Adverse effects of benfluorex on heart valves and pulmonary circulation.

Benfluorex is responsible for the development of restrictive valvular regurgitation due to one of its metabolites, norfenfluramine. The 5-HT2B receptor, expressed on heart valves, acts as culprit receptor for drug-induced valvular heart disease (VHD). Stimulation of this receptor leads to the upregulation of target genes involved in the proliferation and stimulation of valvular interstitial cells through different intracellular pathways. Valve lesions essentially involve the mitral and/or aortic valves. The randomised prospective REGULATE trial shows a threefold increase in the incidence of valvular regurgitation in patients exposed to benfluorex. A cross-sectional trial shows that about 7% of patients without a history of VHD previously exposed to benfluorex present echocardiographic features of drug-induced VHD. The excess risks of hospitalisation for cardiac valvular insufficiency and of valvular replacement surgery were respectively estimated to 0.5 per 1000 and 0.2 per 1000 exposed patients per year. Recent data strongly suggest an aetiological link between benfluorex exposure and pulmonary arterial hypertension (PAH). The PAH development may be explained by serotonin, which creates a pulmonary vasoconstriction through potassium-channel blockade. Further studies should be conducted to determine the subsequent course of benfluorex-induced VHD and PAH, and to identify genetic, biological and clinical factors that determine individual susceptibility to developing such adverse effects.

Low systolic blood pressure at admission predicts long-term mortality in heart failure with preserved ejection fraction.

BACKGROUND: Systolic blood pressure (SBP) at hospital admission predicts in-hospital and postdischarge mortality in patients with left ventricular systolic dysfunction. The relationship between admission SBP and mortality in heart failure with preserved (≥50%) ejection fraction (HFPEF) is still unclear. METHODS AND RESULTS: We aimed to investigate the relationship between admission SBP and 5-year outcome in 368 consecutive patients hospitalized for new-onset HFPEF. Five-year all-cause mortality rates according to admission SBP categories (<120, 120-139, 140-159, 160-179, and ≥180 mm Hg) were 75 ± 7%, 53 ± 6%, 52 ± 7%, 55 ± 4%, and 60 ± 7%, respectively (P = .029). Survival analysis showed an inverse relation between admission SBP and mortality with increased risk of death for SBP <120 mm Hg. SBP <120 mm Hg independently predicted 5-year all-cause mortality (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.08-2.63) and cardiovascular mortality (adjusted HR 1.89, 95% CI 1.21-2.97). In patients discharged alive, after adjustment for medical treatment at discharge, admission SBP <120 mm Hg remained predictive of all-cause mortality (adjusted HR 1.52, 95% CI 1.04-2.43) and cardiovascular mortality (adjusted HR 1.69, 95% CI 1.06-2.73). There was no interaction between any of the therapeutic classes and outcome prediction of SBP. CONCLUSIONS: In HFPEF, low SBP (<120 mm Hg) at the time of hospital admission is associated with excess long-term mortality. Further studies are required to determine the mechanism of this association.

Predicting left ventricular dysfunction after valve repair for mitral regurgitation due to leaflet prolapse: additive value of left ventricular end-systolic dimension to ejection fraction.

AIMS: Left ventricular (LV) dysfunction is the first cause of late mortality after mitral valve surgery. In this retrospective analysis, we studied the association between preoperative echocardiographic LV measures and occurrence of LV dysfunction after mitral valve repair (MVR). METHODS AND RESULTS: Between 1991 and 2009, 335 consecutive patients underwent MVR for severe mitral regurgitation due to leaflet prolapse in our institution. Echocardiography was performed preoperatively and at 10.8 (9.1-12.0) months after surgery in 303 patients who represented the study population. Cardiac events were recorded during follow-up. LV ejection fraction (EF) decreased from 68 ± 9% before surgery to 59 ± 9% post-operatively (P < 0.001). Preoperative EF <64% and LV end-systolic diameter (ESD) ≥ 37 mm were the best cut-off values for the prediction of post-operative LV dysfunction (EF < 50%). On the basis of a combined analysis, the occurrence of post-operative LV dysfunction was 9% when EF was ≥ 64% and LVESD < 37 mm, 21% with EF < 64% or LVESD ≥ 37 mm, and 33% with EF < 64% and LVESD ≥ 37 mm (P for trend < 0.001). The combined variable EF < 64% and LVESD ≥ 37 mm added incremental prognostic value to the multivariable regression model (P = 0.001). CONCLUSION: Simple preoperative echocardiography measures allow the prediction of LV dysfunction after MVR in patients with leaflet prolapse. Patients with preoperative EF ≥ 64% and LVESD < 37 mm incur relatively low risk of post-operative LV dysfunction.

