Cécile Lavoute

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.

Risk score for cardiac surgery in active left-sided infective endocarditis

Objective To develop and validate a calculator to predict the risk of in-hospital mortality in patients with active infective endocarditis (IE) undergoing cardiac surgery. Methods Thousand two hundred and ninety-nine consecutive patients with IE were prospectively recruited (1996–2014) and retrospectively analysed. Left-sided patients who underwent cardiac surgery (n=671) form our study population and were randomised into development (n=424) and validation (n=247) samples. Variables statistically significant to predict in-mortality were integrated in a multivariable prediction model, the Risk-Endocarditis Score (RISK-E). The predictive performance of the score and four existing surgical scores (European System for Cardiac Operative Risk Evaluation (EuroSCORE) I and II), Prosthesis, Age ≥70, Large Intracardiac Destruction, Staphylococcus, Urgent Surgery, Sex (Female) (PALSUSE), EuroSCORE ≥10) and Society of Thoracic Surgeons’s Infective endocarditis score (STS-IE)) were assessed and compared in our cohort. Finally, an external validation of the RISK-E in a separate population was done. Results Variables included in the final model were age, prosthetic infection, periannular complications, Staphylococcus aureus or fungi infection, acute renal failure, septic shock, cardiogenic shock and thrombocytopaenia. Area under the receiver operating characteristic curve in the validation sample was 0.82 (95% CI 0.75 to 0.88). The accuracy of the other surgical scores when compared with the RISK-E was inferior (p=0.010). Our score also obtained a good predictive performance, area under the curve 0.76 (95% CI 0.64 to 0.88), in the external validation. Conclusions IE-specific factors (microorganisms, periannular complications and sepsis) beside classical variables in heart surgery (age, haemodynamic condition and renal failure) independently predicted perioperative mortality in IE. The RISK-E had better ability to predict surgical mortality in patients with IE when compared with other surgical scores.

The role of NMDA and GABAA receptors in the inhibiting effect of 3 MPa nitrogen on striatal dopamine level

Nitrogen pressure exposure, in rats, resulted in a decreased dopamine (DA) level by the striatal terminals of the substantia nigra pars compacta (SNc) dopaminergic neurons, due to the narcotic potency of nitrogen. In the SNc, the nigrostriatal pathway is under glutamatergic and GABAergic control mediated by ion-channel NMDA and GABA(A) receptors, main targets of volatile anesthetics. The aim of this study was to investigate the role of these receptors in the regulation of striatal dopamine level under nitrogen narcosis. Under general anesthesia, male Sprague-Dawley rats were bilaterally implanted in the striatum with dopamine-sensitive electrodes and, in the SNc, with guide cannulae for drug injections. After recovery from surgery, the striatal dopamine level was quantified using differential pulse voltammetric measurements in freely moving rats. Focal injections of agonists (NMDA/muscimol) and antagonists (AP7/gabazine) of NMDA/GABA(A) receptors were made within SNc. Both normobaric condition and 3 MPa nitrogen pressure were studied. Control experiments confirmed a direct glutamatergic control on the striatal DA level through NMDA receptors. Both direct and indirect GABAergic control through two different types of GABA(A) receptors located on GABAergic interneurons and on DA cells were indicated. Under nitrogen pressure, the decrease in dopamine level (20%) was suppressed by both NMDA and GABA(A) agonist infusion. There was an unexpected increasing DA level, induced by AP7 (about 10%) and gabazine (about 30%). These results indicate that NMDA receptors remain functional and suggest a decreased glutamate release. The findings also describe an increase of GABA(A) receptor-mediated inhibition on DA cells under nitrogen pressure exposure.

