Pressure-Volume Loop #1: Preload and Compliance

1. Introduction

The ventricular pressure–volume (PV) loop depicts the relationship between ventricular cavity pressure and volume throughout a single cardiac cycle. It integrates diastolic filling, isovolumetric contraction, systolic ejection, and isovolumetric relaxation into one mechanical representation. Unlike ejection fraction or an isolated pressure measurement, the loop separates the contributions of ventricular loading, intrinsic systolic performance, and diastolic properties [1,2].

This chapter focuses on the three concepts emphasized in the accompanying educational material: the baseline PV loop, increased preload, and decreased ventricular compliance. These perturbations can produce very different hemodynamic consequences even when measured filling pressure increases in both situations. The conventional diagram describes the left ventricle; the underlying principles also apply to the right ventricle, although chamber geometry, loading conditions, and pressure–volume relationships differ.

2. The Baseline Pressure–Volume Loop

2.1. Axes, direction, and phases

Ventricular volume is displayed on the horizontal axis and intracavitary pressure on the vertical axis. A normal left ventricular loop proceeds counterclockwise through four phases:

1. Diastolic filling: The mitral valve opens when ventricular pressure falls below left atrial pressure. Ventricular volume increases along the lower portion of the loop, initially through early filling and subsequently through diastasis and atrial contraction. Filling ends at end-diastolic volume (EDV).
2. Isovolumetric contraction: Mitral valve closure is followed by increasing ventricular pressure while both inlet and outlet valves remain closed. Volume remains approximately constant at EDV.
3. Systolic ejection: Once ventricular pressure exceeds aortic pressure, the aortic valve opens. Ventricular volume decreases as blood is ejected, reaching end-systolic volume (ESV).
4. Isovolumetric relaxation: After aortic valve closure, ventricular pressure declines while volume remains approximately constant at ESV. The next filling phase begins when the mitral valve opens [1,2].

The horizontal width is stroke volume (SV = EDV − ESV); cardiac output is SV multiplied by heart rate. The area enclosed by the loop represents external ventricular stroke work, commonly expressed as pressure–volume work. A wider loop therefore indicates greater stroke volume, but it does not, by itself, establish greater contractility or more efficient myocardial performance.

These four phases are idealized. Significant valvular regurgitation, intracardiac shunting, continuous-flow mechanical support, and some congenital morphologies can alter loop contour or abolish a truly isovolumetric interval.

2.2. End-systolic pressure–volume relationship

The end-systolic pressure–volume relationship (ESPVR) describes the relationship between pressure and volume at end systole across beats studied under different loading conditions. Within the conventional linear approximation, its slope is end-systolic elastance (Ees). A steeper relationship generally signifies increased chamber systolic elastance, while a flatter relationship is compatible with depressed systolic performance [1,3].

The ESPVR is relatively insensitive to loading compared with single-beat ejection fraction, but it is not absolutely load-independent. Its slope and intercept are influenced by chamber geometry, myocardial properties, neurohumoral state, and the range of loading conditions examined. A complete ESPVR is ordinarily derived from multiple beats rather than by drawing a line through one end-systolic point.

2.3. Arterial load and ventricular–arterial interaction

The downward-sloping line labeled Ea represents effective arterial elastance, often approximated as Ea = end-systolic pressure / stroke volume. It is an integrated description of arterial loading that includes resistance, compliance, impedance, and heart rate rather than a direct measurement of systemic vascular resistance.

Together, Ea and ESPVR help determine the operating end-systolic point. The ratio Ea/Ees describes ventricular–arterial coupling. This framework clarifies why the same preload can produce different stroke volumes when contractility or arterial load changes [4]. In this chapter, these properties are assumed to remain broadly stable while preload or diastolic compliance is varied.

3. Increased Preload: A Wider PV Loop

3.1. Preload is a loading state, not a pressure alone

Preload refers to myocardial loading immediately before contraction and is most fundamentally associated with end-diastolic fiber length or wall stress. EDV is a practical surrogate in many settings, but it is not identical to myocardial stretch. End-diastolic pressure is even less interchangeable with preload because the pressure corresponding to a given volume depends on ventricular stiffness and surrounding constraints.

