Degenerative Aortic Valve Research Articles

Serum and Vascular Stiffness Biomarkers Associated with the Severity of Degenerative Aortic Valve Stenosis and Cardiovascular Outcomes.

Background: Although degenerative aortic valve stenosis (DAS) is the most prevalent growth-up congestive heart valve disease, still little known about relationships between DAS severity, vascular stiffness (VS), echocardiographic parameters, and serum biomarkers in patients undergoing transcatheter (TAVR) or surgical aortic valve replacement (SAVR). The objective of this study was to identify biomarkers associated with DAS severity, and those that are associated with cardiovascular death (CVD) and episodes of chronic heart failure (CHF) exacerbation. Methods: A total of 137 patients with initially moderate-to-severe DAS were prospectively evaluated for the relationship between DAS severity, baseline VS, and serum biomarkers (uPAR, GDF-15, Gal-3, IL-6Rα, ET-1, PCSK9, RANTES/CCL5, NT-proBNP, and hs-TnT), and were followed-up for 48 months. The prognostic significance of each variable for CVD and CHF risk was measured by hazard ratio of risk (HR), which was calculated by Cox’s proportional hazard model. Results: DAS severity showed correlations with IL-6Rα (r = 0.306, p < 0.001), uPAR (r = 0.184, p = 0.032), and NT-proBNP (r = −0.389, p < 0.001). Levels of ET-1 and Gal-3 were strongly correlated with VS parameters (r = 0.674, p < 0.001; r = 0.724, p < 0.001). Out of 137 patients, 20 were referred to TAVR, 88 to SAVR, and 29 to OMT. In TAVR patients, the highest levels of ET-1, Gal-3, and VS were found as compared to other patients. The highest incidence of CVD was observed in patients who underwent TAVR (35%), compared to SAVR (8%) and OMT (10.3%) (p = 0.004). In a multivariate analysis, ET-1 occurred predictive of CVD risk (HR 25.1, p = 0.047), while Gal-3 > 11.5 ng/mL increased the risk of CHF exacerbation episodes requiring hospital admission by 12%. Conclusions: Our study indicated that ET-1 and Gal-3 levels may be associated with the outcomes in patients with DAS.

P319 SOMETHING MORE OF SIMPLE CARDIAC CONDUCTION DISORDERS

Abstract Background Cardiac amyloidosis (CA) is an infiltrative disease caused by extracellular deposition of amyloid fibrils. Possible cardiac manifestations include heart failure with preserved ejection fraction (EF), aortic valve stenosis, microvascular coronary artery disease, atrial fibrillation (AF), ventricular arrhythmias, and cardiac conduction disorders (CCD). We report a case of advanced CCD in a patient first diagnosed with wild–type transthyretin amyloidosis (ATTRwt). Case Report An 88–year–old man went to Emergency Room for chest pain with minimal elevation of troponin I and increase in NTproBNP. The patient reported a recent syncope with ribs fractures. The medical history showed hypertension, paroxysmal AF, carotid atherosclerosis, vascular encephalopathy and prostate cancer. Troponin I monitoring showed plateau values and there were no clinical signs of heart failure. ECG showed regular sinus rhythm with marked first degree atrioventricular block, right bundle branch block and left anterior fascicular block (Fig. 1A). Cardiac telemetry recorded brief phases of atrioventricular dissociation (AVD). Transthoracic echocardiography showed severe left ventricular concentric hypertrophy (LVCH) with granular–sparkling appearance and preserved EF, reduced global longitudinal strain with apical sparing (Fig. 1B), mitral–aortic valve degeneration and dilation of the ascending aorta. Given the advanced CCD with AVD and the recent syncope, the patient underwent a dual–chamber pacemaker implantation. In consideration of the echocardiographic suspicion of CA, following Gillmore’s diagnostic algorithm (GDA), serum electrophoresis and assay of serum free light chains were performed and resulted normal, while 99mTc–DPD bone scintigraphy was positive for significant radiotracer cardiac uptake (Perugini grade 3) (Fig. 1C). Based on this result, we carried out the search for transthyretin gene mutations which resulted negative, and therefore the diagnosis of ATTRwt was made. Discussion Advanced CCD in patients with transthyretin CA are present in about 9.5% of cases at the time of diagnosis, especially in older patients. It is therefore essential, in case of concomitant LVCH, to suspect the presence of CA as the cause of CCD by searching for the disease red flags and following the GDA to non–invasively confirm or exclude the diagnosis of CA. A correct and timely diagnosis of CA makes it possible to treat the disease and its complications, improving the prognosis.

