Background: Takotsubo syndrome (TTS) is a reversible form of acute heart failure with still incompletely understood pathophysiology. The comprehensive analysis of altered cardiac hemodynamics provides novel insights into myocardial performance during acute TTS and might elucidate underlying disease mechanisms.

Methods: This prospective, single-center study used a dedicated conductance catheter for invasive recording of left ventricular (LV) pressure-volume loops in 24 consecutive patients with TTS. The control population consisted of 20 participants without cardiovascular diseases.

Results: Patients with TTS showed a severely impaired LV contractility (end-systolic elastance, Ees, 1.74 versus 2.35 mmHg/ml, p=0.024; maximal rate of change in systolic pressure over time, dP/dt_max, 1533.0 versus 1763.4 mmHg/s, p=0.031; end-systolic volume at a pressure of 150 mmHg, ESV150, 77.3 versus 46.4 ml, p=0.002) and a shortened systolic ejection time compared to controls (286.0 versus 342.8 ms; p<0.001). In response, the Frank-Starling mechanism was used excessively to balance this state by shifting the pressure-volume diagram rightward with a significantly increased LV end-diastolic (p=0.031) and end-systolic volume (p<0.001), which preserved the stroke volume (p=0.370) despite a lower ejection fraction (p<0.001). Diastolic function was characterized by prolonged active relaxation (relaxation constant, tau, 69.5 versus 45.9 ms, p<0.001; minimal rate of change in diastolic pressure, -dP/dt_min, -1457.0 versus -2191.5 mmHg/s, p<0.001), while passive stiffness (compliance) was not affected during acute TTS (volume at a pressure of 15 mmHg, EDV15, 96.7 versus 109.0 ml, p=0.942). Mechanical efficiency was significantly reduced in patients with TTS (0.536 versus 0.701, p<0.001) considering a reduced stroke work (5378.5 versus 7902.9 mmHg*ml, p=0.001), a markedly increased potential energy (4741 versus 2936 mmHg*ml, p=0.036) and a similar total pressure volume area compared to controls (10303.2 versus 11454.0 mmHg*ml, p=0.357).

Conclusions: Acute TTS is characterized by reduced cardiac contractility in the presence of a shortened systolic ejection time, prolonged active myocardial relaxation but unaltered diastolic passive stiffness, and inefficient myocardial energetics. The translation of these findings to their molecular implications may suggest post-translational modifications, such as decreased phosphorylation of myofilament proteins like cardiac myosin-binding protein-C, which represents a potential therapeutic target in TTS.