Sex- and Age-Based Temporal Trends in Takotsubo Syndrome Incidence in the United States.

Abstract

HomeJournal of the American Heart AssociationVol. 10, No. 20Sex‐ and Age‐Based Temporal Trends in Takotsubo Syndrome Incidence in the United States Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toOpen AccessLetterPDF/EPUBSex‐ and Age‐Based Temporal Trends in Takotsubo Syndrome Incidence in the United States Varun K. Pattisapu, MD, Hua Hao, PhD, Yunxian Liu, PhD, Trevor‐Trung Nguyen, BS, Amy Hoang, MBS, C. Noel Bairey Merz, MD and Susan Cheng, MD, MPH Varun K. PattisapuVarun K. Pattisapu Barbra Streisand Women's Heart Center, , Smidt Heart Institute, Cedars‐Sinai Medical Center, , Los Angeles, , CA Search for more papers by this author , Hua HaoHua Hao https://orcid.org/0000-0001-5431-7984 University of Southern California Keck School of Medicine, , Los Angeles, , CA Search for more papers by this author , Yunxian LiuYunxian Liu https://orcid.org/0000-0002-3570-103X Department of Cardiology, , Smidt Heart Institute, Cedars‐Sinai Medical Center, , Los Angeles, , CA Search for more papers by this author , Trevor‐Trung NguyenTrevor‐Trung Nguyen Department of Cardiology, , Smidt Heart Institute, Cedars‐Sinai Medical Center, , Los Angeles, , CA Search for more papers by this author , Amy HoangAmy Hoang Department of Cardiology, , Smidt Heart Institute, Cedars‐Sinai Medical Center, , Los Angeles, , CA Search for more papers by this author , C. Noel Bairey MerzC. Noel Bairey Merz https://orcid.org/0000-0002-9933-5155 Barbra Streisand Women's Heart Center, , Smidt Heart Institute, Cedars‐Sinai Medical Center, , Los Angeles, , CA Department of Cardiology, , Smidt Heart Institute, Cedars‐Sinai Medical Center, , Los Angeles, , CA Search for more papers by this author and Susan ChengSusan Cheng * Correspondence to: Susan Cheng, MD, MPH, Department of Cardiology, Smidt Heart Institute, Cedars‐Sinai Medical Center, 127 San Vicente Blvd, Suite A‐3100, Los Angeles, CA 90048. E‐mail E-mail Address: [email protected] https://orcid.org/0000-0002-4977-036X Barbra Streisand Women's Heart Center, , Smidt Heart Institute, Cedars‐Sinai Medical Center, , Los Angeles, , CA Department of Cardiology, , Smidt Heart Institute, Cedars‐Sinai Medical Center, , Los Angeles, , CA Search for more papers by this author Originally published13 Oct 2021https://doi.org/10.1161/JAHA.120.019583Journal of the American Heart Association. 2021;10:e019583Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: October 13, 2021: Ahead of Print Takotsubo syndrome (TTS) is an uncommon but important cause of myocardial infarction that has been increasingly recognized in the United States.1, 2 The extent to which documented TTS incidence in the United States may have changed over time, across age groups as well as by sex, is not well understood.All data supporting the findings are publicly available through the National Inpatient Sample (NIS) database provided by the Healthcare Cost and Utilization Project.We investigated age‐ and sex‐based temporal trends in TTS incidence, using NIS3 data from years 2006 to 2017. We included patients aged ≥18 years with a primary or secondary TTS diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD‐9‐CM] code 429.83 or International Classification of Diseases, Tenth Revision, Clinical Modification [ICD‐10‐CM] code I51.81). We excluded those without coronary angiography or with coronary angiography and subsequent percutaneous coronary intervention. Per Healthcare Cost and Utilization Project analysis guidelines, we applied “trend weights” and estimated incidence (and SEs) using PROC SURVEYMEANS. We used generalized linear regression to test for differences in temporal trends across sex‐stratified age groups. All analyses were performed using SAS v9.4 and R v3.6.3. All study protocols were approved by the Cedars‐Sinai Institutional Review Board, with the requirement for individual informed consent waived.Over the total study period, we identified 135 463 documented cases of TTS. The annual incidence increased steadily in both sexes, with women contributing most cases (88.3%), especially those aged ≥50 years (Figure). In particular, we observed a significantly greater increase in TTS incidence among middle‐aged (128 cases per million per year) and older (96 cases per million per year) women compared with younger (15 cases per million per year) women (P<0.001). Increase in TTS incidence among middle‐aged (20 cases per million per year) men was also significant compared with younger (10 cases per million per year) men (P<0.001), but not significant for older (16 cases per million per year) men (P=0.082). In more granular analyses of TTS incidence by quarter year periods, we observed no appreciable difference in temporal trends across the quarters of year 2015 (ie, the transition from ICD‐9 to ICD‐10 coding). In addition, we observed that the average age of the NIS source sample remained stable for women, with a slight increase for men (0.7 year older per year) over the entire study period (Figure). Accordingly, we also observed relatively stable proportions of sex‐based age groups comprising the larger US population at risk over the entire study period (data not shown).Download figureDownload PowerPointFigure . Two decades of temporal trends in Takotsubo syndrome in the United States.Age‐ and sex‐specific temporal trends in Takotsubo syndrome hospitalizations in the United States are shown from years 2006 through 2017, in women (A) and men (B) as well as in both sexes combined (C).Consistent with reports from national and international cohorts, women have continued to contribute the vast majority of TTS