Early β-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy

Toshiaki Isogai; Hiroki Matsui; Hiroyuki Tanaka; Kiyohide Fushimi; Hideo Yasunaga

doi:10.1136/heartjnl-2015-308712

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Heart failure and cardiomyopathies

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Early β-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy

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Impact of Beta-blocker on The Outcome of Takotsubo Cardiomyopathy
Ibrahim El-Battrawy
Published on: 4 August 2016
Takotsubo syndrome in a Japanese patient cohort: an opportunity to tap into a great resource!
John E. Madias
Published on: 10 June 2016
Response to the letter regarding the article "Early beta-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy"
Toshiaki Isogai
Published on: 10 June 2016

Published on: 4 August 2016
Impact of Beta-blocker on The Outcome of Takotsubo Cardiomyopathy
- Ibrahim El-Battrawy
- Other Contributors:
  Martin Borggrefe and Ibrahim Akin
The article by Isogai et al. published in Heart (1) discuss the use of beta-blockers in patients diagnosed and admitted with takotsubo cardiomyopathy (TTC).
Although no effective guidelines have been prescribed for the treatment of TTC, it is suggested that a parable could be drawn by comparing the use of beta-blocker and angiotensin-converting-enzyme inhibitors in these patients with that of control subjects a...
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The article by Isogai et al. published in Heart (1) discuss the use of beta-blockers in patients diagnosed and admitted with takotsubo cardiomyopathy (TTC).
Although no effective guidelines have been prescribed for the treatment of TTC, it is suggested that a parable could be drawn by comparing the use of beta-blocker and angiotensin-converting-enzyme inhibitors in these patients with that of control subjects as well as those suffering from coronary artery disease. Beta-blockers were considered more likely to be prescribed to control subjects and patients diagnosed with coronary artery disease than to patients diagnosed with TTC. Interestingly, TTC and coronary artery disease patients received angiotensin-converting-enzyme inhibitors / angiotensin receptor blockers more often than control subjects. The concluding suggestion that the 5 year mortality is similar in both disease groups and higher than control subjects furthers our debate on this topic. The large International Takotsubo Registry reported a 5.6% mortality per-patient year (2) and the use of angiotensin-converting- enzyme inhibitors or angiotensin receptor- blockers was associated with improved survival rates. However, evidence establishing a marked survival benefit with beta-blocker use has yet to be documented. The pathogenesis of TTC is yet to be fully understood. A popular hypothesis suggests the involvement of a catecholamine-mediated mechanism. Although all these trials essentially compared the outcome of TTC with matched cohorts of patients with coronary artery disease, a relevant suggestion elucidates the role of an inflammatory and energetic- metabolic pathway as a possible pathophysiological mechanism (3). We retrospectively described a collective of 114 consecutive patients diagnosed with TTC between January 2003 and September 2015 at our institution. Our data showed that the use of beta-blocker was associated with improved survival rates over mean follow-up of 5 years (4). These novel findings necessitate the need for a standardized treatment regimen in TTC patients. We recommend the urgent need of randomized trials to clearly define treatment approaches and management strategies in takotsubo cardiomyopathy thus enabling the practice of evidence-based medicine within guidelines.
References
1. Isogai T, Matsui H, Tanaka H, et al. Early beta-blocker use and in -hospital mortality in patients with Takotsubo cardiomyopathy. Heart 2016;102(13):1029-1035. 2 . Templin C, Ghadri JR, Diekmann J, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med 2015;373(10):929-938. 3. Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, et al. Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA 2011;306(3):277-286. 4. Becher T, El-Battrawy I, Baumann S, et al. Characteristics and long- term outcome of right ventricular involvement in Takotsubo cardiomyopathy. Int J Cardiol 2016;220:371-375.
Conflict of Interest: None declared
Conflict of Interest:
None declared
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Conflict of Interest:
None declared.
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Published on: 10 June 2016
Takotsubo syndrome in a Japanese patient cohort: an opportunity to tap into a great resource!
- John E. Madias, Professor of Medicine (Cardiology)
To the Editor: The report by Isogai al,1 published online ahead of print on February 15, 2016 in the Journal, about the 2672 patients (81.5% women) who had suffered Takotsubo syndrome (TTS) between 2010 and 2014, deriving from the "Diagnosis Procedure Combination nationwide inpatient database in Japan" is an invaluable resource, since it comprises all patients with this pathology admitted to acute-care hospitals in the en...
