COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the ...correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19.
We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT > 14 ng/L, the upper 99th percentile. Levels of NT-proBNP > 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV).
Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87).
Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.
Aims
Cardiac amyloidosis (CA) is associated with an elevation of natriuretic peptides and troponins, predicting outcome. Nevertheless, the diagnostic yield of these biomarkers has not been ...extensively investigated. This study aimed to evaluate the diagnostic performance for CA of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity troponin T (hs‐TnT).
Methods and results
Patients with suspected CA (n = 1149) underwent a diagnostic work‐up in three centres in Italy, France (n = 343, derivation cohort), and United Kingdom (n = 806, validation cohort). Biomarker values with either 100% sensitivity or ≥95% specificity were selected as rule‐out/rule‐in cut‐offs, respectively. In the derivation cohort, 227 patients (66%) had CA, and presented with higher NT‐proBNP and hs‐TnT. NT‐proBNP 180 ng/L and hs‐TnT 14 ng/L were selected as rule‐out cut‐offs, and hs‐TnT 86 ng/L as rule‐in cut‐off. NT‐proBNP <180 ng/L or hs‐TnT <14 ng/L were found in 7% of patients, and ruled out CA without false negatives. In the validation cohort, 20% of patients (2% false negatives) had NT‐proBNP <180 ng/L or hs‐TnT <14 ng/L, and 10% showed both biomarkers below cut‐offs (0.5% false negatives). These cut‐offs refined CA prediction when added to echocardiographic scores in patients with a haematologic disease or an increased wall thickness. In the validation cohort, the 86 ng/L hs‐TnT cut‐off ruled in 20% of patients (2% false positives). NT‐proBNP and hs‐TnT cut‐offs retained their rule‐out and rule‐in performance also in cohorts with CA prevalence of 20%, 10%, 5% and 1% derived from the original cohort through bootstrap analysis.
Conclusions
Cardiac biomarkers can refine the diagnostic algorithm in patients with suspected CA. NT‐proBNP <180 ng/L and hs‐TnT <14 ng/L reliably exclude the diagnosis, both in the overall population and subgroups referred for either AL‐CA or cardiac (pseudo)hypertrophy.
Cardiac biomarkers hold diagnostic value in cardiac amyloidosis (CA). The diagnosis can be reliably excluded when N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is <180 ng/L and high‐sensitivity troponin T (hs‐TnT) is <14 ng/L.
Abstract
Aims
Sodium–glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating ...the effects of this drug class in patients following acute myocardial infarction are lacking.
Methods and results
In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757–2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower 95% confidence interval (CI) −4.4% to −23.6% after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2–2.9%, P = 0.029), mean E/e′ reduction was 6.8% (95% CI 1.3–11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4–11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7–15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups.
Conclusion
In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters.
ClinicalTrials.gov registration
NCT03087773.
Abstract NT-proBNP is marker of acute heart failure. Recent investigation implicate its role in different cardiac and non-cardiac diseases and different mechanism of release in patients with STEMI ...and NSTEMI. Our study included 66 patients with diagnosis of acute myocardial infarction, hospitalized in Clinical Centre Kragujevac. We evaluated standard biochemical analysis including NTproBNP, electrocardiography, transthoracic echocardiography and coronary angiography. The most common cardiovascular risk factors were emotional stress (93,94%), and physical inactivity( 81,82%). NT-proBNP values were higher in patients with AMI vs health volunteers (943 vs. 162,5 pg/ml, p = 0,0001), NSTEMI vs STEMI patients (1427 pg/ml vs. 592 pg/m, p = 0,005), patients with culprit lesion on left vs right coronary artery (1421 vs. 548, p =0.02), and anterior vs inferior location AMI (1714vs. 625, p =0.022). We found positive correlation NT-proBNP values with CRP, urea, creatinine, and negative correlation with triglicerides, hemoglobin, left ventricular ejection fraction. Higher values of NT-proBNP values are recorded in patients with AMI, NSTEMI, anterior location AMI and with culprit lesion on left coronary artery.
Aims
N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), cardiac troponin T (cTnT) and soluble ST2 (sST2) provide complementary prognostic information in heart failure with reduced ejection ...fraction (HFrEF). We aimed to assess the association between changes in these markers with changes in cardiac structure, function and health status.
