Elevated high-sensitivity cardiac troponin (hs-cTn) levels should be expected in about half of all patients with acute ischemic stroke (AIS). Since those patients are at risk of increased morbidity and mortality, often attributable to cardiac causes, an adequate work-up of the underlying etiology is required. This can only be achieved by a team of cardiologists and neurologists. Since underlying causes of hs-cTn elevation in AIS patients are diverse, often atypical or silent in their clinical presentation and some, such as an accompanying myocardial infarction, can be acutely life-threatening, the work-up should follow a standardized clinical algorithm. The vast majority of hs-cTn elevations are caused by non-ischemic myocardial injury associated with AIS. This work presents a practice-oriented approach to differential diagnosis with the update of the Mannheim clinical algorithm for acute ischemic stroke and troponin elevation.
UNASSIGNED: Bei etwa der Hälfte aller Patienten mit akutem ischämischem Schlaganfall (AIS) dürfen erhöhte Werte des hochsensitiven kardialen Troponins (hs-cTn) erwartet werden. Diese Patienten sind von einer erhöhten Morbidität und Mortalität bedroht, die häufig auf eine kardiale Ursache zurückzuführen ist. Daher bedarf es einer adäquaten Aufarbeitung der zugrundeliegenden Ursache, die nur im Team aus Kardiologen und Neurologen gelingen kann. Da die Ursachen vielfältig, in ihrer klinischen Präsentation beim Patienten mit AIS atypisch oder stumm und einige wie ein begleitender Myokardinfarkt akut lebensbedrohlich sein können, sollte die Abklärung einem standardisierten Algorithmus zur Differenzialdiagnostik folgen. Die überwiegende Zahl der hs-cTn-Erhöhungen wird durch nichtischämische Myokardschäden im Zusammenhang mit dem AIS verursacht. Dieser Artikel stellt einen praxisorientierten Ansatz zur Differenzialdiagnostik mit dem Update des Mannheimer Algorithmus zu akutem ischämischem Schlaganfall und Troponinerhöhung vor.

OBJECTIVE: Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays.
METHODS: A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values.
RESULTS: There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL.
CONCLUSIONS: The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.

With increasing age, patients with suspected acute coronary syndromes (ACS) and elevated high-sensitivity troponin T (HsTnT) levels, type-1 myocardial infarction (MI) is diagnosed less often, though associations among these factors, gender, and prognosis is unclear.
Patients presenting to the emergency department (ED) with potential ACS who underwent HsTnT testing were prospectively identified and followed. Diagnoses were adjudicated according to the Fourth Universal Definition of MI as follows: type-1 MI, type-2 MI, acute myocardial injury, chronic myocardial injury, and other diagnoses. Age in years was categorized: younger (<65); elderly (65-79), and very elderly (≥80).
Among 2738 patients with HsTnT measurements, 1611 were suitable for adjudication (42% ages 65 years and younger). Type-2 MI and chronic myocardial injury diagnoses were more common in those ages 65 years and older, whereas younger patients had more type-1 MI diagnoses. Late mortality rates at median 41 months (interquartile range [IQR] 10-57) were 44% (223 out of 506) in those ages 80 years and older, 22% (92 out of 423) in patients 65-79 years, and 7% (46 out of 682) in those 65 years and younger, irrespective of adjudicated diagnoses, log rank P ≤ .001. On multivariable analyses, the adjusted mortality hazard ratios for increasing HsTnT levels irrespective of diagnoses were attenuated in those age 80 years and older compared to younger patients.
Patients ages 65 years and older constituted ~60% of ED attendances of patients with suspected ACS, and more had type 2 MI and chronic myocardial injury diagnoses compared to younger patients. The relative mortality impact of HsTnT levels was lower among elderly patients irrespective of adjudicated diagnoses.

Background Cardiac troponin (cTn) permits early rule-out/rule-in of patients admitted with possible non-ST-segment-elevation myocardial infarction. In this study, we developed an admission and a 0/1 hour rule-out/rule-in algorithm for a troponin assay with measurable results in >99% of healthy individuals. We then compared its diagnostic and long-term prognostic properties with other protocols. Methods and Results Blood samples were collected at 0, 1, 3, and 8 to 12 hours from patients admitted with possible non-ST-segment-elevation myocardial infarction. cTnT (Roche Diagnostics), cTnI(Abbott) (Abbott Diagnostics), and cTnI(sgx) (Singulex Clarity System) were measured in 971 admission and 465 1-hour samples. An admission and a 0/1 hour rule-out/rule-in algorithm were developed for the cTnI(sgx) assay and its diagnostic properties were compared with cTnTESC (European Society of Cardiology), cTnI(Abbott)ESC, and 2 earlier cTnI(sgx) algorithms. The prognostic composite end point was all-cause mortality and future nonfatal myocardial infarction during a median follow-up of 723 days. non-ST-segment-elevation myocardial infarction prevalence was 13%. The novel cTnI(sgx) algorithms showed similar performance regardless of time from symptom onset, and area under the curve was significantly better than comparators. The cTnI(sgx)0/1 hour algorithm classified 92% of patients to rule-in or rule-out compared with ≤78% of comparators. Patients allocated to rule-out by the prior published 0/1 hour algorithms had significantly fewer long-term events compared with the rule-in and observation groups. The novel cTnI(sgx)0/1 hour algorithm used a higher troponin baseline concentration for rule-out and did not allow for prognostication. Conclusions Increasingly sensitive troponin assays may improve identification of non-ST-segment-elevation myocardial infarction but could rule-out patients with subclinical chronic myocardial injury. Separate protocols for diagnosis and risk prediction seem appropriate.

