Introduction
In recent years, cardiologist increasingly recognize the dynamic nature of mitral regurgitation (MR). Handgrip (HG) exercise echocardiography may serve as an alternative to the current gold standard, bicycle exercise, as it can easily be accomplished by the majority of patients. However, there is only scarce data describing the effect of HG exercise on the severity of MR. Here, we hypothesized that HG exercise leads to relevant increases in MR severity in a significant proportion of patients.

Methods
Patients that underwent HG echocardiography between 2018-2020 were prospectively enrolled. Echocardiography at rest and during HG exercise following a standardized protocol was performed when there was a discrepancy between symptoms and echocardiographic findings at rest.

Results
214 patients (77 DMR patients (36%); 137 FMR patients (64%)) that underwent HG echocardiography were included. In the entire cohort, HG exercise provoked a meaningful hemodynamic response (hr +10±2 bpm; systolic bp +13±20 mmHg; diastolic bp +6±15 mmHg; all p<0.001). LV end-diastolic and end-systolic volumes slightly increased, while LV ejection fraction (LVEF) decreased (mean LVEF: 51±15% vs. 47±15%; p=0.030). In both, DMR and FMR, the majority of patients showed increases in MR severity: In DMR, effective orifice area (EROA) increased by 0.04±0.02 cm² (p=0.062), and regurgitation volume (RVol) by 9±3 ml (p=0.007). According to established cut-off values, 27% of patients with DMR experienced a marked increase in MR severity (RVol >15 ml). Twelve patients with non-severe MR at rest (17%) developed severe MR during HG exercise (Fig. 1). In FMR, EROA increased by 0.05±0.01 cm², and RVol increased by 7±1 ml (both p<0.001). Eighteen percent of patients experienced a marked increase in MR (RVol >15 ml). Thirty-nine patients with non-severe MR at rest (32%) developed severe MR during HG exercise (Fig. 1).

In both, DMR and FMR, the increase in RVol was accompanied by a rise in estimated systolic pulmonary artery pressure (DMR: r=0.297, p=0.020; FMR: r=0206, p=0.034). Predictors of marked increases in MR severity (RVol >15 ml) were previous valve surgery (p=0.040), left atrial volume (p=0.020), right atrial volume (p=0.025), and mitral annulus diameter (p=0.035) in DMR patients. In FMR patients, previous ST-elevation myocardial infarction (p=0.025), LV end-systolic volume (p=0.006), LV end-diastolic volume (p=0.007), LVEF (p=0.011), wall motion score index (p=0.018), RV diameter (p=0.012), fractional area change (p=0.018), and mitral annulus diameter (p=0.038) were predictors of dynamic MR (increase in RVol >15ml). 

Conclusions

HG echocardiography may serve as a valuable tool to unmask marked exercise-induced increases in MR severity in about every fourth patient with DMR and every fifth patient with FMR. Moreover, a significant proportion of patients with non-severe MR at rest developed severe MR during HG exercise. Thus, HG exercise may be performed in daily clinical practice as an alternative for bicycle exercise. Future studies need to address the prognostic value of HG echocardiography in the assessment of dynamic MR.

Fig 1. The figure shows echocardiographic examples of MR at rest and during HG exercise (top), distribution of MR severity at rest and during HG exercise (middle), and the correlation between changes in RVol and changes in estimated systolic pulmonary artery pressure during rest and HG exercise in patients with DMR (left) and FMR (right).