Association of Increased Vascular Stiffness with Cardiovascular Death and Heart Failure Episodes Following Intervention on Symptomatic Degenerative Aortic Stenosis.

Background. The resistive (RI) and pulsatile (PI) indices are markers of vascular stiffness (VS) which are associated with outcomes in patients with cardiovascular disease. We aimed to assess whether VS might predict incidence of cardiovascular death (CVD) and heart failure (HF) episodes following intervention on degenerative aortic valve stenosis (DAS). Methods. The distribution of increased VS (RI ≥ 0.7 and PI ≥ 1.3) from supra-aortic arteries was assessed in patients with symptomatic DAS who underwent aortic valve replacement (AVR, n = 127) or transcatheter aortic valve implantation (TAVI, n = 119). During a 3-year follow-up period (FU), incidences of composite endpoint (CVD and HF) were recorded. Results. Increased VS was found in 100% of TAVI patients with adverse event vs. 88.9% event-free TAVI patients (p = 0.116), and in 93.3% of AVR patients with event vs. 70.5% event-free (p = 0.061). Kaplan–Mayer free-survival curves at 1-year and 3-year FU were 90.5% vs. 97.1 % and 78% vs. 97.1% for patients with increased vs. lower VS. (p = 0.014). In univariate Cox analysis, elevated VS (HR 7.97, p = 0.04) and age (HR 1.05, p = 0.024) were associated with risk of adverse outcomes; however, both failed in Cox multivariable analysis. Conclusions. Vascular stiffness is associated with outcome after DAS intervention. However, it cannot be used as an independent outcome predictor.

Sutureless Valve in Bicuspid Aortic Stenosis: Modified Technique and Midterm Outcome.

The sutureless valve has gained popularity for degenerative aortic valve stenosis but not congenital bicuspid aortic valve (BAV) due to anatomical challenges. We reviewed our modified implant techniques for patients with BAV. From June 2015 to June 2019, 66 patients with aortic valve stenosis were treated with the Perceval sutureless valve, 20 of whom had BAV. The demographics, type of BAV (the Sievers classification), and associated pathologies, surgical outcomes, and midterm hemodynamics were recorded. The median age was 64 (range: 49-81) years and the Society of Thoracic Surgeons score was 2.186 (range: 0.407-6.384). Annular plication was performed in 9 (75%) of 12 type 0 and 3 (37.5%) of 8 type I, with implanted valve sizes of M, L, and XL in 6, 10, 4 cases, respectively. Three patients, all type 0 in the initial learning periods, required intraoperative redeployment due to malposition of the valve. The final implant was successful in all without conversion to traditional prosthesis. The median extubation time was 4 hours and the durations of intensive care unit and hospital stay were 1 and 6 days. At a median follow-up of 46 (23-72) months, there was one late mortality due to hemorrhagic stroke sequel. The last echo revealed none had more than mild paravalvular leakage and the mean transvalvular pressure gradient remained stable at 9.70 (range: 6.94-15.0) mm Hg. The sutureless valve can achieve satisfactory outcomes in BAV without paravalvular leakage and excellent hemodynamics. It may serve as the benchmark for transcatheter aortic valve implantation in this unique population.

