Karim Stamboul

Growth Differentiation Factor-15 (GDF-15) Levels Are Associated with Cardiac and Renal Injury in Patients Undergoing Coronary Artery Bypass Grafting with Cardiopulmonary Bypass

Objective Growth differentiation factor-15 (GDF-15) has been identified as a strong marker of cardiovascular disease; however, no data are available concerning the role of GDF-15 in the occurrence of organ dysfunction during coronary artery bypass grafting (CABG) associated with cardiopulmonary bypass (CPB). Methods Five arterial blood samples were taken sequentially in 34 patients from anesthesia induction (IND) until 24 h after arrival at the intensive care unit (ICU). Plasma levels of GDF-15, follistatin-like 1 (FLST1), myeloperoxidases (MPO), hydroperoxides and plasma antioxidant status (PAS) were measured at each time-point. Markers of cardiac (cardiac-troponin I, cTnI) and renal dysfunction (neutrophil gelatinase-associated lipocalin, NGAL) and other classical biological factors and clinical data were measured. Results Plasma GDF-15 levels increased gradually during and after surgery, reaching nearly three times the IND levels in the ICU (3,075±284 ng/L vs. 1,061±90 ng/L, p<0.001). Plasma MPO levels increased dramatically during surgery, attaining their highest level after unclamping (UNCLAMP) (49±11 ng/mL vs. 1,679±153 ng/mL, p<0.001) while PAS significantly decreased between IND and UNCLAMP (p<0.05), confirming the high oxidative status induced by this surgical procedure. ICU levels of GDF-15 correlated positively with cTnI and NGAL (p = 0.006 and p = 0.036, respectively), and also with hemoglobin and estimated glomerular filtration rate (eGFR). Among all the post-operative biomarkers available, only eGFR, NGAL and GDF-15 measured at ICU arrival were significantly associated with the onset of acute kidney injury (AKI). Patients with a EuroSCORE >3 were shown to have higher GDF-15 levels. Conclusions During cardiac surgery associated with CPB, GDF-15 levels increased substantially and were associated with markers of cardiac injury and renal dysfunction.

Incidence and prognostic significance of silent atrial fibrillation in acute myocardial infarction

BACKGROUND Silent atrial fibrillation (AF) has been suggested to be frequent after acute myocardial infarction (MI). Continuous ECG monitoring (CEM) has been shown to improve AF screening in patients at risk of stroke. OBJECTIVES We aimed to assess the incidence and prognosis of silent AF in patients with acute MI. METHODS All the consecutive patients with acute MI were prospectively analyzed by CEM ≥ 48 h after admission. Silent AF was defined as asymptomatic episodes lasting at least 30s. The population was divided into three groups: no-AF, silent AF and symptomatic AF. RESULTS Among the 849 patients, 135 (16%) developed silent AF and 45 (5%) symptomatic AF. Compared with the no-AF group, patients with silent AF were markedly older (80 vs. 62 y, p<0.001), more frequently women (43% vs. 30%, p=0.006) and less likely to be smokers (20% vs. 36%, p<0.001). They had impaired left ventricular ejection fraction (LVEF) and left atrial (LA) enlargement. By multivariate analysis, age, history of AF, indexed LA area and LVEF were identified as independent predictors of silent AF. In-hospital heart failure and death rates were markedly higher in silent AF group when compared with no-AF patients (41.8% vs 21.0% and 10.4% vs. 1.3%, respectively). CONCLUSION Our large prospective study showed for the first time that silent AF is more frequent than symptomatic AF after MI. Our work suggests that indexed LA area could help to predict the risk of developing silent AF. Moreover, the onset of silent AF is associated with worse hospital prognosis.

