Hélène Petit-Eisenmann

Outcome After Aortic Valve Replacement for Low-Flow/Low-Gradient Aortic Stenosis Without Contractile Reserve on Dobutamine Stress Echocardiography

OBJECTIVES This study investigated whether aortic valve replacement (AVR) is associated with improved survival in patients with severe low-flow/low-gradient aortic stenosis (LF/LGAS) without contractile reserve (CR) on dobutamine stress echocardiography (DSE). BACKGROUND Patients with LF/LGAS without CR have a high mortality rate with conservative therapy. The benefit of AVR in this subset of patients remains controversial. METHODS Eighty-one consecutive patients with symptomatic calcified LF/LGAS (valve area <or=1 cm(2), left ventricular ejection fraction <or=40%, mean pressure gradient [MPG] <or=40 mm Hg) without CR on DSE were enrolled. Absence of CR was defined as the absence of increase in stroke volume of >or=20% compared with the baseline value. Multivariable analysis and propensity scores were used to compare survival according to whether or not AVR was performed (n = 55). RESULTS Five-year survival was higher in AVR patients compared with medically managed patients (54 +/- 7% vs. 13 +/- 7%, p = 0.001) despite a high operative mortality of 22% (n = 12). An AVR was independently associated with lower 5-year mortality (adjusted hazard ratio from 0.16 to 5.21 varying with time [95% confidence interval: 0.12-3.16 to 0.21-8.50], p = 0.00026). In 42 propensity-matched patients, 5-year survival was markedly improved by AVR (65 +/- 11% vs. 11 +/- 7%, p = 0.019). Associated bypass surgery (p = 0.007) and MPG <or=20 mm Hg (p = 0.035) were independently predictive of operative mortality. Late survival after AVR (excluding operative death) was 69 +/- 8% at 5 years. CONCLUSIONS In patients with LF/LGAS without CR on DSE, AVR is associated with better outcome compared with medical management. Surgery should not be withheld from this subset of patients solely on the basis of lack of CR on DSE.

Aortic valve replacement for Low-Flow/Low-Gradient aortic stenosis - Operative risk stratification and long-term outcome: A European Multicenter study

OBJECTIVES We evaluated a large multicenter series of patients operated on for low-flow/low-gradient aortic stenosis (LF/LGAS) to stratify the operative risk, assess whether perioperative mortality has decreased over recent years, and analyze the post-operative outcome. BACKGROUND Although LF/LGAS is classically associated with a high operative risk, few data are available concerning the results of surgery in this setting. METHODS A total of 217 consecutive patients (168 men, 77%) with severe aortic stenosis (area <1 cm(2)), low ejection fraction (EF) (<or=35%), and low mean gradient (MG) (<or=30 mm Hg) who underwent aortic valve replacement (AVR) between 1990 and 2005 were included. RESULTS Perioperative mortality was 16% and decreased dramatically from 20% in the 1990 to 1999 period to 10% in the 2000 to 2005 period. Higher European System for Cardiac Operative Risk Evaluation score (EuroSCORE), very low MG and EF, New York Heart Association functional class III or IV, history of congestive heart failure, and multivessel coronary artery disease (MVD) were associated with perioperative mortality. On multivariate analysis, very low pre-operative MG and MVD were predictors of excess perioperative mortality. In the subgroup of patients with dobutamine stress echocardiography, the absence of contractile reserve was a strong predictor of perioperative mortality. Overall 5-year survival rate was 49 +/- 4%. Lower MG, higher EuroSCORE, prior atrial fibrillation, and MVD were identified as independent predictors of overall long-term mortality. CONCLUSIONS In view of the very poor prognosis of unoperated patients, the current operative risk, and the long-term outcome after surgery, AVR is the treatment of choice in the majority of cases of LF/LGAS.

