9.1 Cardiac Cycle, Hemodynamics & Murmurs

Key Takeaways

  • Systole is isovolumetric contraction then ejection; diastole is isovolumetric relaxation then filling; S1 is AV valve closure and S2 is semilunar valve closure, split by delayed pulmonic closure in inspiration.
  • Stroke volume rises with increased preload (Frank–Starling) and contractility and falls with increased afterload; pressure–volume loops display these determinants as changes in EDV, ESV, and loop width/height.
  • AS radiates to carotids; AR is a diastolic decrescendo at the left sternal border; MS is an opening snap plus diastolic rumble; MR and VSD are holosystolic; MVP has a mid-systolic click.
  • HOCM and MVP murmurs intensify with decreased preload (Valsalva, standing); most other left-sided murmurs soften. Handgrip increases afterload and intensifies MR/AR/VSD while softening HOCM and AS.
  • PDA is a continuous machinery murmur; wide fixed S2 splitting points to ASD physiology rather than a classic harsh VSD holosystolic pattern alone.
Last updated: August 2026

9.1 Cardiac Cycle, Hemodynamics & Murmurs

Quick Answer: Map every murmur and heart sound to a pressure gradient across a valve or defect during a defined phase of the cycle. Preload sets end-diastolic stretch (Frank–Starling), afterload opposes ejection, and contractility shifts the end-systolic pressure–volume relationship. Maneuvers that shrink LV volume intensify HOCM and MVP; handgrip (↑ afterload) intensifies regurgitant and VSD murmurs and softens HOCM.

Cardiovascular physiology on the CBSE is tested as integrated mechanism, not as isolated lists. Items pair a physical finding with a pressure gradient, a volume change, or a pharmacologic effect. Build a mental model of one cardiac cycle, then hang murmurs, S3/S4, and pressure–volume loop shifts on that scaffold.

Phases of the Cardiac Cycle

Electrical systole begins with ventricular depolarization. Mechanical systole has two major mechanical phases after AV valves close:

  1. Isovolumetric contraction — ventricular pressure rises with no volume change because all valves are closed. This phase generates the pressure that will open the aortic and pulmonic valves.
  2. Ejection — semilunar valves open when ventricular pressure exceeds arterial pressure; stroke volume leaves the ventricle. Early ejection is rapid; late ejection slows as the pressure gradient narrows.

Diastole likewise has two core mechanical phases:

  1. Isovolumetric relaxation — after semilunar valves close, ventricular pressure falls with volume fixed until atrial pressure exceeds ventricular pressure.
  2. Filling — AV valves open; most filling is early (rapid filling), followed by diastasis, then atrial contraction (atrial kick) that contributes a smaller but important fraction of end-diastolic volume, especially when ventricular compliance is reduced.

Right-sided events mirror left-sided events but occur at lower pressures and are more sensitive to respiratory swings in venous return.

Heart Sounds: S1, S2, and Extra Sounds

S1 is produced primarily by mitral and tricuspid closure at the onset of ventricular systole (isovolumetric contraction). A loud S1 can occur when the mitral valve is still widely open at the start of systole (for example, short PR interval or mild–moderate mitral stenosis with mobile leaflets); a soft S1 may occur with poor coaptation (severe MR) or long PR interval.

S2 is aortic (A2) and pulmonic (P2) closure at the end of ejection. Inspiration increases venous return to the right heart and prolongs right ventricular ejection slightly, delaying P2 and producing physiologic splitting of S2. Expiration brings A2 and P2 together. Wide fixed splitting is classically linked to atrial septal defect (equalization of respiratory variation across the communication). Paradoxical splitting (split on expiration, single on inspiration) occurs when left ventricular ejection is prolonged enough that A2 follows P2 (for example, severe aortic stenosis or left bundle branch block).

S3 is an early diastolic sound related to rapid filling into a volume-overloaded or dilated ventricle (physiologic in some young patients; pathologic with systolic heart failure). S4 is a late diastolic sound from atrial contraction into a stiff ventricle (decreased compliance: hypertrophy, ischemia).

