Functional mitral regurgitation, a dynamic disease: lobbying for greater adoption of handgrip echocardiography!

This editorial refers to ‘Prevalence and prognostic impact of dynamic atrial functional mitral regurgitation assessed by isometric handgrip exercise’, by M. Spieker et al., https://doi.org/10.1093/ehjci/jead336.

Mitral regurgitation (MR) is the most prevalent valvular heart disease and carries a poor prognosis if left untreated.¹ Echocardiography is the cornerstone of MR evaluation and should be performed for diagnosis, risk stratification, and treatment guidance.² Despite the morbidity, mortality, and symptomatic burden of MR, only 15% of patients with MR are referred for mitral valve surgery because of presumed high surgical risk.³ Consequently, mitral valve transcatheter edge-to-edge repair (M-TEER) has emerged as an important alternative for patients unsuitable for surgery. While initially approved for patients with primary MR, current guidelines now consider M-TEER a class IIa recommendation for patients with functional MR (FMR) who meet certain criteria.⁴ Although successful MR reduction via M-TEER has been shown to impact mortality and heart failure hospitalization rates, controversies regarding M-TEER in FMR still remain. FMR remains an opaque concept, and atrial FMR is hardly found as a clear entity in guidelines.⁵

As a matter of fact, new concepts have emerged, and the significance of FMR sub-classifications has been heavily debated in recent years.² Atrial and ventricular FMR have been suggested as two distinct entities driven by different mechanisms, which potentially impact prognosis and responses to treatment.⁵ In 2023, Naser et al.⁶ described the prevalence, pathophysiology, and features associated with atrial FMR. Their conclusions highlight that left atrial and mitral annular dynamics are often underappreciated for their role in provoking FMR. Because of this unique pathophysiology, atrial FMR may need to be individualized for its assessment and management. In 2022, Ooms et al.⁷ introduced the concept of disproportionate MR, which could potentially explain the contradictory results of clinical trials assessing MR-TEER in MR. Although MITRA-FR did not show benefits to M-TEER in patients with advanced MR, the COAPT trial demonstrated the opposite, possibly due to the greater prevalence of atrial FMR in the latter cohort.⁸ Clearly, while non-interventional management of valvular heart disease remains critically important, certain patients remain symptomatic despite optimal medical therapy. Thus, on the patient level, what else besides dynamic testing can demonstrate that a key portion of symptoms come from the dynamic severity of MR?

Bertrand et al.⁹ have previously summarized the effect of different exercise modalities on the cardiovascular system: in dynamic exercises such as running and cycling, multiple muscle groups contract to achieve movement. Such activity is associated with peripheral vasodilation, leading to reduced systemic vascular resistance and increased venous return due to skeletal muscle pumping. This increase in preload and decrease in afterload serve to increase left ventricular forward stroke volume, which therefore increases cardiac output. In contrast, during static/isometric exercises such as hand-gripping, systemic vascular resistance does not decrease; if anything, it occasionally increases. In the absence of afterload reduction, forward stroke volume remains largely unchanged, and any increase in cardiac output is primarily mediated by heart rate (Figure 1). Hence, static exercise imposes a pressure load on the left ventricle, whereas dynamic exercise constitutes a volume load.

Figure 1

Simplified comparison between exercise stress testing and hand-gripping echocardiography, demonstrating the latter’s value in atrial functional mitral regurgitation.

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To date, there has only been one study comparing static exercise with dynamic exercise on the degree of MR.¹⁰ In a cohort of 367 patients, Spieker et al.¹⁰ showed that hand-gripping induces a slight but statistically significant increase in MR compared with that induced by cycling. Moreover, the increase in MR was greater in patients with FMR compared with those with primary MR,¹⁰ highlighting the potential utility of handgrip testing for this subgroup. Whereas multimodality imaging (via cardiac computed tomography, magnetic resonance imaging, and positron emission tomography) has added great value to myocardial imaging, it is possible that echocardiography—bolstered with new, isometric exercise techniques—may add similar value to dynamic MR assessment. Importantly, further studies are urgently required, as the weakness of handgrip testing (bypassed by these authors in their statistical plan) cannot be bypassed in clinical practice.

Nonetheless, the demonstration that a simple, easy-to-perform handgrip test could be so impactful for MR assessment is the key value of Spieker et al.’s work.¹⁰ These authors must be congratulated for conceptualizing this study and demonstrating the prognostic value of this test. They underscore the critical importance of dynamic assessment of MR, particularly as it relates to prognosticating FMR phenotypes. Previously, European Association for Cardiovascular Imaging (EACVI) expert consensus statements have recommended tilt-table exercise stress echocardiography (ESE) for the assessment of MR.¹¹ While tilt-table ESE is now widely used, the level of evidence supporting its impact remains insufficient for being so clearly recommended in guidelines. In expert hands, tilt-table ESE certainly impacts MR, but any conclusions about MR dynamicity may still be discrepant with cardiopulmonary exercise testing (CPET). In atrial FMR, mitral annular dynamics probably play a role in this discrepancy, but more quantitative echocardiographic studies are needed to clarify this mechanism.

In 2023, Coisne et al.¹² introduced the ratio of pre-procedural regurgitant volume to left atrial volume for M-TEER prognostication. Additionally, we recently demonstrated that in addition to CPET, ESE is impactful for MR assessment.^13,14 However, Spieker’s results are perhaps even more groundbreaking, as they suggest that simple handgrip testing could be added to routine echocardiography for every patient—especially those with FMR and atrial FMR phenotypes, even when atrial arrhythmias are present—in order to better quantify dynamic MR¹⁰ (Figure 1). Given that patients with atrial FMR may derive even greater benefit from M-TEER, utilizing the handgrip technique to identify additional patients with atrial FMR could significantly impact MR prognostication and management. As the definition of atrial FMR is still nascent, large, randomized studies are still needed to demonstrate the value of M-TEER for this phenotype. Clearly, inclusion criteria for these studies may need to integrate the handgrip testing.¹⁵

In summary, Spieker’s results should be considered by both imagers and interventional cardiologists, cardiac surgeons, and heart failure specialists each form a part of the MR care team. Dynamic MR assessment via handgrip echocardiography needs to be further evaluated in prospective studies to confirm that isometric exercise really does increase atrial FMR in about one-third of patients.

Funding

None declared.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

References

Author notes