Time Of Valve Replacement Research Articles

Calcific Aortic Stenosis: A Review.

Calcific aortic stenosis (AS) restricts the aortic valve opening during systole due to calcification and fibrosis of either a congenital bicuspid or a normal trileaflet aortic valve. In the US, AS affects 1% to 2% of adults older than 65 years and approximately 12% of adults older than 75 years. Worldwide, AS leads to more than 100 000 deaths annually. Calcific AS is characterized by aortic valve leaflet lipid infiltration and inflammation with subsequent fibrosis and calcification. Symptoms due to severe AS, such as exercise intolerance, exertional dyspnea, and syncope, are associated with a 1-year mortality rate of up to 50% without aortic valve replacement. Echocardiography can detect AS and measure the severity of aortic valve dysfunction. Although progression rates vary, once aortic velocity is higher than 2 m/s, progression to severe AS occurs typically within 10 years. Severe AS is defined by an aortic velocity 4 m/s or higher, a mean gradient 40 mm Hg or higher, or a valve area less than or equal to 1.0 cm2. Management of mild to moderate AS and asymptomatic severe AS consists of patient education about the typical progression of disease; clinical and echocardiographic surveillance at intervals of 3 to 5 years for mild AS, 1 to 2 years for moderate AS, and 6 to 12 months for severe AS; and treatment of hypertension, hyperlipidemia, and cigarette smoking as indicated. When a patient with severe AS develops symptoms, surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) is recommended, which restores an average life expectancy; in patients aged older than 70 years with a low surgical risk, 10-year all-cause mortality was 62.7% with TAVI and 64.0% with SAVR. TAVI is associated with decreased length of hospitalization, more rapid return to normal activities, and less pain compared with SAVR. However, evidence supporting TAVI for patients aged younger than 65 years and long-term outcomes of TAVI are less well defined than for SAVR. For patients with symptomatic severe AS, the 2020 American College of Cardiology/American Heart Association guideline recommends SAVR for individuals aged 65 years and younger, SAVR or TAVI for those aged 66 to 79 years, and TAVI for individuals aged 80 years and older or those with an estimated surgical mortality of 8% or higher. Calcific AS is a common chronic progressive condition among older adults and is diagnosed via echocardiography. Symptomatic patients with severe AS have a mortality rate of up to 50% after 1 year, but treatment with SAVR or TAVI reduces mortality to that of age-matched control patients. The type and timing of valve replacement should be built on evidence-based guidelines, shared decision-making, and involvement of a multidisciplinary heart valve team.

Endocarditis in Bovine Vein Grafts in the Pulmonary Position Placed Surgically & Percutaneously.

Background: Infective endocarditis (IE) is one of the major complications following pulmonary valve replacement (PVR). This analysis hopes to evaluate the incidence, outcomes and possible risk factors of IE associated with trans-catheter and surgical placement of a bovine jugular vein (BJV) graft in the pulmonary position. Methods: In this single-center retrospective study, all records of trans-catheter and surgical PVR from 3/2010 to 12/2019 were reviewed. IE was defined as positive blood cultures, with vegetations seen on echocardiography or sudden increase in peak gradient across the valve or vegetations confirmed at time of valve replacement. Poor dental hygiene:1.dental procedures without S.B.E prophylaxis AND/OR 2.one or more dental cavities, caries, dental abscess. Results: 165 patients had PVR with BJV:107 trans-catheter and 63 surgical. 7%(12/170) of PVRs developed IE(catheter:n = 10, surgery:n = 2) at a median time from valve placement of 38 months. The incidence of IE in the catheter group:3-per-100patient-years and in surgical group:1-per-100patient-years. Multivariate cox regression showed that poor dental hygiene was significantly associated with IE [HR(95% CI):16.9(4.35-66.2)](p value <.001). Kaplan-Meier curves showed a significant difference in freedom from IE between patients with poor and appropriate dental hygiene (p value<.001). Conclusions: There is a 7% incidence of IE with the use of BJV grafts in the pulmonary position at mid-term follow-up. Though the rate in catheter placed BJV seems 3x higher than surgically placed ones, their cohorts are quite different making this comparison flawed. Poor dental hygiene is a strong predictor for post-operative IE and offers a significant opportunity for lowering the rate of infective endocarditis.

TAVR in patients with hip fracture and severe aortic stenosis: how and when?

Comorbidities are common in elderly patients with hip fracture and are associated with an increased mortality after surgery. Internal medicine/geriatric leaded multidisciplinary hip fracture teams may play a pivotal role in the clinical management of complex patients. Treatment strategy is particular relevant in patients with severe aortic stenosis that represent more than 5% of patients with hip fracture. These patients have a high in-hospital mortality and poor 1-year survival (less than 50%). Transcatheter aortic valve replacement (TAVR) may be an option in selected patients; however, the choice to treat and, in the case, the timing of valve replacement in relation to hip surgery is highly dependent on clinical conditions before trauma. In this paper, three different scenario of TAVR timing after hip fracture are reported.

