Cardiac Troponin T and severity of cerebral white matter lesions in acute ischemic stroke

In the literature, there is evidence of an association between cardiac diseases and clinical cognitive impairment as well as subclinical brain injury. We examined whether there is a link between elevated cardiac troponin levels (hs-cTnT) as a marker of subclinical myocardial injury and severity of white matter lesions (WML) as a marker of subclinical brain injury in stroke patients since those patients are a high-risk population in terms of both cognitive decline and cardiac comorbidity. We conducted a retrospective analysis of consecutive acute ischemic stroke patients admitted to Charité-University Hospital, Berlin from 2011-2013. All included participants underwent 3T-cMRI and serial hs-cTnT measurements as part of the clinical routine. Severity of WML was graded using the age- related white matter severity score (ARWMS). Patients with hs-cTnT >52ng/l or dynamic change of hs- cTnT >50%, which may indicate acute myocardial damage, were excluded. We performed unadjusted and adjusted quantile regression models to determine whether there is an association between hs- cTnT (dichotomized at the 99th percentile of a healthy reference population, 14ng/l) and WML. The data of 860 patients were examined (median age 73 years, 44.8% female, median ARWMS 6). In patients with elevated hs-cTnT, WML were more severe than in patients with normal hs-cTnT (median ARWMS 8 vs. 5, adjusted beta for the 50th percentile 1.12, 95% CI 0.41-1.84). There was a more pronounced association between WML and elevated hs-cTnT in patients with moderate to severe WML (beta 1.77, 95% CI 0.26-3.27 for 80th percentile). Further division of patients with elevated hs- cTnT values showed that the association was independent of the severity of hs-cTnT elevation. Our data indicate an association between subclinical myocardial injury and severity of white matter lesions. Longitudinal studies are needed to assess the impact of risk-modifying therapy on the prevention of cognitive impairment and the value of hs-cTnT as a parameter for therapy monitoring.In der Literatur finden sich Hinweise auf einen Zusammenhang zwischen kardialen Erkrankungen und sowohl kognitiver Beeinträchtigung als auch subklinischer Schädigung des Gehirns. In dieser Arbeit wurde untersucht, ob ein Zusammenhang zwischen einer Erhöhung des kardialen Troponins (hs-cTnT) als Marker einer subklinischen Myokardschädigung und dem Schweregrad zerebraler „white matter lesions“ (WML) als Marker einer subklinischen Hirnschädigung bei Schlaganfallpatienten besteht. Es handelt sich um eine retrospektive Auswertung von Patienten mit akutem ischämischem Schlaganfall, die von 2011-2013 am Campus Benjamin Franklin stationär behandelt worden sind. Bei allen eingeschlossenen Patienten wurden im Rahmen der klinischen Routine ein 3T-cMRT und serielle Bestimmungen der Troponinwerte durchgeführt. Der Schweregrad der zerebraler WML wurde anhand des „age-related white matter severity scores“ (ARWMS) bestimmt. Patienten mit einem hs-cTnT > 52 ng/l oder einer Änderung des hs-cTnT > 50% in seriellen Kontrollen wurden ausgeschlossen, da diese Konstellationen auf einen akuten Myokardschaden hindeuten. Es wurden unadjustierte und adjustierte Quantilsregressionsanalysen durchgeführt, um festzustellen, ob ein Zusammenhang zwischen erhöhtem hs-cTnT (cut-off 14 ng/l, entsprechend der 99. Perzentile einer gesunden Kontrollpopulation) und WML besteht. Insgesamt wurden die Daten von 860 Patienten untersucht (medianes Alter 73 Jahre, 44.8% weibliches Geschlecht, medianer ARWMS 6). Patienten mit erhöhtem hs-cTnT hatten ein größeres Ausmaß an WML als Patienten mit normwertigem hs-cTnT (medianer ARWMS 8 vs. 5, adjustiertes beta für die 50. Perzentile 1.12, 95% CI 0.41-1.84). Der Zusammenhang zwischen WML und erhöhtem hs-cTnT war stärker bei Patienten mit höherem Schweregrad an WML (beta 1.77, 95% CI 0.26-3.27 für die 80. Perzentile). Eine weitere Aufteilung der Studienpopulation nach hs-cTnT-Werten zeigte, dass der Zusammenhang unabhängig vom Ausmaß der hs-cTnT-Erhöhung war. Die Ergebnisse weisen auf einen Zusammenhang zwischen subklinischem Myokardschaden und zerebralen WML hin. Es braucht longitudinale Studien, um den Einfluss einer risikomodifizierenden Therapie zur Vorbeugung einer kognitiven Einschränkung und den möglichen Stellenwert von Troponin als Marker eines Therapieerfolgs zu untersuchen

