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Background: An increased acceleration time to ejection time (AT/ET) ratio is associated with increased mortality in patients with aortic stenosis (AS)., Aim: To identify the factors associated with an increased AT/ET ratio., Methods: The relationships between the AT/ET ratio and clinical and Doppler echocardiographic variables of interest in the setting of AS were analysed retrospectively in 1107 patients with AS and preserved left ventricular (LV) ejection fraction (LVEF). The computed tomography aortic valve calcium (CT-AVC) score was studied in a subgroup of 342 patients., Results: In the univariate analysis, the AT/ET ratio was found to correlate with peak aortic jet velocity (r=0.57; P<0.0001), mean pressure gradient (r=0.60; P<0.0001), aortic valve area (r=-0.50; P<0.0001) and CT-AVC score (r=0.24; P<0.0001). The AT/ET ratio had good accuracy in predicting a peak aortic jet velocity≥4 m/s, a mean pressure gradient≥40mmHg and an aortic valve area≤1.0cm 2 , with an optimal cut-off value of 0.34. Multivariable linear regression analysis showed that presence of AS-related symptoms, decreased LV stroke volume index, LVEF, absence of diabetes mellitus, systolic blood pressure, increased LV mass index, relative wall thickness and peak aortic jet velocity were independently associated with an increased AT/ET ratio (all P<0.05). In the subgroup of patients who underwent CT-AVC scoring, the CT-AVC score was independently associated with an increased AT/ET ratio (P<0.05)., Conclusions: The AT/ET ratio is related to echocardiographic and CT-AVC indices of AS severity. However, multiple intricate factors beyond the haemodynamic and anatomical severity of AS influence the AT/ET ratio, including LV geometry, function and systolic blood pressure. These findings should be considered when assessing the AT/ET ratio in patients with AS and preserved LVEF., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The ability to visualize the right atrium (RA) by echocardiography allows a quantitative, highly reproducible assessment of the RA volume (RAV). The aim of this study is to evaluate the relation between RAV and long-term mortality in a prospective cohort of heart failure and reduced ejection fraction patients in sinus rhythm receiving cardiac resynchronization therapy. 172 patients were included. The right atrium volume index (RAVI) was calculated using Simpson's method from the apical four-chamber view and indexed to body surface area. The relation between RAVI and mortality during follow up was studied. Median follow up was 68 months (interquartile range 62 to 73 months). Mean RAVI was 27 ± 14 mL/m² (IQR 22 to 33 mL/m²). Cumulative 5-year all-cause mortality was 22 ± 6% in patients with RAVI ≤ 19 mL/m², 24 ± 6% for RAVI 19 to 29 mL/m² and 58 ± 7% for RAVI >29 mL/m² (p for trend <0.001). After adjustment on clinical and echocardiographic predictors of outcome including indices of right ventricular function, there was a significant increase in overall mortality risk with increasing RAVI (adjusted hazard ratio 1.02 [95% confidence interval, 1.00 to 1.03], per 1 mL/m 2 increment; p = 0.042). Patients in the highest tertile (RAVI >29 mL/m²) had significantly greater risk of death compared with those with RAVI ≤29 mL/m² (adjusted hazard ratio 2.01 [95% confidence interval, 1.15 to 3.50]; p = 0.014). In conclusion, RA enlargement is a powerful and highly reproducible independent predictor of long-term mortality in patients with heart failure and reduced ejection fraction in sinus rhythm receiving cardiac resynchronization therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: We hypothesized that preoperative electromechanical dyssynchrony amenable to cardiac resynchronization therapy (CRT) and QRS narrowing immediately after CRT are both correlated and have a cumulative impact on response and outcome after CRT., Methods: A total of 233 CRT candidates (heart failure New York Heart Association classes II-IV, ejection fraction < 35%, QRS ≥ 120 milliseconds, 44% women, 71 ± 11 years old) were prospectively included. Preoperative electromechanical dyssynchrony amenable to CRT was assessed by septal deformation patterns using speckle tracking echocardiography. QRS narrowing was calculated from 12-lead electrocardiograms