David Attias

Marfan Sartan: a randomized, double-blind, placebo-controlled trial.

AIMS To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS). METHODS AND RESULTS A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when <50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age >10 years old, and receiving standard therapy. 303 patients, mean age 29.9 years old, were randomized. The two groups were similar at baseline, 86% receiving β-blocker therapy. The median follow-up was 3.5 years. The evolution of aortic diameter at the level of the sinuses of Valsalva was not modified by the adjunction of Losartan, with a mean increase in aortic diameter at the level of the sinuses of Valsalva of 0.44 mm/year (s.e. = 0.07) (-0.043 z/year, s.e. = 0.04) in patients receiving Losartan and 0.51 mm/year (s.e. = 0.06) (-0.01 z/year, s.e. = 0.03) in those receiving placebo (P = 0.36 for the comparison on slopes in millimeter per year and P = 0.69 for the comparison on slopes on z-scores). Patients receiving Losartan had a slight but significant decrease in systolic and diastolic blood pressure throughout the study (5 mmHg). During the study period, aortic surgery was performed in 28 patients (15 Losartan, 13 placebo), death occurred in 3 patients [0 Losartan, 3 placebo, sudden death (1) suicide (1) oesophagus cancer (1)]. CONCLUSION Losartan was able to decrease blood pressure in patients with MFS but not to limit aortic dilatation during a 3-year period in patients >10 years old. β-Blocker therapy alone should therefore remain the standard first line therapy in these patients.

Impact of coronary artery disease on indications for transcatheter aortic valve implantation and on procedural outcomes

AIMS To describe the characteristics of coronary artery disease (CAD) in high-risk patients with aortic stenosis (AS), and its impact on indications for transcatheter aortic valve implantation (TAVI), and on outcomes. METHODS AND RESULTS Of 240 patients referred for TAVI, 230 had documented CAD status. Mean age was 81.5±8 years. Hundred and forty-four (63%) had CAD. Compared to patients with no CAD, those with CAD had a higher risk of mortality (EuroSCORE: 31±18%, vs. 23±11%, p=0.004). Overall, 145 patients (63%) underwent TAVI, 31 (13%) surgery, and 54 (24%) medical treatment. No patient was denied intervention because of the CAD. CAD led to re-orientate one patient (0.4%) towards surgery. PCI was performed before TAVI in 11 (7%). Survival rates were respectively 90% and 85% in the CAD and non-CAD groups (p=0.37) at 30 days, and 76.4±5.4% and 70.6±6.8% (p=0.28) at 1-year. At follow-up, functional status was similar in both groups and no further revascularisation was needed. CONCLUSIONS In high-risk patients referred for TAVI, CAD is frequent and associated with worse baseline characteristics. It has a limited impact on indications for TAVI. It seldom requires revascularisation and does not preclude satisfactory outcomes after TAVI.

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.

Mitral regurgitation in patients referred for transcatheter aortic valve implantation using the Edwards Sapien prosthesis: mechanisms and early postprocedural changes.

BACKGROUND Transcatheter aortic valve implantation (TAVI) is an alternative to conventional surgery in high-risk patients with severe aortic stenosis (AS), but data regarding mitral regurgitation (MR) characteristics and changes after TAVI are sparse. METHODS A total of 254 patients with severe AS referred for TAVI were prospectively enrolled. Comprehensive echocardiography was performed at baseline and at 7 days and 1 month in patients who underwent TAVI. MR was semiquantitatively graded from 0 to 4. Overlap of the anterior mitral leaflet and the device was measured using transesophageal echocardiography immediately after TAVI. RESULTS At screening, MR was absent in 26%, grade 1 in 44%, grade 2 in 25%, and grade ≥3 in 5% and was organic in 68% and functional in 32%. TAVI was finally performed using the Edwards Sapien valve in 119 patients, including four with MR grade ≥ 3. MR grade significantly decreased at 7 days (P = .003) but remained unchanged at 1 month (P = .55), whereas reverse remodeling occurred only at 1 month (improvements in left ventricular [LV] end-systolic diameter and ejection fraction; P < .05 for both). MR changes over time significantly differed according to ejection fraction and LV diameters (all P values for interaction < .005) but not according to aortic mean gradient, MR etiology, or overlap of the anterior mitral leaflet and the device (all P values for interaction > .15). CONCLUSIONS In patients referred for TAVI, MR is common, mainly organic, and rarely severe. After TAVI, MR improved within 7 days in both organic and functional MR, was not influenced by overlap of the anterior mitral leaflet and the device, but was associated with improvement in LV ejection fraction. Possible MR improvement should be taken into account in patient selection for TAVI especially, in cases of LV dysfunction or enlargement and MR of borderline severity.

