Valvular Stenosis Research Articles

Norwood procedure for hypoplastic left heart syndrome associated with valvular pulmonary stenosis.

Association between hypoplastic left heart syndrome and valvular pulmonary stenosis is very rare. Severity of valvular pulmonary stenosis in this setting limits management options. Consequently, patients with this condition are considered poor candidates for Norwood stage one reconstruction. Herein, we describe a newborn with hypoplastic left heart syndrome and significantly dysplastic pulmonary valve who successfully underwent the Norwood procedure with neoaortic valve reconstruction. Therefore, the Norwood procedure with neoaortic valve reconstruction might be an option for this difficult condition.

Left ventricular rotational abnormalities in hemophilia-insights from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

Hemophilia is an X-linked inherited disorder primarily affecting males, its major types are type A (deficiency in factor VIII) and B (deficiency in factor IX), and is considered to be the most common severe congenital coagulation factor deficiency. The present study was designed to test whether any differences in left ventricular (LV) rotational mechanics could be demonstrated between male patients with hemophilia and healthy controls using three-dimensional speckle-tracking echocardiography (3DSTE)-derived virtual LV models. The present study consisted of 17 patients with hemophilia, however, 3 patients were excluded due to insufficient image quality. In the remaining patient population, 12 patients had hemophilia A and 2 patients had hemophilia B (mean age: 42.2±18.9 years, all males). The control group comprised 16 age-matched healthy subjects (46.0±5.9 years, all males). None of the routine two-dimensional echocardiographic data differ between patients with hemophilia and controls. None of the patients and controls showed ≥ grade 1 valvular regurgitations and had valvular stenoses. In one subject, the near absence of LV twist called as LV "rigid body rotation" could be detected, data of which were managed separately. While 3DSTE-derived apical LV rotation was 3.65 degrees, basal LV rotation proved to be 3.57 degrees leading to 0.08-degree LV apico-basal gradient suggesting counterclockwise LV "rigid body rotation". In the remaining patients, both LV apical rotation (7.25±6.20 vs. 10.39±4.16 degrees, P<0.02) and LV twist (10.24±5.60 vs. 14.38±3.93 degrees, P<0.003) showed significant impairment in patients with hemophilia. LV rotational abnormalities are present in hemophilia with reduced LV apical rotation and twist.

Anesthetic management of a child with Cornelia de Lange Syndrome undergoing open heart surgery: A case report

BACKGROUNDCornelia de Lange syndrome (CdLS) is a congenital multisystemic genetic disorder. The expected lifespan of children with this disorder has been prolonged in parallel with the advances in medicine in recent years. However, they still more frequently undergo cardiac surgery. There are some challenges for clinicians when faced with CdLS patients. We present the perioperative management of a child with CdLS undergoing open-heart surgery. CASE SUMMARYSevere pulmonic and subpulmonic valvular stenosis, enlargement of the right side of the heart, mild tricuspid regurgitation, atrial septal defect, and patent ductus arteriosus were diagnosed in a 14-month-old boy with manifested cyanosis, developmental delay, and malnutrition. Attempted balloon valvuloplasty was unsuccessful due to a severe stenotic pulmonary valve, therefore it was decided to perform an open surgical repair. Following a successful and uncomplicated intraoperative course, the patient was extubated on postoperative day 5, and adrenalin and dopamine infusions were gradually decreased and stopped on postoperative days 6 and 10, respectively. Moderate laryngomalacia and suboptimal vocal cord movements were diagnosed, and tracheotomy and percutaneous endoscopic gastrostomy were performed under general anesthesia in the same session at postoperative day 32. The patient was discharged on postoperative day 85 after a challenging postoperative period with additional airway and nutritional problems. CONCLUSIONThis is the first report of the perioperative anesthetic and clinical management of a CdLS patient undergoing open-heart surgery.

Identification of Rare Variants in Right Ventricular Outflow Tract Obstruction Congenital Heart Disease by Whole-Exome Sequencing.

