Abnormal cisatracurium pharmacodynamics and pharmacokinetics among patients with severe aortic regurgitation during anesthetic induction.

BACKGROUND: This study was designed to examine whether severe aortic regurgitation will affect the pharmacodynamics (PD) and pharmacokinetics (PK) of cisatracurium during anesthetic induction. METHODS: A total of 32 patients were divided into two groups: the AR group (n = 16) and the control group (n = 16). Arterial blood samples were drawn before and at 1, 2, 4, 6, 8, 10, 16 and 20 min after intravenous injection of 0.15 mg/kg cisatracurium. TOF tests were applied to determine the onset time of maximal muscle relaxation. The concentration of cisatracurium in plasma was determined by high-performance liquid chromatography. RESULTS: The onset time to maximal neuromuscular block was prolonged from 2.07 ± 0.08 min to 4.03 ± 0.14 min, which indicated that the PD responses to cisatracurium were significantly delayed in the AR group (P < 0.05) compared to the control group. A conventional two-compartment PK model showed a higher plasma concentration of cisatracurium among the AR group with markedly reduced intercompartment transfer rate (K12 = 0.19 ± 0.02 and K21 = 0.11 ± 0.01 in the AR group vs. K12=0.26 ± 0.01 and K21 = 0.19 ± 0.01 in the control group, P < 0.01) compared to the control group. CONCLUSION: Backward blood flow during diastole in severe AR impaired distribution of cisatracurium from the central compartment to the peripheral compartment, which accounted for the lagged PD responses. Findings in this study underlie the importance of muscular blockade monitoring among patients with severe aortic regurgitation during anesthetic induction. REGISTRATION: Name of the registry: Abnormal Cisatracurium Pharmacodynamics and Pharmacokinetics among Patients with Severe Aortic Regurgitation during Anesthetic Induction. TRIAL REGISTRATION NUMBER: ChiCTR1800019654. Date of registration: November 20th 2018.

Numerical investigation on the effect of bileaflet mechanical heart valve's implantation tilting angle and aortic root geometry on intermittent regurgitation and platelet activation.

Platelet activation induced by shear stresses and non-physiological flow field generated by bileaflet mechanical heart valves (BMHVs) leads to thromboembolism, which can cause fatal consequences. One of the causes of platelet activation could be intermittent regurgitation, which arises due to asynchronous movement and rebound of BMHV leaflets during the valve closing phase. In this numerical study, the effect of intermittent regurgitation on the platelet activation potential of BMHVs was quantified by modeling a BMHV in the straight and anatomic aorta at implantation tilt angles 0°, 5°, 10°, and 20°. A fully implicit Arbitrary Lagrangian-Eulerian-based Fluid-Structure Interaction formulation was adopted with blood modeled as a multiphase, non-Newtonian fluid. Results showed that the intermittent regurgitation and consequently the platelet activation level increases with the increasing implantation tilt of BMHV. For the straight aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 20° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 8.5°, 3°, and 0°, respectively. For the anatomic aorta, the leaflet of the 20° tilted BMHV underwent a rebound of approximately 24° after initially closing, whereas the leaflet of the 10°, 5°, and 0° tilted BMHVs underwent a rebound of 14°, 10°, and 7°, respectively. For all the implantation orientations of BMHVs, intermittent regurgitation and platelet activation were always higher in the anatomic aorta than in the straight aorta. The study concludes that the pivot axis of BMHV must be implanted parallel to the aortic root's curvature to minimize intermittent regurgitation and platelet activation.

Molecular recognition of aortic valve stenosis and regurgitation.

