**2. Contractile reserve in DCM**

### **2.1. Myocardial contractile reserve**

Myocardial contractile reserve measured by stress testing has been defined as a difference LV function at rest and under load. To date, the assessment of myocardial contractile reserve limitedly applied to evaluate the myocardial viability exclusively in patients with LV dys‐ function and coronary artery disease. Nowadays, glowing evidences suggest the clinical importance to evaluating the contractile reserve in non-ischemic DCM [9, 10]. In particular to the case of DCM, the assessment of myocardial contractile reserve is mainly focused to evaluate the presence of residual LV contractile reserve.

diography, cardiac pool scintigraphy, and cardiac catheterization. Exercise and inotropic stress have been used as stress protocols for the assessment of contractile reserve. Both stresses provoke a generalized increase of regional wall motion with an increment of ejection fraction [27]. Although regional LV wall dysfunction is commonly caused by coronary artery ischemia, regional wall motion abnormality is sometimes shown in non-ischemic cardiomyopathy [28].

Contractile Reserve in Dilated Cardiomyopathy

http://dx.doi.org/10.5772/55413

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The selection of evaluation method and stress modality mainly depends on the patient's

Exercise stress is a very useful and the best physiological stressor. Therefore, exercise testing should be performed in patients who are physically allowed [27]. Images can be obtained by use of pre- and within one minute of post- treadmill, upright or supine cycle exercise. However, the weakness of stress echocardiography is that it depends on image quality and its use by the

Pharmacologic stress testing is preferred for patients unable to exercise. Use of low dose dobutamine seems to be the best stress method for the assessment of myocardial contractile reserve, unless there is a contraindication [29]. The protocol of dobutamine infusions vary from investigators, but the patient usually undergo the stress testing using standardised incremental infusions of 5, 10, and 20 µg/kg/min [30]. The safety dose has been documented as high as 40

In stress echocardiography, global LV function at rest is assessed by calculation of ejection fraction or wall motion score index on the resting images. After collecting stress images, both data are compared for the development of global function. As for the evaluation of regional function, regional wall motion scoring is generally used. Generally, the critical level to define the presence of contractile reserve is defined as an increase of more than 5% in the global LV

Some studies have evaluated the adrenergic contractile reserve by measurement of increase in the maximal first derivative of LV pressure (LV dP/dtmax) using a cardiac catheter in patients

Our protocol for the evaluation of myocardial contractile reserve consists of low-dose dobut‐ amine infusion and cardiac catheterization (Figure 1). Although a lot of investigations which reported dobutamine stress testing were measured by echocardiography, we more accurately

evaluate LV response using catheterization with a high-fidelity micromanometer.

exercise capacity, the purpose of the examination, and medical contraindications.

occasional user may be attached with loss of accuracy.

µg/kg/min and serious complications occurs in about 0.3 %.

**3.1. Exercise stress**

**3.2. Dobutamine stress**

**3.3. Interpretension**

ejection fraction [31].

with non-ischemic LV dysfunction [15, 32].

**3.4. Stress testing protocol in our studies**

#### **2.2. Pathophysiological implications**

Determinant factors of myocardial contractile reserve include the Frank-Starling mechanism, the force-frequency effect, and adrenergic stimulation [11, 12]. In DCM patients, myocardial contractile reserve to adrenergic stimulation is impaired [9].

Myocardial contractile reserve by stress testing provide important prognostic information in DCM [13]. Previous studies reported that patients exhibiting load-induced enhancement of systolic LV function had better clinical outcomes [10, 14 - 17] and LV contractile reserve is a useful marker to predict future LV functional improvement in the treatment of beta blocker or after cardiac resynchrnonization therapy [18 - 21].

In addition, myocardial contractile reserve is associated with other prognostic biomarkers and molecule expressions in cardiomyocyte. Firstly, LV inotropic reserve is associated with exercise capacity [14]. The contractile reserve correlates with peak oxygen consumption (peak VO2) in cardiopulmonary exercise testing [22, 23]. Moreover, patients with greater increase in myocardial contractile reserve achieved a greater peak VO2 [23]. Secondly, impaired LV contractile reserve was reported to be associated with cardiac sympathetic dysfunction measured by myocardial iodine-123-metaiodobenzylgluanidine (123I-MIBG) scintigraphy [24]. Finally, we reported that reduced adrenergic myocardial contractile reserve related to myocardial expression of contractile regulatory protein mRNAs, such as beta1-adrenergic receptor, sarcoplasmic reticulum Ca2+-adrenergic triphosphatase, and phospholamban [25].

Moreover, the assessment of LV response using a stress testing may also help in the screening or monitoring the presence of latent myocardial dysfunction in patients with the initial phase of cardiomyopathy overt normal resting echocardiographic parameters who had exposure to cardiotoxic agents [26].
