.
Serum biomarkers were not routinely assessed in this patient population. At the same time, no consistent threshold of serum N-terminal pro–B-type natriuretic peptide concentration has been defined to select patients for early surgery (4,5).
Patients with severe but asymptomatic primary MR may remain free of indications for surgery for extensive periods of time. In such patients, active surveillance performed in experienced centers is associated with a favorable prognosis, resulting in timely referral to surgery, excellent long-term survival, and good surgical outcomes.
COMPETENCY IN MEDICAL KNOWLEDGE: In patients with severe asymptomatic primary MR, a strategy of active surveillance, comprising regular clinical and echocardiographic follow-up visits in an experienced center, is associated with a favorable prognosis. It results in timely referral to surgery, excellent long-term survival, and good surgical outcomes.
TRANSLATIONAL OUTLOOK: Randomized trials comparing active surveillance and early elective surgery are needed.
Dr. Laufer has done consulting activity for Edwards. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- confidence interval
- cardiopulmonary resuscitation
- heart valve clinic
- left atrium
- left ventricle
- left ventricular systolic function
- mitral regurgitation
- magnetic resonance imaging
- pulmonary hypertension
- standardized mortality ratio
- Received March 30, 2018.
- Revision received April 26, 2018.
- Accepted May 17, 2018.
- 2018 American College of Cardiology Foundation
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