Hemodynamic Profiles Before and After Surgery in Bicuspid Aortic Valve Disease-A Systematic Review of the Literature.

Bicuspid aortic valve (BAV) disease presents a unique management challenge both pre- and post-operatively. 4D flow MRI offers multiple tools for the assessment of the thoracic aorta in aortic valve disease. In particular, its assessment of flow patterns and wall shear stress have led to new understandings around the mechanisms of aneurysm development in BAV disease. Novel parameters have now been developed that have the potential to predict pathological aortic dilatation and may help to risk stratify BAV patients in future. This systematic review analyses the current 4D flow MRI literature after aortic valve and/or ascending aortic replacement in bicuspid aortic valve disease. 4D flow MRI has also identified distinct challenges posed by this cohort at the time of valve replacement compared to standard management of tri-leaflet disorders, and may help tailor the type and timing of replacement. Eccentric pathological flow patterns seen after bioprosthetic valve implantation, but not with mechanical prostheses, might be an important future consideration in intervention planning. 4D flow MRI also has promising potential in supporting the development of artificial valve prostheses and aortic conduits with more physiological flow patterns.

Acute kidney injury rates during a single hospitalization undergoing tavr with or without pci in high-risk surgical candidates. a study using the national inpatient sample: 2011–2014

Abstract Introduction Aortic valve stenosis (AS) and atherosclerosis share similar risk factors, therefore patients referred for replacement have incidental obstructive coronary lesions in 40–70% of the cases. Using the surgical approach of replacement, guidelines from observational studies give a class IIa recommendation for revascularization through CABG of major coronary arteries with &amp;gt;70% luminal stenosis or left main artery with &amp;gt;50% luminal stenosis at the time of valve replacement. In the event of high-risk surgical patients, TAVR is prompted and current recommendations support combined TAVR and percutaneous coronary intervention (PCI) for treatment of ostial/proximal lesions, or in unstable patients. Further characterization of complications is needed to allow experts to make a supported decision. Purpose One of the biggest concerns when performing both procedures without a washing period is the increased renal burden. In the present study, we evaluated the outcomes and complications in patients undergoing TAVR and PCI during the same hospitalization. Methods The patient population was obtained from the Nation Inpatient Sample database in the U.S. ICD-9 billing codes were used to identify all patients with severe AS undergoing PCI and TAVR during the same admission between 2011:2014. At this timeframe, only high-risk surgical patients were candidates for TAVR. Multivariate logistic regression was used to adjust for patient and procedural confounders. Results Between 2011 and 2014, 31945 patients underwent TAVR out of which 1069 had a PCI during the same hospital admission. The adjusted odds ratio (OR) of an AKI was 2.44 (95% CI: 0.85–7.00) times greater in those who underwent a TAVR+PCI during the same admission compared to TAVR alone; however, this was not statistically significant (p=0.097). Mean length of stay was 10.6 days in the TAVR+PCI group, compared to 7.1 days in those who underwent a TAVR alone, p-value &amp;lt;0.05. In-hospital, all-cause mortality was 4.4 times greater in those receiving TAVR+PCI than TAVR alone (95% CI: 2.81–7.14). A multivariate regression model controlling for potential confounders was used to evaluate the likelihood of developing an AKI in the setting of CKD: the adjusted OR of stage I was 0.51 (95% CI: 0.09–2.92), stage II was 1.36 (95% CI: 0.52–3.51), stage III was 3.24 (95% CI: 1.10–9.58), stage IV was 0.96 (95% CI: 0.16–5.73), and stage V was 1.58 (95% CI: 0.59–4.24) when compared to normal renal function. Conclusion Periprocedural PCI and TAVR during the same hospitalization have increased length of stay and in-hospital mortality compared to TAVR alone. However, the likelihood of an AKI in the setting of a concurrent PCI with TAVR was not statistically significant compared to a TAVR alone. Those with CKD Stage III were noted to have an increased likelihood of developing an AKI during their admission. This might give new insight for operators on the so feared contrast-associated nephropathy. Funding Acknowledgement Type of funding source: None

Association of Natriuretic Peptide Levels After Transcatheter Aortic Valve Replacement With Subsequent Clinical Outcomes

