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For patients with symptomatic severe mitral stenosis (MS), percutaneous transvenous mitral commissurotomy (PTMC) using an Inoue (or Inoue-like) balloon is the most reasonable initial treatment option.1 For asymptomatic patients, however, there are no reliable data to guide therapy. Guideline recommendations are therefore based largely on consensus, and have varied over time, due perhaps to differing interpretations of the existing data (table 1). The greatest uncertainty pertains to the management of asymptomatic patients with mitral valve area (MVA) between 1 and 1.5 cm2. Kang and colleagues attempt to address this knowledge gap. They randomly allocated 167 asymptomatic patients with rheumatic MS and MVA 1–1.5 cm2, to either undergo PTMC within 3 months of randomisation or to remain on medical treatment.2 Over a median follow-up of just over 6 years, the composite primary outcome, consisting of PTMC-related complications, cardiovascular mortality, ischaemic stroke and systemic embolism, occurred in 7/84 (8.3%) patients in the PTMC arm and 9/83 (10.8%) patients (HR 0.77, 95% CI 0.29 to 2.07; p=0.61). The authors conclude that a strategy of initial PTMC does not reduce the incidence of adverse cardiovascular events and suggest that medical treatment with careful follow-up should continue to remain the standard of care for these patients.
Guideline recommendations for the management of asymptomatic patients with significant mitral stenosis (mitral valve area ≤1.5 cm2)
These are important data in a field almost bereft of evidence from randomised trials. However, these results should be interpreted with caution for several reasons. First, the authors powered their study on the assumption of an unrealistically large (about 85%) relative risk reduction with PTMC, based on event rates from their previous observational cohort.3 The effect of PTMC, if any, in this population is likely to be modest at best, and this trial is grossly underpowered to detect an effect of this magnitude. The correct interpretation should therefore be that this is an inconclusive trial. The wide CIs around the effect estimate do not allow us to rule out both large benefits and large downsides that may be associated with early PTMC. Second, it is not clear how successful the commissurotomy was. Although the authors report that 97% of patients had a successful PTMC, the average post-PTMC MVA was about 1.8 cm2, with only a 2 mmHg fall in the mean trans-mitral gradient. This is in contrast to an average post-PTMC MVA of over 2 cm2 in their own previous experience.3 Finally, components of the primary outcome may not be sensitive to the intervention. In this older population (average age 55 years), half of whom were in atrial fibrillation (AF), 45% with hypertension and 5% with diabetes, stroke risk may be influenced to a greater extent by conventional risk factors than by the severity of MS.4 5 The effect of PTMC on stroke risk may consequently be smaller than that seen in younger populations without risk factors. Rates of symptomatic deterioration requiring acute care (including urgent PTMC), and the need for mitral valve replacement (due to disease progression rendering patients ineligible for PTMC), may be more appropriate outcomes. A greater proportion of patients in the medical therapy group did undergo mitral valve replacement compared with those assigned to early PTMC (20.5 vs 11.9%, p=0.19). However, it is not clear whether this was because of unsuitable valve morphology or some other reasons.
Given the lack of conclusive outcomes data, the most reasonable approach to treating patients with asymptomatic severe MS is to be guided by our understanding of the haemodynamics of severe MS and assumptions on the risk–benefit trade-offs with intervening early. Experience with PTMC over the years suggests that intervening early in patients with severe MS may not be associated with increased procedural risks. In fact, a greater pre-procedural MVA may be associated with higher procedural success.6 In contrast, both procedural success and longer-term outcomes are worse with increasing age and long-standing disease (characterised by the presence of valve calcification, higher echo score and AF).6 The less settled question, however, relates to the categorisation of MS severity and the ability of symptoms to reliably identify significant MV obstruction.
What is significant MS?
