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Data obtained from echocardiographic studies are used on a daily basis to guide clinical decision-making regarding patient management and the need for additional diagnostic investigations. Interrogation of blood flow in the pulmonary veins by spectral, most often pulsed-wave, Doppler is an important component of any comprehensive echocardiographic study. Whereas it is most often used to help assess left-sided filling pressure and quantify the severity of mitral regurgitation, the pulmonary vein Doppler profile provides added diagnostic insights into several disorders that affect heart function and allows assessment of their hemodynamic consequences on the heart. The aim of this review is to summarize current knowledge in the field of PV Doppler interrogation, highlight the physiological and pathological parameters that influence it, and delineate the manifestations of various cardiovascular disorders on the flow profile.

Background The prognostic value of aortic valve calcification (AVC) measured by using multidetector computed tomography imaging has been well validated in native aortic stenosis, and sex-specific thresholds have been proposed. However, few data are available regarding the impact of leaflet calcification on outcomes after biological aortic valve replacement (AVR). Objectives The goal of this study was to analyze the association of quantitative bioprosthetic leaflet AVC with hemodynamic and clinical outcomes, as well as its possible interaction with sex. Methods From 2008 to 2010, a total of 204 patients were prospectively enrolled with a median of 7.0 years (interquartile range: 5.1 to 9.2 years) after biological surgical AVR. AVC measured by using the Agatston method was indexed to the cross-sectional area of aortic annulus measured by echocardiography to calculate the AVC density (AVCd). Presence of hemodynamic valve deterioration (HVD; increase in mean gradient [MG] ≥10 mm Hg and/or increase in transprosthetic regurgitation ≥1) was assessed by echocardiography in 137 patients at the 3-year follow-up. The primary clinical endpoint was mortality or aortic valve re-intervention. Results There was no significant sex-related difference in the relationship between bioprosthetic AVCd and the progression of MG. Baseline AVCd showed an independent association with HVD at 3 years. During follow-up, there were 134 (65.7%) deaths (n = 100) or valve re-interventions (n = 47). AVCd ≥58 AU/cm2 was independently associated with an increased risk of mortality or aortic valve re-intervention (adjusted hazard ratio: 2.23; 95% confidence interval: 1.44 to 3.35; p Conclusions Aortic bioprosthetic leaflet calcification is strongly and independently associated with HVD and the risk of death or aortic valve re-intervention. As opposed to native aortic stenosis, there is no sex-related differences in the relationship between AVCd and hemodynamic or clinical outcomes.

High-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate, and cardiac cavities’ size and function in endurance-trained adults. Seventeen endurance-trained men underwent 24-h ambulatory blood pressure monitoring and Doppler echocardiography at baseline and after 6 wk of HIIT. Participants were divided into 2 groups [85% maximal aerobic power (HIIT85), n = 8 and 115% maximal aerobic power (HIIT115), n = 9] to compare the impact of different HIIT intensities. Ambulatory blood pressure monitoring and cardiac chambers’ size and function were similar between groups at baseline. HIIT reduced heart rate (55 ± 8 vs. 51 ± 7 beats/min; P = 0.003), systolic blood pressure (121 ± 11 vs. 118 ± 9 mmHg; P = 0.01), mean arterial pressure (90 ± 8 vs. 89 ± 6 mmHg; P = 0.03), and pulse pressure (52 ± 6 vs. 49 ± 5 mmHg; P = 0.01) irrespective of training intensity. Left atrium volumes increased after HIIT (maximal: 50 ± 14 vs. 54 ± 14 mL; P = 0.02; minimal: 15 ± 5 vs. 20 ± 8 mL; P = 0.01) in both groups. Right ventricle global longitudinal strain lowered after training in the HIIT85 group only (20 ± 4 vs. 17 ± 3%, P = 0.04). In endurance-trained men, 6 wk of HIIT reduced systolic blood pressure and mean arterial pressure and increased left atrium volumes irrespective of training intensity, whereas submaximal HIIT deteriorated right ventricle systolic function. NEW & NOTEWORTHY The novel findings of this study are that 6 wk of high-intensity interval training increases left atrial volumes irrespective of training intensity (85 or 115% maximal aerobic power), whereas the submaximal training decreases right ventricular systolic function in endurance-trained men. These results may help identify the exercise threshold for potential toxicity of intense exercise training for at-risk individuals and ideal exercise training regimens conferring optimal cardiovascular protection and adapted endurance training for athletes.

High-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate and cardiac cavities size and function in endurance-trained adults. Seventeen endurance-trained males underwent 24-hour ambulatory blood pressure monitoring (ABPM) and Doppler echocardiography at baseline and after 6 weeks of HIIT. Participants were divided in 2 groups (85% maximal aerobic power (MP); HIIT85, n=8 and 115% MP; HIIT115, n = 9) in order to compare the impact of different HIIT intensities. ABPM and cardiac chambers size and function were similar between groups at baseline. HIIT reduced heart rate (55 ± 8 vs. 51 ± 7 bpm; p= 0.003), systolic blood pressure (SBP; 121 ± 11 vs 118 ± 9 mmHg; p = 0.01), mean arterial pressure (MAP; 90 ± 8 vs 89 ± 6 mmHg; p = 0.03) and pulse pressure (52 ± 6 vs 49 ± 5 mmHg; p = 0.01), irrespective of training intensity. Left atrium (LA) volumes increased after HIIT (maximal: 50 ± 14 vs 54 ±14 ml; p= 0.02; minimal: 15 ± 5 vs 20 ± 8 ml; p = 0.01) in both groups. Right ventricle (RV) global longitudinal strain lowered after training in the HIIT85 group only (20 ± 4 vs. 17 ± 3%, p = 0.04). In endurance-trained males, six weeks of HIIT reduce SBP and MAP and increase LA volumes irrespective of training intensity, whereas submaximal HIIT deteriorates RV systolic function.Key pointsHigh-intensity interval training improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse.We evaluated the impact of submaximal (85% maximal aerobic power) and supramaximal (115% maximal aerobic power) high-intensity interval training on ambulatory blood pressure, heart rate and cardiac cavities size and function in endurance-trained adults.Irrespective of training intensity, six weeks of high-intensity interval training increase left atrial volumes in endurance-trained adults, whereas the submaximal training decreases right ventricular systolic function.These results may help identify the exercise threshold for potential toxicity of intense exercise training for at-risk individuals and ideal exercise training regimens conferring optimal cardiovascular protection and adapted endurance training for athletes.