Outcomes of pseudo-severe aortic stenosis under conservative treatment

AIMS In the setting of low-flow/low-gradient aortic stenosis (LF/LGAS), outcomes of pseudo-severe aortic stenosis (AS) remain poorly described. This study was aimed to assess the outcome of patients with pseudo-severe AS under conservative treatment. METHODS AND RESULTS Among 305 patients from the European Registry of LF/LGAS, the outcomes of the 107 patients followed under conservative treatment were analysed. Based on the results of dobutamine echocardiography, patients were divided into group IA [left ventricular (LV) contractile reserve present with true-severe AS, n = 43], group IB [pseudo-severe AS (n = 29) defined as LV contractile reserve with a final aortic valve area ≥1.2 cm(2) and a mean transaortic pressure gradient <40 mmHg at peak dobutamine infusion], or group II (exhausted LV contractile reserve, n = 35). The rate of death within 5 years was significantly lower in the group IB (43 ± 11%, n = 10), when compared with the group IA (91 ± 6%, n = 33; P = 0.001) and the group II (100%, n = 23; P < 0.001). The Cox proportional hazard model analysis demonstrated that the hazard ratio for death in the group IB remained significantly lower than in the other groups, even after adjustment for currently established risk factors. Furthermore, the 5-year survival of pseudo-severe AS patients was comparable with that of propensity-matched patients with systolic heart failure and no evidence of valve disease. CONCLUSION In patients with pseudo-severe AS, the 5-year survival under conservative treatment is better than in true-severe AS and comparable with that of propensity-matched patients with LV systolic dysfunction and no evidence of valve disease. Further studies are needed to define optimal therapeutic management in these patients.

Valvuloarterial impedance does not improve risk stratification in low-ejection fraction, low-gradient aortic stenosis: results from a multicentre study

OBJECTIVES In a multicentre series of patients with low-ejection fraction/low-gradient aortic stenosis (LEF/LGAS), we evaluated the prognostic impact of valvuloarterial impedance (Zva). BACKGROUND Zva in AS, a measure of global afterload taking into account systemic arterial compliance, has been proposed for risk stratification in paradoxical LGAS. We hypothesized that Zva could help risk stratification in LEF/LGAS. METHODS AND RESULTS We retrospectively calculated Zva (5.6 ± 1.7 mmHg/mL/m(2)) of 184 consecutive patients (mean age: 71 ± 10 years) with severe symptomatic LEF/LGAS (valve area ≤1 cm2;, EF ≤40%, mean transaortic pressure gradient ≤40 mmHg) included between 1995 and 2005 in a multicentre registry. Zva was higher in patients with LVEF at rest ≤20% (6.6 ± 2.3 vs. 5.5 ± 1.6; P = 0.05) and correlated negatively with LVEF at rest (R = -0.25; P = 0.001). Zva was lower in patients without contractile reserve (CR) on dobutamine stress echocardiography (DSE) compared with patients with true severe AS (5.3 ± 1.3 vs. 5.8 ± 1.8 mmHg/mL/m(2); P = 0.048). Zva and the variation in stroke volume during DSE were positively correlated (P = 0.0001) but Zva did not allow distinction between true and pseudo-severe AS (5.8 ± 1.8 vs. 5.3 ± 1.8 mm Hg/mL/m(2); P = 0.30). In the total population, Zva was not predictive of long-term mortality. In the 128 patients who underwent aortic valve replacement, Zva was not predictive of operative death and of long-term mortality. CONCLUSIONS Increased Zva is related to low LVEF and more frequent CR on DSE in LEF/LGAS. However, Zva did not allow an accurate distinction between true and pseudo-severe AS and failed to predict operative and long-term mortality after aortic valve replacement, in LEF/LGAS.

Effects of Transcutaneous Aortic Valve Implantation on Aortic Valve Disease-Related Hemostatic Disorders Involving von Willebrand Factor

BACKGROUND Aortic valve stenosis (AVS) can be complicated by bleeding associated with acquired type 2A von Willebrand syndrome. The association of AVS and gastrointestinal bleeding from angiodysplasia is defined as Heyde syndrome. We sought to evaluate the effect of transcutaneous aortic valve implantation (TAVI) on hemostasis disorders and to assess its effectiveness to treat Heyde syndrome. METHODS We prospectively enrolled 49 consecutive patients with severe AVS addressed for TAVI at our institution. Biological hemostasis parameters involving von Willebrand factor (vWF) were assessed at baseline and 1 week after the procedure. RESULTS At baseline, a significant link between vWF abnormalities and the severity of AVS was evidenced: mean aortic transvalvular gradient was negatively correlated with the levels of vWF antigen (vWF:Ag) (r = -0.29; P < 0.05), vWF ristocetin cofactor activity (r = -0.402; P = 0.006), and vWF collagen-binding activity (vWF:CB; r = -0.441; P = 0.005). One week after the procedure, a significant increase of vWF:Ag, vWF ristocetin cofactor activity, and vWF:CB was evidenced in the whole cohort (respectively, 3.32 vs. 2.29 IU/mL, P < 0.001; 2.98 vs. 1.86 IU/mL, P < 0.001; and 3.16 vs. 2.16 IU/mL, P < 0.001). Patients with pre-TAVI vWF abnormalities consistent with a type 2A vWF syndrome (ratio vWF:CB/vWF:Ag < 0.7) preferentially improved their vWF function with respect to patients with a normal ratio (relative increase of vWF:CB of 63.8% vs. 3.5%). CONCLUSIONS Hemostasis parameters involving vWF are improved after TAVI, especially in patients with pre-existing abnormalities consistent with acquired type 2A von Willebrand syndrome.