BackgroundPulmonary atresia (PA) is a kind of congenital heart disease characterized by right ventricular outflow tract obstruction. It is divided into PA with intact ventricular septum (PA/IVS) whose favorable form is pulmonary valvular stenosis (PS), and PA with ventricular septal defect (PA/VSD) whose favorable form is tetralogy of Fallot (TOF). Due to limitations in genetics etiology, whole-exome sequencing (WES) was utilized to identify new variants associated with the diseases.MethodsThe data from PS-PA/IVS (n = 74), TOF-PA/VSD (n = 100), and 100 controls were obtained. The common sites between PS and PA/IVS, PA/VSD and TOF, were compared. The novel rare damage variants, and candidate genes were identified by gene-based burden analysis. Finally, the enrichment analysis of differential genes was conducted between case and control groups.ResultsSeventeen rare damage variants located in seven genes were predicted to be associated with the PS through burden analysis. Enrichment analysis identified that the Wnt and cadherin signaling pathways were relevant to PS-PA/IVS.ConclusionThis study put forth seven candidate genes (APC, PPP1R12A, PCK2, SOS2, TNR, MED13, and TIAM1), resulting in PS-PA/IVS. The Wnt and cadherin signaling pathways were identified to be related to PS-PA/IVS by enrichment analysis. This study provides new evidence for exploring the genetic mechanism of PS-PA/IVS.

Propofol‐dexmedetomidine continuous infusion in a dog with pulmonic stenosis undergoing balloon valvuloplasty

AbstractA 6‐month‐old, 4 kg, male pomeranian, was referred for investigations of a heart murmur found during a routine clinical examination. A severe valvular pulmonic stenosis was diagnosed and medical management with atenolol was started. One month later, the dog underwent percutaneous balloon valvuloplasty. Anaesthesia was maintained with propofol‐dexmedetomidine continuous infusion, and a minimally invasive cardiac output monitor was used to assess haemodynamic variations. Intraoperatively, lidocaine was started because the frequency of the premature ventricular complexes increased before ballooning. A reduction in pressure gradient across the pulmonic valve was achieved. No other intraoperative complications were recorded. Recovery from general anaesthesia was uneventful, and the dog was discharged from the hospital 26 hours following the procedure.

COMBINED SEVERE AORTIC AND PULMONARY VALVULAR STENOSIS IN A CHILD AND ITS MANAGEMENT: A CASE REPORT

Combined congenital aortic and pulmonary valvular stenosis is a rare congenital heart defect. Prevalence of severe combined valvular stenosis of aortic and pulmonary valve accounts about 0.01% and also has association with many syndromes. This combination presents unusual diagnostic as well as management problems. Apart from a few case reports, there is little in the literature on the combined stenosis of both semilunar valves and its management. We present this rare combination in a 9 year old boy which was promptly managed with the balloon valvoplasty without any complications in the same setting under local anesthesia with sedation.

Simplified art of balloon pulmonary valvuloplasty: Does the presence of mild supravalvular pulmonary stenosis preclude successful balloon pulmonary valvuloplasty?

We present a case of successful balloon pulmonary valvuloplasty (BPV) in a 37-year-old female with severe valvular pulmonary stenosis with peak gradient of 82 mmHg with history of exertional presyncope. The crux of our case was that patient also had associated mild supravalvular pulmonary stenosis which did not preclude a successful BPV outcome. The patient had rare Bombay negative blood group, and the requisite units were not available across all the blood banks in the state to subject the patient for surgical correction. Although the art of BPV is dying among budding young interventionists, this simple procedure is as good as surgical pulmonary valvotomy so far as the immediate and late outcome is concerned and the presence of mild supravalvular pulmonary stenosis does not preclude a successful outcome. Our case is a unique illustration of feasibility of successful balloon pulmonary valvuloplasty in the presence of associated mild supravalvular stenosis.

Intracardiac Repair in Late Adolescent and Adult Tetralogy of Fallot - Early and Midterm Results from a Tertiary Care Centre.