Background: The incidence of structural valve deterioration after bioprosthesis (BP) aortic valve replacement (AVR) established on the basis of reoperation may substantially underestimate the true incidence. The objective is to determine the rate, timing, correlates, and association between hemodynamic valve deterioration (HVD) and outcomes assessed by Doppler echocardiography after surgical BP AVR. Methods: A total of 1387 patients (62.2% male, 70.5±7.8 years of age) who underwent BP AVR were included in this retrospective study. Baseline echocardiography was performed at a median time of 4.1 (1.3–6.5) months after AVR. All patients had an echocardiographic follow-up ≥2 years after AVR (926 at least 5 years and 385 at least 10 years). HVD was defined by Doppler assessment as a ≥10 mm Hg increase in mean gradient or worsening of transprosthetic regurgitation ≥1/3 class. HVD was classified according to the timing after AVR: “very early,” during the first 2-years; “early,” between 2 and 5 years; “midterm,” between 5 and 10 years; and “long-term,” >10 years. Results: A total of 428 patients (30.9%) developed HVD. Among these patients, 52 (12.0%) were classified as “very early,” 129 (30.1%) as “early,” 158 (36.9%) as “midterm,” and 89 (20.8%) as “long-term” HVD. Factors independently associated with HVD occurring within the first 5 years after AVR were diabetes mellitus ( P =0.01), active smoking ( P =0.01), renal insufficiency ( P =0.01), baseline postoperative mean gradient ≥15 mm Hg ( P =0.04) or transprosthetic regurgitation ≥mild ( P =0.04), and type of BP (stented versus stentless, P =0.003). Factors associated with HVD occurring after the fifth year after AVR were female sex ( P =0.03), warfarin use ( P =0.007), and BP type ( P P Conclusions: HVD as identified by Doppler echocardiography occurred in one third of patients and was associated with a 2.2-fold higher adjusted mortality. Diabetes mellitus and renal insufficiency were associated with early HVD, whereas female sex, warfarin use, and stented BPs (versus stentless) were associated with late HVD.

BACKGROUND: Dysmetabolic profile has been associated with native aortic valve stenosis. However, there are limited data on the effects of an atherogenic milieu and its potential implications on the structural and hemodynamic deterioration of aortic bioprosthetic valves. OBJECTIVES: This prospective longitudinal study sought to determine the predictors and impact on outcomes of hemodynamic valve deterioration (HVD) of surgically implanted aortic bioprostheses. METHODS: A total of 137 patients with an aortic bioprosthesis implanted for a median time of 6.7 (interquartile range: 5.1 to 9.1) years prospectively underwent a first (baseline) assessment with complete Doppler echocardiography, quantitation of bioprosthesis leaflet calcification by multidetector computed tomography (CT), and a fasting blood sample to assess cardiometabolic risk profile. All patients underwent a second (follow-up) Doppler echocardiography examination at 3 (interquartile range: 2.9 to 3.3) years post-baseline visit. HVD was defined by an annualized change in mean transprosthetic gradient ≥3 mm Hg/year and/or worsening or transprosthetic regurgitation by ≥1/3 class. The primary endpoint was a nonhierarchical composite of death from any cause or aortic reintervention procedure (redo surgical valve replacement or transcatheter valve-in-valve implantation) for bioprosthesis failure. RESULTS: Thirty-four patients (25.6%) had leaflet calcification on baseline CT, and 18 patients (13.1%) developed an HVD between baseline and follow-up echocardiography. Fifty-two patients (38.0%) met the primary endpoint during subsequent follow-up after the second echocardiographic examination. Leaflet calcification (hazard ratio [HR]: 2.58; 95% confidence interval [CI]: 1.35 to 4.82; p = 0.005) and HVD (HR: 5.12; 95% CI: 2.57 to 9.71; p \textless 0.001) were independent predictors of the primary endpoint. Leaflet calcification, insulin resistance (homeostatic model assessment index ≥2.7), lipoprotein-associated phospholipase A2 activity (Lp-PLA2 per 0.1 nmol/min/ml increase), and high level of proprotein convertase subtilisin/kexin 9 (PCSK9) (≥305 ng/ml) were associated with the development of HVD after adjusting for age, sex, and time interval since aortic valve replacement. CONCLUSIONS: HVD identified by Doppler echocardiography is independently associated with a marked increase in the risk of valve reintervention or mortality in patients with a surgical aortic bioprosthesis. A dysmetabolic profile characterized by elevated plasma Lp-PLA2, PCSK9, and homeostatic model assessment index was associated with increased risk of HVD. The presence of leaflet calcification as detected by CT was a strong predictor of HVD, providing incremental risk-predictive capacity.

