scholarly journals Can Circulating Cardiac Biomarkers Be Helpful in the Assessment of LMNA Mutation Carriers?

2020 ◽  
Vol 9 (5) ◽  
pp. 1443 ◽  
Author(s):  
Przemyslaw Chmielewski ◽  
Ewa Michalak ◽  
Ilona Kowalik ◽  
Maria Franaszczyk ◽  
Malgorzata Sobieszczanska-Malek ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Clinical Laboratory ◽  
Troponin T ◽  
Multivariable Analysis ◽  
High Sensitivity ◽  
Cardiac Biomarkers ◽  
Lamin A ◽  
Lmna Mutation ◽  
Mutation Carriers

Mutations in the lamin A/C gene are variably phenotypically expressed; however, it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment of cardiolaminopathies. We sought to assess (1) clinical characteristics including serum biomarkers: high sensitivity troponin T (hsTnT) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in clinically stable cardiolaminopathy patients, and (2) outcome among pathogenic/likely pathogenic lamin A/C gene (LMNA) mutation carriers. Our single-centre cohort included 53 patients from 21 families. Clinical, laboratory, follow-up data were analysed. Median follow-up was 1522 days. The earliest abnormality, emerging in the second and third decades of life, was elevated hsTnT (in 12% and in 27% of patients, respectively), followed by the presence of atrioventricular block, heart failure, and malignant ventricular arrhythmia (MVA). In patients with missense vs. other mutations, we found no difference in MVA occurrence and, surprisingly, worse transplant-free survival. Increased levels of both hsTnT and NT-proBNP were strongly associated with MVA occurrence (HR > 13, p ≤ 0.02 in both) in univariable analysis. In multivariable analysis, NT-proBNP level > 150 pg/mL was the only independent indicator of MVA. We conclude that assessment of circulating cardiac biomarkers may help in the detection and risk assessment of cardiolaminopathies.

scholarly journals Titin-Related Dilated Cardiomyopathy: The Clinical Trajectory and the Role of Circulating Biomarkers in the Clinical Assessment

Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 13
Author(s):  
Przemysław Chmielewski ◽  
Grażyna Truszkowska ◽  
Ilona Kowalik ◽  
Małgorzata Rydzanicz ◽  
Ewa Michalak ◽  
...  
Keyword(s):  
Heart Failure ◽  
Risk Assessment ◽  
Dilated Cardiomyopathy ◽  
Troponin T ◽  
Left Ventricular Systolic Dysfunction ◽  
Multivariable Analysis ◽  
Disease Onset ◽  
Left Ventricular ◽  
Cardiac Biomarkers

Titin truncating variants (TTNtv) are known as the leading cause of inherited dilated cardiomyopathy (DCM). Nevertheless, it is unclear whether circulating cardiac biomarkers are helpful in detection and risk assessment. We sought to assess 1) early indicators of cardiotitinopathy including the serum biomarkers high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in clinically stable patients, and 2) predictors of outcome among TTNtv carriers. Our single-center cohort consisted of 108 TTNtv carriers (including 70 DCM patients) from 43 families. Clinical, laboratory and follow-up data were analyzed. The earliest abnormality was left ventricular dysfunction, present in 8, 26 and 47% of patients in the second, third and fourth decade of life, respectively. It was followed by symptoms of heart failure, linked to NT-proBNP elevation and severe left ventricular systolic dysfunction, and later by arrhythmias. Hs-cTnT serum levels were increased in the late stage of the disease only. During the median follow-up of 5.2 years, both malignant ventricular arrhythmia (MVA) and end-stage heart failure (esHF) occurred in 12% of TTNtv carriers. In multivariable analysis, NT-proBNP level ≥650 pg/mL was the best predictor of both composite endpoints (MVA and esHF) and of MVA alone. In conclusion, echocardiographic abnormalities are the first detectable anomalies in the course of cardiotitinopathies. The assessment of circulating cardiac biomarkers is not useful in the detection of the disease onset but may be helpful in risk assessment.

scholarly journals Titin-Related Dilated Cardiomyopathy: The Sequence of Events and The Role of Circulating Biomarkers in The Clinical Assessment

2021 ◽  
Author(s):  
Przemysław Chmielewski ◽  
Grażyna Truszkowska ◽  
Ilona Kowalik ◽  
Małgorzata Rydzanicz ◽  
Ewa Michalak ◽  
...  
Keyword(s):  
Heart Failure ◽  
Risk Assessment ◽  
Dilated Cardiomyopathy ◽  
Troponin T ◽  
Left Ventricular Systolic Dysfunction ◽  
Multivariable Analysis ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Sequence Of Events