Exclusive Low-Molecular-Weight Heparin as Bridging Anticoagulant After Mechanical Valve Replacement

BACKGROUND Unfractionated heparin has been the standard anticoagulant used immediately after mechanical heart valve replacement (MHVR). The purpose of this study was to assess a postoperative anticoagulation protocol with low-molecular-weight heparin (LMWH) immediately after MHVR without the use of unfractionated heparin or anti-factor Xa monitoring. METHODS We performed a prospective, single-center, observational study of 1,063 consecutive patients undergoing elective MHVR with postoperative LMWH anticoagulation treatment. The exclusion criteria were as follows: renal failure, intraaortic balloon counterpulsation, critical perioperative state, or a recent neurologic event. The postoperative anticoagulation protocol used subcutaneous enoxaparin as a bridging anticoagulant treatment beginning on the first postoperative day and continuing until vitamin K antagonist treatment was fully effective. Patients were followed for 6 weeks. The primary endpoints were the incidence of thromboembolic or major bleeding events. RESULTS Eleven (1%) thromboembolic events occurred. Ten of these events were transient or permanent strokes. Major bleeding events occurred in 44 patients (4.1%), 7 of which were observed before the enoxaparin treatment period. At the time of discharge, 570 patients (53.6%) were no longer receiving LMWH treatment due to achieving the target international normalized ratio. The mean length of hospital stay was 8.5 ± 2.9 days. There were no deaths during the 6-week follow-up period. CONCLUSIONS In our highly selected population, after MHVR, postoperative anticoagulation using LMWH is associated with a low rate of thromboembolic and major bleeding events. This large observational study demonstrates that the use of LMWH as an anticoagulant is effective and safe after MHVR.

CT-ADP Point-of-Care Assay Predicts 30-Day Paravalvular Aortic Regurgitation and Bleeding Events following Transcatheter Aortic Valve Replacement

BACKGROUND Paravalvular aortic regurgitation (PVAR) remains a frequent postprocedural concern following transcatheter aortic valve replacement (TAVR). Persistence of flow turbulence results in the cleavage of high-molecular-weight von Willebrand multimers, primary haemostasis dysfunction and may favour bleedings. Recent data have emphasized the value of a point-of-care measure of von Willebrand factor-dependent platelet function (closure time [CT] adenosine diphosphate [ADP]) in the monitoring of immediate PVAR. This study examined whether CT-ADP could detect PVAR at 30 days and bleeding complications following TAVR. METHODS CT-ADP was assessed at baseline and the day after the procedure. At 30 days, significant PVAR was defined as a circumferential extent of regurgitation more than 10% by transthoracic echocardiography. Events at follow-up were assessed according to the Valve Academic Research Consortium-2 consensus classification. RESULTS Significant PVAR was diagnosed in 44 out of 219 patients (20.1%). Important reduction of CT-ADP could be found in patients without PVAR, contrasting with the lack of CT-ADP improvement in significant PVAR patients. By multivariate analysis, CT-ADP > 180 seconds (hazard ratio [HR]: 5.1, 95% confidence interval [CI]: 2.5-10.6; p < 0.001) and a self-expandable valve were the sole independent predictors of 30-day PVAR. At follow-up, postprocedural CT-ADP >180 seconds was identified as an independent predictor of major/life-threatening bleeding (HR: 1.7, 95% CI [1.0-3.1]; p = 0.049). Major/life-threatening bleedings were at their highest levels in patients with postprocedural CT-ADP > 180 seconds (35.2 vs. 18.8%; p = 0.013). CONCLUSION Postprocedural CT-ADP > 180 seconds is an independent predictor of significant PVAR 30 days after TAVR and may independently contribute to major/life-threatening bleedings.

Impact of prosthesis-patient mismatch on early haemodynamic status after aortic valve replacement.

