David Messika-Zeitoun

Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis.

OBJECTIVES We sought to describe the results of a strategy offering either transfemoral or transapical aortic valve implantation in high-risk patients with severe aortic stenosis. BACKGROUND Results of transfemoral and transapical approaches have been reported separately, but rarely following a uniform assessment to select the procedure. METHODS Of 160 consecutive patients at high risk or with contraindications to surgery, referred between October 2006 and November 2008, 75 were treated with transcatheter aortic valve implantation. The transfemoral approach was used as the first option and the transapical approach was chosen when contraindications to the former were present. The valve used was the Edwards Lifesciences SAPIEN prosthesis. RESULTS Patients were age 82 +/- 8 years (mean +/- SD), in New York Heart Association functional classes III/IV, with predicted mean surgical mortalities of 26 +/- 13% using the European System for Cardiac Operative Risk Evaluation and 16 +/- 7% using the Society of Thoracic Surgeons Predicted Risk of Mortality. Fifty-one patients were treated via the transfemoral approach, and 24 via the transapical approach. The valve was implanted in 93% of the patients. Hospital mortality was 10%. Mean (+/- SD) 1-year survivals were 78 +/- 6% in the whole cohort, 81 +/- 7% in the transfemoral group, 74 +/- 9% in the transapical group (p = 0.22), and 60 +/- 10% in the first 25 patients versus 93 +/- 4% in the last 50 patients treated (p = 0.001). In multivariate analysis, early experience was the only significant predictor of late mortality. CONCLUSIONS Being able to offer either transfemoral or transapical aortic valve implantation, within a uniform assessment, expands the scope of the treatment of aortic stenosis in high-risk patients and provides satisfactory results at 1 year in this population. The results are strongly influenced by experience.

Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction

Background Measurement of the degree of aortic valve calcification (AVC) using electron beam computed tomography (EBCT) is an accurate and complementary method to transthoracic echocardiography (TTE) for assessment of the severity of aortic stenosis (AS). Whether threshold values of AVC obtained with EBCT could be extrapolated to multislice computed tomography (MSCT) was unclear and AVC diagnostic value in patients with low ejection fraction (EF) has never been specifically evaluated. Methods Patients with mild to severe AS underwent prospectively within 1 week MSCT and TTE. Severe AS was defined as an aortic valve area (AVA) of less than 1 cm2. In 179 patients with EF greater than 40% (validation set), the relationship between AVC and AVA was evaluated. The best threshold of AVC for the diagnosis of severe AS was then evaluated in a second subset (testing set) of 49 patients with low EF (≤40%). In this subgroup, AS severity was defined based on mean gradient, natural history or dobutamine stress echocardiography. Results Correlation between AVC and AVA was good (r=−0.63, p<0.0001). A threshold of 1651 arbitrary units (AU) provided 82% sensitivity, 80% specificity, 88% negative-predictive value and 70% positive-predictive value. In the testing set (patients with low EF), this threshold correctly differentiated patients with severe AS from non-severe AS in all but three cases. These three patients had an AVC score close to the threshold (1206, 1436 and 1797 AU). Conclusions In this large series of patients with a wide range of AS, AVC was shown to be well correlated to AVA and may be a useful adjunct for the evaluation of AS severity especially in difficult cases such as patients with low EF.

B-type natriuretic peptide in organic mitral regurgitation : Determinants and impact on outcome

Background—B-type natriuretic peptide (BNP) activation observed in cardiac diseases is a predictor of poor outcome; however, in organic mitral regurgitation (MR), BNP determinants and prognostic value are unknown. Methods and Results—We prospectively enrolled 124 patients with chronic organic MR (aged 63±15 years, 60% males) in whom we measured BNP level and simultaneously quantified MR degree, left ventricular (LV) remodeling, and left atrial (LA) volumes and analyzed long-term outcome. Baseline BNP level (54±67 pg/mL, median 31 pg/mL) was associated univariately with multiple clinical and echocardiographic characteristics, but in multivariate analysis, independent determinants of BNP, beyond age and sex (both P≤0.01), were LV end-systolic volume index, LA volume, atrial fibrillation, and symptoms (all P<0.02). Conversely, MR degree was not independently associated with BNP. During follow-up, patients with high versus low BNP (≥31 versus <31 pg/mL) displayed lower survival rates (at 5 years, 72±10% versus 95±5%, P=0.03) and higher rates of the combined end point of death and heart failure (at 5 years, 42±10% versus 16±7%, P=0.03). In multivariate analysis, with adjustment for age, sex, functional class, MR severity, and ejection fraction, BNP was independently predictive of mortality (hazard ratio per 10 pg/mL, 1.23 [95% CI 1.07 to 1.48], P=0.004) and of death or heart failure (hazard ratio per 10 pg/mL, 1.09 [95% CI 1.001 to 1.19], P=0.04). Conclusions—BNP activation in organic MR reflects primarily ventricular and atrial consequences rather than degree of MR. Higher BNP level in patients with organic MR independently predicts adverse events under conservative management. Therefore, BNP activation in organic MR is an emerging biomarker of severity of MR consequences and of poor clinical outcome, and its assessment should be considered in the clinical evaluation and risk stratification of patients with MR.