Impact of mitral annular calcification on hemodynamic effect in mitral stenosis in multiple valve disease: relevant or not

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Prevalence of mitral annulus calcification (MAC) and degenerative mitral stenosis thus elevated transmitral gradient (TMG) is increased with age and multivalve involvement. The management of degenerative multivalve disease is challenging, as is identification of the presence of multivalve involvement and its hemodynamic impact because of interaction between two or more valve lesions especially in degenerative valve disease. Hemodynamic interaction between significant aortic stenosis and mitral annular calcification is often combined with diastolic disfunction which can result in LA enlargement and abnormal atrioventricular coupling and left atrial and ventricular remodeling. Purpose Study aimed to assess the effect of MAC on mitral valve stenosis in patients with multiple valve disease of degenerative origin. Method We retrospectively analyzed 78 patients with elevated transmitral gradient defined as an elevated TMG &amp;gt;4mmHg, MAC in multivalve involvement, mainly degenerative significant aortic valve stenosis who were treated in our clinic from 2018 to 2021. We excluded patients with prior cardiac surgery, congenital heart disease, hypertrophic obstructive cardiomyopathy and with heart rate &amp;gt;100 bpm at time of study and significant mitral regurgitation. Baseline demographic data were extracted from the electronic medical record and echocardiographic data were analyzed from electronic saved data. Results Study identified a total of 78 patients (average age 71,89 years, 64% females). Of 57 analyzed patients 32% patients had severe MAC and calcification of chordae, and 68% patients had MAC and mild or no significant chordae calcification. Patients with aortic gradients, severe aortic stenosis (AVAi 0,80 cm/m2) were observed more often in patients with severe MAC and significant chordae calcification than in those with nonsevere MAC (p &amp;lt; 0.043).There was no significant difference in mitral annular distension between groups. Baseline mean MV gradients were 6,5+-1.5 mm Hg. Mean MVA (continuity equation) was 1,5+-0.4 cm2, and MVAi 0,8+-0,2 cm/m2, mean LA volume 70 ml/m2, mean E/e 35, mean EF LV 68% and mean GLS -14. Conclusion Result suggest that increasing transmitral gradient if superimposed on severe MAC with only modest mitral stenosis will result in a high mean transmitral gradient. The presence of elevated pressure transmitral gradient in patients with more severe aortic stenosis and more severe MAC combined with chordae calcification may imply hemodynamic effect or stress on mitral valve degeneration in multiple valve involvement. Other imaging modalities and further investigation for better understanding effect of hemodynamic stress in multiple valve disease are needed. These observations need to be evaluated on larger cohorts of patients during a longer period of time.

Serotonin-A Driver of Progressive Heart Valve Disease.

It is well known that some serotoninergic drugs and neuroendocrine tumors producing serotonin (5-HT) may induce valvular heart disease by stimulation of proliferation of valvular cells via interaction with a 5-HT receptor type 2B. Serotonin could play a role in the pathogenesis of progressive valvular disease for example as a complication of rheumatic fever, in patients with congenital bicuspid aortic valves or in degenerative aortic valve stenosis. The initial inflammation in acute rheumatic fever seems to affect both right and the left-side cardiac valves. Some patients develop chronic right-sided valve disease, particularly in connection with septum defects, though left-sided valves typically are predominantly affected, indicating that high flow velocity and systemic pressure close to the valves may be central in the pathogenesis. Serotonin is transported in granules in blood platelets. Changes in platelet number and concentrations of substances released from platelets in patients with valvular disease indicate that serotonin is released locally by shear stress when passing through an abnormal valve. Accordingly, any functional changes (like bicuspid aortic valves and changes secondary to degeneration) in the valves may progress due to locally released serotonin. Unfortunately, due to serotonin release by sampling and preparation of plasma, local serotonin assessment is not possible. Nevertheless, we suggest that serotonin may play a role in valvular disease in general and that patients may benefit from treatment reducing the effect of serotonin on the heart.

Heme in Cardiovascular Diseases: A Ubiquitous Dangerous Molecule Worthy of Vigilance.