Among those with aortic stenosis, natriuretic peptide levels can provide risk stratification, predict symptom onset, and aid decisions regarding the timing of valve replacement. Less is known about the prognostic significance and potential clinical utility of natriuretic peptide levels measured after valve replacement. To determine the associations of elevated B-type natriuretic peptide (BNP) levels after transcatheter aortic valve replacement (TAVR) and change in BNP levels between follow-up time points with risk of subsequent clinical outcomes. In this cohort study, patients with severe symptomatic aortic stenosis at intermediate, high, or prohibitive surgical risk for aortic valve replacement who underwent TAVR from the PARTNER IIA cohort, PARTNER IIB cohort, SAPIEN 3 intermediate-risk registry, and SAPIEN 3 high-risk registry were included. B-type natriuretic peptide levels were obtained at baseline and discharge as well as 30 days and 1 year after TAVR. For each measurement, a BNP ratio was calculated using measured BNP level divided by the upper limit of normal for the assay used. Outcomes were evaluated in landmark analyses out to 2 years. Data were collected from April 2011 to January 2019. All-cause death, cardiovascular death, rehospitalization, and the combined end point of cardiovascular death or rehospitalization. Among 3391 included patients, 1969 (58.1%) were male, and the mean (SD) age was 82 (7.5) years. Most patients had a BNP ratio greater than 1 at each follow-up time point, including 2820 of 3256 (86.6%) at baseline, 2652 of 2995 (88.5%) at discharge, 1779 of 2209 (80.5%) at 30 days, and 1799 of 2391 (75.2%) at 1 year. After adjustment, every 1-point increase in BNP ratio at 30 days (approximately equivalent to an increase of 100 pg/mL in BNP) was associated with an increased hazard of all-cause death (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.07-1.15), cardiovascular death (aHR, 1.16; 95% CI, 1.11-1.21), and rehospitalization (aHR, 1.08; 95% CI, 1.03-1.14) between 30 days and 2 years. Among those with a BNP ratio of 2 or more at discharge, after adjustment, every 1-point decrease in BNP ratio between discharge and 30 days was associated with a decreased hazard of all-cause death (aHR, 0.92; 95% CI, 0.88-0.96) between 30 days and 2 years. Elevated BNP levels after TAVR was independently associated with increased subsequent mortality and rehospitalizations. Further studies to determine how best to mitigate this risk are warranted.

Morbidity in Pregnant Women with a Prosthetic Heart Valve

Women with a prosthetic heart valve are perceived to be at higher risk for adverse outcomes, but their absolute and relative risk of experiencing maternal morbidity and cardiac complications is largely unknown. The objective of the study was to determine the risk of maternal morbidity and cardiac complications in women with a prior heart valve replacement, compared with matched counterparts without known cardiac disease. A retrospective population-based matched cohort study was completed in the province of Ontario, Canada, where there is universal health care. Included were all women of child-bearing age who had bioprosthetic or mechanical replacement of the mitral or aortic valve, April 1994 to March 2016 (valve replacement group). Those in the valve replacement group, and who had at least 1 birth, were 1:4 matched to a community comparison group without heart disease and who also had at least 1 birth. Matching was by maternal age at cohort entry, year of cohort entry, geographic area, income level, and age at first birth. Maternal outcomes included severe maternal morbidity, all-cause mortality, and cardiac morbidity as well as a prolonged hospital length of stay >7 days. Relative risks and 95% confidence intervals were further adjusted for age at birth and immigration status. There were 90 live births among the 64 women in the valve replacement group and 404 live births among the 253 women in the matched community comparison group. There were no stillbirths. Severe maternal morbidity occurred in 13 pregnancies (14.4%) in the valve replacement group and 6 (1.5%) in the community comparison group (adjusted relative risk, 9.73, 95% confidence interval, 3.70-25.59); there were no maternal deaths. The corresponding rates of prolonged hospital length of stay were 37.8% and 18.8% (adjusted relative risk, 2.33, 95% confidence interval, 1.48-3.67). Pregnant women who had aortic or mitral valve replacement were more likely to experience severe maternal morbidity, as well as prolonged hospital length of stay, than matched counterparts without heart disease. This information can enhance shared decision making about the timing of valve replacement and pregnancy planning in young and middle-aged women. To determine the absolute and relative risk of maternal morbidity and cardiac complications in women with prior heart valve replacement, a retrospective population-based matched cohort study was completed in the province of Ontario, Canada, where there is universal health care. Included were all women of child-bearing age who had bioprosthetic or mechanical replacement of the mitral or aortic valve, April 1994 to March 2016 (valve replacement group). Those in the valve replacement group, and who had at least one birth, were 1:4 matched to a community comparison group without heart disease and who also had at least 1 birth. There were 90 live births among the 64 women in the valve replacement group and 404 live births among the 253 women in the matched community comparison group. Severe maternal morbidity occurred in 13 pregnancies (14.4%) in the valve replacement group and 6 (1.5%) in the community comparison group (adjusted relative risk, 9.73); there were no maternal deaths. The corresponding rates of prolonged hospital length of stay were 37.8% and 18.8% (adjusted relative risk, 2.33). In summary, pregnant women who had an aortic or mitral valve replacement were more likely to experience severe maternal morbidity, as well as prolonged hospital length of stay, than matched counterparts without heart disease.

