Dr Rachel Bastiaenen, PhD, St George's University of London, St George's Hospital London, UK

Takotsubo or ‘stress’ cardiomyopathy, first described in 1990, is characterised by transient left ventricular dysfunction. The term Takotsubo, from the Japanese word for lobster pot, describes ballooning of the left ventricular apex seen on cardiac imaging. It predominantly affects older women and is often preceded by a physical or emotional trigger. In the acute phase, clinical features, electrocardiographic findings and troponin elevations resemble an acute coronary syndrome (ACS) but at angiography obstructive coronary disease and/or signs of acute plaque rupture are absent. The condition has been regarded as benign, and although patients remain at risk of recurrence, the clinical outcomes have been considered good. (1)

Recent data published by Templin et al. disputes this. (2) The International Takotsubo Registry is a consortium of 26 centres in Europe and the US established to investigate clinical features, prognostic predictors and outcome of Takotsubo cardiomyopathy. 1750 patients from this registry were evaluated and a subset was compared with age and sex matched ACS patients. Takotsubo patients had higher rates of neurological and psychiatric disorders (55.8% vs 25.7%; p<0.001) and lower left ventricular ejection fractions (LVEF; 40.7±11.2% vs 51.5±12.3%; p<0.001) than ACS patients. In-hospital complications (including shock and death) were similar for both groups. In Takotsubo cardiomyopathy the independent predictors of in-hospital complications were physical triggers, acute neurological or psychiatric diseases, high Troponin levels and low admission LVEF. During follow-up the rate of major adverse events was 9.9% per patient year and rate of death was 5.6% per patient year. Retrospective analysis using propensity scoring suggested that use of angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) but not beta-blockers was associated with improved survival.

The authors conclude that Takotsubo cardiomyopathy is an acute heart failure syndrome with substantial morbidity and mortality and that risk of complications was previously underestimated due to the selection bias of previous reports toward low-risk patients. The potential for ACE-I and ARB medications to improve survival in Takotsubo patients is thought stimulating but requires prospective study data before conclusions can be drawn.

References

  1. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 2008;155(3):408-17.
  2. Templin C, Ghadri JR, Diekmann J et al. Clinical features and outcomes of Takotsubo (stress) cardiomyopathy. NEJM 2015;373(10):929-38.
Cardio Debate Expert Comments

New Insights on Takotsubo (Stress) Cardiomyopathy

The results of the International Takotsubo Registry (1) are at variance with those of several single center reports but are consistent with those of the COUNTS study (2), which was the largest cooperative investigation regarding Takotsubo cardiomyopathy so far. Results reported by both The International Takotsubo Registry and COUNTS emphasise the fact that Takotsubo patients differ from “conventional” -coronary artery disease related- ACS patients, as the former have an increased prevalence not only of neurologic and psychiatric disorders (1) but also of pulmonary, kidney, liver and connective tissue diseases (2). Similarly, the observation that Takotsubo (stress) cardiomyopathy is associated with substantial mortality is not an unexpected finding as two previous studies had already shown increased mortality rates in Takotsubo patients as compared with individuals in the general population, matched for age and sex (3, 4). Altogether, the novel scientific information summarized in the accompanying Cardionote provide clear evidence that Takotsubo (stress) cardiomyopathy should be considered to represent a condition frequently associated with relevant comorbidities, which might at least in part contribute to the observed mortality excess reported in larger studies.

REFERENCES

  1. Templin C, Ghadri JR, Diekmann J, et al. Clinical features and outcomes of takotsubo (stress) cardiomyopathy. New Engl J Med 2015;373:929-38.
  2. Pelliccia F, Parodi G, Greco C, et al. Comorbidities frequency in takotsubo syndrome: An international collaborative systematic review including 1,109 patients. Am J Med 2015;128:654.e11-9.
  3. Sharkey SW , Windenburg DC , Lesser JR , et al . Natural history and expansive clinical profile of stress (Tako-Tsubo) cardiomyopathy. J Am Coll Cardiol 2010; 55: 333–41.
  4. Parodi G, Bellandi B, Del Pace S, et al. Natural history of tako-tsubo cardiomyopathy. Chest 2011;139:887-92.

As highlighted by Dr Bastianen in her ‘cardio note’, takotsubo cardiomyopathy is often considered be a relatively benign condition. Data from the recently published International Takotsubo Registry provide extremely useful information regarding the potential for a poor clinical outcome in patients affected by this condition, as well as the high prevalence of serious comorbidities affecting a sizeable proportion of patients with Takotsubo cardiomyopathy.  LV function is markedly affected during the acute phase of the process and albeit function tends to recover within weeks in most patients (a major criterion for the diagnosis of Takotsubo stress cardiomyopathy!), a proportion of patients show a reduced EF during follow up. The problem is that patients in whom LV dysfunction does not recover, are not included in the Takotsubo series thus creating a major bias regarding the assessment of prognosis in these individuals.

The paper by Templin et al (1), the basis of Dr Bastianen’s ‘cardio note’, reported a rate of major adverse events in the region of 10% per patient year and a rate of death greater than  5.0% per patient year, during follow-up. These data indicate that Takotsubo cardiomyopathy is an acute condition associated with  heart failure and substantial morbidity and mortality.  Physicians should therefore be made aware that the risk of complications and a poor clinical outcome over time was previously underestimated by smaller, single centre, studies, probably due to selection bias. Another important aspect that will ned to be revised is that of the diagnostic criteria for Takotsubo cardiomyoptahy, particularly the reversibility of LV dysfunction, which may have contributed to the selection bias mentioned above, which in turn could be responsible for the underestimation of the risk associated with this condition.