Prognostic value of fragmented QRS on a 12-lead ECG in patients with acute myocardial infarction

OBJECTIVE To investigate the determinants and the prognostic value of fragmented QRS (fQRS) after AMI. PATIENTS AND METHODS Prospective cohort of 307 consecutive patients with AMI. MAIN OUTCOMES MEASURED MACE (death plus non-fatal recurrent MI), hospitalization for an episode of heart failure, ventricular arrhythmia (VT or VF) at two years follow-up. RESULTS On the serial 12-lead ECG recorded during the in-hospital stay, 162 (53%) had no fQRS (no fQRS group). 145 (47%) presented an fQRS, which was persistent in 108 (34%) patients (persistent fQRS group) and transient in 37 (12%) patients (transient fQRS group). Patients with a fragmented QRS (transient or persistent) were older, more likely to be hypertensive and less likely to be smokers than were patients without fQRS. By multivariate logistic regression analysis, only hypertension (OR (95% CI): 1.66 (1.00-2.74); p = 0.047) was associated with an fQRS. During a mean follow-up of 846 ± 297 days, there were 82 MACE recorded: 17 patients died from a CV cause (10% event rate) among patients without fQRS, 22 (20% event rate) among patients with persistent fQRS and 3 (8% event rate) among patients with transient fQRS. Similarly, non-fatal recurrent MI occurred more frequently in patients with fQRS (18 (16%) and 10 (27%)) for persistent and transient fQRS, respectively, vs. 16 (10%) in the no fQRS group (p = 0.019). However, the occurrence of heart failure symptoms and ventricular arrhythmia was not significantly different (p = 0.162 and p = 0.242, respectively). Survival analysis by the Kaplan-Meier method showed a significant difference (log rank p = 0.026) between groups, and only persistent fQRS was associated with decreased survival. In multivariate cox regression analysis, the GRACE score, blood glucose on admission, and B-blockers in the acute phase were independent predictors of MACE at two years. fQRS was not a significant independent predictor of MACE (HR (95% CI): 1.57 (0.95-2.60); p = 0.08). Moreover, fQRS was not a predictor of heart failure or ventricular arrhythmia in univariate analysis. CONCLUSIONS Persistent fQRS on a 12-lead ECG is a marker of decreased survival after AMI, whereas transient fQRS correlates with recurrent MI.

Atrial Fibrillation Is Associated with a Marker of Endothelial Function and Oxidative Stress in Patients with Acute Myocardial Infarction

Background Atrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI. Methods 273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) ≥48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample. Results The incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly older than patients without AF (≈ 20 y). There was a trend towards higher ADMA levels in patients with symptomatic AF than in patients with silent AF or no AF (0.53 vs 0.49 and 0.49 μmol/L, respectively, p = 0.18,). After matching on age, we found that patients with symptomatic AF had a higher heart rate on admission and a higher rate of patients with LV dysfunction (28% vs. 3%, p = 0.025). Patients who developed symptomatic AF had a higher ADMA level than patients without AF (0.53 vs. 0.43 μmol/L; p = 0.001). Multivariate logistic regression analysis to estimate symptomatic AF occurrence showed that ADMA was independently associated with symptomatic AF (OR: 2.46 [1.21–5.00], p = 0.013) beyond history of AF, LVEF<40% and elevated HR. Conclusion We show that high ADMA level is associated with the occurrence of AF. Although no causative role can be concluded from our observational study, our work further supports the hypothesis that endothelial dysfunction is involved in the pathogenesis of AF in AMI.

Prognosis of silent atrial fibrillation after acute myocardial infarction at 1-year follow-up

Background Silent atrial fibrillation (AF), assessed by continuous ECG monitoring (CEM), has recently been shown to be common in acute myocardial infarction (AMI), and associated with higher hospital mortality. However, the long-term prognosis is still unknown. We aimed to assess 1-year prognosis in patients experiencing silent AF in AMI. Methods All consecutive patients with AMI who were prospectively analysed by CEM during the first 48 h after admission and who survived at hospital discharge were included. Silent AF was defined as asymptomatic episodes lasting at least 30 s. Patients were followed up at 1 year for cardiovascular (CV) outcomes. Results Among the 737 patients analysed, 106 (14%) developed silent AF and 32 (4%) symptomatic AF. Compared with the no-AF group, patients with silent AF were markedly older (79 vs 62 years, p<0.001), more frequently hypertensive (71% vs 49%, p<0.001) and less likely to be smokers (23% vs 37%, p<0.001). Also, they were more likely to have impaired LVEF (50% vs 55%, p<0.001). Risk factors in patients with silent AF were similar to those in patients with symptomatic AF. However, a history of stroke or AF was less frequent in silent AF than in symptomatic-AF patients (10% vs 25% and 10% vs 38%, respectively). At 1 year, CV events including hospitalisation for heart failure (HF) and CV mortality were markedly higher in silent-AF patients than in no-AF patients (6.6% vs 1.3% and 5.7% vs 2.0%, p<0.001, respectively). Conclusions Our large prospective study showed for the first time that silent AF is associated with worse 1-year prognosis after AMI. Systematic screening and specific management should be investigated in order to improve outcomes of patients after AMI.