OBJECTIVE: Aortic valve stenosis (AS) presents a disease during which there are changes of the aortic valve structure that modify the blood structure of patients. The aim of this study was to improve the effectiveness of differential diagnostics of aortic stenosis and aortic regurgitation using molecular techniques on both mRNA (RT-PCR) and protein (biochip protein). PATIENTS AND METHODS: An experimental group (n = 58) consisting of patients with aortic valve stenosis (n = 26) and aortic regurgitation (AR, n = 32) was compared with a control group (n = 35). Both blood serum and valve tissue samples were used for the determination of gene expression specific genes related to inflammatory response (CRP, IL6, IL2R, IL6R, TNFR1, and 2) as well as genes and proteins involved in remodeling of the extracellular matrix (MMP9, TIMP, Emilin-1). RESULTS: We found that hsCRP and IL6 plasma levels of patients with AS were higher than both controls and patients with AR (mean 5.6 ng/ml). The differences between AS and AR were detected only in mRNA levels of MMP9 and TIMP where increased levels characteristic for AS were found (about 74%, p < 0.01 and 87%, p < 0.001 higher than AR). CONCLUSIONS: The achieved results could contribute to the improvement of early diagnosis of selected cardiovascular disease in the future and improve the quality of patient's life.

High-sensitivity troponin T in asymptomatic severe aortic stenosis.

Background: In asymptomatic severe aortic stenosis (ASAS), treatment decisions are made on an individual basis, and case management presents a clinical conundrum. Methods: We prospectively phenotyped consecutive patients with ASAS using echocardiography, exercise echocardiography, cardiac MRI and biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT) and ST2) (n = 58). The primary endpoint was a composite of cardiovascular death, new-onset symptoms, cardiac hospitalization, guideline-driven indication for valve replacement and cardiovascular death at 12 months. Results: During the first year, 46.6% patients met primary endpoint. In multivariable analysis, aortic regurgitation ≥2 (p = 0.01) and hs-TnT (p = 0.007) were the only independent predictors of the primary endpoint. The best cutoff value was identified as hs-TnT >10ng/L, which was associated with a ∼10-fold greater risk of the primary endpoint (HR, 9.62; 95% CI, 2.27-40.8; p = 0.002). A baseline predictive model including age, sex and variables showing p < 0.10 in univariable analyses showed an area under the curve (AUC) of 0.79(0.66-0.91). Incorporation of hs-TnT into this model increased the AUC to 0.90(0.81-0.98) (p = 0.03). Patient reclassification with the model including hs-TnT yielded an NRI of 1.28(0.46-1.78), corresponding to 43% adequately reclassified patients. Conclusions: In patients with ASAS, hs-TnT >10ng/L was associated with high risk of events within 12 months. Including hs-TnT in routine ASAS management markedly improved prediction metrics.

The usefulness of selected biomarkers in aortic regurgitation.

BACKGROUND: The aim of the study was to investigate the prognostic value of selected biomarkers in patients with aortic regurgitation undergoing valve surgery. METHODS: A prospective study was conducted on a group of consecutive patients with hemodynamically significant aortic regurgitation that underwent elective aortic valve surgery. The primary endpoint was 30-day mortality and any major adverse event within 30 days. RESULTS: The study group included 205 consecutive patients who underwent replacement or repair of the aortic valve. The primary endpoint occurred in 72 patients. At multivariate analysis red cell distribution width (RDW; p = 0.03) and high-sensitivity troponin T (hs-TnT; p = 0.02) remained independent predictors of the major complications including death. CONCLUSIONS: Elevated preoperative RDW and hs-TnT were associated with a poorer outcome following aortic valve surgery.

Early changes in N-terminal pro-B-type natriuretic peptide levels after transcatheter aortic valve replacement and its impact on long-term mortality.

