Concurrence of supravalvular aortic stenosis and peripheral pulmonary stenosis in three generations of a family: A form of arterial dysplasia

Isolated supravalvular aortic stenosis (SVAS) commonly is an autosomal dominant trait; it may also occur in the Williams syndrome (WS). While peripheral pulmonary stenosis (PPS) can occur in the same individual with familial isolated SVAS, concurrence of these lesions in different relatives of a family is uncommon. We describe five affected individuals in one family; three had isolated SVAS, one had isolated PPS, and one had SVAS and PPS. Based on this family and review of literature, we suggest that SVAS is a form of arterial dysplasia encompassing PPS in its spectrum. It is developmentally distinct from other left heart obstructive lesions that are hypothesized to be related to blood flow abnormalities in the developing embryo. We also conclude that the clinical disorder in this family represents one that is distinct from WS. © 1993 Wiley-Liss, Inc.     

Regression of valvular aortic stenosis due to homozygous familial hypercholesterolemia following plasmapheresis

Summary A 39-year-old male with homozygous familial hypercholesterolemia confirmed by tissue culture suffered from mild aortic insufficiency and valvular stenosis with a gradient of 20 mm Hg across the aortic valve. Plasmapheresis carried out every 2 weeks for 4 years resulted in a marked reduction in the serum cholesterol level and in a regression of the valvular stenosis, as shown by echocardiography and by left heart catheter.Abbreviations ECG electrocardiogram - LVH left ventricular hypertrophy - USP US pharmacopoea These studies were partly supported by a grant from the Deutsche Forschungsgemeinschaft     

Cytomegalic type of congenital adrenal hypoplasia due to autosomal recessive inheritance

Five sets of monozygotic (MZ) twins with Williams–Beuren syndrome (WBS) have been reported so far. We report on an additional pair of mz twins concordant for WBS but variable expression for the syndrome. Although both faces look different monozygosity of the twins was proven by DNA fingerprint analysis. HLA, and blood group pattern. Both girls had the typical facial appearance with strabismus. Both had developmental delay, mild supravalvular aortic stenosis (SVAS), hypoplasia of both pulmonary arteries and multiple peripheral pulmonary stenoses, and inguinal hernia. Unilateral renal agenesis was seen in one of the twins. In addition the pedigree pointed to a second disorder with probably autosomal dominant inheritance. Both twins had a cleft palate, but their father had cleft lip and the grandfather as well as the greatgrandfather had cleft lip/palate. Findings of linkage analysis in pedigrees with nonsyndromic oral facial cleft were taken to suggest that a major locus for nonsyndromal oral facial cleft is located on the distal portion of chromosome 6. Linkage studies could serve as a starting point to examine a locus associated with WBS. Our observation and reports on the literature support the hypothesis that WBS is a genetic disorder. © 1993 Wiley-Liss, Inc.     

Novel ELN mutation in a family with supravalvular aortic stenosis and intracranial aneurysm

Pathogenic germline mutations in ELN can be detected in patients with supravalvular aortic stenosis. The mutation might occur de novo or be inherited following an autosomal dominant pattern of inheritance. In this report we describe a three-generation family suffering from supravalvular aortic stenosis, various other arterial stenoses, sudden death, and intracranial aneurysms. A frameshift mutation in exon 12, not described before, was detected in the affected family members. This report emphasises the importance of family history, genetic counselling, and demonstrates the great variability in the phenotype within a single SVAS family.     

大动脉转位患儿行大动脉调转术后的中长期随访

目的 探讨大动脉调转术（ASO）治疗大动脉转位（TGA）患儿的中、长期疗效,及观察术后主动脉瓣反流及吻合口梗阻情况.方法 以2003年1月至2009年12月在本研究所行ASO的TGA患儿166例为研究对象,按室间隔是否完整分为TGA合并室间隔缺损组（Ⅰ组）94例、TGA并室间隔完整组（Ⅱ组）72例.所有术后生存患儿均进行随访,超声心动图观察主动脉瓣反流及吻合口梗阻情况.结果 Ⅰ组和Ⅱ组分别有14例和10例患儿住院死亡.所有术后生存患儿平均随访时间（57.41±15.45）个月.随访发现51例患儿出现主动脉瓣反流,多发生于术后3～5年.相关性分析显示主动脉瓣反流面积与随访时间呈正相关（r=0.436,P=0.028）.所有随访病例没有出现主动脉吻合口梗阻（压差＞50 mm Hg,1 mm Hg=0.133 kPa）.Ⅰ组和Ⅱ组肺动脉吻合口梗阻（压差＞50 mm Hg）的发生率分别为6.25％（5/80）和3.23％ （2/62）.结论 ASO是治疗TGA的理想术式,具有良好的中、长期疗效.术后定期随访有助于改善患儿的长期预后.     