before and immediately after CRT implantation. The primary endpoint was overall mortality during long-term follow-up. The NTC clinical trial number is NCT02986633., Results: Eighty-seven percent of patients with preoperative electromechanical dyssynchrony experienced QRS narrowing after CRT (118/136), whereas 69% of patients without preoperative electromechanical dyssynchrony (67/97) experienced QRS narrowing after CRT (P < 0.001). By Cox multivariate analysis, both preoperative electromechanical dyssynchrony and lack of postoperative QRS narrowing were independently associated with an increased risk of mortality during follow-up (adjusted hazards ratio [HR] 2.24, 95% confidence interval [CI] 1.43-3.50 and HR 1.90, 95% CI 1.06-3.38, respectively). Compared with patients with preoperative electromechanical dyssynchrony, patients without both electromechanical dyssynchrony and postoperative QRS narrowing experienced a considerable increased risk of mortality during follow-up (adjusted HR 3.70, 95% CI 1.96-6.97)., Conclusions: Lack of postoperative QRS narrowing after CRT is associated with preoperative electromechanical dyssynchrony. Both preoperative electromechanical dyssynchrony and postoperative QRS narrowing have a favourable cumulative impact on outcome after CRT., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The frequency of paradoxical low-gradient severe aortic stenosis (AS) varies widely across studies. The impact of misalignment of aortic flow and pressure recovery phenomenon on the frequency of low-gradient severe AS with preserved left ventricular ejection fraction (LVEF) has not been evaluated in prospective studies., Aims: To investigate prospectively the impact of aortic flow misalignment by Doppler and lack of pressure recovery phenomenon correction on the frequency of low-gradient (LG) severe aortic stenosis (AS) with preserved LVEF., Methods: Aortic jet velocities and mean pressure gradient (MPG) were obtained by interrogating all windows in 68 consecutive patients with normal LVEF and severe AS (aortic valve area [AVA] ≤1cm 2 ) on the basis of the apical imaging window alone (two-dimensional [2D] apical approach). Patients were classified as having LG or high-gradient (HG) AS according to MPG <40mmHg or ≥40mmHg, and normal flow (NF) or low flow (LF) according to stroke volume index >35mL/m 2 or ≤35mL/m 2 , on the basis of the 2D apical approach, the multiview approach (multiple windows evaluation) and AVA corrected for pressure recovery., Results: The proportion of LG severe AS was 57% using the 2D apical approach alone. After the multiview approach and correction for pressure recovery, the proportion of LG severe AS decreased from 57% to 13% (LF-LG severe AS decreased from 23% to 3%; NF-LG severe AS decreased from 34% to 10%). As a result, 25% of patients were reclassified as having HG severe AS (AVA ≤1cm 2 and MPG ≥40mmHg) and 19% as having moderate AS. Hence, 77% of patients initially diagnosed with LG severe AS did not have "true" LG severe AS when the multiview approach and the pressure recovery phenomenon correction were used., Conclusions: Aortic flow misevaluation, resulting from lack of use of multiple windows evaluation and pressure recovery phenomenon correction, accounts for a large proportion of incorrectly graded AS and considerable overestimation of the frequency of LG severe AS with preserved LVEF., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Ivabradine is an original drug that has been approved in two indications (systolic heart failure and angina). The aim of this short review is to draw the attention of clinician prescribers to the evidence base of ivabradine. Three large randomized trials testing ivabradine versus placebo have been performed. The BEAUTIFUL and SIGNIFY trials were in fact negative in the treatment of angina while the SHIFT trial found a marginal benefit of ivabradine over placebo in the treatment of heart failure. These important results are put into perspective in order to improve the assessment of risk-cost/benefit balances when ivabradine is considered. Ideally, a further clinical trial investigating the use of ivabradine in heart failure should be carried out with optimal treatment of the patient population in order to identify the subgroup of patients who respond to ivabradine.