The Role of Coronary Catheterization with Angiography in Surgically Managed Infectious Endocarditis

BackgroundCoronary catheterization with angiography is often performed prior to surgical valve replacement in infectious endocarditis. There are no existing data as to whether this intervention is clinically necessary or leads to a change in surgical management. In order to determine the frequency with which coronary angiography impacts surgical management in infectious endocarditis, we conducted a retrospective review of surgically managed endocarditis cases at a tertiary care medical center. MethodsUtilizing the institutional Society of Thoracic Surgeon's database, we identified 598 patients with surgically managed endocarditis between April 29, 2011 and December 31, 2018. Patient variables were recorded, including risk factors for coronary artery disease, whether the patient received coronary angiography prior to surgery, and if the patient underwent coronary artery bypass grafting as part of their valve surgery. ResultsThere were 430 patients who received coronary catheterization with angiography prior to surgical valve replacement for infectious endocarditis, and 168 patients proceeded to surgery without coronary angiography. Nine percent of patients underwent coronary artery bypass grafting at the time of valve replacement as a result of coronary angiography findings. There was no significant difference in 30-day mortality for patients with endocarditis who underwent coronary angiography when compared with those who did not receive coronary angiography (2.6 vs 2.4%; P = 0.89). ConclusionsLeft heart catheterization with coronary angiography prior to surgical valve replacement leads to coronary artery bypass grafting in the minority of infective endocarditis patients.

Reciprocating compressor valve damage estimation under varying speeds through the acoustic emission technique

Purpose The purpose of this paper is to examine the effect of reciprocating compressor speeds and valve conditions on the roor-mean-square (RMS) value of burst acoustic emission (AE) signals associated with the physical motion of valves. The study attempts to explore the potential of AE signal in the estimation of valve damage under varying compressor speeds. Design/methodology/approach This study involves the acquisition of AE signal, valve flow rate, pressure and temperature at the suction valve of an air compressor with speed varrying from 450 to 800 rpm. The AE signals correspond to one compressor cycle obtained from two simulated valve damage conditions, namely, the single leak and double leak conditions are compared to those of the normal valve plate. To examine the effects of valve conditions and speeds on AE RMS values, two-way analysis of variance (ANOVA) is conducted. Finally, regression analysis is performed to investigate the relationship of AE RMS with the speed and valve flow rate for different valve conditions. Findings The results showed that AE RMS values computed from suction valve opening (SVO), suction valve closing (SVC) and discharge valve opening (DVO) events are significantly affected by both valve conditions and speeds. The AE RMS value computed from SVO event showed high linear correlation with speed compared to SVC and DVO events for all valve damage conditions. As this study is conducted at a compressor running at freeload, increasing speed of compressor also results in the increment of flow rate. Thus, the valve flow rate can also be empirically derived from the AE RMS value through the regression method, enabling a better estimation of valve damages. Research limitations/implications The experimental test rig of this study is confined to a small pressure ratio range of 1.38–2.03 (free-loading condition). Besides, the air compressor is assumed to be operated at a constant speed. Originality/value This study employed the statistical methods namely the ANOVA and regression analysis for valve damage estimation at varying compressor speeds. It can enable a plant personnel to make a better prediction on the loss of compressor efficiency and help them to justify the time for valve replacement in future.

P3702Aortic stenosis and inappropriate myocardial hypertrophy: is there a difference related to gender?

Abstract Introduction Degenerative aortic valve presents distinct patterns according to gender. Inappropriate myocardial hypertrophy in response to severe aortic stenosis (AS) and their clinical repercussions is of recent interest. Purpose To evaluate the influence of gender on the pattern of ventricular remodelling in patients with AS and inappropriate ventricular hypertrophy. Methods Retrospective study, analysing clinical and echocardiographic characteristics of 145 patients, between 2008 and 2018, with severe aortic stenosis and inappropriate ventricular hypertrophy, defined as septal wall thickness greater than 14 mm. Results Women were 42% of the patients, with higher mean age compared to men (75.23±12.78 vs 70.01±12.59 years, p=0.01), lower body surface (1.68±0.17 vs 1.94±0.68 m2, p=0.004), lower ventricular volumes (94.33±32.88x3856±23.81 vs 122.68±43.24x50.34±28.10 ml/m2, p&lt;0.001), increased LV wall thickness (0.65±0.19 vs 0.58±0.10, p&lt;0.001). There were no differences in LV mass (163.22±37.92 vs 170.51±39.08g, p=0.26), septal wall thickness (16.08±1.63 vs 15.71±1.02mm, p=0.24), posterior wall thickness (13.35±1.63 vs 13.67±1.58mm, p=0.23), left ventricular ejection fraction (61.31±10.36 vs 58.92±10.33%, p=0.17), indexed aortic valve area (0.41±0.10 x 0.39±0.08 cm/m2, p=0.23), medium transaortic gradient (57.50±16.42 x 55.08±17.11mmHg, p=0.39), BNP (896.28±1432.44 x 591.09±1007.71pg/ml, p=0.365) and troponin I (7.17±26.36 x 1.01±2.64 mcg/L, p=0.29). The difference between the septum and posterior wall indexed to the body surface was significantly higher in women (1.60±1.06 x 1.10±0.83 mm/m2, p=0.02), as well as the septal wall thickness indexed by the body surface (9.60±1.40 x 8.48±1.30 mm/m2, p&lt;0.001). Conclusions Septal wall thickness indexed by body surface and difference between septum and the posterior wall in ventricles with smaller volumes suggest that myocardial hypertrophy in response to severe AS is more severe in women than in men. Since inappropriate myocardial hypertrophy is a predictor of outcomes in AS, it is possible that the optimal timing for valve replacement should be earlier in women.

