Cardiac Cycle (Pressure-Volume Loops, Heart Sounds)

Foundations and mechanisms

The Wiggers diagram integrates left ventricular, left atrial and aortic pressures with ventricular volume, ECG timing and heart sounds. At a heart rate of 75 min^-1, one cycle lasts approximately 0.8 s: systole about 0.3 s and diastole about 0.5 s. This diastolic reserve is clinically important because tachycardia disproportionately shortens filling time and coronary perfusion. Typical left-sided values are: aortic pressure 120/80 mmHg with mean arterial pressure near 90–95 mmHg; left ventricular pressure 0–10 mmHg in diastole and about 120 mmHg in systole; left atrial mean pressure 5–12 mmHg; end-diastolic volume 110–130 ml; end-systolic volume 40–60 ml; stroke volume about 70 ml; and ejection fraction 55–70%.

Integrated phases of the cardiac cycle

Phase	Valve state	Pressure-volume behaviour	Key sounds/events
Late diastole and atrial systole	Mitral open, aortic closed	Passive filling followed by atrial contraction; atrial systole contributes approximately 10–20% of LV filling at rest, more with impaired relaxation.	P wave precedes the atrial a wave; S4 may occur in a stiff ventricle.
Isovolumetric contraction	Mitral closes, aortic closed	LV pressure rises steeply at constant volume; duration about 40–60 ms.	S1 from AV valve closure and ventricular wall acceleration.
Ventricular ejection	Aortic open, mitral closed	Rapid then reduced ejection; LV and aortic pressures rise together, then fall; about two-thirds of stroke volume is ejected early.	Peak aortic velocity normally less than 1.7 m s-1.
Isovolumetric relaxation	Aortic closes, mitral closed	LV pressure falls rapidly at constant ESV; duration about 60–90 ms.	S2 from semilunar valve closure; aortic incisura follows valve closure.
Early filling and diastasis	Mitral open, aortic closed	Rapid filling driven by LA-LV gradient and elastic recoil, then slow filling as pressures equilibrate.	S3 may be physiological in youth but pathological with volume overload or systolic failure.

Atrial and arterial pressure waves

The left atrial pressure trace comprises a, c and v waves with descents. The a wave reflects atrial systole and follows the P wave; it is absent in atrial fibrillation and exaggerated when ventricular compliance is reduced, as in hypertrophy or restrictive physiology. The c wave occurs in early systole due to bulging of the closed mitral valve into the atrium and transmission of carotid/ventricular pulsation. The x descent reflects atrial relaxation and downward displacement of the AV ring during systole. The v wave represents atrial filling against a closed mitral valve, peaking just before mitral opening; giant v waves suggest mitral regurgitation or reduced atrial compliance. The y descent follows mitral opening and early ventricular filling.

Aortic pressure rises once LV pressure exceeds aortic diastolic pressure. During ejection, kinetic energy and Windkessel storage in the elastic aorta maintain forward flow. Aortic valve closure occurs when ventricular pressure falls below aortic pressure, producing brief retrograde flow that snaps the valve shut. The incisura or dicrotic notch is the small upstroke on the descending aortic pressure limb caused by abrupt interruption of reverse flow and elastic recoil of the aortic root; it marks end-systole mechanically and precedes the dicrotic wave.

Pressure-volume loop biophysics

The left ventricular PV loop plots instantaneous LV pressure against volume and is traversed counter-clockwise. Its width is stroke volume and its area is external stroke work, normally approximately 0.8–1.2 J beat^-1 for the LV. The lower boundary is diastolic filling; the right vertical limb is isovolumetric contraction; the upper limb is ejection; and the left vertical limb is isovolumetric relaxation.