Background The timing of mitral valve surgery in asymptomatic patients with primary mitral regurgitation ( MR ) is controversial. We hypothesized that the forward left ventricular (LV) ejection fraction ( LVEF ; ie, LV outflow tract stroke volume divided by LV end‐diastolic volume) is superior to the total LVEF to predict outcomes in MR . The objective of this study was to examine the association between echocardiographic parameters of MR severity and LV function and outcomes in patients with MR . Methods and Results The clinical and Doppler‐echocardiographic data of 278 patients with ≥mild MR and no class I indication of mitral valve surgery at baseline were retrospectively analyzed. The primary study end point was the composite of mitral valve surgery or death. During a mean follow‐up of 5.4±3.2 years, there were 147 (53%) events: 96 (35%) MV surgeries and 66 (24%) deaths. Total LVEF and global longitudinal strain were not associated with the occurrence of events, whereas forward LVEF ( P LV end‐systolic diameter ( P =0.0003) were. After adjustment for age, sex, MR severity, Charlson probability, coronary artery disease, and atrial fibrillation, forward LVEF remained independently associated with the occurrence of events (adjusted hazard ratio: 1.09, [95% confidence interval]: 1.02–1.17 per 5% decrease; P =0.01), whereas LV end‐systolic diameter was not ( P =0.48). Conclusions The results of this study suggest that the forward LVEF may be superior to the total LVEF and LV end‐systolic diameter to predict outcomes in patients with primary MR . This simple and easily measurable parameter may be useful to improve risk stratification and select the best timing for intervention in patients with primary MR .

Objectives In this study, we sought to determine the metabolic markers associated with structural valve degeneration (SVD). Background Structural valve degeneration (SVD) is the major cause of bioprosthetic valve failure leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the SVD of BPs. Methods We included 197 patients who underwent aortic valve replacement with a bioprosthetic valve and had echocardiographic follow-up to evaluate valve function. Moreover, explanted BPs (n = 39) were analysed by immunohistochemistry for the expression of Lp-PLA2. Results After a mean follow-up of 7·9 ±0·2 years, forty-one patients (21%) were identified as developing SVD. Patients with SVD had significantly higher plasma level of Lp-PLA2 mass (151·8 ± 9·2 ng/mL vs. 133·2 ± 3·4 ng/mL, P = 0·03) and activity (27·6 ± 0·9 nmol/min/mL vs. 25·0 ± 0·4 nmol/min/mL, P = 0·005). Multivariate analysis revealed that Lp-PLA2 activity (OR: 1·09, 95% CI: 1·01–1·18; P = 0·03) was the strongest independent predictor of SVD. Immunohistochemistry studies of explanted BP showed that 77% of explanted BPs had the expression of Lp-PLA2, which correlated with the density of macrophages (CD68), and ox-LDL levels in bioprosthetic tissues. Conclusions Increased blood plasma activity of Lp-PLA2 is associated with higher prevalence of SVD. These findings open new avenues for the identification of patients at risk for SVD and for the development of pharmacotherapy aiming at the prevention of SVD.

Aims There are very few data regarding the assessment and prognostic value of left ventricular contractile reserve (LVCR) in asymptomatic patients with primary mitral regurgitation (MR). We aimed to quantify LVCR and to evaluate its usefulness for risk stratification in asymptomatic patients with primary MR. Methods and results Comprehensive resting and exercise (EX) transthoracic echocardiography, including two-dimensional speckle tracking quantification, were performed in 115 consecutive asymptomatic patients with ≥moderate degenerative MR and no LV dysfunction/dilatation. Left ventricular contractile reserve was defined as an EX-induced increase in LV ejection fraction (LVCRLVEF) ≥4% or in LV global longitudinal strain (LVCRGLS) ≥2%. LVCRLVEF was present in 54 patients (47%) and LVCRGLS in 58 (50%). The brain natriuretic peptide (BNP) level was significantly correlated with EX-induced changes in GLS ( r = 0.45, P < 0.0001), but not in LVEF ( r = 0.09, P = 0.31). Patients with no LVCRGLS had significant lower 3-year cardiac event-free survival (42 ± 8 vs. 69 ± 7%, P = 0.0008). In contrast, there was no significant difference in outcome regarding to the presence or absence of LVCRLVEF (60 ± 7 vs. 51 ± 8%, P = 0.40). The multivariable Cox proportional hazard model showed that the absence of LVCRGLS was a strong independent predictor of cardiac events (HR = 2.27, 95% CI: 1.05–4.76, P = 0.037), even after adjustment for Ex-echo variables and BNP level. The association between LVCRGLS and outcome remained significant (HR = 1.6, 95% CI: 1.1–2.3, P = 0.01) after further adjustment for the resting echocardiographic parameters included in the ESC Guidelines. Conclusion In asymptomatic primary MR, LVCR seems to be better assessed using EX-induced changes in LV myocardial longitudinal function rather than in LVEF. In patients with preserved LV function, the absence of LVCR is independently associated with two-fold increase in risk of cardiac events. Left ventricular contractile reserve may be useful to improve risk stratification and clinical decision-making in these patients.