An increase in effective venous return can increase ventricular filling and EDV. When contractility, arterial loading, and diastolic properties are unchanged, the right-hand boundary of the PV loop moves toward a larger volume. The end-systolic operating point may also change modestly, but the increase in EDV usually produces a wider loop and greater stroke volume.

3.2. The Frank–Starling mechanism

The Frank–Starling mechanism links increased end-diastolic myocardial length to augmented force development and ejection during the subsequent contraction. Length-dependent activation increases myofilament responsiveness to calcium and supports adaptation of stroke volume to venous return [5].

In the schematic illustration, the original loop is shown as a dotted contour and the increased-preload loop as a solid, wider contour. The principal change is increased EDV, not a shift in the intrinsic ESPVR. Accordingly, a larger stroke volume after fluid administration should not automatically be interpreted as improved myocardial contractility.

Preload responsiveness also has limits. On a relatively flat portion of the functional Frank–Starling relationship, additional filling produces little increase in forward output. Excessive loading may instead increase atrial and venous pressures, pulmonary congestion, wall stress, and myocardial oxygen demand. Changes in ventricular interaction, afterload, and valvular regurgitation may further modify the observed response.

3.3. Pressure response along the same EDPVR

Increasing EDV without changing intrinsic chamber compliance moves the end-diastolic operating point upward and rightward along the existing end-diastolic pressure–volume relationship (EDPVR). End-diastolic pressure will usually rise as the ventricle fills, particularly at larger volumes where the curve becomes steep.

This is an essential distinction: movement along an unchanged EDPVR is not the same as an upward shift of the EDPVR. A high filling pressure after a large volume load can occur in a ventricle whose intrinsic compliance has not changed. Conversely, a substantial increase in EDV can sometimes occur with only a small pressure rise in a highly compliant chamber.

4. Decreased Compliance: Higher Pressure at a Given Volume

4.1. Compliance and passive stiffness

Ventricular compliance is the change in volume produced by a given change in filling pressure (dV/dP). Its inverse, chamber stiffness (dP/dV), describes how rapidly pressure rises as volume increases. Because ventricular filling is nonlinear, neither compliance nor stiffness is a single fixed value across the entire diastolic range [6].

The EDPVR describes the passive chamber pressure–volume relationship after adequate relaxation. Its curvilinear shape reflects myocardial tissue properties, chamber geometry, and mechanical interactions with surrounding structures. A less compliant ventricle displays an EDPVR displaced upward and/or leftward, so a given ventricular volume is associated with greater filling pressure [1,6].

The illustrated decreased-compliance panel shows precisely this change: the solid EDPVR is higher than the dashed baseline relationship. At a comparable EDV, filling pressure is elevated. If upstream filling pressure cannot increase sufficiently to sustain volume, EDV may fall and stroke volume may decline, even when intrinsic systolic contractility is preserved.

4.2. Why the ventricle becomes stiff

Reduced chamber compliance may result from ventricular hypertrophy, fibrosis, infiltrative disease, ischemic remodeling, or abnormalities in myocardial extracellular matrix and titin-related passive tension. The relationship can also change with chamber size and ventricular geometry.

An increase in measured diastolic pressure, however, does not always indicate a primary myocardial stiffness abnormality. Pericardial restraint, elevated intrathoracic pressure, right ventricular dilation, and interventricular septal interaction can increase the external pressure surrounding the ventricle or constrain cavity expansion. Measured intracavitary pressure should therefore be distinguished conceptually from transmural distending pressure.

Active relaxation and passive stiffness are also separate properties. Delayed relaxation can elevate early diastolic pressure or impair filling, especially during tachycardia, without necessarily implying the same shift in the fully relaxed passive EDPVR. Clinical investigation of diastolic dysfunction has demonstrated that relaxation abnormalities and increased passive stiffness can coexist [7].

