Abstract Background Recent studies suggest that mitral regurgitation (MR) is a dynamic condition influenced by global and regional left ventricular (LV) remodeling as well as mitral valvular deformation. Exercise testing plays a substantial role in assessing the hemodynamic relevance of MR and is recommended by current guidelines. Handgrip exercise may serve as alternative exercise intervention to bicycle exercise, as it is easy to perform even bedside. However, there are no data yet, on the prevalence, mechanisms and prognostic impact of dynamic MR in patients with dilated cardiomyopathy using isometric exercise testing. Aims We aimed to assess the prevalence, hemodynamic consequences, and prognostic impact of exercise-induced changes in MR in patients with hypokinetic non-dilated and dilated cardiomyopathy. Methods Patients with hypokinetic non-dilated and dilated cardiomyopathy and at least mild MR who underwent handgrip echocardiography at the University Hospital Duesseldorf between January 2018 and September 2021 were enrolled.Patients were followed-up for one year to assess clinical outcomes. We assessed all-cause mortality, HF-associated hospitalizations, MV surgery, transcatheter edge-to-edge repair (TEER), left ventricular assist device implantation and heart transplantation during follow-up. Results Fifty-eight patients were included (mean age 70±15 years; 41% female; mean LVEF 37±10%). At rest, 28 patients (48%) presented with mild MR, and 30 patients (52%) had moderate MR. Fifteen patients (26%) with non-severe MR at rest, developed dynamic severe MR during handgrip exercise. Patients with dynamic severe MR had advanced MR at rest, larger left atrial dimensions, and increased mitral annulus diameter (all p<0.01). During exercise, LVEDVi, LVESVi and parameters of local left ventricular remodeling (tenting height, tenting area) were increased in patients with dynamic severe MR compared to those with non-severe MR (all p<0.05). During one-year follow-up, there was no difference regarding all-cause mortality and HF hospitalizations in patients with dynamic severe MR and non-severe MR (Log-rank test Chi2 0.262; p=0.609)(Figure 1). However, patients with dynamic severe MR more often underwent mitral valve surgery/intervention than patients with non-severe MR (Log-rank test Chi2 29.41; p<0.001)(Figure 1). Conclusion Our results demonstrate that the evaluation of non-ischemic MR only at rest underestimates the full severity of the lesion. Handgrip exercise unmasks severe MR in every fourth patient with non-severe MR at rest. These data may have implications for therapeutic decision-making in symptomatic patients with hypokinetic non-dilated and dilated cardiomyopathy and non-severe MR at rest. TEER might present an effective treatment option to improve clinical outcomes in patients with non-ischemic cardiomyopathy and non-severe MR at rest but dynamic severe MR during exercise.Figure 1

Abstract Background Mitral regurgitation (MR) is frequent in patients with ischemic heart disease and carries a dismal prognosis. Previous studies already demonstrated the prognostic benefit of bicycle exercise testing in patients with ischemic MR. Thus, current guidelines emphasize the role of exercise testing in patients with valvular heart disease. Isometric handgrip exercise resembles an alternative exercise intervention, that can also be performed in frail, comorbid patients. Until now, there are no data on the prognostic impact of handgrip echocardiography in heart failure patients with ischemic MR. Purpose To assess the prognostic benefit of isometric handgrip testing in heart failure patients with ischemic MR. Methods We prospectively enrolled patients with ischemic cardiomyopathy (left ventricular ejection fraction <50%) and at least mild MR that underwent echocardiography at rest and during handgrip exercise between January 2019 and September 2021. Patients were followed-up for one year to assess clinical outcomes. The combined endpoint included all-cause mortality, heart failure hospitalisation, ventricular assist device implantation (VAD), heart transplantation and mitral valve (MV) surgery/intervention. Results We included 133 patients (mean age was 75±10 years, 21% were female). Seventy patients (53%) presented with mild MR, while 54 patients had moderate MR (41%), and 9 patients (7%) showed severe MR at rest. Twenty-five patients (20%) with non-severe MR at rest, developed severe MR during handgrip exercise. One-year follow-up (median 321 (162-427) days) was complete in 128 patients (96%). Seventy-one patients (56%) experienced an adverse event: 13 patients (10%) died, 33 patients (26%) were re-admitted to hospital due to heart failure symptoms, 30 patients (24%) underwent MV transcatheter edge-to-edge repair, six patients (5%) received MV surgery, one patient (1%) underwent VAD implantation, and another three patients (4%) underwent heart transplantation. According to MR severity at rest, there was no difference in outcomes in patients with mild, moderate and severe MR (p=0.189). As expected, patients with severe MR at rest more often tended to undergo mitral valve surgery/interventions compared to the other groups (p=0.064). However, patients with non-severe MR at rest and exercise-induced severe MR presented with adverse outcomes similar to patients with severe MR at rest (p=0.005). Furthermore, patients with severe MR at rest and patients with dynamic severe MR underwent mitral valve surgery/interventions more frequently than patients with non-severe MR (p<0.001). Conclusion(s) In heart failure patients with ischemic MR, isometric handgrip testing unmasks severe MR in approximately every fifth patient with non-severe MR at rest. These patients showed similar clinical outcomes as compared to patients with severe MR already at rest. Thus, handgrip exercise testing might be a useful tool to guide further therapeutic decision making.