Impact of Left Atrial Volume on Clinical Outcome in Organic Mitral Regurgitation

OBJECTIVES The purpose of this paper was to assess the link between left atrial (LA) volume at diagnosis and outcome of patients with mitral regurgitation (MR). BACKGROUND Left atrial enlargement is a consequence of organic MR, but its association with clinical outcome independently of MR severity is uncertain. METHODS We prospectively enrolled 492 patients (age 63 +/- 15 years, 60% men) in sinus rhythm with organic MR (regurgitant volume 68 +/- 42 ml/beat) and performed at baseline triple echocardiographic quantitation (MR severity, LA volume, and left ventricular characteristics). Outcome with medical and surgical management was analyzed. RESULTS Left atrial volume indexed to body surface area (LA index) was 55 +/- 26 ml/m(2) (<40 ml/m(2) in 158 patients, 40 to 59 ml/m(2) in 160 patients, and > or =60 ml/m(2) in 174 patients). Under medical management, 5-year survival was 80 +/- 2.9% and cardiac events 28 +/- 3%. Adjusting for established predictors of outcome, LA index was independently associated with survival after diagnosis (hazard ratio [HR]: 1.3 [95% confidence interval (CI): 1.1 to 1.5] per 10 ml/m(2) increment, p = 0.001). Patients with LA index > or =60 ml/m(2) had lower 5-year survival than those with no or mild LA enlargement (p < 0.0001) and than the rates of survival expected in the U.S. population (53 +/- 8.6% vs. 76%, p = 0.017). Compared with patients with LA index <40 ml/m(2), those with LA index > or =60 ml/m(2) had increased mortality (HR: 2.8 [95% CI: 1.2 to 6.5], p = 0.016) and cardiac events (HR: 5.2 [95% CI: 2.6 to 10.9], p < 0.0001) with medical management. Mitral surgery was associated with decreased mortality (HR: 0.46 [95% CI: 0.26 to 0.84], p = 0.01) and cardiac events (HR: 0.38 [95% CI: 0.23 to 0.62], p = 0.0001) and after surgery patients with LA index > or =60 ml/m(2) versus <60 ml/m(2) did not incur excess mortality or cardiac events (both p > 0.30). CONCLUSIONS In organic MR, LA index at diagnosis predicts long-term outcome, incrementally to known predictors of outcome. This marker of risk is particularly important because mitral surgery in these patients markedly improves outcome and restores life expectancy. LA index should be measured in routine clinical practice for risk-stratification and for clinical decision making in patients with organic MR.

Incidence, Predictors, and Implications of Access Site Complications With Transfemoral Transcatheter Aortic Valve Implantation

Our study objective was to assess the incidence, predictors, and implications of access site complications related to transfemoral transcatheter aortic valve implantation (TAVI). We pooled the prospective TAVI databases of 5 experienced centers in Europe enrolling only transfemoral cases for this analysis. Access site complications were defined according to the Valve Academic Research Consortium end-point definitions. The global transfemoral TAVI database contained 986 patients. Percutaneous access and closure was performed in 803 patients (81%) and a surgical strategy in 183 (19%). Incidences of major vascular complications, life-threatening/disabling bleeding, and major bleeding were 14.2%, 11%, and 17.8% respectively. In the patient cohort with a completely percutaneous access strategy, major vascular complications and life-threatening/disabling bleedings were related to closure device failure in 64% and 29%, respectively. Female gender (odds ratio 1.63, 95% confidence interval 1.12 to 2.36) and use of >19Fr system (2.87, 1.68 to 4.91) were independent predictors for major vascular complications. Female gender (odds ratio 2.04, 95% confidence interval 1.31 to 3.17), use of >19Fr system (1.86, 1.02 to 3.38), peripheral arterial disease (2.14, 1.27 to 3.61), learning effect (0.45, 0.27 to 0.73), and percutaneous access strategy (2.39, 1.16 to 4.89) were independently associated with life-threatening/disabling bleedings. In conclusion, transfemoral TAVI is associated with a >10% incidence of major vascular-related complications. A considerable number of these events is related to arteriotomy closure failure. Arterial sheath size and female gender are important determinants of major vascular complications and life-threatening/disabling bleeding.

