Laurent Lepage

Contemporary surgical or percutaneous management of severe aortic stenosis in the elderly

AIMS To assess patient characteristics, therapeutic options, and their results in patients referred to a tertiary centre with on-site capabilities for surgical and percutaneous valvular interventions for the management of severe symptomatic aortic stenosis (AS). METHODS AND RESULTS Sixty-six consecutive patients >70 years (83 +/- 6 years) were referred for severe AS. Their mortality risk predicted by the logistic European System for Cardiac Operative Risk Evaluation and the Society of Thoracic Surgeons-Predicted Risk of Mortality scores were on average 20 +/- 14% and 17 +/- 7%, respectively. Thirty-nine patients (59%) were considered at high-risk for surgery or inoperable after multidisciplinary evaluation: 12 (31%) underwent a transfemoral aortic valve implantation and 27 were considered unsuitable and treated medically (n = 16) or with valvuloplasty (n = 7), or were re-directed towards surgery (n = 4). The 27 other patients underwent valve replacement. In-hospital mortality was 9% (6 of 66). There were three hospital deaths in patients treated percutaneously, two in those treated medically, and one after surgery. At 6 months, 10% (6 of 60) of the survivors died: two after valvuloplasty and four after medical treatment. CONCLUSION A large proportion of elderly patients referred for management of severe AS have a high-risk profile. The availability of percutaneous valvular interventions increases the number of those who are offered interventions.

Effect of early cerebral magnetic resonance imaging on clinical decisions in infective endocarditis: a prospective study.

BACKGROUND Neurologic complications of endocarditis can influence diagnosis, therapeutic plans, and prognosis. OBJECTIVE To describe how early cerebral magnetic resonance imaging (MRI) affects the diagnosis and management of endocarditis in hospitalized adults. DESIGN Single-center prospective study between June 2005 and October 2008. (ClinicalTrials.gov registration number: NCT00144885) SETTING Tertiary care university hospital in France. PATIENTS 130 patients with endocarditis. INTERVENTION Cerebral MRI with angiography performed up to 7 days after admission and before any surgical intervention. MEASUREMENTS 2 experts jointly established the endocarditis diagnostic classification (according to Duke-modified criteria) and therapeutic plans just before and after MRI and then compared them. RESULTS Endocarditis was initially classified as definite in 77 patients and possible in 50 and was excluded in 3. Sixteen patients (12%) had acute neurologic symptoms. Cerebral lesions were detected by MRI in 106 patients (82% [95% CI, 75% to 89%]), including ischemic lesions in 68, microhemorrhages in 74, and silent aneurysms in 10. Solely on the basis of MRI results and excluding microhemorrhages, diagnostic classification of 17 of 53 (32%) cases of nondefinite endocarditis was upgraded to either definite (14 patients) or possible (3 patients). Endocarditis therapeutic plans were modified for 24 (18%) of the 130 patients, including surgical plan modifications for 18 (14%). Overall, early MRI led to modifications of diagnosis or therapeutic plan in 36 patients (28% [CI, 20% to 36%]). LIMITATION Investigators did not assess whether the MRI-related changes in diagnosis and therapeutic plans improved patient outcomes or led to unnecessary procedures and increased costs. CONCLUSION Cerebral lesions were identified by MRI in many patients with endocarditis but no neurologic symptoms. The MRI findings affected both diagnostic classifications and clinical management plans. PRIMARY FUNDING SOURCE French Ministry of Health.

Respective Performance of 18F-FDG-PET and Radiolabeled Leukocyte Scintigraphy for the Diagnosis of Prosthetic Valve Endocarditis