Abstract Titin truncating variants (TTNtv) are known as the leading cause of inherited dilated cardiomyopathy (DCM). Nevertheless, the clinical course is not fully understood and it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment. We sought to assess: 1) early signs of cardiotitinopathy including serum biomarkers: high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in clinically stable patients, and 2) indicators of outcome among TTNtv carriers. Our single-centre cohort included 108 carriers (including 70 DCM patients) from 43 families. Clinical, laboratory and follow-up data were analyzed. The earliest abnormality was left ventricular dysfunction, present in 8, 26 and 47% of patients in the 2nd, 3rd and 4th decade of life, respectively. It was followed by symptoms of heart failure and elevation of NT-proBNP, linked to severe (persistent or transient) left ventricular systolic dysfunction, and later by arrhythmias, preceding both malignant ventricular arrhythmia (MVA) and end-stage heart failure (esHF). Hs-cTnT serum levels were increased in the late stage of the disease only. During the median follow-up of 5.2 years both MVA and esHF occurred in 12% of TTNtv carriers. In multivariable analysis, NT-proBNP level ≥650 pg/ml was the best predictor of both composite endpoint (MVA and esHF), and of MVA alone. We conclude that assessment of circulating cardiac biomarkers is not useful in the detection of cardiotitinopathies but may be helpful in the risk assessment.

Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kellisha Harley ◽  
Sarah Bissonnette ◽  
Rosanna Inzitari ◽  
Karen Schulz ◽  
Fred S. Apple ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Clinical Laboratory ◽  
Troponin T ◽  
High Sensitivity ◽  
Combined Effects ◽  
Over The Counter ◽  
Heparin Plasma ◽  
Abbott Architect ◽  
Roche Cobas

Abstract Objectives This study compared the independent and combined effects of hemolysis and biotin on cardiac troponin measurements across nine high-sensitivity cardiac troponin (hs-cTn) assays. Methods Parallel cTn measurements were made in pooled lithium heparin plasma spiked with hemolysate and/or biotin using nine hs-cTn assays: Abbott Alinity, Abbott ARCHITECT i2000, Beckman Access 2, Ortho VITROS XT 7600, Siemens Atellica, Siemens Centaur, Siemens Dimension EXL cTnI, and two Roche Cobas e 411 Elecsys Troponin T-hs cTnT assays (outside US versions, with and without increased biotin tolerance). Absolute and percent cTn recovery relative to two baseline concentrations were determined in spiked samples and compared to manufacturer’s claims. Results All assays except the Ortho VITROS XT 7600 showed hemolysis and biotin interference thresholds equivalent to or greater than manufacturer’s claims. While imprecision confounded analysis of Ortho VITROS XT 7600 data, evidence of biotin interference was lacking. Increasing biotin concentration led to decreasing cTn recovery in three assays, specifically both Roche Cobas e 411 Elecsys Troponin T-hs assays and the Siemens Dimension EXL. While one of the Roche assays was the most susceptible to biotin among the nine studied, a new version showed reduced biotin interference by approximately 100-fold compared to its predecessor. Increasing hemolysis also generally led to decreasing cTn recovery for susceptible assays, specifically the Beckman Access 2, Ortho VITROS XT 7600, and both Roche Cobas e 411 Elecsys assays. Equivalent biotin and hemolysis interference thresholds were observed at the two cTn concentrations considered for all but two assays (Beckman Access 2 and Ortho VITROS XT 7600). When biotin and hemolysis were present in combination, biotin interference thresholds decreased with increasing hemolysis for two susceptible assays (Roche Cobas e 411 Elecsys and Siemens Dimension EXL). Conclusions Both Roche Cobas e 411 Elecsys as well as Ortho VITROS XT assays were susceptible to interference from in vitro hemolysis at levels routinely encountered in clinical laboratory samples (0–3 g/L free hemoglobin), leading to falsely low cTn recovery up to 3 ng/L or 13%. While most assays are not susceptible to biotin at levels expected with over-the-counter supplementation, severely reduced cTn recovery is possible at biotin levels of 10–2000 ng/mL (41–8,180 nmol/L) for some assays. Due to potential additive effects, analytical interferences should not be considered in isolation.