Supravalvular aortic stenosis cosegregates with a familial 6;7 translocation which disrupts the elastin gene

Supravalvular aortic stenosis (SVAS) is an autosomal dominant disorder characterized by abnormalities of development of the great vessels. SVAS is also commonly part of Williams syndrome. Linkage to the elastin gene on chromosome 7q11 has recently been reported in two kindreds with SVAS. Previous reports of patients with 7q11 deletions have noted great vessel abnormalities in some. We report on a family in which SVAS is cosegregating with a balanced reciprocal translocation, t(6:7) (p21.1;q11.23), providing further evidence that SVAS is the result of mutation of elestin at 7q11.23 region. The propositus of the translocation family has some minor anomalies which occur in Williams syndrome, Suggesting that elestin abnormalities may cause some of the abnormalities found in Williams syndrome. © 1993 Wiley-Liss, Inc. © 1993 Wiley-Liss, Inc.     

Spectrum of elastin sequence variants and cardiovascular phenotypes in 49 patients with Williams–Beuren syndrome

Haploinsufficiency of the elastin gene (ELN) on 7q11.23 is responsible for supravalvular aortic stenosis (SVAS) and other arteriopathies in patients with Williams–Beuren syndrome (WBS). These defects occur with variable penetrance and expressivity, but the basis of this is unknown. To determine whether DNA variations in ELN could serve as genetic modifiers, we sequenced the 33 exons and immediately surrounding sequence of the ELN gene (9,455 bp of sequence) in 49 DNAs from patients with WBS and compared cardiovascular phenotypes. Four missense, and four novel intronic variants were identified from a total of 24 mostly intronic single nucleotide variations and one indel. Two missense changes were present in one patient each, one published, p.Gly610Ser in exon 27 (MAF, 0.003) and one novel, p.Cys714Tyr, in exon 33 (MAF, 0.001), were rare in the general population. To identify a statistical association between the variants identified here and cardiovascular phenotypes a larger cohort would be needed. © 2013 Wiley Periodicals, Inc.     

Williams-Beuren syndrome: phenotypic variability and deletions of chromosomes 7, 11, and 22 in a series of 52 patients.

Fluorescence in situ hybridisation (FISH) and conventional chromosome analysis were performed on a series of 52 patients with classical Williams-Beuren syndrome (WBS), suspected WBS, or supravalvular aortic stenosis (SVAS). In the classical WBS group, 22/23 (96%) had a submicroscopic deletion of the elastin locus on chromosome 7, but the remaining patient had a unique interstitial deletion of chromosome 11 (del(11)(q13.5q14.2)). In the suspected WBS group 2/22 (9%) patients had elastin deletions but a third patient had a complex karyotype including a ring chromosome 22 with a deletion of the long arm (r(22)(p11-->q13)). In the SVAS group, 1/7 (14%) had an elastin gene deletion, despite having normal development and minimal signs of WBS. Overall, some patients with submicroscopic elastin deletions have fewer features of Williams-Beuren syndrome than those with other cytogenetic abnormalities. These results, therefore, emphasise the importance of a combined conventional and molecular cytogenetic approach to diagnosis and suggest that the degree to which submicroscopic deletions of chromosome 7 extend beyond the elastin locus may explain some of the phenotypic variability found in Williams-Beuren syndrome.     

一例表现为主动脉瓣狭窄的非典型Williams-Beuren综合征患儿的遗传学诊断及分析

目的对1例主动脉瓣狭窄的患儿进行遗传学诊断,分析其发病机制。方法采用常规G显带染色体分析、微阵列比较基因组杂交(array comparative genomic hybridization,aCGH)及多重连接探针扩增(multiplex ligation-dependent probe amplification,MLPA)技术分析患儿及其父母的染色体核型和基因组拷贝数变异。结果患儿及其父母的外周血染色体核型均未见异常。aCGH检测显示患儿7q11.23区存在278 kb杂合缺失,与Williams-Beuren综合征(Williams-Beuren syndrome,WBS)关键区部分重叠,涉及WBS的关键致病基因之一ELN。MLPA检测证实患儿存在上述缺失,患儿父母未发现染色体微重复/微缺失。结论患儿7q11.23区杂合缺失为新发突变。ELN基因单倍剂量不足可能是其发生主动脉瓣狭窄的原因,诊断为非典型WBS。     

Prognostic value of low-dose dobutamine stress echocardiography in patients with aortic stenosis and impaired left ventricular function

Introduction

The aim of this multicenter, prospective study was to evaluate the long-term prognostic value of low-dose dobutamine stress echocardiography (LDDSE) in patients with aortic stenosis (AS) and depressed left ventricular (LV) function.