Prevalence, Characteristics, and Outcomes of Patients Presenting With Cardiogenic Unilateral Pulmonary Edema

Background— Cardiogenic unilateral pulmonary edema (UPE) is a rare entity, frequently leading to initial misdiagnosis. We sought to assess the prevalence of UPE and to determine its impact on prognosis compared with bilateral pulmonary edema. Methods and Results— We studied the characteristics and outcomes of patients admitted to our institution for cardiogenic pulmonary edema during an 8-year period. The study population included 869 consecutive patients. The prevalence of UPE was 2.1%: 16 right-sided UPE (89%) and 2 left-sided UPE (11%). In patients with UPE, blood pressure was significantly lower (P≤0.01), whereas noninvasive or invasive ventilation and catecholamines were used more frequently (P=0.0004 and P<0.0001, respectively). The prevalence of severe mitral regurgitation in patients with bilateral pulmonary edema and UPE was 6% and 100%, respectively (P<0.0001). In patients with UPE, use of antibiotic therapy and delay in treatment were significantly higher (P<0.0001 and P=0.003, respectively). In-hospital mortality was 9%: 39% for UPE versus 8% for bilateral pulmonary edema (odds ratio, 6.9; 95% confidence interval, 2.6 to 18; P<0.001). In multivariate analysis, unilateral location of pulmonary edema was independently related to death whatever the model used (adjusted odds ratio, 6.5; 95% confidence interval, 1.3 to 32; P=0.021 for model A; and adjusted odds ratio, 6.8; 95% confidence interval, 1.1 to 41; P=0.037 for model B). Conclusions— Unilateral pulmonary edema represented 2.1% of cardiogenic pulmonary edema in our study, usually appeared as an opacity involving the right lung, and was always associated with severe mitral regurgitation. Unilateral pulmonary edema is related to an independent increased risk of mortality and should be promptly recognized to avoid delays in treatment.

Immediate and mid-term results of transfemoral aortic valve implantation using either the Edwards Sapien transcatheter heart valve or the Medtronic CoreValve System in high-risk patients with aortic stenosis.

OBJECTIVE We sought to describe the results of transfemoral aortic valve implantation using either the Sapien prosthesis or the CoreValve System. BACKGROUND Results of transfemoral aortic valve implantation using both commercially available prostheses have rarely been studied. PATIENTS Of 236 patients at high-risk or with contraindications to surgery, consecutively referred for transcatheter aortic valve implantation between October 2006 and June 2009, 83 were treated with transfemoral aortic valve implantation. The Sapien was the only prosthesis available until May 2008 and, since then, was used as the first option, while the CoreValve System was used when contraindications to the Sapien prosthesis were present. RESULTS Patients were aged 81+/-9 years, 98% in New York Heart Association classes III/IV, with predicted surgical mortalities of 26+/-14% using the EuroSCORE and 15+/-8% using the Society of Thoracic Surgeons Predicted Risk of Mortality score. Seventy-two patients were treated with the Sapien prosthesis and 11 with the CoreValve System. The valve was implanted in 94% of the cases. Thirty-day mortality was 7%. Overall, 1- and 2-year survival rates were 78+/-5% and 71+/-7%, respectively. Among patients treated with the Sapien, the 1-year survival rate was 67+/-12% in the first 20% of patients versus 86+/-5% in the last 80% of patients (p=0.02). In univariate analysis, early experience was the only significant predictor of 1-year mortality. CONCLUSION Combining the use of the Sapien and the CoreValve prostheses increases the number of patients who can be treated by transfemoral aortic valve implantation and provides satisfactory results at 2 years in this high-risk population. The results are strongly influenced by experience.

Aortic stenosis and transthyretin cardiac amyloidosis: the chicken or the egg?

BACKGROUND Aortic stenosis (AS) and transthyretin cardiac amyloidosis (TTR-CA) are both frequent in elderly. The combination of these two diseases has never been investigated. AIMS To describe patients with concomitant AS and TTR-CA. METHODS Six cardiologic French centres identified retrospectively cases of patients with severe or moderate AS associated with TTR-CA hospitalized during the last 6 years. RESULTS Sixteen patients were included. Mean ± SD age was 79 ± 6 years, 81% were men. Sixty per cent were NYHA III-IV, 31% had carpal tunnel syndrome, and 56% had atrial fibrillation. Median (Q1;Q4) NT-proBNP was 4382 (2425;4730) pg/mL and 91% had elevated cardiac troponin level. Eighty-eight per cent had severe AS (n = 14/16), of whom 86% (n = 12) had low-gradient AS. Mean ± SD interventricular septum thickness was 18 ± 4 mm. Mean left ventricular ejection fraction and global LS were 50 ± 13% and -7 ± 4%, respectively. Diagnosis of TTR-CA was histologically proven in 38%, and was based on strong cardiac uptake of the tracer at biphosphonate scintigraphy in the rest. Eighty-one per cent had wild-type TTR-CA (n = 13), one had mutated Val122I and 19% did not had genetic test (n = 3). Valve replacement was surgical in 63% and via transcatheter in 13%. Median follow-up in survivors was 33 (16;65) months. Mortality was of 44% (n = 7) during the whole follow-up period. CONCLUSIONS Combination of AS and TTR-CA may occur in elderly patients particularly those with a low-flow low-gradient AS pattern and carries bad prognosis. Diagnosis of TTR-CA in AS is relevant to discuss specific treatment and management.

Comparison of 2-Dimensional, 3-Dimensional, and Surgical Measurements of the Tricuspid Annulus Size: Clinical Implications.