Prosthesis-patient mismatch (PPM) occurs when the effective orifice area (EOA) of a normally functioning prosthesis is too small in relation to the patient’s body size, resulting in abnormally high postoperative gradients. PPM is frequent following aortic valve replacement (AVR), and it is associated with increased risk of morbidity and mortality proportionally to its severity. Differential diagnosis between PPM and prosthetic valve stenosis is made by comparing the measured valve effective orifice area, by assessing the changes in valve area and gradient during follow-up and by evaluating leaflet morphology and mobility. Preventive strategies to avoid or minimize PPM should be implemented especially in the patients who are at high risk for severe PPM and in those who have vulnerability factors to PPM. Transcatheter AVR may be superior to surgical AVR for the prevention of PPM and associated adverse cardiac events, particularly in the subset of patients with a small (

Background Bioprosthesis (BP) structural deterioration after aortic valve replacement (AVR) is generally defined by re-operation for BP failure. This approach underestimates the incidence of structural valve deterioration. We intended to determine the incidence, predictors and impact of valve hemodynamic deterioration (VHD) assessed by echocardiography (TTE). Methods A total of 1387 patients (62.2% male; 70.5 ± 7.8 years old) were retrospectively included. A baseline TTE was performed at a median time of 4.1 (1.3–6.5) months post-AVR. TTE follow-up was performed at least 2-years post-AVR in all patients, at least 5-years in 926 patients and at least 10-years in 385 patients. VHD was defined as: > 10 mmHg increase in mean gradient (MG) and/or worsening of regurgitation > 1/3 grade from baseline to last TTE follow-up. Results Overall, VHD was identified in 428 patients (30.9%). The VHD occurred within the first 5 years in 181 (42.3%) patients and after 5 years in 247(57.7%) patients. VHD was a predictor of death (HR: 2.18, 95% CI: 1.86 to 2.57, P 15 mmHg (HR: 1.30, 95% CI: 1.05 to 1.62, P = 0.02), severe PPM (HR: 1.85, 95% CI: 1.12 to 2.87, P = 0.02) and type of BP (P 15 mmHg (P = 0.04), post-surgery > mild transprosthetic regurgitation (P = 0.04) and type of BP (P = 0.003). Predictors of late VHD (i.e. after the 5 years) were: female sex (P = 0.03), coumadin (P = 0.007) and type of BP (P Conclusions VHD as documented by TTE is frequent (30%) following AVR and associated with 2.2-fold increase in mortality. The main factors associated with VHD were female sex, diabetes, smoking, coumadin, presence of severe prosthesis-patient mismatch, high residual gradient, and/or regurgitation early after AVR.

To identify the determinants and the impact on outcome of brain natriuretic peptide (BNP) in asymptomatic patients with degenerative mitral regurgitation (MR).Comprehensive transthoracic echocardiography including two-dimensional speckle tracking quantification was performed in 135 consecutive asymptomatic patients (60±14 years, 56% men) with moderate to severe degenerative MR and preserved left ventricular (LV) function. Blood samples were collected at the time of the echocardiography and plasma BNP levels were measured.BNP level and cardiac events.BNP was correlated with age, indexed LV end-systolic diameter, indexed left atrium (LA) volume, estimated LV filling pressure with E/Ea ratio, systolic pulmonary arterial pressure and global longitudinal strain (GLS). In multiple regression analysis, indexed LA volume (p=0.008), mitral deceleration time (p=0.003) and GLS (p0.0001) were independently associated with BNP. During follow-up (mean=23±19 months), 54 events occurred resulting in 4-year event-free survival of 50±6%. There was a graded relationship between the increase in BNP (ie, according to quartile) and reduced event-free survival (p0.0001). In Cox multivariable analysis, indexed LA volume (HR=1.04, p=0.003), GLS (HR=1.14, p=0.007) and 3rd and 4th quartiles of BNP (HR=8.5, p=0.002 and HR=8.8, p=0.002) were independent determinants of event-free survival.In asymptomatic degenerative MR, LV longitudinal function and LA volume are the main determinants of BNP release. BNP is a powerful independent predictor of cardiac events. Measurement of plasma BNP may help to improve risk stratification and management of asymptomatic patients with degenerative MR.

Aims The aim of this study was to explore the range of pulmonary artery systolic pressure (PASP) at rest and with exercise in healthy individuals of various ages, as most studies assumed PASP . 35 mmHg with exercise as the upper limits of normal. Methods and results Seventy healthy volunteers, with a good continuous wave Doppler tricuspid regurgitation signal at rest, underwent quantitative Doppler echocardiographic measurements at rest and during semi-supine exercise test. Pulmonary artery systolic pressure was estimated at rest, at low level (25 W), and at peak exercise using four times tricuspid valve regurgitation velocity squared adding a right atrial pressure of 5 mmHg. During exercise, PASP increased from rest (27+4 mmHg) to peak (51+9 mmHg). None of the individuals reached a PASP � 60 mmHg at 25 W. Pulmonary artery systolic pressure at peak was higher in individuals � 60 years old compared with those from 20 to 59 years old (56+9 vs. 49+7 mmHg, P ¼ 0.02). Pulmonary artery systolic pressure at peak exercise � 60 mmHg was found in 36% of the individuals aged from 60 to 70 and in 50% after 70. Age, LV mass, and PASP at rest were independent predictors of PASP at peak exercise. Conclusion Pulmonary artery systolic pressure at peak exercise can reach values � 60 mmHg in many healthy individuals older than 60 with good exercise capacity. However, high levels of PASP . 60 mmHg for low level of exercise should be considered abnormal.

SummaryBackgroundEchocardiography is recommended for all patients with a clinical diagnosis of heart failure (HF). Management of HF in daily practice differs from guidelines.AimTo evaluate the prognostic impact of echocardiography in patients hospitalized for a first episode of HF.MethodsConsecutive patients (n=799) hospitalized for a first episode of HF were prospectively enrolled during 2000. Propensity scores and multivariable analyses were used to reduce the imbalance in baseline covariates between the Echo and No-Echo groups.ResultsDuring hospitalization, echocardiography was not performed in 151 patients (19%). Patients in the No-Echo group were older, more likely to be female, less frequently admitted to cardiology departments, and had lower rates of life-saving drugs prescribed at discharge. After adjustment for covariates of prognostic importance, use of echocardiography was associated with lower relative risk of three-year overall mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.48–0.78, p

