Patients with chronic systolic heart failure have as cardinal symptoms dyspnea and/or fatigue at rest or during exercise. The mechanisms involved in exercise intolerance in such patients are complex and involve the intimate interaction between the cardiovascular, respiratory and musculoskeletal systems. Not all mechanisms of exercise intolerance can be clearly identified, individualized and correlated with symptoms in each heart failure patient. Fatigue seems to be related to heart’s inability to pump enough blood to meet the metabolic requirements of tissues during exercise and is related to LV stroke volume. Dyspnea is more related to the increase in LV filling pressures that leads to chronic pulmonary congestion, high systolic pulmonary pressures and ultimately to associated right ventricular dysfunction. However, in certain patients with symptoms of heart failure during exercise, the degree of LV systolic and diastolic dysfunction and the severity of the SMR at rest do not seem to explain entirely the development of dyspnea or extreme fatigue during exercise. In such patients the aggravation of SMR’s severity with exercise may explain, at least in some proportion, the symptom development [8]. Backward systolic flow from the LV to the left atrium (LA) during exercise has 2 hemodynamic consequences: (1) limits LV forward stroke volume resulting in reduced cardiac output and fatigue and (2) contributes to the increase in LA pressure and pulmonary venous pressure during exercise leading to dyspnea. Development or aggravation of SMR during exercise in heart failure patients can explain why some patients may have important exercise intolerance. Exercise-induced changes in regurgitant volume and in systolic pulmonary artery pressure proved to be larger in patients who stop exercising because of dyspnea as compared to those who stop for fatigue [9]. The magnitude of increase in regurgitant volume was also greater in patients hospitalized for pulmonary edema in the context of chronic systolic LV dysfunction [8].

Exercise induced increase in SMR’s severity is not the rule. Moreover, the severity of SMR at rest is not related to exercise induced changes in EROA or regurgitant volume [5]. Some patients might have only a modest increase of SMR with exercise, while others might have a decrease of SMR’s severity, irrespective of SMR’s severity at rest. In patients with LV contractile reserve a significant increase in LV closing forces during exercise may lead to a decrease in SMR’s severity. The prerequisite being that the increase in closing forces during exercise to be able to overcome the exercise induced increase in tethering forces of the MV.

The exercise induced changes in SMR’s severity depends on the complex and intimate interaction between MV apparatus (MV leaflets, MV annulus, papillary muscles), LV systolic dimensions and systolic function, and LA compliance and pressure during exercise [2, 5]. The strongest correlation is observed with the changes in MV configuration during exercise. The increase in EROA during exercise results from the increase in systolic tenting area (the area enclosed between the MV leaflets and the annulus plane), in coaptation distance (the distance between the coaptation point of the leaflets and the mitral annulus plane) and from systolic dysfunction of the mitral annulus (decrease of its “sphincter” function). It is very important to understand that such changes occur even in the absence of detectable myocardial ischemia and are independent of exercise induced changes in heart rate or arterial blood pressure. A more spherical LV during exercise and changes in the regional LV geometry (such as systolic expansion of an aneurismal lateral wall) are also related to changes in the MV configuration, and thus contribute to the increase in MV severity during exercise. LV dyssynchrony during exercise is also a contributor to the increase of SMR during exercise in patients with LV systolic dysfunction [10].

There are several stress methods used to explore the dynamic nature of SMR. Each of them may be clinically useful, depending on the question to be asked.

Dobutamine stress echocardiography (DSE) is essentially used to assess the presence of myocardial viability in patients with SMR. Identification of viable myocardium predicts the likelihood of functional recovery and positive reverse remodeling after revascularization [11], beta blocker treatment [12] or after cardiac resynchronization therapy [13] in patients with SMR. However, dobutamine is known to decrease preload and afterload and increase LV contractility, creating thus hemodynamic conditions that are not usually encountered in every-day life activities. Overall, dobutamine induced hemodynamic changes usually lead to a decrease in SMR’s severity, with few exceptions. Patients with inducible ischemia in the anterolateral, inferior and inferolateral LV wall may show a increase in SMR’s severity. In such patients the severity of SMR may increase due to transient regional LV systolic dysfunction that leads to leaflet tethering and a concomitant decrease in closing forces. The result is the development of secondary “ischemic” MR. In these patients revascularization of the coronary artery responsible for myocardial ischemia abolishes MR and positively influences prognostic. In some other patients, the increase in contractility of non-ischemic myocardial segments may not be enough to properly close the MV in systole. The increase in intracavitary systolic pressure determined by the increase in contractility of the uneffected myocardial segments may lead to expansion of scarred inferior, posterior or lateral walls that will increase the tethering forces and lead to an increase in SMR’s severity. Thus, decrease in SMR’s severity is not the rule with DSE.

Post exercise echocardiography (PEE) performed immediately after treadmill or ergometric bicycle exercise is another modality used to explore the dynamic component of SMR. In our experience, there is a considerable variability between peak and post-exercise measurements even if the echocardiographic recording is made less than 2 min after exercise cessation. This applies to all assessed parameters and, in particular, to the measurement of transtricuspid gradient, used to derive systolic pulmonary artery pressure values, which rapidly declines after exercise cessation. Because of this limitation, PEE might miss some of the key information regarding the behavior of SMR during exercise.

A more appropriate and physiologic approach in assessing the dynamic character of SMR is, in our view, exercise stress echocardiography (ESE) performed on a dedicated tilting table. It is the only modality that allows continuous echocardiographic evaluation throughout exercise. Unlike DSE, this modality has the advantage of not altering loading conditions in an artificial manner, being much closer to real-life stress on MV apparatus. Unlike PEE, it enables continuous observation of all mechanisms involved in SMR genesis during each step of the exercise: changes in MV geometry during exercise (such as tenting area, coaptation distance and posterior leaflet angle), changes in global and regional LV systolic function (identifying viable or ischemic myocardium), detection of LV dyssynchrony and most importantly, accurate and reproducible quantification of SMR through the measurement of EROA and RV by PISA method or Doppler volumetric method. Additionally, it enables assessment of the upstream consequences of SMR, with estimation of pulmonary artery systolic pressure during each step of the exercise (Fig. 6.2, Panel h).