4.3. Preserved ejection fraction does not exclude impaired filling

A stiff ventricle may maintain near-normal fractional ejection while operating at a smaller EDV and higher diastolic pressure. Because ejection fraction is SV divided by EDV, a preserved percentage does not guarantee adequate absolute stroke volume or cardiac output.

The energetic and clinical consequences may be considerable. Greater atrial pressure is required to achieve the same EDV, increasing pulmonary venous congestion or systemic venous congestion depending on the affected ventricle. Atrial contraction may become important for late filling, and loss of atrioventricular synchrony or tachycardia may disproportionately reduce forward output.

Research-derived methods can estimate an EDPVR from a single beat, but such estimates require mathematical assumptions and are generally less reliable for an individual patient than carefully obtained multibeat measurements [8].

5. Increased Preload Versus Decreased Compliance

The two PV-loop changes may both be accompanied by a higher ventricular end-diastolic pressure, yet they represent different mechanisms.

A filling pressure is not sufficient to distinguish these states. Two patients with the same ventricular end-diastolic pressure can have markedly different EDVs, passive stiffness, and subsequent responses to a fluid bolus. Similarly, a rising central venous pressure or left atrial pressure cannot establish that ventricular preload has improved.

Interpretation requires consideration of chamber size, ventricular function, diastolic filling, valve lesions, heart rate, rhythm, intrathoracic pressure, and whether flow increases after an intervention.

6. Clinical Applications

6.1. Fluid administration and postoperative circulation

In a preload-responsive ventricle, carefully administered volume can increase EDV and stroke volume. A stiff ventricle, however, may show a large increase in filling pressure with little improvement in forward flow. Fluid responsiveness and fluid tolerance are therefore distinct questions.

After cardiac surgery, ventricular edema, ischemia–reperfusion effects, altered geometry, residual outflow obstruction, and pericardial constraint may affect diastolic filling. When cardiac output remains low despite elevated filling pressures, further volume loading may worsen congestion without meaningfully increasing stroke volume. This mechanism is an interpretation of the PV framework, not a treatment threshold validated by the diagram alone [2,9].

Dynamic reassessment should integrate cardiac output or stroke-volume trends, echocardiography, perfusion indices, pressure waveforms, and response to interventions rather than relying on filling pressure in isolation.

6.2. Congenital heart disease and right ventricular physiology

PV analysis is particularly instructive in congenital lesions because loading conditions and ventricular geometry can change dramatically after intervention. Chronic left-to-right shunting produces ventricular volume loading appropriate to the lesion and shunt pathway. Elimination of a significant shunt can reduce EDV, with changes in apparent systolic indices that need not represent a primary decline in myocardial contractility.

In a hypertrophied or restrictive right ventricle, increased filling pressure may reflect reduced compliance rather than adequate or excessive effective preload. Interventricular dependence becomes especially relevant when both ventricles share a constrained pericardial space. In single-ventricle and Fontan physiology, ventricular filling is additionally limited by upstream pulmonary vascular and pathway resistance; therefore, higher systemic venous pressure does not necessarily translate into greater EDV [10].

These are physiologic applications, not claims that a standard left ventricular schematic accurately reproduces every congenital or Fontan pressure–volume contour.

6.3. Practical assessment and limitations

Direct PV analysis usually requires simultaneous, high-fidelity pressure and ventricular volume measurements, commonly obtained invasively with conductance-based systems. Accurate interpretation depends on pressure calibration, volume calibration, catheter position, and consistent loading conditions. Three-dimensional echocardiography combined with pressure measurements has been investigated as a less invasive approach in pediatric congenital heart disease, but feasibility does not establish routine bedside validity [2,11].

The classical ESPVR and EDPVR are constructed from changing loading conditions across several beats. Single-beat techniques make the framework more accessible but depend on model-derived assumptions, and the predicted relationships should not be treated as direct independent measurements [8,12]. Furthermore, regurgitation, shunts, and continuous-flow support can change the relationship between loop width, forward systemic flow, and effective stroke work.

