Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

Abstract

Cardiac alterations are frequently observed after acute neurological disorders. Takotsubo syndrome (TTS) represents an acute heart failure syndrome and is increasingly recognized as part of the spectrum of cardiac complications observed after neurological disorders. A systematic investigation of TTS patients with neurological disorders has not been conducted yet. The aim of the study was to expand insights regarding neurological disease entities triggering TTS and to investigate the clinical profile and outcomes of TTS patients after primary neurological disorders. The International Takotsubo Registry is an observational multicenter collaborative effort of 45 centers in 14 countries (ClinicalTrials.gov, identifier NCT01947621). All patients in the registry fulfilled International Takotsubo Diagnostic Criteria. For the present study, patients were included if complete information on acute neurological disorders were available. 2402 patients in whom complete information on acute neurological status were available were analyzed. In 161 patients (6.7%) an acute neurological disorder was identified as the preceding triggering factor. The most common neurological disorders were seizures, intracranial hemorrhage, and ischemic stroke. Time from neurological symptoms to TTS diagnosis was ≤ 2 days in 87.3% of cases. TTS patients with neurological disorders were younger, had a lower female predominance, fewer cardiac symptoms, lower left ventricular ejection fraction, and higher levels of cardiac biomarkers. TTS patients with neurological disorders had a 3.2-fold increased odds of in-hospital mortality compared to TTS patients without neurological disorders. In this large-scale study, 1 out of 15 TTS patients had an acute neurological condition as the underlying triggering factor. Our data emphasize that a wide spectrum of neurological diseases ranging from benign to life-threatening encompass TTS. The high rates of adverse events highlight the need for clinical awareness.

Conflict of interest statement

Dr. Nolte received research grants from German Ministry of Research and Education (BMBF), German Center for Neurodegenerative Diseases (DZNE), German Center for cardiovascular Research (DZHK) and speaker and/or consultation fees from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer Pharma, Alexion, Abbott and W.L. Gore and Associates, all outside the submitted work. Dr. Endres reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis, Pfizer, all outside the submitted work. Dr. Templin reports receiving fees outside the submitted work for serving on advisory boards from Abbott Vascular, Astra Zeneca, Boston Scientific, Fresenius Medical Care, The Medicines Company fees for serving on steering boards from Sanofi-Aventis, serving as a consultant for Schnell Medical, travel support from Abbott Vascular, Biosensors, Boston Scientific, Edwards Lifesciences, and Medtronic, and research grant support from Abbott Vascular and Biosensors, all outside the submitted work. All other authors have nothing to disclose.

© 2021. The Author(s).

Figures

Figure 1

Study population. *7 patients had overlap of 2 acute neurological conditions and were classified twice: 2 with focal onset seizure and ischemic stroke, 2 with generalized onset seizure and PRES, 1 with status epilepticus and PRES, 1 with status epilepticus and SAH, and 1 with generalized onset seizure and SAH. InterTAK Registry International Takotsubo Registry, PRES Posterior reversible encephalopathy syndrome, SAH Subarachnoid hemorrhage.

Figure 2

Time link between neurological disorders and takotsubo syndrome. Of the 150 patients included in the analysis median time from neurological disorders to TTS was 0 (IQR 0–1) days. Notably, time from neurological disorder to TTS was less than 2 days in 87.3% of cases. In 62% of cases the neurologic event and TTS were diagnosed on the same day, while 38% of patients were already hospitalized for the underlying neurologic conditions and TTS diagnosed during the clinical course. Numbers in boxes are the number of patients diagnosed with neurological disorders on the respective day. X-axis: days from neurological event to TTS. Y-axis: different types of neurological disorders triggering TTS. 7 patients with overlap of 2 acute neurological conditions and were excluded (2 with focal onset seizure and ischemic stroke, 2 with generalized onset seizure and PRES, 1 with status epilepticus and PRES, 1 with status epilepticus and SAH, and 1 with generalized onset seizure and SAH). In 4 cases the exact time of onset of neurological disorders was unknown (1 patient with subarachnoid hemorrhage, 1 patient with ischemic stroke, 1 patient with unknown onset seizure, and 1 patient with left frontal lobe tumor with progressive aphasia). IQR Interquartile range, PRES Posterior reversible encephalopathy syndrome, SAH Subarachnoid hemorrhage, TTS Takotsubo syndrome.

Figure 3

Factors associated with in-hospital mortality. Acute neurological disorders, left ventricular ejection fraction  10 × 103 cells/µ were identified as factors associated with in-hospital mortality. Bpm beats per minute; C.I. confidence interval; LVEF left ventricular ejection fraction; OR odds ratio; ULN upper limit of normal; WBC white blood cell count. Errors bars indicate 95% confidence intervals. Black indicates statistically significant variables, while grey is not significant.