Echocardiography plays a key role in the diagnosis of infective endocarditis (IE) but can be inconclusive in patients in whom prosthetic valve endocarditis (PVE) is suspected. The incremental diagnostic value of 18F-FDG PET and radiolabeled leukocyte scintigraphy in IE patients has already been reported. The aim of this study was to compare the respective performance of 18F-FDG PET and leukocyte scintigraphy for the diagnosis of PVE in 39 patients. Methods: 18F-FDG PET and leukocyte scintigraphy were performed on 39 consecutive patients admitted because of clinically suspected PVE and inconclusive echocardiography results. The results of 18F-FDG PET and leukocyte scintigraphy were analyzed separately and retrospectively by experienced physicians masked to the results of the other imaging technique and to patient outcome. The final Duke–Li IE classification was made after a 3-mo follow-up. Results: Of the 39 patients, 14 were classified as having definite IE, 4 as having possible IE, and 21 as not having IE. The average interval between 18F-FDG PET and leukocyte scintigraphy was 7 ± 7 d. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93%, 71%, 68%, 94%, and 80%, respectively, for 18F-FDG PET and 64%, 100%, 100%, 81%, and 86%, respectively, for leukocyte scintigraphy. Discrepancies between the results of 18F-FDG PET and leukocyte scintigraphy occurred in 12 patients (31%). In patients with definite IE, 5 had true-positive 18F-FDG PET results but false-negative leukocyte scintigraphy results. Of these 5 patients, 3 had nonpyogenic microorganism IE (Coxiella or Candida). Of patients for whom endocarditis had been excluded, 6 had true-negative leukocyte scintigraphy results but false-positive 18F-FDG PET results. These 6 patients had been imaged in the first 2 mo after the last cardiac surgery. The last patient with a discrepancy between 18F-FDG PET and leukocyte scintigraphy was classified as having possible endocarditis and had positive 18F-FDG PET results and negative leukocyte scintigraphy results. Conclusion: 18F-FDG PET offers high sensitivity for the detection of active infection in patients with suspected PVE and inconclusive echocardiography results. Leukocyte scintigraphy offers a higher specificity, however, than 18F-FDG PET for diagnosis of IE and should be considered in cases of inconclusive 18F-FDG PET findings or in the first 2 mo after cardiac surgery.

Reappraisal of percutaneous aortic balloon valvuloplasty as a preliminary treatment strategy in the transcatheter aortic valve implantation era.

AIMS To assess the results of percutaneous aortic balloon valvuloplasty (PABV) as a potential bridge to further intervention in patients referred for transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS Two hundred and fifty-three patients referred for TAVI were studied: 41 (16%) were considered transiently unsuitable for either aortic valve replacement (AVR) or TAVI and underwent PABV as a bridge to intervention. In the others, primary TAVI or AVR was performed in 140 cases, and medical therapy alone in 72.The overall population was at high risk: 82 ± 8 years, logistic EuroSCORE: 28 ± 16%, STS score: 16 ± 10%. There was no PABV-related death. Twenty-three patients underwent secondary TAVI (n=19) or AVR (n=4), 18 did not undergo further intervention. One and two year survival rates were respectively 94 ± 5% and 85 ± 10% after bridge PABV, and 33 ± 11 and 6 ± 5% after PABV alone. There was no difference in survival between the primary TAVI / AVR and bridge PABV (p=0.08), and between medical treatment and PABV alone (p=0.36). CONCLUSION In high-risk patients with aortic stenosis and temporary contraindications to AVR or TAVI, PABV may be used as a bridge to intervention with good mid-term outcomes. In others, PABV can be safely used but is associated with a poor outcome.

Role of radiolabelled leucocyte scintigraphy in patients with a suspicion of prosthetic valve endocarditis and inconclusive echocardiography

AIMS In patients with a suspicion of prosthetic valve endocarditis (PVE), detection of perivalvular infection can be difficult based only on echocardiography. The aim of this retrospective study was to test the interest of radiolabelled leucocyte scintigraphy (LS) for the detection of perivalvular infection in patients with a suspicion of PVE and inconclusive transoesophageal echocardiography (TEE). METHODS AND RESULTS LS was performed in 42 patients. The results of LS were classified as positive in the cardiac area (intense or mild), or negative. Macroscopical aspects and bacteriology were obtained from patients who underwent cardiac surgery (n = 10). Clinical outcome was collected in patients treated medically (n = 32). Among patients with intense signal with LS who underwent surgery (n = 6), five had an abscess confirmed during intervention and one, post-operatively. Patients with intense accumulation of radiolabelled leucocytes with scintigraphy and treated medically (n = 3) had a poor outcome: death (n = 1); prosthetic valve dehiscence (n = 1); and recurrent endocarditis (n = 1). Among patients with mild activity with LS (n = 5), one patient developed a large prosthetic valve dehiscence during the follow-up. The remaining four patients were treated medically and did not present any recurrent endocarditis after a median follow-up of 14 months. No abscess was detected in patients with negative LS who underwent surgery (n = 4). Among the patients with negative LS treated medically (n = 24), none presented recurrent endocarditis after a mean follow-up of 15 ± 16 months. Patient management was influenced by the results of LS in 12 out of 42 patients (29%). CONCLUSION This study suggests that LS is useful for the identification of perivalvular infection in patients with a suspicion of PVE and inconclusive TEE.