Heart Rate Variability and Recurrent Stroke and Myocardial Infarction in Patients With Acute Mild to Moderate Stroke

Objectives: In patients with acute ischemic stroke, reduced heart rate variability (HRV) may indicate poor outcome. We tested whether HRV in the acute phase of stroke is associated with higher rates of mortality, recurrent stroke, myocardial infarction (MI) or functional outcome. Materials and Methods: Patients with acute mild to moderate ischemic stroke without known atrial fibrillation were prospectively enrolled to the investigator-initiated Heart and Brain interfaces in Acute Ischemic Stroke (HEBRAS) study (NCT 02142413). HRV parameters were assessed during the in-hospital stay using a 10-min section of each patient's ECG recording at day- and nighttime, calculating time and frequency domain HRV parameters. Frequency of a combined endpoint of recurrent stroke, MI or death of any cause and the respective individual events were assessed 12 months after the index stroke. Patients' functional outcome was measured by the modified Rankin Scale (mRS) at 12 months. Results: We included 308 patients (37% female, median NIHSS = 2 on admission, median age 69 years). Complete follow-up was achieved in 286/308 (93%) patients. At 12 months, 32 (9.5%), 5 (1.7%) and 13 (3.7%) patients had suffered a recurrent stroke, MI or death, respectively. After adjustment for age, sex, stroke severity and vascular risk factors, there was no significant association between HRV and recurrent stroke, MI, death or the combined endpoint. We did not find a significant impact of HRV on a mRS ≥ 2 12 months after the index stroke. Conclusion: HRV did not predict recurrent vascular events in patients with acute mild to moderate ischemic stroke

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

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

PRediction of acute coronary syndrome in acute ischemic StrokE (PRAISE) – protocol of a prospective, multicenter trial with central reading and predefined endpoints

Background: Current guidelines recommend measurement of troponin in acute ischemic stroke (AIS) patients. In AIS patients, troponin elevation is associated with increased mortality and worse outcome. However, uncertainty remains regarding the underlying pathophysiology of troponin elevation after stroke, particularly regarding diagnostic and therapeutic consequences. Troponin elevation may be caused by coronary artery disease (CAD) and more precisely acute coronary syndrome (ACS). Both have a high prevalence in stroke patients and contribute to poor outcome. Therefore, better diagnostic algorithms are needed to identify those AIS patients likely to have ACS or other manifestations of CAD. Methods/design: The primary goal of the "PRediction of Acute coronary syndrome in acute Ischemic StrokE" (PRAISE) study is to develop a diagnostic algorithm for prediction of ACS in AIS patients. The primary hypothesis will test whether dynamic high-sensitivity troponin levels determined by repeat measurements (i.e., "rise or fall-pattern") indicate presence of ACS when compared to stable (chronic) troponin elevation. PRAISE is a prospective, multicenter, observational trial with central reading and predefined endpoints guided by a steering committee. Clinical symptoms, troponin levels as well as findings on electrocardiogram, echocardiogram, and coronary angiogram will be recorded and assessed by central academic core laboratories. Diagnosis of ACS will be made by an endpoint adjudication committee. Severe adverse events will be evaluated by a critical event committee. Safety will be judged by a data and safety monitoring board. Follow-up will be conducted at three and twelve months and will record new vascular events (i.e., stroke and myocardial infarction) as well as death, functional and cognitive status. According to sample size calculation, 251 patients have to be included. Discussion: PRAISE will prospectively determine the frequency of ACS and characterize cardiac and coronary pathologies in a large, multicenter cohort of AIS patients with troponin elevation. The findings will elucidate the origin of troponin elevation, shed light on its impact on necessary diagnostic procedures and provide data on the safety and diagnostic yield of coronary angiography early after stroke. Thereby, PRAISE will help to refine algorithms and develop guidelines for the cardiac workup in AIS. Trial registration: NCT03609385 registered 1st August 2018

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.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.The International Takotsubo Registry was supported by the Biss Davies Charitable Trust. Dr. Scheitz has been supported by the Corona Foundation. Dr. Templin has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation.info:eu-repo/semantics/publishedVersio

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

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

Coronary angiography in acute ischemic stroke patients: frequency and determinants of pathological findings in a multicenter cohort study.