Attained pregnancy among women with a prosthetic heart valve

BackgroundWomen with prosthetic heart valves are at higher risk for adverse outcomes during pregnancy. The rates of achieved pregnancy, regardless of the pregnancy outcome, are largely unknown in this group of women. ObjectiveTo determine the rate of pregnancy in women with prior heart valve replacement, and compare that to women without known heart disease. Study DesignA retrospective matched population-based cohort study was done between April 1994 and March 2017, in Ontario, Canada, where universal health care is available. Administrative healthcare databases were used to identify study participants, exposures and outcomes. Each woman of child-bearing age who had a bioprosthetic or mechanical mitral or aortic valve replacement (valve replacement group) was matched to four women without heart disease (community comparison group) -- by age, year of cohort entry, any recent prior pregnancy, geographic area of residence and income level. Starting after the date of cohort entry (defined as the date valve replacement date in the valve replacement group), participants were assessed for a recognized pregnancy, namely, a livebirth, stillbirth, miscarriage or induced abortion. Hazard ratios (HR) and 95% confidence intervals (CI) were further adjusted for age, immigrant status and comorbid medical conditions. Results1596 women with a valve replacement were matched with 6378 women in the community comparison group. After a median (interquartile range, IQR) duration of follow-up of 3.1 (1.0–5.6) and 2.7 (1.0–6.0) years, respectively, 98 women in the valve replacement group achieved a recognized pregnancy (0.63 per 100 person-years), compared to 607 women in the community comparison group (0.88 per 100 person-years) – an adjusted HR of 0.72 (95% CI 0.57-0.89). Within the valve replacement group, those with a mechanical valve were less likely to achieve a recognized pregnancy than those with a bioprosthetic valve (adjusted HR 0.57, 95% CI 0.38-0.87). ConclusionWomen who undergo aortic or mitral valve replacement are less likely to achieve a pregnancy than matched counterparts without heart disease. This information, and the reasons for why this is so, can inform decisions about the timing of valve replacement and pregnancy planning.

Dobutamine Stress Echocardiography for Management of Low-Flow, Low-Gradient Aortic Stenosis

BackgroundIn the American College of Cardiology/American Heart Association guidelines, patients are considered to have true-severe stenosis when the mean gradient (MG) is ≥40 mm Hg with an aortic valve area (AVA) ≤1 cm2 during dobutamine stress echocardiography (DSE). However, these criteria have not been previously validated. ObjectivesThe aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with low-flow, low-gradient aortic stenosis (LF-LG AS). MethodsOne hundred eighty-six patients with low left ventricular ejection fraction (LVEF) LF-LG AS were prospectively recruited and underwent DSE, with measurement of the MG, AVA, and the projected AVA (AVAProj), which is an estimate of the AVA at a standardized normal flow rate. Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients, by measurement of the aortic valve calcium by computed tomography in 25 patients, and by both methods in 8 patients. According to these assessments, 50 of 87 (57%) patients in the study cohort had true-severe stenosis. ResultsPeak stress MG ≥40 mm Hg, peak stress AVA ≤1 cm2, and the combination of peak stress MG ≥40 mm Hg and peak stress AVA ≤1 cm2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVAProj ≤1 cm2 was better than all the previous markers (p < 0.007), with 70% correct classification. Among the subset of 88 patients managed conservatively (47% of the cohort), 52 died during a follow-up of 2.8 ± 2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure, and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVAProj ≤1 cm2 was a strong predictor of mortality under medical management (hazard ratio: 3.65; p = 0.0003). ConclusionsIn patients with low LVEF LF-LG AS, the DSE criteria of a peak stress MG ≥40 mm Hg, or the composite of a peak stress MG ≥40 mm Hg and a peak stress AVA ≤1 cm2 proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVAProj better distinguishes true-severe AS from pseudo-severe AS and is strongly associated with mortality in patients under conservative management. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028)

Aortic Stenosis in Dialysis Patients.

Aortic valve stenosis occurs 10-20 years earlier in patients on dialysis compared with the general population. This is likely related to the exposure of the valve to a milieu that predisposes to calcification as well as increased shear stress across the valve. Objective assessment of stenosis severity is largely made using echocardiography though accurate interpretation requires an understanding of the potential pitfalls of the technique and the influence of cardiac output upon the gradient measured across the valve. Timing of valve replacement in severe aortic stenosis is predominantly guided by exercise-induced symptoms (breathlessness, chest pain and [pre] syncope), which are often difficult to assess in the dialysis population who may have limited exercise capacity and symptoms due to renal failure and other comorbidities. Finally, treatment of aortic stenosis remains a constantly evolving area with advances in both conventional surgery and percutaneous techniques.

