Correspondence on 'Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome’ by Silverio et al

To the Editor We have read the article by Silverio et al regarding betablockers reducing allcause mortality in patients with Takotsubo syndrome (TTS). The beneficial effect of betablockers particularly applies to TTS patients with hypertension or cardiogenic shock. While this exciting finding validates an important risk reduction strategy in TTS survivors at longterm followup, Silverio et al’s results also bring up a seemingly paradoxical therapeutic dilemma in TTS patients with cardiogenic shock. Dynamic left ventricular outflow tract (LVOT) obstruction and worsening mitral regurgitation (MR) play important roles in TTSassociated cardiogenic shock. 3 Preceding myocardial structural abnormalities (hypertensive heart disease and basal septal hypertrophy, etc) may exacerbate LVOT obstruction on top of hyperdynamic motion of basal ventricular walls. There is a growing body of evidence that preexisting myocardial pathologies not only increase adverse haemodynamic events during TTS episodes but also are associated with persistent postTTS diastolic dysfunction and adverse outcomes. 4 5 This signifies the presence of certain specific conditions in some patients with TTS that warrants particular therapeutic strategies for longterm management and secondary prevention. A recent subset analysis of the DOREMI trial showed an outcome improvement in patients with cardiogenic shock who presented with betablockers on admission. Silverio et al’s results further highlight the possible prognostic benefits of early betablockade in TTS patients with cardiogenic shock. Betablockers are traditionally contraindicated in cardiogenic shock. Paradoxically, patients with TTS expected to benefit the most from early β-blockade are not expected to ‘tolerate’ this medication due to concern for worsening haemodynamic instability. In realworld practice, this may also result in an extended medication gap from the immediate hospitalisation period until outpatient followup visits, potentially depriving patients with TTS of the prognostic benefit from appropriate pharmacotherapy in the critical therapeutic window. Uncovering the unique pathophysiology underlying TTS may help solidify timely and effective therapeutic strategies. Brain natriuretic peptide (BNP) release in patients with TTS is usually more prominent than that in patients with acute myocardial infarction. Other than being a prognostic parameter, BNP release also causes natriuresis, vasodilatation and inhibition of the reninaldosterone system, which decreases mean arterial pressure and pulmonary capillary wedge pressure. Natriuresis, when combined with diuresis, may cause patients with TTS to become preload sensitive, precipitating hypotension and reflex tachycardia, resulting in ‘cardiogenic’ shock. In addition, a significant ventricular dilation during TTS episode easily leads to an assumption of pump failure and volume overload. Strict volume restriction or overdiuresis can cause inappropriately low ventricular preload for the stunned ventricle, precipitate LVOT obstruction, worsen MR (secondary to systolic anterior motion of the mitral valve) and further decrease cardiac output. This would prevent frontline clinicians from starting and titrating up betablockers. Timely ventricular preload titration guided by realtime haemodynamic measurement (using right heart catheterisation or quantitative Doppler echocardiography) helps avoid haemodynamic compromise and support early and adequate β-blockade to maximise its prognostic benefits.