Restrictive organic mitral regurgitation associated with benfluorex therapy.

AIMS: To investigate the association between benfluorex use and organic restrictive mitral regurgitation (MR) in patients admitted to hospital for diagnostic work-up of MR of unclear aetiology. METHODS AND RESULTS: Among patients referred between 2003 and 2008 to our tertiary centre for diagnostic work-up of MR, we retrospectively identified 22 consecutive patients (65 +/- 12 years, 64% women) with restrictive organic MR of unclear aetiology. Using propensity scores, 22 out of 156 patients who underwent surgery for dystrophic MR due to flail leaflets during the same time period were matched for age, sex, height, body weight, and diabetes with the study population. Eight of the 22 patients with restrictive organic MR of unclear aetiology (36.4%) had a history of benfluorex use, and in one patient (4.5%) we identified previous exposure to both benfluorex and fenfluramine. The frequency of benfluorex treatment in patients with restrictive organic MR of unclear aetiology was significantly higher compared with that observed in the dystrophic MR group (36.4 vs. 4.5%; P-value 0.039). Patients with restrictive MR treated with benfluorex (body mass index 31 +/- 6 kg/m(2)) were all dyslipidaemic and 67% had diabetes. Echocardiography identified moderate or severe restrictive organic MR in all cases. Median total duration of benfluorex therapy was 63(12-175) months, at a daily dose of 450 (300-450) mg, leading to a cumulative dose of 850 (108-2363) g. CONCLUSION: Although it cannot affirm a definitive causal relationship, the present study strongly suggests that patients treated with benfluorex might incur a risk of restrictive organic valvular heart disease. Therefore, echocardiography should be performed in patients exposed to benfluorex in case of occurrence of symptoms or signs of valvular disease. Further data are needed to confirm these findings.

Effects of age on pulmonary artery systolic pressure at rest and during exercise in normal adults.

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 > or = 60 mmHg at 25 W. Pulmonary artery systolic pressure at peak was higher in individuals > or =60 years old compared with those from 20 to 59 years old (56 +/- 9 vs. 49 +/- 7 mmHg, P = 0.02). Pulmonary artery systolic pressure at peak exercise > or =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 > or =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.

Prognostic impact of angiotensin-converting enzyme inhibitor therapy in diastolic heart failure.

The angiotensin-converting enzyme (ACE) inhibitor has a well defined place in the treatment of systolic heart failure (HF). Evidence for routine prescription of an ACE inhibitor in patients with diastolic HF (DHF) is inconsistent. Therefore, our aim was to evaluate the prognostic impact of ACE inhibitor in patients with DHF. The present prospective study included patients with normal or slightly impaired ejection fraction (> or =50%) surviving a first hospitalization for HF. We assessed the long-term prognosis of these patients according to prescription of an ACE inhibitor at discharge. ACE inhibitor therapy prescribed at discharge in 46% (n = 165) of the 358 included patients was associated with a 30% relative decrease in the risk of 5-year mortality (hazard ratio 0.70, 95% confidence interval 0.53 to 0.93, p = 0.013). On multivariable Cox analysis, the relation between ACE inhibitor prescription and mortality remained significant (hazard ratio 0.73, 95% confidence interval 0.54 to 0.99, p = 0.045). Using propensity score analysis, 120 patients receiving an ACE inhibitor were matched with 120 patients not receiving this medication. In the postmatch group, prescription of ACE inhibitor was associated with a significant decrease in the risk of 5-year mortality (hazard ratio 0.61, 95% confidence interval 0.43 to 0.87, p = 0.006). Five-year relative survival (observed/expected survival) of the ACE inhibitor group was better than that of the no-ACE inhibitor group (65% vs 57%). In conclusion, we demonstrate that in this cohort of patients with DHF, prescription of ACE inhibitor was associated with a significant decrease in long-term mortality.

Effect of atrial fibrillation on long-term survival in patients hospitalised for heart failure with preserved ejection fraction.