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To the Editor: The report by Isogai al,1 published online ahead of print on February 15, 2016 in the Journal, about the 2672 patients (81.5% women) who had suffered Takotsubo syndrome (TTS) between 2010 and 2014, deriving from the "Diagnosis Procedure Combination nationwide inpatient database in Japan" is an invaluable resource, since it comprises all patients with this pathology admitted to acute-care hospitals in the entire nation, where TTS was originally described. The authors, employing score-matching and instrumental variable analyses, analyzed 2110 patients from 615 hospitals (422 who received ?-blocker therapy on hospitalization day 1 or 2, and 1688 patients who did not receive ?-blockers), and found that there was no difference between these 2 subgroups in regards to 30-day mortality.
It has been reported recently that a history of diabetes mellitus (DM) has a low prevalence in patients admitted with TTS.2 The hypothesized pathophysiological connotation of this observation is that DM may have a "protective" effect for the expression of TTS under stress, via a mediating (ameliorating) effect of the underlying diabetic neuropathy (and presumably autonomic nervous system [ANS] neuropathy), which provides a "bridling" CNS effect on "the catecholamine-mediated mechanism, which has been implicated in the pathogenesis of TTS.1 The authors, in their article's Table 1, provided details of the prevalence of chronic (malignancy, chronic pulmonary disease, chronic liver disease, chronic renal failure, peptic ulcer disease, thyrotoxicosis, rheumatic disease, psychiatric disease), and acute diseases for the unmatched, and the "1:4 propensity score-matched" groups of the entire cohort,1 but curiously have not included information about hypertension (HTN) or DM in their patients with TTS. Since the authors have access to data in the "Diagnosis Procedure Combination nationwide inpatient database in Japan", it will be of interest to provide the readers of the Journal with information on the prevalence of HTN and DM in their 2672 patients with TTS.
Conflicts of Interest None.
References
1.Isogai T, Matsui H, Tanaka H, Fushimi K, Yasunaga H. Early ?- blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy. Heart. 2016 Feb 15. pii: heartjnl-2015-308712. doi: 10.1136/heartjnl-2015-308712. [Epub ahead of print]. 2. 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 (2015) [Epub ahead of print; 11 Feb, pii: 2048872615570761].
Conflict of Interest:
None declared
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Conflict of Interest:
None declared.
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Published on: 10 June 2016
Response to the letter regarding the article "Early beta-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy"
- Toshiaki Isogai
- Other Contributors:
  Hideo Yasunaga
We would like to thank Professor Madias for his comments and interest in our study.[1] We appreciate the editors of Heart for giving us the opportunity to reply. The Diagnosis Procedure Combination database in Japan contains hospital administrative claims data and discharge abstracts representing approximately 50% of all inpatient admissions to acute-care hospitals in Japan.[2] As per the request by Professor Madias, we...
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We would like to thank Professor Madias for his comments and interest in our study.[1] We appreciate the editors of Heart for giving us the opportunity to reply. The Diagnosis Procedure Combination database in Japan contains hospital administrative claims data and discharge abstracts representing approximately 50% of all inpatient admissions to acute-care hospitals in Japan.[2] As per the request by Professor Madias, we additionally extracted data on diabetes mellitus (DM) and hypertension (HTN) in our 2672 study patients with Takotsubo cardiomyopathy (TC), using the International Classification of Diseases, 10th Revision codes (DM, E10- 14.x; HTN, I10.x). Of the 2672 patients, 367 (13.7%) had a diagnosis of DM and 1201 (44.9%) had a diagnosis of HTN as a comorbidity at admission. We also performed a 1:4 propensity score-matching analysis including DM and HTN as covariates, and obtained results consistent with those in our main analysis [1] (30-day in-hospital mortality, early beta-blocker group 2.4% [10/413] vs. control group 2.5% [42/1652]; P=1.000). The proportions of DM and HTN in our study patients with TC were comparable to those recently reported by Professor Madias.[3] However, it remains uncertain whether the prevalence of DM was lower in patients with TC compared with general population in Japan because the contemporary data on the prevalence of DM in the general population were not available in our dataset.
References 1. Isogai T, Matsui H, Tanaka H, et al. Early beta-blocker use and in- hospital mortality in patients with Takotsubo cardiomyopathy. Heart 2016 Feb 15. pii: heartjnl-2015-308712. doi:10.1136/heartjnl-2015-308712. [Epub ahead of print]. 2. Isogai T, Yasunaga H, Matsui H, et al. Out-of-hospital versus in- hospital Takotsubo cardiomyopathy: Analysis of 3719 patients in the Diagnosis Procedure Combination database in Japan. Int J Cardiol 2014;176:413-7. 3. 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;5:164-70.
Conflict of Interest:
None declared
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Conflict of Interest:
None declared.
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