Medical Clinic II, University Heart Center Lübeck, Lübeck, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg-Kiel-Lübeck, Lübeck, Germany.
Medical Clinic II, University Heart Center Lübeck, Lübeck, Germany; Department of General and Interventional Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany.
J Am Coll Cardiol. 2023 May 23;81(20):1979-1991. doi: 10.1016/j.jacc.2023.03.398.
Takotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology.
This study analyzed altered cardiac hemodynamics during TTS to elucidate underlying disease mechanisms.
Left ventricular (LV) pressure-volume loops were recorded in 24 consecutive patients with TTS and a control population of 20 participants without cardiovascular diseases.
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).
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).
心肌顿抑综合征（TTS）是一种具有不完全明确病理生理学机制的可逆性心力衰竭形式。
本研究分析了 TTS 期间心脏血液动力学的变化，以阐明潜在的疾病机制。
在 24 例 TTS 患者和 20 例无心血管疾病的对照组参与者中记录左心室（LV）压力-容积环。
TTS 与 LV 收缩功能障碍相关（收缩末期弹性 1.74mm Hg/mL 与 2.35mm Hg/mL[P=0.024]；收缩期压力随时间变化的最大变化率 1,533mm Hg/s 与 1,763mm Hg/s[P=0.031]；收缩末期压力为 150mm Hg 时的终末容积，77.3mL 与 46.4mL[P=0.002]）；和缩短的收缩期（286ms 与 343ms[P<0.001]）。作为响应，压力-容积图向右移动，LV 舒张末期（P=0.031）和收缩末期（P<0.001）容积显著增加，尽管 LV 射血分数较低（P<0.001），但 LV 每搏量仍保持不变。舒张功能的特征是主动松弛时间延长（松弛常数 69.5ms 与 45.9ms[P<0.001]；舒张期压力的最小变化率 -1,457mm Hg/s 与 -2,192mm Hg/s[P<0.001]），而 TTS 期间舒张僵硬度（1/顺应性）不受影响（舒张末期压力为 15mm Hg 时的容积，96.7mL 与 109.0mL[P=0.942]）。TTS 患者的机械效率显著降低（P<0.001），考虑到每搏功降低（P=0.001）、势能增加（P=0.036），以及与对照组相比总压力-容积面积相似（P=0.357）。
TTS 的特征是心肌收缩力降低、收缩期缩短、能量效率降低和主动松弛时间延长，但舒张期被动僵硬度不变。这些发现可能表明肌丝蛋白的磷酸化减少，这可能是 TTS 的潜在治疗靶点。（通过获得压力-容积环优化心肌顿抑综合征的特征描述[OCTOPUS]；NCT03726528）。