BACKGROUND Myocardial injury as indicated by cardiac troponin elevation is associated with poor prognosis in acute stroke patients. Coronary angiography (CAG) is the diagnostic gold-standard to rule-out underlying obstructive coronary artery disease (CAD) in these patients. However, weighing risks and benefits of coronary angiography (CAG) against each other is particularly challenging, because stroke patients undergoing CAG may have a higher risk for secondary intracranial bleeding. Current guidelines remain vague. Thus, the aim of this study was to analyze frequency of pathological findings of CAG and associated clinical factors. METHODS We analyzed indications and frequency of CAG performed in acute ischemic stroke patients in clinical routine in two European tertiary care hospitals from 2011 to 2018. All data were obtained retrospectively. Multiple logistic regression analyses were performed to identify variables associated with absence of obstructive coronary artery disease defined as presence of at least one coronary vessel stenosis ≥ 50%. RESULTS A total of 139 AIS patients underwent CAG. Frequent indications for CAG were suspected acute coronary syndrome (N = 114) or scheduled cardiac surgery (N = 25). Acute coronary stenting was applied in 51/139 patients. Among patients with suspected acute coronary syndrome, no obstructive CAD was found in 27/114 patients. Absence of obstructive CAD was associated with insular cortex lesions, no clinical symptoms for ACS, less than three cardiovascular risk factors, younger age and normal wall motion. CONCLUSION Several variables suggest absence of CAD in AIS patients and may help in clinical decision making in stroke patients with myocardial injury

Sex Differences in Outcomes of Acute Myocardial Injury After Stroke

Background Sex differences in presentation, treatment, and prognosis of cardiovascular disorders are well recognized. Although an association between acute myocardial injury and mortality after ischemic stroke has been demonstrated, it is unclear whether prevalence and outcome of poststroke acute myocardial injury differ between women and men. Methods and Results We prospectively screened consecutive patients with acute ischemic stroke and serial high‐sensitivity cardiac troponin T measurements admitted to our center. Acute myocardial injury was defined as at least 1 high‐sensitivity cardiac troponin T value above the upper reference limit (14 ng/L) with a rise/fall of >20%. Rates of acute myocardial injury were also calculated using sex‐specific high‐sensitivity cardiac troponin T cutoffs (women upper reference limit, 9 ng/L; men upper reference limit, 16 ng/L). Logistic regression analyses were performed to evaluate the association between acute myocardial injury and outcomes. Of 1067 patients included, 494 were women (46%). Women were older, had a higher rate of known atrial fibrillation, were more likely to be functionally dependent before admission, had higher stroke severity, and more often had cardioembolic strokes (all P values <0.05). The crude prevalence of acute myocardial injury differed by sex (29% women versus 23% men, P=0.024). Statistically significant associations between acute myocardial injury and outcomes were observed in women (7‐day in‐hospital mortality: adjusted odds ratio [aOR], 3.2 [95% CI, 1.07–9.3]; in‐hospital mortality: aOR, 3.3 [95% CI, 1.4–7.6]; modified Rankin Scale score at discharge: aOR, 1.6 [95% CI, 1.1–2.4]) but not in men. The implementation of sex‐specific cutoffs did not increase the prognostic value of acute myocardial injury for unfavorable outcomes. Conclusions The prevalence of acute myocardial injury after ischemic stroke and its association with mortality and greater disability might be sex‐dependent. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03892226

New Cerebral Microbleeds After Catheter‐Based Structural Heart Interventions: An Exploratory Analysis

Background Cerebral microbleeds (CMBs) are increasingly recognized as “covert” brain lesions indicating increased risk of future neurological events. However, data on CMBs in patients undergoing catheter‐based structural heart interventions are scarce. Therefore, we assessed occurrence and predictors of new CMBs in patients undergoing catheter‐based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Methods and Results We conducted an exploratory analysis using data derived from 2 prospective, observational studies. Eligible patients underwent cerebral magnetic resonance imaging (3 Tesla) examinations and cognitive tests (using the Montreal Cognitive Assessment) before and after catheter‐based left atrial appendage closure and percutaneous mitral valve repair. Forty‐seven patients (53% men; median age, 77 years) were included. New CMBs occurred in 17 of 47 patients (36%) following catheter‐based structural heart interventions. Occurrences of new CMBs did not differ significantly between patients undergoing catheter‐based left atrial appendage closure and percutaneous mitral valve repair (7/25 versus 10/22; P=0.348). In univariable analysis, longer procedure time was significantly associated with new CMBs. Adjustment for heparin attenuated this association (adjusted odds ratio [per 30 minutes]: 1.77 [95% CI, 0.92–3.83]; P=0.090). Conclusions New CMBs occur in approximately one‐third of patients after catheter‐based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Our data suggest that longer duration of the procedure may be a risk factor for new CMBs. Future studies in larger populations are needed to further investigate their clinical relevance. Clinical Trial Registration German Clinical Trials Register: DRKS00010300 (https://drks.de/search/en/trial/DRKS00010300); ClinicalTrials.gov : NCT03104556 (https://clinicaltrials.gov/ct2/show/NCT03104556?term=NCT03104556&draw=2&rank=1)

Toward Individual Treatment in Cervical Artery Dissection: Subgroup Analysis of the TREAT-CAD Randomized Trial.

OBJECTIVE Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. METHODS This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. RESULTS All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. INTERPRETATION Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024