Heme, the protoporphyrin IX iron complex is widely present in the human body and it is involved in oxygen storage, electron transfer, and enzymatic reactions. However, free heme can be toxic as it catalyzes the production of reactive oxygen species, oxidizes lipids and proteins, and causes DNA damage, thereby inducing a pro-inflammatory environment. The generation, metabolism, and degradation of heme in the human body are regulated by precise mechanisms to ensure that heme remains non-toxic. However, in several types of cardiovascular diseases, impaired metabolism and exposure to heme may occur in pathological processes, including neovascularization, internal hemorrhage, ischemia, and reperfusion. Based on years of research, in this review, we aimed to summarize the underlying mechanisms by which heme contributes to the development of cardiovascular diseases through oxidative stress, relative pathway gene expression regulation and phenotypic changes in cells. Excess heme plays a detrimental role in atherosclerosis, heart failure, myocardial ischemia-reperfusion injury, degenerative aortic valve stenosis, cardiac iron overload. Recent researches revealed that in some cases heme involved in cardiac damage though ferroptosis. Thus, heme concentrations beyond normal levels are dangerous. Further research on the role of heme in cardiovascular diseases is needed.

Structural valve degeneration of bioprosthetic aortic valves: A network meta-analysis

ObjectiveTo compare the rate of structural valve degeneration (SVD) following surgical aortic valve replacement associated with the Trifecta (TF) valve (St Jude Medical) versus other bioprosthetic valves. MethodsA systematic literature search was conducted for studies comparing durability of the TF prosthesis to other valve types, including Perimount (Edwards Lifesciences), Carpentier-Edwards Perimount Magna Ease (ME) (Edwards Lifesciences), and Mitroflow (LivaNova USA) after surgical aortic valve replacement. Random effect pairwise and network meta-analyses were performed to compare the incident rate ratio of the composite primary outcome of SVD or reintervention due to SVD. ResultsTen studies with 31,029 patients were included, of whom 6832 received TF, 19,023 received Perimount, 3514 received ME, and 713 received Mitroflow. When compared with TF, ME was associated with lower rates of SVD or reintervention for SVD (incident rate ratio, 0.13; 95% CI, 0.02-0.92; P = .04). Similarly, at network meta-analysis, when compared with TF, only ME was associated with significantly lower rates of SVD or reintervention for SVD (incident rate ratio, 0.13; 95% CI, 0.02-0.97). ME (incident rate ratio, 0.18; 95% CI, 0.07-0.47) and PM (incident rate ratio, 0.34; 95% CI, 0.12-0.98) were associated with significantly lower rate of all-cause reintervention when compared with TF. No differences in the other secondary outcomes were found. ConclusionsThe TF valve is associated with significantly higher rates of SVD or reintervention for SVD than the ME valve, but not the Mitroflow valve. The TF valve was also associated with higher rates of all-cause reintervention than ME and Perimount valves. The underlying mechanism(s) of these findings warrant further investigation.

Bioprosthetic Aortic Valve Degeneration: a Review from a Basic Science Perspective.

IntroductionThe increase in the prevalence of aortic stenosis due to an aging population has led to an increasing number of surgical aortic valve replacements. Over the past 20 years, there has been a major shift in preference from mechanical to bioprosthetic valves. However, despite efforts, there is still no "ideal" bioprosthesis. It is crucial to understand the structure, biology, and function of native heart valves to design more intelligent, strong, durable, and physiological heart valve tissues.MethodsA comprehensive review of the literature was performed to identify articles reporting the basic mechanisms of bioprosthetic valve dysfunction and the biology of native valve cells. Searches were run in PubMed, MEDLINE® (the Medical Literature Analysis and Retrieval System Online), and Google Scholar. Terms for subject heading and keywords search included “biological heart valve dysfunction”, “bioprosthesis dysfunction”, “bioprosthesis degeneration”, and “tissue heart valves”.ResultsAll the relevant findings are summarized in the appropriate subsections. Structural dysfunction is a logical and expected consequence of the chemical, mechanical, and immunological processes that occur during fixation, manufacture, and implantation.ConclusionBiological prosthesis valve dysfunction is a clinically significant process. It has become a major issue considering the growing rate of bioprosthesis implantation and improved long-term patient survival. Understanding bioprosthetic aortic valve degeneration from a basic science perspective is a key point to improve technologic advances and specifications that lead to a new generation of bioprostheses.