BACKGROUND: The prognostic importance of atrial fibrillation (AF) in heart failure (HF) is not clearly established. Studies conducted in systolic HF have led to discordant results. AIMS: To evaluate the relation between AF and long-term survival in patients with heart failure and preserved ejection fraction (HFPEF). METHODS AND RESULTS: We prospectively included 368 consecutive patients hospitalised for a first episode of HFPEF during 2000 and compared the 5-year outcome of patients according to the presence or absence of AF on the baseline electrocardiogram. Propensity scores were used to reduce imbalance in baseline characteristics. Baseline AF was observed in 36% (n=132) of the study population. Patients with AF were older and more often had hypertensive heart disease. On univariate analysis, baseline AF was associated with an increased risk of 5-year overall mortality (HR=1.36; 95%CI 1.03-1.79; p=0.03). After adjustment for covariates, baseline AF was no longer a predictor of reduced survival. The risk of adjusted cardiovascular death in patients with and without AF was comparable. In the propensity-matched patients, AF was not related to a poorer outcome (HR=1.08; 95%CI 0.78-1.51; p=0.63). CONCLUSION: In patients hospitalised for HFPEF, AF is frequent and associated with an excess mortality mainly related to the advanced age of these patients. After adjustment for covariates, baseline AF is not an independent predictor of long-term mortality.

Long-term survival in patients older than 80 years hospitalised for heart failure. A 5-year prospective study.

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 >or=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.

Prognostic significance of left ventricular concentric remodelling in patients with aortic stenosis.

BACKGROUND: Four patterns of left ventricular (LV) geometry (normal, concentric remodelling, concentric hypertrophy and eccentric hypertrophy) have been described in aortic stenosis (AS). Although LV concentric remodelling (LVCR), characterized by normal LV mass despite increased LV wall thickness, is frequently observed in AS, its prognostic implication has been not specifically studied. AIM: We aimed to assess, using echocardiography, the prognostic implication of LVCR in asymptomatic or minimally symptomatic patients with AS. METHODS: Overall, 331 patients (mean age 73±13 years; 45% women) with AS (aortic valve area≤1.3cm2) and an ejection fraction >50% were enrolled. The endpoints were mortality with conservative management and mortality with conservative and/or surgical management. RESULTS: Sixty-three (19%) patients died under conservative management (follow-up 29±1 months). The highest risk of mortality under conservative management compared with patients with normal LV geometry was observed for LVCR (adjusted hazard ratio [HR]: 3.53, 95% confidence interval [CI]: 1.19-10.46; P=0.023), followed by concentric LVH (adjusted HR: 2.97, 95% CI: 1.02-8.60; P=0.045). Aortic valve replacement was performed in 96 patients (29%) during the entire follow-up (37±1 months); 72 (22%) patients died. Only LVCR remained independently associated with an increased risk of mortality when surgical management during the entire follow-up was considered (adjusted HR: 2.93, 95% CI: 1.19-7.23; P=0.020). CONCLUSIONS: Among the patterns of LV geometry in AS, LVCR portends the worst outcome. Patients with LVCR and AS have a considerable increased risk of mortality, regardless of clinical management.

Prognostic value of preoperative atrial fibrillation in patients with aortic stenosis and low ejection fraction having aortic valve replacement.

Aortic valve replacement in severe aortic stenosis (AS) with a low left ventricular ejection fraction (EF) is associated with high perioperative mortality. The aim of this study was to assess the prognostic value of preoperative atrial fibrillation (AF) in patients with AS and low EFs who undergo aortic valve replacement. Eighty-three consecutive patients with severe AS (area <1 cm2) and low EFs (< or =35%) were prospectively included. Perioperative mortality was 12%. Twenty-nine patients (35%) had preexisting paroxysmal or permanent AF. Perioperative mortality was higher in the AF group than in the non-AF group (24% vs 5.5%, p = 0.03). Preoperative AF was identified as an independent predictor of perioperative mortality (odds ratio 7.5, 95% confidence interval 1.19 to 47.06, p = 0.03). Five-year overall survival was lower in the AF group than in the non-AF group (47% vs 77%, p = 0.0017). Associated multivessel coronary artery disease and preoperative AF were identified as 2 independent predictors of overall mortality. In conclusion, in patients with AS with low left ventricular EFs, preoperative AF is associated with higher operative risk and lower postoperative survival. The presence of AF in patients with severe AS and low EFs should be taken into account for operative risk stratification, along with low pressure gradient and associated multivessel coronary artery disease.