7. Key Clinical Principles

• PV-loop width represents stroke volume: SV = EDV − ESV; a wider loop does not necessarily mean greater contractility.
• Increased preload generally increases EDV: a preload-responsive ventricle produces more stroke volume through the Frank–Starling mechanism.
• An unchanged EDPVR can still have higher filling pressure: the operating point moves upward along the curve as EDV increases.
• Reduced compliance shifts the EDPVR upward/leftward: filling pressure is higher for the same ventricular volume.
• High filling pressure is not synonymous with high effective preload: assess chamber volume, external pressure, ventricular interaction, and forward flow.
• Preserved ejection fraction does not exclude important diastolic dysfunction: absolute stroke volume and filling reserve may remain limited.
• Fluid responsiveness differs from fluid tolerance: a pressure rise without a meaningful increase in forward flow should prompt reassessment of the underlying physiology.

References

[1] Burkhoff D, Mirsky I, Suga H. Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers. Am J Physiol Heart Circ Physiol. 2005;289:H501–H512. DOI: 10.1152/ajpheart.00138.2005. PMID: 16014610.

[2] Bastos MB, Burkhoff D, Malý J, et al. Invasive left ventricle pressure–volume analysis: overview and practical clinical implications. Eur Heart J. 2020;41:1286–1297. DOI: 10.1093/eurheartj/ehz552. PMID: 31435675.

[3] Suga H, Sagawa K. Instantaneous pressure-volume relationships and their ratio in the excised, supported canine left ventricle. Circ Res. 1974;35:117–126. DOI: 10.1161/01.RES.35.1.117. PMID: 4841253.

[4] Sunagawa K, Maughan WL, Sagawa K. Optimal arterial resistance for the maximal stroke work studied in isolated canine left ventricle. Circ Res. 1985;56:586–595. DOI: 10.1161/01.RES.56.4.586. PMID: 3978773.

[5] Moss RL, Fitzsimons DP. Frank-Starling relationship: long on importance, short on mechanism. Circ Res. 2002;90:11–13. DOI: 10.1161/RES.90.1.11. PMID: 11786511.

[6] Grossman W, McLaurin LP. Diastolic properties of the left ventricle. Ann Intern Med. 1976;84:316–326. DOI: 10.7326/0003-4819-84-3-316. PMID: 769626.

[7] Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure—abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004;350:1953–1959. DOI: 10.1056/NEJMoa032566. PMID: 15128895.

[8] Klotz S, Hay I, Dickstein ML, et al. Single-beat estimation of end-diastolic pressure-volume relationship: a novel method with potential for noninvasive application. Am J Physiol Heart Circ Physiol. 2006;291:H403–H412. DOI: 10.1152/ajpheart.01240.2005. PMID: 16428349.

[9] Protti I, van den Enden A, Van Mieghem NM, Meuwese CL, Meani P. Looking Back, Going Forward: Understanding Cardiac Pathophysiology from Pressure–Volume Loops. Biology (Basel). 2024;13:55. DOI: 10.3390/biology13010055. PMID: 38275731.

[10] Hiremath GM, Batlivala S, Callahan R, et al. Clinical Applications of Pressure-Volume Assessment in Congenital Heart Disease. J Soc Cardiovasc Angiogr Interv. 2023;2:100599. DOI: 10.1016/j.jscai.2023.100599. PMID: 39130717.

[11] Herberg U, Gatzweiler E, Breuer T, Breuer J. Ventricular pressure-volume loops obtained by 3D real-time echocardiography and mini pressure wire—a feasibility study. Clin Res Cardiol. 2013;102:427–438. DOI: 10.1007/s00392-013-0548-3. PMID: 23397593.

[12] Senzaki H, Chen CH, Kass DA. Single-beat estimation of end-systolic pressure-volume relation in humans: a new method with the potential for noninvasive application. Circulation. 1996;94:2497–2506. DOI: 10.1161/01.CIR.94.10.2497. PMID: 8921794.