The end-systolic pressure-volume relationship is the line joining end-systolic points under different loading conditions. Its slope is end-systolic elastance, Ees or Es, a relatively load-independent index of contractility; typical human LV Ees is about 2–4 mmHg ml^-1, higher with sympathetic stimulation and lower in systolic failure or volatile anaesthesia. The x-axis intercept, V₀, is the theoretical volume at zero pressure. The end-diastolic pressure-volume relationship is curvilinear, reflecting passive chamber stiffness: small volume increments at high EDV cause large pressure increases. LVEDP is normally 5–12 mmHg; values above 16–18 mmHg generally indicate raised filling pressure, although interpretation depends on pleural pressure and ventricular compliance.

Arterial elastance, Ea, is an integrated measure of afterload, approximated by end-systolic pressure divided by stroke volume: Ea ≈ ESP/SV. Normal values are roughly 1.5–2.2 mmHg ml^-1. Ventriculo-arterial coupling is often expressed as Ea/Ees; mechanical efficiency is near optimal when Ea/Ees is about 0.5–1.0, whereas severe systolic failure commonly raises the ratio above 1.0. Clinically, phenylephrine boluses of 50–100 micrograms increase Ea and may reduce stroke volume if contractile reserve is limited; noradrenaline at 0.02–0.5 micrograms kg^-1 min^-1 increases vascular tone with some beta-1 support; glyceryl trinitrate infusions around 0.5–10 micrograms kg^-1 min^-1 reduce preload and may shift the loop leftwards with lower filling pressures.

Valve mechanics

Valves open and close according to instantaneous pressure gradients, but sound generation depends on rapid deceleration of blood and vibration of valve-cardiohaemic structures rather than simple leaflet apposition. The mitral valve opens when LV pressure falls below LA pressure and closes when LV pressure exceeds LA pressure. The aortic valve opens when LV pressure exceeds aortic diastolic pressure and closes when the gradient reverses. Therefore, valve timing is altered by loading and pathology: increased afterload delays aortic opening and prolongs ejection; impaired relaxation delays mitral opening; and regurgitant lesions abolish true isovolumetric phases, distorting the PV loop and Wiggers relationships.

Clinical assessment and investigations

Acoustic physics and timing of heart sounds

Heart sounds are transient vibrations of the cardiohaemic system, not simply the sound of valve cusps striking. They arise from abrupt deceleration of blood, tensing of valve apparatus, ventricular walls and great vessels, and are transmitted through thoracic tissues as low-frequency acoustic energy. Most clinically useful components lie between approximately 20 and 200 Hz; the bell accentuates low-frequency sounds such as S3 and S4, whereas the diaphragm favours higher-frequency sounds and murmurs. Timing against the carotid upstroke, apex beat and ECG is essential: S1 follows the QRS; S2 follows the T wave; S3 is early diastolic; S4 is presystolic.

S1 is produced predominantly by mitral closure, followed by tricuspid closure. The M1-T1 interval is usually about 20-30 ms and is not normally appreciated as a split sound. S1 intensity increases when atrioventricular valves are widely open at the onset of systole, as in short PR interval or mild mitral stenosis with mobile leaflets, and decreases with long PR interval, severe calcific mitral stenosis, impaired LV contractility or mitral regurgitation. S2 consists of A2 followed by P2. A2 is normally louder and widely transmitted; P2 is best heard at the left upper sternal edge and becomes loud in pulmonary hypertension.

Splitting of S2

Pattern	Mechanism	Typical causes and examination clue
Physiological splitting	Inspiration increases systemic venous return, prolonging RV ejection and delaying P2; simultaneously pulmonary venous capacitance transiently reduces LV filling and may slightly advance A2. Normal inspiratory split is approximately 20-50 ms and narrows or disappears in expiration.	Best heard in the pulmonary area in young adults; accentuated by deep inspiration.
Wide splitting	Persistent delay of P2 or early A2 with preserved respiratory variation.	Right bundle branch block, pulmonary stenosis, pulmonary hypertension with prolonged RV ejection, or severe mitral regurgitation causing early A2 from shortened LV ejection.
Reversed or paradoxical splitting	A2 is delayed beyond P2; inspiration delays P2 towards A2, so the split narrows or disappears on inspiration and is heard in expiration.	Left bundle branch block, RV pacing, severe aortic stenosis, hypertrophic obstructive cardiomyopathy. Clinically important because it implies delayed LV systolic emptying or electrical activation.
Fixed splitting	Respiratory variation is lost because RV volume is chronically increased and interatrial shunting buffers phasic venous return changes.	Classically secundum atrial septal defect. Associated findings include ejection systolic flow murmur at the pulmonary area and mid-diastolic tricuspid flow murmur when shunt is large.