IntroductionIn developing countries like India, it is common for late presentation of Tetralogy of Fallot (TOF) patients to a hospital as compared to that of developed countries. The objective of this study is to analyze the surgical outcome of TOF patients with age > 15 years.MethodsThis is a retrospective descriptive study of the surgical outcomes of 45 adult patients undergoing correction for TOF. Epidemiology, symptomology, and preoperative evaluation were performed.ResultsMost of the patients were male (33 [73%]). The median age was 21 years. A total of 42 (93.33%) patients had subaortic ventricular septal defect (VSD), while three (6.6%) patients presented with doubly committed VSD. The most common type of right ventricular outflow tract (RVOT) obstruction was combined infundibular and valvular types, accounting for 34 cases (75.5%). Six patients had infundibular RVOT obstruction, while three patients (6.6%) had predominantly valvular pulmonary stenosis. We performed trans-right atrial repair in 33 patients. Right atrium-pulmonary artery approach was used in five patients (11.1%). The most common postoperative complication was right bundle branch block, seen in 14 patients, with a mortality rate of 2% in the early postoperative period. We achieved excellent early and midterm survival results and significant improvement in functions and disease-free quality of life.ConclusionIntracardiac repair in adult TOF can be performed with low mortality, less residual RVOT obstruction, and need for revision of RVOT far less frequent by using the Jhajhria Infundibular Resection Adequacy Assessment technique (JIRAAT) to assess for adequacy of infundibular resection.

Medical Decision Making for Cardiac MRI with CFD “Detection of Severe Stenosis Using a 5D Model of the Descending Aorta”

The aim of this study is to develop a reliable 5D (x, y, z, time, flow dimension) model for medical decision making. Sophisticated techniques for the assessment of serious stenosis were developed using time-dependent instantaneous pressure gradients through the aorta (flow rate, Reynolds number, velocity, etc.). A 74 cardiac MRI scan and 3057 scans were performed on a 10-year-old patient with congenital valve and valvular aortic stenosis on sensitive MRI and coarctation (operated and then dilated) in the sense of shone syndrome. The occlusion rate was estimated to be 80.5%. The stenosis area was approximately 15 mm long and 10 mm high. The fluid solver (NS) exhibited a significant shear stress of −3.735 × 10−5 Pa within the first 10 iterations. There was a significant drop in the flux mass of −0.0050 (kg/s), as well as high blood turbulence in vortex field lines and low geometry Reynolds cells. The fifth dimension was used for negative velocity prediction (−81.4 cm/s). The discoveries of the 5D aortic simulation are convincing based on the evaluation of its physical and biomedical features.

Ретроспективный анализ распространения типов врожденного стеноза легочной артерии у собак

Objective: to determine the occurrence and clinical characteristics of different types of PS (pulmonary stenosis) in dogs &#x0D; Reseach tasks: to identify the breed predisposition to PS, to study the clinical, echocardiographic and electrocardiographic characteristics of various types of PS and to analyse their dependence on the severity of the heart defect.&#x0D; Materials and methods: a retrospective analysis of Biocontrol veterinary clinic medical records throughout six years (2014–2020). Cardiological examination of dogs presented to the primary ambulatory appointment included physical examination, echocardiography using the Philips HD15 ultrasound system, radiography and electrocardiography.&#x0D; Animals: 31 dogs with isolated pulmonary artery stenosis (17 males and 14 females). Breeds: French Bulldog, English Bulldog, Yorkshire Terrier, German Spitz, American Pit Bull Terrier, Staffordshire Terrier, Toy Terrier, Cane Corso, Whippet, Biewer Yorkshire Terrier, Chihuahua, Entlebucher, German Boxer, East European Shepherd, American Bully.&#x0D; Results and discussion: 43 dogs with a PS were examined from 1 January 2014 to 31 December 2020. Of these, 31 dogs (72 %) with isolated PS and 12 dogs (28 %) with a combination of PS with other congenital heart defects. The most common combinations were PS with aortic stenosis (25 %) and PS with ventricular septal defect (25 %). The most common form of isolated PS was type A valve stenosis (68 %). Severe stenosis prevailed (58 %). The most common breeds were French Bulldogs (22.6 %), English Bulldogs (16.1 %) and Yorkshire Terriers (9.7 %). Males were more prevalent (55 %). 61 % of animals from the group of dogs with severe PS visited clinic because of signalment, and syncope was the most frequently reported symptom (28 %).&#x0D; The symptoms associated with congenital heart defect were not identified in the group of animals with moderate and mild degrees of PS. ECG showed that 100 % of dogs were diagnosed with sinus rhythm. Electrical right axis deviation of the heart was detected in 45 % of dogs. Direct dependency was between the severity of the stenosis and the severity of electrical right axis deviation. According to echocardiographic studies — 100 % of animals with severe and moderate stenosis and 14% with mild stenosis were diagnosed with concentric, eccentric or mixed forms of right ventricle myocardial hypertrophy, enlargement of the right atrial. Direct dependency is founded between the severity of stenosis, the type of right ventricle hypertrophy and the size of the right atrium.&#x0D; The more severe stenosis, the more mixed form of hypertrophy; increase of the right atrium was recorded in dogs with mixed right ventricular hypertrophy. Post-stenotic dilatation of the trunk and branches of the pulmonary artery was determined in all dogs with single right coronary artery type R2A.&#x0D; Conclusions: PS is most commonly found in French Bulldogs. The most common type of PS is type A valvular stenosis in the form of an isolated defect. Severe PS is prevalent. There is direct dependency is between the severity of the defect and the severity of right ventricular myocardial hypertrophy, the large size of the right atrium and electrical right axis deviation of the heart.