BACKGROUND: N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) levels correlate with higher peri-procedural mortality after transcatheter aortic valve replacement (TAVR). The long-term prognostic value of NT-proBNP within the first days after TAVR, however, remains unclear. This study examined early changes in NT-proBNP prior to and within 6 days after TAVR, the diagnostic value of this biomarker regarding aortic regurgitation (AR), and its prognostic value regarding one-year mortality. METHODS AND RESULTS: NT-proBNP concentrations were measured in 504 consecutive patients undergoing transapical (TA) or transfemoral (TF) TAVR before and directly after TAVR as well as 4 h and 1, 2, 3, and 6 days after TAVR. The follow-up period was 1 year. NT-proBNP was elevated in all patients at baseline (median 2141 ng/L [IQR 1021-5319 ng/L]). NT-proBNP changes in the first 6 days after TAVR showed significant differences depending on the approach, with a greater and more prolonged rise evident in TA-TAVR patients. NT-proBNP was an independent predictor of mortality in TA patients with AR, with an AUC of 0.794 (95% CI 0.663-0.925; P = 0.003) when measured on day 3 after TAVR. For TF patients with AR and reduced left ventricular systolic function, the AUC for prediction of mortality was 0.897 (95% CI 0.778-1.0; P = 0.004) on day 2. CONCLUSIONS: The prognostic information of early post-procedural NT-proBNP concentrations is superior to pre-procedural values regarding all-cause mortality within 1 year. Post-procedural NT-proBNP must be interpreted in relation to the TAVR approach. NT-proBNP predicts mortality in TF-TAVR patients with AR and reduced left ventricular function.

CT-ADP Point-of-Care Assay Predicts 30-Day Paravalvular Aortic Regurgitation and Bleeding Events following Transcatheter Aortic Valve Replacement.

BACKGROUND: Paravalvular aortic regurgitation (PVAR) remains a frequent postprocedural concern following transcatheter aortic valve replacement (TAVR). Persistence of flow turbulence results in the cleavage of high-molecular-weight von Willebrand multimers, primary haemostasis dysfunction and may favour bleedings. Recent data have emphasized the value of a point-of-care measure of von Willebrand factor-dependent platelet function (closure time [CT] adenosine diphosphate [ADP]) in the monitoring of immediate PVAR. This study examined whether CT-ADP could detect PVAR at 30 days and bleeding complications following TAVR. METHODS: CT-ADP was assessed at baseline and the day after the procedure. At 30 days, significant PVAR was defined as a circumferential extent of regurgitation more than 10% by transthoracic echocardiography. Events at follow-up were assessed according to the Valve Academic Research Consortium-2 consensus classification. RESULTS: Significant PVAR was diagnosed in 44 out of 219 patients (20.1%). Important reduction of CT-ADP could be found in patients without PVAR, contrasting with the lack of CT-ADP improvement in significant PVAR patients. By multivariate analysis, CT-ADP > 180 seconds (hazard ratio [HR]: 5.1, 95% confidence interval [CI]: 2.5-10.6; p < 0.001) and a self-expandable valve were the sole independent predictors of 30-day PVAR. At follow-up, postprocedural CT-ADP >180 seconds was identified as an independent predictor of major/life-threatening bleeding (HR: 1.7, 95% CI [1.0-3.1]; p = 0.049). Major/life-threatening bleedings were at their highest levels in patients with postprocedural CT-ADP > 180 seconds (35.2 vs. 18.8%; p = 0.013). CONCLUSION: Postprocedural CT-ADP > 180 seconds is an independent predictor of significant PVAR 30 days after TAVR and may independently contribute to major/life-threatening bleedings.

Perioperative anticoagulation management during aortic valve replacement complicated by antiphospholipid syndrome.

Patients with antiphospholipid syndrome (APS) are at high-risk for thrombotic and bleeding complications during cardiopulmonary bypass. We report an APS patient who successfully underwent aortic valve replacement while heparin concentrations were monitored using a patient-specific titration curve using viscoelastic coagulation testing.

Troponin I and echocardiography in patients with systemic sclerosis and matched population controls.

