Letters to the editor
J Cardiovasc Med 2019, 20:409–410
Takotsubo cardiomyopathy: prognostication
is affected by the underlying trigger
Nauman Khalida, Sarah Aftab Ahmadb, Evan Shlofmitza,
Affan Umercand Lovely Chhabrad a
Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, District of Columbia,b
Department of Cardiovascular Surgery, Saint Francis Medical Center, Monroe, Louisiana,c
Department of Radiology, Saint Louis University School of Medicine, St. Louis, Missouri andd
Heartland Regional Medical Center, Marion, Illinois, USA
Correspondece to Nauman Khalid, MD, MedStar Washington Hospital Center, 110 Irving St., NW, Suite 4B-1X, Washington, DC 20010, USA
Tel: +1 860 977 2879; e-mail: naumankhalid84@hotmail.com Received1 December 2018 Revised 20 December 2018 Accepted20 December 2018
To the Editor
Cusma`-Piccione et al.1 published an excellent review focusing on latest updates and clinical facts related to Takotsubo Cardiomyopathy (TC) as well as addressing its prognostication. In our opinion, it is crucial for clin-icians to be cognizant of some clinical factors which dictate the prognosis.
Prognosis depends upon the underlying trigger and thus it is important to subclassify TC into the primary and secondary forms.2 Primary TC occurs in the setting of emotional or psychological stimuli or without clearly identifiable triggers (idiopathic), whereas secondary TC occurs in the backdrop of physical stressors that activate the sympathetic nervous system with resultant catecholamine spillover and TC. Secondary TC typically occurs in hospitalized patients with conditions such as sepsis, intracranial hemorrhage or cerebrovascular acci-dent, trauma, surgery, or other critical illnesses. Second-ary TC portends much worse short- and long-term prognosis whereas primary TC usually has a benign outcome, unless complicated by cardiogenic shock. The management pathway for primary TC should be directed to the specific complications whereas in second-ary TC, the treatment should focus on both the disease process as well as the causative trigger.
The often-overlooked diastolic dysfunction is present in both acute and recovery phases of TC. A recent study reported the prevalence of diastolic dysfunction on admis-sion in 53% (108/205) of cases.3 Among these, 60% of patients had grade I diastolic dysfunction while about 12% developed grade III diastolic dysfunction. Follow-up evaluation demonstrated normalized diastolic function only in 28% of patients while the rest had unchanged or worsened diastolic impairment.3 Furthermore, recent
speckle strain imaging studies show that despite the apparent recovery of regional LV systolic function on echocardiography at follow-up, the strain assessment demonstrated subclinical LV systolic dysfunction (global longitudinal strain) and diastolic deformation abnormal-ities (untwist rate and time to peak untwisting) suggesting that these changes may persist beyond the acute phase of TC.4
The coronary microvascular dysfunction has been reported by several invasive and noninvasive studies such as prolonged Thrombolysis in Myocardial Infarction frame count, reduced apical uptake of F-18 fluorodeox-yglucose in positron-emission tomography studies, and reduced coronary flow reserve velocity.5 – 8However, the quantitative contribution by this specific mechanism as a lone contributor still remains elusive. Lastly, recent studies have demonstrated diabetes mellitus as a relative protective factor in development of TC, likely related to possible blunting of sympathetic responses in patients with diabetic autonomic neuropathy. This association remains to be further elucidated in randomized control investigations.9 – 11
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
References
1 Cusma`-Piccione M, Longobardo L, Oteri A, et al. Takotsubo cardiomyopathy: queries of the current era. J Cardiovasc Med (Hagerstown) 2018; 19:624–632.
2 Gowdar S, Chhabra L. Takotsubo cardiomyopathy outcomes should be stratified based on the triggering etiology. J Am Coll Cardiol 2016; 68:1708–1709.
3 Sun T, Ming Z, Liu Z, et al. Prevalence of diastolic function and clinical impact on long-term outcome in Takotsubo cardiomyopathy. Int J Cardiol 2017; 244:7–12.
4 Schwarz K, Ahearn T, Srinivasan J, et al. Alterations in cardiac deformation, timing of contraction and relaxation, and early myocardial fibrosis accompany the apparent recovery of acute stress-induced (Takotsubo) cardiomyopathy: an end to the concept of transience. J Am Soc Echocardiogr 2017; 30:745–755.
5 Khalid N, Iqbal I, Coram R, et al. Thrombolysis in myocardial infarction frame count in Takotsubo cardiomyopathy. Int J Cardiol 2015; 191: 107–108.
6 Khalid N, Chhabra L. Takotsubo cardiomyopathy and microcirculatory dysfunction. Nat Rev Cardiol 2015; 12:497.
7 Khalid N. Microcirculatory disorder hypothesis in Takotsubo cardiomyopathy. Int J Cardiol 2015; 195:29.
8 Khalid N, Ahmad SA, Umer A. Mechanisms of Takotsubo cardiomyopathy; role of microcirculatory dysfunction. Int Cardiovas Forum J 2016; 5:30–32. 9 Chhabra L, Khalid N, Kluger J, et al. Lupus myopericarditis as a preceding stressor for Takotsubo cardiomyopathy. Proc (Bayl Univ Med Cent) 2014; 27:327–330.