Preload, Afterload, Contractility, and Frank–Starling

Preload is the load stretching myocardium before contraction—clinically approximated by end-diastolic volume (EDV) or filling pressure. Increased venous return or blood volume raises preload. Within a physiologic range, greater sarcomere stretch increases stroke volume (Frank–Starling mechanism) by optimizing actin–myosin cross-bridge formation and length-dependent calcium sensitivity.

Afterload is the impedance the ventricle must overcome to eject—approximated by aortic pressure / wall stress for the left ventricle. Elevated systemic vascular resistance or aortic stenosis increases left ventricular afterload, reducing stroke volume for a given contractility and preload. Wall stress relates to Laplace’s law: wall stress ≈ (pressure × radius) / (2 × wall thickness). Compensatory hypertrophy reduces wall stress for a given pressure.

Contractility (inotropy) is the intrinsic strength of contraction independent of preload and afterload. Catecholamines (β1 signaling → cAMP → PKA → more trigger Ca2+ and SR uptake kinetics) increase contractility. Myocardial ischemia, many cardiomyopathies, and negative inotropes decrease it.

DeterminantPhysiologic meaningStroke volume effect when increased
Preload (EDV)End-diastolic stretch↑ SV (Frank–Starling) until overstretch/failure
AfterloadOpposition to ejection↓ SV
ContractilityIntrinsic inotropy↑ SV; lower ESV
Heart rateCycles per minuteCO = HR × SV; extreme tachycardia shortens filling

Cardiac output (CO) = heart rate × stroke volume. Mean arterial pressure ≈ CO × systemic vascular resistance (plus central venous pressure conceptually). These relations explain why pure vasodilators can raise CO in afterload-sensitive failure and why dehydration (low preload) causes low SV even with normal heart muscle.

Pressure–Volume Loop Concepts

The left ventricular pressure–volume (PV) loop plots pressure versus volume over one cycle:

  • Bottom-right corner: end-diastole (EDV, end-diastolic pressure).
  • Vertical rise: isovolumetric contraction.
  • Top horizontal-ish path: ejection to end-systolic volume (ESV).
  • Vertical fall: isovolumetric relaxation.
  • Bottom path: diastolic filling.

Stroke volume is the horizontal width (EDV − ESV). The end-systolic pressure–volume relationship (ESPVR) slope reflects contractility; a steeper ESPVR means stronger inotropy. The end-diastolic pressure–volume relationship (EDPVR) reflects compliance; a stiffer ventricle shifts EDPVR up/left so higher pressure is needed for the same volume.

Conceptual shifts high-yield for exams:

  • ↑ Preload: EDV moves right; SV usually increases.
  • ↑ Afterload: ESV increases (less complete emptying); loop may be taller (higher pressure) and narrower.
  • ↑ Contractility: ESV decreases; loop widens.
  • Decreased compliance (diastolic dysfunction): higher filling pressures at similar EDV.

Valvular and Structural Murmurs: Timing, Radiation, Mechanisms

Murmurs are turbulent flow from high- to low-pressure chambers/vessels when a valve orifice is narrowed (stenosis), fails to coapt (regurgitation), or an abnormal communication exists.

LesionTiming / qualityRadiation / location cluesCore mechanism
Aortic stenosis (AS)Systolic crescendo–decrescendo (ejection)Right upper sternal border → carotidsFixed LV outflow obstruction; high LV–aorta gradient in systole
Aortic regurgitation (AR)Early diastolic decrescendoLeft sternal border (or right if aortic root dilated)Diastolic reverse flow aorta → LV
Mitral stenosis (MS)Opening snap + mid-diastolic rumbleApex, left lateral decubitusRestricted mitral orifice; LA–LV diastolic gradient
Mitral regurgitation (MR)Holosystolic, high-pitchedApex → axillaSystolic reverse flow LV → LA
HOCM (dynamic LVOTO)Systolic, harshLeft sternal border; may mimic ASDynamic subaortic obstruction + often MR from SAM
VSDHolosystolicLeft sternal border; thrills possibleLV → RV systolic shunt (when LV > RV pressure)
PDAContinuous “machinery”Left infraclavicularAorta → PA continuous gradient
MVPMid-systolic click ± late systolic murmurApexRedundant leaflet prolapse; click timing moves with volume