Methods and results
Patients in the EVALUATE‐HF trial (n = 464) were randomized to sacubitril/valsartan or enalapril for 12 weeks, followed by 12‐week open‐label sacubitril/valsartan. Cardiac biomarkers, echocardiography, and Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed at baseline, and after 12 and 24 weeks. A total of 410 patients (88%) had serial biomarker measurements available (mean age 67 ± 9 years, 75% male and 75% white). After 24 weeks of treatment, NT‐proBNP, sST2 and cTnT decreased by median (Q1, Q3) −31% (−55%, +6%), −6% (−19%, +8%) and − 3% (−13%, +8%), respectively (all p < 0.001). Decreases in NT‐proBNP were associated with reductions in cardiac volumes and improvements in systolic and diastolic function and health status. Decreases in cTnT were associated with reductions in left ventricular mass, but not with changes in left ventricular function or KCCQ. Decreases in sST2 were consistently associated with improvements in health status, but not with measures of cardiac structure or function. There was no effect modification from treatment on the associations investigated (p for interaction >0.05)
Conclusion
In HFrEF, serial changes in NT‐proBNP correlate with changes in several key measures of cardiac structure and health status. cTnT changes correlate with changes in left ventricular mass and sST2 with changes in health status. These data highlight possible complementary pathophysiologic implications of changes in NT‐proBNP, cTnT and sST2.
Clinical Trial Registration:
ClinicalTrials.gov Identifier: NCT02874794.
Changes from baseline to week 24 in quartiles of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), soluble ST2 (sST2) and cardiac troponin T (cTnT), and the association with changes in measures of cardiac structure and health status. P‐values are for trends across quartiles and adjusted for age, sex, race, body mass index, New York Heart Association class, estimated glomerular filtration rate and baseline value of each exposure and outcome variable. KCCQ‐OS, Kansas City Cardiomyopathy Questionnaire overall summary; LA, left atrial; LV, left ventricular.
Background
During COVID‐19 outbreak, Italy was the first country in Europe to be heavily affected with an intensive care unit mortality of 26%. In order to reduce this percentage, physicians should ...establish clear and objective criteria to stratify COVID‐19 patients at high risk of in‐hospital death. Thus, the aim has been to test a large spectrum of variables ranging from clinical evaluation to laboratory biomarkers to identify which parameter would best predict all‐cause in‐hospital mortality in COVID‐19 patients.
Design
observational study.
Results
Multivariate Cox regression analysis showed that each 5 years of increase in age corresponded to a hazard ratio (HR) of 1.28 (95% CI 1.00‐1.65, P = .050); each increment of 803 ng/L of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) corresponded to a HR of 1.24 (95% CI 1.11‐1.39, P < .001); each increment of 58 ng/L of interleukin (IL)‐6 corresponded to a HR of 1.23 (95% CI 1.09‐1.40, P < .001), and each increment of 250 U/L of lactate dehydrogenase (LDH) corresponded to a HR of 1.23 (95% CI 1.10‐1.37, P < .001). According to the calculated cut‐points for age (≥70 years), NT‐proBNP (≥803 ng/L), IL‐6 (≥58 ng/L) and LDH (≥371 U/L) when 2 out of these 4 were overcome, the HR was 2.96 (95% CI 1.97‐4.45, P < .001).
Conclusion
In COVID‐19 patients, besides age, the evaluation of three biochemical parameters, available in few hours after hospital admission can predict in‐hospital mortality regardless of other comorbidities.
Aims
Biomarkers can be used for diagnosis, risk stratification, or management of patients with heart failure (HF). Knowledge about the biological variation is needed for proper interpretation of ...serial measurements. Therefore, we aimed to determine and compare the biological variation of a large panel of biomarkers in healthy subjects and in patients with chronic HF.
