Randomised study for the Optimal Treatment of symptomatic patients with low-gradient severe Aortic valve Stenosis and preserved left ventricular ejection fraction (ROTAS trial).

BACKGROUND: The best management of symptomatic patients with low-gradient (LG) severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) has not been established. The Randomised study for the Optimal Treatment of symptomatic patients with low-gradient severe Aortic valve Stenosis (ROTAS) trial aimed to assess the superiority of aortic valve replacement (AVR) versus medical treatment (MT) in this specific group of AS patients. METHODS: Patients with symptomatic LG severe AS and preserved LVEF (>50%) underwent dobutamine stress echocardiography and/or CT-aortic calcium score to confirm AS severity and were then randomised 1:1 to AVR or MT. The primary endpoint was a composite of overall death and/or cardiovascular hospitalisation. RESULTS: The ROTAS study was stopped early because of insufficient recruitment. In the end, only 52 patients (age 79±7 years; women 54%; NYHA III-IV 27%; median STS score 3.3%) were included in the study. During follow-up (mean: 14±7 months), the primary endpoint occurred in 12 (23%) patients. Compared with MT, AVR was not associated with a significant prognostic benefit (events: 5/26 (19%) vs 7/26 (27%) (HR 0.76, 95% CI 0.24 to 2.39, p=0.63). During follow-up, 11 (42%) patients in the MT group developed class I criteria for AVR or severe symptoms justifying a cross-over to the AVR group. CONCLUSIONS: Because of the small number of included patients and short follow-up the ROTAS trial was underpowered and unable to demonstrate a difference in the study endpoint between treatment arms. In patients in the MT arm, a regular echocardiographic and clinical assessment might be useful to disclose those developing class I indications of AVR or severe AS-related symptoms. TRIAL REGISTRATION NUMBER: NCT01835028.

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.

Influence of preoperative left ventricular contractile reserve on postoperative ejection fraction in low-gradient aortic stenosis.

BACKGROUND: Dobutamine stress hemodynamics (DSH) has the potential to stratify operative risk in low-gradient aortic stenosis (AS), but little is known about the relation between left ventricle contractile reserve and postoperative left ventricular ejection fraction (LVEF). We sought to assess the value of DSH to predict postoperative improvement in LVEF. METHODS AND RESULTS: Sixty-six consecutive patients with symptomatic severe AS (aortic valve area < or =1 cm2), LVEF < or =40%, and mean pressure gradient < or =40 mm Hg prospectively enrolled in the French multicenter study on low-gradient AS and who survived to aortic valvular replacement (AVR) were included. Preoperative contractile reserve was present in 46 patients (group I; 70%) and absent in 20 patients (group II; 30%). In the overall sample, 58% of patients improved by 2 New York Heart Association (NYHA) classes after AVR. Mean LVEF improved from 29+/-6% to 47+/-11% (P<0.0001). LVEF improved by > or =10 EF units in 38 patients (83%) in group I and in 13 patients (65%) in group II. Mean LVEF improvement was similar in the 2 groups (19+/-10% versus 17+/-11%; P=0.54). On multivariable analysis, multivessel coronary artery disease (P=0.05) and baseline mean transaortic pressure gradient (P=0.01) were related to LVEF improvement, whereas contractile reserve was not. CONCLUSIONS: LVEF increases in the majority of patients with low-gradient AS who survive after AVR. Although the absence of contractile reserve on DSH is related to high operative mortality, it does not predict the absence of LVEF recovery in patients surviving to AVR. These data further support the concept that surgery should not be contraindicated on the basis of absence of contractile reserve alone.