NT-proBNP and exercise capacity in adult patients with congenital heart disease and aprosthetic valve: amulticentre PROSTAVA study.

ObjectivesN-terminal B‑type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with a prosthetic valve and investigate its relationship with cardiac function and exercise capacity.MethodsIn this multi-centre cross-sectional observational study, data regarding medical history, echocardiography, exercise testing (VO2peak) and laboratory blood evaluation (including NT-proBNP) were collected in ACHD patients with a single prosthetic valve (either homografts, heterografts or mechanical valves).ResultsA total of 306 ACHD patients with pulmonary valve replacement (PVR, n = 139), aortic valve replacement (n = 141), mitral valve replacement (n = 21) or tricuspid valve replacement (n = 5) were investigated. The majority of patients (77 %) were in NYHA class I or II. Elevated NT-proBNP levels (cut-off ≥125 pg/ml) were found in 50 % of the patients, with the highest levels in patients with mitral valve replacements. In this study population, NT-proBNP levels were associated with gender (p = 0.029) and VO2max (p < 0.001). In PVR patients, NT-proBNP levels were associated with lower VO2peak, also after adjustment for age, gender and age at valve replacement in a multivariate model (p = 0.015).ConclusionsIn patients with ACHD and a prosthetic valve, elevated NT-proBNP levels are frequently observed despite preserved NYHA class. In PVR patients, a higher NT-proBNP level was associated with a lower VO2peak. These results may be of importance in the ongoing discussion about the timing of valve replacement in patients with CHD.

PROSTHESIS-PATIENT MISMATCH IN VALVULAR HEART DISEASE: AN EVALUATION OF ECHOCARDIOGRAPHIC FINDINGS

Guidelines for reporting echocardiographic studies in prosthetic heart valve patients have recently been published. Prothesis-patient mismatch (PPM) was first described in 1978 and is present when the effective orifice area (EOA) of an implanted surgical prosthetic valve is too small in relation to a patient’s body surface area (BSA). PPM remains a common occurrence and has been reported in the literature in up to 20-70% of AVR patients. This is concerning, since undersized prostheses relative to body size may result in higher transprosthetic gradients, worse hemodynamic function and adverse patient outcomes. We examined reporting trends in patients with prosthetic aortic and mitral valves at London Health Sciences Centre (LHSC)and St Joseph's Health Care, with particular focus on PPM in these patient populations. Patients with prosthetic aortic valve replacement (AVR) and/or mitral valve replacement (MVR) undergoing echocardiography between September 2003 and August 2013 were identified. Studies with complete patient data for whom PPM could be measured were included for further analysis. PPM was defined as EOA/BSA ≤ 0.85 cm2/m2 in the aortic position (0.65-0.85 cm2/m2 moderate, <0.65 cm2/m2 severe), and as ≤ 1.3 cm2/m2 in the mitral position. Demographic and echocardiographic parameters were evaluated. Overall 8901 studies from 3378 patients were identified (61% male; mean age 68 ± 13 years). Echocardiographic studies (mean 2.6 studies/patient) were performed in patients with AVR (6290, 71%), MVR (1904, 21%) or both (707, 8%). Complete data sets were obtained for 2391 AVR studies. PPM was present in 44% of AVR studies (severe in 3%). AVR patients with PPM were older at the time of valve replacement (71 vs. 63 years) and at follow-up (73 vs. 65 years), had greater body weight (86 vs. 81kg), larger BSA (1.97 vs. 1.92kg/m2), smaller left ventricular dimensions (47 vs. 49mm), LVOT (19 vs. 20mm) and aortic roots (30 vs. 32mm), with higher transprosthetic gradients (34 vs. 26mmHg) and lower Doppler velocity index (0.41 vs. 0.44) in comparison to patients without PPM (p<0.001 for all). PPM was more common in females (48% vs. 41%, p=0.002), in those with bioprosthetic AVR (56% vs. 9%, p<0.001), with concurrent CABG (52% vs. 39%, p<0.001) and without concurrent aortic root enlargement surgery (46% vs. 32%, p<0.001). The presence of PPM in AVR patients in our study population was common. Our data analysis identified patient subsets with a higher prevalence of PPM, which co-localized with indices of impaired cardiac performance.

Paradoxical low-flow, low-gradient aortic stenosis despite preserved left ventricular ejection fraction: new insights from weights of operatively excised aortic valves.