Outcome Implication of Aortic Valve Area Normalized to Body Size in Asymptomatic Aortic Stenosis.

BACKGROUND: Current guidelines define severe aortic stenosis in patients with aortic valve area normalized to body surface area (AVA/BSA) <0.6 cm2/m2; yet, this cutoff has never been validated. Moreover, it is not known whether AVA normalization to other body size indexes allows improved outcome prediction. We aim to test the value of AVA normalized to body size for outcome prediction in asymptomatic aortic stenosis. METHODS AND RESULTS: We included 289 patients with asymptomatic aortic stenosis, preserved ejection fraction, and AVA<1.3 cm2 at diagnosis. The outcome measure was the occurrence of aortic valve replacement or all-cause death or during follow-up. AVA was normalized to BSA, height, weight, and body mass index. For each normalized index, patients in the lowest tertile were at high risk of events whereas outcome was similar for the other tertiles. High risk of events was observed with AVA/BSA <0.4 cm2/m2 (adjusted hazard ratio [HR], 3.42 [2.09-5.60]), AVA/height <0.45 cm2/m (adjusted HR, 3.99 [2.42-6.60]), AVA/weight <0.01 cm2/kg (adjusted HR, 3.37 [2.07-5.49]), and AVA/body mass index <0.029 cm2/kg per meter square (adjusted HR, 3.23 [1.99-5.24]). Mortality risk was high with AVA/height <0.45 cm2/m (adjusted HR, 2.18 [1.28-3.71]), followed by AVA/BSA <0.40 cm2/m2 (adjusted HR, 1.84 [1.09-3.11]), AVA/weight <0.01 cm2/kg (adjusted HR, 1.78 [1.07-2.98]), and AVA/body mass index <0.029 cm2/kg per meter square (adjusted HR, 1.75 [1.04-2.93]). AVA/height showed better predictive performance than AVA/BSA with improved reclassification and better discrimination (net reclassification improvement: 0.33 versus 0.28; integrated discrimination improvement: 0.10 versus 0.08; C statistic: 0.67 versus 0.65), whereas AVA/weight and AVA/body mass index showed lower predictive capacity. CONCLUSIONS: Among AVA normalization methods, AVA/height <0.45 cm2/m followed by AVA/BSA <0.40 cm2/m2 seem as robust parameters for defining high risk in asymptomatic aortic stenosis. The prognostic value of AVA/height deserves future research.

Assessment of the physiologic significance of coronary disease with dipyridamole real-time myocardial contrast echocardiography. Comparison with technetium-99m sestamibi single-photon emission computed tomography and quantitative coronary angiography.

OBJECTIVES: The purposes of this study were to test whether quantitative real-time myocardial contrast echocardiography (RT-MCE) can detect coronary disease during pharmacologic stress and to compare this approach with single-photon emission computed tomography (SPECT). BACKGROUND: Assessing myocardial perfusion during stress is important for the diagnosis and risk stratification of patients with coronary disease. METHOD: Thirty-five patients referred for coronary angiography underwent RT-MCE and technetium-99m methoxyisobutylisonitrile (MIBI) SPECT at baseline and after 0.84 mg/kg dipyridamole. The modalities of RT-MCE and SPECT were analyzed both qualitatively and quantitatively. For this purpose, myocardial flow reserve was calculated from microbubble replenishment curves, and regional MIBI uptake was measured on circumferential profiles. Segments and vascular territories were categorized into five groups with increasing stenosis severity by quantitative coronary angiography. RESULTS: With dipyridamole, beta and A x beta increased in all but the highest stenosis severity group. The increase in beta and A x beta was significantly lower in territories supplied by stenotic arteries than in those supplied by arteries with <50% stenosis. Graded decreases in beta and A x beta reserves were noted with increasing stenosis severity. Using the cutoff value of 2.00 for beta reserve, quantitative RT-MCE correctly identified 97% of the territories supplied by significant stenoses and 82% of those supplied by normal arteries. In contrast, quantitative SPECT correctly identified only 71% of the territories supplied by significant stenoses and 81% of those supplied by normal arteries. CONCLUSIONS: This study shows that RT-MCE, with dipyridamole, can define the presence and severity of coronary disease in a manner that compares favorably with quantitative SPECT.