As assessment of patients with suspected acute coronary syndromes (ACS) in emergency departments (EDs) represents a major workload because high-sensitivity troponin (HsTn) T and I levels are frequently measured, and a minority of patients have final diagnosis of myocardial infarction (MI). We determined the relative frequencies of three patients groups: Type-I MI, Type-II MI (including acute myocardial injury).
Among 2738 consecutive patients with suspected ACS presenting to ED at Liverpool Hospital, Australia, between March and June 2014. We studied the use of invasive and pharmacological therapies, and 4-year outcomes. Adjudication of MI was according to the 4th universal definition as follows: (i) Type-I MI; (ii) Type-II MI (including acute myocardial injury), and (iii) chronic myocardial injury. Of 995 patients (36%) [median age 76 years (interquartile range 65-83)] with ≥2 HsTnT measurements and one >14 ng/L, 727 (73%) had chronic myocardial injury, 171 (17%) had Type-II MI, and 97 (9.7%) had Type-I MI; respective late mortality rates to 48 months were 33%, 43%, and 14% (P < 0.001). In-hospital angiography rates were 95% for patients with Type-I MI, [62% had percutaneous coronary intervention (PCI)] 24% (7% PCI) for those with Type-II MI, and 3.4% for chronic myocardial injury. On Cox modelling for mortality relative to Type 1 MI, adjusted hazard ratios were 1.94 [95% confidence intervals (CIs) 1.06-3.57]; P = 0.032 for Type 2 MI, and for chronic myocardial injury 1.14 (95% CIs 0.64-2.02); P = 0.66.
Among unselected patients undergoing HsTnT testing in EDs, Type-II MI including acute myocardial injury was more common than Type-I MI. Chronic myocardial injury, which occurred in three of four patients. Whereas patients with Type-II MI had higher late mortality than those with Type-I MI, after multivariable analyses mortality rates were marginally different.

BACKGROUND: The Wake-Up T2MI Registry is a retrospective cohort study investigating patients with type 2 myocardial infarction (T2MI), acute myocardial injury, and chronic myocardial injury. We aim to explore risk stratification strategies and investigate clinical characteristics, management, and short- and long-term outcomes in this high-risk, understudied population.
METHODS: From 1 January 2009 to 31 December 2010, 2846 patients were identified with T2MI or myocardial injury defined as elevated cardiac troponin I with at least one value above the 99th percentile upper reference limit and coefficient of variation of 10% (>40 ng/L) and meeting our inclusion criteria. Data of at least two serial troponin values will be collected from the electronic health records to differentiate between acute and chronic myocardial injury. The Fourth Universal Definition will be used to classify patients as having (a) T2MI, (b) acute myocardial injury, or (c) chronic myocardial injury during the index hospitalization. Long-term mortality data will be collected through data linkage with the National Death Index and North Carolina State Vital Statistics.
RESULTS: We have collected data for a total of 2205 patients as of November 2018. The mean age of the population was 65.6 ± 16.9 years, 48% were men, and 64% were white. Common comorbidities included hypertension (71%), hyperlipidemia (35%), and diabetes mellitus (30%). At presentation, 40% were on aspirin, 38% on β-blockers, and 30% on statins.
CONCLUSIONS: Improved characterization and profiling of this cohort may further efforts to identify evidence-based strategies to improve cardiovascular outcomes among patients with T2MI and myocardial injury.

Chronic myocardial injury, defined as persistent troponin levels >99th percentile values when measured with high-sensitivity assays (hs-cTn), is common. The association between chronic myocardial injury and stroke is unknown. This study aimed to investigate the association between chronic myocardial injury and stroke.
From 2011 to 2014, we included patients with chest pain and high-sensitivity cardiac troponin T levels measured concurrently but without acute conditions associated with elevated high-sensitivity cardiac troponin T levels. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for stroke in patients with stable high-sensitivity cardiac troponin T levels of 5-9, 10-14, 15-29, 30-49, and ≥50 ng/L, using <5 ng/L as reference group. Categories >14 ng/L were defined as chronic myocardial injury.
A total of 19,460 patients were included, among whom 1528 (7.9%) had chronic myocardial injury. During a mean follow-up of 2.1 years, there were 244 (1.2%) strokes. With increasing high-sensitivity cardiac troponin T levels yearly stroke rates increased from 0.24% to 4.0%. Adjusted hazard ratios with 95% confidence intervals for stroke were 1.83 (1.27-2.64) in patients with high-sensitivity cardiac troponin T levels of 5-9 ng/L, increasing to 1.95 (1.21-3.14), 3.38 (1.80-6.35), and 4.32 (1.89-9.91) in patients with high-sensitivity cardiac troponin T levels of 15-29, 30-49, and ≥50 ng/L, respectively.
Patients with chronic myocardial injury have up to a 4-fold increased risk of stroke compared with patients with high-sensitivity cardiac troponin T levels <5 ng/L. Our findings indicate that patients with any detectable high-sensitivity cardiac troponin T level, in particular those with chronic myocardial injury, have an increased risk of stroke and require further attention.