SummaryIntroductionHeart failure (HF) is associated with high morbidity and mortality. A significant component of HF-related adverse outcome occurs during hospitalization.ObjectiveTo assess features and in-hospital outcomes of patients hospitalized for a first episode of HF.MethodsWe prospectively recruited 799 consecutive patients hospitalized for a first episode of HF during 2000 in the Somme department (France). We evaluated in-hospital mortality in this cohort, identified factors predictive for hospital death, and compared the mortality in patients with preserved or reduced ejection fraction (EF).ResultsThe mean age of the study population was 75±12 years. EF, assessed in 662 patients (83%), was preserved (≥50%) in 56% of cases. During hospitalization, 64 deaths (8%) were recorded. The major causes of in-hospital death were acute pulmonary oedema (50%) and cardiogenic shock (22%). Coronary artery disease, low systolic blood pressure on admission, increased heart rate on admission, renal failure, reduced EF (

Chronic obstructive pulmonary disease (COPD) is a frequently neglected co-morbidity in patients with heart failure (HF). The aim of this study was to evaluate the prognostic impact of COPD in patients hospitalized for HF. Consecutive patients (n=799) admitted for a first episode of HF in all healthcare establishments of the Somme department (France) during 2000 were prospectively enrolled. Baseline characteristics and long-term prognosis were compared according to COPD status. COPD was diagnosed in 156 patients (19.5%). Compared with the no-COPD group, patients with COPD were predominantly men, more often smokers, and had lower discharge prescription rates of beta blockers (6% vs 27%, p0.001). Five-year survival rate in patients with COPD was significantly lower than that of the no-COPD group (31% vs 42%, p=0.03). Compared with the expected survival of the age- and gender-matched general population, the 5-year survival rate in patients with COPD was dramatically lower (31% vs 71%). On multivariable analysis, COPD was a strong predictor of poorer outcome (hazard ratio 1.53, 95% confidence interval 1.21 to 1.94, p0.001). COPD was an independent predictor of mortality in patients with preserved left ventricular ejection fraction and in patients with reduced ejection fraction. In conclusion, patients with HF and associated COPD have a poor prognosis with an impressive excess mortality compared to HF patients without COPD and the general population. Beta-blocker prescription rates remain deceptively low in this category of patients with HF.

Aims This study was designed to identify the characteristics and long-term prognosis of heart failure with preserved ejection fraction (HFPEF) in patients hospitalized for a first episode of HF. Methods and results Consecutive patients ( n = 799) hospitalized for a first episode of HF during 2000 in the Somme department (France) were recruited. EF was available in 662 (83%) patients, representing the study population. Patients with HFPEF (55.6% of cases) were significantly older, with a high proportion of women. During the 5 year follow-up, 370 patients (56%) died. Patients with HFPEF had a significantly lower 5 year survival than the age- and sex-matched general population (43 vs. 72%). Five year survival rates were not significantly different in patients with preserved and reduced EF (43 vs. 46%; P = 0.95). Both groups had similar relative 5 year survival rates compared with the general population. Multivariable analysis identified age, stroke, chronic obstructive pulmonary disease, cancer, diabetes, low glomerular filtration rate, and hyponatraemia as independent predictors of 5 year mortality in patients with HFPEF. Conclusions Heart failure with preserved ejection fraction has a poor prognosis, comparable with that of HF with reduced EF, with a 5 year survival rate after a first episode of 43% and a high excess mortality compared with the general population.

Introduction Structural valve degeneration (SVD) leads to the failure of aortic valve bioprostheses. It is suspected that lipid-derived factors could play a role in SVD. We hypothesised that oxidised low-density lipoprotein (OxLDL), OxLDL/LDL, OxLDL/high-density lipoprotein (OxLDL/HDL) and proprotein convertase subtilisin/kexin 9 (PCSK9) may be associated with SVD. Methods We included 199 patients who underwent an aortic valve replacement with a bioprosthesis and had an echocardiography follow-up to evaluate the function of the prosthesis. SVD was defined as an increase in mean transprosthetic gradient (≥10 mm Hg) or a worsening of transprosthetic regurgitation (≥1/3) during the follow-up. Results After a mean follow-up of 8±3.5 years, 41(21%) patients developed SVD. The univariate predictors of SVD were LDL (p=0.03), apolipoprotein B (p=0.01), OxLDL (p=0.02), OxLDL/HDL (p=0.009) and LDL associated with small, dense particles (LDL-C ) (p=0.02). In a model adjusted for covariates, only OxLDL/HDL (OR 1.49, 95%CI 1.08 to 2.07 per 10 units, p=0.01) remained associated with SVD. There was a significant interaction between OxLDL/HDL and PCSK9 on SVD (p=0.05). After adjustment, compared with patients with low OxLDL/HDL (median, Conclusions OxLDL/HDL ratio is independently associated with SVD.

Background We previously reported that plasma Lp-PLA2 was associated with aortic valve disease progression and degeneration of bioprostheses. Low systemic arterial compliance and high valvuloarterial impedance (Z va ) are predictors of poor survival in patients with aortic valve disease. However, the prevalence of high Z va after AVR is largely unknown and whether Lp-PLA2 could predict Z va has not been documented. We investigated the relationships between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity and valvuloarterial impedance (Z va ), an index of global LV hemodynamic load, in patients that underwent aortic valve replacement (AVR). Methods A total of 195 patients with aortic bioprostheses underwent echocardiographic assessment of the prosthetic aortic valve function 8 ± 3.4 years after AVR. Lp-PLA2 mass and activity were measured. Results In this group of patients, the mean Z va was elevated (5.73 ± 1.21 mm Hg·ml − 1 ·m 2 ). In univariate analyses, Lp-PLA2 mass (p = 0.003) and Lp-PLA2 activity (p = 0.046) were associated with Z va . After adjustment for covariates including age, gender, clinical risk factors, anti-hypertensive medications, body mass index and prosthesis size, Lp-PLA2 mass was associated with high Z va (≥ 4.5 mm Hg·ml − 1 ·m 2 ) (OR: 1.29, 95%CI: 1.10–1.53; p = 0.005) and was inversely related with the systemic arterial compliance (β = − 0.01, SEM = 0.003; p = 0.003). Conclusions An increased Z va , an index of excessive hemodynamic load, was highly prevalent 8-year post-AVR and was independently related to circulating Lp-PLA2.