Infective endocarditis in octogenarians

Objective To describe the characteristics of infective endocarditis (IE) in octogenarians and assess their prognosis. Methods Patients with definite IE hospitalised at a referral centre between July 2008 and July 2013 were prospectively included. A total of 454 patients were divided into three groups: 230 patients under 65 years old, 173 patients between 65 and 80 years old, and 51 patients over 80 years old. The main end point was 1-year mortality. Results One-year mortality was higher in the ≥80 years old group (37.3%) than in the <65 years old group (13%; p<0.001) and the 65–80 years old group (19.7%; p=0.009). Enterococci and Streptococcus gallolyticus were the more frequent micro-organisms. Embolism under antibiotic therapy (n=11 (21.6%), p=0.03) and renal failure (n=23 (51%), p=0.004) were more frequent in the ≥80 years old group. Among the ≥80 years old group, 38 patients had theoretical indication for surgery. Mortality was low (6.3%) in the 16 operated patients, but very high (72.7%) in the 22 patients not operated. Even if octogenarians were less often operated, their survival after surgery was excellent like younger patients (93.7%, 89.9% and 90.4%, respectively), whereas the absence of surgery was associated with very poor prognosis. Conclusions IE in octogenarians is a different disease, with Enterococci as the most frequent micro-organisms and with higher mortality than younger patients. ESC recommendations for surgery are less implemented than in younger patients, yielding dramatic mortality in patients not operated despite a theoretical indication for surgery, while operated patients have an excellent prognosis. These results suggest that surgery is underused in octogenarians.

Diagnosis of Infective Endocarditis After TAVR: Value of a Multimodality Imaging Approach

Diagnosis of infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) remains difficult to establish using modified Duke criteria. We present the value of multi-imaging approach (European Society of Cardiology [ESC]-2015 modified criteria) [(1)][1] in 16 patients referred for

Evaluation of empirical treatment for blood culture-negative endocarditis

Objectives Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous antibiotics used or fastidious pathogens) are available. We performed this study to evaluate the effectiveness of our therapeutic protocol in BCNE, based on compliance with the protocol, outcome and 1 year mortality. Patients and methods We collected prospectively and analysed retrospectively cases of BCNE between 2002 and 2014, using a simplified and standardized protocol developed by our multidisciplinary team. We apply two kinds of protocols to treat BCNE, which include only four intravenous antimicrobial agents: amoxicillin, vancomycin, gentamicin and amphotericin B. Results We had 177 patients with definite BCNE. There were 154 (87.0%) patients treated with both appropriate antimicrobial agents and appropriate duration of treatment. We analysed the causes of inappropriate treatment in 13 (7.3%) cases and inappropriate duration in 10 (5.6%) cases. The treatment changes were justified in all cases except one of discharge against medical advice. The fatality rate was 5.1% (nine cases) and all deaths occurred in the group of patients who were treated with appropriate treatment; however, four deaths were not attributable to empirical treatment failure. Concerning the other deaths, the lack of surgical management, in association with empirical treatment, could explain our protocols failure, such as poorly tolerated surgery. Conclusions Our protocol is efficient and our mortality rate was low, compared with the literature review. This may result from a strategy that uses a sampling procedure and a standardized protocol at the same time.

Coronary events complicating infective endocarditis

Objective Acute coronary syndromes (ACS) are a rare complication of infective endocarditis (IE). Only case reports and small studies have been published to date. We report the largest series of ACS in IE. The aim of our study was to describe the incidence and mechanisms of ACS associated with IE, to assess their prognostic impact and to describe their management. Methods In a bicentre prospective observational cohort study, all patients with a definite diagnosis of IE were prospectively included. The incidence, mechanism and prognosis of patients with ACS were studied. Results Among 1210 consecutive patients with definite IE, 26 patients (2.2%) developed an ACS. Twenty-three patients (88%) had a coronary embolism. Two patients had coronary compression by an abscess or a pseudoaneurysm and one patient had an obstruction of his bioprosthesis and left coronary ostium by a large vegetation. Nineteen (73%) patients with ACS developed heart failure and this complication was 2.5 times more frequent than in patients without ACS (p<0.0001). In the ACS population, mortality rate was twice than the population without ACS. Conclusions ACS is a rare complication of IE but is associated with an increased risk of heart failure and high mortality rate.

Dopamine, Neurochemical Processes, and Oxygen Toxicity at Pressure.

All mammals, including man, exposed to breathing gas mixtures at high pressures exhibit central nervous system disturbances, which differ according to the gas used. With the use of compressed air, the increased oxygen partial pressure induces hyperoxic disturbances that consist of epileptic seizures that occur, on average, after 30 min exposure to 2.8 ATA in man or to 5 ATA in rats. Increased oxygen partial pressure induces reactive oxygen species and reactive nitrogen species production that could be related to neurotransmitter changes reported for the preepileptic phase or at pressures that produce epileptic seizures. In rats, oxygen pressures lower than 5 ATA induce a decrease of dopamine release in the stratum that could be due to disturbances of neurotransmitter regulatory processes that are different from those implicated for hyperbaric oxygen-induced epileptic seizures.

