Tricuspid regurgitation is associated with increased risk of mortality in patients with low-flow low-gradient aortic stenosis and reduced ejection fraction : results of the multicenter TOPAS study (true or pseudo-severe aortic stenosis)

Objectives : This study sought to examine the impact of tricuspid regurgitation (TR) on mortality in patients with low-flow, low-gradient (LF-LG) aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF). Background : TR is often observed in patients with LF-LG AS and low LVEF, but its impact on prognosis remains unknown. Methods : A total of 211 patients (73 ± 10 years of age; 77% men) with LF-LG AS (mean gradient <40 mm Hg and indexed aortic valve area [AVA] =0.6 cm2/m2) and reduced LVEF (=40%) were prospectively enrolled in the TOPAS (True or Pseudo-Severe Aortic Stenosis) study and 125 (59%) of them underwent aortic valve replacement (AVR) within 3 months following inclusion. The severity of AS was assessed by the projected AVA (AVAproj) at normal flow rate (250 ml/s), as previously described and validated. The severity of TR was graded according to current guidelines. Results : Among the 211 patients included in the study, 22 (10%) had no TR, 113 (54%) had mild (grade 1), 50 (24%) mild-to-moderate (grade 2), and 26 (12%) moderate-to-severe (grade 3) or severe (grade 4) TR. During a mean follow-up of 2.4 ± 2.2 years, 104 patients (49%) died. Univariable analysis showed that TR =2 was associated with increased risk of all-cause mortality (hazard ratio [HR]: 1.82, 95% confidence interval [CI]: 1.22 to 2.71; p = 0.004) and cardiovascular mortality (HR: 1.85, 95% CI: 1.20 to 2.83; p = 0.005). After adjustment for age, sex, coronary artery disease, AVAproj, LVEF, stroke volume index, right ventricular dysfunction, mitral regurgitation, and type of treatment (AVR vs. conservative), the presence of TR =2 was an independent predictor of all-cause mortality (HR: 1.88, 95% CI: 1.08 to 3.23; p = 0.02) and cardiovascular mortality (HR: 1.92, 95% CI: 1.05 to 3.51; p = 0.03). Furthermore, in patients undergoing AVR, TR =3 was an independent predictor of 30-day mortality compared with TR = 0/1 (odds ratio [OR]: 7.24, 95% CI: 1.56 to 38.2; p = 0.01) and TR = 2 (OR: 4.70, 95% CI: 1.00 to 25.90; p = 0.05). Conclusions : In patients with LF-LG AS and reduced LVEF, TR is independently associated with increased risk of cumulative all-cause mortality and cardiovascular mortality regardless of the type of treatment. In patients undergoing AVR, moderate/severe TR is associated with increased 30-day mortality. Further studies are needed to determine whether TR is a risk marker or a risk factor of mortality and whether concomitant surgical correction of TR at the time of AVR might improve outcomes for this high-risk population

Natural history of very severe aortic stenosis

We sought to assess the outcome of asymptomatic patients with very severe aortic stenosis

A Single Lung Transplant in a Patient with Fabry Disease: Causality or Far-Fetched? A Case Report

Introduction. Fabry disease is a rare X-linked lysosomal storage disorder, characterized by an α-galactosidase A deficiency resulting in globotriaosylceramide storage within cells. Subsequently, various organ systems are involved, clinically the most important are kidneys, the heart, and the peripheral and central nervous systems. Although obstructive lung disease is a common pathological finding in Fabry disease, pulmonary involvement is a clinically disregarded feature. Case Presentation. We report a patient with a diagnosis of chronic obstructive pulmonary disease (COPD) who received a single lung transplant in 2007. Later, a kidney biopsy revealed the diagnosis of Fabry disease, which was confirmed by enzymatic and genetic testing. Ultrastructural changes in a native lung biopsy were consistent with the diagnosis. Although the association of a lung transplant and Fabry disease appears far-fetched on first sight, respiratory impairment cannot be denied in Fabry disease. Conclusion. With this case presentation, we would like to stimulate discussion about rare differential diagnoses hidden beneath widespread disease and that a correct diagnosis is the base of an optimal treatment strategy for each patient. Overall, the patient might have benefited from specific enzyme replacement therapy, especially in view of the chronic kidney disease

Predictors of outcomes in low-flow, low-gradient aortic stenosis: results of the multicenter TOPAS Study.

