Elsevier

The Lancet

Volume 391, Issue 10124, 10–16 March 2018, Pages 960-969
The Lancet

Articles
Outcome and undertreatment of mitral regurgitation: a community cohort study

https://doi.org/10.1016/S0140-6736(18)30473-2Get rights and content

Summary

Background

Mitral regurgitation is the most common valve disease worldwide but whether the community-wide prevalence, poor patient outcomes, and low rates of surgical treatment justify costly development of new therapeutic interventions remains uncertain. Therefore, we did an observational cohort study to assess the clinical characteristics, outcomes, and degree of undertreatment of mitral regurgitation in a community setting.

Methods

We used data from Mayo Clinic electronic health records and the Rochester Epidemiology Project to identify all cases of moderate or severe isolated single-valvular mitral regurgitation (with no other severe left-sided valvular disease or previous mitral surgery) diagnosed during a 10-year period in the community setting in Olmsted County (MN, USA). We assessed clinical characteristics, mortality, heart failure incidence, and results of cardiac surgery post-diagnosis.

Findings

Between Jan 1, 2000, and Dec 31, 2010, 1294 community residents (median age at diagnosis 77 years [IQR 66–84]) were diagnosed with moderate or severe mitral regurgitation by Doppler echocardiography (prevalence 0·46% [95% CI 0·42–0·49] overall; 0·59% [0·54–0·64] in adults). Left-ventricular ejection fraction below 50% was frequent (recorded in 538 [42%] patients), and these patients had a slightly lower regurgitant volume than those with an ejection fraction of 50% or higher (mean 39 mL [SD 16] vs 45 mL [21], p<0·0001). Post-diagnosis mortality was mainly cardiovascular in nature (in 420 [51%] of 824 patients for whom the cause of death was available) and higher than expected for residents of the county for age or sex (risk ratio [RR] 2·23 [95% CI 2·06–2·41], p<0·0001). This excess mortality affected all subsets of patients, whether they had a left-ventricular ejection fraction lower than 50% (RR 3·17 [95% CI 2·84–3·53], p<0·0001) or of 50% or higher (1·71 [1·53 −1·91], p<0·0001) and with primary mitral regurgitation (RR 1·73 [95% CI 1·53–1·96], p<0·0001) or secondary mitral regurgitation (2·72 [2·48–3·01], p<0·0001). Even patients with a low comorbidity burden combined with favourable characteristics such as left-ventricular ejection fraction of 50% or higher (RR 1·28 [95% CI 1·10–1·50], p<0·0017) or primary mitral regurgitation (1·29 [1·09–1·52], p=0·0030) incurred excess mortality. Heart failure was frequent (mean 64% [SE 1] at 5 years postdiagnosis), even in patients with left-ventricular ejection fraction of 50% or higher (49% [2] at 5 years postdiagnosis) or in those with primary mitral regurgitation (48% [2]). Mitral surgery was ultimately done in only 198 (15%) of 1294 patients, of which the predominant type of surgery was valve repair (in 149 [75%] patients). Mitral surgery was done in 28 (5%) of 538 patients with left-ventricular ejection fraction below 50% and in 170 (22%) of 756 patients with ejection fraction of 50% or higher, and in 34 (5%) of 723 with secondary mitral regurgitation versus 164 (29%) of 571 with primary regurgitation. All other types of cardiac surgery combined were performed in only 3% more patients (237 [18%] patients) than the number who underwent mitral surgery.

Interpretation

In the community, isolated mitral regurgitation is common and is associated with excess mortality and frequent heart failure postdiagnosis in all patient subsets, even in those with normal left-ventricular ejection fraction and low comorbidity. Despite these poor outcomes, only a minority of affected patients undergo mitral (or any type of cardiac) surgery even in a community with all means of diagnosis and treatment readily available and accessible. This suggests that in a wider population there might be a substantial unmet need for treatment for this disorder.

Funding

Mayo Clinic Foundation.

Introduction

Recent epidemiological studies have shown that the global valvular heart disease burden is high and increasing, with serious implications for affected patients worldwide.1, 2, 3 However, the outcomes and treatment standards of each individual patient with heart valve disease cannot be inferred from these studies, which included multi-valvular diseases, previous cardiac surgeries, and associated cardiac disorders, all of which have major confounding effects on outcome and treatment. The standard of care for valve diseases is surgical repair or replacement,4 but many patients do not undergo surgery and remain untreated. Such undertreatment in the community was suspected in the case of aortic stenosis,5 but was ultimately confirmed by increasing numbers of percutaneous aortic valve replacements while the rate of surgical valve replacements remained steady worldwide.6 However, no such data exist for mitral regurgitation, despite its importance as the most common heart valve disease,2 its growing burden,2, 3 and favourable reparability.7 Mitral regurgitation is the focus of intense minimally invasive device development,8 but whether serious outcomes or an unmet need for treatment really exist remains unclear.