Significant mitral obstruction may be presumed if stroke volume is reduced at rest or cannot be increased without a rise in trans-mitral gradients. Haemodynamic studies suggest that virtually all patients with an MVA ≤1.5 cm2 have reduced cardiac output at rest,7 particularly if they have associated tricuspid regurgitation. Furthermore, when MVA is ≤1.5 cm2, resting cardiac output and left atrial pressures do not appear to differ significantly between severely symptomatic patients and those with minimal or no symptoms.7 Moreover, in a study of patients with significant MS (a third of whom had MVA >1 cm2), virtually all had an increase in trans-mitral gradients with treadmill exercise, and there was little correlation between resting trans-mitral gradients and exercise time.8 The observed discordance between haemodynamics and symptoms could have several explanations. Symptoms are subjective, and patients may consciously or unconsciously limit activity to remain free of dyspnoea. Symptoms may also be attenuated by compensatory changes such as dilated pulmonary lymphatics, and alveolar thickening that occur to varying degrees, as MS progresses.8 9 Nevertheless, echocardiographic MVA remains the most objective, readily measured, reliable and reproducible metric available for assessing severity of MS. Arguably, therefore, MS can be considered to be severe enough to need intervention once the MVA is ≤1.5 cm2, irrespective of symptoms, if PTMC can be performed safely. The only caveat being that since normal cardiac output is dependent on the body surface area (BSA), and MVA is typically reported without indexing to BSA, the threshold for significant MS may correspond to ≤1.3 cm2 in populations with lower BSA (South Asian patients with MS have BSAs in the range of 1.4–1.5 m,2 10 compared with an average of 1.65 m2 in other populations).2 7 Other surrogate markers of left atrial hypertension and stasis may also support the need for intervention in asymptomatic patients (box 1). Atrial fibrillation in patients with MS is a consequence of adverse atrial remodelling initiated by chronic left atrial hypertension. The presence of AF signals the presence of haemodynamically significant MS and also predisposes patients to acute deterioration (due to increases in ventricular rate during exercise and other adrenergic triggers) and systemic embolism. Elevated brain natriuretic peptide (BNP) levels may provide supportive evidence of raised left atrial pressures. A high BNP level is associated with lower exercise capacity and an increased likelihood of adverse events during follow-up.11
Parameters suggesting haemodynamically significant mitral stenosis in asymptomatic patients with mitral valve area ≤1.5 cm2 (or ≤1.3 cm2 if body surface area is <1.5 m2)
Elevated pulmonary artery systolic pressure >50 mmHg
Presence of dense spontaneous echo-contrast
History of stroke or systemic embolism
Atrial fibrillation (new-onset, paroxysmal, persistent or permanent)
Elevated levels of BNP or NT-pro BNP
Left atrial diameter >55 mm (in the absence of significant mitral regurgitation)
Exercise testing to unmask symptoms in asymptomatic patients with MS is rarely performed in developing countries. When performed, the elevation of transmitral gradients to >10 mmHg (with or without the development of symptoms) may be considered as evidence of haemodynamically significant MS. A low resting cardiac output (indexed to body surface area) at cardiac catheterisation may also support the need for early intervention.
The evidence base guiding the management of asymptomatic MS (and rheumatic heart disease in general) is limited, draws heavily on studies done in the pre-echocardiographic era and is of low quality. Randomised trials such as the one by Kang et al 2 are therefore commendable and need to be replicated among larger populations in endemic countries. Until such time, management of asymptomatic patients with significant MS should be guided mainly by pathophysiological considerations, taking into account local expertise and resource availability. Clinical experience in poor countries suggests that even minimally symptomatic patients with severe MS often deteriorate, due to AF and fast ventricular rates, triggered by drug noncompliance or inter-current illness. In such situations, patients may not have timely access to acute care (and emergency PTMC), which may be life-saving. Therefore, a case can be made for performing early PTMC in asymptomatic patients with significant MS (MVA ≤1.5 cm2, or ≤1.3 cm2 if BSA is <1.5 m2), provided the procedure can be performed safely (procedure-related death or mitral regurgitation requiring surgery <3%). Close medical follow-up should be reserved for patients in sinus rhythm, without evidence of left atrial hypertension, or a propensity for haemodynamic deterioration or systemic embolism (box 1).
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Twitter @drkarthik2010
Contributors GK is the sole contributor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Commissioned; internally peer reviewed.