Dataset Information

Impact of Mean Transaortic Pressure Gradient on Long-Term Outcome in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

ABSTRACT:

Background

Mean transaortic pressure gradient (MTPG) has never been validated as a predictor of mortality in patients with severe aortic stenosis. We sought to determine the value of MTPG to predict mortality in a large prospective cohort of severe aortic stenosis patients with preserved left ventricular ejection fraction and to investigate the cutoff of 60 mm Hg, proposed in American guidelines.

Methods and results

A total of 1143 patients with severe aortic stenosis defined by aortic valve area ?1 cm² and MTPG ?40 mm Hg were included. The population was divided into 3 groups according to MTPG: between 40 and 49 mm Hg, between 50 and 59 mm Hg, and ?60 mm Hg. The end point was all-cause mortality. MTPG was ?60 mm Hg in 392 patients. Patients with MTPG ?60 mm Hg had a significantly increase risk of mortality compared with patients with MTPG <60 mm Hg (hazard ratio [HR]=1.62 [1.27-2.05] P<0.001), even for the subgroup of asymptomatic or minimally symptomatic patients (HR=1.56 [1.04-2.34] P=0.032). After adjustment for established outcome predictors, patients with MTPG ?60 mm Hg had a significantly higher risk of mortality than patients with MTPG <60 mm Hg (HR=1.71 [1.33-2.20] P<0.001), even after adjusting for surgery as a time-dependent variable (HR=1.71 [1.43-2.11] P<0.001). Similar results were observed for the subgroup of asymptomatic or minimally symptomatic patients (HR=1.70 [1.10-2.32] P=0.018 and HR=1.68 [1.20-2.36] P=0.003, respectively).

Conclusions

This study shows the negative prognostic impact of high MTPG (?60 mm Hg), on long-term outcome of patients with severe aortic stenosis with preserved left ventricular ejection fraction, irrespective of symptoms.

SUBMITTER: Bohbot Y

PROVIDER: S-EPMC5669186 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Impact of Mean Transaortic Pressure Gradient on Long-Term Outcome in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

Bohbot Yohann Y Kowalski Cedric C Rusinaru Dan D Ringle Anne A Marechaux Sylvestre S Tribouilloy Christophe C

Journal of the American Heart Association 20170601 6

<h4>Background</h4>Mean transaortic pressure gradient (MTPG) has never been validated as a predictor of mortality in patients with severe aortic stenosis. We sought to determine the value of MTPG to predict mortality in a large prospective cohort of severe aortic stenosis patients with preserved left ventricular ejection fraction and to investigate the cutoff of 60 mm Hg, proposed in American guidelines.<h4>Methods and results</h4>A total of 1143 patients with severe aortic stenosis defined by a ...[more]

PMID: 28572283

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Project description:AimsWe reported that patients with small aortic valve area (AVA) and low flow despite preserved left ventricular ejection fraction (LVEF), i.e. 'paradoxical' low flow (PLF), have worse outcomes compared with patients with normal flow (NF), although they generally have a lower mean gradient (MG). The aortic valve weight (AVW) excised at the time of valve replacement is a flow-independent marker of stenosis severity. The objective of this study was to compare the AVW of patients with PLF and MG<40 mmHg with the AVW of patients with NF and MG≥40 mmHg.Methods and resultsWe recruited 250 consecutive patients undergoing valve replacement (Cohort A) for severe stenosis. Among them, 33 (13%) were in PLF [LVEF > 50% but stroke volume index (SVi) ≤ 35 mL/m(2)] with MG < 40 mmHg (PLF-LG group) and 105 (42%) were in NF (LVEF > 50% and SVi > 35 mL/m(2)) with MG ≥ 40 mmHg (NF-HG group). Despite a much lower MG (29 ± 7 vs. 53 ± 10 mmHg; P < 0.0001), patients in the PLF-LG group had a similar AVA (0.73 ± 0.12 vs. 0.69 ± 0.13; P = 0.19) compared with those in the NF-HG group. The AVW [median (interquartile): 1.90 (1.63-2.50) vs. 2.60 (1.66-3.32)] and prevalence of bicuspid phenotype (15 vs. 42%) were lower in the PLF-LG group than in the NF-HG group. However, AVWs analysed separately in the tricuspid and bicuspid valves were similar in both groups [tricuspid valves: 1.80 (1.63-2.50) vs. 2.30 (1.58-3.00) g; P = 0.26 and bicuspid valves: 2.72 (1.73-3.61) vs. 2.60 (2.10-3.55) g; P = 0.93]. When using cut-point values of AVW established in another series of non-consecutive patients (n = 150, Cohort B) with NF and concordant Doppler-echocardiographic findings, we found that the percentage of patients with evidence of severe stenosis in Cohort A was 70% in patients with PLF-LG and 86% in patients with NF-HG.ConclusionThe aortic valve weight data reported in this study provide evidence that a large proportion of patients with PLF and low-gradient have a severe stenosis and that the gradient may substantially underestimate stenosis severity in these patients. A multi-parametric approach including all Doppler-echocardiographic parameters of valve function as well as other complementary diagnostic tests may help correctly identify these patients.

