Stéphane Cade

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/m2, 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 cm2 versus 0.86±0.14 cm2), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m2), 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.

Exercise Response in Hypertrophic Cardiomyopathy: Blunted Left Ventricular Deformational and Twisting Reserve with Altered Systolic-Diastolic Coupling

Background— Abnormal left ventricular (LV) deformational mechanics have been demonstrated in patients with hypertrophic cardiomyopathy (HCM) at rest, but there is a lack of information on their adaptation to exercise. The aim of this study was to assess the adaptability of LV strains and torsional mechanics during exercise in HCM patients. Methods and Results— Twenty nonobstructive HCM patients (age, 48.3±12.3 years; 14 men) and 20 control subjects underwent speckle-tracking echocardiographic measurement of longitudinal, radial, and circumferential strains, systolic twist, and diastolic untwisting rate (UTR) at rest and submaximal exercise. HCM patients showed lower resting longitudinal (−15.7±5.0% versus −19.4±2.6%, P<0.001) and radial (38.1±11.3% versus 44.7±14.4%, P<0.05) strains but higher circumferential strain (−21.9±4.0% versus −18.8±2.3%, P<0.05) and twist (15.7±3.6° versus 9.3±2.6°, P<0.0001) than control subjects. Exercise induced an increase in all strains in control subjects but only a moderate increase in longitudinal strain (to −18.4±5.0%), without significant changes in radial and circumferential strains or twist in HCM patients. Exercise peak UTR was lower (−119.0±31.5°/s versus −137.3±41.1°/s) and occurred later (137±18% versus 125±11% systolic time, P<0.05) in HCM than in control subjects. A significant relationship between twist and UTR was obtained in control subjects (ß=−0.0807, P<0.001) but not in HCM patients (ß=−0.0051, P=0.68). Conclusions— HCM patients had severely limited strain adaptability and no LV twisting reserve at exercise. They had reduced and delayed UTR with reduced systolic-diastolic coupling efficiency by twist-untwist mechanics.Background— Abnormal left ventricular (LV) deformational mechanics have been demonstrated in patients with hypertrophic cardiomyopathy (HCM) at rest, but there is a lack of information on their adaptation to exercise. The aim of this study was to assess the adaptability of LV strains and torsional mechanics during exercise in HCM patients. Methods and Results— Twenty nonobstructive HCM patients (age, 48.3±12.3 years; 14 men) and 20 control subjects underwent speckle-tracking echocardiographic measurement of longitudinal, radial, and circumferential strains, systolic twist, and diastolic untwisting rate (UTR) at rest and submaximal exercise. HCM patients showed lower resting longitudinal (−15.7±5.0% versus −19.4±2.6%, P <0.001) and radial (38.1±11.3% versus 44.7±14.4%, P <0.05) strains but higher circumferential strain (−21.9±4.0% versus −18.8±2.3%, P <0.05) and twist (15.7±3.6° versus 9.3±2.6°, P <0.0001) than control subjects. Exercise induced an increase in all strains in control subjects but only a moderate increase in longitudinal strain (to −18.4±5.0%), without significant changes in radial and circumferential strains or twist in HCM patients. Exercise peak UTR was lower (−119.0±31.5°/s versus −137.3±41.1°/s) and occurred later (137±18% versus 125±11% systolic time, P <0.05) in HCM than in control subjects. A significant relationship between twist and UTR was obtained in control subjects (s=−0.0807, P <0.001) but not in HCM patients (s=−0.0051, P =0.68). Conclusions— HCM patients had severely limited strain adaptability and no LV twisting reserve at exercise. They had reduced and delayed UTR with reduced systolic-diastolic coupling efficiency by twist-untwist mechanics.

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.

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

Abstract 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.

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.

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 (123I-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 123I-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 123I-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, 123I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

Prevalence of obstructive sleep apnoea in acute coronary syndrome: Routine screening in intensive coronary care units

