Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T.

BACKGROUND: Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a noncardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMDs). METHODS: We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in 4 hospitals in 2 countries. After a cardiac workup, patients were adjudicated into 3 predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed with high-sensitivity (hs-) cTnT (hs-cTnT-Elecsys) and 3 hs-cTnI assays (hs-cTnI-Architect, hs-cTnI-Access, hs-cTnI-Vista) and compared with those of control subjects without SMD presenting with adjudicated noncardiac chest pain to the emergency department (n=3508; mean age, 55 years; 37% female). In patients with available skeletal muscle biopsies, TNNT/I1-3 mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD. RESULTS: Among 211 patients (mean age, 57 years; 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) to having mild disease, and 59 (28%) to having severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no to those with mild and severe cardiac disease for all assays (all P<0.001). hs-cTnT-Elecsys concentrations were significantly higher in patients with SMD versus control subjects (median, 16 ng/L [interquartile range (IQR), 7-32.5 ng/L] versus 5 ng/L [IQR, 3-9 ng/L]; P<0.001), whereas hs-cTnI concentrations were mostly similar (hs-cTnI-Architect, 2.5 ng/L [IQR, 1.2-6.2 ng/L] versus 2.9 ng/L [IQR, 1.8-5.0 ng/L]; hs-cTnI-Access, 3.3 ng/L [IQR, 2.4-6.1 ng/L] versus 2.7 ng/L [IQR, 1.6-5.0 ng/L]; and hs-cTnI-Vista, 7.4 ng/L [IQR, 5.2-13.4 ng/L] versus 7.5 ng/L [IQR, 6-10 ng/L]). hs-cTnT-Elecsys concentrations were above the upper limit of normal in 55% of patients with SMD versus 13% of control subjects (P<0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from individuals with noninflammatory myopathy and myositis, showed 8-fold upregulation of TNNT2, encoding cTnT (but none for TNNI3, encoding cTnI) versus control subjects (n=16, PWald<0.001); the expression correlated with pathological disease activity (R=0.59, Pt-statistic<0.001) and circulating hs-cTnT concentrations (R=0.26, Pt-statistic=0.031). CONCLUSIONS: In patients with active chronic SMD, elevations in cTnT concentrations are common and not attributable to cardiac disease in the majority. This was not observed for cTnI and may be explained in part by re-expression of cTnT in skeletal muscle. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03660969.

Incidence, clinical presentation, management, and outcome of acute pericarditis and myopericarditis.

AIMS: Little is known about the epidemiology, clinical presentation, management, and outcome of acute pericarditis and myopericarditis. METHODS AND RESULTS: The final diagnoses of acute pericarditis, myopericarditis, and non-ST-segment elevation myocardial infarction (NSTEMI) of patients presenting to seven emergency departments in Switzerland with acute chest pain were centrally adjudicated by two independent cardiologists using all information including serial measurements of high-sensitivity cardiac troponin T. The overall incidence of pericarditis and myopericarditis was estimated relative to the established incidence of NSTEMI. Current management and long-term outcome of both conditions were also assessed. Among 2533 chest pain patients, the incidence of pericarditis, myopericarditis, and NSTEMI were 1.9% (n = 48), 1.1% (n = 29), and 21.6% (n = 548), respectively. Accordingly, the estimated incidence of pericarditis and myopericarditis in Switzerland was 10.1 [95% confidence interval (95% CI) 9.3-10.9] and 6.1 (95% CI 5.6-6.7) cases per 100 000 population per year, respectively, vs. 115.0 (95% CI 112.3-117.6) cases per 100 000 population per year for NSTEMI. Pericarditis (85% male, median age 46 years) and myopericarditis (62% male, median age 56 years) had male predominance, and commonly (50% and 97%, respectively) resulted in hospitalization. No patient with pericarditis or myopericarditis died or had life-threatening arrhythmias within 30 days [incidence 0% (95% CI 0.0-4.8%)]. Compared with NSTEMI, the 2-year all-cause mortality adjusted hazard ratio of pericarditis and myopericarditis was 0.40 (95% CI 0.05-2.96), being 0.59 (95% CI 0.40-0.88) for non-cardiac causes of chest pain. CONCLUSION: Pericarditis and myopericarditis are substantially less common than NSTEMI and have an excellent short- and long-term outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, number NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.

External Validation and Extension of a Clinical Score for the Discrimination of Type 2 Myocardial Infarction.

