Kinetics of high-sensitivity cardiac troponin T or troponin I compared to creatine kinase in patients with revascularized acute myocardial infarction.

BACKGROUND: Cardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI). METHODS: We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines. RESULTS: Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9-12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1-99.9) vs. cTnI by 86.8% (76.6-92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9-42.9) when compared with CK that fell by 79.5% (64.3-90.7). CONCLUSIONS: Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.

Cardiac Fatigue in Male Athletes with Exercise-Induced Pulmonary Impairments After a Very Long-Distance Triathlon.

INTRODUCTION: Prolonged strenuous exercise can transiently decrease cardiac function. Other studies have identified three major exercise-induced pulmonary changes: bronchoconstriction, dynamic hyperinflation and pulmonary oedema with reduced alveolar-capillary membrane diffusing capacity. This study investigated whether athletes with one of these pulmonary dysfunctions following a very long-distance triathlon exhibit similar cardiac alterations as those without dysfunctions. METHODS: Sixty trained male triathletes (age 39 ± 9 years) underwent baseline and post-race assessments, including echocardiography (with standard, 2D-strain and myocardial work assessments), spirometry and double-diffusion technique to evaluate alveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO). Cardiac function in athletes with exercise-induced bronchoconstriction (> 10% decrease FEV1), dynamic hyperinflation (> 10% decrease inspiratory capacity) or impaired diffusion capacity (> 20% decrease DMCO/alveolar volume) were compared with those without these dysfunctions. RESULTS: The race lasted 14 h 20 min ± 1 h 26 min. Both systolic and diastolic cardiac functions declined post-race. Post-race, 18% of athletes had bronchoconstriction, 58% dynamic hyperinflation and 40% impaired diffusing capacity. Right and left ventricular standard and 2D-strain parameters were similar before the race in all subgroups and changed similarly post-race, except E/E', which decreased in the bronchoconstriction subgroup and increased in those with diffusion impairment. Global constructive work decreased by ~ 19% post-race (2302 ± 226 versus 1869 ± 328 mmHg%, P < 0.001), more pronounced in athletes with diffusion impairment compared with others (- 26 ± 13 versus - 15 ± 9%, P = 0.001) and positively correlated with DMCO/alveolar volume reduction. CONCLUSION: After a very long-distance triathlon, bronchoconstriction and hyperinflation were not associated with significant cardiac changes, whereas impaired alveolar-capillary membrane diffusing capacity was associated with a more significant decline in myocardial function. These findings highlight the complex relationship between pulmonary gas exchange abnormalities and cardiac fatigue following prolonged strenuous exercise.

Delayed postconditioning in the mouse heart in vivo.

BACKGROUND: Reperfusion during acute myocardial infarction remains the best treatment for reducing infarct size. Postconditioning, applied at the onset of reperfusion, reduces myocardial infarction both in animals and humans. The objective of this study was to identify the time delay to apply postconditioning at reperfusion, allowing preservation of cardioprotection in the mouse myocardium. This is a major issue in the management of acute myocardial infarction patients. METHODS AND RESULTS: Mice were subjected to 40 minutes of ischemia and 60 minutes of reperfusion (IR(60')). Postconditioning protocols corresponding to repetitive ischemia (3 cycles of 1 minute of ischemia and 1 minute of reperfusion) were applied during early reperfusion at various time durations (Δt) after reopening of the coronary artery (Δt=10 seconds, 1, 5, 10, 15, 20, 30, and 45 minutes; PostC(Δt)). Infarct size/area at risk was reduced by 71% in PostC(Δ1) compared with IR(60') mice (P=5×10(-6)). There was a linear correlation (r(2)=0.91) between infarct size and Δt, indicating that the cardioprotective effect of delayed postconditioning was progressively attenuated when Δt time increased. The protective effect of PostC(Δ1) and PostC(Δ15) was still effective when the duration of reperfusion was prolonged to 24 hours (IR(24 hours); PostC(Δ1) and PostC(Δ15) versus IR(24 hours), P=0.001). Similar results were obtained for internucleosomal DNA fragmentation and lactate dehydrogenase release. CONCLUSIONS: This study in our in vivo mouse model of myocardial IR shows for the first time that delaying the intervention of postconditioning to 30 minutes does not abrogate the cardioprotective effect of postconditioning. This finding provides evidence that the time window of protection afforded by postconditioning may be larger than initially reported.