Participation of transcriptional factor ZBTB16 in the processes of physiological bone tissue formation and in pathological calcification of the aortic valve

Degenerative calcific aortic valve stenosis is the most common type of heart valve disease in the Western world. Patients with severe stenosis are associated with 50 percent chance of mortality within two years in the absence of intervention. Surgical interventions are the only treatment method for severe calcific aortic valve stenosis to date. Pharmacological approaches have so far failed to affect the course of the disease. Thus, there is an urgent need to develop novel treatment strategies that could slow down the progression of the stenosis. ZBTB16 is a zinc finger protein with N-term BTB/POZ domain (protein-protein interaction motif) and 9 zinc finger domains (DNA binding motif) in C-term. There is growing evidence proving the participation of ZBTB16 in skeletal development. ZBTB16 has been shown to play a role in the specification of limb and axial skeleton patterning. Moreover, the expression of ZBTB16 is increased in patients with ectopic bone formation. Nowadays, the evidence supports that the mechanisms that play key roles in the formation of bone tissue are similar to the processes occurring during the development of ectopic ossification of the aortic valve. Thus, it can be assumed that ZBTB16 is heavily involved in osteogenic transformation in the aortic valve. Understanding similarities and differences in the mechanisms that mediate osteogenic differentiation of stem cells during bone formation and pathological ossification of tissues can help to find the ways to control the osteogenic differentiation in the human body. The aim of this review is to summarize data on the role of ZBTB16 and its products in the regulation of differentiation and proliferation of cells involved in osteogenesis and in the development of ectopic calcification of the aortic valve. The study of the dynamic changes of ZBTB16 expression in aortic valve calcification is a new and relevant study field.

Degenerative changes of the aortic valve during left ventricular assist device support.

AimsDonor heart shortage leads to increasing use of left ventricular assist device (LVAD) as bridge‐to‐transplant or destination therapy. Prolonged LVAD support is associated with aortic valve insufficiency, representing a relevant clinical problem in LVAD patients. Nevertheless, the impact of LVAD support on inflammation, remodelling, and chondro‐osteogenic differentiation of the aortic valve is still not clearly understood. The aim of the study is to evaluate the impact of LVAD support on structural and molecular alterations of the aortic valve.Methods and resultsDuring heart transplantation, aortic valves of 63 heart failure patients without (n = 22) and with LVAD support (n = 41) were collected and used for analysis. Data on clinical course as well as echocardiographic data were analysed. Calcification and markers of remodelling, chondro‐osteogenic differentiation, and inflammation were evaluated by computed tomography, by mRNA analysis and by histology and immunohistochemistry. Expression of inflammation markers of the LVAD group was analysed with regard to levels of C‐reactive protein and driveline infections. Calcium accumulation and mRNA expression of determined markers were correlated with duration of LVAD support. Data were also analysed relating to aortic valve opening and aortic valve insufficiency. There was no difference in the frequency of cardiovascular risk factors or comorbidities between the patient groups. Expression of matrix metalloproteinase‐9 (P = 0.007), alpha‐smooth muscle actin (P = 0.045), and osteopontin (P = 0.003) were up‐regulated in aortic valves of LVAD patients. Histological appearance of the aortic valve was similar in patients with or without LVAD, and computed tomography‐based analysis not yet revealed significant difference in tissue calcification. Expression of interferon gamma (P = 0.004), interleukin‐1 beta (P < 0.0001), and tumour necrosis factor alpha (P = 0.04) was up‐regulated in aortic valves of LVAD patients without concomitant inflammatory cell infiltration and independent from unspecific inflammation. Expression of matrix metalloproteinase‐2 (P = 0.038) and transforming growth factor beta (P = 0.0504) correlated negatively with duration of LVAD support. Presence of aortic valve insufficiency led to a significantly higher expression of interferon gamma (P = 0.007) in LVAD patients. There was no alteration in the determined markers in relation to aortic valve opening in LVAD patients.ConclusionsLeft ventricular assist device support leads to signs of early aortic valve degeneration independent of support duration. Thus, the aortic valve of patients with LVAD support should be closely monitored, particularly in patients receiving destination therapy as well as in the prospect of using aortic valves of LVAD patients as homografts in case of bridge‐to‐transplant therapy.

