COVID-19 in a Patient with Accidental Drug-Induced Neutropenia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) presents with a wide range of illness severity, from asymptomatic disease to severe acute respiratory distress syndrome (ARDS). Immunosuppression is considered a risk factor for severe COVID-19, but there are only few reports on disease progression in immunocompromised patients. CASE SUMMARY: We report the case of a 50-year-old patient with acute COVID-19 pneumonia, who had iatrogenic, clinically relevant bone marrow suppression due to accidental overdose with hydroxyurea, and decreased lung capacity due to a left-sided pneumonectomy 6 months earlier. Symptomatic treatment with oxygen supplementation and pulmonary physical therapy was initiated, and hydroxyurea was discontinued. Over 14 days, the patient's blood counts slowly recovered, and his clinical condition gradually improved, such that supplemental oxygen was no longer necessary and he could be discharged. DISCUSSION: A gradual increase in neutrophil and lymphocyte counts may be preferable to dampen a potentially detrimental immunological response triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether patients with severe COVID-19 benefit from immunosuppressive therapy should be further evaluated. LEARNING POINTS: Acute respiratory distress syndrome is a serious complication in COVID-19 and appears to be triggered by a proinflammatory cytokine storm.Immunosuppression may avoid an immune hyper-response triggered by SARS-CoV-2.

Clinical benefit of high-sensitivity cardiac troponin I in the detection of exercise-induced myocardial ischemia.

BACKGROUND: A pilot study using a novel high-sensitivity cardiac troponin I (hs-cTnI) assay suggested that cTnI might be released into blood during exercise-induced myocardial ischemia. We investigated the potential clinical value of this signal. METHODS: We included 819 patients with suspected exercise-induced myocardial ischemia referred for rest/bicycle myocardial perfusion single-photon emission computed tomography. The treating cardiologist used all available clinical information to quantify clinical judgment regarding the presence of myocardial ischemia using a visual analog scale twice: prior and after stress testing. High-sensitivity cTnI measurements were obtained before, immediately after peak stress, and 2 hours after stress testing in a blinded manner. Myocardial ischemia was adjudicated using perfusion single-photon emission computed tomography and coronary angiography findings. RESULTS: Exercise-induced myocardial ischemia was detected in 278 (34%) patients. High-sensitivity cTnI levels were significantly higher at all time points in patients with myocardial ischemia as compared with those without (P < .001 for all). Combining clinical judgment prior exercise testing with baseline hs-cTnI levels increased diagnostic accuracy as quantified by the area under the receiver operating characteristics curve (AUC) from 0.672 to 0.757 (P < .001). Combining clinical judgment after exercise testing (AUC 0.704) with baseline or poststress hs-cTnI levels also increased the diagnostic accuracy (AUC 0.761-0.771, P < .001 for all). In contrast, exercise-induced changes in hs-cTnI during exercise did not seem useful, as they were small and similar in patients with or without myocardial ischemia. CONCLUSIONS: High-sensitivity cTnI concentrations at rest and after exercise, but not its exercise-induced changes, provide substantial incremental value to clinical judgment including exercise electrocardiography regarding the presence of myocardial ischemia.

Early rule-out and rule-in of myocardial infarction using sensitive cardiac Troponin I.

BACKGROUND: It is currently unknown, whether and to what extent sensitive cardiac troponin (s-cTn) allows shortening of the time required for safe rule-out and rule-in of acute myocardial infarction (AMI). METHODS: We aimed to develop and validate early rule-out and rule-in algorithms for AMI using a thoroughly-examined and commonly used s-cTnI assay in a prospective multicenter study including 2173 patients presenting to the emergency department with suspected AMI. S-cTnI was measured in a blinded fashion at 0 h, 1 h, and 2 h. The final diagnosis was centrally adjudicated by two independent cardiologists. In the derivation cohort (n = 1496), we developed 1h- and 2h-algorithms assigning patients to "rule-out", "rule-in", or "observe". The algorithms were then prospectively validated in the validation cohort (n = 677). RESULTS: AMI was the adjudicated diagnosis in 17% of patients. After applying the s-cTnI 1h-algorithm developed in the derivation cohort to the validation cohort, 65% of patients were classified as "rule-out", 12% as "rule-in", and 23% to "observe". The negative predictive value for AMI in the "rule-out" group was 98.6% (95% CI, 96.9-99.5), the positive predictive value for AMI in the "rule-in" group 76.3% (95% CI, 65.4-85.1). Overall, 30-day mortality was 0.2% in the "rule-out" group, 1.0% in the "observe" group, and 3.0% in the "rule-in" group. Similar results were obtained for the 2h-algorithm. CONCLUSION: When used in conjunction with other clinical information including the ECG, a simple algorithm incorporating s-cTnI values at presentation and after 1h (or 2h) will allow safe rule-out and accurate rule-in of AMI in the majority of patients.

Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay.