S3 and S4: gallop rhythms

S3 occurs in early diastole, typically 120-180 ms after S2, during rapid ventricular filling. It is a low-frequency sound, best heard with the bell at the apex in the left lateral position for LV S3, or at the left lower sternal edge increasing with inspiration for RV S3. Mechanistically, it reflects rapid inflow into a dilated or volume-loaded ventricle with abrupt limitation of longitudinal expansion. It may be physiological in children, young adults, pregnancy and trained athletes, but after approximately 40 years of age it is pathological until proven otherwise. Important causes include systolic heart failure, dilated cardiomyopathy, acute severe mitral regurgitation, aortic regurgitation and high-output states. As a sign of heart failure it is specific but insensitive; reported sensitivities are often only 13-40%, with specificity commonly above 90%, so absence does not exclude elevated filling pressures.

S4 is a presystolic low-frequency sound occurring just before S1, generated by atrial contraction into a non-compliant ventricle. It requires sinus rhythm and disappears in atrial fibrillation. Causes include hypertensive LV hypertrophy, aortic stenosis, hypertrophic cardiomyopathy, myocardial ischaemia, restrictive cardiomyopathy and acute pulmonary hypertension for RV S4. S4 correlates with increased late diastolic chamber stiffness and reliance on atrial kick; in anaesthesia this is clinically relevant because loss of atrial contraction, tachycardia or vasodilatation may markedly reduce preload-dependent stroke volume.

Investigations and pressure-volume loop correlations

Bedside auscultation should be integrated with ECG, chest radiography, biomarkers and, definitively, transthoracic echocardiography. Doppler echocardiography uses the simplified Bernoulli equation, pressure gradient = 4v², and continuity principles to quantify stenotic lesions. Guideline thresholds from contemporary ACC/AHA and ESC/EACTS valve guidance include severe aortic stenosis when peak velocity is ≥4.0 m s^-1, mean gradient ≥40 mmHg or valve area ≤1.0 cm²; severe mitral stenosis when mitral valve area is ≤1.5 cm², with very severe disease ≤1.0 cm². Severe aortic regurgitation is suggested by vena contracta >6 mm, regurgitant volume ≥60 ml beat^-1 or regurgitant fraction ≥50%. Severe primary mitral regurgitation is suggested by effective regurgitant orifice area ≥0.40 cm² or regurgitant volume ≥60 ml beat^-1.

Lesion	PV loop distortion	Clinical acoustic correlate
Aortic stenosis	Markedly increased LV systolic pressure, increased afterload, prolonged ejection, often reduced stroke volume and concentric hypertrophy; isovolumetric phases preserved.	Ejection systolic murmur, slow-rising pulse, soft or absent A2; paradoxical S2 splitting in severe disease.
Aortic regurgitation	No true isovolumetric relaxation or contraction because the LV communicates with the aorta throughout diastole; increased EDV and stroke volume, low aortic diastolic pressure, widened loop.	Early diastolic decrescendo murmur, bounding pulse, possible S3; Austin Flint rumble in severe AR.
Mitral stenosis	Reduced LV filling, low EDV and stroke volume; elevated LA pressure is not displayed on the LV loop but drives pulmonary venous hypertension.	Loud S1 if mobile valve, opening snap, low-pitched mid-diastolic rumble; shorter A2-opening snap interval implies higher LA pressure.
Mitral regurgitation	Loss of true isovolumetric contraction and relaxation; LV ejects into both aorta and low-pressure LA, increasing total stroke volume but reducing forward stroke volume; EDV rises and LA V waves enlarge.	Pansystolic murmur radiating to axilla, soft S1, S3 in significant volume overload.