OBJECTIVES Prosthesis-patient mismatch (PPM) has been reported to impact early haemodynamic status and early mortality after prosthetic aortic valve replacement (AVR) in patients with aortic stenosis (AS). The aim of this study was to assess the impact of PMM on early haemodynamic status after AVR using vasoactive-inotropic dependency index (VDI), postoperative pressures and end-organ perfusion. METHODS A total of 183 patients with AS were included in this prospective cohort study, and underwent elective AVR with or without combined coronary artery bypass graft surgery. PPM was defined as a projected indexed effective orifice area of ≤0.85 cm2/m2, and was present in 27.9% of the patients. The primary end-point was the VDI [VDI = vasoactive-inotropic score/mean arterial pressure] measured upon admission to the intensive care unit (POD0) and on the morning of the first postoperative day (POD1). The secondary end-points were the following: mean left atrial pressure, mean central venous pressure, fluid balance, brain natriuretic peptide, troponin I, glomerular filtration rate and lactate levels on POD0 and POD1. RESULTS No significant differences in VDI were observed between the no PPM and PPM groups on POD0 (0.08 ± 0.48 vs 0.05 ± 0.13, respectively, P = 0.622) or on POD1 (0.09 ± 0.40 vs 0.06 ± 0.13, respectively; P = 0.583). The mean arterial pressure, mean left atrial pressure, central venous pressure, troponin I, glomerular filtration rate and lactate levels did not differ between the two groups on POD0 and POD1, as well as fluid balance and brain natriuretic peptide on POD1. CONCLUSIONS PPM is not associated with early haemodynamic status impairment and end-organ perfusion after AVR. CLINICAL TRIAL NUMBER ClinicalTrials.gov number, NCT00699673.

Drug-induced aortic valve stenosis: An under recognized entity

BACKGROUND We have been intrigued by the observation that aortic stenosis (AS) may be associated with characteristic features of mitral drug-induced valvular heart disease (DI-VHD) in patients exposed to valvulopathic drugs, thus suggesting that beyond restrictive heart valve regurgitation, valvulopathic drugs may be involved in the pathogenesis of AS. METHODS Herein are reported echocardiographic features, and pathological findings encountered in a series of patients suffering from both AS (mean gradient >15mmHg) and mitral DI-VHD after valvulopathic drugs exposure. History of rheumatic fever, chest radiation therapy, systemic disease or bicuspid aortic valve disease were exclusion criteria. RESULTS Twenty-five (19 females, mean age 62years) patients having both AS and typical features of mitral DI-VHD were identified. Mean transaortic pressure gradient was 32+/-13mmHg. Aortic regurgitation was ≥ mild in 24 (96%) but trivial in one. Known history of aortic valve regurgitation following drug initiation prior the development of AS was previously diagnosed in 17 patients (68%). Six patients underwent aortic valve replacement and 3 both aortic and mitral valve replacement. In the 9 patients with pathology analysis, aortic valvular endocardium was markedly thickened by dense non-inflammatory fibrosis, a characteristic feature of DI-VHD. CONCLUSION The association between AS and typical mitral DI-VHD after valvulopathic drug exposure may not be fortuitous. Aortic regurgitation was usually associated to AS and preceded AS in most cases but may be lacking. Pathology demonstrated the potential role of valvulopathic drugs in the development of AS.

0353: Impact of TAVI on primary hemostasis, von Willebrand factor and Heyde’s syndrome: a prospective monocenter study

Background Aortic valve stenosis (AVS) can be complicated by bleeding associated with acquired type 2A von Willebrand syndrome. The association of AVS and gastrointestinal bleeding from angiodysplasia is defined as Heyde’s syndrome. We sought to evaluate the impact of TAVI on primary hemostasis disorders and to assess its effectiveness to treat Heyde’s syndrome. Methods We prospectively enrolled 49 consecutive patients with severe AVS referred to our institution for TAVI. Biological primary hemostasis parameters were assessed at baseline and one week after the procedure. Results At baseline, a significant link between vWF abnormalities and the severity of AVS was evidenced: mean aortic transvalvular gradient was negatively correlated with the levels of vWF antigen (vWF: Ag) (r=–0.29, p Conclusion Primary hemostasis parameters involving vWF are improved after TAVI, especially in patients with preexisting abnormalities consistent with acquired type 2A von Willebrand syndrome. Moreover, our observations, although limited to a small single-center study, suggest that Heyde’s syndrome can be cured by TAVI.