Cardiac screening before returning to elite sport after SARS-CoV-2 infection.

BACKGROUND: SARS-CoV-2 infection can induce cardiac damage. Therefore, in the absence of clear data, a cardiac evaluation was recommended for athletes before returning to play after recent SARS-CoV-2 infection. AIM: To assess the proportion of anomalies detected by this cardiac screening. METHODS: We reviewed the medical files of elite athletes referred for cardiac evaluation before returning to play after a non-hospitalized SARS-CoV-2 infection (based on a positive polymerase chain reaction or antigen test) from March 2020 to July 2021 in 12 French centres. RESULTS: A total of 554 elite athletes (professional or national level) were included (median age 22 years, 72.0% male). An electrocardiogram (ECG), echocardiogram and exercise test were performed in 551 (99.5%), 497 (89.7%) and 293 (52.9%) athletes, respectively. We found anomalies with a potential link with SARS-CoV-2 infection in four ECGs (0.7%), three echocardiograms (0.6%) and three exercise tests (1.0%). Cardiac magnetic resonance imaging was performed in 34 athletes (6.1%), mostly due to abnormal first-line examinations, and was abnormal in one (2.9%). The rates of those abnormalities were not higher among athletes with cardiac symptoms or more severe forms of non-hospitalized SARS-CoV-2 infection. Only one athlete had a possible SARS-CoV-2 myocarditis and sport was temporally contraindicated. None had a major cardiac event declared during the follow-up. CONCLUSION: The proportion of cardiac involvement after non-hospitalized forms of SARS-CoV-2 infection in athletes are very low. Systematic cardiac screening before returning to play seems to be unnecessary.

[Cardiac conduction disorders in the elderly]. / Troubles conductifs cardiaques chez le sujet âgé.

While the left bundle branch block frequently reflects underlying cardiac disease, conductive disorders occurring at three levels (sinus node, atrioventricular node, and branches of the bundle of His), are usually part of the aging heart. In addition, AV nodal block and sinus node dysfunction are readily compounded with drugs, often indispensable (beta-blockers, calcium-blockers, digoxin, antiarrhythmic), and very common among the elderly. Indications for permanent pacing are accurately described and come in four classes: I, recommended (mandatory) - IIa, raisonable - IIb, possible - III, contraindicated. In 2009, 24H ECG Holter and electrophysiological study are generally disappointing in the positive diagnosis of syncope, so the clinical characteristics of syncope are essential in the decision of device implantation. Indeed, in the absence of ECG recorded at the time of the syncope, the diagnosis of BAV or BSA cannot be certain, and on the contrary, vague symptoms should not be attributed to a patent bradycardia of sinus or AV block origin without any precaution. Finally, the relationship between sinus dysfunction and carotid sinus syndrome remain poorly understood, dysautonomia is common among the elderly, and the existence of conduction disorders associated with syndrome of sleep apnea should not be ignored.

Myocardial expression of a dominant-negative form of Daxx decreases infarct size and attenuates apoptosis in an in vivo mouse model of ischemia/reperfusion injury.

BACKGROUND: Apoptosis has been described extensively in acute myocardial infarction and chronic heart failure. Because Daxx (death-associated protein) appears to be essential for stress-induced cell death and acts as an antisurvival molecule, we tested the hypothesis that Daxx is involved in myocardial ischemia/reperfusion-induced cell death in vivo. METHODS AND RESULTS: Transgenic mice overexpressing a dominant-negative form of Daxx (Daxx-DN) under the control of the beta-actin promoter and control wild-type mice underwent an ischemia/reperfusion protocol: 40 minutes of left coronary artery occlusion and 60 minutes of reperfusion. Area at risk and infarct size were measured after dual staining by triphenyltetrazolium chloride and phthalocyanine blue dye. Apoptosis was measured in the ischemic versus the nonischemic part of the left ventricle by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining, enzyme-linked immunosorbent assay, and Western blotting of caspase-3, caspase-8, and poly(ADP-ribose) polymerase. The mitogen-activated protein kinase status was investigated by Western blot analysis. Comparison between groups was assessed by ANOVA or Student t test (statistical significance: P<0.05). Left ventricle tissues from transgenic mice expressed Daxx-DN at the protein level. Area at risk/left ventricle values were comparable among groups. Infarct size/area at risk was 45% reduced in Daxx-DN versus wild-type mice (P<0.001). This cardioprotection was maintained for a 4-hour reperfusion. Ischemia/reperfusion-induced apoptosis was significantly decreased and ERK1/2 prosurvival pathway was activated in ischemic Daxx-DN hearts. CONCLUSIONS: Our study clearly indicates that Daxx participates in myocardial ischemia/reperfusion proapoptotic signaling in vivo.