Management, pharmacology and procedures

Pharmacological and ventilatory interventions are best understood by separating effects on preload (EDV; rightward/leftward movement along the EDPVR), afterload (effective arterial elastance, Ea ≈ ESP/SV), and contractility (slope of ESPVR, Ees). Myocardial oxygen demand broadly tracks pressure-volume area; therefore a drug may improve arterial pressure while worsening ventricular-arterial coupling and energetics.

Pharmacological manipulation of the pressure-volume loop

Intervention	Typical anaesthetic dose	Dominant mechanism	PV-loop signature	Examination cautions
Phenylephrine	50-100 μg IV bolus; infusion 0.1-1 μg/kg/min; onset <1 min, duration 5-10 min	Pure α1 agonism: arteriolar and venous constriction; increases SVR and mean systemic filling pressure	Ea increases: steeper arterial elastance line, higher ESP, increased ESV, reduced SV if contractility unchanged. EDV may rise slightly from venoconstriction and baroreflex bradycardia	Useful for vasodilatory hypotension with adequate CO. May reduce CO in LV dysfunction, severe aortic stenosis, or bradycardia. In septic shock, Surviving Sepsis Campaign favours noradrenaline first-line; phenylephrine is reserved for selected tachyarrhythmia/high-output states
Dobutamine	2.5-20 μg/kg/min IV; plasma half-life ≈2 min	β1 inotropy and chronotropy with β2 vasodilatation at usual doses	ESPVR shifts up/left; ESV falls; SV and EF rise. Ea often falls modestly, so loop becomes wider and may occur at lower ESP	Increases myocardial oxygen consumption and arrhythmias; may worsen hypotension if vasodilatory reserve predominates. Often combined with vasopressor in shock
Milrinone	Loading 25-50 μg/kg over 10 min often omitted perioperatively; infusion 0.25-0.75 μg/kg/min; half-life 2-3 h, renal clearance	PDE-3 inhibition: ↑cAMP independent of β receptors; inotropy, lusitropy, systemic and pulmonary vasodilatation	ESPVR up/left and EDPVR functionally more compliant via lusitropy; Ea and PVR decrease. SV increases despite lower pressure; RV afterload reduction improves LV filling through less septal shift	Hypotension common; reduce dose in renal impairment. Particularly useful in pulmonary hypertension/RV failure or β-blocked low-output states
β-blockers	Esmolol 0.5-1 mg/kg bolus then 50-300 μg/kg/min; half-life ≈9 min. Metoprolol 1-5 mg IV aliquots	Negative chronotropy and inotropy; prolonged diastole; reduced renin release	ESPVR slope decreases: lower ESP for a given volume, higher ESV, smaller SV. EDV may increase if filling time improves; pressure-volume area and oxygen demand fall	Beneficial for rate-related ischaemia and dynamic LVOT obstruction; hazardous in decompensated systolic failure, high-grade AV block, severe bronchospasm. POISE highlighted harm from indiscriminate perioperative high-dose β-blockade
Glyceryl trinitrate	5-200 μg/min IV titrated; sublingual 400 μg; half-life 1-4 min	NO-mediated venodilatation at low dose; arterial dilatation at higher dose; coronary vasodilatation	Reduces stressed volume and venous return: EDV falls and loop shifts left/down. SV may fall markedly when preload dependent; wall stress and LVEDP decrease	Useful in pulmonary oedema and myocardial ischaemia with hypertension. Avoid or use extreme caution in RV infarction, severe aortic stenosis, hypovolaemia, and within 24-48 h of PDE-5 inhibitors

Induction of anaesthesia and positive pressure ventilation

Induction commonly narrows the PV loop by simultaneously reducing preload, SVR and contractility. Propofol 1-2.5 mg/kg causes venodilatation, arterial vasodilatation and sympatholysis; dose requirements fall substantially in elderly, shocked or hypovolaemic patients. Volatile agents reduce SVR and depress contractility in a dose-dependent manner. Etomidate 0.2-0.3 mg/kg is haemodynamically stable but inhibits 11β-hydroxylase; ketamine 0.5-2 mg/kg preserves pressure via sympathetic activation but is directly myocardial depressant in catecholamine-depleted states.