We reported that patients with small aortic valve area (AVA) and low flow despite preserved left ventricular ejection fraction (LVEF), i.e. 'paradoxical' low flow (PLF), have worse outcomes compared with patients with normal flow (NF), although they generally have a lower mean gradient (MG). The aortic valve weight (AVW) excised at the time of valve replacement is a flow-independent marker of stenosis severity. The objective of this study was to compare the AVW of patients with PLF and MG<40 mmHg with the AVW of patients with NF and MG≥40 mmHg. We recruited 250 consecutive patients undergoing valve replacement (Cohort A) for severe stenosis. Among them, 33 (13%) were in PLF [LVEF > 50% but stroke volume index (SVi) ≤ 35 mL/m(2)] with MG < 40 mmHg (PLF-LG group) and 105 (42%) were in NF (LVEF > 50% and SVi > 35 mL/m(2)) with MG ≥ 40 mmHg (NF-HG group). Despite a much lower MG (29 ± 7 vs. 53 ± 10 mmHg; P < 0.0001), patients in the PLF-LG group had a similar AVA (0.73 ± 0.12 vs. 0.69 ± 0.13; P = 0.19) compared with those in the NF-HG group. The AVW [median (interquartile): 1.90 (1.63-2.50) vs. 2.60 (1.66-3.32)] and prevalence of bicuspid phenotype (15 vs. 42%) were lower in the PLF-LG group than in the NF-HG group. However, AVWs analysed separately in the tricuspid and bicuspid valves were similar in both groups [tricuspid valves: 1.80 (1.63-2.50) vs. 2.30 (1.58-3.00) g; P = 0.26 and bicuspid valves: 2.72 (1.73-3.61) vs. 2.60 (2.10-3.55) g; P = 0.93]. When using cut-point values of AVW established in another series of non-consecutive patients (n = 150, Cohort B) with NF and concordant Doppler-echocardiographic findings, we found that the percentage of patients with evidence of severe stenosis in Cohort A was 70% in patients with PLF-LG and 86% in patients with NF-HG. The aortic valve weight data reported in this study provide evidence that a large proportion of patients with PLF and low-gradient have a severe stenosis and that the gradient may substantially underestimate stenosis severity in these patients. A multi-parametric approach including all Doppler-echocardiographic parameters of valve function as well as other complementary diagnostic tests may help correctly identify these patients.

Tetralogy of fallot and pulmonary valve replacement: timing and techniques in the asymptomatic patient.

An increasing number of survivors of congenital heart disease will require repeat surgical intervention. In the tetralogy of Fallot population, the primary indication is for pulmonary valve replacement secondary to pulmonary regurgitation. Although pulmonary valve disruption during repair is initially well tolerated, by the second decade following repair, patients develop increased right ventricular size with potentially decreased function. It is now well accepted that patients experiencing symptoms of heart failure secondary to chronic pulmonary insufficiency undergo pulmonary valve replacement. However, in the asymptomatic population, indications and timing of valve replacement are less clear. This article examines the current literature and presents guidelines regarding pulmonary valve replacement in the asymptomatic patient. Also, in the current era of percutaneous valve replacement, certain technical considerations should be given toward valve replacement and are discussed as well.

Prognostic value of low-dose dobutamine testing in asymptomatic patients with moderate or severe aortic stenosis and preserved ejection fraction

Purpose: In Aortic Stenosis (AS) most Doppler-echocardiographic indices that are used for assessing AS severity are flow dependent. The aim of this study was to assess prognostic value of low-dose Dobutamine Testing (DT) in patients with moderate or severe AS and preserved Ejection Fraction (EF). Method: A total of 126 asymptomatic patients with aortic valve area (AVA) ≤1.5 cm2 and EF >50% were enrolled in this prospective study. The follow-up period was 14±2 months. Mean age was 66.47±10.53; (58.73% males), mean EF was 72,03±6,69%, mean pressure gradient (Pmean) 41.94±11.22 mmHg and mean AVA 0.82±0.22 cm2. Patients with ≥2+ valvular regurgitation or more than mild mitral stenosis were excluded. The dobutamine infusion protocol was begun at 5 μg/kg/min body weight up to 20 μg/kg/min, titrated upwards at steps of 5 μg/kg/min every 3 min. The composite outcome endpoint (MACE) was defined as cardiac death, aortic valve replacement and hospitalization caused by AS symptoms according to patient's medical record. Results: No patient experienced a serious adverse event during or after DT. A total of 70 patients had MACE (55.55%), of which 9 patients (7.14%) have died during follow-up. Out of 70 patients, 56 patients (80%) had an Aortic Valve Replacement (RAV). Patients who had an increase in AVA during DT ≤0.2 cm2 and/or final AVA ≤1 cm2 had more often RAV (hi=9.5311; df=1; p=0.002). The lasso penalized Cox regression, conducted solely on the variables at rest, showed that the greatest predictive capacity has the aortic valve resistance (AVR). At the same time, the AUC for the all analyzed pre-dobutamine variables combined, evaluated at time = 12 months, was 0.76. On the other hand, the L1 procedure, when applied on all variables (pre and during DT), chooses only dobutamine variables as the most valuable in predictive sense, improving AUC by 6% (AUC =0.82, at time = 12 months). The value of the AVR obtained during the DT was the strongest independent one-year MACE predictor (according to bootstrapped p values) of all pre and during DT varaibles, with the value of 195.12 dynes s cm-5 having the highest sensitivity ans specificity in predicting MACE (0.78 and 0.73 respectively). In addition, patients who have experienced symptoms (11/126, 8.73%) during DT had more often MACE comparing to asymptomatic patients (hi=6,7408; p<0,001; df=1). Conclusion: The present study demonstrates that AVR, as well as flow-mediated changes during DT, can provide new, clinically relevant information in terms of outcome and timing of valve replacement in asymptomatic patients with moderate and severe AS and preserved EF.