Latest Advances in Multimodality Imaging of Aortic Stenosis.

Aortic stenosis is a common condition associated with major morbidity, mortality, and health-care costs. Nevertheless, we currently lack any effective medical therapies that can treat or prevent disease development or progression. Modern advances in echocardiography and CT have helped improve the assessment of aortic stenosis severity and monitoring of disease progression, whereas cardiac MRI informs on myocardial health and the development of fibrosis. In a series of recent studies, 18F-NaF PET/CT has been shown to assess valvular disease activity and progression, providing mechanistic insights that can inform potential novel therapeutic approaches. This review will examine the latest advances in the imaging of aortic stenosis and bioprosthetic valve degeneration and explore how these techniques can assist patient management and potentially accelerate novel therapeutic developments.

Spontaneous Degenerative Aortic Valve Disease in New Zealand Obese Mice.

BackgroundDegenerative aortic valve (AoV) disease and resulting aortic stenosis are major clinical health problems. Murine models of valve disease are rare, resulting in a translational knowledge gap on underlying mechanisms, functional consequences, and potential therapies. Naïve New Zealand obese (NZO) mice were recently found to have a dramatic decline of left ventricular (LV) function at early age. Therefore, we aimed to identify the underlying cause of reduced LV function in NZO mice.Methods and ResultsCardiac function and pulmonary hemodynamics of NZO and age‐matched C57BL/6J mice were monitored by serial echocardiographic examinations. AoVs in NZO mice demonstrated extensive thickening, asymmetric aortic leaflet formation, and cartilaginous transformation of the valvular stroma. Doppler echocardiography of the aorta revealed increased peak velocity profiles, holodiastolic flow reversal, and dilatation of the ascending aorta, consistent with aortic stenosis and regurgitation. Compensated LV hypertrophy deteriorated to decompensated LV failure and remodeling, as indicated by increased LV mass, interstitial fibrosis, and inflammatory cell infiltration. Elevated LV pressures in NZO mice were associated with lung congestion and cor pulmonale, evident as right ventricular dilatation, decreased right ventricular function, and increased mean right ventricular systolic pressure, indicative for the development of pulmonary hypertension and ultimately right ventricular failure.ConclusionsNZO mice demonstrate as a novel murine model to spontaneously develop degenerative AoV disease, aortic stenosis, and the associated end organ damages of both ventricles and the lung. Closely mimicking the clinical scenario of degenerative AoV disease, the model may facilitate a better mechanistic understanding and testing of novel treatment strategies in degenerative AoV disease.

A Role for Peroxisome Proliferator-Activated Receptor Gamma Agonists in Counteracting the Degeneration of Cardiovascular Grafts.