Background—Associated tricuspid annuloplasty is recommended during left-heart valve surgery when the tricuspid annulus (TA) is dilated but methodology for the measurement of TA size and thresholds for TA enlargement are not clearly defined. Methods and Results—Measurement of the TA diameter (TAD) was prospectively performed using 2-dimensional transthoracic echocardiography (2D-TTE) in 282 patients in 4 different views (parasternal long axis, parasternal short axis, apical 4-chamber [A4C], and subcostal). TAD was also measured using 3D-transesophageal echocardiography in 183 patients (long axis), peroperatively in 120 patients who underwent a tricuspid valve surgery and using TTE (A4C) in 66 healthy volunteers. TAD was significantly different between the 4 2D-TTE views (3.85±0.58, 3.87±0.61, 4.02±0.69, and 3.92±0.65 cm, respectively; P<0.0001) but differences were small and the A4C was the most feasible (76%, 65%, 92%, and 73%, respectively; P<0.0001) and offered the highest reproducibility. TAD measured in A4C view was smaller than when measured by 3D-transesophageal echocardiography (3.90±0.63 versus 4.33±0.62 cm; P<0.0001) but correlation was excellent (r=0.84; P<0.0001) with a systematic 4-mm underestimation. In contrast, 2D-TTE measurements were significantly smaller and only modestly correlated to surgical measurements (4.11±0.61 versus 4.37±0.75 cm; P<0.0001; r=0.57; P<0.0001) which were poorly reproducible. In healthy volunteers, we suggested 42 mm or 23 mm/m2 as pathological values for the TAD in A4C. Conclusions—Measurements of the TAD using 2D-TTE in A4C were highly feasible and reproducible and despite being systematically smaller than 3D measurements, accurately reflected the degree of TA enlargement as assessed using 3D transesophageal echocardiography. We proposed the thresholds that may be used in future prospective studies to demonstrate whether a preventive strategy would improve the outcome.

Real-time 3D transoesophageal measurement of the mitral valve area in patients with mitral stenosis.

AIMS Planimetry measured by two-dimensional transthoracic echocardiography (TTE, MVA2D) is the reference method for the evaluation of the severity of mitral stenosis (MS) but requires experienced operators and good echocardiographic windows. Real-time three-dimensional transoesophageal echocardiography (3D-TEE, MVA3D) may overcome these limitations but its accuracy has never been evaluated. METHODS AND RESULTS We prospectively enrolled 80 patients (58±15 years, 86% female) referred for MS evaluation who underwent, within 1 week, a clinically indicated TTE and TEE. MVA2D was measured by experienced operators (Level III), MVA3D by one experienced and one non-experienced (Level I) operators blinded of any clinical or TTE information. MVA3D measured by the experienced operator [1.11±0.32 cm2; median, 1.1 cm2; range (0.45-2.20)] did not differ from and correlated well with MVA2D [1.10±0.34 cm2; median, 1.05 cm2; range (0.45-2.30)], P=0.87; r=0.79, P<0.0001; ICC=0.79) and mean difference between methods was small (+0.004±0.21 cm2). MVA3D measured by the non-experienced operator [1.08±0.34 cm2; median 1.02 cm2; range (0.45-2.23)] also did not differ from and correlated well with MVA2D measured by experienced operators (P=0.25; r=0.86, P<0.0001; mean difference -0.02±0.18 cm2; ICC=0.86). Intra and interobserver variability were 0.02±0.25 and 0.01±0.33 cm2. CONCLUSION 3D-TEE provides accurate and reproducible MVA measurements similar to 2D planimetry performed by experienced operators. Thus, 3D-TEE could be considered as a second-line alternative tool for the evaluation of MS severity in patients with poor echocardiographic windows or for team less accustomed to evaluate MS patients.

First-in-man full percutaneous transfemoral valve-in-valve implantations using Edwards SAPIEN 3 prostheses to treat a patient with degenerated mitral and aortic bioprostheses

We report the case of a 64-year old man presenting with pulmonary oedema due to the degeneration of mitral and aortic bioprostheses. Baseline transthoracic and 3D transoesophageal echocardiography showed severe stenotic degeneration of the mitral bioprosthesis (Carpentier-Edwards bioprosthesis n°31), severe intraprosthetic aortic regurgitation (Perimount bioprosthesis n°27), left ventricular dilatation, decreased left ventricular ejection fraction at 50% and pulmonary hypertension. Because of severe comorbidities, the patient was denied redo surgery by the Heart Team (logistic EuroSCORE 2: 23, 85%). Transcatheter transfemoral mitral valve-in-valve implantation was first performed using a 29-mm SAPIEN 3 valve. Two weeks later, aortic valve-in-valve implantation was performed with the same approach using a 26-mm SAPIEN 3 valve. Four months later, the patient remained asymptomatic with good haemodynamic results for both prostheses. This case report illustrates that valve-in-valve implantations using a full percutaneous transfemoral approach may be a valuable alternative to conventional surgery in high-risk patients presenting with concomitant mitral and aortic bioprosthesis dysfunction.