Frank-Starling curve

**Definition:** The Frank-Starling law states that the force of ventricular contraction (stroke volume) is proportional to the initial length of the cardiomyocyte sarcomere, i.e., end-diastolic volume (EDV) or preload. "The heart pumps out what it receives."

**Mechanism:** - Increased preload stretches sarcomeres toward optimal length (~2.2 µm), where actin-myosin overlap is optimal. - Stretch increases troponin C sensitivity to Ca2+ (length-dependent activation) and increases myofilament lattice spacing effects, so contraction is stronger without a change in intracellular Ca2+ transients. - Ascending limb = normal physiologic range. Beyond optimal overlap (the descending limb, seen mainly in overdistended failing hearts), force declines.

**Axes:** X-axis = preload (EDV, LVEDP, PCWP, or right atrial pressure as surrogates). Y-axis = stroke volume, cardiac output, or stroke work.

**Curve shifts (key for boards):** - *Upward and left (increased contractility):* sympathetic stimulation (β1), digoxin, dobutamine, milrinone, increased Ca2+. Same preload gives a higher SV, and ESV decreases. - *Downward and right (decreased contractility):* systolic heart failure (e.g., dilated cardiomyopathy, MI), β-blockers, non-dihydropyridine CCBs, acidosis, hypoxia. The same preload gives a lower SV, and ESV increases. - *Preload changes move along the same curve:* venous return up (exercise, fluid bolus, venoconstriction) moves up the curve. Venous return down (hemorrhage, venodilators such as nitroglycerin, diuretics) moves down the curve. - *Afterload:* Increased afterload (e.g., vasoconstrictors) lowers SV at a given preload (downward shift). Decreased afterload (ACEi, hydralazine) raises SV (upward shift).

**Clinical significance:** - Beat-to-beat balancing of right and left ventricular outputs. For example, increased RV output raises LV preload, so LV output rises to match. - Inspiration increases venous return to the right heart, increasing RV SV. The LV then receives less blood, and its SV decreases (an exaggerated version is pulsus paradoxus). - Heart failure: compensatory preload increase (fluid retention via RAAS) initially maintains SV along the curve. On the flat or descending portion, additional preload only causes pulmonary congestion and edema, not more output. Diuretics and venodilators reduce preload and symptoms without much loss of SV on the flat part of the curve. - Diastolic dysfunction (HFpEF): the problem is a stiff ventricle with a steeper end-diastolic pressure-volume relationship, so a given EDV gives higher pressures. This is not primarily a contractility problem. - Pressure-volume loops: Increased preload widens the loop (EDV increases, SV increases). Increased contractility shifts the ESPVR up and to the left and decreases ESV. - Frank-Starling is an intrinsic regulatory mechanism. It operates independently of neural input, as shown by the transplanted denervated heart, which increases output with exercise via preload (and later circulating catecholamines).

**Relationship to related concepts:** - Preload ≈ EDV (venous return, blood volume, venous tone). Afterload ≈ aortic pressure/wall stress (LaPlace: T = Pr/2h). Contractility is the intrinsic ability independent of preload and afterload. - Ejection fraction = SV/EDV; EF is reduced in systolic dysfunction (<40% in HFrEF). - The cardiac output (Guyton) curve plotted against the Frank-Starling curve determines the equilibrium operating point of the circulation.

**High-yield pearls:** - Increased contractility: increased SV, increased EF, decreased ESV. - Exercise: increased venous return, increased HR, and increased contractility together raise CO. - Hypovolemia and hemorrhage reduce preload, which decreases SV (move down the same curve).