INTRODUCTION Increased evidence has shown that, despite the maximum care afforded to patients admitted with acute coronary syndromes (ACS), a residual risk of mortality remains, in which obstructive sleep apnoea (OSA) appears to be a largely undiagnosed factor, particularly in the intensive cardiac care unit (ICCU). The purpose of this study is to determine whether the systematic screening for sleep-disordered breathing (SDB) is feasible and may be recommended. The aims of our study are to determine: (1) The estimated prevalence of OSA in patients admitted to the ICCU for ACS determined by a validated, user-friendly portable screening device; (2) The feasibility of the screening in this context; (3) To assess any negative impact of OSA on the severity of ACS. PATIENTS AND METHODS This is an observational study of 101 patients admitted to the ICCU for ACS showing no clinical evidence of heart failure (HF). In the 24-72hours following admission, they underwent an overnight sleep study using a 3-channel portable screening device with automatic analysis. RESULTS Sixty-two out of the 101 patients proved positive to the screening test, and its feasibility was acceptable. OSA patients tended to have greater peak levels of hs-cTnT (3685±3576ng/L versus 2830±3333ng/L, P=0.08) than the non-OSA group. Compared with the non-OSA group, OSA patients presented more severe ACS, with a greater average GRACE score at admission of 112.2±26.3 (versus 98.4±19.2, P<0.001). In the OSA group, we found a statistically significant inverse correlation between the apnoea-hypopnea index (AHI) and the left ventricular ejection fraction (LVEF) in the linear regression analysis (r=-0.26; P=0.037). CONCLUSIONS A systematic screening of patients in the ICCU is acceptable. OSA is frequently found in the acute phase of ischaemic heart disease and its presence is associated with more severe ACS and a poorer left ventricle systolic function.

083 - Medical hypothesis: heart rate on admission and CRP are correlated, in acute pericarditis: a link between heart rate and pericardial inflammation?

Introduction 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 in our center for acute pericarditis. Diagnosis criteria included 2 among the following: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical ECG findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. We evaluated also recurrences and clinical events during hospitalization and at one month. Results We included 73 patients. Median age was 38.0 y (CI 25-75% 28.0-51.0) and median hospitalization duration was 2.0 d (1.5-3.0). 27% of the patients presented pericardial effusion. Heart rate on admission was 88.0 bpm (CI 25-75%: 76.0-100.0) and on discharge 72.0 (65.0-80.0)). Heart rate on admission was significantly correlated with CRP on admission (r=0.34, n=69; p=0.004), CRP peak (r=0.54; n=61; p Conclusion In acute pericarditis, HR on admission is independently correlated with CRP levels. These observations could suggest a link between HR and pericardial inflammation.

325: Ivabradine and dobutamine associated as a pure inotropic drug in cardiogenic shock?

Introduction Dobutamine remains gold-standard treatment in cardiogenic shock. However, it exacerbates tachycardia, worsening heart failure. Ivabradine, a specific inhibitor of If channel, could reduce this deleterious effect in association with dobutamine in patients with cardiogenic shock. We report the case of a 41-year-old woman admitted in intensive care unit for a severe heart failure with hemodynamic shock. She had no medical history. She suffered from thoracic and epigastric pain and cholecystis was initially diagnosed with an indication of sphincterotomy. However, her clinical status progressively worsened with severe dyspnea and global heart failure requiring appropriate treatment. ECG showed inverted T waves in the lateral leads and echocardiography showed a dilated cardiomyopathy with severe systolic alteration (LVEF: 35%). Coronary angiogram was strictly normal. Finally, no evidence was found on cardiac MRI for ischemic process or myocarditis. She progressively worsened with renal and hepatic dysfunction. Troponin and inflammation markers remained negative. It was necessary to introduce dobutamine and intravenous diuretics but we noticed an initial increase in heart rate concomitantly with blood pressure. We added ivabradine in order to reduce heart rate without effect on blood pressure (fig). Her clinical status improved and dobutamine could be stopped after 5 days and beta-blockers were then introduced. Discussion Heart rate is a well-known marker of prognosis and tachycardia worsened by dobutamine could be deleterious to evolution of patient with cardiogenic shock. Ivabradine could be helpful in reducing heart rate without effect on blood pressure. However, this drug is indicated in stable heart failure but, to this day, hemodynamic instability is excluded. New prospective studies seem necessary to evaluate this benefit. Conclusion In cardiogenic shock, association of dobutamine and ivabradine could be interesting to create a pure inotropic drug. Download full-size image

Response to Letter Regarding Article, “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”

Response: We read the comments of Dr Ozkan and would like to answer his questions and remarks. Concerning left ventricular midwall fractional shortening, it is known for a long time that it is impaired in severe aortic stenosis (AS). Midwall fractional shortening has been shown to be particularly reduced in low-flow, low-gradient AS, as shown by Hachicha et al1 and confirmed in our study.2 In both studies, midwall fractional shortening was particularly low in the group of low-flow AS, although the difference was not significant in our study ( P =0.07), probably related to the small sample size in each subgroup. Dr Ozkan underlines that values of basal strain as low as −13.9% have been reported in normal individuals,3,4 meaning that the low basal strain observed in patients with AS in our study does not systematically represent left ventricular dysfunction. However, a …