Material and methods

The study group comprised 39 patients (34 male, mean age 59 ±13 years) with AS (peak gradient > 25 mm Hg), LV ejection fraction (LVEF) ≤ 45% and low transaortic gradient (peak gradient ≤ 45 mm Hg, mean gradient ≤ 35 mm Hg). The qualification for subsequent therapeutic procedures was based on generally accepted indications. All patients underwent LDDSE and coronary angiography. Twelve months after LDDSE patients underwent control resting echocardiography and clinical evaluation.

Results

Twenty-seven (69.2%) patients had preserved contractile reserve. In this subgroup, true-severe AS was diagnosed in 12 patients, whereas pseudo-severe AS was found in 15 patients. Nine patients with true-severe AS, 2 patients with pseudo-severe AS and 7 patients without contractile reserve were referred for surgical treatment. The independent risk factors of death during follow-up were: aortic valve area (AVA) at peak stress < 0.8 cm² (OR 1.4; p = 0.003) and LVEF at rest < 35% (OR 6.8; p = 0.05). The independent risk factors of composite end-point (death or myocardial infarctions or pulmonary edema) were: AVA at stress < 0.8 cm² (OR 4.0; p = 0.03), absence of AVA increase during LDDSE (OR 5.7; p = 0.005), absence of contractile reserve (OR 4.5; p = 0.01) and presence of significant CAD (OR 6.9; p = 0.02).

Conclusions

In patients with AS and depressed LVEF, LDDSE is a useful tool for long-term risk stratification.     

The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome

The Williams-Beuren syndrome (WBS) is a complex developmental disorder with multisystemic manifestations including supravalvular aortic stenosis (SVAS), a so-called elfin face, a hoarse voice, and a specific cognitive phenotype. Most WBS patients have a >1 Mb deletion on one of their chromosomes 7 in q11 but except for elastin, whose haploinsufficiency causes the cardiovascular malformations, it is unknown which genes in the deletion area contribute to the phenotype. We have investigated a family with a cytogenetically balanced translocation t(7;16)(q11.23;q13) in which affected individuals manifested a broad spectrum of clinical phenotypes ranging from a hoarse voice as the only feature to the full WBS phenotype. Molecular cytogenetic and DNA sequence analyses of the translocation breakpoint showed that the cytogenetic rearrangement disrupts the elastin gene locus within intron 5 in the exact same manner in all translocation carriers. The recently described large inversion of the 7q11.23 region was not present in this family. Our data demonstrate that disruption of the elastin gene by a translocation breakpoint may cause classical WBS, atypical WBS, SVAS, or no recognisable phenotype, and provide a clear example for extensive phenotypic variability associated with a position effect in humans.     

Surgical repair of congenital supravalvular aortic stenosis in adult

Supravalvular aortic stenosis is a rare congenital cardiac anomaly occurring mainly as a part of Williams-Beuren syndrome. Aortic narrowing above the level of the aortic valve causes obstruction of the left ventricular outflow tract, and a pressure gradient between the left ventricle and the aorta causes left ventricle hypertrophy. We report here a case of a 22-year-old man who underwent extended patch aortoplasty because of supravalvular aortic stenosis accompanying Williams-Beuren syndrome. He was in New York Heart Association functional class III with localized hourglass type supravalvular aortic stenosis. Related to arterial hypertension he was in a cardiac decompensation. Mean pressure gradient was 73 mm Hg and maximum gradient 104 mm Hg. Electrocardiography indicated left ventricle hypertrophy, which was also seen in x-ray, as heart enlargement. We successfully treated this patient with extended patch aortoplasty and immediate postoperative echocardiography showed reduction of gradient. Good surgical outcome of congenital supravalvular aortic stenosis in adults can be achieved with this treatment. This technique provides symmetric reconstruction of the aorta with good postoperative results and no gradient across aortic valve and aortic valve insufficiency remains, providing excellent long-term relief of localized supravalvular gradients and preservation of aortic valve competence.     