Dilation-Dependent Activation of Platelets and Prothrombin in Human Thoracic Ascending Aortic Aneurysm

Objectives—The purpose of this study was to investigate whether thoracic ascending aortic aneurysm (TAAA) induces platelet activation as mural thrombus participates in aortic dilatation in abdominal aortic aneurysm and TAAA are associated with rheological factors favoring coagulation activation. Methods and Results—We studied the relation between coagulation activation and aortic diameter in Marfan patients (MFS) with various aortic diameters (n=52). We then studied patients presenting large aneurysms associated with bicuspid aortic valve (BAV) and degenerative form. Lastly, we used immunochemistry and biochemistry to investigate prothrombin/thrombin retention within the aortic wall. Microparticles, sGPV, tissue factor, and TAT complexes were increased in plasma from MFS with large aneurysms (≥45 mm) compared to MFS with limited aortic dilatation (<45 mm). Similar elevations were observed in all patients with large aortic aneurysms, regardless of the etiology, the site of maximal aortic dilation, associated valvulopathy, risk factors, or treatments. P-selectin and platelet-bound fibrinogen were also increased, demonstrating platelet activation in large aneurysms. Significant increase in sCD146 plasma concentration suggested alteration of endothelium. Conclusions—Platelet activation occurs in patients with large aneurysms of the ascending aorta, is dependent on aortic dilation, and is associated with thrombin generation, part of which appears to be retained in mucoid degeneration areas.

Determinants of Cerebral Lesions in Endocarditis on Systematic Cerebral Magnetic Resonance Imaging: A Prospective Study

Background and Purpose— Cerebral lesions are frequent complications of infective endocarditis (IE) and have a prognostic impact. Cerebral MRI identifies lesions in a high number of patients. However, their determinants have not been identified. The aim of the study was to define the determinants of cerebral lesions in patients with IE undergoing systematic cerebral MRI. Methods— Determinants of ischemic lesions and of microbleeds were prospectively analyzed in 120 patients with left-sided IE, using systematic cerebral MRI. Results— Median age was 60 years (interquartile range 51–72); IE occurred on a prosthetic valve in 37 patients (30.8%) and was due to Streptococci in 47 patients and Staphylococci in 36; 15 (12.5%) had neurological symptoms. MRI detected ischemic lesions in 64 patients (53.3%; territorial lesions in 32 and small lesions in 57) and microbleeds in 72 (60.0%). In multivariate analysis, ischemic lesions were associated with vegetation length (odds ratio 1.10/mm; 95% confidence interval 1.03–1.16; P=0.003) and Staphylococcus aureus IE (odds ratio 2.65; 95% confidence interval 1.01–6.96; P=0.05). A vegetation length >4 mm identified ischemic lesions with a sensitivity of 74.6% and a specificity of 51.5%. Microbleeds were associated with prosthetic IE (odds ratio 8.01; 95% confidence interval 2.58–24.90; P=0.0003) and not with prior anticoagulant therapy (P=0.67). Conclusions— Systematic cerebral MRI frequently detects ischemic lesions and microbleeds during acute IE. The high sensitivity of MRI shows that each millimeter increase in vegetation length is associated with a 10% increase in the rate of ischemic lesions. Conversely, microbleeds are associated only with prosthetic IE in this study. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00144885.

Size-Adjusted Left Ventricular Outflow Tract Diameter Reference Values: A Safeguard for the Evaluation of the Severity of Aortic Stenosis

OBJECTIVE We sought to evaluate the relationship among left ventricular outflow tract diameter (LVOTd), gender, and body surface area (BSA) and to evaluate the usefulness of size-adjusted LVOTd reference values in patients with aortic stenosis (AS). AS grading is based on the echocardiographic calculation of the aortic valve area (AVA) and requires LVOTd measurements, one main potential source of error. Transesophageal echocardiography (TEE) is reputed to be more accurate than transthoracic echocardiography (TTE), but validation studies are rare. A safeguard for LVOTd measurements is thus desirable. METHODS Since January 2006, 3 subsets of patients have been prospectively and concurrently enrolled: 1) TEE group: In 120 patients with and without AS, we prospectively measured LVOTd during both TTE and TEE. 2) Validation set: In 382 patients without aortic valve or ascending aorta diseases, we evaluated the relationship among LVOTd, gender, and BSA. 3) Testing set: In 173 patients with AS, we compared the AVA obtained using measured LVOTd (AVA(MEAS)) and calculated LVOTd derived from a regression determined in the validation set (AVA(CALC)). RESULTS TTE did not differ from and correlated well with TEE measurements overall (23 +/- 2 mm vs 23 +/- 2 mm, P = .26; r = 0.95, P < .0001) and in patients with AS (N = 43) (24 +/- 2 mm vs 24 +/- 3 mm, P = .15; r = 0.92, P < .0001). LVOTd was linearly correlated to BSA independently of gender (LVOTd = 5.7 * BSA+12.1; r = 0.55, P < .0001). In the testing set, AVA(CALC) did not differ from and correlated well with AVA(MEAS) (1.20 +/- 0.42 cm2 vs 1.23 +/- 0.40 cm2; P = .08; r = 0.89; P < .0001). CONCLUSION TTE and TEE measurements of the LVOTd provided similar results. LVOTd was significantly associated to BSA and LVOTd, derived from a linear regression linked to BSA independently of gender, provided an acceptable approximation of the AVA. Thus, although accurate measurement of LVOTd is a crucial part of the echocardiographic evaluation of AS severity, the present equation may be used as a safeguard when this measurement is difficult or not possible with TTE.

