Cardiology Research and Practice Cardiac output + ﬂuid + ﬂuid Normal ΔCO Increase in preload (a) Right atrial pressure 5 Cardiac output ΔCO Heart failure Increase in preload (b) Right atrial pressure Figure 4: The eﬀect of ﬂuid administration on cardiac output. Fluid administration results in an upward shift in venous return curve. As a result, there is an increase in preload hence cardiac output (ΔCO) (a). Note that the crossing points between the two curves are on the steep part of the cardiac function (Frank-Starling) curve. In heart failure, the Frank-Starling curve is lowered, and the crossing point is at the ﬂat portion of the curve (b). Fluid administration, although it increases the preload, does not result in an increase in CO in the latter case. ΔSV Stroke volume Normal Stroke volume Right atrial pressure ΔSV Changes in ITP (a) Changes in ITP (b) Heart failure Right atrial pressure Figure 5: The eﬀect of intrathoracic pressure on cardiac output. Both spontaneous breathing and mechanical ventilation result in a cyclical change in intrathoracic pressure (ITP). Depending on the mode of ventilation, the change in ITP is accompanied by a cyclical shift in the Frank-Starling (cardiac function) curve which results in a cyclical change in preload. If the crossing point is on the steep part of the curve, shifting of the curve would result in a change in stroke volume (SV) (or cardiac output). This respiratory induced cyclical change in SV is known as SV variation (a). In heart failure, such change in SV may be less apparent because the crossing point is at the ﬂat portion of the curve (b). (PLR) or (b) volume challenge—rapid infusion of a ﬁxed vol- ume (e.g., 500 mL) of ﬂuid within 15–30 min [19]. In res- ponse to acute volume expansion, an increase in SV or its surrogates, such as echocardiographic LVOT or aortic ﬂow VTI (and CO), are expected. In patients whose ventricles are operating at the ﬂat portion of the Frank-Starling curve, the change in stoke volume is less apparent (Figure 4). Studies involving the use of PLR reported that an increase in CO by 12–15% oﬀers high speciﬁcities (>90%) and sen- sitivities (>80%) in discriminating ﬂuid responder from nonresponder [17]. PLR-induced increase in SV or CO dis- plays a good correlation with volume challenge [17, 19]. While SV and CO are reported, their surrogates such as VTILVOT or aortic ﬂow VTI (VTIaortic) are normally used. VTIaortic can be measured either in the apical-5-chamber window or the suprasternal window using continuous wave Doppler. 4.2. Respiratory Variation. During steady respiratory eﬀort, changes in intrathoracic pressure alters the heart-lung inter- action mechanics leading to a regular ﬂuctuation of SV [20]. In mechanically ventilated patients, the LV SV is at its greatest at the end of the inﬂation period. This is due to an increase in pleural pressure and LV preload. During expi- ration, the reduction in LV preload decreases the SV. This respiratory variation in SV (SV variation or SVV) is exag- gerated in ﬂuid responders whose ventricles are operating at the steep part of the Frank-Starling curve (Figure 5). For those (non-responders) whose ventricles are operating at the ﬂat portion of the curve, the SVV is blunted (Figure 5) [19]. SVV is deﬁned as (SVmax− SVmin)SVmean× 100%, where the subscripts max, min, and mean stand for maximum, mini- mum, and average, respectively. In TTE, the percentage var- iation in VTILVOT or VTIaortic is normally used as a surrogates for SVV [21, 22].