Abstract Background In the last years, cardiologist increasingly recognize "atrial functional mitral regurgitation" (AFMR) frequently associated with heart failure with persevered ejection fraction and atrial fibrillation. Exercise echocardiography is recommended by current guidelines in patients with secondary mitral regurgitation (MR) in several clinical scenarios. However, there are no data on the prognostic impact of exercise induced AFMR yet. We hypothesise that handgrip exercise during echocardiography unravels dynamic changes of MR severity that may impact further clinical decision making. Purpose We aimed to assess the prognostic impact of isometric exercise-induced changes in patients with AFMR. Methods Patients with atrial fibrillation and at least mild AFMR who underwent handgrip exercise echocardiography between January 2019 and September 2021 were included. Patients were followed-up for one year to assess clinical outcomes. The combined endpoint included all-cause mortality, heart failure hospitalisation and mitral valve surgery/intervention. Results We included 80 patients with AFMR (median age was 80 (77-83) years; 53.8%were female). Echocardiography at rest showed mild MR in half of the patients (53.8%), moderate MR in 20 patients (25.0%), and severe MR in 17 patients (21.2%). In nearly every fifth patient (17.5%) with non-severe MR at rest, the MR became severe during exercise. Median follow-up duration was 12 months (IQR: 4-17 months). Follow-up was completed in 78 of the 80 patients (97.5%). Thirty-five patients (44.9%) experienced adverse events. Kaplan-Meier survival analysis revealed adverse clinical outcomes more often in patients with severe MR during exercise (76.9%) compared to patients with non-severe MR during exercise (33.3%)(p<0.001). Addition of handgrip exercise testing to echocardiographic assessment at rest improved the global chi-square (from 21.2 to 30.2) and the Harrell’s c-index (from 0.69 to 0.78) for prediction of mitral valve surgery/interventions during follow-up. Conclusions Isometric handgrip exercise testing unmasks severe MR in a significant proportion of patients with non-severe MR at rest and improves further risk stratification in these patients.

Abstract Background Pulmonary hypertension (PH) is an established prognosticator in patients with mitral regurgitation (MR). However, a substantial proportion of patients with MR presents without PH at rest but may develop PH during exercise. Previous studies already demonstrated the prevalence and prognostic impact of PH during bicycle exercise. Until now, there are no data on exercise PH assessed by handgrip exercise. Purpose To assess prevalence and predictors of exercise-induced PH during handgrip exercise in patients with MR. Methods We prospectively included patients with MR and at least mild severity that underwent echocardiography at rest and during three minutes of handgrip exercise according to a standardized protocol. PH was defined by systolic pulmonary artery pressure (SPAP) >50 mmHg. Results The final patient cohort included 371 patients with primary and secondary MR. Mean age was 74±11 years, 48% were female and 59% had atrial fibrillation. Median NT-proBNP was 2017 (845–4976) ng/l. Thirty-eight percent of patients had primary MR, while 62% presented with secondary MR. At rest, MR severity was graded as mild in 56% of patients, moderate in 32% and severe in 12%. Mean SPAP at rest was 40±12 mmHg, and 63 patients (17%) revealed PH at rest (SPAP >50 mmHg). Handgrip exercise leads to an increase in SPAP by 7±12 mmHg. Thus, during exercise 137 patients (37%) exhibited SPAP >50 mmHg. Together, 110 patients (32%) of those patients without PH at rest, showed PH during handgrip exercise. Left- (OR 1.021 (1.010 to 1.033); p<0.001), and right atrial volume index (OR 1.020 (1.009 to 1.035); p<0.001), RV fractional area change (OR 0.972 (0.949 to 0.994); p=0.013), tricuspid regurgitation (OR 1.863 (1.434 to 2.445); p<0.001) and SPAP at rest (OR 1.131 (1.100 to 1.167); p<0.001) were the predictors of exercise PH. Moreover, there was a linear correlation between the change in MR severity assessed by effective regurgitant orifice area (r=0.359; p<0.001) and regurgitation volume (r=0.370; p<0.001) and the change in SPAP. Patients with exercise PH and patients with PH at rest were more symptomatic according to NYHA functional class than patients without PH (p=0.008) (Fig. 1). Conclusion(s) In patients with primary and secondary MR, handgrip echocardiography unmasks exercise PH in every third patient without PH at rest. Bi-atrial dilatation, right ventricular function, tricuspid regurgitation and SPAP at rest were predictors of exercise PH, while changes in MR severity during handgrip exercise correlate with changes in pulmonary pressures. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University Düsseldorf to Maximilian Spieker for a Clinician Scientist Track.