Recent studies have demonstrated that the rate of acute complications in TTS is comparable to what has been reported in acute coronary syndromes.
The in-hospital course can be complicated by serious mechanical complications, including dynamic left ventricular outflow tract obstruction (LVOTO), which has been described in a non-negligible proportion of patients and can lead to haemodynamic deterioration.
LVOTO is a dynamic phenomenon precipitated by the hypercontractility of basal left ventricular segments in the context of structural and rheological changes involving the left ventricle, mitral valve apparatus, preload and afterload. Predisposing factors for LVOTO may include a smaller ventricular cavity and hypertrophy of the interventricular septum. As the basal segments contract vigorously and the septum thickens due to myocardial edema, high-velocity flow through the narrowed LVOT creates a Venturi effect, leading to systolic anterior motion of the anterior mitral leaflet and, subsequently, to secondary mitral regurgitation due to leaflet malcoaptation. Furthermore, the increase in afterload caused by LVOTO may exacerbate apical and midventricular myocardial dysfunction by elevating shear stress and disrupting the balance between oxygen supply and demand. These combined factors impair cardiac output, which can ultimately lead to cardiogenic shock and pulmonary hypertension, especially in patients with severe mitral regurgitation and compromised left atrial compliance.
Vila-Sanjuan et al explored the impact of LVOTO in patients with TTS and cardiogenic shock in the Spanish National Takotsubo Registry (RETAKO).
Of the 1248 patients included in RETAKO, LVOTO was detected in 10%, a slightly higher incidence compared to the 7% reported in a recent study from the Takotsubo Italian Network (TIN) on patients with TTS and LVOTO.
The investigators focused their analysis on 322 patients with TTS complicated by cardiogenic shock, categorising them based on the presence or absence of LVOTO. Several important observations emerged. First, LVOTO was present in 18% of those with TTS and cardiogenic shock, and it was associated with a higher risk of complications such as ventricular arrhythmias and acute kidney failure. However, after adjusting for confounders, LVOTO had no independent association with in-hospital mortality. Second, the study provided valuable insights into the therapeutic strategies for managing patients with TTS with cardiogenic shock, particularly regarding the use of vasoactive agents, inotropes and beta-blockers. Among patients with LVOTO, about 38% were treated with monotherapy, primarily with norepinephrine, followed by beta-blockers. Approximately 33% of patients with LVOTO required dual therapy, typically a combination of norepinephrine and beta-blockers, while about 17% received more intensive triple therapy, often including phenylephrine. About 12% of patients with LVOTO did not require any vasoactive agents or beta-blockers, and no patients with LVOTO were treated with inotropic drugs. The use of mechanical circulatory support (MCS) was limited across the cohort. The intra-aortic balloon pump (IABP) was employed in 24 patients (7.5%), including 4 with LVOTO and 20 without. It is noteworthy that no TTS patients developed LVOTO following IABP insertion. Impella, used only in about 1% of patients, was only implemented in those without LVOTO. A small proportion of around 2% of patients required extracorporeal membrane oxygenation, with three of these cases occurring in patients with LVOTO.Third, the study found that the presence of LVOTO during the in-hospital course was not associated with an increased risk of long-term mortality.
This study holds significant strengths, particularly in its comprehensive in-hospital management data. One important finding is the higher rate of adverse events, including ventricular arrhythmias and acute kidney failure, observed in patients with LVOTO compared with those without it. The adverse impact of LVOTO on the in-hospital course of patients with TTS was also highlighted in the recent TIN Study, which reported an increased risk for cardiogenic shock, acute heart failure and in-hospital mortality after adjusting for confounders.
However, unlike the TIN cohort, LVOTO in this study was not identified as an independent factor associated with mortality. This difference may be attributed to differences in the patient populations. Vila-Sanjuan et al focused exclusively on patients with TTS complicated by cardiogenic shock, a high-risk group with inherently elevated mortality, regardless of the presence of LVOTO. In contrast, the TIN Study included a broader cohort of all-comer TTS patients, including those without cardiogenic shock. The inclusion of lower-risk patients in the TIN Study may have highlighted the negative prognostic impact of LVOTO more distinctly, whereas in the higher-risk cohort studied by Vila-Sanjuan et al, the elevated baseline mortality associated with cardiogenic shock may have attenuated the relative impact of LVOTO on in-hospital mortality. Another important aspect of this study is the detailed analysis of in-hospital treatment strategies for patients with TTS and cardiogenic shock, highlighting the differences in therapeutic approaches between patients with and without LVOTO. Prompt clinical and echocardiographic evaluation is crucial to distinguish LVOTO from other causes of haemodynamic instability, as treatment varies significantly depending on the underlying etiology. For instance, in patients with cardiogenic shock due to primary pump failure without LVOTO, non-adrenergic inotropic agents such as levosimendan may be considered, alongside diuretics in cases of cardiopulmonary congestion. However, in patients with TTS complicated by LVOTO, positive inotropic agents can worsen basal hypercontractility and further increase the intraventricular pressure gradient. In addition, diuretics can decrease preload, exacerbating the obstruction and worsening mitral regurgitation. In these cases, careful fluid administration and the use of beta-blockers, particularly short-acting agents like esmolol or landiolol, may help to reduce basal hypercontractility and improve left ventricular filling.
One limitation of this study is the relatively small number of patients treated with MCS which limits the generalisability of findings related to its use in this population. The observation that IABP use was not associated with the onset or worsening of LVOTO in patients with TTS and cardiogenic shock is notable but should be interpreted with caution. Given that IABP reduces afterload, its impact on LVOTO dynamics warrants further investigation in larger studies. Similarly, the lack of Impella use in patients with LVOTO represents an important gap in understanding, as previous case reports have suggested that Impella may be a valuable option for patients with TTS with LVOTO and cardiogenic shock. In critical cases, Impella could help maintain systemic blood pressure by bypassing the obstructed LVOT and providing mechanical stabilisation, serving as a bridge to recovery.
Future studies should further explore the role of MCS devices in patients with TTS and LVOTO, as these could offer important therapeutic options in the most challenging clinical scenarios.
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