BACKGROUND: We aimed to prospectively validate a novel 1-hour algorithm using high-sensitivity cardiac troponin T measurement for early rule-out and rule-in of acute myocardial infarction (MI). METHODS: In a multicentre study, we enrolled 1320 patients presenting to the emergency department with suspected acute MI. The high-sensitivity cardiac troponin T 1-hour algorithm, incorporating baseline values as well as absolute changes within the first hour, was validated against the final diagnosis. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data and serial measurements of high-sensitivity cardiac troponin T levels. RESULTS: Acute MI was the final diagnosis in 17.3% of patients. With application of the high-sensitivity cardiac troponin T 1-hour algorithm, 786 (59.5%) patients were classified as "rule-out," 216 (16.4%) were classified as "rule-in" and 318 (24.1%) were classified to the "observational zone." The sensitivity and the negative predictive value for acute MI in the rule-out zone were 99.6% (95% confidence interval [CI] 97.6%-99.9%) and 99.9% (95% CI 99.3%-100%), respectively. The specificity and the positive predictive value for acute MI in the rule-in zone were 95.7% (95% CI 94.3%-96.8%) and 78.2% (95% CI 72.1%-83.6%), respectively. The 1-hour algorithm provided higher negative and positive predictive values than the standard interpretation of highsensitivity cardiac troponin T using a single cut-off level (both p < 0.05). Cumulative 30-day mortality was 0.0%, 1.6% and 1.9% in patients classified in the rule-out, observational and rule-in groups, respectively (p = 0.001). INTERPRETATION: This rapid strategy incorporating high-sensitivity cardiac troponin T baseline values and absolute changes within the first hour substantially accelerated the management of suspected acute MI by allowing safe rule-out as well as accurate rule-in of acute MI in 3 out of 4 patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00470587.

Incremental value of a single high-sensitivity cardiac troponin I measurement to rule out myocardial ischemia.

BACKGROUND: The aim of this study was to investigate the value of a novel high-sensitivity cardiac troponin I measurement to rule out exercise-induced myocardial ischemia in patients without known coronary artery disease. METHODS: We included 714 patients without previously known coronary artery disease who were referred for rest/stress myocardial perfusion single photon emission tomography. All clinical information available to the treating cardiologist was used to quantify the clinical judgment regarding the presence of exercise-induced myocardial ischemia using a visual analogue scale twice: once before and once after bicycle exercise stress testing. High-sensitivity cardiac troponin I measurements were obtained before stress testing in a blinded manner. The presence of exercise-induced myocardial ischemia was adjudicated on the basis of myocardial perfusion single photon emission tomography combined with coronary angiography findings. RESULTS: Exercise-induced myocardial ischemia was detected in 167 participants (23.4%). High-sensitivity cardiac troponin I levels were significantly higher in patients with exercise-induced myocardial ischemia (4.0 ng/L [95% confidence interval, 2.8-8.6] vs 2.6 ng/L [95% confidence interval, 1.8-4.1], P < .001) and remained an independent predictor of ischemia in multivariable analysis (P < .001). Combining clinical judgment before exercise testing with high-sensitivity cardiac troponin I levels increased diagnostic accuracy as quantified by the area under the receiver operating curve from 0.64 to 0.73 (P < .001), which also tended to be superior to clinical judgment after exercise testing (0.69, P = .056). A single resting high-sensitivity cardiac troponin I measurement provided similar diagnostic accuracy as integrated clinical judgment after exercise testing including work load, as well as symptoms and electrocardiogram changes (0.70 vs 0.69, P = not significant). CONCLUSIONS: High-sensitivity cardiac troponin I measurements seem to complement noninvasive clinical assessment in patients with suspected coronary artery disease.

Prevalence, characteristics and outcome of non-cardiac chest pain and elevated copeptin levels.

OBJECTIVE: Copeptin, a quantitative marker of endogenous stress, seems to provide incremental value in addition to cardiac troponin in the early rule-out of acute myocardial infarction (AMI). Prevalence, characteristics and outcome of acute chest pain patients with causes other than AMI and elevated copeptin are poorly understood. METHODS: A total of 984 consecutive patients with non-cardiac chest pain were selected from a prospective multicentre study of acute chest pain patients presenting to the emergency department. Levels of copeptin were determined in a blinded fashion and considered elevated if above 13 pmol/L (the 97,5th centile of healthy individuals). The final diagnosis was adjudicated by two independent cardiologists. Median duration of follow-up was 756 days. RESULTS: Elevated copeptin levels were seen in 215 patients (22%). In comparison to patients with normal copeptin levels, patients with elevated levels were older, had more pre-existing cardiac and non-cardiac disorders, more silent cardiomyocyte injury and increased haemodynamic stress as quantified by levels of high-sensitivity cardiac troponin T (9.6 ng/L (3.6-18.3) vs 5.8 ng/L (2.9-9.4)) and B-type natriuretic peptide (75 ng/L (37-187) vs 35 ng/L (15-77)) (both p<0.001), more electrocardiographic abnormalities, more often an adjudicated diagnosis of gastroesophageal reflux or bronchitis/pneumonia and higher 2- year mortality (HR 2.9, 95% CI 1.5  to 5.7). The increased mortality rate seemed to be largely explained by age and comorbidities. CONCLUSIONS: Elevated levels of copeptin are present in about one in five patients with non-cardiac chest pain and are associated with aging, cardiac and non-cardiac comorbidities as well as mortality.