**3. How to evaluate contractile reserve?**

Myocardial contractile reserve is usually defined as a difference between LV function at rest and under load. LV function has been evaluated by a variety of modalities, such as echocar‐ 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].

The selection of evaluation method and stress modality mainly depends on the patient's exercise capacity, the purpose of the examination, and medical contraindications.

#### **3.1. Exercise stress**

**2. Contractile reserve in DCM**

48 Cardiomyopathies

**2.1. Myocardial contractile reserve**

the presence of residual LV contractile reserve.

contractile reserve to adrenergic stimulation is impaired [9].

or after cardiac resynchrnonization therapy [18 - 21].

**3. How to evaluate contractile reserve?**

**2.2. Pathophysiological implications**

cardiotoxic agents [26].

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

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

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

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

Myocardial contractile reserve is usually defined as a difference between LV function at rest and under load. LV function has been evaluated by a variety of modalities, such as echocar‐ 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 occasional user may be attached with loss of accuracy.

#### **3.2. Dobutamine stress**

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

### **3.3. Interpretension**

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 ejection fraction [31].

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

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

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.

Initially, routine diagnostic left and right heart catheterization are performed. A 6-F fluid-filled pigtail catheter with a high-fidelity micromanometer (CA-61000-PLB Pressure-tip Catheter, CD Leycom, Zoetermeer, The Netherlands) is placed in the LV cavity for measurement of LV pressure. We evaluate LV dP/dtmax as an index of LV contractility [33]. After collection of baseline hemodynamic data, dobutamine is infused intravenously at incremental doses of 5, 10, and 15 µg/kg/min and hemodynamic measurements are made at the end of each 5-minute infusion period. In addition, we calculate ΔLV dP/dtmax as an index of myocardial contractile reserve [25]. ΔLV dP/dtmax is defined as the percentage increase in LV dP/dtmax induced by dobutamine, and this index is defined on the basis of the formula.

Recently, we reported the association between myocardial contractile reserve and exercise capacity in 38 idiopathic DCM patients [23]. Peak VO2 was significantly correlated with ΔLV dP/dtmax, but not with LV dP/dtmax at baseline. In addition, the correlation became more pronounced as the dose of dobutamine was increased (Figure 2). Multivariate regression analysis revealed that ΔLV dP/dtmax was independently correlated with peak VO2 (p=0.011). There was no correlation between minute ventilation/carbon dioxide production (VE/VCO2)

Contractile Reserve in Dilated Cardiomyopathy

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

51

ΔLV dP/dtmax was significantly correlated with peak VO2, and the correlation became more pronounced as the dose of dobutamine was increased. In contrast, no significant inverse correlation between ΔLV dP/dtmax and VE/VCO2 slope was apparent, even at the maximum dose of dobutamine. ΔLV dP/dtmax is the percentage increase in LV dP/dtmax in‐

**Figure 2.** Correlation between myocardial contractile reserve and peak VO2, VE/VCO2 slope.

slope and ΔLV dP/dtmax.

duced by dobutamine. [23]

ΔLV dP/dtmax(x) = LV dP/dtmax(x) - LV dP/dtmax(baseline) / LV dP/dtmax(baseline)

where x = the dose of dobutamine (µg/kg/min)

**Figure 1.** Protocol for evaluating myocardial contractile reserve in DCM