OBJECTIVES: Cardiac manifestations in systemic sclerosis (SSc) are associated with poor prognosis. Few studies have investigated cardiac troponins in SSc. We studied the relationships between echocardiographic abnormalities, cardiac biomarkers, and disease manifestations in a population-based cohort of patients with SSc and controls. METHOD: The study comprised 110 patients with SSc and 105 age- and sex-matched population-based controls. We examined ventricular function, heart valves, and estimated pulmonary arterial pressure (ePAP) by echocardiography in all participants. Disease characteristics, manifest ischaemic heart disease (IHD), and measurements of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were tabulated. RESULTS: NT-proBNP and hs-cTnI levels were higher in SSc patients than controls. Both NT-proBNP and hs-cTnI were associated with the presence of echocardiographic abnormalities. Forty-four SSc patients and 23 control subjects had abnormal echocardiograms (p = 0.002). As a group, SSc patients had lower (but normal) left ventricular ejection fraction (LVEF, p = 0.02), more regional hypokinesia (p = 0.02), and more valve regurgitations (p = 0.01) than controls. Thirteen patients and four controls had manifest IHD. Decreased right ventricular (RV) function (n = 7) and elevated ePAP (n = 15) were exclusively detected among SSc patients. CONCLUSIONS: Both NTproBNP and hs-cTnI were associated with echocardiographic abnormalities, which were more prevalent in SSc patients than in controls. Our results thus suggest that hs-cTnI could be a potential cardiac biomarker in SSc. Low RV function and signs of pulmonary hypertension (PH) were uniquely found in the SSc group. SSc patients had more valve regurgitation than controls, an observation that warrants more clinical attention.

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.

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. METHODS: We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. RESULTS: After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. CONCLUSIONS: The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).

Platelet activation is less enhanced in the new balloon expandable Edwards Sapien 3 valve compared to its predecessor model (Edwards Sapien XT).

Stroke and thromboembolic events after transfemoral aortic valve replacement (TAVR) continue to be a problem. The aim of our study was to compare platelet aggregation (Agg) and platelet activation (PA) observed with two different catheter valves, the ESV-XT and the newer ESV-3 valve in patients (pts) undergoing TAVR on dual antiplatelet therapy (DAPT). A total of 174 patients with severe aortic stenosis and high surgical risk successfully underwent TAVR (60 ESV-XT; 114 ESV-3). Platelet Agg and PA (CD62P expression) were evaluated before and the following three days after TAVR under DAPT. Platelet Agg was inhibited to the same extent in both valve types and there was no significant difference in platelet drop between both valve types between day 0 and day 3 [ESV-XT vs ESV-3: median (25th-75th percentile): platelet count (x1000): 55 (42-74) vs 61(42-93), p=0.280]. However, there was an enhanced CD62P expression directly after TAVR with the ESV-XT compared to the ESV-3 [CD62P (MIF): 7.4 (6.8-8.6) vs 6.6 (6-7.9), p=0.014]. Surface expression of platelet CD62P was associated with the occurrence of residual aortic regurgitation (AR) and was significantly higher in patients with residual AR [CD62P (mild AR) vs CD 62P (no or trace AR): 7.9 (7.3-9.1) vs 7.1 (6.4-8.0), p < 0.001)]. PA was significantly enhanced in patients with the ESV-XT compared to the ESV-3 valve and was associated with the amount of residual AR which was significantly reduced by ESV-3. This may have implications for thromboembolic events following TAVR procedure.

Controlled release metoprolol for aortic regurgitation: a randomised clinical trial.

OBJECTIVE: Chronic aortic regurgitation (AR) creates a volume load on the left ventricle, which induces adaptive responses. With time, excessive left ventricular (LV) dilatation may precipitate heart failure. ß-adrenergic receptor antagonists (ß-blockers) are beneficial in patients with heart failure, but their effect in AR is unclear. This trial was designed to evaluate the effect of controlled release metoprolol on LV remodelling in patients with AR. METHODS: In this double blind trial, 75 asymptomatic patients aged 44±14 years, 89% males, fulfilling at least two echocardiographic criteria for moderate or severe chronic AR, were randomised to receive metoprolol CR/XL up-titrated to 200 mg/day, or matching placebo. The primary endpoint was LV end diastolic volume, measured by MRI after 6 months of treatment. RESULTS: After 6 months, the difference in the baseline-adjusted LV end diastolic volume between patients allocated to metoprolol and those allocated to placebo was 8 (95% CI -8 to 25) mL (p=0.32). The adjusted LV ejection fraction was 2.7 (95% CI 0.1 to 5.3) percentage points higher in the metoprolol group than in the placebo group (p=0.04). The exercise capacity and peak oxygen consumption did not differ between treatment arms. Serum concentrations of N-terminal pro-B-type natriuretic peptide were 138 (95% CI 71 to 205) pg/mL higher in the metoprolol group (p<0.001). There were no serious adverse events in either treatment arm. CONCLUSIONS: Treatment with metoprolol of adults with chronic, moderate to severe AR had no effect on LV volumes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01157572-results.