C69. Percutaneous Balloon Pulmonary Valvuloplasty for Critical Pulmonary Stenosis Baby as A Challenging Management in Resource-Limited Hospital: A Case Report

Abstract Background Severe or critical right ventricular outflow tract obstructions are life-threatening conditions. Percutaneous balloon pulmonary valvuloplasty is the preferred therapy for pulmonary valve stenosis. Case Summary A-50-day-old cyanotic baby girl, weighing 4.4 kg, was admitted to hospital with a bluish appearance insidiously progressing over the preceding 2 weeks. Transthoracic echocardiogram (TTE) revealed critical pulmonary valvular stenosis with pulmonary valve annulus diameter 7 mm, severe tricuspid regurgitation (TR), restrictive intraatrial mixing physiology, and an almost spontaneously closed Patent Ductus Arteriosus. The patient underwent percutaneous balloon pulmonary valvuloplasty (BPV). The available balloon, Tyshak mini balloon 9.0 mm x 20 mm, failed to across stenotic lession. It was replaced with coronary balloon 2 mm x 10 mm and inflated several times with a maximum pressure of 10 mmHg within 10 seconds. After the valve was adequately opened, the coronary balloon was replaced by previous Tyshak mini balloon. It was inflated once with pressure of 3 mmHg for 5 seconds. Successful dilatation is indicated by the disappearance of the waist around the balloon under cineangiography. RV-PA gradient decreased from 67 mmHg to 38 mmHg, a 43% reduction. After the procedure, the patient was no longer cyanotic. TTE after BPV demonstrated no pulmonary stenosis, TR TVG decreased from 100 mmHg to 20 mmHg, and no pulmonary regurgitation. Discussion Our successful results suggest that percutaneous balloon pulmonary valvuloplasty is a potential and safe intervention for babies with critical Pulmonal Stenosis that was conducted in resource-limited hospital.

C89. Simultaneous Aortic Stenosis (AS) and Pulmonary Stenosis (PS) in A Middle-Aged Man: A Rare Case Report

Abstract Background Combined valvular lesions is very rare. Only 16 cases of combined valvular stenosis of the aortic and pulmonary valves have been reported. Failure to recognize and adequately correct both lesions may be catastrophic for the patient. Case Illustration A 38-year-old male came to the outpatient department with shortness of breath, fatigue, and swollen ankles. He had a short posture, broad forehead, bitemporal narrowing, broad nasal tip, long philtrum, wide mouth, and large earlobes. Cardiac examination revealed systolic murmurs over the pulmonary valve and at the aortic valve radiating to the apex (galliverdin phenomenon), rales in both lungs, and bilateral ankle edema. Electrocardiogram revealed sinus rhythm, extreme axis, RA enlargement, RBBB, and bifascicular block. Chest radiograph showed cardiomegaly, pulmonary edema, and left pleural effusion. Echocardiography demonstrated a dilated LA and concentric LVH with good LV function, HF/HG severe AS, a bicuspid aortic valve causing moderate aortic regurgitation, mild mitral regurgitation, mild tricuspid regurgitation, and severe valvular or supravalvular PS with RV hypertrophy. The patient was administered diuretics, a beta blocker, and an anti-platelet. Discussion Most patients with combined aortic and pulmonary obstruction at sub-valvular level have hypertrophic cardiomyopathy. Cases with both aortic and pulmonary valve stenoses are exceedingly rare. The age of presentation ranges from neonate to 55 years. It is more common in males. Most patients present with murmur since birth, dyspnea, and fatigue. Our patient is suspected to have Williams syndrome based on the physical appearance and cardiac examination findings.