Aortic Valve Calcification Determinants and Progression in the Population

Background—Aortic valve calcification (AVC) is considered degenerative. Recent data suggested links to atherosclerosis or coronary disease (CAD). Methods and Results—AVC and coronary artery calcifications (CAC) were prospectively assessed by Electron-Beam-Computed-Tomography in 262 population-based research participants ≥60 years. AVC was frequent (27%) with aging (P<0.01) and in men (P<0.05). AVC was associated with diabetes, hypertension, higher body-mass-index, and serum glucose (all P<0.05). AVC was a marker of higher prevalence (P<0.01) and severity of CAD (CAC score: 441±802 versus 265±566, P<0.05) independently of age. After follow-up of 3.8±0.9 years, AVC score increased (94±271 versus 54±173, P<0.01, +11±32 U/year), faster with higher baseline AVC score (P<0.01). Compared with participants remaining free of AVC, de novo acquisition of AVC was associated with higher LDL-cholesterol (141±31 versus 121±27 mg/dL, P<0.05) and faster CAC progression (+78±87 versus +28±47 U/year, P<0.05). In multivariate analysis, LDL-cholesterol independently determined AVC acquisition while higher baseline AVC scores determined faster progression of existing AVC. Conclusion—In the population, AVC is frequent with aging and atherosclerotic risk factors. AVC is a marker of subclinical CAD. AVC is progressive, appearing de novo with progressive atherosclerosis whereas established AVC progresses independently of atherosclerotic risk factors and faster with increasing initial AVC loads.

Treatment and Clinical Outcomes of Transcatheter Heart Valve Thrombosis

Background—Valve thrombosis has yet to be fully evaluated after transcatheter aortic valve implantation. This study aimed to report the prevalence, timing, and treatment of transcatheter heart valve (THV) thrombosis. Methods and Results—THV thrombosis was defined as follows (1) THV dysfunction secondary to thrombosis diagnosed based on response to anticoagulation therapy, imaging modality or histopathology findings, or (2) mobile mass detected on THV suspicious of thrombus, irrespective of dysfunction and in absence of infection. Between January 2008 and September 2013, 26 (0.61%) THV thromboses were reported out of 4266 patients undergoing transcatheter aortic valve implantation in 12 centers. Of the 26 cases detected, 20 were detected in the Edwards Sapien/Sapien XT cohort and 6 in the Medtronic CoreValve cohort. In patients diagnosed with THV thrombosis, the median time to THV thrombosis post–transcatheter aortic valve implantation was 181 days (interquartile range, 45–313). The most common clinical presentation was exertional dyspnea (n=17; 65%), whereas 8 (31%) patients had no worsening symptoms. Echocardiographic findings included a markedly elevated mean aortic valve pressure gradient (40.5±14.0 mm Hg), presence of thickened leaflets or thrombotic apposition of leaflets in 20 (77%) and a thrombotic mass on the leaflets in the remaining 6 (23%) patients. In 23 (88%) patients, anticoagulation resulted in a significant decrease of the aortic valve pressure gradient within 2 months. Conclusions—THV thrombosis is a rare phenomenon that was detected within the first 2 years after transcatheter aortic valve implantation and usually presented with dyspnea and increased gradients. Anticoagulation seems to have been effective and should be considered even in patients without visible thrombus on echocardiography.

Feasibility and Outcomes of Transcatheter Aortic Valve Implantation in High-Risk Patients With Stenotic Bicuspid Aortic Valves

Little is known about transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve stenosis, which usually represents a contraindication. The aim of this study was to assess the feasibility and the results of TAVI in this patient subset. Of 316 high-risk patients with severe aortic stenosis who underwent TAVI from January 2009 to January 2012, 15 (5%) had documented bicuspid aortic valves. They were treated using a transarterial approach, using the Medtronic CoreValve system. Patients were aged 80 ± 10 years, in New York Heart Association functional classes III and IV. The mean aortic valve area was 0.8 ± 0.3 cm(2), and the mean gradient was 60 ± 19 mm Hg. The mean calcium score, calculated using multislice computed tomography, was 4,553 ± 1,872 arbitrary units. The procedure was successful in all but 1 patient. Major adverse events, according to Valvular Academic Research Consortium definitions, were encountered in 1 patient (death). The mean postimplantation prosthetic gradient was 11 ± 4 mm Hg, and ≤1+ periprosthetic leaks were observed in all but 2 patients. The mean prosthetic ellipticity index was 0.7 ± 0.2 at the level of the native annulus and 0.8 ± 0.2 at the level of the prosthetic leaflets. After a mean follow-up period of 8 ± 7 months, 1 patient had died from aortic dissection; there were no additional adverse events. All but 2 hospital survivors were in New York Heart Association class I or II. In conclusion, the present series suggests that transarterial Medtronic CoreValve implantation is feasible in selected patients with bicuspid aortic valve and may lead to short-term hemodynamic and clinical improvement.