Abstract P048: Segment-Specific Pulse Wave Velocity and Subclinical Cardiac Overload and Damage in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Shuiqing Liu ◽  
Esther Kim ◽  
Aozhou Wu ◽  
Michelle L Meyer ◽  
Susan Cheng ◽  
...  
Keyword(s):  
Older Adults ◽  
Arterial Stiffness ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Cardiac Disease ◽  
Pulse Wave ◽  
Troponin T ◽  
High Sensitivity ◽  
Clinical History ◽  
Cardiac Biomarkers

Background: Pulse wave velocity (PWV) independently predicts cardiovascular disease. However, few studies simultaneously explored the associations of segment-specific PWV measures with markers of both cardiac overload (natriuretic peptide [NT-proBNP]) and damage (high-sensitivity cardiac troponin T [hs-cTnT]) among adults without cardiac disease. Methods: We examined 2,845 whites and blacks (67-90 years) without clinical history of cardiac disease during ARIC visit 5 (2011-13). The association of PWV quartiles (cf [carotid-femoral], hc [heart-carotid], hf [heart-femoral], ha [heart-ankle], ba [brachial-ankle], and fa [femoral-ankle]) with log-transformed NT-proBNP and hs-cTnT was evaluated using linear and logistic regression models to adjust for potential confounders. Results: Most PWV measures demonstrated J- or U-shaped associations with NTpro-BNP and hs-cTnT [Figure]. The highest vs. the second lowest quartile of central PWV measures (cfPWV, hfPWV, and hcPWV) was associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were weaker for hs-cTnT. These associations were attenuated after further adjustment, but hcPWV and NT-proBNP remained borderline significant (p=0.069). haPWV, baPWV, and faPWV including peripheral elements had less evident positive associations after adjusting for traditional risk. Conclusion: The positive associations between PWV and cardiac biomarkers were stronger for central vs. peripheral arterial stiffness and for NT-proBNP vs. hs-cTnT among older adults without prevalent cardiac disease. Our findings indicate the relative importance of central arterial stiffness behind subclinical cardiac overload.

scholarly journals Enhanced Inflammation is a Marker for Risk of Post-Infarct Ventricular Dysfunction and Heart Failure

2020 ◽  
Vol 21 (3) ◽  
pp. 807 ◽  
Author(s):  
Iwona Świątkiewicz ◽  
Przemysław Magielski ◽  
Jacek Kubica ◽  
Adena Zadourian ◽  
Anthony N. DeMaria ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Multivariable Analysis ◽  
High Sensitivity ◽  
Left Ventricular ◽  
St Segment Elevation ◽  
Reactive Protein

Acute ST-segment elevation myocardial infarction (STEMI) activates inflammation that can contribute to left ventricular systolic dysfunction (LVSD) and heart failure (HF). The objective of this study was to examine whether high-sensitivity C-reactive protein (CRP) concentration is predictive of long-term post-infarct LVSD and HF. In 204 patients with a first STEMI, CRP was measured at hospital admission, 24 h (CRP24), discharge (CRPDC), and 1 month after discharge (CRP1M). LVSD at 6 months after discharge (LVSD6M) and hospitalization for HF in long-term multi-year follow-up were prospectively evaluated. LVSD6M occurred in 17.6% of patients. HF hospitalization within a median follow-up of 5.6 years occurred in 45.7% of patients with LVSD6M vs. 4.9% without LVSD6M (p < 0.0001). Compared to patients without LVSD6M, the patients with LVSD6M had higher CRP24 and CRPDC and persistent CRP1M ≥ 2 mg/L. CRP levels were also higher in patients in whom LVSD persisted at 6 months (51% of all patients who had LVSD at discharge upon index STEMI) vs. patients in whom LVSD resolved. In multivariable analysis, CRP24 ≥ 19.67 mg/L improved the prediction of LVSD6M with an increased odds ratio of 1.47 (p < 0.01). Patients with LVSD6M who developed HF had the highest CRP during index STEMI. Elevated CRP concentration during STEMI can serve as a synergistic marker for risk of long-term LVSD and HF.

scholarly journals Trends in Blood Pressure and High-Sensitivity Cardiac Troponin-T With Cardiovascular Disease: The Cardiovascular Health Study

2019 ◽  
Vol 32 (10) ◽  
pp. 1013-1020 ◽  
Author(s):  
David M Tehrani ◽  
Wenjun Fan ◽  
Vijay Nambi ◽  
Julius Gardin ◽  
Calvin H Hirsch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Troponin ◽  
Cardiovascular Health ◽  
Troponin T ◽  
High Sensitivity ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Cvd Risk ◽  
Over Time

