Haïfa Mahjoub

Left ventricular contractile reserve in asymptomatic primary mitral regurgitation

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 (LVCR(LVEF)) ≥ 4% or in LV global longitudinal strain (LVCR(GLS)) ≥ 2%. LVCR(LVEF) was present in 54 patients (47%) and LVCR(GLS) 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 LVCR(GLS) 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 LVCR(LVEF) (60 ± 7 vs. 51 ± 8%, P = 0.40). The multivariable Cox proportional hazard model showed that the absence of LVCR(GLS) 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 LVCR(GLS) 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.

Prognostic importance of brain natriuretic peptide and left ventricular longitudinal function in asymptomatic degenerative mitral regurgitation

Objectives To identify the determinants and the impact on outcome of brain natriuretic peptide (BNP) in asymptomatic patients with degenerative mitral regurgitation (MR). Method 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. Main outcome measures BNP level and cardiac events. Results 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 (p<0.0001) 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 (p<0.0001). 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. Conclusion 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.

ApoB/ApoA-I ratio is associated with increased risk of bioprosthetic valve degeneration.

OBJECTIVES This study sought to identify the clinical and metabolic determinants of bioprosthetic valve degeneration. BACKGROUND Structural valve degeneration (SVD) is the major cause of bioprosthetic valve failure. Recent retrospective studies have reported an association between atherosclerotic risk factors and development of SVD. METHODS A total of 203 consecutive patients with aortic bioprosthetic valves were recruited. Doppler echocardiography and multidetector computed tomography (CT) examinations were performed for assessment of bioprosthesis calcification and abdominal adiposity. A cardiometabolic risk profile was also obtained. SVD was defined as an increase in mean transprosthetic gradient of ≥ 10 mm Hg and/or a worsening of transprosthetic regurgitation ≥ 1/3 class between 1-year post-operative echo and last follow-up echo (mean follow-up time was 8 ± 3 years). RESULTS Forty-two patients (20%) were identified as developing SVD. Patients with SVD had significantly higher plasma total-cholesterol (4.6 ± 1.1 mmol/l vs. 4.1 ± 0.9 mmol/l, p = 0.05), low-density lipoprotein-cholesterol (2.5 ± 1.0 mmol/l vs. 2.2 ± 0.7 mmol/l, p = 0.02), and apolipoprotein B (ApoB) levels (0.71 ± 0.22 g/l vs. 0.64 ± 0.17 g/l, p = 0.02) and higher ApoB/ApoA-I ratios (0.48 ± 0.17 vs. 0.41 ± 0.11, p = 0.004) than those with no SVD. Multivariate analysis revealed that increased ApoB/ApoA-I ratio (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.10 to 1.82 per 0.1 increment; p = 0.007) and the use of bisphosphonates (OR: 3.57, 95% CI: 1.14 to 10.80 p = 0.02) were the strongest independent predictors of SVD. CONCLUSIONS This is the first study to report a strong association between increased ApoB/ApoA-I ratio and the risk of developing SVD among patients with aortic bioprosthetic valves. Further studies are needed to determine if an elevated ApoB/ApoA-I ratio, which reflects the balance of proatherogenic and antiatherogenic lipoproteins, is a risk marker or a risk factor for SVD.

Impact of exercise pulmonary hypertension on postoperative outcome in primary mitral regurgitation

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.

Prognostic importance of exercise brain natriuretic peptide in asymptomatic degenerative mitral regurgitation.

The exercise Doppler echocardiographic stress test can be of interest in the management of asymptomatic patients with primary mitral regurgitation (MR). The resting brain natriuretic peptide (BNP) level is a good surrogate marker of the consequences of MR 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 BNP level and to evaluate its prognostic value in asymptomatic patients with primary MR.

Determinants of aortic bioprosthetic valve calcification assessed by multidetector CT

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 mm3. 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 mm3). 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.

Lp-PLA2 is associated with structural valve degeneration of bioprostheses.

In this study, we sought to determine the metabolic markers associated with structural valve degeneration (SVD).

Evolution and prognostic impact of low flow after transcatheter aortic valve replacement

Objective Low flow (LF), defined as stroke volume index (SVi) <35 mL/m2, 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). Methods 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). Results Patients with EP-SVi <35 mL/m2 (n=138; 54%) had increased mortality (HR 1.97, p=0.003) compared with those with EP-SVi ≥35 mL/m2 (n=117; 46%). Furthermore, patients with baseline SVi (B-SVi) <35 mL/m2 and EP-SVI ≥35 mL/m2, that is, normalised flow, had better survival (HR 0.46, p=0.03) than those with both B-SVi and EP-SVi <35 mL/m2, that is, persistent LF, and similar survival compared with those with both B-SVi and EP-SVi ≥35 mL/m2, 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/m2 decrease, p=0.03). The preprocedural/intraprocedural factors associated with lower EP-SVi were lower B-SVi (standardised β [β] 0.36, p<0.001) atrial fibrillation (β −0.13, p=0.02) and transapical approach (β −0.22, p<0.001). Conclusions The measurement of EP-SVi is useful to assess the immediate haemodynamic benefit of TAVR and to predict the risk of late mortality.

Parathyroid hormone is associated with the LV mass after aortic valve replacement

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.

Association between plasma lipoprotein levels and bioprosthetic valve structural degeneration

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<255Å) (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, <25.4) and low PCSK9 (median, <298 ng/mL) (referent), patients with both an elevated OxLDL/HDL ratio and PCSK9 had a higher risk of SVD (OR 2.93, 95% CI 1.02 to 9.29, p=0.04). Conclusions OxLDL/HDL ratio is independently associated with SVD.