Prognostic value of B-type natriuretic peptide in elderly patients with aortic valve stenosis: the COFRASA–GENERAC study

Objective Previous studies suggested an independent prognostic value of B-type natriuretic peptide (BNP) in aortic valve stenosis (AS) but were impeded by small sample sizes and inclusion of relatively selected young patients. We aimed to evaluate the relationship among N-terminal fragment of proBNP (Nt-proBNP), AS severity, symptoms and outcome in a large cohort of elderly patients with AS. Design Observational cohort study, COhorte Française de Retrecissement Aortique du Sujet Agé (clinicalTrial.gov number-NCT00338676) and GENEtique du Retrecissement Aortique (clinicalTrial.gov number-NCT00647088). Setting Single-centre study. Patients Patients older than 70 years with at least mild AS. Interventions None. Measurements A comprehensive clinical, biological and echocardiographic evaluation was performed at study entry. Asymptomatic patients were prospectively followed on a 6-months basis and AS-related events (sudden death, congestive heart failure or new onset of AS-related symptoms) collected. Results We prospectively enrolled 361 patients (79±6 years, 230 severe AS). Nt-proBNP increased with the grade of AS severity and the NYHA class (all p<0.0001) but there was an important overlap between grades/classes. Consequently, diagnostic value of Nt-proBNP for the diagnosis of severe symptomatic AS was only modest (area under the curve of the receiver operator characteristic analysis=0.73). At 2 years, 28 AS-related events occurred among 142 asymptomatic patients prospectively followed. Nt-proBNP was associated with outcome in univariate analysis (p=0.04) but not after adjustment for age, gender and AS severity (p=0.40). Conclusions The present study clearly highlights the limitations of Nt-proBNP for the evaluation and management of AS patients. Our results suggest that Nt-proBNP should be considered cautiously, at least as a single criterion, in the decision-making process of AS patients especially in the elderly population.

Usefulness of Left Atrial Volume Versus Diameter to Assess Thromboembolic Risk in Mitral Stenosis

In patients with mitral stenosis (MS) in sinus rhythm (SR), guidelines recommend anticoagulation if the left atrium is enlarged based on diameter measurements. We sought to compare the association of left atrial (LA) diameter and LA volume with markers of thromboembolic risk (peak LA appendage emptying velocity [LAAv] and LA spontaneous contrast density) measured during transesophageal echocardiography in 152 patients with moderate to severe MS. High thromboembolic risk was defined by a peak LAAv < 25 cm/s and/or dense spontaneous contrast. Mean LA diameter (50 ± 7 mm, 32 to 77) and LA volume (152 ± 70 ml, 67 to 720) were significantly correlated (r = 0.71, p < 0.0001), but the relation was curvilinear and the 95% confidence interval increased with LA diameter. In the subset of 80 patients in SR who underwent clinically indicated transesophageal echocardiography, body surface area (BSA)-indexed LA volume but not LA diameter differentiated patients with normal from those with low LAAv (86 ± 17 vs 71 ± 17 ml/m(2), p < 0.01, and 50 ± 6 vs 48 ± 6 mm, p = 0.13, respectively) and patients with dense spontaneous contrast from those with no or mild spontaneous contrast (81 ± 16 vs 63 ± 15 ml/m(2), p < 0.01, and 49 ± 6 vs 46 ± 5 mm, p = 0.11, respectively). BSA-indexed LA volume provided the highest area under the curve (0.85) for high thromboembolic risk and LA diameter the lowest (0.65). A BSA-indexed LA volume > 60 ml/m(2) provided an excellent 90% sensitivity despite 44% specificity, 76% positive predictive value, and 70% negative predictive value. Use of this threshold instead of 50 or 55 mm would have changed the indication for anticoagulation in 51% to 77% of patients. In conclusion, LA volume was more strongly associated with markers of thromboembolic risk than LA diameter, which poorly reflected LA size. Our results support the use of BSA-indexed LA volume to guide the decision for anticoagulation in patients with MS in SR, which may lead to significant change in the management of those patients. We suggest a threshold of 60 ml/m(2), which has good sensitivity, albeit with low specificity.