AbstractBackgroundHigh-sensitivity cardiac troponin T (hs-cTnT) is individually associated with incident hypertension (HTN) and cardiovascular disease (CVD) events. We hypothesize that the increases in hs-cTnT with increases in blood pressure will be related to higher incidence of CVD.METHODSThe Cardiovascular Health Study is a longitudinal cohort of older adults. Those with hs-cTnT data and CVD risk factors at baseline and follow-up (2–3 years later) were stratified based on systolic blood pressure (SBP; optimal: <120 mm Hg, intermediate: 120–139 mm Hg, elevated: ≥140 mm Hg) and hs-cTnT (undetectable: <5 ng/l, detectable: 5–13 ng/l, elevated: ≥14 ng/l) categories. SBP and hs-cTnT were classified as increased or decreased if they changed categories between exams, and stable if they did not. Cox regression evaluated incident CVD events over an average 9-year follow-up.RESULTSAmong 2,219 adults, 510 (23.0 %) had decreased hs-cTnT, 1,279 (57.6 %) had stable hs-cTnT, and 430 (19.4 %) had increased hs-cTnT. Those with increased hs-cTnT had a higher CVD risk with stable SBP (hazard ratio [HR]: 1.28 [1.04–1.57], P = 0.02) or decreased SBP (HR: 1.57 [1.08–2.28], P = 0.02) compared to those within the same SBP group but a stable hs-cTnT. In those with lower SBP at follow-up, there was an inverse relation between diastolic blood pressure (DBP) and risk of CVD events in those with increased hs-cTnT (HR: 0.44 per 10 mm Hg increase, P < 0.01).CONCLUSIONAn increase in hs-cTnT over time is associated with a higher risk of CVD even when the blood pressure is stable or decreases over time.

scholarly journals Use of Cardiac Biomarkers for Monitoring Improvement of Left Ventricular Function by Immunoadsorption Treatment in Dilated Cardiomyopathy

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 654
Author(s):  
Weinmann ◽  
Werner ◽  
Koenig ◽  
Rottbauer ◽  
Walcher ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Troponin I ◽  
Troponin T ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Lv Function ◽  
Long Term Follow Up ◽  
Acute Changes

Immunoadsorption and subsequent administration of intravenous immunoglobulin (IVIG) have shown beneficial effects on cardiac function and symptoms in patients with dilated cardiomyopathy. Biomarkers play an emerging role in disease monitoring and outcome prediction of heart failure (HF) patients. We aimed to analyze cardiac biomarkers as predictor for improvement of left ventricular (LV) function after immunoadsorption treatment in dilated cardiomyopathy (DCM). Thirty-one patients with dilated cardiomyopathy on optimized HF pharmacotherapy received a single cycle of immunoadsorption for five days followed by IVIG administration. Left ventricular ejection fraction (LVEF) and heart failure biomarkers (hs troponin T, hs troponin I, NT-proBNP and sST2) were evaluated before treatment, after the last cycle of immunoadsorption and during a median follow-up of 30.5 months. We correlated HF biomarkers before immunoadsorption and acute changes of HF biomarkers by immunoadsorption with LV improvement during the long-term follow-up. LV function improved significantly after immunoadsorption from 28.0 to 42.0% during the long-term follow-up (p < 0.0001). Evaluation of biomarker levels showed a significant decrease for hs troponin I (from 9.2 to 5.5 ng/L, p < 0.05) and NT-proBNP (from 789.6 to 281.2 pg/mL, p < 0.005). Correlation of biomarker levels before immunoadsorption and LVEF at the long-term follow-up show good results for hs troponin T (r = −0.40, r2 = 0.16, p < 0.05), hs troponin I (r = −0.41, r2 = 0.17, p < 0.05) and sST2 (r = −0.46, r2 = 0.19, p < 0.05). Correlation of biomarker levels before immunoadsorption and the individual increase in LV function was significant for hs troponin T (r = −0.52, r2 = 0.27, p < 0.005) and hs troponin I (r = −0.53, r2 = 0.29, p < 0.005). To imply a tool for monitoring outcome immediately after immunoadsorption treatment, we investigated the correlation of acute changes of biomarker levels by immunoadsorption treatment and individual increase in LV function. A drop in hs troponin T (r = −0.41, r2 = 0.17, p < 0.05) and hs troponin I (r = −0.53, r2 = 0.28, p < 0.005) levels demonstrate a good correlation to improvement in LVEF during the long-term follow-up. Conclusion: Hs troponin T and I levels correlate with LV function improvement during long-term follow-up. Acute decrease of troponins by immunoadsorption treatment is paralleled by individual improvement of LVEF at the long-term follow-up. Thus, troponins could serve as a monitoring tool for the improvement of LV function after immunoadsorption treatment in dilated cardiomyopathy.

scholarly journals Elevated high-sensitivity troponin T levels at 1-year follow-up are associated with increased long-term mortality after TAVR