The specific flow pattern and imaging features of prosthetic heart valves poses major challenges for the Doppler echocardiographic assessment of prosthetic valve structure and function. A comprehensive approach that integrates several semi-quantitative and quantitative parameters obtained from multiple views is key to appropriately detect and quantitate prosthetic valve dysfunction and complications. In patients with prosthetic valves, and particularly in those with mitral prostheses, transesophageal echocardiography is often required to confirm and/or complement information obtained by transthoracic echocardiography. Three-dimensional echocardiography may provide incremental information for the identification of the underlying etiology of prosthetic valve stenosis or regurgitation. Transcatheter aortic valve implantation has rapidly expanded in the past 10 years and paravalvular regurgitation is frequent following this procedure. Given that paravalvular regurgitant jets are often multiple, irregular, and eccentric, the grading of this type of regurgitation is particularly challenging and requires an integrative multiwindow, multiplane, multiparametric approach.

International audience; AIMS:The management of asymptomatic patients with mitral regurgitation (MR) remains controversial. Exercise-induced pulmonary hypertension (ExPHT) was recently reported as a strong predictor of rapid onset of symptoms. We hypothesised that ExPHT is a predictor of postoperative cardiovascular events in patients with primary MR.METHODS AND RESULTS:One hundred and two patients with primary MR, no or mild symptoms (New York heart association (NYHA) ≤2), and no LV dysfunction/dilatation, were prospectively recruited in 3 centres and underwent exercise-stress echocardiography. The presence of ExPHT was defined as an exercise systolic pulmonary arterial pressure >60 mm Hg. All patients were closely followed up and operated on when indication for surgery was reached. Postoperative events were defined as the occurrence of atrial fibrillation (AF), stroke, cardiac-related hospitalisation or death. Among the 102 patients included, 59 developed ExPHT (58%). These patients were significantly older than those without ExPHT (p=0.01). During a mean postoperative follow-up of 50±23 months, 28 patients (26%) experienced a predefined cardiovascular event. Patients with ExPHT had significantly higher rate of postoperative events (39% vs 12%, p=0.005); the rate of events was still higher in these patients (32% vs 9%, p=0.013), even when excluding early postoperative AF (ie, within 48 h). Event-free survival was significantly lower in the ExPHT group (all events: 5-year: 60±8% vs 88±5%, p=0.007, events without early AF: 5-year: 67±7% vs 90±4%, p=0.02). Using Cox multivariable analysis, ExPHT remained independently associated with higher risk of postoperative events in all models (all p≤0.04).CONCLUSIONS:ExPHT is associated with increased risk of adverse cardiac events following mitral valve surgery in patients with primary MR.

Background Cusp calcification is the main mechanism leading to bioprosthetic heart valve (BPV) failure. Recent studies suggest that BPV calcification is an active rather than passive process probably modulated by several mechanisms including lipid-mediated inflammation and dysfunctional phosphocalcic metabolism. Objective To identify the clinical and metabolic determinants of BPV calcification assessed by multidetector CT (MDCT). Methods and results Presence of BPV calcification was assessed by MDCT in 194 patients who had undergone aortic valve replacement. A calcification score was individually calculated and expressed in mm 3 . Patients also underwent a clinical evaluation, a Doppler echocardiographic exam, and a plasma lipid and phosphocalcic profile. 46 patients (24%) had BPV calcification (cusp calcification score >0 mm 3 ). After adjustment for age, gender, and time interval since BPV implantation, increased calcium–phosphorus product (OR 1.11, 95% CI 1.01 to 1.23 per 1 unit; p=0.02) and the presence of prosthesis-patient mismatch (OR 3.67, 95% CI 1.25 to 10.6; p=0.01) were the strongest independent factors associated with BPV calcification. Calcium supplement intake, age and female gender were independently associated with increased calcium–phosphorus product. Conclusions This study suggests that higher calcium–phosphorus product and prosthesis–patient mismatch promote BPV calcification. Furthermore, this study reports that calcium supplements, which are extensively prescribed in elderly patients, are independently associated with higher calcium–phosphorus product.

Low flow (LF), defined as stroke volume index (SVi)35 mL/m(2), prior to the procedure has been recently identified as a powerful independent predictor of early and late mortality in patients undergoing transcatheter aortic valve replacement (TAVR). The objectives of this study were to determine the evolution of SVi following TAVR and to assess the determinants and impact on mortality of early postprocedural SVi (EP-SVi).We retrospectively analysed the clinical, Doppler echocardiographic and outcome data prospectively collected in 255 patients who underwent TAVR. Echocardiograms were performed before (baseline), within 5 days after procedure (early post procedure) and 6 months to 1 year following TAVR (late post procedure).Patients with EP-SVi35 mL/m(2) (n=138; 54%) had increased mortality (HR 1.97, p=0.003) compared with those with EP-SVi ≥35 mL/m(2) (n=117; 46%). Furthermore, patients with baseline SVi (B-SVi)35 mL/m(2) and EP-SVI ≥35 mL/m(2), that is, normalised flow, had better survival (HR 0.46, p=0.03) than those with both B-SVi and EP-SVi35 mL/m(2), that is, persistent LF, and similar survival compared with those with both B-SVi and EP-SVi ≥35 mL/m(2), that is, maintained normal flow. In a multivariable model analysis, EP-SVi was independently associated with increased risk of mortality (HR 1.41 per 10 mL/m(2) decrease, p=0.03). The preprocedural/intraprocedural factors associated with lower EP-SVi were lower B-SVi (standardised β [β] 0.36, p0.001) atrial fibrillation (β -0.13, p=0.02) and transapical approach (β -0.22, p0.001).The measurement of EP-SVi is useful to assess the immediate haemodynamic benefit of TAVR and to predict the risk of late mortality.