Frequency and Predictors of Stroke After Acute Myocardial Infarction Specific Aspects of In-Hospital and Postdischarge Events

Background and Purpose— Stroke is a serious complication after acute myocardial infarction (AMI) and is closely associated with decreased survival. This study aimed to investigate the frequency, characteristics, and factors associated with in-hospital and postdischarge stroke in patients with AMI. Methods— Eight thousand four hundred eighty-five consecutive patients admitted to a cardiology intensive care unit for AMI, between January 2001 and July 2010. Stroke/transient ischemic attack were collected during 1-year follow-up. Results— One hundred twenty-three in-hospital strokes were recorded: 65 (52.8%) occurred on the first day after admission for AMI, and 108 (87%) within the first 5 days. One hundred six patients (86.2%-incidence rate 1.25%) experienced in-hospital ischemic stroke, and 14 patients (11.4%-incidence rate 0.16%) were diagnosed with an in-hospital hemorrhagic stroke. In-hospital ischemic stroke subtypes according to the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification showed that only 2 types of stroke were identified more frequently. As expected, the leading subtype of in-hospital ischemic stroke was cardioembolic stroke (n=64, 60%), the second was stroke of undetermined pathogenesis (n=38, 36%). After multivariable backward regression analysis, female sex, previous transient ischemic attack (TIA)/stroke, new-onset atrial fibrillation, left ventricular ejection fraction (odds ratio per point of left ventricular ejection fraction), and C-reactive protein were independently associated with in-hospital ischemic stroke. When antiplatelet and anticoagulation therapy within the first 48 hours was introduced into the multivariable model, we found that implementing these treatments (≥1) was an independent protective factor of in-hospital stroke. In-hospital hemorrhagic stroke was dramatically increased (5-fold) when thrombolysis was prescribed as the reperfusion treatment. However, the different parenteral anticoagulants were not predictors of risk in univariable analysis. Finally, only 45 postdischarge strokes were recorded. Postdischarge stroke subtypes showed a more heterogeneous distribution of mechanisms. The annual rate of stroke post-AMI remained stable throughout the 10-year study period. Conclusions— The present study describes specific predictors of in-hospital and postdischarge stroke in patients with AMI. It showed a marked increase in the risk of death, both during hospitalization and in the year after AMI. After hospital discharge, stroke remains a rare event and is mostly associated with high cardiovascular risk.

Dual Diagnostic Role of 123I-MIBG Scintigraphy in Inverted-Takotsubo Pattern Cardiomyopathy.

We highlight the dual role of I-MIBG scintigraphy in inverted-Takotsubo pattern cardiomyopathy, the diagnosis of which is sometimes challenging: Firstly, I-MIBG scintigraphy can show myocardial sympathetic dysfunction (low I-MIBG uptake) in the hypokinetic basal segments, sparing the left ventricle apex. It is helpful in the imaging diagnosis of inverted-Takotsubo pattern cardiomyopathy and confirms that acute dysfunction of myocardial sympathetic nerve endings occurs with this cardiomyopathy. Secondly, I-MIBG scintigraphy is an accurate imaging examination to detect and localize pheochromocytoma; it can help in the search for an endogenous cause of this adrenergic stress-related cardiomyopathy.

High rate of recurrence at long-term follow-up after new-onset atrial fibrillation during acute myocardial infarction