Background: Assessment of vascular endothelial function lacks consistency, and microvascular endothelial function has been only partly assessed in heart failure with preserved ejection fraction (HFpEF)., Methods: The study population consisted of 90 patients: 45 had well documented HFpEF, and 45 had hypertension and no history or evidence of heart failure. Patients with hypertension but no heart failure were matched with HFpEF patients for age, sex, and diabetes. They served as control subjects. All patients underwent 2-dimensional Doppler echocardiography and vascular function measurements, including assessment of arterial wave reflections and arterial stiffness, brachial artery flow-mediated dilation (FMD), and forearm cutaneous blood flow with the use of a laser Doppler flow probe at rest and after release of arterial occlusion for 5 minutes., Results: Brachial artery FMD was lower in HFpEF than in control subjects (median (IQR) 3.6 (0.4-7.4) vs. 7.2 (3.2-17.2)%, P = .001). Forearm cutaneous blood flow at rest was similar in HFpEF and control subjects (P = .68). After release of arterial occlusion, forearm cutaneous peak blood flow was lower in HFpEF than in control subjects (P = .03). Estimated aortic systolic and mean blood pressures were similar in HFpEF and control subjects, whereas pulse pressure and pressure augmentation were greater in HFPEF than in control subjects (both P < .05)., Conclusion: Compared with hypertensive control subjects, patients with HFpEF had a depressed endothelial function in the forearm vasculature and microvasculature., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To identify electrocardiographic and echocardiographic predictors of mortality and hospitalizations for heart failure (HF) in the KaRen study., Background: KaRen is a prospective, observational study of the long-term outcomes of patients presenting with heart failure and a preserved ejection fraction (HFpEF)., Method: We identified 538 patients who presented with acute cardiac decompensation, a >100 pg/mL serum b-type natriuretic peptide (BNP) or >300 pg/mL N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and a left ventricular ejection fraction (LVEF) >45%. After 4-8 weeks of standard treatment, 413 patients (mean age = 76 ± 9 years, 55.9% women) returned for analyses of their clinical status, laboratory screen, and detailed electrocardiographic and Doppler echocardiographic recordings. They were followed for a mean of 28 months thereafter. The primary study endpoint was time to death from all causes or first hospitalization for heart failure., Results: Mean LVEF was 62.4 ± 6.9% and median NT-proBNP 1410 pmol/L. PR interval >200 ms was present in 11.2% of patients and 14.9% had a >120 ms QRS duration, with left bundle branch block in only 6.3%. Over a mean follow-up of 28 months, 177 patients (42.9%) reached a primary study endpoint, including 61 deaths and 116 hospitalizations for heart failure. After adjustment for age, gender, New York Heart Association class, atrial fibrillation history, creatinine, sodium, BNP, ejection fraction, and right ventricular fractional shortening, only E/e' remained as a predictor, with a hazard ratio = 1.49 and P = 0.0012., Conclusion: The incidence of hospitalizations for HF and deaths in KaRen was high and E/e' predicted adverse clinical outcomes. These observations should help in the risk stratification and therapy of HFpEF., (© 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.)

Background: Previous studies have found a high frequency of mechanical dyssynchrony in patients with heart failure (HF) with preserved ejection fraction (HFpEF), hence suggesting that cardiac resynchronization therapy (CRT) may be considered in HFpEF. The present study was designed to compare the amount of mechanical dyssynchrony between HFpEF patients and (1) HF with reduced EF (HFrEF) patients with an indication for CRT (HFrEF-CRT(+)) group, (2) HFrEF patients with QRS duration < 120 ms (HFrEF-QRS < 120 ms) group, and (3) hypertensive controls (HTN)., Methods: Electrical (ECG) and mechanical dyssynchrony (atrio-ventricular dyssynchrony, interventricular dyssynchrony, intraventricular dyssynchrony) were assessed using conventional, tissue Doppler, and Speckle Tracking strain echocardiography