BACKGROUND: The early non-invasive discrimination of Type 2 versus Type 1 Myocardial Infarction (T2MI, T1MI) is a major unmet clinical need. We aimed to externally validate a recently derived clinical score (Neumann) combing female sex, no radiating chest pain, and high-sensitivity cardiac troponin I (hs-cTnI) concentration ≤40.8 ng/L. METHODS: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. The final diagnoses of T2MI and T1MI were centrally adjudicated by two independent cardiologists using all information including cardiac imaging and serial measurements of hs-cTnT/I according to the fourth universal definition of MI. Model performance for T2MI diagnosis was assessed by formal tests and graphical means of discrimination and calibration. RESULTS: Among 6684 enrolled patients, MI was the adjudicated final diagnosis in 1079 (19%) patients, of which 242 (22%) had T2MI. External validation of the Neumann Score showed a moderate discrimination (C-statistic 0.67 (95%CI 0.64-0.71)). Model calibration showed underestimation of the predicted probabilities of having T2MI for low point scores. Model extension by adding the binary variable heart rate >120/min significantly improved model performance (C-statistic 0.73 (95% CI 0.70-0.76, p < 0.001) and had good calibration. Patients with the highest score values of 3 (Neumann Score, 9.9%) and 5 (Extended Neumann Score, 3.3%) had a 53% and 91% predicted probability of T2MI, respectively. CONCLUSION: The Neumann Score provided moderate discrimination and suboptimal calibration. Extending the Neumann Score by adding heart rate >120/min improved the model's performance.

Incidence and outcomes of perioperative myocardial infarction/injury diagnosed by high-sensitivity cardiac troponin I.

BACKGROUND:  Perioperative myocardial infarction/injury (PMI) diagnosed by high-sensitivity troponin (hs-cTn) T is frequent and a prognostically important complication of non-cardiac surgery. We aimed to evaluate the incidence and outcome of PMI diagnosed using hs-cTnI, and compare it to PMI diagnosed using hs-cTnT. METHODS: We prospectively included 2455 patients at high cardiovascular risk undergoing 3111 non-cardiac surgeries, for whom hs-cTnI and hs-cTnT concentrations were measured before surgery and on postoperative days 1 and 2. PMI was defined as a composite of perioperative myocardial infarction (PMIInfarct) and perioperative myocardial injury (PMIInjury), according to the Fourth Universal Definition of Myocardial Infarction. All-cause mortality was the primary endpoint. RESULTS: Using hs-cTnI, the incidence of overall PMI was 9% (95% confidence interval [CI] 8-10%), including PMIInfarct 2.6% (95% CI 2.0-3.2) and PMIInjury 6.1% (95% CI 5.3-6.9%), which was lower versus using hs-cTnT: overall PMI 15% (95% CI 14-16%), PMIInfarct 3.7% (95% CI 3.0-4.4) and PMIInjury 11.3% (95% CI 10.2-12.4%). All-cause mortality occurred in 52 (2%) patients within 30 days and 217 (9%) within 1 year. Using hs-cTnI, both PMIInfarct and PMIInjury were independent predictors of 30-day all-cause mortality (adjusted hazard ratio [aHR] 2.5 [95% CI 1.1-6.0], and aHR 2.8 [95% CI 1.4-5.5], respectively) and, 1-year all-cause mortality (aHR 2.0 [95% CI 1.2-3.3], and aHR 1.8 [95% CI 1.2-2.7], respectively). Overall, the prognostic impact of PMI diagnosed by hs-cTnI was comparable to the prognostic impact of PMI using hs-cTnT. CONCLUSIONS: Using hs-cTnI, PMI is less common versus using hs-cTnT. Using hs-cTnI, both PMIInfarct and PMIInjury remain independent predictors of 30-day and 1-year mortality.

Clinical presentation of patients with prior coronary artery bypass grafting and suspected acute myocardial infarction.

AIMS: Diagnosis of acute myocardial infarction (AMI) can be challenging in patients with prior coronary artery bypass grafting (CABG). METHODS AND RESULTS: Final diagnoses were adjudicated by two independent cardiologists using the universal definition of AMI among patients presenting to the emergency department (ED) with suspected AMI. Diagnostic accuracy of 34 chest pain characteristics (CPCs) and four electrocardiogram (ECG) signatures stratified according to the presence or absence of prior CABG were prospectively quantified. Among 4015 patients (no prior CABG: n = 3686; prior CABG: n = 329), prevalence of AMI and unstable angina were higher in patients with prior CABG (35% vs. 18%; 26% vs. 8%; both P < 0.001). Three CPCs (9%) and two electrocardiographic findings (50%) showed a different diagnostic performance (interaction P < 0.05) with loss of diagnostic value in patients with prior CABG. The diagnostic accuracy as quantified by the area under the curve (AUC) of the integrated clinical judgement was moderate to good in patients with prior CABG, and significantly lower compared to patients without prior CABG [AUC 0.80 (95% confidence interval (CI) 0.75-0.84) vs. AUC 0.87 (95% CI 0.86-0.89); P = 0.004]. Time to discharge from the ED was significantly longer in patients with prior CABG [359 (215-525) min vs. 300 (192-435) min; P < 0.001]. Key findings were confirmed in a large independent external validation cohort (n = 13 653). CONCLUSIONS: Patients with prior CABG presenting with suspected AMI have a high prevalence of AMI and unstable angina and lower diagnostic accuracy of CPCs and the ECG, possibly justifying liberal use of early coronary angiography in these vulnerable patients. CLINICALTRIALS.GOV REGISTRY: Number NCT00470587.

