Aims
Concern has been raised that treatment with angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers may increase the expression of angiotensin‐converting enzyme 2 (ACE2), ...which acts as the entry receptor for SARS‐CoV‐2, and lead to an increased risk of death from SARS‐CoV‐2. We aimed to address this concern by evaluating the in vivo relationship of treatment with ACE inhibitors and angiotensin receptor blockers (ARB) with circulating plasma concentrations of ACE2 in a large cohort of patients with established cardiovascular disease (n = 1864) or cardiovascular risk factors (n = 2144) but without a history of heart failure.
Methods and results
Angiotensin‐converting enzyme 2 was measured in 4008 patients (median age 68, 33% women, 31% on ACE‐inhibitors, 31% on ARB) using the SOMAscan proteomic platform (SomaLogic Inc, Colorado, USA). Plasma concentration of ACE2 was comparable in 1250 patients on ACE inhibitors (mean 5.99) versus patients without ACE inhibitors (mean 5.98, P = 0.54). Similarly, plasma concentration of ACE2 was comparable in 1260 patients on ARB (mean 5.99) versus patients without ARB (mean 5.98, P = 0.50). Plasma concentration of ACE2 was comparable in 2474 patients on either ACE inhibitors or ARB (mean 5.99) versus patients without ACE inhibitors or ARB (mean 5.98, P = 0.31). Multivariable quantile regression model analysis confirmed the lack of association between treatment with ACE inhibitors or ARB and ACE2 concentrations. Body mass index showed the only positive association with ACE2 plasma concentration (effect 0.015, 95% confidence interval 0.002 to 0.028, P = 0.024).
Conclusions
In a large cohort of patients with established cardiovascular disease or cardiovascular risk factors but without heart failure, ACE inhibitors and ARB were not associated with higher plasma concentrations of ACE2.
The novel high-sensitivity cardiac troponin (hs-cTn) 0h/1h-algorithm substantially improves the early triage of patient's assigned “rule-out” or “rule-in” of acute myocardial infarction (AMI), while ...diagnostic uncertainty remains in that 25–30% of patients assigned to “observe”. We aimed to better characterize these patients.
In a prospective multicenter diagnostic study, we applied the hs-cTnT 0h/1h-algorithm in 2213 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists using all available information. Survival at 720-days was the prognostic endpoint. Findings were validated using a hs-cTnI 0h/1h-algorithm.
Twenty-four percent (n=523) of patients were assigned to “observe” by the hs-cTnT 0h/1h-algorithm. These patients differed significantly in multiple characteristics from “rule-out” and “rule-in” patients: they were older, in 75% male, and very often (57%) had pre-existing coronary artery disease (CAD). Diagnostic uncertainty for the presence of an AMI/UA was high. Only 39% of patients were suitable for coronary computed tomography angiography (CCTA). The most common final adjudicated diagnoses were non-cardiac disease (38%), non-coronary cardiac disease (24%), unstable angina (UA, 21%), and AMI (15%). Absolute hs-cTnT-changes within 3h had the highest diagnostic accuracy for AMI (AUC 0.86). Cumulative 720-day survival rate was 86%, which was significantly lower as compared to “rule-out” (p<0.001) and comparable to “rule-in” (p=ns). Findings were similar for the hs-cTnI “observe” zone.
“Observe” patients are typically elderly men with pre-existing CAD and high long-term mortality. Absolute hs-cTn-changes within 3h, functional stress imaging and coronary angiography are the key diagnostic modalities.
What Cardiologists Should Know About Copeptin Rubini Gimenez, Maria; Wildi, Karin; Mueller, Christian
Revista española de cardiología (English ed.),
July 2014, 2014-Jul, 2014-07-00, 20140701, Letnik:
67, Številka:
7
Journal Article
Release kinetics of high-sensitivity cardiac troponin (hs-cTn) T and I in patients with acute myocardial infarction (AMI) are incompletely understood. We aimed to assess whether hs-cTnT/I release in ...early AMI is near linear.
In a prospective diagnostic multicenter study the acute release of hs-cTnT and hs-cTnI within 1 and 2hours from presentation to the emergency department was quantified using 3 hs-cTnT/I assays in patients with suspected AMI. The primary endpoint was correlation between hs-cTn changes from presentation to 1 hour vs changes from presentation to 2hours, among all AMI patients and different prespecified subgroups. The final diagnosis was adjudicated by 2 independent cardiologists, based on serial hs-cTnT from the serial study blood samples and additional locally measured hs-cTn values.
Among 2437 patients with complete hs-cTnT data, AMI was the adjudicated diagnosis in 376 patients (15%). For hs-cTnT, the correlation coefficient between 0- to 1-hour change and 0- to 2 hour change was 0.931 (95%CI, 0.916-0.944), P <.001. Similar findings were obtained with hs-cTnI (Architect) with correlation coefficients between 0- to 1-hour change and 0- to 2 hour change of 0.969 and hs-cTnI (Centaur) of 0.934 (P <.001 for both). Findings were consistent among type 1 and type 2 AMI and in the subgroup of patients presenting very early after chest pain onset.
Patients presenting with early AMI showed a near linear release of hs-cTnT and hs-cTnI. This near linearity provides the pathophysiological basis for rapid diagnostic algorithms using 0- to 1-hour changes as surrogates for 0- to 2 hour or 0- to 3 hour changes.
Registered at ClinicalTrials.gov (Identifier: NCT00470587).