in 40 HFpEF patients, 40 age- and sex-matched HTN controls, 40 HFrEF-QRS < 120 ms patients, and 40 HFrEF-CRT(+) patients., Results: The frequency of left bundle branch block was low in HFpEF patients (5%) and similar to HTN controls (5%, P = 0.85). Indices of dyssynchrony were similar between HFpEF and HTN patients or HFrEF-QRS < 120 ms patients. In contrast, most indices of dyssynchrony differed between HFpEF and HFrEF-CRT(+) patients. The principal components analysis on the entire cohort of 160 patients yielded 2 homogeneous groups of patients in terms of dyssynchrony, the first comprising HFrEF-CRT(+) patients and the second comprising HTN, HFrEF-QRS < 120 ms and HFpEF patients., Conclusions: Mechanical dyssynchrony in HFpEF does not differ from that of patients with HTN or patients with HFrEF and a narrow QRS. This data raises concerns regarding the role of dyssynchrony in the pathophysiology of HFpEF and thereby the potential usage of CRT in HFpEF., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Left ejection fraction (LVEF)--resulting from the difference between end-diastolic volume (EDV) and end-systolic volume (ESV), divided by EDV--is a poor index of left ventricular (LV) systolic performance due to its dependency on load conditions, inotropic state and LV remodelling. The characteristic impedance of the ascending aorta (Zc) integrates factors opposing LV ejection during the early ejection period when arterial wave reflection can be neglected. Zc is related to the pressure wave velocity (C) and the cross-sectional area of the aorta. The aim is to demonstrate that LV performance and geometry are closely related to the physical properties of the arterial system. LV pressure-volume loops were obtained from simultaneous measurements of LV (or aortic) pressure and LV volume. The slope Ees (also called LV end-systolic elastance) of the ESP-ESV relationship was assessed. Aortic diameters, pressure and flow measurements were synchronized to evaluate C, aortic forward and backward pressure waves, the elasticity of the aorta (Ep) and thereby Zc. In contrast to LVEF, LV end-systolic elastance (Ees), which reflects the stiffness of the chamber at maximal myofilament activation, is relatively insensitive to load conditions and may be considered as an index of ventricular chamber contractility. For a given Ees value, the end-systolic pressure (ESP) determines the LV end-systolic volume. Ees is determined by cardiac myocytes contractility and density, and thereby concentric remodelling. A tight correlation between Zc and the degree of LV concentric remodelling was found in hypertensive and in normal subjects. Zc was found to increase throughout the full lifespan and also with hypertension. Both Zc and wave reflections determine aortic input impedance estimated from the aortic pressure-flow relationship. Increased arterial stiffness resulted in increasing C and overlap of forward and backward waves and thereby in greater pulse pressure and ESP and a greater difference between ESP and diastolic pressure. Ees is an accurate index of LV systolic performance. Besides the inotropic state of myofibers, Ees depends on the concentric remodelling and thereby on the characteristic impedance of the aorta., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Aims: The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction (HFPEF) remain poorly characterized. This study aimed to investigate this., Methods and Results: The Karolinska-Rennes (KaRen) Study was a multinational prospective observational study designed to characterize HFPEF. Inclusion required acute HF, defined by the Framingham criteria, LVEF ≥ 45%, and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospectively for 18 months. Predictors of the primary (HF hospitalization or all-cause mortality) and secondary (all-cause mortality) outcomes were assessed with multivariable Cox regression. A total of 539 patients [56% women; median (interquartile range) age 79 (72-84) years; NT-pro-BNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Known history of HF was present in 40%. Co-morbidities included hypertension (78%), atrial fibrillation/flutter (65%), anaemia (51%), renal dysfunction (46%), CAD (33%), diabetes (30%), lung disease (25%), and cancer (16%). The primary outcome occurred in 268 patients [50%; 106 deaths (20%) and 162 HF hospitalizations (30%)]. Important independent predictors of the primary and/or secondary outcomes were age, history of non-cardiovascular syncope, valve disease, anaemia, lower sodium, and higher potassium, but no cardiovascular co-morbidities. Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis., Conclusion: HFPEF was associated with higher age, female gender, hypertension, atrial fibrillation/flutter, and numerous non-cardiovascular co-morbidities. Prognosis was determined by non-cardiovascular co-morbidities, but use of conventional heart failure medications may still be associated with improved outcomes., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Background: Karolinska Rennes (KaRen) is a prospective observational study to characterize heart failure patients with preserved ejection fraction (HFpEF) and to identify prognostic factors for long-term mortality and morbidity., Aims: To report characteristics and echocardiography at entry and after 4-8 weeks of follow-up., Methods: Patients were included following an acute heart failure presentation with B-type natriuretic peptide (BNP)>100 ng/L or N-terminal pro-BNP (NT-proBNP)>300 ng/L and left ventricular ejection fraction (LVEF)>45%., Results: The mean ± SD age of 539 included patients was 77 ± 9 years and 56% were women. Patient history included hypertension (78%), atrial tachyarrhythmia (44%), prior heart failure (40%) and anemia (37%), but left bundle branch block was rare (3.8%). Median NT-proBNP was 2448 ng/L (n=438), and median BNP 429 ng/L (n=101). Overall, 101 patients did not return for the follow-up visit, including 13 patients who died (2.4%). Apart from older age (80 ± 9 vs. 76 ± 9 years; P=0.006), there were no significant differences in baseline characteristics between patients who did and did not return for follow-up. Mean LVEF was lower at entry than follow-up (56% vs. 62%; P<0.001). At follow-up, mean E/e' was 12.9 ± 6.1, left atrial volume index 49.4±17.8mL/m(2). Mean global left ventricular longitudinal strain was -14.6 ± 3.9%; LV mass index was 126.6 ± 36.2g/m(2)., Conclusions: Patients in KaRen were old with slight female dominance and hypertension as the most prevalent etiological factor. LVEF was preserved, but with increased LV mass and depressed LV diastolic and longitudinal systolic functions. Few patients had signs of electrical dyssynchrony (ClinicalTrials.gov.- NCT00774709)., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Pulmonary hypertension (PH) is prevalent in decompensated heart failure with preserved ejection fraction (HFpEF). We investigated the effect of a return to a compensated state on pulmonary artery systolic pressure (PASP) and functional mitral regurgitation (FMR)., Methods and Results: Two-dimensional Doppler echocardiography was prospectively performed before initiation of standard therapy and 48 hours later in 37 patients hospitalized for HFpEF-related dyspnea and in 26 patients hospitalized for non-HFpEF-related dyspnea. Left atrial volume index, and E/e' ratio, and PASP were significantly greater and E-wave deceleration time significantly shorter in HFpEF than in non-HFpEF patients. Thirty-two of the 37 HFpEF had FMR on admission whereas none of the non-HFpEF patients had FMR. After 48 hours of therapy, the reduction in PASP was significantly greater in the 26 HFpEF patients who improved than in the 11 HFpEF patients who did not (-24 vs -9 mm Hg, respectively; P < .0001), whereas PASP remained unchanged in non-HFpEF patients. The decrease in PASP correlated in HFpEF patients with reductions in blood pressure, heart rate, left ventricular end-diastolic volume, inferior vena cava diameter, E/A ratio, E/e' ratio, mitral effective regurgitant orifice area (EROA), and E-wave deceleration time. The correlation between PASP and mitral EROA was the only one that remained significant by multivariate analysis., Conclusions: Noninvasive monitoring of PASP and FMR during an episode of HFpEF decompensation reveals that the return to a compensated state is associated with a significant reduction in PASP and FMR., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The objective of this study was to examine the value of stress-echocardiography