Aortic valve replacement for severe stenosis is a standard procedure in cardiovascular medicine. However, the use of biological prostheses has limitations especially in young patients because of calcifying degeneration, resulting in implant failure. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, was shown to decrease the degeneration of native aortic valves. In this study, we aim to examine the impact of pioglitazone on inflammation and calcification of aortic valve conduits (AoC) in a rat model. Cryopreserved AoC (n = 40) were infrarenally implanted into Wistar rats treated with pioglitazone (75 mg/kg chow; n = 20, PIO) or untreated (n = 20, controls). After 4 or 12 weeks, AoC were explanted and analyzed by histology, immunohistology, and polymerase chain reaction. Pioglitazone significantly decreased the expression of inflammatory markers and reduced the macrophage-mediated inflammation in PIO compared with controls after 4 (P = 0.03) and 12 weeks (P = 0.012). Chondrogenic transformation was significantly decreased in PIO after 12 weeks (P = 0.001). Calcification of the intima and media was significantly reduced after 12 weeks in PIO versus controls (intima: P = 0.008; media: P = 0.025). Moreover, echocardiography revealed significantly better functional outcome of the AoC in PIO after 12 weeks compared with control. Interestingly, significantly increased intima hyperplasia could be observed in PIO compared with controls after 12 weeks (P = 0.017). Systemic PPAR-gamma activation prevents inflammation as well as intima and media calcification in AoC and seems to inhibit functional impairment of the implanted aortic valve. To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for.

Heydeho syndróm

Gastrointestinal bleeding is a severe and potentially life-threatening condition associated with significant morbidity and mortality. In clinical practice, its differential dia­gnosis can sometimes be complicated, especially when bleeding is recurrent. One of the lesser-known reasons for recurrent gastrointestinal bleeding is the so called Heyde’s syndrome. It is a combination of bleeding from gastrointestinal angiodysplasia, aortic stenosis and acquired type 2A von Willebrand syndrome. In the submitted article, authors present a summary of the current knowledge on etiology and pathogenesis of the disease. The degenerative aortic valve disease, typically present in elderly patients, causes changes in the blood flow through stenotic opening. This results in elongation of otherwise globular von Willebrand’s factor (vWF) molecules, resulting in its reduced efficacy in hemostasis. According to new scientific discoveries, vWF also plays a role in angiogenesis and therefore in gastrointestinal angiodysplasia formation. This combination of factors results in recurrent bleeding typical for Heyde’s syndrome. Surgical aortic valve replacement is the gold standard treatment. A vicious circle can often be created between the gastroenterologist, who refers the patient for cardiac surgery procedures, and the cardiothoracic surgeon, who is waiting for a time when the patient will stop bleeding. A close communication and cooperation between the gastroenterologist, hematologist and cardiothoracic surgeon is required to properly manage the patient. The presence of angiodysplasia in an elderly patient, associated with recurrent gastrointestinal bleeding, should lead clinicians to look for aortic stenosis and consider Heyde’s syndrome as a potential dia­gnosis. Its interesting etiopathogenesis and rare occurrence led the authors to further investigate this topic. They also present a short summary of their own group of patients. Key words: Heyde’s syndrome – aortic stenosis – angiodysplasia – von Willebrand’s syndrome

Decreased Glucagon-Like Peptide-1 Is Associated With Calcific Aortic Valve Disease: GLP-1 Suppresses the Calcification of Aortic Valve Interstitial Cells

Objectives: This study explores the concentration and role of glucagon-like peptide-1 (GLP-1) in calcific aortic valve disease (CAVD).Background: Calcific aortic valve disease is a chronic disease presenting with aortic valve degeneration and mineralization. We hypothesized that the level of GLP-1 is associated with CAVD and that it participates in the calcification of aortic valve interstitial cells (AVICs).Methods: We compared the concentration of GLP-1 between 11 calcific and 12 normal aortic valve tissues by immunohistochemical (IHC) analysis. ELISA was used to measure GLP-1 in serum of the Control (n = 197) and CAVD groups (n = 200). The effect of GLP-1 on the calcification of AVICs and the regulation of calcific gene expression were also characterized.Results: The GLP-1 concentration in the calcific aortic valves was 39% less than that in the control non-calcified aortic valves. Its concentration in serum was 19.3% lower in CAVD patients. Multivariable regression analysis demonstrated that GLP-1 level was independently associated with CAVD risk. In vitro, GLP-1 antagonized AVIC calcification in a dose- and time-dependent manner and it down-regulated RUNX2, MSX2, BMP2, and BMP4 expression but up-regulated SOX9 expression.Conclusions: A reduction in GLP-1 was associated with CAVD, and GLP-1 participated in the mineralization of AVICs by regulating specific calcific genes. GLP-1 warrants consideration as a novel treatment target for CAVD.