Aims LV hypertrophy (LVH) is frequent after aortic valve replacement (AVR) and is often associated with comorbidities, including hypertension, obesity, renal failure and prosthesis-patient mismatch (PPM). However, whether other biological mechanism(s) may participate to LVH after AVR is still unknown. Parathyroid hormone (PTH) may play a role in LVH. However, it is presently unknown whether PTH is associated with LVH in patients that have undergone an AVR. Methods In this cross-sectional study, 195 patients have been investigated at a mean of 8±3.5 years following AVR. LV function and mass were evaluated by Doppler echocardiography. The plasma levels of PTH, 25-hydroxyvitamin D (25-OHD), calcium and phosphate were measured. Results There were 102 (52%) patients with LVH after AVR. In univariate analyses, PTH blood level was associated with LV mass (LVMi) and LVH. After adjustment for other risk factors, elevated PTH remained associated with LVMi (p=0.003) and LVH (p=0.02). In turn, the blood levels of 25-OHD and the renal function (GFR) were independently and inversely related to the blood level of PTH. Conclusions After AVR, the level of PTH is independently associated with LVH. In turn, the level of PTH is related with the renal function and the level of 25-OHD.

Perflutren cardiac ultrasound agents improve diagnostic accuracy in patients whose imaging is technically difficult. This report describes a case of sudden death approximately 5 minutes after the intravenous administration of 0.5 mL of perflutren contrast agent (Definity) during transthoracic echocardiography with suboptimal baseline images performed 10 days after coronary artery bypass graft surgery because of hypotension and tachycardia in a 73-year-old patient with severe left ventricular systolic dysfunction. Autopsy did not reveal a clear direct relationship between perflutren and death. This is the first reported case of death related temporally to an echocardiographic contrast agent occurring in Canada and could represent a case of pseudocomplication.

Objective: To evaluate the prognostic impact of diabetes mellitus (DM) in patients with heart failure and preserved ejection fraction (HFPEF) Design: A five-year prospective observational study Setting: Population of 368 consecutive patients from 11 healthcare establishments Patients: All patients hospitalised for a first episode of HFPEF in 2000 in the Somme department, France. Interventions: Diagnosis of heart failure (HF) was validated during the index hospitalisation by two independent cardiologists. Diabetic and non-diabetic groups were compared. After discharge, patients were managed by the general practitioner or referring cardiologist. Main outcome measures: Overall and cardiovascular mortality. Results: The 96 diabetic patients (26%) were younger and had a higher prevalence of clinical coronary artery disease (CAD) than non-diabetic patients. Patients with DM had higher discharge prescription rates of angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, nitrates and statins. During the five-year follow-up, 208 patients died (43.5%). DM was a potent independent predictor of five-year overall mortality (HR 1.77, 95% CI 1.27 to 2.48, p = 0.001). Compared to the expected survival of the age-matched and gender-matched general population, the five-year survival of patients with DM was dramatically lower (32% vs 79%). The five-year relative survival (observed/expected survival) of diabetic patients was lower than that of the non-diabetic group (41% vs 68%). Cardiovascular causes were responsible for >60% of deaths in the DM group. DM was associated with an increased risk of death in patients with clinical CAD (HR 1.82, 95% CI 1.02 to 3.25, p = 0.04), as well as in patients without clinical CAD (HR 1.85, 95% CI 1.22 to 2.82, p = 0.004). Conclusion: In patients with HFPEF, DM is a strong predictor of poorer long-term survival.

Background: Although heart failure (HF) is frequent in elderly patients, few studies have focused on patients older than 80 years. Aims: To evaluate the clinical features, treatment and long-term prognosis of HF in patients older than 80 years. Methods and results: Consecutive patients hospitalised for a first HF episode in the Somme Department (France) during 2000 were prospectively included. Of the 799 included patients, 305 (38%) were aged over 80 years. The elderly patients were mostly women with a high prevalence of atrial fibrillation, ischaemic and hypertensive heart disease. Ejection fraction (EF) was assessed in 68.5% of elderly patients and 61% had EF ≥50%. Angiotensin-converting enzyme inhibitors, beta-blockers, oral anticoagulants and statins were prescribed less frequently in elderly patients. The 5-year survival in elderly patients was 19%, dramatically lower than the survival of age- and sex-matched general population (48%). Cardiovascular causes were recorded in over 60% of deaths. On multivariable analysis, cancer, renal insufficiency, old myocardial infarction, diabetes, hyponatraemia and age were predictors of mortality in elderly patients. Reduced EF was a potent predictor of death (HR 1.72, 95%CI 1.24–2.37, p=0.001) in elderly patients. Conclusion: Long-term prognosis in HF patients older than 80 years is poor, with a dramatic excess mortality compared to the elderly general population. Life-saving drugs are largely underused in elderly HF patients.