Aims Silent and symptomatic atrial fibrillation (AF) are common during acute myocardial infarction (AMI), and associated with higher in-hospital and 1-year mortality. Are silent and symptomatic AF associated with higher rates of AF recurrence after hospitalization for AMI? Methods and results All consecutive patients admitted for AMI between January 2012 and August 2015 were prospectively analysed by continuous electrocardiogram monitoring <48 h after admission. Silent AF was defined as asymptomatic episodes lasting at least 30 s. The population was divided into three groups: no-AF, silent AF, and symptomatic AF. Altogether, 1621 patients were included in the prospective study and discharged alive from hospital. After excluding those with previous AF, permanent AF since the AMI and coronary artery bypass grafting surgeries and those lost to follow-up, 1282 remained. During the AMI, 1058 patients (83%) had a persistent sinus rhythm (SR), 168 (13%) had silent AF, and 55 (4%) had symptomatic AF. After a median follow-up of 1037 days (interquartile range 583-1342), new AF episodes were recorded in 59 patients (6%) of the SR group, 21 (13%) in the silent AF group, and 13 (24%) in the symptomatic AF group (P < 0.001). After Cox multivariate analysis, AF during AMI, indexed left atrial volume, age, and creatinine at discharge were identified as independent risk factors of AF after AMI. Conclusion The results of our large-scale study suggest that patients experiencing paroxysmal new-onset AF (silent or symptomatic) during AMI are at higher risk of AF at follow-up. Our data raise the question of implementing anticoagulation therapy following these brief and often neglected episodes.

Increased Symmetric Dimethylarginine Level Is Associated with Worse Hospital Outcomes through Altered Left Ventricular Ejection Fraction in Patients with Acute Myocardial Infarction.

Objectives We aimed to investigate whether SDMA- symmetric dimethylarginine -the symmetrical stereoisomer of ADMA- might be a marker of left ventricular function in AMI. Background Asymmetric dimethylarginine (ADMA) has been implicated in the prognosis after acute myocardial infarction (AMI) and heart failure (HF). Methods Cross sectional prospective study from 487 consecutive patients hospitalized <24 hours after AMI. Patients with HF on admission were excluded. Serum levels of ADMA, SDMA and L-arginine were determined using HPLC. Glomerular filtration rate (eGFR) was estimated based on creatinine levels. Outcomes were in-hospital severe HF, as defined by Killip class >2, and death. Results Patients were analysed based on SDMA tertiles. Sex, diabetes, dyslipidemia, and prior MI were similar for all tertiles. In contrast, age and hypertension increased across the tertiles (p<0.001). From the first to the last tertile, GRACE risk score was elevated while LVEF and eGFR was reduced. The rate of severe HF and death were gradually increased across the SDMA tertiles (from 0.6% to 7.4%, p = 0.006 and from 0.6% to 5.0%, p = 0.034, respectively). Backward logistic multivariate analysis showed that SDMA was an independent estimate of developing severe HF, even when adjusted for confounding (OR(95%CI): 8.2(3.0–22.5), p<0.001). Further, SDMA was associated with mortality, even after adjustment for GRACE risk score (OR(95%CI): 4.56(1.34–15.52), p = 0.015). Conclusions Our study showed for the first time that SDMA is associated with hospital outcomes, through altered LVEF and may have biological activity beyond renal function.

Relation between high levels of myeloperoxidase in the culprit artery and microvascular obstruction, infarct size and reverse remodeling in ST-elevation myocardial infarction

Main objective To better understand the role of myeloperoxidases (MPO) in microvascular obstruction (MO) phenomenon and infarct size (IS) using cardiac magnetic resonance (CMR) data in patients with acute myocardial infarction (AMI). Method 40 consecutive patients classified according to the median level of MPO in the culprit artery. A CMR study was performed during the week following AMI and at 6 months, with late gadolinium enhancement sequences. Results Persistent MO was observed in the same proportion (50 vs. 65%, p = 0.728) between the low vs. high MPO group levels. However, the extent of the microvascular obstruction was significantly greater in the high-MPO group (6 (0–9) vs.16.5 (0–31), p = 0.027), together with a greater infarct size, and a trend towards a lower left ventricular ejection fraction (LVEF) (p = 0.054) at one week. CMR data at 6 months showed that reverse systolic remodeling was two fold more present in the low-MPO group (p = 0.058). Interestingly, the extent of MO (8.5 (6.5–31) vs. 4.1 (3–11.55), p = 0.042) and IS remained significantly greater (24.5 (9.75–35) vs. 7.5 (2.5–18.75), p = 0.022) in the high-MPO group. Moreover, MPO in the culprit artery appeared to correlate positively with MPO in non-culprit arteries and serum, and with troponin levels and peak CK. Conclusion This patient-based study revealed in patients after AMI that high MPO levels in the culprit artery were associated with more severe microvascular obstruction and greater IS. These findings may provide new insights pathophysiology explanation for the adverse prognostic impact of MO.