Características clínicas de las pericarditis y miopericarditis diagnosticadas en urgencias y factores asociados con la necesidad de hospitalización / Clinical features of pericarditis with and without myocardial involvement diagnosed in the emergency department and factors associated with need for hospitalization

Objetivo: Analizar los episodios de pericarditis aguda (PA) diagnosticados en urgencias en función de la edad y de la afectación miocárdica (miopericarditis, MioP), y determinar los factores asociados a hospitalización. Método: Estudio observacional, descriptivo, unicéntrico de casos consecutivos, con análisis retrospectivo de todos los casos diagnosticados de PA en urgencias durante 10 años (2008-2017), y revisión de las características clínicas, ECG, analíticas y ecográficas (en MioP). Se compararon características clínicas según la edad (< 50 y $ 50 años) y existencia de MioP. Los factores asociados a hospitalización (PA y MioP) se identificaron de forma cruda y ajustada por las diferencias clínicas entre grupos. Resultados: Se diagnosticaron 983 PA (34% mujeres, mediana de edad: 42 años). Los pacientes más jóvenes referían con mayor frecuencia dolor torácico (DT) punzante y modificable con la respiración o cambios posturales, y los más mayores tenían más comorbilidades cardiovasculares, refirieron más frecuentemente DT opresivo y generaron mayor sospecha de síndrome coronario agudo. Las alteraciones en el ECG (OR = 4,26; IC95% = 1,89-9,59) se asociaron a MioP (72 casos, 7%). Ingresaron 62 PA (6%), hecho asociado a antecedente de insuficiencia renal (OR = 4,83; IC95% = 1,66-14,05), DT que se modifica con movimientos respiratorios/posturales (OR = 0,54, IC95% = 0,29-0,99), taquicardia (OR = 2,29, IC95% = 1,15-4,55) y MioP (OR = 8,73, IC95% = 4,65-16,38). Ingresaron 24 MioP (33%), hecho asociado a alteraciones en la ecoscopia dirigida (protocolo FOCUS; OR = 13,72, IC95% = 1,80-104). Conclusiones: La edad puede condicionar la presentación clínica en los pacientes con PA. Las alteraciones en el segmento ST en el ECG son sugestivos de implicación miocárdica. La insuficiencia renal, la taquicardia y la MioP son factores que incrementan la decisión de hospitalización en las PA; mientras que en las MioP, las alteraciones ecográficas

Objectives: To analyze the clinical features of acute pericarditis diagnosed in the emergency department according to patient age and myocardial involvement (myopericarditis) and to determine factors associated with hospitalization. Methods: Retrospective, descriptive, observational, single-center study of consecutive patients. We analyzed all cases of pericarditis diagnosed in the emergency department over a period of 10 years (2008-2017), reviewing clinical, electrocardiographic, and laboratory findings as well as ultrasound imaging for myocardial involvement. Characteristics were analyzed by age (under 50 years or 50 or older) and presence or not of myocardial involvement. Factors associated with hospitalization for both pericarditis and myopericarditis were identified by crude and adjusted odds ratios (ORs). Results: A total of 983 patients were diagnosed with pericarditis (34% women, mean age, 42 years). The younger patients more often reported sharp chest pain modified by breathing or posture changes. Older patients had more concurrent cardiovascular disease and described chest pain as pressure (oppressive); acute coronary syndrome was suspected more often in the older patients. The only independent predictor of myopericarditis was a finding of electrocardiographic abnormalities, recorded in 72 cases (7%) (OR, 4.26; 95% CI, 1.89-9.59). Sixty-two patients (6%) were admitted for pericarditis. Associated factors were renal insufficiency (OR, 4.83; 95% CI, 1.66-14.05), pain modified by breathing or posture changes (OR, 0.54; 95% CI, 0.29-0.99), tachycardia (OR, 2.29; 95% CI, 1.15-4.55), and myopericarditis (OR, 8.73; 95% CI, 4.65-16.38). Admission of 24 patients (33%) for myocarditis was related to focused cardiac ultrasound findings (OR, 13.72; 95% CI, 1.80-104). Conclusions: Age may affect the presentation of pericarditis. ST segment abnormalities on an electrocardiogram suggest myocardial involvement. Renal insufficiency, tachycardia, and myocardial involvement are the factors associated with a decision to admit patients with pericarditis. Ultrasound findings are associated with admission for myopericarditis

Clinical features of pericarditis with and without myocardial involvement diagnosed in the emergency department and factors associated with need for hospitalization. / Características clínicas de las pericarditis y miopericarditis diagnosticadas en urgencias y factores asociados con la necesidad de hospitalización.