C89. Simultaneous Aortic Stenosis (AS) and Pulmonary Stenosis (PS) in A Middle-Aged Man: A Rare Case Report

Abstract Background Combined valvular lesions is very rare. Only 16 cases of combined valvular stenosis of the aortic and pulmonary valves have been reported. Failure to recognize and adequately correct both lesions may be catastrophic for the patient. Case Illustration A 38-year-old male came to the outpatient department with shortness of breath, fatigue, and swollen ankles. He had a short posture, broad forehead, bitemporal narrowing, broad nasal tip, long philtrum, wide mouth, and large earlobes. Cardiac examination revealed systolic murmurs over the pulmonary valve and at the aortic valve radiating to the apex (galliverdin phenomenon), rales in both lungs, and bilateral ankle edema. Electrocardiogram revealed sinus rhythm, extreme axis, RA enlargement, RBBB, and bifascicular block. Chest radiograph showed cardiomegaly, pulmonary edema, and left pleural effusion. Echocardiography demonstrated a dilated LA and concentric LVH with good LV function, HF/HG severe AS, a bicuspid aortic valve causing moderate aortic regurgitation, mild mitral regurgitation, mild tricuspid regurgitation, and severe valvular or supravalvular PS with RV hypertrophy. The patient was administered diuretics, a beta blocker, and an anti-platelet. Discussion Most patients with combined aortic and pulmonary obstruction at sub-valvular level have hypertrophic cardiomyopathy. Cases with both aortic and pulmonary valve stenoses are exceedingly rare. The age of presentation ranges from neonate to 55 years. It is more common in males. Most patients present with murmur since birth, dyspnea, and fatigue. Our patient is suspected to have Williams syndrome based on the physical appearance and cardiac examination findings.

C69. Percutaneous Balloon Pulmonary Valvuloplasty for Critical Pulmonary Stenosis Baby as A Challenging Management in Resource-Limited Hospital: A Case Report

Abstract Background Severe or critical right ventricular outflow tract obstructions are life-threatening conditions. Percutaneous balloon pulmonary valvuloplasty is the preferred therapy for pulmonary valve stenosis. Case Summary A-50-day-old cyanotic baby girl, weighing 4.4 kg, was admitted to hospital with a bluish appearance insidiously progressing over the preceding 2 weeks. Transthoracic echocardiogram (TTE) revealed critical pulmonary valvular stenosis with pulmonary valve annulus diameter 7 mm, severe tricuspid regurgitation (TR), restrictive intraatrial mixing physiology, and an almost spontaneously closed Patent Ductus Arteriosus. The patient underwent percutaneous balloon pulmonary valvuloplasty (BPV). The available balloon, Tyshak mini balloon 9.0 mm x 20 mm, failed to across stenotic lession. It was replaced with coronary balloon 2 mm x 10 mm and inflated several times with a maximum pressure of 10 mmHg within 10 seconds. After the valve was adequately opened, the coronary balloon was replaced by previous Tyshak mini balloon. It was inflated once with pressure of 3 mmHg for 5 seconds. Successful dilatation is indicated by the disappearance of the waist around the balloon under cineangiography. RV-PA gradient decreased from 67 mmHg to 38 mmHg, a 43% reduction. After the procedure, the patient was no longer cyanotic. TTE after BPV demonstrated no pulmonary stenosis, TR TVG decreased from 100 mmHg to 20 mmHg, and no pulmonary regurgitation. Discussion Our successful results suggest that percutaneous balloon pulmonary valvuloplasty is a potential and safe intervention for babies with critical Pulmonal Stenosis that was conducted in resource-limited hospital.