Management of Takotsubo cardiomyopathy in non-academic hospitals in France: The Observational French SyndromEs of TakoTsubo (OFSETT) study.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is a rare condition characterized by a sudden temporary weakening of the heart. TTC can mimic acute myocardial infarction and is associated with a minimal release of myocardial biomarkers in the absence of obstructive coronary artery disease. AIMS: To provide an extensive description of patients admitted to hospital for TTC throughout France and to study the management and outcomes of these patients. METHODS: In 14 non-academic hospitals, we collected clinical, electrocardiographic, biological, psychological and therapeutic data in patients with a diagnosis of TTC according to the Mayo Clinic criteria. RESULTS: Of 117 patients, 91.5% were women, mean ± SD age was 71.4 ± 12.1 years and the prevalence of risk factors was high (hypertension: 57.9%, dyslipidaemia: 33.0%, diabetes: 11.5%, obesity: 11.5%). The most common initial symptoms were chest pain (80.5%) and dyspnoea (24.1%). A triggering psychological event was detected in 64.3% of patients. ST-segment elevation was found in 41.7% of patients and T-wave inversion in 71.6%. Anterior leads were most frequently associated with ST-segment elevation, whereas T-wave inversion was more commonly associated with lateral leads, and Q-waves with septal leads. The ratio of peak B-type natriuretic peptide (BNP) or N-terminal prohormone BNP (NT-proBNP) level to peak troponin level was 1.01. No deaths occurred during the hospital phase. After 1 year of follow-up, 3 of 109 (2.8%) patients with available data died, including one cardiovascular death. Rehospitalizations occurred in 17.4% of patients: 2.8% due to acute heart failure and 14.7% due to non-cardiovascular causes. There was no recurrence of TTC. CONCLUSIONS: This observational study of TTC included primarily women with atherosclerotic risk factors and mental stress. T-wave inversion was more common than ST-segment elevation. There were few adverse cardiovascular outcomes in these patients after 1-year follow-up.

Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics.

BACKGROUND: The prognostic value of dobutamine stress hemodynamic data in the setting of low-gradient aortic stenosis has been addressed in small, single-center studies. Larger studies are needed to define the criteria for selecting the patients who will benefit from valve replacement. METHODS AND RESULTS: Six centers prospectively enrolled 136 patients with aortic stenosis (96 men; median age, 72 years [range, 65 to 77 years]; median aortic valve area, 0.7 cm2 [range, 0.6 to 0.8]; mean transaortic gradient, 29 mm Hg [range, 23 to 34 mm Hg]; cardiac index, 2.11 L x min(-1) x m(-2) [range, 1.75 to 2.55 L x min(-1) x m(-2)]). Left ventricular contractile reserve on the dobutamine stress Doppler study was present in 92 patients (group I) and absent in 44 patients (group II). Operative mortality was 5% (3 of 64 patients) in group I compared with 32% (10 of 31 patients) in group II (P=0.0002). Predictors for operative mortality were the lack of contractile reserve (odds ratio, 10.9; 95% confidence interval [CI], 2.6 to 43.4; P=0.001) and a mean transaortic gradient < or =20 mm Hg (odds ratio, 4.7; 95% CI, 1.1 to 21.0; P=0.04). Predictors for long-term survival were valve replacement (hazard ratio, 0.30; 95% CI, 0.17 to 0.53; P=0.001) and left ventricular contractile reserve (hazard ratio, 0.40; 95% CI, 0.23 to 0.69; P=0.001). CONCLUSIONS: In the setting of low-gradient aortic stenosis, surgery seems beneficial for most of the patients with left ventricular contractile reserve. In contrast, the postoperative outcome of patients without reserve is compromised by a high operative mortality. Thus, dobutamine stress Doppler hemodynamics may be factored into the risk-benefit analysis for each patient.

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=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

Low-gradient aortic stenosis: impact of prosthesis-patient mismatch on survival.

AIMS: To assess the prognostic impact of prosthesis-patient mismatch (PPM) in a large consecutive series of patients operated for low-gradient aortic stenosis (AS). METHODS AND RESULTS: Outcomes after surgery for low-gradient AS were prospectively assessed in 152 consecutive patients from seven institutions. There were 113 men (74%); mean age was 72 years (64-76); valve area, 0.7 cm(2) (0.6-0.8); left ventricular (LV) ejection fraction 0.31 (0.25-0.37) and baseline mean transaortic pressure gradient (MPG), 30 mmHg (25-35) Among 139 patients with available prosthetic valve effective orifice area (EOA), PPM (defined by an indexed EOA < or = 0.85 cm(2)/m(2)) was present in 79 patients (57%) and had no significant impact on post-operative mortality. Independent predictors of overall mortality were LV contractile reserve [hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.35-0.78; P = 0.002], associated coronary artery bypass grafting (HR 1.87; 95% CI 1.24-2.82; P =0.003), baseline MPG (per 1 mmHg decrease to 10 mmHg; HR 1.03; 95% CI 1.01-1.06; P = 0.021), previous cancer (HR 2.13; 95% CI 1.05-4.29; P = 0.037), and logistic EuroSCORE (per 1% increase; HR 1.02; 95% CI 1.01-1.04; P = 0.040). CONCLUSION In this large multicentre series of patients with low-gradient AS, we found that PPM (moderate in most cases) had no influence on post-operative mortality. Therefore, the performance of more complex interventions in order to avoid moderate PPM may not be justified in the setting of low-gradient AS, because their higher risk probably outweighs the expected benefit.