Molecular Plasticity of Vascular Wall During NG-Nitro-l-Arginine Methyl Ester–Induced Hypertension : Modulation of Proinflammatory Signals

It has previously been reported that hypertension induced by the chronic blockade of NO production is characterized by a proinflammatory phenotype of the arterial wall associated with a periarterial accumulation of inflammatory cells. In the present study, the cellular and molecular mechanisms involved in the luminal and perivascular accumulation of inflammatory cells were evaluated in the aortas of N(G)-nitro-L-arginine methyl ester (L-NAME)-treated rats. Because the medial layer remains intact, putative markers of the resistance of the vascular wall to cell migration and to oxidative stress were also explored. For this purpose, monocyte adhesion, cytokine expression, superoxide anion production, and nuclear factor-kappa B (NF-kappa B) activation were assessed in the aortas of L-NAME-treated rats. Expressions of tissue inhibitor of metalloproteinases-1 (TIMP-1) and heme oxygenase-1 (HO-1) in the aortic wall were also studied as possible markers of such resistance. Chronic blockade of NO production increased ex vivo monocyte adhesion to the endothelium, increased the production of superoxide anions, and activated the NF-kappa B system. In concert with this modification of the redox state of the vascular wall in L-NAME-treated rats, the expression of proinflammatory cytokines interleukin-6, monocyte chemoattractant protein-1, and macrophage colony-stimulating factor was increased. In parallel, expressions of both TIMP-1 and HO-1 were increased. All these changes were prevented by treatment with an angiotensin-converting enzyme inhibitor (Zofenopril). Hypertension associated with a proinflammatory phenotype of the vascular wall induced by blockade of NO production could be due to an increase in oxidative stress, which, in turn, activates the NF-kappa B system and increases gene expression. In parallel, the arterial wall overexpresses factors such as TIMP-1 and HO-1, which could participate in the resistance to cell migration and oxidative stress.

Quantitative Echocardiographic Determinants of Clinical Outcome in Asymptomatic Patients With Aortic Regurgitation : A Prospective Study

OBJECTIVES The purpose of this study was to define the link between aortic regurgitation (AR) quantitation and clinical outcome in asymptomatic patients with AR. BACKGROUND Quantitative American Society of Echocardiography (QASE) thresholds are recommended for AR assessment, but impact on clinical outcome is unknown. METHODS We prospectively enrolled (1991 to 2003) 251 asymptomatic patients (age 60 +/- 17 years) with isolated AR and ejection fraction > or =50% with quantified AR and left ventricular (LV) volumes using Doppler-echocardiography. RESULTS Survival under medical management was independently determined by baseline regurgitant volume (RVol) (adjusted hazard ratio [HR] 1.22 [95% confidence interval (CI) 1.08 to 1.35] per 10 ml/beat, p = 0.002) and effective regurgitant orifice (ERO) (adjusted HR 1.52 [95% CI 1.19 to 1.91] per 10 mm(2), p = 0.002), which superseded traditional AR grading. Patients with QASE-severe AR (RVol > or =60 ml/beat or ERO > or =30 mm(2)) versus QASE-mild AR (RVol <30 ml and ERO <10 mm(2)) had lower survival (10 years: 69 +/- 9% vs. 92 +/- 4%, p = 0.05) independently of all clinical characteristics (adjusted HR 4.1 [95% CI 1.4 to 14.1], p = 0.01) and lower survival free of surgery for AR (10 years: 20 +/- 5% vs. 92 +/- 4%, p < 0.001, adjusted HR 12.9 [95% CI 5.4 to 38.5]). Cardiac events were considerably more frequent with QASE-severe versus -moderate or -mild AR (10 years: 63 +/- 8% vs. 34 +/- 6% and 21 +/- 8%, p < 0.0001). Independent determinants of cardiac events were quantitative AR grading (QASE-severe adjusted HR 5.2 [95% CI 2.2 to 14.8], p < 0.001; QASE-moderate adjusted HR 2.4 [95% CI 1.06 to 6.6], p = 0.035), which superseded traditional AR assessment (p < 0.001) and LV end-systolic volume index (ESVI) (adjusted HR 1.09 [95% CI 1.03 to 1.14 per 10 ml/m(2)], p = 0.002), which superseded LV M-mode diameters. In QASE-severe AR, patients with ESVI > or =45 versus <45 ml/m(2) had higher cardiac event rates (10 years: 87 +/- 8% vs. 40 +/- 10%, p < 0.001). Cardiac surgery for AR reduced cardiac events in patients with QASE-severe AR (adjusted HR 0.23 [95% CI 0.09 to 0.57], p = 0.002). CONCLUSIONS Echocardiographic quantitation of AR severity and ESVI provides independent and superior predictors of clinical outcome in asymptomatic patients with AR and ejection fraction > or =50% and should be widely clinically applied. Patients with QASE-severe AR and ESVI > or =45 ml/m(2) should be carefully considered for cardiac surgery, which reduces cardiac events risk.