Acute cardiac sympathetic disruption and left ventricular wall motion abnormality in takotsubo syndrome

Abstract

Takotsubo syndrome (TS) is characterized by a unique pattern of transient circumferential left ventricular wall motion abnormality (LVWMA). The LVWMA in TS may be localized to the apical, mid-apical, mid-ventricular, mid-basal or basal regions of the left ventricle. Focal and generialized (global) LVWMA have also been reported. In the acute phase of TS, the hyperkinetic valve-like motion of the basal segments and/or the hyperkinetic slingshot-like motion of the apical segments combined with the firm stunned a-, hypokinetic segments result in a conspicuous left ventricular ballooning during systole. The LVWMA in TS follows most probably the local cardiac sympathetic nerve distribution and caused by local cardiac sympathetic disruption and noradrenaline spillover.

Keywords::

• Sepsis
• takotsubo
• heart failure
• broken heart syndrome
• myocardial infarction
• neurogenic stunned myocardium

I am pleased that Dr Madias enjoyed reading the article entitled ‘Sepsis-induced myocardial depression and takotsubo syndrome’ recently published in Acute Cardiac Care (1). The author also greatly appreciates the very encouraging comment by Dr Madias, in the August 2014 issue of Acute Cardiac Care (2). Two questions were raised.

1. Generalized left ventricular hypokinesis in takotsubo syndrome (TS)

I agree with Dr Madias that patients with sepsis—but even other physical or emotionally triggered TS may have transient generalized (global) left ventricular a- or hypokinesis. The left ventricular wall motion abnormality (LVWMA) in TS may be localized to the apical, mid-apical, mid-ventricular, mid-basal, or basal regions of the left ventricle (even right ventricle). Focal and global hypokinesis have also been reported. Reports on reversible generalized LVWMA in TS may be underestimated for a number of reasons. The LVWMA in TS is a very dynamic process and global hypokinesis may be missed if the cardiac image study is done late (days after admission) in the course of the disease. The author has previously reported on a case of capecitabine-triggered TS presented with cardiogenic shock. The pattern of LVWMA in that case was generalized at admission and turned into regional (mid-basal) four days after admission (3). Critical review of the literature dealing with sepsis-induced myocardial depression reveals that there was a tendency to describe the LVWMA as generalized and low ejection fraction in the older literatures. With the increasing knowledge on TS, the description of the pattern and localization of LVWMA have improved markedly during the last 10 years. The LVWMA is described as left ventricular apical ballooning in all patients with sepsis-induced left ventricular dysfunction in a study by Park et al. in 2005 (4). Furthermore, global involvement of the left ventricle in TS may be incompatible with survival and the patients may die before reaching medical care.

2. Local cardiac sympathetic disruption in TS

In a recently published article, I have presented substantial evidences for the involvement of the local cardiac sympathetic nerve terminals and local noradrenaline spillover in the etiopathogenesis of TS and I have coined the term acute cardiac sympathetic disruption syndrome for the condition (5). The disturbances in the local cardiac sympathetic nerve terminals may account for the striking circumferential ballooning of the left ventricle, which is regarded as the hoofmark of TS. In the majority of cases with TS, two types of LVWMA are observed in the acute stage of the disease: the first one is the stunned a- or hypokinetic segments and the second one is the hyperkinetic segments with a sharp transition between the two regions of LVWMA. In mid-apical and mid-ventricular types of TS, the firm stunned myocardium in the affected segments results in pulling the basal elastic hyperkinetic segments inwards and backwards resulting in a valve-like motion of the basal hyperkinetic segments. This valve-like motion in some patients may account for the left ventricular outflow tract obstruction. In apical sparing types of TS, the firm stunned myocardium in the affected segments results in pulling the apical hyperkinetic segments inwards and forwards, resulting in a slingshot-like motion of the hyperkinetic apical segments. The combination of the firm stunned akinetic segments with the valve-like motion of the basal segments and/or slingshot-like motion of the apical segments are the cause of the striking ballooning appearance of left (right) ventricle during systole. The hyperkinetic segments are often described in the literature as compensatory; I believe that the hyperkinetic segments may also be induced by the inotropic effects of hyper-activated but not disrupted sympathetic nerve terminals. The stunned a-, hypokinetic segments is probably due to the hyperactivated disrupted sympathetic nerve terminals associated with noradrenaline spillover. The extent and the degree of the sympathetic disruption and the degree of noradrenaline spillover may determine the severity of the disease, the clinical manifestation and the findings detected by different types of cardiac image studies and scintigraphies. I believe that the local cardiac sympathetic disruption and noradrenaline spillover causes ‘cardiac muscle cramp’, which typically results in a firm and a-, hypokinetic circumferential band of myocardium across the left ventricle. The evidence for this assertion is the so-called ‘contraction band necrosis’, due to hypercontracted sarcomeres, which is a typical histopathological finding in TS (5). In some cases of TS, the catecholamine spillover may result in catecholamine induced myocarditis. Cases of both biopsy-proven myocarditis and cardiac magnetic resonance (CMR) imaging changes consistent with myocarditis have been reported in patients with TS (6). Acute myocardial oedema, which may be secondary to inflammation, is a well-recognized CMR finding in the stunned myocardial regions of the left ventricle in patients with TS. Noradrenaline spillover may also result in injury of the local cardiac sympathetic nerve terminals and down-regulation of the uptake-1 pathway in the sympathetic nerve terminals. The evidence for that is the decreased Iodine 123 meta-iodobenzylguanindine (¹²³I-MIBG) uptake via the uptake-1 pathway and increased ¹²³I-MIBG washout rate during ¹²³I-MIBG scintigraphy. This scintigraphic finding is the sign of what has been called cardiac sympathetic denervation. This denervation is most probably partial and usually reversible. However, the reversibility of cardiac sympathetic denervation may take a long time to normalize, much longer than the normalization of the LVWMA.

Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.