Timing of Dynamic NT-proBNP and hs-cTnT Response to Exercise Challenge in Asymptomatic Children with Moderate Aortic Valve Regurgitation or Moderate Aortic Valve Stenosis.

Patients with congenital aortic valve stenosis (AVS) can remain asymptomatic but may develop progressive and often underestimated exercise intolerance. The risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated patients warrants earlier intervention. The timing for curative therapy for severe AVS is clear, but optimal timing for moderate stenosis (modAS) is unknown. AVS often coexists with aortic regurgitation, which adds a volume overload to an already pressure-overloaded LV, adding an additional challenge to the estimation of disease severity. We investigated the possible value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) upon treadmill exercise challenge in children with asymptomatic modAS versus moderate regurgitation (modAR). The aim was to determine optimal timing of peak biochemical response. Blood samples were obtained at rest, and then at 20, 40 and 60 min after peak exercise comparing modAS and modAR to healthy controls. Exercise performance was equivalent in all groups, with no difference for biomarker levels at rest. The increase in NT-proBNP was significant in modAR at 40 min (99.2 ± 48.6 ng/L; p = 0.04) and 60 min into recovery (100.0 ± 53.7 ng/L; p = 0.01), but not in modAS. The increase in hs-cTnT was significant only at 60 min into recovery for modAS and modAR. NT-proBNP and hs-cTnT following exercise challenge are possible discriminant biomarkers of modAR from modAS and controls at 60 min into recovery despite comparable exercise performance. This offers a promising avenue for future stratification of aortic valve disease and optimal timing of intervention.

Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions.

RATIONALE: Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures. OBJECTIVE: To investigate the time course of HMW multimers changes in models and patients with instantaneous induction/reversal of pathological high shear and its related bedside assessment. METHODS AND RESULTS: We investigated the time course of the induction/recovery of HMW multimers defects under instantaneous changes in shear stress in an aortic stenosis rabbit model and in patients undergoing implantation of a continuous flow left ventricular assist device. We further investigated the recovery of HMW multimers and monitored these changes with PFA-CADP in aortic stenosis patients undergoing transcatheter aortic valve implantation or balloon valvuloplasty. Experiments in the aortic stenosis rabbit model and in left ventricular assist device patients demonstrated that induction/recovery of HMW multimers occurs within 5 minutes. Transcatheter aortic valve implantation patients experienced an acute decrease in shear stress and a recovery of HMW multimers within minutes of implantation which was sustained overtime. In patients with residual high shear or with residual aortic regurgitation, no recovery of HMW multimers was observed. PFA-CADP profiles mimicked HMW multimers recovery both in transcatheter aortic valve implantation patients without aortic regurgitation (correction) and transcatheter aortic valve implantation patients with aortic regurgitation or balloon valvuloplasty patients (no correction). CONCLUSIONS: These results demonstrate that variations in von Willebrand factor multimeric pattern are highly dynamic, occurring within minutes after changes in blood flow. It also demonstrates that PFA-CADP can evaluate in real time the results of transcatheter aortic valve procedures.

Aortic insufficiency in patients with sustained left ventricular systolic dysfunction after axial flow assist device implantation.