Methods and results
The biological variability of established biomarkers NT‐proBNP and high‐sensitivity troponin T (hsTnT), novel biomarkers galectin‐3, suppression of tumorigenicity 2 (ST2), and growth differentiation factor 15 (GDF‐15), and renal/neurohormonal biomarkers (aldosterone, phosphate, parathyroid hormone, plasma renin concentration, and creatinine) was determined in 28 healthy subjects and 83 HF patients, over a period of 4 months and 6 weeks, respectively. The analytical (CVa), intraindividual (CVi), and interindividual (CVg) variations were calculated, as well as the reference change value (RCV), which reflects the percentage of change that may indicate a ‘relevant’ change. All crude biomarker levels were significantly increased or decreased in HF patients compared with controls (all P < 0.01). Variation indices were comparable in healthy individuals and HF patients. CVi was not influenced by the individual levels of the biomarker itself. NT‐proBNP and GDF‐15 had relatively high CVi (21.8% and 16.6%) and RCV (61.7% and 64.3%), whereas ST2 (CVi, 15.0; RCV, 42.9%), hsTnT (CVi, 11.1; RCV, 31.4%), and galectin‐3 (CVi, 8.1; RCV, 25.0%) had lower indices of variation.
Conclusion
Biological variation indices are comparable between healthy subjects and HF patients for a broad spectrum of biomarkers. NT‐proBNP and GDF‐15 have substantial variation, with lower variation for ST2, hsTnT, and galectin‐3. These data are instrumental in proper interpretation of biomarker levels in HF patients.
Aims
Viral‐induced cardiac inflammation can induce heart failure with preserved ejection fraction (HFpEF)‐like syndromes. COVID‐19 can lead to myocardial damage and vascular injury. We hypothesised ...that COVID‐19 patients frequently develop a HFpEF‐like syndrome, and designed this study to explore this.
Methods and results
Cardiac function was assessed in 64 consecutive, hospitalized, and clinically stable COVID‐19 patients from April–November 2020 with left ventricular ejection fraction (LVEF) ≥50% (age 56 ± 19 years, females: 31%, severe COVID‐19 disease: 69%). To investigate likelihood of HFpEF presence, we used the HFA‐PEFF score. A low (0–1 points), intermediate (2–4 points), and high (5–6 points) HFA‐PEFF score was observed in 42%, 33%, and 25% of patients, respectively. In comparison, 64 subjects of similar age, sex, and comorbidity status without COVID‐19 showed these scores in 30%, 66%, and 4%, respectively (between groups: P = 0.0002). High HFA‐PEFF scores were more frequent in COVID‐19 patients than controls (25% vs. 4%, P = 0.001). In COVID‐19 patients, the HFA‐PEFF score significantly correlated with age, estimated glomerular filtration rate, high‐sensitivity troponin T (hsTnT), haemoglobin, QTc interval, LVEF, mitral E/A ratio, and H2FPEF score (all P < 0.05). In multivariate, ordinal regression analyses, higher age and hsTnT were significant predictors of increased HFA‐PEFF scores. Patients with myocardial injury (hsTnT ≥14 ng/L: 31%) vs. patients without myocardial injury, showed higher HFA‐PEFF scores median 5 (interquartile range 3–6) vs. 1 (0–3), P < 0.001 and more often showed left ventricular diastolic dysfunction (75% vs. 27%, P < 0.001).
Conclusion
Hospitalized COVID‐19 patients frequently show high likelihood of presence of HFpEF that is associated with cardiac structural and functional alterations, and myocardial injury. Detailed cardiac assessments including echocardiographic determination of left ventricular diastolic function and biomarkers should become routine in the care of hospitalized COVID‐19 patients.
Summary
Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among ...children in the United States. While histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first‐line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)‐1 receptor antagonist (IL‐1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG‐resistant patients. In this study, we sought to investigate the effect of IL‐1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell‐wall extract (LCWE)‐induced murine model of KD vasculitis and investigated the effect of IL‐1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL‐1Ra pretreatment significantly reduced KD‐induced myocardial inflammation and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) release. Both MRI and echocardiographic studies on LCWE‐injected KD mice demonstrated that IL‐1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL‐1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.
Here we show that similar to what is observed in children with Kawasaki Disease (KD), LCWE‐induced KD vasculitis in mice is also associated with myocarditis and myocardial dysfunction with ventricular enlargement. We found that treatment with the IL‐1R antagonist (Anakinra) improved myocardial function, ejection fraction and left ventricular function in this experimental mouse model of KD vasculitis. These findings further support the potential beneficial effects of IL‐1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.
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