Cardiovascular manifestations in 75 patients with Williams syndrome

Objective: The prevalence and types of various cardiovascular diseases in different age groups as well as the outcomes of cardiac surgery and other interventions were assessed in a population of 75 Williams syndrome (WS) patients aged 4 months to 76 years (median 22.7 years).

Study design: The diagnosis of WS was in each case confirmed by the clinical phenotype and by a FISH test showing elastin hemizygosity. Clinical and operative data were collected from all hospitals where the patients had been treated.

Results: Cardiovascular symptoms were evident in 35 of 75 (47%) WS children at birth. During follow up, 44 of 75 (53%) WS patients were found to have cardiovascular defects. Among them, the definitive diagnosis was made before 1 year of age in 23 (52%) infants, between 1 year and 15 years of age in 14 (32%) children, and older than 15 years of age in 7 (16%) adults. Multiple obstructive cardiovascular diseases were found in six infants. Supravalvular aortic stenosis (SVAS) was diagnosed in 32/44 (73%), pulmonary arterial stenosis (PAS) in 18/44 (41%), aortic or mitral valve defect in 5/44 (11 %) of cases, and tetralogy of Fallot in one (2%) case. Altogether, 17/44 (39 %) underwent surgery or intervention. Surgery was most frequently performed in the infant group (6% v 21% v 0%, p=0.004). After 1 year of age, seven patients underwent SVAS relief and two cases PAS relief. Postoperatively there was no mortality (median follow up time 6.9 years). Arterial hypertension was found in 55% of adults. In three adults, arterial vasculopathy was not diagnosed until necropsy.

Conclusions: Our data indicate the following in WS. Cardiac symptoms are common in neonates. Heart disease diagnosed in infancy frequently requires operation. After 1 year of age, PAS tends to improve and SVAS to progress. Life long cardiac follow up is necessary because of the risks of developing vasculopathy or arterial hypertension.

     

Prognostic Factors for Tracheal Restenosis after Stent Removal in Patients with Post-Intubation and Post-Tracheostomy Tracheal Stenosis

PurposeLong-term tracheal stent placement can increase the risk of stent-related complications; hence, removal of the stent after stabilization is attempted. However, little evidence has been established regarding the risk factors for tracheal restenosis. We aimed to identify the risk factors for tracheal restenosis in patients with post-intubation tracheal stenosis (PITS) and post-tracheostomy tracheal stenosis (PTTS).Materials and MethodsWe retrospectively analyzed patients with PITS and PTTS between January 2004 and December 2019. Patients were classified into a success or failure group according to treatment outcomes. Patients with successful stent removal were defined as patients who did not require additional intervention after stent removal during the follow-up period. Multiple logistic regression analysis was performed to identify the factors associated with tracheal restenosis.ResultsAmong 269 stented patients, 130 patients who had removed the stent were enrolled in this study. During the follow-up period, 73 (56.2%) patients had a stable clinical course; however, 57 (43.8%) patients had restenosis. The proportion of trauma-induced intubation was higher in the success group than in the failure group (p=0.026), and the median stent length was shorter in the success group (45 mm) than in the failure group (50 mm, p=0.001). On multivariate analysis, trauma-induced intubation [adjusted odds ratio (aOR), 0.329; 95% confidence interval (CI), 0.117–0.927; p=0.036], and stent length <50 mm (aOR, 0.274; 95% CI, 0.130–0.578; p=0.001) were associated with a decreased risk of restenosis.ConclusionTrauma-induced intubation and stent length were associated with successful stent removal.     

Depressed Systemic Arterial Compliance is Associated with the Severity of Heart Failure Symptoms in Moderate-to-Severe Aortic Stenosis: a Cross-Sectional Retrospective Study