Area at risk can be assessed by iodine-123-meta-iodobenzylguanidine single-photon emission computed tomography after myocardial infarction: a prospective study.

BACKGROUND: Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI). AIM: The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard). PATIENTS AND METHODS: A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment. RESULTS: I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P<0.0001). CMR and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002). Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable myocardium) was significantly higher than by CMR (P=0.02). CONCLUSION: In patients with STEMI, I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

COLIN trial: Value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response.

BACKGROUND: Inflammation is involved during acute myocardial infarction, and could be an interesting target to prevent ischaemia-reperfusion injuries. Colchicine, known for its pleiotropic anti-inflammatory effects, could decrease systemic inflammation in this context. AIMS: To evaluate the impact of colchicine on inflammation in patients admitted for ST-segment elevation myocardial infarction (STEMI). METHODS: All patients admitted for STEMI with one of the main coronary arteries occluded, and successfully treated with percutaneous coronary intervention, were included consecutively. Patients were randomized to receive either 1mg colchicine once daily for 1 month plus optimal medical treatment or optimal medical treatment only. C-reactive protein (CRP) was assessed at admission and daily until hospital discharge. The primary endpoint was CRP peak value during the index hospitalization. RESULTS: Forty-four patients were included: 23 were treated with colchicine; 21 received conventional treatment only. At baseline, both groups were well balanced regarding age, sex, risk factors, thrombolysis in myocardial infarction flow and reperfusion delay. The culprit artery was more often the left anterior descending artery in the colchicine group (P=0.07), reflecting a more severe group. There was no significant difference in mean CRP peak value between the colchicine and control groups (29.03mg/L vs 21.86mg/L, respectively; P=0.36), even after adjustment for type of culprit artery (26.99 vs 24.99mg/L, respectively; P=0.79). CONCLUSION: In our study, the effect of colchicine on inflammation in the context of STEMI could not be demonstrated. Further larger studies may clarify the impact of colchicine in acute myocardial infarction.

Kinetics of high-sensitivity cardiac troponin T and I differ in patients with ST-segment elevation myocardial infarction treated by primary coronary intervention.

PURPOSE: Cardiac biomarkers including troponins are the cornerstone of the biological definition of acute myocardial infarction. New high-sensitivity cardiac assays determining troponin T (hs-cTnT) as well as I ((hs-cTnI) from Abbott and s-cTnI from Siemens) raise concerns because of their unclear kinetics following the peak. AIMS: This study aims to compare kinetics of creatine kinases, hs-cTnT, hs-cTnI and s-cTnI in patients with ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention. METHODS: We prospectively studied 106 consecutive patients admitted in our institution for STEMI and treated by percutaneous coronary intervention. We evaluated for all the patients simultaneously kinetics of creatine kinases, hs-cTnT (Roche) and two different cTnIs (hs-cTnI from Abbott and s-cTnI from Siemens). Modelling of kinetics was realized using mixed effects with cubic splines. RESULTS: Kinetics of markers showed a first peak at 10.7h (8.0-12.0) for creatine kinases, 11.8h (10.4-13.3) for hs-cTnT (Roche); 11.8h (10.7-11.8) for hs-cTnI from Abbott and 10.2h (8.7-11.6) for s-cTnI from Siemens, respectively. This peak was followed by a nearly log linear decrease for hs-cTnI/s-cTnI and creatine kinases in contrast to hs-cTnT, which appeared with a biphasic shape curve marked by a second peak at 76.9h (69.5-82.8). The analysis of the decrease in percentage of the peak value at 77h showed that hs-cTnT follows a twice lower decrease than other markers. CONCLUSION: Kinetics of hs-cTnT, hs-cTnI and s-cTnI differ significantly with a linear decrease regarding both cTnI assays contrasting with a biphasic shape curve for hs-cTnT. This is of importance for clinical management of patients in routine settings especially in follow-up after STEMI including the suspicion of reinfarction.

Intracoronary administration of darbepoetin-alpha at onset of reperfusion in acute myocardial infarction: results of the randomized Intra-Co-EpoMI trial.