Abstract 9316: Role of Bile Acids in Calcific Aortic Valve Stenosis

Introduction: Calcific aortic valve stenosis (CAVS) is the most common valvular pathology seen in the Western world. Patients with symptomatic CAVS have a poor prognosis with the only therapy being valvular intervention. There is currently no known mechanism and therefore medical therapy for controlling the progression of CAVS. Our recent metabolomics analysis of human aortic valve tissue identified bile acid biosynthesis as a potential mitigator of valvular stenosis. In this study, utilizing a targeted metabolomics approach, we investigated the role of valvular and plasma bile acids in the degree of severity and the rate of progression of CAVS. Methods: Human aortic valves from 102 patients who underwent AVR surgery were collected. Bile acid profiling (80 bile acids) of valvular tissues along with 19 plasma samples was carried out by a targeted mass spectrometry approach. The explanted aortic valves were graded from mild, moderate, and severe categories based on mean pressure gradient (MPG) and valvular calcification score by transthoracic echocardiography. CAVS progression was determined in a subset of our cohort (N=49), categorizing patients as “fast” and “slow” progressors based on echocardiography measures of the peak jet velocity. Results: Bile acids nordeoxycholic acid, norcholic acid, and glycodeoxycholic acid were significantly altered (p&lt;0.05) across CAVS severity stages based on MPG. Similarly, six bile acids namely nordeoxycholic acid, norcholic acid, 3β,7α-diOH-5-cholestenoic acid, 3β-OH-5-cholestenoic acid, glycolithocholic acid, and glycoallocholic acid were significantly altered (p&lt;0.05) based on valvular calcification scores. Taurodeoxycholic acid showed a significant difference (p&lt;0.05) between the slow and fast progressors. Additionally, valvular tissue levels of these bile acids correlate with plasma levels. Conclusions: In this report, we present a potential novel mechanistic pathway correlating bile acids with the pathogenesis of CAVS. Our goal is to validate these findings in a large cohort of patients with CAVS. Given that bile acid modulating therapies are already used in clinical practice, this represents a potential novel therapeutic target to prevent or delay the progression of CAVS.

Pericardial tamponade during balloon pulmonary valvuloplasty in a dog

AbstractA 4‐month‐old entire male Coton de Tulear dog was referred for balloon valvuloplasty for treatment of severe valvular pulmonic stenosis. During the procedure, when attempting to pass the guide wire into the ventricle, the dog developed cardiac arrest. After initial resuscitation with chest compressions, manual ventilation, adrenaline and intravenous fluids, focused cardiac ultrasound revealed pericardial effusion and cardiac tamponade. Pericardiocentesis resolved the haemodynamic emergency. This case report should raise awareness of pericardial tamponade as a possible complication during pulmonic stenosis balloon valvuloplasty. It describes the clinical signs observed during anaesthesia as well as how to treat it with a positive outcome.

Lipoprotein(a) and Cardiovascular Disease: A Missing Link for Premature Atherosclerotic Heart Disease and/or Residual Risk.

Lipoprotein(a) or lipoprotein "little a" [Lp(a)] is an under-recognized causal risk factor for cardiovascular (CV) disease (CVD), including coronary atherosclerosis, aortic valvular stenosis, ischemic stroke, heart failure, and peripheral arterial disease. Elevated plasma Lp(a) (≥50 mg/dL or ≥100 nmol/L) is commonly encountered in almost 1 in 5 individuals and confers a higher CV risk compared with those with normal Lp(a) levels, although such normal levels have not been generally agreed upon. Elevated Lp(a) is considered a cause of premature and accelerated atherosclerotic CVD. Thus, in patients with a positive family or personal history of premature coronary artery disease (CAD), Lp(a) should be measured. However, elevated Lp(a) may confer increased risk for incident CAD even in the absence of a family history of CAD, and even in those who have guideline-lowered LDL cholesterol (<70 mg/dL) and continue to have a persisting CV residual risk. Thus, measurement of Lp(a) will have a significant clinical impact on the assessment of atherosclerotic CVD risk, and will assume a more important role in managing patients with CVD with the advent and clinical application of specific Lp(a)-lowering therapies. Conventional therapeutic approaches like lifestyle modification and statin therapy remain ineffective at lowering Lp(a). Newer treatment modalities, such as gene silencing via RNA interference with use of antisense oligonucleotide(s) or small interfering RNA molecules targeting Lp(a), seem very promising. These issues are herein reviewed, accumulated data are scrutinized, meta-analyses and current guidelines are tabulated, and Lp(a)-related CVDs and newer therapeutic modalities are pictorially illustrated.