Abstract 309: Osteogenic Induction of p-ERK 1/2 Signaling Associated with NOTCH1 Inactivation in Human Aortic Valvar Interstitial Cells

Introduction Heart valve disease affects over 2% of the population, leading to at least 20,000 deaths and $1 billion in direct costs in the US each year. Calcific aortic valve disease (CAVD) is linked to loss of function mutations in NOTCH1 that result in osteogenic gene induction. In vitro animal studies have established that multiple osteogenic targets are mediated through induction of p-ERK 1/2 signaling; however, the relationship between NOTCH1 and p-ERK has not been examined in primary human aortic valvar interstitial cells (AVICs). Hypothesis We tested the hypothesis that chemically-induced NOTCH1 suppression results in mineralization due to p-ERK 1/2 activation in human AVICs. Methods Human AVICs were isolated from CAVD specimens at the time of valve replacement. AVICs were cultured for two weeks in complete media containing DMEM and 10% FBS, and treated with calcific media (10mM b-glycerol phosphate; 60μM ascorbic acid-2-phosphate; 1μM dexamethasone), which has been shown to suppress NOTCH1 signaling. Standard real-time RT-PCR, western blot, and immunocytochemistry were used to compare groups. Results Treatment with calcific media resulted in a 2.3 fold decrease in the level of NOTCH1 expression and a 3 fold increase in p-ERK 1/2 expression, assessed with both western blots and immunocytochemistry. Interestingly, calcific media also induced a 3.5 fold decrease in VEGF, consistent with early osteogenic differentiation. Additionally, the AVICs treated with calcific media demonstrated overt calcification by Alizarin Red staining. Conclusions Human AVICs demonstrated calcification associated with p-ERK 1/2 activation and reduced NOTCH1 levels, suggesting p-ERK inhibition may mitigate the effects of NOTCH loss of function, thereby representing a potential pharmacologic therapy for CAVD. Further investigation of the molecular mechanisms linking NOTCH1 and p-ERK are warranted, including studies that specifically inhibit NOTCH1 signaling and define the impact of mechanical forces on molecular pathways, thereby identifying mechanisms underlying CAVD progression.

Infective Endocarditis with Symptomatic Cerebral Complications: Contribution of Cerebral Magnetic Resonance Imaging

Background: Cerebral complications are well-identified causes of morbidity and mortality in patients with infective endocarditis (IE). Few studies have analysed the impact of brain magnetic resonance imaging (MRI) in IE patients with neurological manifestations. Objectives: The aims of this study were to assess the MRI contribution to the management of patients with IE neurological manifestations and to compare cerebral CT and MRI findings. Material and Methods: Patients with definite or probable IE and neurological manifestations were prospectively enrolled from 2005 to 2008, in a university hospital (Bichat Claude Bernard Hospital, Paris). Clinical and radiological characteristics and echocardiographic findings were systematically recorded. Brain MRI with angiography was performed and compared to available CT scans. The contribution of MRI results to cerebral involvement staging and to therapeutic plans was evaluated. Results: Thirty patients, 37-89 years old, were included. Nineteen suffered from pre-existing heart disease. Blood cultures were positive in 29 cases and the main micro-organisms were streptococci (n = 14) and staphylococci (n = 13). The IE was mainly located on mitral (n = 15) and aortic valves (n = 13). Neurological events were strokes (n = 12), meningitis (n = 5), seizures (n = 1), impaired consciousness (n = 11) and severe headache (n = 1). MRI findings included ischaemic lesions (n = 25), haemorrhagic lesions (n = 2), subarachnoid haemorrhage (n = 5), brain abscess (n = 6), mycotic aneurysm (n = 7), vascular occlusion (n = 3) and cerebral microbleeds (n = 17). In 19/30 cases, neurological manifestations were observed before the diagnosis of IE. MRI was more sensitive than CT scan in detecting both clinically symptomatic cerebral lesions (100 and 81%, respectively) and additional asymptomatic lesions (50 and 23%, respectively). Therapeutic plans were modified according to MRI results in 27% of patients: antibiotherapy regimen modifications in 7% (switch for molecules with high cerebral diffusion) and surgical plan modifications in 20% (indication of valvular replacement due to the embolic nature of the vegetations revealed by MRI or postponement of surgery due to haemorrhagic lesions). None of the 16/30 (51%) operated-on patients experienced postoperative neurological worsening. In-hospital death occurred in 4 patients. Conclusion: In patients with IE neurological manifestations, MRI revealed a broader involvement of the brain (type and number of lesions) than indicated by clinical signs and/or CT scan. With a better disease staging of neurological manifestations, MRI brain imaging may help in patient management and the decision-making process especially for cardiac surgery indication and timing of valve replacement.