Venous return is governed by VR = (Pmsf − RAP)/RVR. Positive pressure ventilation increases pleural pressure and right atrial pressure, thereby reducing the gradient for venous return; the right ventricular PV loop becomes smaller after one to two beats, followed by reduced LV preload after pulmonary transit. PEEP, typically 5 cmH2O but sometimes 10-15 cmH2O in recruitment strategies, further increases intrathoracic pressure and reduces transmural LV afterload, which may benefit LV failure. However, high lung volumes increase pulmonary vascular resistance by compressing alveolar vessels, increasing RV afterload, RV ESV and end-diastolic pressure.

The clinically important consequence is ventricular interdependence: RV dilatation within a non-compliant pericardium shifts the interventricular septum leftwards, reducing LV compliance and EDV. Thus in RV failure or pulmonary hypertension, fluid loading may enlarge the right-sided loop while paradoxically shrinking the LV loop and reducing systemic output. Auto-PEEP produces the same physiology but is often missed; disconnecting the circuit transiently may be diagnostic in extremis.

Dynamic assessment at the bedside

Fluid responsiveness indices are physiological stress tests of preload reserve. Pulse pressure variation >13% or stroke volume variation >10-15% predicts preload responsiveness in fully mechanically ventilated patients with sinus rhythm, tidal volume about 8 ml/kg, closed chest and no major RV failure. They are unreliable with spontaneous breathing, arrhythmias, low tidal volume ventilation, open abdomen/chest, severe right heart dysfunction or high respiratory rate-to-compliance interactions. For the Primary FRCA, always state that the desired endpoint is not a large EDV but an improved stroke volume at acceptable filling pressure, afterload and myocardial oxygen cost.

Exam controversies and advanced synthesis

Myocardial oxygen demand and coronary perfusion dynamics

For FRCA purposes, myocardial oxygen balance is best conceptualised as a competition between pressure-time work, wall stress and heart rate versus predominantly diastolic coronary perfusion. Coronary blood flow is approximately 225–250 mL/min at rest, 4–5% of cardiac output, with high oxygen extraction of 70–80%; therefore increased oxygen demand is met mainly by flow augmentation rather than further extraction. Normal myocardial oxygen consumption is approximately 8–10 mL O₂/min/100 g myocardium.

Left coronary flow occurs mainly in diastole because systolic intramyocardial pressure compresses subendocardial vessels. A pragmatic coronary perfusion pressure is aortic diastolic pressure − LVEDP; for the right ventricle it is closer to aortic pressure − RAP/RVEDP, and may occur during both systole and diastole when RV pressure is low. The Buckberg subendocardial viability ratio, DPTI:SPTI, compares diastolic pressure-time index with systolic pressure-time index; values below approximately 0.7–0.8 imply subendocardial ischaemic risk. Tachycardia is uniquely harmful because it simultaneously increases oxygen demand and shortens diastole.

Variable	Effect on MVO2	Exam implication
Heart rate	Major determinant; reduces diastolic perfusion time	Target often 60–80 min−1 in severe CAD/AS if tolerated
Afterload and systolic pressure	Increase pressure-time work and wall stress	Treat hypertension, but avoid low diastolic pressure
Preload/LVEDP	Increases radius and reduces CPP gradient	Congestion may worsen ischaemia despite higher filling pressure
Contractility	Increases activation energy and PVA	Inotropes improve output but may provoke ischaemia
Anaemia/hypoxaemia	Reduce oxygen delivery	Maintain SaO2, Hb and perfusion pressure; thresholds individualised

Stroke work, pressure-volume area and Laplace synthesis

External stroke work is the area enclosed by the pressure-volume loop:

SW = ∮ P dV, approximated clinically by SV × (MAP − LVEDP). Since 1 mmHg·mL = 1.333 × 10⁻⁴ J, a stroke volume of 70 mL ejected against a mean effective pressure of 100 mmHg corresponds to about 0.93 J per beat, or approximately 56 J/min at 60 min⁻¹.