Clinical applicability of echocardiographic strict negative criteria for suspected infective endocarditis

Abstract Introduction Infective endocarditis (IE) is an uncommon but potentially lethal disease that requires a timely diagnosis. Echocardiography has a pivotal role in EI diagnosis, but this may lead to an overuse of this technology in clinical daily practice, and it is unclear which patients can benefit from a follow-up study if the initial transthoracic echocardiogram (TTE) shows no signs of IE. The strict negative criteria (good ultrasound quality and no high-risk features such as significant valvular regurgitations or stenosis, pericardial effusion or intracardiac devices) have been recently proposed to avoid unnecessary follow-up echocardiograms. Purpose The objective of this study is to review the contemporary, real-world use of echocardiography in patients with suspected IE and analyze the potential applicability of the strict negative criteria. Methods We retrieved all the echocardiograms that were performed in our center for suspected or confirmed IE between January 2014 and December 2018. We defined different groups according to the strict negative criteria and reviewed the electronic clinical history to check if a definitive diagnosis of IE was established or not. Results We included a total of 905 TTEs. 451 (49.8%) of them fulfilled the strict negativity criteria (Group 1). In this group, IE was seldom diagnosed (n=4, 0.9%). In 338 (37.4%) patients no signs of IE were evident but they didn't fulfill the strict negative criteria (Group 2). A follow-up echocardiogram and definitive diagnosis of IE were more frequent (n=48, 14.2% and n=20, 5.9%). Finally, in 116 (12.8%) patients the initial TEE showed typical or suggestive signs of IE, in whom the diagnosis was confirmed in 48 (41.4%). The independent predictors of follow-up echocardiography were the previous history of valvular heart disease (HR 2.38 [1.39–3.89], p=0.001) or cancer (HR 0.47 [0.27–0.84], p=0.01), positive blood cultures for Enterococcus (HR 5.01 [2.34–10.73], p&amp;lt;0.001), methicillin-sensitive Staphylococcus aureus (HR 2.8 [1.27–6.17], p=0.011) or Streptococcus (HR 2.36 [1.12–5], p=0.024), and the presence of typical or suggestive signs of infective endocarditis on initial TTE (HR 13.77 [8.6–22.05], p&amp;lt;0.001). A definitive diagnosis of IE was confirmed in a minority of the study population (n=72, 8%). Only one readmission for underdiagnosis of IE during index hospitalization was noted on Group 2. Conclusions In a real-life, observational setting only a minority of patients in whom IE was suspected had a definite diagnosis. An initial TTE for suspected IE fulfilling the strict negative criteria predicts both a low probability of requesting a follow-up study and of a definitive diagnosis of IE. Further research should be performed to rationalize echocardiogram requests for suspected IE. Funding Acknowledgement Type of funding sources: None.

