Takotsubo syndrome is characterized by reduced cardiac contractility, shortened systolic period, inefficient energetics, and prolonged active relaxation, suggesting decreased phosphorylation of myofilament proteins as a potential therapeutic target.
BACKGROUND Takotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology. OBJECTIVES This study analyzed altered cardiac hemodynamics during TTS to elucidate underlying disease mechanisms. METHODS Left ventricular (LV) pressure-volume loops were recorded in 24 consecutive patients with TTS and a control population of 20 participants without cardiovascular diseases. RESULTS TTS was associated with impaired LV contractility (end-systolic elastance 1.74 mm Hg/mL vs 2.35 mm Hg/mL P = 0.024; maximal rate of change in systolic pressure over time 1,533 mm Hg/s vs 1,763 mm Hg/s P = 0.031; end-systolic volume at a pressure of 150 mm Hg, 77.3 mL vs 46.4 mL P = 0.002); and a shortened systolic period (286 ms vs 343 ms P < 0.001). In response, the pressure-volume diagram was shifted rightward with significantly increased LV end-diastolic (P = 0.031) and end-systolic (P < 0.001) volumes, which preserved LV stroke volume (P = 0.370) despite a lower LV ejection fraction (P < 0.001). Diastolic function was characterized by prolonged active relaxation (relaxation constant 69.5 ms vs 45.9 ms P < 0.001; minimal rate of change in diastolic pressure -1,457 mm Hg/s vs -2,192 mm Hg/s P < 0.001), whereas diastolic stiffness (1/compliance) was not affected during TTS (end-diastolic volume at a pressure of 15 mm Hg, 96.7 mL vs 109.0 mL P = 0.942). Mechanical efficiency was significantly reduced in TTS (P < 0.001) considering reduced stroke work (P = 0.001), increased potential energy (P = 0.036), and a similar total pressure-volume area compared with that of control subjects (P = 0.357). CONCLUSIONS TTS is characterized by reduced cardiac contractility, a shortened systolic period, inefficient energetics, and prolonged active relaxation but unaltered diastolic passive stiffness. These findings may suggest decreased phosphorylation of myofilament proteins, which represents a potential therapeutic target in TTS. (Optimized Characterization of Takotsubo Syndrome by Obtaining Pressure Volume Loops OCTOPUS; NCT03726528).
“Taking all this information together, we believe that it is likely that decreased phosphorylation of myofilament proteins – which may be caused by some kind of disturbance in calcium metabolism – may partially account for the impaired contractility and shortened systolic period seen in Takotsubo syndrome.”
Stiermaier et al. (Mon,) studied this question.