Background—Patients with low-flow, low-gradient aortic stenosis have a poor prognosis with conservative therapy but a high operative mortality if treated surgically. Recently, we proposed a new index of aortic stenosis severity derived from dobutamine stress echocardiography, the projected aortic valve area at a normal transvalvular flow rate, as superior to other conventional indices to differentiate true-severe from pseudosevere aortic stenosis. The objective of this study was to identify the determinants of survival, functional status, and change in left ventricular ejection fraction during follow-up of patients with low-flow, low-gradient aortic stenosis. Methods and Results—One hundred one patients with low-flow, low-gradient aortic stenosis (aortic valve area 1.2 cm2 , left ventricular ejection fraction 40%, and mean gradient 40 mm Hg) underwent dobutamine stress echocardiography and an assessment of functional capacity using the Duke Activity Status Index. A subset of 72 patients also underwent a 6-minute walk test. Overall survival was 70 5% at 1 year and 57 6% at 3 years. After adjusting for age, gender, and the type of treatment (aortic valve replacement versus no aortic valve replacement), significant predictors of mortality during follow-up were a Duke Activity Status Index 20 (P0.0005) or 6-minute walk test distance 320 m (P0.0001, in the subset of 72 patients), projected aortic valve area at a normal transvalvular flow rate 1.2 cm2 (P0.03), and peak dobutamine stress echocardiography left ventricular ejection fraction 35% (P0.03). More severe stenosis, defined as projected aortic valve area 1.2 cm2 , was a predictor of mortality only in the no aortic valve replacement group. The Duke Activity Status Index, 6-minute walk test, and left ventricular ejection fraction improved significantly during follow-up in the aortic valve replacement group, but remained unchanged or decreased in the no aortic valve replacement group. Conclusion—In patients with low-flow, low-gradient aortic stenosis, the most significant risk factors for poor outcome were (1) impaired functional capacity as measured by Duke Activity Status Index or 6-minute walk test distance; (2) more severe valve stenosis as measured by projected aortic valve area at a normal transvalvular flow rate; and (3) reduced peak stress left ventricular ejection fraction, a composite measure accounting for both resting left ventricular function and contractile reserve

The impact of cardiopulmonary resuscitation (CPR) manikin chest stiffness on motivation and CPR performance measures in children undergoing CPR training-A prospective, randomized, single-blind, controlled trial.

BACKGROUND:Cardio-pulmonary-resuscitation (CPR) training starting at the age of 12 years is recommended internationally. Training younger children is not recommended because young children lack the physical ability to perform adequate CPR and discouragement to perform CPR later is apprehended. The aim of this study was to answer the following questions: Are younger children discouraged after CPR training? Is discouragement caused by their lack in physical ability to perform adequate chest compressions on a standard manikin and would the use of manikins with a reduced resistance affect their motivation or performance? METHODS:We investigated the motivation and CPR performance of children aged 8-13 years after CPR training on manikins of different chest stiffness in a prospective, randomized, single-blind, controlled trial. 322 children underwent randomization and received 30 minutes CPR training in small groups at school. We used two optically identical resuscitation manikins with different compression resistances of 45kg and 30kg. Motivation was assessed with a self-administered questionnaire. Performance was measured with the Resusci®Anne SkillReporter™. FINDINGS:Motivation after the training was generally high and there was no difference between the two groups in any of the questionnaire items on motivation: Children had fun (98 vs. 99%; P = 0.32), were interested in the training (99 vs. 98%; P = 0.65), and were glad to train resuscitation again in the future (89 vs. 91%; P = 0.89). CPR performance was generally poor (median compression score (8, IQR 1-45 and 29, IQR 11-54; P<0.001) and the mean compression depth was lower in the 45kg-resistance than in the 30kg-resistance group (33±10mm vs. 41±9; P<0.001). CONCLUSIONS:Compression resistances of manikins, though influencing CPR performance, did not discourage 8 to 13 year old children after CPR training. The findings refute the view that young children are discouraged when receiving CPR training even though they are physically not able to perform adequate CPR

Validation of conventional and simplified methods to calculate projected valve area at normal flow rate in patients with low flow, low gradient aortic stenosis : the multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) study

Background : It has been previously demonstrated that a new index of aortic stenosis (AS) severity derived from dobutamine stress echocardiography (DSE), the projected aortic valve area (AVA) at a normal transvalvular flow rate (AVAproj), is superior to traditional Doppler echocardiographic indices to discriminate true severe from pseudosevere low-gradient AS. The objectives of this study were to prospectively validate the diagnostic and prognostic value of AVAproj in a large series of patients and to propose a new clinically applicable simplified method to estimate AVAproj. Methods : AVAproj was calculated in 142 patients with low-flow AS using 2 methods. In the conventional method, AVA was plotted against mean transvalvular flow (Q) at each stage of DSE, and AVA at a standardized flow rate of 250 ml/s was projected from the slope of the regression line fitting the plot of AVA versus Q: AVAproj = AVArest + slope × (250 - Qrest). In the simplified method, using this equation, the slope of the regression line was estimated by dividing the DSE-induced change in AVA from baseline to the peak stage of DSE by the change in Q. Results : There was a strong correlation between AVAproj calculated by the two methods (r = 0.95, P < .0001). Among the 142 patients, 52 underwent aortic valve replacement and had underlying AS severity assessed by the surgeon. Conventional and simplified AVAproj demonstrated similar performance in discriminating true severe from pseudosevere AS (percentage of correct classification of AVAproj = 1 cm2, 94% and 92%, respectively) and were superior to traditional dobutamine stress echocardiographic indices (percentage of correct classification, 60%-77%). Both conventional and simplified AVAproj correlated well with valve weight (r = 0.52 and r = 0.58, respectively), whereas traditional dobutamine stress echocardiographic indices did not. In the 84 patients who were treated medically, conventional AVAproj = 1.2 cm2 (hazard ratio, 1.65; P = .02) and simplified AVAproj = 1.2 cm2 (hazard ratio, 2.70; P < .0001) were independent predictors of mortality. Traditional dobutamine stress echocardiographic indices were not predictive. Conclusion : In patients with low-flow AS, AVAproj better predicts underlying AS severity and patient outcomes than traditional dobutamine stress echocardiographic indices. Simplified AVAproj is easier to calculate than conventional AVAproj, facilitating the use of AVAproj in clinical practice

Two-dimensional strain for the assessment of left ventricular function in low flow-low gradient aortic stenosis, relationship to hemodynamics, and outcome : a substudy of the multicenter TOPAS study.