Apical four-chamber longitudinal left ventricular strain in patients with aortic stenosis and preserved left ventricular ejection fraction: analysis related with flow/gradient pattern and association with outcome

Aims To evaluate the prognostic value of apical four-chamber (A4-C) longitudinal strain (LS) in patients with aortic stenosis (AS). Methods and results In a multicentre cohort, 582 patients (74.3 ± 10.9 years) with moderate or severe AS and preserved left ventricular (LV) ejection fraction (≥50%) were included in this retrospective study. Patients with severe AS were classified in four subgroups according to flow and gradient: low flow (LF) was defined as a stroke volume index <35 mL/m2 compared with normal flow (NF); low-gradient (LG) as a mean gradient <40 mmHg compared with high gradient (HG). The end point was all-cause of mortality. A4-C LS was measured by two-dimensional speckle tracking and was feasible in all patients. The degree of A4-C LV longitudinal dysfunction increased according to the severity and subgroups of severe AS: from the least to the most impaired: moderate AS, NF/HG, NF/LG, LF/HG, and LF/LG AS (P < 0.001). During a mean follow-up of 2.6 ± 0.2 years, 58(10%) patients died. The 2-year survival was 76.8% in patients with LF/LG vs. 89.3% in patients with other groups. The best threshold of A4-C LS associated with overall mortality was an absolute cut-off value of |13.75%|. According to this cut-off, the 2-year survival was higher both in patients with moderate AS (96.3 vs. 70%, P = 0.02) and those with severe AS (92.9 vs. 80.9%, P = 0.005). However when dichotomized according to flow/gradient patterns, the association was only statistically significant in the subgroup of patients with NF/HG. By multivariable cox regression analysis, A4-C LS <|13.75| remained independently associated with overall mortality (hazard ratio: 1.8; P = 0.045). Conclusion A4-C LS is independently associated with death in patients with AS and preserved LVEF, however the flow/gradient pattern should also be considered as an important parameter. The management of these patients may use A4-C LS as a new parameter of evaluation of LV function and prognosis.

Intracranial haemorrhage in infective endocarditis

BACKGROUND Although intracranial cerebral haemorrhage (ICH) complicating infective endocarditis (IE) is a critical clinical issue, its characteristics, impact, and prognosis remain poorly known. AIMS To assess the incidence, mechanisms, risk factors and prognosis of ICH complicating left-sided IE. METHODS In this single-centre study, 963 patients with possible or definite left-sided IE were included from January 2000 to December 2015. RESULTS Sixty-eight (7%) patients had an ICH (mean age 57±13 years; 75% male). ICH was classified into three groups according to mechanism: ruptured mycotic aneurysm (n=22; 32%); haemorrhage after ischaemic stroke (n=27; 40%); and undetermined aetiology (n=19; 28%). Five variables were independently associated with ICH: platelet count<150×109/L (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.01-5.4; P=0.049); severe valve regurgitation (OR 3.2, 95% CI 1.3-7.6; P=0.008); ischaemic stroke (OR 4.2, 95% CI 1.9-9.4; P<0.001); other symptomatic systemic embolism (OR 14.1, 95% CI 5.1-38.9; P<0.001); and presence of mycotic aneurysm (OR 100.2, 95% CI 29.2-343.7; P<0.001). Overall, 237 (24.6%) patients died within 2.3 (0.7-10.4) months of follow-up. ICH was not associated with increased mortality (P not significant). However, the 1-year mortality rate differed according to ICH mechanism: 14%, 15% and 45% in patients with ruptured mycotic aneurysm, haemorrhage after ischaemic stroke and undetermined aetiology, respectively (P=0.03). In patients with an ICH, mortality was higher in non-operated versus operated patients when cardiac surgery was indicated (P=0.005). No operated patient had neurological deterioration. CONCLUSIONS ICH is a common complication of left-sided IE. The impact on prognosis is dependent on mechanism (haemorrhage of undetermined aetiology). We observed a higher mortality rate in patients who had conservative treatment when cardiac surgery was indicated compared with in those who underwent cardiac surgery.