diagnoses over time.2, 4 Although TTS case diagnoses have steadily increased in both sexes, and across all age groups, the increase over time has been especially pronounced among women aged ≥50 years. Notwithstanding the importance of increased recognition, advancing diagnostic techniques, and improved documentation of the TTS diagnosis, additional factors contributing to the observed temporal trends may include the following: (1) continued increase in size of the at‐risk population, which includes aging adults and aging women in particular; (2) secular changes in socioeconomic and environmental stressors that may be particularly relevant to susceptible middle‐aged and particularly older‐aged individuals; and (3) potential evolution in the nature of TTS as a disease entity, which is known to be heterogeneous in cause as well as presentation.5 Notably, potential drivers appear more relevant to older women than older men at risk, for reasons that are currently unclear. Intriguingly, the most prominent at‐risk group was women aged 50 to 74 years. This finding could be caused by the greater propensity for excess sympathetic activation in younger age, combined with a greater susceptibility to cardiac stress and injury in older age, converging in middle‐aged people at risk and particularly women.5Our analyses using NIS data were limited by dependence on appropriate ICD‐9 or ICD‐10 coding of diagnoses, procedures, and other in‐hospital measures. Notwithstanding uniform labeling of TTS codes over time and consistent results observed for temporal trends, data from before and after the ICD‐9 to ICD‐10 coding transition should be interpreted with caution. In addition, NIS data do not include biomarkers, echocardiographic measures, and angiographic measures typically used to evaluate TTS cases. Thus, follow‐up studies that can more comprehensively differentiate between TTS and alternate or overlapping diagnoses (eg, myocarditis, pericarditis, or coronary vasospasm) are warranted. Nonetheless, the availability of diagnosis data on >135 000 cases documented over a span of almost 2 decades offered ample statistical power to detect not only increasing incidence of TTS in the United States, but a steep increase among especially middle‐aged to older women. This overall trend was disproportionate to that seen in other subgroups and appears not completely explained by improvements in clinical recognition. Future studies are needed to validate and extend from our results as part of efforts to clarify the susceptibility, pathophysiological features, and outcomes related to TTS for those individuals at the highest risk.Sources of FundingThis study was funded in part by National Institutes of Health grants R01‐HL134168, R01‐HL131532, R01‐HL143227, R01‐HL142983, R01‐HL146158, and U54‐AG065141; National Center for Advancing Translational Sciences grant UL1TR000124; and the Edythe L. Broad and the Constance Austin Women's Heart Research Fellowships, the Barbra Streisand Women's Cardiovascular Research and Education Program, the Linda Joy Pollin Women's Heart Health Program, the Erika J. Glazer Women's Heart Health Project, and the Adelson Family Foundation, Cedars‐Sinai Medical Center. The funding sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.DisclosuresDr Bairey Merz reports a grant from Sanofi ACT14656; personal fees from the Bayer Advisory Board, iRhythm, and Med Intelligence; and fees paid through Cedars‐Sinai Medical Center from Abbott Diagnostics and Sanofi, all outside of the submitted work. The remaining authors have no disclosures to report.Footnotes* Correspondence to: Susan Cheng, MD, MPH, Department of Cardiology, Smidt Heart Institute, Cedars‐Sinai Medical Center, 127 San Vicente Blvd, Suite A‐3100, Los Angeles, CA 90048. E‐mail susan.[email protected]org*V.K. Pattisapu and H. Hao contributed equally.For Sources of Funding and Disclosures, see page 3.REFERENCES1 Deshmukh A, Kumar G, Pant S, Rihal C, Murugiah K, Mehta JL. Prevalence of Takotsubo cardiomyopathy in the United States. Am Heart J. 2012; 164:66–71.e1. doi: 10.1016/j.ahj.2012.03.020CrossrefMedlineGoogle Scholar2 Khera R, Light‐McGroary K, Zahr F, Horwitz PA, Girotra S. Trends in hospitalization for Takotsubo cardiomyopathy in the United States. Am Heart J. 2016; 172:53–63. doi: 10.1016/j.ahj.2015.10.022CrossrefMedlineGoogle Scholar3 Khera R, Angraal S, Couch T, Welsh JW, Nallamothu BK, Girotra S, Chan PS, Krumholz HM. Adherence to methodological standards in research using the National Inpatient Sample. JAMA. 2017; 318:2011–2018. doi: 10.1001/jama.2017.17653CrossrefMedlineGoogle Scholar4 Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, Cammann VL, Sarcon A, Geyer V, Neumann CA, et al. Clinical features and outcomes of Takotsubo (stress) cardiomyopathy. N Engl J Med. 2015; 373:929–938. doi: 10.1056/NEJMoa1406761CrossrefMedlineGoogle Scholar5 Pelliccia F, Kaski JC, Crea F, Camici PG. Pathophysiology of Takotsubo syndrome. Circulation. 2017; 135:2426–2441. doi: 10.1161/CIRCULATIONAHA.116.027121LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited BySingh T, Khan H, Gamble D, Scally C, Newby D and Dawson D (2022) Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications, Circulation, 145:13, (1002-1019), Online publication date: 29-Mar-2022. October 19, 2021Vol 10, Issue 20Article InformationMetrics Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.https://doi.org/10.1161/JAHA.120.019583PMID: 34641717 Manuscript receivedSeptember 29, 2020Manuscript acceptedAugust 23, 2021Originally publishedOctober 13, 2021 KeywordsTakotsubo syndromesex differencesmyocardial infarctionage differencesPDF download SubjectsMyocardial Infarction