Research in context

Evidence before this study

We searched the Cochrane Library and PubMed for publications about the prevalence and outcomes of isolated moderate to severe mitral regurgitation between Jan 1, 1990, and June 1, 2016, using the search terms “epidemiology”, “prevalence”, “outcomes”, “mitral insufficiency”, “regurgitation”, and “isolated”. Mitral regurgitation is generally considered the most common heart valve disorder worldwide, but only a few studies have reported on its epidemiology. In particular, outcome after diagnosis, which has been analysed previously only in selected populations, remains undefined in the community setting. Although mitral surgery is established as the only guideline-recommended treatment for moderate to severe mitral regurgitation, access to care and treatment might be insufficient in some settings. However, access to care and treatment for isolated mitral regurgitation has not been evaluated in an entire community with state-of-the-art facilities, good access to treatment, and high availability of specialised providers, or over the long-term. In summary, prevalence, survival, heart failure rates, and surgical outcomes of rigorously defined isolated mitral regurgitation (diagnosed by Doppler echocardiography) over the long-term, in an entire community with no or minimal impediment to access to care, is unknown; therefore, the unmet need for treatment for this heart valve disorder remains uncertain.

Added value of this study

We analysed a cohort of patients with isolated mitral regurgitation in Olmsted County, MN, USA, that included all community-wide consecutive cases diagnosed, to define the prevalence of the disorder and—most importantly—to assess its management and outcomes across the community and in the long term. Because this community has modern facilities, diagnostic methods, expertise, and cardiac surgery easily accessible, it provides an ideal setting to ascertain whether mitral regurgitation therapeutic needs are met. In this context, we can report a high community prevalence of isolated mitral regurgitation. We also found that from all diagnosed cases, isolated moderate or severe mitral regurgitation is associated with excess mortality compared to that expected in the same county, both overall and in all subsets of patients, even those who seem to have the most benign types of the disorder. Similarly, heart failure is very frequent in all subsets of patients with mitral regurgitation, even in those without any other predisposing factor or comorbidity. Most importantly, long-term outcome analysis showed that despite all available facilities and expertise, only 15% of patients ultimately underwent surgical correction of the mitral regurgitation. It is particularly notable that women were operated on less than half as often as men. Hence, for the first time, we show that in a community with very well-equipped medical facilities and good access to treatment, moderate-to-severe isolated mitral regurgitation is common, and is associated with a high incidence of heart failure, and severe excess mortality, and is substantially undertreated.

Implications of all the available evidence

All evidence, especially our lifelong population-based data, point towards a substantial unmet need for treatment of mitral regurgitation, which contrasts with the high excess mortality and high frequency of heart failure, with few patients receiving the only treatment available (surgery) and represents a call for action. Beyond the necessary education of care providers regarding medical knowledge and clinical guidelines for mitral regurgitation, referral of patients with the disorder to cardiology teams for decision-making, integrating all clinical information and therapeutic approaches available, is a critical step for these patients to obtain access to care. Simultaneously, new approaches to treatment of mitral regurgitation in all subsets of patients warrant development and testing in appropriate clinical trials.

The 2007 Euro Heart Survey9 suggested that patients referred to cardiology centres with mitral regurgitation in Europe were frequently denied surgical treatment. However, such undertreatment might reflect these patients being referred to cardiology centres too late, with an overwhelming number presenting with heart failure.9 Conversely, it might be a caveat of a brief cross-sectional analysis that did not take into account later treatments given to these patients. In a real-world community setting (in Olmsted County, Rochester, MN, USA), subsets of mitral diseases have been reported,10 but no overall characterisation of isolated, single-valvular mitral regurgitation and its long-term treatment standards has been done. At the national level in the USA, the sharp contrast between the few isolated mitral surgeries performed11 and the large burden of mitral regurgitation inferred from epidemiological studies2 suggest undertreatment in this setting, but comprehensive information is not available.

Olmsted County provides a unique opportunity to study mitral regurgitation because it has a single echocardiographic laboratory centralising diagnoses, large samples of patients with single-valve heart disorders, and health-care providers linked through the Rochester Epidemiology Project.12 Furthermore, facilities and expertise for the diagnosis and treatment of valve diseases are readily available, so that performance versus non-performance of repair or replacement cannot be ascribed to access limitations. Therefore, we aimed to assess the community-wide prevalence, clinical characteristics, survival, and heart-failure post-diagnosis in Olmsted County, to evaluate standards of treatment for native, moderate-to-severe mitral regurgitation, and to ascertain whether or not an unmet need for treatment really exists.

Section snippets

Study design, eligibility criteria, and source data

In this observational cohort study, we used the Mayo Clinic electronic health records to identify eligible patients who met the following criteria: permanent residents (≥3 months) of Olmsted County (and not solely resident there for medical treatment at the Mayo Clinic) who had undergone clinically indicated Doppler echocardiography between Jan 1, 2000, and Dec 31, 2010, leading to a diagnosis of moderate-to-severe mitral regurgitation that was isolated in nature. We used data from the

Results

Between Jan 1, 2000, and Dec 31, 2010, 29 390 Olmsted County residents underwent Doppler echocardiography and 1294 residents fulfilled eligibility criteria with isolated (single-valvular) moderate-to-severe mitral regurgitation. During the study period, more than 30 staff cardiologists were assigned to the Echocardiographic Laboratory, and nine staff surgeons performed around 3000 cardiac surgeries at that centre per year.

The prevalence of isolated moderate-to-severe mitral regurgitation in the

Discussion

The results of our study show that mitral regurgitation, even isolated, is associated with sizeable excess mortality, notable subsequent heart failure, and is rarely treated by the only approach recommended—ie, mitral valve surgery. No subgroup of patients is spared, with these results recorded in all possible subsets and classifications of mitral regurgitation. Although rationales for non-referral are undefined, such undertreatment is not a simple delay but rather affects patients throughout

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