Thread by @Thind888

Part 1:
*Defining ventricular preload*

The conceptual definition of preload is quite straightforward: end-diastolic myocardial load/stretch. At the microscopic level, it's the sarcomere length we are interested in, which would increase with higher end-diastolic load (preload)
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The importance of preload is in effecting the Frank-Starling mechanism: increase in ventricular performance with ⬆️ preload. The basis of F-S relationship is primarily the sarcomere Force-Length relation.

At sarcomere length of ~2.3 μm, actin-myosin interaction is optimized.

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Any further increase in sarcomere length does not improve ventricular performance (flat part of F-S curve).

So when we give fluids, what we're really trying to achieve is an ⬆️in the average sarcomere length.

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The clinical definition of preload is much more controversial!

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For LV, the two most commonly used measures are LVEDV and LVEDP

Before we compare these, let's model the ventricle as a fluid-filled perfectly spherical balloon (obviously an approximation). If we fill the balloon with more fluid, it's size (LVEDV) and pressure (LVEDP) will⬆️

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*Core point*
To have any load/stretch on the wall of the balloon, it needs to be filled beyond its "unstressed volume". E.g. if the balloon is not filled enough to cause a stress on its walls (all volume = unstressed volume; no stressed volume), the "load" on its wall is zero!

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**Pitfalls with LVEDV**
(i) For a given LVEDV, the wall stretch (and LVEDP) would vary depending on the physical characteristics of the ventricle. E.g. 110cc is a normal adult LVEDV but would generate enormous LVEDP in kids!

Another example is eccentric hypertrophy (in DCM).

7/ As new sarcomeres are added in series, the unstressed volume of LV ⬆️. So the same LVEDV would generate ⬇️LVEDP compared to normal hearts.

(ii) Secondly, LVEDV disregards unstressed volume. E.g. in our model, balloon A has some volume (LVEDV) but its pressure (LVEDP) is zero!

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**Pitfalls of LVEDP**
In my mind, LVEDP is a much more robust measure of LV preload and circumvents the pitfalls of LVEDV. However, a few considerations:

(i) It's the *transmural* LVEDP that matters (more on this later)
(ii) A given LVEDP doesn't fully describe wall stress

9/ Why? Enter LaPlace's law! {T=PR/2w}

For a given LVEDP, the amount of wall tension is dependent on the curvature of the sphere. If curvature is low (bigger sphere), same pressure causes higher wall tension.

Here's an excellent tweetorial on this -

https://twitter.com/AndrewCAhn2/status/1129510075259793413

10/ *Wall stress/tension* provides the complete description of ventricular preload. Wall tension is the orthogonal stress on the LV wall that would be proportional to average sarcomere length.

LaPlace's law states that:

Tension (T) = (Pressure x radius) / 2.width (LV thickness)

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Summary:

For a *stressed LV*, preload is a function of LVEDP, LVEDV and LV thickness (w)

Mathematically, volume is the cube root of radius, so the influence of LVEDP > LVEDV.

Also, a thick LV (⬆️w) (e.g. HTN), would result in a lower wall stress for a given LVEDP/LVEDV.

12/ **Special scenario: RV**

Here's the kicker with RV preload: normal human RV operates at or below its unstressed volume! (PMID: 27613549).

Volume loading a normal RV initially does not invoke the F-S mechanism as its wall stress (preload) is zero! (RVEDV < unstressed volume)

13/ Of course, a volume overloaded RV would operate via the F-S curve.

This under-appreciated fact has critical implications:
(i) (Transmural) RA pressure is normally zero.
(ii) Hence, in an unstressed RV, a CVP reading > zero reflects pericardial pressure (more on this later).

Here's a beautiful commentary unifying wall stress to explain both preload and afterload: PMID: 11824209

Submitting for peer-review with the Heart Failure community!

@FH_Verbrugge @VerwerftJan @TheWrightHeart @CharlieJainMD @yreddyhf @RyanTedfordMD @OKiamanesh @SunitChaudhryMD