1558-2027 ß 2019 Italian Federation of Cardiology - I.F.C. All rights reserved.
10 Khalid N, Ahmad SA, Umer A, et al. Role of microcirculatory disturbances and diabetic autonomic neuropathy in Takotsubo cardiomyopathy. Crit Care Med 2015; 43:e527.
11 Khalid N, Ahmad SA, Chhabra L, et al. Autonomic dysfunction and Takotsubo cardiomyopathy. Am J Med 2015; 128: e45 – e46.
DOI:10.2459/JCM.0000000000000759
Takotsubo cardiomyopathy: prognostication
is affected by the underlying trigger: the reply
Maurizio Cusma`-Piccionea, Luca Longobardoa,
Scipione Carerja, Bijoy K. Khandheriaband Concetta Zitoa a
Department of Clinical and Experimental Medicine - Section of Cardiology, University of Messina, Azienda Ospedaliera Universitaria ‘Policlinico G. Martino’ and Universita’ degli Studi di Messina, Piazza Pugliatti, 1, Messina, Italy and b
Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke’s Medical Centers, University of Wisconsin School of Medicine and Public Health, Marcus Family Fund for Echocardiography (ECHO) Research and Education, Milwaukee, Wisconsin, USA
Correspondence to Bijoy K. Khandheria, MD, Aurora Cardiovascular Services, Aurora St. Luke’s Medical Center, 2801 W. Kinnickinnic River Parkway, Ste. 880, Milwaukee, WI 53215, USA
Tel: +1 414 649 3909; fax: +1 414 649 3578; e-mail: publishing22@aurora.org Received30 January 2019 Accepted 7 February 2019
To the Editor
We read with great interest the important notes that Khalid et al.1discussed in their letter to the Editor. First of all, the authors focused their attention on the prognosis of Takotsubo cardiomyopathy, underlining that patients with secondary Takotsubo cardiomyopathy have a much worse prognosis than patients with primary Takotsubo cardiomyopathy. This statement has a certain foundation, given that patients with secondary Takot-subo cardiomyopathy very often show severe comorbid-ities. Indeed, Templin et al.2 reported that elderly patients with emotional triggers were at a lower risk, whereas younger patients with physical triggers and acute neurologic or psychiatric diseases had an increased inci-dence of acute complications. However, it should be kept in mind that a significant percentage of severe compli-cations that affect the outcome, including left ventricular thrombosis, acute heart failure and cardiogenic shock, can be found in patients with primary Takotsubo cardiomyo-pathy too. Moreover, patients with primary Takotsubo cardiomyopathy can frequently develop diastolic dysfunc-tion, which can worsen the prognosis.3Thus, our opinion is that we are still far from completely elucidating Takotsubo cardiomyopathy pathophysiology and fully characterizing this syndrome as benign or not. This heterogeneity of the
data supports the opportunity of creating long-term regis-tries to better monitor these patients.
The development of diastolic dysfunction in patients with Takotsubo cardiomyopathy is another element that Khalid et al.1discussed in their letter. As already outlined, it has been reported that a significant percentage of patients with Takotsubo cardiomyopathy had diastolic dysfunction3,4 that usually improved during recovery.4 However, Sun et al.3 demonstrated that patients with unimproved diastolic function at recovery phase had the worst mid-term survival. Thus, this element should be carefully investigated with echocardiography and assessed during follow-up because persistent diastolic dysfunction could indicate a high-risk patient who could need close re-evaluations.
Lastly, Khalid et al.1speculated that diabetes mellitus could be a relative protective factor in the development of Takotsubo cardiomyopathy, likely related to possible blunting of sympathetic responses in patients with dia-betic autonomic neuropathy. This hypothesis has been postulated previously,5but currently did not find a full confirmation. Moreover, it would be reasonable to specu-late that the severity and chronicity of diabetes mellitus, presence of diabetes mellitus neuropathy and type and doses of anti- diabetes mellitus drugs used in the manage-ment of the patients could influence the ‘protective’ effect of diabetes mellitus. Thus, this statement should be considered with caution until broader and more standardized studies can elucidate this new element in the huge and still mysterious puzzle of Takotsubo cardiomyopathy.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
References
1 Khalid N, Ahmad SA, Shlofmitz E, et al. Takotsubo cardiomyopathy: prognostication is affected by the underlying trigger. J Cardiovasc Med 2019.
2 Templin C, Ghadri JR, Diekmann J, et al. Clinical features and outcomes of Takotsubo (stress) cardiomyopathy. N Engl J Med 2015; 373:929– 938.
3 Sun T, Ming Z, Liu Z, et al. Prevalence of diastolic function and clinical impact on long-term outcome in takotsubo cardiomyopathy. Int J Cardiol 2017; 244:7–12.
4 Kumar S, Waldenborg M, Bhumireddy P, et al. Diastolic function improves after resolution of takotsubo cardiomyopathy. Clin Physiol Funct Imaging 2016; 36:17–24.
5 Madias JE. Low prevalence of diabetes mellitus in patients with Takotsubo syndrome: a plausible ’protective’ effect with pathophysiologic connotations. Eur Heart J Acute Cardiovasc Care 2016; 5:164–170.
DOI:10.2459/JCM.0000000000000782
410 Journal of Cardiovascular Medicine 2019, Vol 20 No 6