BACKGROUND: Predicting the occurrence of aortic insufficiency (AI) during left ventricular assist device (LVAD) support has remained unsolved. METHODS AND RESULTS: We enrolled 52 patients who had received continuous flow LVAD (14 axial and 38 centrifugal pumps) and who been followed for ≥6 months between Jun 2006 and Dec 2013. Native aortic valve (AV) opening was observed in 18 patients (35%) with improved LV systolic function, and none of them had AI. On multivariate logistic regression analysis preoperative shorter heart failure duration was the only independent predictor of postoperative native AV opening (P=0.042; odds ratio [OR], 0.999). Of the remaining 34 patients (65%) with closed AV, 11 had AI with enlargement of the aortic root and narrow pulse pressure. Among those with closed AV, axial pump use (n=13) was the only significant predictor of the development of AI (P=0.042; OR, 4.950). Patients with AI had lower exercise capacity and a higher readmission rate than those without AI during 2-year LVAD support (55% vs. 8%; P<0.001). CONCLUSIONS: Native AV opening during LVAD support is profoundly associated with reversal of LV systolic function, especially in patients with preoperative shorter heart failure duration. Among those in whom the native AV remains closed, low pulsatility of axial flow pump may facilitate aortic root remodeling and post-LVAD AI development that results in worse clinical outcome.

Clinical impact of paravalvular leaks on biomarkers and survival after transcatheter aortic valve implantation.

BACKGROUND: There is accumulating evidence that up to 20% of the implanted devices after TAVI are associated with a significant degree of paravalvular leaks, which appear to be associated with a negative clinical outcome. METHODS: A total of 355 patients with severe aortic valvular stenosis (AVS) were treated by TAVI (Corevalve n = 222, Edwards Sapien n = 133). Survival, NT-proBNP and the grade of PVL were quantified up to 12 months after implantation. RESULTS: Technical success rate was 97.8%. Thirty-day mortality was 9.6%. Post-procedural transvalvular aortic regurgitation was seen only in a minority of cases (5%), whereas PVL were frequently observed (grade: <1+ in 58.2%, ≥1-<2 in 33.9%, and ≥2 in 7.9%). There was a clear relation-ship between PVL and adverse outcome (P < 0.001). After a transient increase, NT-proBNP showed a significant decline. Interestingly, a PVL ≥2+ was associated with a much higher rise in NT-proBNP compared to the other groups (P < 0.01), and a post-procedural increase in NT-proBNP by more than 1640 ng L(-1) within 5 days was associated with a significant increase in rate of death (P < 0.01). CONCLUSIONS: TAVI is an efficient treatment option for high-risk patients with severe AVS. The incidence of PVL is an inacceptable clinical problem. Serial measurement of NT-proBNP can be used for risk-stratification in patients with a significant PVL. In general, PVL graded ≥2+ is associated with a dramatically increased 6-month mortality. Therefore, any action to reduce paraprosthetical regurgitation is highly recommended.

The role of biomarkers in valvular heart disease: focus on natriuretic peptides.

The optimal timing of valve surgery remains controversial. Biomarkers can be serially monitored and are objective laboratory measurements. Plasma B-type natriuretic peptide (BNP) and its N-terminal pro-form are well known predictors in heart failure. Diastolic stretch induces cardiomyocyte BNP expression in volume-loaded conditions like aortic or mitral regurgitation (MR) or pressure-loaded conditions like aortic stenosis (AS). Here, we review the value of natriuretic peptide measurements in valve disease. Cardiac decompensation is reflected by increased BNP in AS and in MR. Repeated marked increases in natriuretic peptides are a potential indication for valve replacement in severe asymptomatic AS with normal ejection fraction and exercise test results. High BNP level also predicts postoperative outcome. Increased BNP level is associated with low-flow AS, impaired left ventricular longitudinal strain, and myocardial fibrosis. The BNP ratio to the reference value for age and sex incrementally predicts mortality in AS. Increased BNP reflects the hemodynamic consequences of MR and is associated with exercise-induced pulmonary-arterial hypertension and reduced contractile reserve. In severe primary MR, increased and serially increasing BNP or N-terminal pro-form BNP might be helpful in guiding early mitral replacement. In conclusion, baseline (N-terminal pro-form) BNP should be obtained in all severe valve disease patients and interpreted together with clinical and echocardiography findings. Very high BNP values are associated with increased mortality and should lead to close monitoring peri- and postoperatively. Progressively increasing BNP in asymptomatic patients points to advancing valve disease. BNP adds important incremental prognostic information that is useful for valve patient management and for optimal timing of surgery in particular.