La cinética de liberación de troponinas cardiacas ultrasensibles (Tnc-us) T e I en pacientes con sospecha de infarto agudo de miocardio (IAM) se desconoce completamente a día de hoy. Nuestro objetivo fue evaluar si la liberación de Tnc-us T/I en las fases iniciales del IAM sigue un patrón linear.
Estudio multicéntrico prospectivo diagnóstico donde se evaluó la liberación aguda de Tnc-us T/I durante la primera y segunda hora tras la presentación en servicios de urgencias utilizando 3 ensayos diferentes de Tnc-us T/I en pacientes con sospecha de IAM. El objetivo principal del estudio fue la correlación entre los cambios de valores de Tnc-us durante la presentación y 1h con respecto a los cambios durante la presentación y 2h en pacientes con IAM y diferentes subgrupos pre-especificados. El diagnóstico final fue adjudicado por 2 cardiólogos independientes, basándose en los valores seriados de Tnc-us T de las muestras del estudio y los valores adicionales de Tnc-us utilizados localmente.
Entre los 2.437 pacientes con todas las muestras disponibles de Tnc-usT, el IAM fue el diagnóstico final en 376 pacientes (15%). Para Tnc-usT el coeficiente de correlación entre los cambios 0/1h y 0/2h fue 0,931 (IC95%, 0,916-0,944), p <0,001. Resultados similares se obtuvieron con Tnc-usI (Architect) con coeficiente de correlación de 0,969 y con Tnc-usI (Centaur) con coefficiente de correlación de 0,934 (p <0,001 para los dos). Los resultados fueron consistentes entre los IAM tipo 1 y 2 y entre el subgrupo de pacientes con una presentación temprana tras el inicio del dolor torácico.
Pacientes que presentan en la fase temprana de IAM muestran una linearidad en la liberación de Tnc-usT y Tnc-usI. Esta linearidad ofrece la base fisiopatológica para usar con seguridad los algoritmos 0/1h anticipando los cambios que se producirán durante 0/2h y 0/3h.
Registrado en ClinicalTrials.gov (Identificador: NCT00470587).
While prolongation of QRS duration and QTc interval during acute myocardial infarction (AMI) has been reported in animals, limited data is available for these readily available electrocardiography ...(ECG) markers in humans.
Diagnostic and prognostic value of QRS duration and QTc interval in patients with suspected AMI in a prospective diagnostic multicentre study were prospectively assessed. Digital 12-lead ECGs were recorded at presentation. QRS duration and QTc interval were automatically calculated in a blinded fashion. Final diagnosis was adjudicated by two independent cardiologists. The prognostic endpoint was all-cause mortality during 24 months of follow-up.
Among 4042 patients, AMI was the final diagnosis in 19% of patients. Median QRS duration and median QTc interval were significantly greater in patients with AMI compared to those with other final diagnoses (98 ms IQR 88-108 vs. 94 ms IQR 86-102 and 436 ms IQR 414-462 vs. 425 ms IQR 407-445, p < 0.001 for both comparisons). The diagnostic value of both ECG signatures however was only modest (AUC 0.56 and 0.60). Cumulative mortality rates after 2 years were 15.9% vs. 5.6% in patients with a QRS > 120 ms compared to a QRS duration ≤ 120 ms (p < 0.001), and 11.4% vs. 4.3% in patients with a QTc > 440 ms compared to a QRS duration ≤ 440 ms (p < 0.001). After adjustment for age and important ECG and clinical parameters, the QTc interval but not QRS duration remained an independent predictor of mortality.
Prolongation of QRS duration > 120 ms and QTc interval > 440 ms predict mortality in patients with suspected AMI, but do not add diagnostic value.
Background
Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. ...Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD.
Methods
BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures.
Results
Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure,
p
= 0.09), systemic inflammation (IL-6 -
p
= 0.025, IL-8 -
p
= 0.002) and cardiac injury (cardiac troponin I,
p
= 0.048), requiring vasopressor support (vasopressor dependency index, VDI,
p
= 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI -
p
= 0.592, heart rate -
p
= 0.747) and metabolic (blood lactate,
p
= 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures.
Conclusions
We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation.
Background
Hypoxia precedes cardiomyocyte necrosis in acute myocardial infarction (AMI). We therefore hypothesized that uric acid – as a marker of oxidative stress and hypoxia – might be useful in ...the early diagnosis and risk stratification of patients with suspected AMI.
Materials and methods
In this prospective observational study, uric acid was measured at presentation in 892 consecutive patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by two independent cardiologists. Patients were followed 24 months regarding mortality. Primary outcome was the diagnosis of AMI, secondary outcome was short‐ and long‐term mortality.
Results
Uric acid at presentation was higher in patients with AMI than in patients without (372 μM vs. 336 μM; P < 0·001). The diagnostic accuracy of uric acid for AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0·60 (95%Cl 0·56–0·65). When added to cardiac troponin T (cTnT), uric acid significantly increased the AUC of cTnT from 0·89 (95%Cl 0·85–0·93) to 0·92 (95%Cl 0·89–0·95, P = 0·020 for comparison). Cumulative 24‐month mortality rates were 2·2% in the first, 5·4% in the second and the third and 15·6% in the fourth quartile of uric acid (P < 0·001 for log‐rank). Uric acid predicted 24‐month mortality independently. Adding uric acid to TIMI and GRACE risk score improved their prognostic accuracy as shown by an integrated discrimination improvement of 0·04 (P = 0·007) respective 0·02 (P = 0·021).
Conclusions
Uric acid, an inexpensive widely available biomarker, improves both the early diagnosis and risk stratification of patients with suspected AMI.
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