Aortic stenosis pathophysiology centers on chronic pressure overload hypertrophy, reduced coronary perfusion reserve, and a fixed obstruction that limits stroke volume increase with exercise. Aortic regurgitation produces volume overload of the LV (increased EDV) with wide pulse pressure when severe and chronic. Mitral stenosis elevates left atrial pressure, promotes atrial enlargement/fibrillation, and can cause pulmonary hypertension; the opening snap reflects tense leaflet doming. Mitral regurgitation elevates LA volume/pressure in systole; acute MR (for example, papillary muscle rupture) is poorly tolerated because the LA is noncompliant.

Hypertrophic obstructive cardiomyopathy (HOCM) features dynamic left ventricular outflow tract obstruction worsened by smaller LV cavity size (less preload, more contractility, less afterload). Systolic anterior motion (SAM) of the mitral valve contributes to obstruction and secondary MR. VSD produces a holosystolic left-to-right shunt while systemic pressure exceeds right ventricular pressure; large defects risk pulmonary overcirculation and later pulmonary vascular disease. PDA shunts continuously because aortic pressure exceeds pulmonary pressure in both systole and diastole after birth. Mitral valve prolapse produces a mid-systolic click when the leaflet billows; the regurgitant murmur, if present, is late systolic.

Maneuvers: Preload and Afterload as Diagnostic Tools

Bedside maneuvers change loading conditions predictably:

ManeuverPrimary hemodynamic effectMurmurs that intensifyMurmurs that soften
Valsalva (strain) / standing↓ Preload (↓ venous return)HOCM, MVP (click/murmur longer/earlier)Most other left-sided murmurs (AS, MR, etc.)
Squatting / passive leg raise↑ Preload (± ↑ afterload with squat)Most murmurs that depend on flow across fixed orificesHOCM, MVP (click delayed, murmur shorter)
Handgrip↑ Afterload (↑ SVR)MR, AR, VSDHOCM; often AS relatively less intense vs HOCM
Amyl nitrite (conceptual)↓ AfterloadHOCM, AS (relatively)MR, AR, VSD

Mechanistic logic to memorize: smaller LV cavity brings the hypertrophic septum and mitral apparatus into tighter opposition → HOCM louder. MVP leaflets reach critical prolapse earlier when underfilled → click moves earlier and murmur lengthens. Handgrip raises systemic pressure, increasing regurgitant and left-to-right shunt gradients (MR, AR, VSD) while reducing the dynamic gradient of HOCM.

Inspiration augments right-sided murmurs (tricuspid regurgitation, pulmonic stenosis) via increased venous return; expiration relatively augments left-sided murmurs. Always pair timing (systolic vs diastolic), shape (crescendo–decrescendo vs holosystolic vs continuous), radiation, and maneuver response before naming the lesion.

Integrating Cycle Physiology with Clinical Stems

A high-yield stem pattern: older patient with syncope, angina, and a late-peaking systolic murmur radiating to carotids → fixed AS with limited CO reserve. Another: young athlete with syncope, family history of sudden death, murmur louder with standing → HOCM. Another: rheumatic history, dyspnea, opening snap and diastolic rumble → MS with elevated LA pressure. Use the cardiac cycle to explain why diastolic lesions (MS, AR) are heard when the relevant AV or semilunar pressure gradient exists, and why holosystolic lesions maintain a gradient throughout systole.

Mastery check: if you can redraw isovolumetric phases, place S1/S2, state how EDV/ESV move on a PV loop with preload/afterload/inotropy changes, and predict Valsalva versus handgrip effects on HOCM versus MR, you have the CBSE core of this section.

Test Your Knowledge

During bedside exam, a harsh systolic murmur at the left sternal border becomes louder with Valsalva strain and softer with passive leg raise. Which mechanism best explains this response?

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B
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D
Test Your Knowledge

Which pressure–volume loop change best matches an isolated acute increase in left ventricular afterload with contractility held constant?

A
B
C
D
Test Your Knowledge

A patient has a holosystolic murmur at the apex radiating to the axilla that intensifies with isometric handgrip. Which lesion physiology fits best?

A
B
C
D