Background: Patients with aortic stenosis (AS) may develop heart failure even in the absence of severe valve stenosis. Our aim was to assess the contribution of systemic arterial properties and the global left ventricular afterload to graded heart failure symptoms in AS.Methods: We retrospectively reviewed medical records of 157 consecutive subjects (mean age, 71±10 years; 79 women and 78 men) hospitalized owing to moderate-to-severe degenerative AS. Exclusion criteria included more than mild aortic insufficiency or disease of another valve, atrial fibrillation, coronary artery disease, severe respiratory disease or anemia. Heart failure symptoms were graded by NYHA class at admission. Systemic arterial compliance (SAC) and valvulo-arterial impedance (Zva) were derived from routine echocardiography and blood pressure.Results: Sixty-one patients were asymptomatic, 49 presented mild (NYHA II) and 47 moderate-to-severe (NYHA III-IV) heart failure symptoms. Mild symptoms were associated with lower SAC and transvalvular gradients, while more severe exercise intolerance coincided with older age, lower systolic blood pressure, smaller aortic valve area and depressed ejection fraction. By multiple ordinal logistic regression, the severity of heart failure symptoms was related to older age, depressed ejection fraction and lower SAC. Each decrease in SAC by 0.1 ml/m² per mmHg was associated with an increased adjusted odds ratio (OR) of a patient being in one higher category of heart failure symptoms graded as no symptoms, mild exercise intolerance and advanced exercise intolerance (OR: 1.16 [95% CI, 1.01-1.35], P=0.045).Conclusions: Depressed SAC may enhance exercise intolerance irrespective of stenosis severity or left ventricular systolic function in moderate-to-severe AS. This finding supports the importance of non-valvular factors for symptomatic status in AS.     

一个先天性主动脉瓣上狭窄家系的分子遗传性分析

目的 检测一个临床诊断为"先天性升主动脉狭窄"家系患者的基因组拷贝数变异,明确其发病的遗传学基础.方法 以一个先天性升主动脉狭窄家系为研究对象,收集患儿及其患病父亲、正常母亲外周血标本,常规提取基因组DNA.应用Affymetrix人类全基因组SNP 6.0芯片对患儿及1例正常健康对照个体进行检测,应用实时定量PCR(real-time quantitative polymerase-chain-reaction,qPCR)方法对芯片分析结果进行验证.结果 经Affymetrix SNP 6.0 芯片分析显示患儿染色体7q11.23区域内弹力蛋白基因(elastin,ELN)5′端大部分及基因上游区域共约80 kb发生杂合性缺失.在ELN基因内设计4对qPCR引物,在家系内进行验证,结果显示ELN的缺失向下游至少累及至第22外显子,且患儿父亲携带与患儿相同的杂合性缺失.结论 ELN 基因部分杂合性缺失为该患儿及其父亲发病的原因,二者之先天异常为主动脉瓣上狭窄(supravalvular aortic stenosis,SVAS).

Abstract：

Objective To detect the copy number variations(CNVs)in a family with congenital narrowing of the ascending aorta,and to explore the underlying genetic causes of the disease.Methods Peripheral blood samples were collected from an affected boy,his affected father and his apparently normal mother.Genomic DNA Was extracted and genotyped using Affymetrix Genome-Wide Human SNP Array 6.0.CNVs were confirmed by real-time quantitative PCR(qPCR).Results Our SNP Array 6.0analysis showed in the boy an about 80kb heterozygous deletion affecting part of the elastin gene(ELN).Further qPCR assays for four confirmed the presence of the deletion in the boy and his father,and indieated that the deletion involved at least the first 22 ELN exons.Conclusion A heterozygous deletion affecting part of the ELN gene has been identified in the boy and his father, A diagnosis of supravalvular aortic stenosis(SVAS)could he made based on the molecular finding.     

Presenting phenotype and clinical evaluation in a cohort of 22 Williams-Beuren syndrome patients

Williams-Beuren syndrome (WS) is a rare multi-system genomic disorder, caused by 7q11.23 microdeletion with a prevalence of 1/7500-1/20,000 live births. Clinical phenotype includes typical facial dysmorphism (elfin face), mental retardation associated with a peculiar neuropsychological profile and congenital heart defects. We investigated 22 WS patients (mean age of 9.7 years, range 1 day to 39 years) with a multi-specialist follow-up protocol comprehensive of neuropsychological, cardiologic, nephrologic, ophthalmologic, endocrinologic, gastroenterologic, odontostomatologic and orthopaedic evaluations. The mean age at diagnosis was 5.38 years, being 1.02 years when genetic evaluation was requested for congenital heart defects (CHD) and 10.68 years in case of mental retardation and/or abnormal neuropsychological profile without an evident CHD. All patients showed facial dysmorphisms, with supravalvular aortic stenosis (SVAS) as the most common cardiovascular anomaly (12/22), followed by peripheral pulmonary stenosis (9/22); interestingly, in one patient we detected a total anomalous pulmonary venous return (TAPVR), confirming the possible association of this rare CHD with WS. Hypertension was detected by 24-h ambulatory blood pressure monitoring in 7/22 cases. A cognitive assessment was performed in 13 patients older than 6 years, showing various degrees of mental retardation in 12 and a normal intelligence quotient (IQ) in a single patient; evaluation of developmental milestones revealed various grades of developmental delay in all the patients younger than 6 years. Chiari malformation type 1 was found in 3 patients. Our study underlines a remarkable diagnostic delay in patients who present to genetic evaluation because of mental retardation and/or peculiar neuropsychological profile lacking an evident cardiopathy and confirms the multi-systemic nature of WS leading to a high clinical presentation's variability and complex follow-up strategies.     

ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype

Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity. Three novel loss of function (LoF) variants were identified in six patients from three families. Clinically, all patients presented anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. Three patients had (recurrent) subaortic membrane, suggesting that ADAMTS19 is the first gene identified related to discrete subaortic stenosis. One case presented a bi-commissural pulmonary valve. All patients displayed some degree of atrioventricular valve insufficiency. Other cardiac anomalies included atrial/ventricular septal defects, persistent ductus arteriosus, and mild dilated ascending aorta. Our findings confirm that biallelic LoF variants in ADAMTS19 are causative of a specific and recognizable cardiac phenotype. We recommend considering ADAMTS19 genetic testing in all patients with multiple semilunar valve abnormalities, particularly in the presence of subaortic membrane. ADAMTS19 screening in patients with semilunar valve abnormalities is needed to estimate the frequency of the HVD related phenotype, which might be not so rare.     

Partial aortic root remodeling for root reconstruction in patients with acute type A dissection

In the present study, we reported our experience with partial aortic root remodeling for root reconstruction in patients with acute type A dissection, which involves in non-coronary sinus and/or the right coronary sinus with just one trimmed Dacron graft. Between February 2001 and May 2010, we performed partial aortic root remode-ling in 40 patients, who underwent emergency surgical intervention. The dissected sinuses were excised leaving a 3-5 mm rim of the aortic wall from the attached aortic valve cusps. A short piece (4-5 cm) of collagen coated woven polyester vascular prosthesis was trimmed with one or two "tongues" to reconstruct the non-coronary sinus and/ or the right coronary sinus, but without using separated patches. Additional procedures were including hemi-arch replacement in 11 patients, and total arch replacement plus stent-elephant trunk in 20 patients. The mean follow-up time was 36.4±3.6 months. In-hospital mortality was only 5.0% (2/40); furthermore, 3 (8.6%) patients underwent re-operation of the aortic valve and 2 (5.7%) patients died during follow-up. At the end of follow-up, trivial or no aortic regurgitation was found in 33 patients, but mild aortic regurgitation was found in 2 patients. Our data suggest that the early and mid-term results of partial aortic root remodeling were favorable, and it restored valve durability and function. Thus, the use of technique for root reconstruction in patients with acute type A dissection should be vigorously encouraged.     

Incidence and outcomes of infective endocarditis after transcatheter aortic valve implantation versus surgical aortic valve replacement

ObjectivesTranscatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in aortic stenosis (AS). Infective endocarditis (IE) in patients with prosthetic heart valves is associated with significant morbidity and mortality. Data on the incidence, risk factors, and outcomes of IE after TAVI are conflicting. We evaluated these issues in patients with percutaneous TAVI vs. isolated surgical AVR (SAVR) at a nationwide level.MethodsBased on the administrative hospital discharge database, the study collected information for all patients with aortic stenosis treated with AVR in France between 2010 and 2018.ResultsA total of 47 553 patients undergoing TAVI and 60 253 patients undergoing isolated SAVR were identified. During a mean follow-up of 2.0 years (median (25th to 75th percentile) 1.2 (0.1–3.4) years), the incidence rates of IE were 1.89 (95% confidence interval (CI) 1.78–2.00) and 1.40 (95% CI 1.34–1.46) events per 100 person-years in unmatched TAVI and SAVR patients, respectively. In 32 582 propensity-matched patients (16 291 with TAVI and 16 291 with SAVR), risk of IE was not different in patients treated with TAVI vs. SAVR (incidence rates of IE 1.86 (95% CI 1.70–2.04) %/year vs 1.71 (95% CI 1.58–1.85) %/year respectively, relative risk (RR) 1.09, 95% CI 0.96–1.23). In these matched patients, total mortality was higher in TAVI patients with IE (43.0% 95% CI 37.3–49.3) than in SAVR patients with IE (32.8% 95% CI 28.6–37.3; RR 1.32, 95% CI 1.08–1.60).DiscussionIn a nationwide cohort of patients with AS, treatment with TAVI was associated with a risk of IE similar to that following SAVR. Mortality was higher for patients with IE following TAVI than for those with IE following SAVR.