“Thinking Outside the Box” on Takotsubo Syndrome

“Thinking Outside the Box” on Takotsubo Syndrome

1832 The American Journal of Cardiology (www.ajconline.org) surgery) and the absence of common and relevant parameters normally associated with thes...

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The American Journal of Cardiology (www.ajconline.org)

surgery) and the absence of common and relevant parameters normally associated with these interventions (such as liver dysfunction or porcelain aorta) very likely weaken this predictive model because of its inability to discriminate the risk. We therefore agree with these investigators1 when claiming for a new and reliable risk score for transcatheter procedures. However, creating predictive risk models in cardiac surgery seems to be difficult. In 1995, the EuroSCORE I2 was a risk model derived from data collected from 14,799 consecutive patients in 100 European centers. Despite its thoroughness, this system overpredicted the mortality risk for patients who underwent cardiac surgery. A reason for this may be that a highly heterogenous patient group was chosen for cardiac procedures, but most had coronary artery disease, thus favoring the model in patients undergoing coronary artery surgery. Another reason may be that the model accounted for only the most common and prevalent risk factors for 30-day mortality but not for rare ones. Lastly, the surgical techniques and the postoperative patient management are constantly changing and improving over the years, which currently make the EuroSCORE I a redundant model.3 The EuroSCORE II4 was published 13 years later to overcome the previous limitations. This model is based on the results of >22,000 patients who underwent cardiac surgery in 2010 in 154 hospital centers. The core of risk factors is almost the same but 2 variables were removed, 3 were added, and 4 were defined more precisely and categorized.1 However, the promising results published by the investigators of the score4 (discrimination tested by area under the receiver operating characteristic curve was 0.81) proved again to be disappointing when the external validation of the model was assessed by independent researchers.5 The reasons why the updated scoring system have failed may be because the EuroSCORE II developers included variables that were not significantly associated with mortality by multivariate regression, they removed one of the major risk factors of EuroSCORE I (postinfarction ventricular septal rupture) because of its low incidence, and they failed to analyze other variables that could have had a major weight in an updated score.5

Thus, a reliable risk score for transcatheter aortic valve implantation techniques seems to have to be based on recent data of a homogenous sample formed by a large number of patients and should include the most clinically relevant variables. Ultimately, this predictive model is a utopic desire by cardiologists and cardiac surgeons who could identify patients who may benefit from transcatheter techniques. However, it seems to be a titanic undertaking. Rocio Diaz, MD Daniel Hernandez-Vaquero, MD, PhD Juan C. Llosa, MD, PhD Oviedo, Spain Zain Khalpey, MD, PhD Tucson, Arizona 7 April 2013

1. Durand E, Borz B, Godin M, Tron C, Litzler PY, Bessou JP, Dacher JN, Bauer F, Cribier A, Eltchaninoff H. Performance analysis of EuroSCORE II compared to the original logistic EuroSCORE and STS scores for predicting 30-day mortality after transcatheter aortic valve replacement. Am J Cardiol 2013;111:891e897. 2. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16: 9e13. 3. Osswald BR, Gegouskov V, Badowski-Zyla D, Tochtermann U, Thomas G, Hagl S, Blackstone EH. Overestimation of aortic valve replacement risk by EuroSCORE: implications for percutaneous valve replacement. Eur Heart J 2009;30:74e80. 4. Nashef SA, Roques F, Sharples LD, Nilsson J, Smith C, Goldstone AR, Lockowandt U. EuroSCORE II. Eur J Cardiothorac Surg 2012;41:734e744. 5. Barili F, Pacini D, Capo A, Rasovic O, Grossi C, Alamanni F, Di Bartolomeo R, Parolari A. Does EuroSCORE II perform better than its original versions? A multicentre validation study. Eur Heart J 2013;34:22e29. http://dx.doi.org/10.1016/j.amjcard.2013.04.006

“Thinking Outside the Box” on Takotsubo Syndrome Reading the rapidly expanding data on Takotsubo syndrome (TTS), one can sense that some stagnation has been creeping into the field. All the case studies and review articles appear identical and stereotypical in their exposition, almost “carbon copies” in the particulars they have reported, the specific references they have cited, and the pathophysiologic speculations they have attempted. Perusing the most recent entries, of the 1,607 reports

retrievable as of April 14, 2013 in PubMed, using the search term “Takotsubo” (http://www.ncbi.nlm.nih. gov/pubmed/?term¼takotsubo), one will be exposed to a fixed litany of facts and hypotheses, ending with the conclusion that we have a number of conundrums of an affliction with an unknown pathophysiology. Perhaps the following “thoughts outside the box” will be worth pursuing and could provide a needed spur to reenergize the field in new directions. First, it is unknown whether a change occurs in the topography of the left ventricular (LV) wall contraction abnormalities in individual patients during the acute phase of the clinical presentation of TTS. Second, we do not know whether the LV basal hypercontractility is more intense in the hyperacute phase of the illness than later, during the first day of hospital admission. Third, it is unknown whether gradations of the apical “ballooning” (dyskinesis) occur during the acute course of TTS in individual patients. Fourth, do all patients with TTS experience a LV intraventricular pressure gradient during the hyperacute phase of the illness and are such gradients dynamic in nature, starting as very intense and ending, in most patients, completely abolished? Fifth, we wonder whether the ST-segment elevation on the electrocardiogram is temporally associated with the LV apical “ballooning,” with simultaneous conversion from dyskinesis to akinesis, in terms of the wall contraction abnormalities, and from ST-segment elevation to T-wave inversion with QTc prolongation, in terms of the electrocardiogram. Sixth, do these conversions result from the development of myocardial edema, with resultant LV regional stiffening and akinesis? Seventh, is it possible that the apical “ballooning,” modest biomarker release, ST-segment elevation, myocardial edema, microcirculation abnormality, pathoanatomic, histochemical, and inflammatory myocardial changes, and sympathetic nervous system denervation result from the mechanical stress engendered by a LV hypercontractile base on the mechanically paralyzed LV apex and LV midventricular wall? Eighth, do some patients with TTS reach resolution within hours after the onset of the illness? Ninth, it is unknown whether mild or forme fruste cases of TTS exist. Tenth, are “TTS

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components” superimposed on the clinical phenotype of other common illnesses, including acute coronary syndromes? Eleventh, could cases of sudden cardiac death, either fatal or with successful resuscitation, in particular in men, be due to TTS? Finally, is TTS at the root of unexplained transient T-wave inversions

and/or QTc prolongation on the electrocardiogram or wall contraction abnormalities on the echocardiogram, in particular, in postmenopausal women? Researching these speculations and implementing more often than is currently the case, electrocardiography, echocardiography, and cardiac magnetic resonance


imaging might unravel the TTS conundrum sooner. John E. Madias, MD New York, New York 14 April 2013