Background Although heart failure (HF) is frequent and causes significant morbidity and mortality in women, data on the prognosis of women hospitalized for a first episode of HF are scarce. This study was designed to describe the clinical characteristics and treatment of HF in women and to assess the effect of gender on long-term survival. Methods We prospectively included consecutive patients admitted for a first episode of HF in all healthcare establishments of the Somme department (France) during the year 2000. Baseline characteristics and long-term prognosis were evaluated and compared according to gender. Results 799 patients were included (389 women and 410 men). Women were older, had a higher prevalence of hypertension and renal insufficiency, and a lower prevalence of coronary artery disease. Prescription of HF medication at discharge was not significantly different between women and men. The prevalence of HF with preserved ejection fraction was higher in women. Five-year overall survival rates were not significantly different between women and men (39% vs. 41%, p =0.58). Cardiovascular mortality in women with HF was comparable with that observed in men. The 5-year survival in women was dramatically lower than the expected 5-year survival of the age-matched general population of women. On multivariable analysis, older age, cancer, stroke, diabetes, renal insufficiency, and lower natraemia were independent predictors of 5-year mortality in women. Conclusions The prognosis after a first episode of HF in women is severe, comparable to that observed in men, with a 5-year survival rate of 39% and a dramatic excess mortality compared to the general population of women.

Introduction: The management and the timing of surgery of asymptomatic patients with primary mitral regurgitation (MR) remain controversial. Exercise-induced pulmonary hypertension (ExPHT) was recently reported as a strong predictor of rapid and frequent occurrence of symptoms, leading to surgery. However, the postoperative outcome of patients with ExPHT is unknown. We aimed to describe the postop. outcome of patients with primary MR, purposely according to the presence of preop. ExPHT. Method: We prospectively included 129 asymptomatic patients (70% male, 68±12 yrs) with primary MR and no left ventricular dysfunction/dilatation, in whom we performed exercise echocardiography, in 3 centers (Fr, Bel and Can). Patients with concomitant >mild other valve disease or atrial fibrillation (AF) were excluded. The presence of ExPHT was defined as an exercise systolic pulmonary arterial pressure >60mmHg. All patients were closely followed up and operated when indication for surgery, according to most recent guidelines, was reached. Postop. events were defined as the occurrence of AF, stroke, cardiac-related hospitalization or death. Results: Among the 129 patients included, 70 have developed ExPHT (54%) and these patients were significantly older than those without ExPHT (70±11 vs. 64±14, p=0.03). There was no difference between the 2 groups regarding gender distribution, baseline LV ejection fraction, left atrial volume or MR severity. Only 15 patients underwent mitral valve replacement (12%), without significant difference between the 2 groups (ExPHT: 10% vs. no ExPHT: 14%, p=0.55). The 114 remaining patients had successful mitral valve repair. Following surgery, 28 predefined end-point were reached (22%): 17 (61%) postop. AF, 5 (18%) strokes, 3 (11%) cardiac-related hospitalization and 3 (11%) cardiac deaths. Of interest, patients with ExPHT had significant higher rate of postop. cardiac event (82% vs. 18%, p=0.0006) and all strokes occurred in ExPHT group. Using multivariate analysis, after adjustment for age, gender and preoperative NYHA functional class, ExPHT was independently associated with higher risk of postop. cardiovascular events (odds-ratio: 5.4, 95% of confidence interval: 1.8-20, p=0.002). Conclusion: The present study show that ExPHT is associated with reduced postop. event-free survival in asymptomatic patients with primary MR and no LV dysfunction/dilatation. These results emphasize the use of exercise echocardiography and suggest that early surgery could be considered to improve the outcome of these patients. Nevertheless, further data are needed to confirm these findings.

Background Despite a symptom-based management recommended by current guidelines in patients with primary mitral regurgitation (MR), the assessment of maximal exercise capacity (MEC) is rarely performed. MEC is relatively unexplored in these patients and its exercise determinants remain unknown. Method and results We prospectively studied 63 asymptomatic patients (60±13 years, 52% of male) with at least moderate MR and with preserved left ventricular (LV) systolic function in whom comprehensive resting and exercise echocardiography and cardiopulmonary exercise test were performed. MEC was assessed using peak exercise VO2 and widely varied over patients (mean: 23.6±7, median: 22.7, range: 10.2–42.4 ml/kg/min). According to the median of peak VO2, patients with reduced MEC were significantly older (p=0.0052) and were more frequently women (p=0.02). There was no other significant difference between the 2 groups (reduced vs. preserved MEC) regarding demographic and clinical data and medication. During exercise, Peak VO2 was significantly correlated with exercise LV stroke volume (r=−0.33, p=0.02) and there was a trend for significant correlation with exercise RegV and effective regurgitant orifice area (r=−0.32, p=0.05 and r=−0.3, p=0.07, respectively). In addition, the best correlations with peak VO2 were found with exercise SPAP (r=−0.52, p Conclusion In asymptomatic patients with primary MR and preserved LV systolic function, MEC may vary considerably. The main independent determinants of MEC are related to MR consequences on LA and SPAP, in particular during exercise.

BackgroundExercise Doppler echocardiographic stress test can be of interest in the management of asymptomatic patients with primary MR. The resting BNP level is a good surrogate marker of MR consequences and is a powerful predictor of outcome. The incremental prognostic value of BNP response during exercise is unknown. We aimed to identify the determinants of exercise brain natriuretic peptide (BNP) level and to evaluate its prognostic value in asymptomatic patients with primary mitral regurgitation (MR).MethodsComprehensive resting and exercise transthoracic Dopplerechocardiography was performed in 113 consecutive asymptomatic patients with moderate to severe degenerative MR and preserved LV function. Blood samples were collected both at rest and exercise.ResultsThe BNP level significantly increased from rest to exercise (p