Project description:Background Moderate aortic stenosis ( MAS ) has not been extensively studied and characterized, as no published study has been specifically devoted to this condition. Methods and Results We aimed to describe the characteristics of patients with MAS and to evaluate their long-term survival compared with that of the general population. This study included 508 patients (mean±SD age, 75±11 years) with MAS (aortic valve area between 1 and 1.5 cm2; mean±SD aortic valve area, 1.2±0.15 cm2) and preserved left ventricular ejection fraction. Patients were mostly (86.4%) asymptomatic or minimally symptomatic, 78.3% had hypertension, 36.2% were diabetics, and 48.3% had dyslipidemia. Each patient with MAS was matched for the average survival (per year) of all patients of the same age and same sex from our region (Somme department, north of France). During follow-up (median 47 months), 113 patients (22.2%) underwent aortic valve replacement for severe AS. The mean±SD time between inclusion and surgery was 37±22 months. During follow-up, 255 patients (50.2%) died. The 6-year survival of patients with MAS was lower than the expected survival (53±2% versus 65%). In multivariate analysis, age (hazard ratio, 1.04 [95% CI, 1.02-1.05]; P<0.001), prior atrial fibrillation (hazard ratio, 1.35 [95% CI, 1.05-1.73]; P=0.019), and Charlson comorbidity index (hazard ratio, 1.11 [95% CI, 1.05-1.18]; P=0.002) were associated with increased mortality. Aortic valve replacement was associated with better survival (hazard ratio, 0.38 [95% CI, 0.27-0.54]; P<0.001). Conclusions The results of this study show that patients with MAS present many cardiovascular risk factors, a high rate of surgery during follow-up, and increased mortality compared with the general population mainly related to associated comorbidities. Patients with MAS should, therefore, be managed for their cardiovascular risk factors and comorbidities. They require close follow-up, especially when the aortic valve area is close to 1 cm2, as aortic valve replacement performed when patients transition to severe AS and develop indications for surgery during follow-up is associated with better survival.

Project description:BACKGROUND:Why some but not all patients with severe aortic stenosis (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity and flux is associated with this transition. METHODS:We recruited 102 participants to 5 groups: moderate aortic stenosis (ModAS) (n=13), SevAS, left ventricular (LV) ejection fraction ?55% (SevAS-preserved ejection fraction, n=37), SevAS, LV ejection fraction <55% (SevAS-reduced ejection fraction, n=15), healthy volunteers with nonhypertrophied hearts with normal systolic function (normal healthy volunteer, n=30), and patients with nonhypertrophied, non-pressure-loaded hearts with normal systolic function undergoing cardiac surgery and donating LV biopsy (non-pressure-loaded heart biopsy, n=7). All underwent cardiac magnetic resonance imaging and 31P magnetic resonance spectroscopy for myocardial energetics. LV biopsies (AS and non-pressure-loaded heart biopsy) were analyzed for CK total activity, CK isoforms, citrate synthase activity, and total creatine. Mitochondria-sarcomere diffusion distances were calculated by using serial block-face scanning electron microscopy. RESULTS:In the absence of failure, CK flux was lower in the presence of AS (by 32%, P=0.04), driven primarily by reduction in phosphocreatine/ATP (by 17%, P<0.001), with CK kf unchanged (P=0.46). Although lowest in the SevAS-reduced ejection fraction group, CK flux was not different from the SevAS-preserved ejection fraction group (P>0.99). Accompanying the fall in CK flux, total CK and citrate synthase activities and the absolute activities of mitochondrial-type CK and CK-MM isoforms were also lower (P<0.02, all analyses). Median mitochondria-sarcomere diffusion distances correlated well with CK total activity (r=0.86, P=0.003). CONCLUSIONS:Total CK capacity is reduced in SevAS, with median values lowest in those with systolic failure, consistent with reduced energy supply reserve. Despite this, in vivo magnetic resonance spectroscopy measures of resting CK flux suggest that ATP delivery is reduced earlier, at the moderate AS stage, where LV function remains preserved. These findings show that significant energetic impairment is already established in moderate AS and suggest that a fall in CK flux is not by itself a necessary cause of transition to systolic failure. However, because ATP demands increase with AS severity, this could increase susceptibility to systolic failure. As such, targeting CK capacity and flux may be a therapeutic strategy to prevent and treat systolic failure in AS.

Project description:ObjectivesTo determine clinical and prognostic differences between preserved and deteriorated systolic function (defined as left ventricular (LV) ejection fractions > or = 50% and < 50%, respectively) in patients with heart failure satisfying modified Framingham criteria.Patients and methodsRecords were studied of 1252 patients with congestive heart failure (CHF) (mean (SD) age 69.4 (11.7) years; 485 women, 767 men) who had been admitted to a cardiology service for CHF in the period 1991-2002 and whose LV systolic function had been echocardiographically evaluated within two weeks of admission. Data were collected on the main clinical findings, supplementary examinations, treatment, and duration of hospitalisation. Whether the patient was alive in the spring of 2003 was evaluated by searching the general archives of the hospital and by telephone survey.ResultsLV systolic function was preserved in 39.8% of patients. Age, female to male sex ratio, and prevalence of atrial fibrillation, valve disease, and other non-ischaemic, non-dilated cardiopathies were all significantly greater in the group with preserved systolic function. New York Heart Association functional class IV, third heart sound, jugular vein congestion, cardiomegaly, radiological signs of lung oedema, pathological Q waves, left bundle branch block, sinus rhythm, ischaemic cardiopathy, and dilated cardiomyopathy were all significantly more prevalent in the group with deteriorated systolic function, as was treatment with angiotensin converting enzyme inhibitors and most other antihypertensive drugs on discharge from hospital. There was no significant difference in survival between the groups with preserved and deteriorated systolic function (either survival regardless of age at admission or in subgroups aged < 75 and > or = 75 years at admission). In the whole group, survival rates after one, three, and five years were 84.0%, 66.7%, and 50.9%, respectively.ConclusionIn view of the poor prognosis of patients with CHF with preserved LV systolic function, who are currently treated empirically, it is to be hoped that relevant controlled clinical trials under way will afford information allowing optimisation of their treatment.

Dataset Information

Impact of Mean Transaortic Pressure Gradient on Long-Term Outcome in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

Background

Methods and results

Conclusions

Publications

Impact of Mean Transaortic Pressure Gradient on Long-Term Outcome in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

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