in patients with paradoxical low-flow, low-gradient (PLFLG) aortic stenosis (AS). The projected aortic valve area (AVAProj) at a normal flow rate was calculated in 55 patients with PLFLG AS. In the subset of patients (n = 13) who underwent an aortic valve replacement within 3 months after stress echocardiography, AVA(Proj) correlated better with the valve weight compared to traditional resting and stress echocardiographic parameters of AS severity (AVA(Proj): r = -0.78 vs. other parameters: r = 0.46 to 0.56). In the whole group (N = 55), 18 (33%) patients had an AVA(Proj) >1.0 cm(2), being consistent with the presence of pseudo severe AS. The AVA(Proj) was also superior to traditional parameters of stenosis severity for predicting outcomes (hazard ratio: 1.32/0.1 cm(2) decrease in AVA(Proj)). In patients with PLFLG AS, the measurement of AVA(proj) derived from stress echocardiography is helpful to determine the actual severity of the stenosis and predict risk of adverse events., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Functional renal impairment is a common feature of heart failure with preserved ejection fraction (HFpEF). The link between functional renal impairment and HFpEF remains incompletely understood. With hypertension and diabetes as frequent co-morbidities, patients with HFpEF are at risk of developing intra-renal vascular hemodynamic alterations that may lead to functional renal impairment and impact on prognosis., Methods: Renal resistive index (RRI) was non-invasively determined by Doppler ultrasonic examination in 90 HFpEF patients and 90 age- and sex-matched hypertensive patients without evidence of heart failure (HF) who served as controls. Clinical, laboratory and cardiac echocardiography data were obtained in HFpEF patients and controls. To investigate its possible clinical relevance, RRI was evaluated as a prognostic index of all-cause mortality and hospitalization for HF., Results: Mean RRI was substantially greater in HFpEF patients than in controls (P < 0.0001), while mean blood pressure, glomerular filtration rate, hemoglobin and serum protein levels were significantly lower in HFpEF patients than in controls. On multivariable analysis, mean RRI was independently associated with HFpEF. In addition, increased mean RRI was an independent predictor of poor outcome [hazard ratio = 1.06 95% confidence interval (1.01-1.10), P = 0.007] and remained significantly associated with the outcome after adjustment for univariate predictors that included low mean blood pressure, low hemoglobin concentration and low glomerular filtration rate. Conclusion. Patients with HFpEF exhibit intra-renal vascular hemodynamic alterations. The severity of intra-renal vascular hemodynamic alterations correlates with a poor outcome.

The relative impact of comorbidities and parameters of left ventricular diastolic function on clinical outcome has not been thoroughly investigated in patients who are hospitalized for heart failure decompensation and found to have preserved ejection fraction. We identified 98 HFpEF patients among 1452 patients admitted with acute heart failure. Clinical characteristics, hemoglobin levels, estimated glomerular filtration rate (eGFR), B-type natriuretic peptide (BNP) and Doppler-echocardiographic parameters were analyzed. The primary end point of the study combined death and rehospitalization for decompensated heart failure after the index hospitalization. Mean age was 76 ± 9 years. LV ejection fraction, E/E (a) ratio, and estimated systolic pulmonary artery pressure were 61 (55-67)%, 12.9 (9.4-15.1), 40 (32-46) mmHg, respectively. BNP values, hemoglobin and eGFR were 287 (164-562) pg/mL, 11.3 (10.4-12.4) g/dL and 45 (37-74) mL/min/m(2), respectively. During a mean follow-up of 17 ± 11 months, 56% reached the primary endpoint of the study: 31 died and 24 were re-hospitalised for heart failure. Diabetes [HR = 1.76 (1.03-3.00), P = 0.039], lower systolic blood pressure [HR = 0.99 (0.97-0.99), P = 0.016], hemoglobin [HR = 0.62 (0.49-0.76), P < 0.0001], and eGFR [HR = 0.98 (0.97-0.99), P = 0.004] were associated with a poor outcome. Neither BNP nor echocardiographic parameters were correlated with outcome. Comorbidities primarily correlate with outcome in patients with HFpEF.