Determinants and prognosis of atrial fibrillation in patients with aortic stenosis.

Atrial fibrillation (AF) is frequently encountered in patients with aortic stenosis (AS) and its incidence also increases with age. In the general population, AF is known to increase cardiovascular risk. We sought to investigate the prognostic importance of AF associated with AS in the context of routine clinical practice. This analysis was based on 809 patients (75 ± 12 years) diagnosed with AS (aortic valve area <2 cm(2)) and normal (≥50%) ejection fraction (EF). Patients were grouped according to the presence of sinus rhythm (SR) or AF at study enrollment. The AF group comprised 141 patients (17.5%) with AF, whereas 668 patients (82.5%) were in SR at inclusion. Four-year estimates of all-cause mortality with medical and surgical management were 60 ± 5% for the AF group compared with 24 ± 2% for the SR group (p = 0.0001). On multivariate analysis, the risk of all-cause mortality was higher in the AF group than in the SR group (adjusted hazard ratio [HR] 2.47 [1.83 to 3.33], p = 0.0001). AF remained associated with excess mortality risk when the analysis was limited to asymptomatic patients (adjusted HR 2.31 [1.38 to 3.89], p = 0.002) and, respectively, patients with severe AS (adjusted HR 2.22 [1.41 to 3.49], p = 0.001). Among patients managed medically, AF was independently associated with increased risk of death in the overall study population (adjusted HR 2.52 [1.81 to 3.51], p = 0.0001), in asymptomatic AS (adjusted HR 2.12 [1.19 to 3.76], p = 0.01), and in severe AS (adjusted HR 2.23 [1.30 to 3.81], p = 0.004). In conclusion, AF is a major predictor of mortality, in both medically and surgically managed patients with AS, irrespective of the functional status and the severity. AF is, therefore, a strong marker of risk in AS and should be considered for clinical decision making.

Assessment of myocardial blood flow using myocardial contrast echocardiography.

Advances over the past 10 years have enabled the widespread use of myocardial contrast echocardiography (MCE) to assess myocardial perfusion. This assessment is critical in evaluating the severity of coronary artery disease and the efficacy of pharmacologic, mechanical, or surgical interventions. MCE measures myocardial blood flow (MBF) by investigating flow velocity and myocardial blood volume. Although there are potential limitations to the use of MCE for determining MBF, its use is feasible in the experimental laboratory and in the clinical environment.

Elevated serum lipoprotein(a) level is an independent marker of severity of thoracic aortic atherosclerosis.

STUDY OBJECTIVE: Lipoprotein(a) (Lp[a]) level is a risk factor for ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. However, few data are available concerning the relationship between Lp(a) level and severity of thoracic aortic atherosclerosis. We hypothesized in this transesophageal echocardiography (TEE) study that Lp(a) level is a marker of severity of thoracic aortic atherosclerosis. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENTS: Risk factors, coronary angiographic features, and TEE findings were analyzed prospectively in 119 patients with valvular disease. MEASUREMENTS AND RESULTS: The following risk factors were recorded: age, gender, hypertension, smoking, lipid parameters, diabetes, body mass index, and family history of coronary artery disease. Serum levels of Lp(a) were measured for each patient. By univariate analysis, age, diabetes, hypertension, smoking, Lp(a), total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were significant predictors of thoracic aortic atherosclerosis. There was a positive and significant correlation between the Lp(a) levels and the score of severity of thoracic aortic atherosclerosis (p = 0.0001). Multivariate regression analysis revealed that Lp(a) was an independent predictor of severity of thoracic aortic atherosclerosis (p = 0.0001). CONCLUSION: This prospective study indicates that serum Lp(a) level is an independent marker of severity of thoracic aortic atherosclerosis detected by multiplane TEE. These findings emphasize the role of Lp(a) as a marker of atherosclerotic lesions in the major arterial locations.

Monitoring of respiratory variations of aortic blood flow velocity using esophageal Doppler.