Predictors of increased mortality in untreated moderate aortic stenosis

Abstract Background The natural history of native valvular moderate aortic stenosis (AS) is poorly understood. Purpose To examine the prognosis of patients with native valvular moderate AS, and identify high risk-features associated with increased mortality. Methods Natural language processing of electronic health records in the claims-linked Optum® database (2011–2018) from over 200 hospitals and 7000 clinics in the United States identified severity of AS (mild/moderate/severe) from echocardiograms and physician notes of patients more than 65 years old. Our cohort included 30,204 patients (3594 with mild, 9938 with moderate, and 16672 with severe AS). We used competing risk Kaplan-Meier analysis to compare 5-year mortality (obtained from the Social Security Death Masterfile) between the different AS severity groups adjusted for demographics and comorbidities, censoring for aortic valve replacement. The relationship between AS severity and survival was examined during median 1049 days (interquartile range: 597 to 1652 days) of follow-up. We performed Fine-Gray modeling to examine risk factors associated with long-term mortality in patients with moderate AS. Results A higher proportion of comorbidities like atrial fibrillation, diabetes, and coronary artery disease were observed with increasing severity of AS (Figure 1). After adjustment, compared with mild AS (5-year mortality: 31.6%), patients with untreated moderate (5-year mortality: 40.0%, HR 1.34, 95% CI 1.25 – 1.44) and untreated severe AS (5-year mortality: 51.1%, HR 1.88, 95% CI 1.75– 2.01) have increasing risk of long-term mortality (Figure 2). Significant predictors of 5-year mortality in patients with moderate AS include older age (HR 1.38, 95% CI 1.29 –1.47), male sex (HR 1.21, 95% CI 1.15 – 1.27), heart failure (HR 1.37, 95% CI 1.29 – 1.44), coronary artery disease (HR 1.20, 95% CI 1.13 – 1.27), and atrial fibrillation (HR 1.08, 95% CI 1.02 – 1.14). In a subcohort of 5189 patients for whom left ventricular ejection fraction (LVEF) information was available, reduced LVEF was associated with worse long-term mortality (LVEF&amp;lt;40%: HR 1.17, 95% CI 1.05 –1.31; LVEF 40–50%: HR 1.08, 95% CI 0.97 –1.20). Conclusion Our findings suggest that moderate AS is associated with poor long-term survival with higher risk associated with LVEF &amp;lt;40%, and comorbidities including heart failure, coronary artery disease and atrial fibrillation. Whether patients with moderate AS, particularly with high-risk features, benefit from treatment remains unknown. Funding Acknowledgement Type of funding sources: None. Baseline CharacteristicsAdjusted KM curves with Competing Risk

Circulating metabolome does not predict development of aortic stenosis

Abstract Background Calcific aortic valve disease (CAVD) is the most common valvular heart disease in Western world. CAVD is ranging from mild aortic valve sclerosis to severe obstructive aortic stenosis (AS). The development of AS has been associated with several risk factors including age, sex and hypertension. However, there is limited knowledge about factors that predict the development of aortic stenosis. Purpose We investigated if the circulating metabolite profile can predict the development of aortic stenosis in Finnish males. Methods We did a non-targeted LC-MS metabolomics analysis to baseline (1984–1989) serum samples from a prospective population-based Kuopio Ischemic Heart Disease risk factor study (KIHD) cohort of 2682 random Finnish males aged from 42 to 60 years. During the follow-up (until year 2020), 53 subjects developed either moderate (peak flow gradient 36–64mmHg or mean flow gradient 20–40mmHg) or severe aortic valvular stenosis (peak flow gradient over 64mmHg or mean gradient over 40mmHg). The AS patients were collected from the KIHD database using appropriate ICD-10 -codes for aortic valvular disease (from baseline to the end of the year 2017) and the diagnosis was checked manually using hospital medical records of the individuals. Results The AS patients seemed to have altered lipid metabolism and possibly altered composition of gut microbiota, since several acylcarnitines (e.g. octanoylcarnitine [Cohen's d=−0.40], decanoylcarnitine [d=−0.43], layroylcarnitine [d=−0.41], and oleoylcarnitine [d=−0.40]), and branched chain amino acids (BCAA, e.g. leucine [d=0.39], and isoleucine [d=0.49]) had p-values below 0.05. However, after correction for multiple testing, there were no significant differences between the cases and controls. Conclusions The present preliminary results, in need of verification with a larger set of samples, suggest that subjects, who will later develop AS might have reduced levels of acylcarnitines and increased levels of BCAA when compared to matched controls. However, these changes do not have large effects sizes and are likely not good candidates for biomarkers to predict future diagnosis of AS. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Finnish Cultural Foundation, The Finnish Foundation for Cardiovascular Research.