However, stroke work underestimates total myocardial energy expenditure. Suga’s pressure-volume area concept states that PVA = external work + potential energy, where potential energy is the triangular area bounded by the end-systolic pressure-volume relationship, end-diastolic pressure-volume relationship and end-systolic point. PVA correlates linearly with myocardial oxygen consumption per beat; the intercept represents basal metabolism and excitation-contraction coupling. Thus, an isovolumic high-pressure beat may perform no external stroke work yet consume substantial oxygen.

The Law of Laplace links PVA to myocardial fibre stress: wall stress σ = P × r / 2h for a spherical approximation, where P is transmural pressure, r cavity radius and h wall thickness. Pressure overload increases P; dilatation increases r; hypertrophy increases h and is initially compensatory. This is why a dilated failing ventricle may have high oxygen demand despite poor mechanical output, and why reducing afterload or ventricular radius can improve energetic efficiency.

The paradox of anaesthetic-induced diastolic dysfunction

A common viva controversy is that anaesthesia often reduces MVO₂ by lowering sympathetic tone, afterload and contractility, yet may unmask or worsen diastolic dysfunction. Relaxation is an active ATP-dependent process requiring cytosolic calcium removal via SERCA and sarcolemmal exchange. Volatile agents, propofol and hypothermia may impair lusitropy, while positive-pressure ventilation reduces venous return and alters ventricular interaction. The result may be a lower-pressure, lower-demand circulation that is nevertheless preload-sensitive and prone to pulmonary congestion or hypotension.

Relevant perioperative doses include propofol induction 1–2 mg/kg and infusion 50–150 microgram/kg/min, sevoflurane around 1 MAC at 2.0% end-tidal in a 40-year-old, remifentanil 0.05–0.2 microgram/kg/min with context-sensitive half-time 3–5 min, phenylephrine 50–100 microgram boluses, noradrenaline 0.02–0.2 microgram/kg/min and esmolol 0.5 mg/kg bolus followed by 50–200 microgram/kg/min, half-life about 9 min. Echocardiographic diastolic dysfunction criteria from ASE/EACVI include septal e′ less than 7 cm/s, lateral e′ less than 10 cm/s, average E/e′ greater than 14, LA volume index greater than 34 mL/m² and TR velocity greater than 2.8 m/s.

West zones under mechanical ventilation and RV-LV coupling

Classical West zones are not static under anaesthesia. Positive-pressure ventilation and PEEP increase alveolar pressure, converting dependent or overdistended units towards Zone 1 or 2 behaviour: Zone 1, P_A > P_a > P_v; Zone 2, P_a > P_A > P_v; Zone 3, P_a > P_v > P_A. At low lung volumes, extra-alveolar vessel narrowing produces Zone 4 physiology. Pulmonary vascular resistance is U-shaped against lung volume: it rises with atelectasis and hypoxic pulmonary vasoconstriction, and also with overdistension. ARDSNet-style protective ventilation uses tidal volume about 6 mL/kg predicted body weight, plateau pressure less than 30 cmH₂O; driving pressure below about 15 cmH₂O is supported by Amato’s 2015 NEJM analysis as prognostically important.

The feedback loop is direct: excessive PEEP, hypercapnia above 45 mmHg, acidosis below pH 7.25 or hypoxia increases PVR; RV afterload rises; RV dilatation shifts the septum leftward; LV compliance and preload fall; systemic pressure falls; right coronary perfusion, approximated by aortic pressure minus RAP, deteriorates. RV ischaemia then further reduces RV output, worsening LV filling. Thus cardiac cycle interpretation in ventilated patients must integrate PV loops, coronary perfusion pressure and pulmonary zone physiology rather than treating them as separate systems.