OBJECTIVE: The purpose of this study was to determine whether monitoring of respiratory changes in aortic blood flow velocity, recorded by esophageal Doppler, could be used to detect changes in volume depletion. DESIGN: Animal study. ANIMALS AND INTERVENTIONS: After general anesthesia and tracheotomy, ten New Zealand female rabbits, weighing 4-4.5 kg were studied under mechanical ventilation at a fixed tidal volume; during this time 5-ml blood samples were withdrawn (in increments up to a total of 30 ml) and then retransfused. MEASUREMENTS AND RESULTS: At each step, systolic (SBP), diastolic (DBP), pulse (PP) pressures and maximum descending aortic blood flow (V) were recorded. Respiratory changes of V (DeltaV), SBP (DeltaSBP) and PP (DeltaPP) were calculated as the difference of maximal and minimal values divided by their respective means and expressed as a percentage. The amount of blood withdrawn correlated negatively with SBP, DBP, PP and V and positively with DeltaSBP, DeltaPP and DeltaV. Among these parameters, DeltaV correlated best with the amount of blood withdrawn ( r=0.89, p<0.001) and it was the most accurate index of volume depletion. CONCLUSION: Monitoring of the respiratory variation in V, calculated by esophageal Doppler technique, seems to be a highly accurate index of blood volume depletion and restitution.

The value of cardiopulmonary exercise testing in individuals with apparently asymptomatic severe aortic stenosis: a pilot study.

BACKGROUND: Risk stratification in asymptomatic patients with severe aortic stenosis (AS) is based on exercise test results. However, differentiating between pathological and physiological breathlessness during exercise is sometimes challenging. Cardiopulmonary exercise testing (CPET) may improve quantification of cardiopulmonary exercise capacity in patients with valve diseases. AIMS: To assess the ability of CPET to detect abnormal responses to exercise and a clinical endpoint (occurrence of European Society of Cardiology guidelines surgical class I triggers). METHODS: Forty-three consecutive patients (mean age 69±13 years; 31 men) with no reported symptoms and severe AS (aortic valve surface area<1 cm2 or indexed aortic valve surface area ≤0.6 cm2/m2) prospectively underwent symptom-limited CPET. RESULTS: Twelve (28%) patients had an abnormal exercise test (AET) with symptoms (abnormal dyspnoea n=11; angina n=1). Both VE/VCO2 slope>34 (hazard ratio [HR]=5.76, 95% confidence interval [CI] 1.086-30.587; P=0.04) and peak VO2≤14 mL/kg/min (HR 6.01, 95% CI 1.153-31.275; P=0.03) were independently associated with an AET. Furthermore, VE/VCO2 slope>34 (HR 3.681, 95% CI 1.318-10.286; P=0.013) and peak VO2≤14 mL/kg/min (HR 3.058, 95% CI 1.074-8.713; P=0.036) were independent predictors of reaching the clinical endpoint. CONCLUSIONS: Cardiopulmonary exercise testing is a useful tool for characterizing breathlessness during an exercise test in apparently asymptomatic patients with AS. Peak VO2≤14 mL/kg/min and VE/VCO2 slope>34 were associated with an AET and the occurrence of European Society of Cardiology guideline surgical class I triggers.

Long-term outcome after a first episode of heart failure. A prospective 7-year study.

BACKGROUND: Heart failure (HF) is a major issue of public health in contemporary aging populations. The objectives of the present study were to assess the long-term survival of a contemporary cohort of patients discharged after a first hospitalization for HF and identify variables associated with adverse outcome. METHODS: We prospectively included consecutive patients (n=735) discharged from 11 healthcare establishments of the Somme department (France) after a first hospitalization for HF during 2000. The 7-year observed survival was compared with the expected survival of the general population. RESULTS: Mean age of the study group was 75+/-12 years and 48% of patients were women. Left ventricular ejection fraction was measured in 628 patients (85%). During the 7-year follow-up, 483 patients (67%) died. The 5- and 7-year observed survival rates were dramatically lower than the expected survival of the matched general population (42% vs. 70%, and 33% vs. 59%, respectively). Relative survival (observed/expected survival) was 60% at 5 years and 55% at 7 years. Multivariable analysis identified cancer, stroke, diabetes, prior myocardial infarction, chronic obstructive pulmonary disease, chronic atrial fibrillation, age, and hyponatraemia as independent predictors of 7-year mortality. CONCLUSIONS: In Europe, the long-term outcome of patients with new-onset HF is still extremely poor. Better implementation of guideline-oriented therapeutic strategies is needed to improve prognosis of this increasingly prevalent condition.