Background: Left ventricular (LV) longitudinal deformation is a good marker of intrinsic myocardial dysfunction in pressure overload cardiomyopathies., Aim: To assess the effect of valvuloarterial haemodynamic load on LV longitudinal deformation in patients with aortic valve stenosis (AVS) and preserved LV ejection fraction (LVEF)., Methods: Global LV longitudinal strain (GLS) was measured using speckle tracking imaging in a series of 82 consecutive patients with AVS (mean age 75+/-10 years; 50% men). The global (valvular+arterial) haemodynamic load imposed on the LV was estimated by the valvuloarterial impedance (Z(va)), and was calculated using either arm-cuff systolic peripheral blood pressure or systolic central aortic blood pressure estimated by SphygmoCor., Results: Among this series of 82 patients with preserved LVEF, 79% had reduced LV GLS (<-18%). LV GLS correlated weakly with AVS severity, systemic vascular resistance and systemic arterial compliance. However, there was a good inverse correlation between increase in Z(va) and impairment of LV GLS (r=0.41 p<0.0001). On multivariable analysis, impaired GLS was associated with increased Z(va) (p<0.0001), increased E/Ea ratio (p=0.001) and increased LV end-diastolic volume index (p=0.021), while indices of valvular load were not. Utilization of estimated central aortic blood pressure in place of brachial pressure did not improve the performance of Z(va) to predict GLS., Conclusion: The magnitude of the global haemodynamic load as reflected by Z(va) is a powerful determinant of altered LV longitudinal deformation in AVS patients with preserved LVEF. The calculation of Z(va) may be useful to identify the patients who are potentially at higher risk for the development of myocardial dysfunction. Use of estimated central aortic pressure in the calculation of Z(va) does not appear to provide any incremental predictive value over that calculated with the simple measurement of brachial pressure., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Aims: Heart failure with preserved ejection fraction (HFPEF) is common but not well understood. Electrical dyssynchrony in systolic heart failure is harmful. Little is known about the prevalence and the prognostic impact of dyssynchrony in HFPEF., Methods and Results: We have designed a prospective, multicenter, international, observational study to characterize HFPEF and to determine whether electrical or mechanical dyssynchrony affects prognosis. Patients presenting with acute heart failure (HF) will be screened so as to identify 400 patients with HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria for HF, left ventricular ejection fraction>or=45%, brain natriuretic peptide (BNP)>100 pg/mL or NT-proBNP>300 pg/mL. Once stabilized, 4-8 weeks after the index presentation, patients will return and undergo questionnaires, serology, ECG, and Doppler echocardiography. Thereafter, patients will be followed for mortality and HF hospitalization every 6 months for at least 18 months. Sub-studies will focus on echocardiographic changes from the acute presentation to the stable condition and on exercise echocardiography, cardiopulmonary exercise testing, and serological markers., Conclusion: KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results might improve our understanding of HFPEF and generate answers to the question whether dyssynchrony could be a target for therapy in HFPEF.

BACKGROUND: Risk stratification of patients with low-gradient (LG) severe aortic stenosis (AS) despite preserved left ventricular ejection fraction remains challenging. We sought to evaluate the relationship between the dimensionless index (DI)—the ratio of the left ventricular outflow tract time-velocity integral to that of the aortic valve jet—and mortality in these patients. METHODS: Seven hundred fifty-five patients with LG severe AS (defined by aortic valve area ≤1 cm² or aortic valve area indexed to body surface area ≤0.6 cm²/m² and mean aortic pressure gradient <40 mm Hg) and preserved left ventricular ejection fraction ≥50% were studied. Flow status was defined according to stroke volume index <35 mL/m² (low flow, LF) or ≥35 mL/m² (normal flow, NF). RESULTS: After adjustment for age, sex, body mass index, Charlson comorbidity index, history of hypertension, history of atrial fibrillation, AS-related symptoms, left ventricular ejection fraction, indexed left ventricular ventricular mass, aortic valve area, and aortic valve replacement as a time-dependent covariate, patients with LG-LF and DI<0.25 exhibited a considerable increased risk of death compared with patients with LG-NF and DI≥0.25 (adjusted hazard ratio, 2.41 [95% CI, 1.61–3.62]; P<0.001), LG-NF and DI<0.25 (adjusted hazard ratio, 1.84 [95% CI, 1.24–2.73]; P=0.003), and LG-LF and D≥0.25 (adjusted hazard ratio, 2.27 [95% CI, 1.42–3.63]; P<0.001). In contrast, patients with LG-LF and DI≥0.25, LG-NF and DI<0.25, and LG-NF and DI≥0.25 had similar outcome. DI<0.25 showed incremental prognostic value in patients with LG-LF severe AS but not in patients with LG-NF severe AS. CONCLUSIONS: Among patients with LG severe AS and preserved left ventricular ejection fraction, decreased DI<0.25 is a reliable parameter in patients with LF to identify a subgroup of patients at higher risk of death who may derive benefit from aortic valve replacement. [ABSTRACT FROM AUTHOR]