OBJECTIVES: To analyze the clinical features of acute pericarditis diagnosed in the emergency department according to patient age and myocardial involvement (myopericarditis) and to determine factors associated with hospitalization. MATERIAL AND METHODS: Retrospective, descriptive, observational, single-center study of consecutive patients. We analyzed all cases of pericarditis diagnosed in the emergency department over a period of 10 years (2008-2017), reviewing clinical, electrocardiographic, and laboratory findings as well as ultrasound imaging for myocardial involvement. Characteristics were analyzed by age (under 50 years or 50 or older) and presence or not of myocardial involvement. Factors associated with hospitalization for both pericarditis and myopericarditis were identified by crude and adjusted odds ratios (ORs). RESULTS: A total of 983 patients were diagnosed with pericarditis (34% women, mean age, 42 years). The younger patients more often reported sharp chest pain modified by breathing or posture changes. Older patients had more concurrent cardiovascular disease and described chest pain as pressure (oppressive); acute coronary syndrome was suspected more often in the older patients. The only independent predictor of myopericarditis was a finding of electrocardiographic abnormalities, recorded in 72 cases (7%) (OR, 4.26; 95% CI, 1.89-9.59). Sixty-two patients (6%) were admitted for pericarditis. Associated factors were renal insufficiency (OR, 4.83; 95% CI, 1.66-14.05), pain modified by breathing or posture changes (OR, 0.54; 95% CI, 0.29-0.99), tachycardia (OR, 2.29; 95% CI, 1.15- 4.55), and myopericarditis (OR, 8.73; 95% CI, 4.65-16.38). Admission of 24 patients (33%) for myocarditis was related to focused cardiac ultrasound findings (OR, 13.72; 95% CI, 1.80-104). CONCLUSION: Age may affect the presentation of pericarditis. ST segment abnormalities on an electrocardiogram suggest myocardial involvement. Renal insufficiency, tachycardia, and myocardial involvement are the factors associated with a decision to admit patients with pericarditis. Ultrasound findings are associated with admission for myopericarditis.

OBJETIVO: Analizar los episodios de pericarditis aguda (PA) diagnosticados en urgencias en función de la edad y de la afectación miocárdica (miopericarditis, MioP), y determinar los factores asociados a hospitalización. METODO: Estudio observacional, descriptivo, unicéntrico de casos consecutivos, con análisis retrospectivo de todos los casos diagnosticados de PA en urgencias durante 10 años (2008-2017), y revisión de las características clínicas, ECG, analíticas y ecográficas (en MioP). Se compararon características clínicas según la edad (< 50 y $ 50 años) y existencia de MioP. Los factores asociados a hospitalización (PA y MioP) se identificaron de forma cruda y ajustada por las diferencias clínicas entre grupos. RESULTADOS: Se diagnosticaron 983 PA (34% mujeres, mediana de edad: 42 años). Los pacientes más jóvenes referían con mayor frecuencia dolor torácico (DT) punzante y modificable con la respiración o cambios posturales, y los más mayores tenían más comorbilidades cardiovasculares, refirieron más frecuentemente DT opresivo y generaron mayor sospecha de síndrome coronario agudo. Las alteraciones en el ECG (OR = 4,26; IC95% = 1,89-9,59) se asociaron a MioP (72 casos, 7%). Ingresaron 62 PA (6%), hecho asociado a antecedente de insuficiencia renal (OR = 4,83; IC95% = 1,66-14,05), DT que se modifica con movimientos respiratorios/posturales (OR = 0,54, IC95% = 0,29-0,99), taquicardia (OR = 2,29, IC95% = 1,15-4,55) y MioP (OR = 8,73, IC95% = 4,65-16,38). Ingresaron 24 MioP (33%), hecho asociado a alteraciones en la ecoscopia dirigida (protocolo FOCUS; OR = 13,72, IC95% = 1,80-104). CONCLUSIONES: La edad puede condicionar la presentación clínica en los pacientes con PA. Las alteraciones en el segmento ST en el ECG son sugestivos de implicación miocárdica. La insuficiencia renal, la taquicardia y la MioP son factores que incrementan la decisión de hospitalización en las PA; mientras que en las MioP, las alteraciones ecográficas.