2020 ◽  
Author(s):  
Hatim Seoudy ◽  
Moritz Lambers ◽  
Vincent Winkler ◽  
Linnea Dudlik ◽  
Sandra Freitag-Wolf ◽  
...  
Keyword(s):  
Troponin T ◽  
High Sensitivity ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Chronic Obstructive ◽  
High Sensitivity Troponin ◽  
High Sensitivity Troponin T ◽  
Long Term Mortality

Abstract Background Elevated pre-procedural high-sensitivity troponin T (hs-TnT) levels predict adverse outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). It is unknown whether elevated troponin levels still provide prognostic information during follow-up after successful TAVR. We evaluated the long-term implications of elevated hs-TnT levels found at 1-year post-TAVR. Methods and results The study included 349 patients who underwent TAVR for severe AS from 2010–2019 and for whom 1-year hs-TnT levels were available. Any required percutaneous coronary interventions were performed > 1 week before TAVR. The primary endpoint was survival time starting at 1-year post-TAVR. Optimal hs-TnT cutoff for stratifying risk, identified by ROC analysis, was 39.4 pg/mL. 292 patients had hs-TnT < 39.4 pg/mL (median 18.3 pg/mL) and 57 had hs-TnT ≥ 39.4 pg/mL (median 51.2 pg/mL). The high hs-TnT group had a higher median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, greater left ventricular (LV) mass, higher prevalence of severe diastolic dysfunction, LV ejection fraction < 35%, severe renal dysfunction, and more men compared with the low hs-TnT group. All-cause mortality during follow-up after TAVR was significantly higher among patients who had hs-TnT ≥ 39.4 pg/mL compared with those who did not (mortality rate at 2 years post-TAVR: 12.3% vs. 4.1%, p = 0.010). Multivariate analysis identified 1-year hs-TnT ≥ 39.4 pg/mL (hazard ratio 2.93, 95% CI 1.91–4.49, p < 0.001), NT-proBNP level > 300 pg/mL, male sex, an eGFR < 60 mL/min/1.73 m2 and chronic obstructive pulmonary disease as independent risk factors for long-term mortality after TAVR. Conclusions Elevated hs-TnT concentrations at 1-year after TAVR were associated with a higher long-term mortality. Graphic abstract

scholarly journals Recent-onset atrial fibrillation: a study exploring the elements of Virchow’s triad after cardioversion

2021 ◽  
Author(s):  
Panagiotis Arvanitis ◽  
Anna-Karin Johansson ◽  
Mats Frick ◽  
Helena Malmborg ◽  
Spyridon Gerovasileiou ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Troponin T ◽  
High Sensitivity ◽  
Cardiac Biomarkers ◽  
Prior History ◽  
Recent Onset ◽  
Reactive Protein ◽  
Peak Longitudinal Strain ◽  
History Of

Abstract Purpose Atrial fibrillation (AF) imposes an inherent risk for stroke and silent cerebral emboli, partly related to left atrial (LA) remodeling and activation of inflammatory and coagulation systems. The aim was to explore the effects of cardioversion (CV) and short-lasting AF on left atrial hemodynamics, inflammatory, coagulative and cardiac biomarkers, and the association between LA functional recovery and the presence of a prior history of AF. Methods Patients referred for CV within 48 h after AF onset were prospectively included. Echocardiography and blood sampling were performed immediately prior, 1–3 h after, and at 7–10 days after CV. The presence of chronic white matter hyperintensities (WMH) on magnetic resonance imaging was related to biomarker levels. Results Forty-three patients (84% males), aged 55±9.6 years, with median CHA2DS2-VASc score 1 (IQR 0–1) were included. The LA emptying fraction (LAEF), LA peak longitudinal strain during reservoir, conduit, and contractile phases improved significantly after CV. Only LAEF normalized within 10 days. Interleukin-6, high-sensitivity cardiac-troponin-T (hs-cTNT), N-terminal-pro-brain-natriuretic peptide, prothrombin-fragment 1+2 (PTf1+2), and fibrinogen decreased significantly after CV. There was a trend towards higher C-reactive protein, hs-cTNT, and PTf1+2 levels in patients with WMH (n=21) compared to those without (n=22). At 7–10 days, the LAEF was significantly lower in patients with a prior history of AF versus those without. Conclusion Although LA stunning resolved within 10 days, LAEF remained significantly lower in patients with a prior history of AF versus those without. Inflammatory and coagulative biomarkers were higher before CV, but subsided after 7–10 days, which altogether might suggest an enhanced thrombogenicity, even in these low-risk patients.

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