Background—Decision making in patients with low flow–low gradient aortic stenosis mainly depends on the actual stenosis severity and left ventricular function, which is of prognostic importance. We used 2-dimensional strain parameters measured by speckle tracking at rest and during dobutamine stress echocardiography to document the extent of myocardial impairment, its relationship with hemodynamic variables, and its prognostic value. Methods and Results—In 47 patients with low flow–low gradient aortic stenosis, global peak systolic longitudinal strain (PLS) and peak systolic longitudinal strain rate (PLSR) were analyzed. PLS and PLSR at rest and peak stress were -7.56±2.34% and -7.41±2.89% (P=NS) and -0.38±0.12 s-1 and -0.53±0.18 s-1 (P<0.001), respectively. PLS and PLSR inversely correlated with left ventricular ejection fraction at rest (rs =-0.52; P<0.0001 and -0.38; P=0.008) and peak stress (rs =-0.39; P=0.007 and -0.45; P=0.002). The overall 2-year survival rate was 60%. Univariate predictors of survival were peak stress left ventricular ejection fraction (P=0.0026), peak stress PLS (P=0.0002), peak stress PLSR (P<0.0001), and N-terminal pro–B-type natriuretic peptide (P<0.0001). Three hierarchically nested multivariable Cox regression models were constructed—model 1: The Society of Thoracic Surgeons score as an indicator of clinical risk (area under the receiver operating characteristic=0.59); model 2: model 1+N-terminal pro–B-type natriuretic peptide and peak stress left ventricular ejection fraction (area under the receiver operating characteristic=0.83; incremental P<0.0001); model 3: model 2+peak stress PLSR (area under the receiver operating characteristic=0.89; incremental P=0.035). Conclusions—In patients with low flow–low gradient aortic stenosis, 2-dimensional strain parameters are strong predictors of outcome. Peak stress PLSR may add incremental prognostic value beyond what is obtained from N-terminal pro–B-type natriuretic peptide and peak stress left ventricular ejection fraction. A larger study is needed to confirm these findings

Myocardial blood flow in patients with low-flow, low-gradient aortic stenosis : differences between true and pseudo-severe aortic stenosis. Results from the multicentre TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study

BACKGROUND: Impairment of myocardial flow reserve (MFR) in aortic stenosis (AS) with normal left ventricular function relates to the haemodynamic severity. OBJECTIVES: To investigate whether myocardial blood flow (MBF) and MFR differ in low-flow, low-gradient AS depending on whether there is underlying true-severe AS (TSAS) or pseudo-severe AS (PSAS). METHODS: In 36 patients with low-flow, low-gradient AS, dynamic [13N]ammonia PET perfusion imaging was performed at rest (n = 36) and during dipyridamole stress (n = 20) to quantify MBF and MFR. Dobutamine echocardiography was used to classify patients as TSAS (n = 18) or PSAS (n = 18) based on the indexed projected effective orifice area (EOA) at a normal flow rate of 250 ml/s (EOAI(proj )0.55 cm(2)/m(2)). RESULTS: Compared with healthy controls (n = 14), patients with low-flow, low-gradient AS had higher resting mean (SD) MBF (0.83 (0.21) vs 0.69 (0.09) ml/min/g, p = 0.001), reduced hyperaemic MBF (1.16 (0.31) vs 2.71 (0.50) ml/min/g, p<0.001) and impaired MFR (1.44 (0.44) vs 4.00 (0.91), p<0.001). Resting MBF and MFR correlated with indices of AS severity in low-flow, low-gradient AS with the strongest relationship observed for EOAI(proj) (r(s) = -0.50, p = 0.002 and r(s) = 0.61, p = 0.004, respectively). Compared with PSAS, TSAS had a trend to a higher resting MBF (0.90 (0.19) vs 0.77 (0.21) ml/min/g, p = 0.06), similar hyperaemic MBF (1.16 (0.31) vs 1.17 (0.32) ml/min/g, p = NS), but a significantly smaller MFR (1.19 (0.26) vs 1.76 (0.41), p = 0.003). An MFR <1.8 had an accuracy of 85% for distinguishing TSAS from PSAS. CONCLUSIONS: Low-flow, low-gradient AS is characterised by higher resting MBF and reduced MFR that relates to the AS severity. The degree of MFR impairment differs between TSAS and PSAS and may be of value for distinguishing these entities