BACKGROUND: Several trials investigating erythropoietin as a novel cytoprotective agent in myocardial infarction (MI) failed to translate promising preclinical results into the clinical setting. These trials could have missed crucial events occurring in the first few minutes of reperfusion. Our study differs by earlier intracoronary administration of a longer-acting erythropoietin analogue at the onset of reperfusion. AIM: To evaluate the ability of intracoronary administration of darbepoetin-alpha (DA) at the very onset of the reperfusion, to decrease infarct size (IS). METHODS: We randomly assigned 56 patients with acute ST-segment elevation MI to receive an intracoronary bolus of DA 150 µg (DA group) or normal saline (control group) at the onset of reflow obtained by primary percutaneous coronary intervention (PCI). IS and area at risk (AAR) were evaluated by biomarkers, cardiac magnetic resonance (CMR) and validated angiographical scores. RESULTS: There was no difference between groups regarding duration of ischemia, Thrombolysis in Myocardial Infarction flow grade at admission and after PCI, AAR size and extent of the collateral circulation, which are the main determinants of IS. The release of creatine kinase was not significantly different between the two groups even when adjusted to AAR size. Between 3-7 days and at 3 months, the area of hyperenhancement on CMR expressed as a percentage of the left ventricular myocardium was not significantly reduced in the DA group even when adjusted to AAR size. CONCLUSION: Early intracoronary administration of a longer-acting erythropoietin analogue in patients with acute MI at the time of reperfusion does not significantly reduce IS.

Low-flow, low-gradient severe aortic stenosis despite normal ejection fraction is associated with severe left ventricular dysfunction as assessed by speckle-tracking echocardiography: a multicenter study.

BACKGROUND: Low-flow low-gradient (LFLG) is sometimes observed in severe aortic stenosis (AS) despite normal ejection fraction, but its frequency and mechanisms are still debated. We aimed to describe the characteristics of patients with LFLG AS and assess the presence of longitudinal left ventricular dysfunction in these patients. METHODS AND RESULTS: In a multicenter prospective study, 340 consecutive patients with severe AS and normal ejection fraction were studied. Longitudinal left ventricular function was assessed by 2D-strain and global afterload by valvulo-arterial impedance. Patients were classified according to flow and gradient: low flow was defined as a stroke volume index ≤35 mL/m(2), low gradient as a mean gradient ≤40 mm Hg. Most patients (n=258, 75.9%) presented with high-gradient AS, and 82 patients (24.1%) with low-gradient AS. Among the latter, 52 (15.3%) presented with normal flow and low gradient and 30 (8.8%) with LFLG. As compared with normal flow and low gradient, patients with LFLG had more severe AS (aortic valve area=0.7±0.12 cm(2) versus 0.86±0.14 cm(2)), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m(2)), and worse longitudinal left ventricular function (basal longitudinal strain=-11.6±3.4 versus -14.8±3%; P<0.001 for all). CONCLUSIONS: LFLG AS is observed in 9% of patients with severe AS and normal ejection fraction and is associated with high global afterload and reduced longitudinal systolic function. Patients with normal-flow low-gradient AS are more frequent and present with less severe AS, normal afterload, and less severe longitudinal dysfunction. Severe left ventricular longitudinal dysfunction is a new explanation to the concept of LFLG AS.

Could heart rate play a role in pericardial inflammation?

UNLABELLED: PURPOSE AND MEDICAL HYPOTHESIS: Rest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit "mechanical inflammation". Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported. METHODS: Between March 2007 and February 2010, we conducted a retrospective study on all patients admitted to our center for acute pericarditis. Diagnosis criteria included two of the following ones: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical electrocardiogram (ECG) findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. RESULTS: We included 73 patients. Median age was 38 years (interquartiles 28-51) and median hospitalization duration was 2.0 days (1.5-3.0). Median heart rate was 88.0 beats per minute (bpm) on admission (interquartiles 76.0-100.0) and 72.0 on discharge (65.0-80.0). Heart rate on admission was significantly correlated with CRP peak (p<0.001), independently of temperature on admission, hospitalization duration and age. Recurrences occurred within 1 month in 32% of patients. Heart rate on hospital discharge was correlated with recurrence, independently of age. CONCLUSION: In acute pericarditis, heart rate on admission is independently correlated with CRP levels and heart rate on discharge seems to be independently correlated to recurrence. This could suggest a link between heart rate and pericardial inflammation.