Letter by Y-Hassan Regarding Article, “Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy”
Authors: Shams Y-Hassan
Journal: Circulation (2018)

To the Editor: I read with great interest the report on long-term structural, functional, and metabolic changes in 37 patients with previous (>12 months) Takotsubo syndrome (TS) compared with 37 age-, sex-, and comorbidity-matched control subjects in the recent article by Scally et al 1 published in Circulation.Among the objective findings on cardiac magnetic resonance imaging is that the whole heart native T1 values were significantly higher in patients with previous TS.The differences were seen in basal, midventricular, and apical segments of the left ventricle.It is interesting that these persisting abnormalities were observed in a TS patient group with most favorable reported outcomes because most of the patients belonged to emotionalinduced TS; only 11% of the patients had physical-induced TS.However, some of the abnormal findings need to be explained by the investigators.On cardiac magnetic resonance imaging, the heart native T1 values were higher even in the basal segments despite the absence of inverted (basal) TS in the studied patients.The higher native T1 values seen, including in the initially unaffected basal segments, may argue for the fact that they were not consequences of TS but rather they predate and possibly predisposed to TS.Nonetheless, the findings of persistent changes in patients with prior TS in the current study will pave the way for further research on persistent and chronic phenotypes in other TS patient groups.Support for the suggestion of existence of chronic phenotypes of TS is found in the literature.One important histopathologic change in TS is the finding of contraction band necrosis (CBN).CBN (also known as focal or coagulative myocytolysis, and myofibrillar degeneration) consists of aggregated clumps of disorganized actinomyosin filaments, and is associated with adjacent areas of myoplasm devoid of myofilaments accounting for the use of terms mentioned above.Noteworthy, the pathogenesis of CBN had been under discussion decades before the introduction of the term Takotsubo in 1990.It has been found that the evolving pathology of contraction band necrosis can be distinguished by (1) hypercontraction/cross-bands as an early change, (2) progressive destruction of myofibrillar remnants associated with monocytes/macrophages leading to an alveolar pattern formed by empty sacrolemmal tubes infiltrated by macrophages loaded by lipofuscin, and (3) a healing phase with progressive collagenization ending in fibrous scar. 2 Such evolving pathology of CBN in TS implies that the disease may have an acute reversible course or progressive course resulting in persistent subclinical, as observed in the current report by Scally et al, 1 or chronic phenotype.Critical review of the literature dealing with the pathogenesis of CBN since 1955 and that of TS since 1990 suggests that the cardiac sympathetic hyperactivation disruption is the most probable cause of the disease. 3The chronic sympathetic hyperactivation with acute exacerbation may result in repetitive myocardial stunning, a pathophysiology identical to that of TS, and may occur in patients with heart failure with acute exacerbation 4 or in sympathetic reno-cardial syndrome 5 in patients with chronic kidney disease.