Associations between aortic regurgitation severity and risk of incident myocardial infarction and stroke among patients with degenerative aortic valve disease: insights from a large Chinese population-based cohort study

ObjectivesFew studies have explored whether the risk of myocardial infarction (MI) or stroke varies among patients with degenerative aortic valve disease (DAVD) with different severity of aortic regurgitation (AR) or...

Autograft Wrapping Reinforcement in Adolescents Undergoing Ross Operation: A Tailored Coat

BackgroundThe Ross operation is a good surgical option for the pediatric population with aortic valve disease. However, the need for reoperation due to aortic root dilatation remains the principal limitation of this procedure. We report a small series of adolescents who underwent the Ross operation with Gore-Tex (W. L. Gore & Associates, Flagstaff, AZ) membrane reinforcement to avoid the progressive dilatation of the neoaortic root. MethodsBetween March 2002 and March 2010, 15 adolescent patients underwent a modified Ross procedure with the autograft wrapping with 0.1-mm Gore Preclude (W. L. Gore & Associates) pericardial membrane. Follow-up was performed by clinical and echocardiographic controls. ResultsThese patients were a mean age of 15 ± 1.4 years. The mean aortic cross-clamp time was 130 ± 17 minutes. The mean cardiopulmonary bypass time was 187 ± 27 minutes. There was no hospital mortality. The mean follow-up was 15 ± 2.5 years (range, 9.7-17.7 years). During the follow-up, 1 patient required aortic valve reoperation for cusps prolapse. The mean diameters of annulus (22.8 ± 1.8 mm vs 23.3 ± 1.5 mm, P = .12), aortic root (27.4 ± 1.4 mm vs 28.2 ± 0.8 mm, P = .09), and sinotubular junction (24.3 ± 1.1 mm vs 25.1 ± 0.7 mm, P = .11) were not statistically different between discharge and follow-up. ConclusionsThe wrapping reinforcement autograft in the Ross procedure with Gore-Tex membrane is simple, safe, and does not require significant additional time. Our results showed good early and long-term outcomes for reoperation, aortic root dilatation, and aortic valve degeneration.

Impact of osteogenic activity on degenerative aortic valve disease in patients with osteoporotic hip fracture

BackgroundPrevious studies have proposed that osteogenic and apoptotic processes of valve interstitial cells contribute to the mineralization and then calcification of the aortic valve. Osteoblast-like cells subsequently mediate calcification of the aortic valve as part of a highly regulated process analogous to skeletal bone formation. The objective of this study was to evaluate the pathogenesis of the sclerotic/calcific changes in the aortic valve from histological and biological findings, and investigate the role of osteoblasts in the calcified pathway of aortic stenosis. MethodsPreoperative echocardiography in 550 consecutive patients with osteoporotic hip fracture were retrospectively examined (475 females, mean 25th–75th, 89 [85–93] years). One hundred sixteen patients were under medical treatment with anti-osteoporosis drugs. We evaluated the prevalence and degree of degenerative changes in the aortic valve and examined the associations of bone turnover biomarkers N-terminal pro-peptide of type 1 collagen (P1NP) and serum tartrate-resistant acid phosphatase (TRACP-5b) with degenerative calcific changes in the aortic valve. ResultsOf 550 patients, 112 patients (20.9%) showed no leaflet calcification; 296 (53.8%), 1 leaflet calcification; and 142 (25.8%), 2 ≥ leaflets calcification. Significant (peak velocity ≥ 3.0m/s) Aortic stenosis was found in 43 patients (7.8%). In patients who were not taking anti-osteoporotic drugs, P1NP was higher in the 2 ≥ leaflets calcification group than in the other groups (p < 0.01). TRACP-5b was not significantly different among the three groups (p = 0.15). ConclusionsDegenerative changes in the aortic valve were related to bone biomarker activation in osteoporotic hip fracture patients.

Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement.

Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.