Three decades of follow-up of aortic and pulmonary vascular lesions in the Williams-Beuren syndrome

The diagnostic criteria of the Williams-Beuren syndrome (WBS) were established almost 3 decades ago. Until now there has been little knowledge about the natural and post-surgical history of vascular lesions in this syndrome. In order to evaluate the long term follow-up of aortic and pulmonary vascular lesions, we have analysed the catheterization data, angiocardiograms, and Doppler-echo measurements in 59 patients who were seen at least twice in our institution between 1961 and 1993. Their follow-up periods ranged from 2.1 to 28.2 years. Of 45 patients with supravalvular aortic stenosis (SVAS) with a mean follow-up period of 12.9 years, it became evident that pressure gradients of less than 20 mm Hg in infancy generally remained unchanged during the first two decades of life. Pressure gradients exceeding 20 mm Hg increased from an average of 35.5 mm Hg to 52.7 mm Hg in 13 patients. Of these, 8 required surgical relief of the narrowing. In 7 patients aortic hypoplasia was documented. In 5 of them the caliber of the aorta showed a tendency towards normalisation within a period of 11.9 to 23.9 years. Of 6 individuals with aortic hypoplasia and surgical relief of SVAS, 4 patients developed restenosis at the distal end of the aortoplasty patch. In contrast, 9 patients with operated SVAS—but without aortic hypoplasia—remained free of restenosis over a period of 11 years (mean). Coarctation occurred in 4/59 patients; restenosis was seen in 2 after 5 and 16 years. Peripheral pulmonary stenosis was followed in 23 patients over 14.4 years (mean). During this period the systolic pressure gradients fell from 23 to 9.3 mm Hg (mean). In adolescence and adulthood the gradients were below 20 mm Hg in 22/23 individuals. In WBS there is a good long-term prognosis for SVAS if gradients during infancy are low. SVAS with gradients above 20 mm Hg tend to increase; 60% of them require surgical relief with good long-term results. But aortic hypoplasia impairs the prognosis of operated SVAS, because restenosis may occur. Peripheral pulmonary stenosis generally shows a good long-term prognosis. © 1994 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     

Discrete subvalvular aortic stenosis

Discrete Subaortic Stenosis is one of the many lesions responsible for left ventricular outflow tract (LVOT) obstruction. It may present as in an isolated from as membranous or fibromuscular ring below the aortic valve or in association with other congenital anamolies such as VSD, PDA, coarctation of aorta, hypoplastic aortic annulus, double chamber right ventricle among others. The condition is rarely diagnosed antenataly or in infancy but often manifests in the first decade of life with features of progressive LVOT obstruction, LV hypertrophy and dysfunction aortic regurgitation due to damage to the aortic cusps because of the jet from the subaortic narrowing which may also render the aortic valve prone to infective endocarditis. Interaction of genetic predisposition and morphologically deformed long and narrow LVOT cause rheological abnormalities and increased shear stress in the region of subaortic stenosis and seem to be the main etiological factor alongwith poorly defined role of more extensive but subtle changes in the LV endocardium. Condition can be easily diagnosed by cross-sectional and Doppler echocardiography and confirmed by demonstrating a pressure gradient below aortic valve on cardiac catheterisation and LV angiography. Surgical membranectomy alongwith myotomy or myomectomy remain the mainstay of treatment but long term results are not satisfactory as there is a high rate of recurrences requiring reoperations. A close follow up with serial echocardiographic examinations is very helpful in early detection of subaortic obstruction in patients who have so called functional murmurs in the childhood.     

A reproducible model of moderate to severe concentric left ventricular hypertrophy.

A reproducible model for the production of moderate to severe concentric left ventricular hypertrophy has been developed in this laboratory. Coarctation-banding of the ascending aorta was performed successfully in 10 puppies. There were no late deaths related to aortic rupture, and in the dogs surviving for 1 yr no evidence of congestive heart failure was present. A second operative procedure was performed in seven dogs for chronic instrumentation, and all survived. Severe supravalvular aortic stenosis with a marked peak systolic pressure gradient was noted in each dog. Postmortem examination revealed a substantial increase in left ventricular mass and in the ratio of left ventricular to body weight.     

The heart after surgery for congenital heart disease

The pathology of the heart following surgical correction for congenital cardiac defects has not been fully explored. This study is based on valvar aortic stenosis, atrioventricular septal defect, complete transposition of the great arteries, and Fallot's tetralogy. Emphasis has been put on preexistent gross pathology, with histological verification, and postoperative complications. Among patients with aortic valve stenosis preexistent anomalies dominated (left ventricular hypoplasia, mitral valve abnormalities, left ventricular endocardial fibroelastosis). The findings suggest that the cases represent an extreme within a spectrum and could explain the late postoperative dismal results in patients suffering from congenital left heart obstruction. In patients with atrioventricular septal defects the important pathology related predominantly to the operative procedure (injury to the atrioventricular bundle, patch dehiscence at the site of the atrioventricular node, inadequate repair of the left atrioventricular valve leaflets) and to pulmonary obstructive vascular disease. In complete transposition of the great arteries, with or without ventricular septal defects, technical problems dominated. Obstruction of the systemic and pulmonic venous pathways, atrial dysrhythmia, and tricuspid valve injury were the most serious complications following Mustard's procedure. The Rastelli-type procedure was complicated by degeneration and calcification of the porcine valve and crowding of the left ventricle. The arterial switch was complicated by abnormal origin and course of the left circumflex artery, which led to kinking and myocardial infarction. In Fallot's tetralogy surgical complications (injury to the atrioventricular bundle and the tricuspid valve) were the most important. The study discloses that the heart after surgery for congenital heart disease cannot be considered without taking preexistent pathology into account. Careful preoperative investigations are mandatory, since most anomalies could have been detected and, hence, might have changed the operative result.     

Autosomal dominant inheritance of left ventricular outflow tract obstruction

Most nonsyndromic congenital heart malformations (CHMs) in humans are multifactorial in origin, although an increasing number of monogenic cases have been reported recently. We describe here four new families with presumed autosomal dominant inheritance of left ventricular outflow tract obstruction (LVOTO), consisting of hypoplastic left heart (HLHS) or left ventricle (HLV), aortic valve stenosis (AS) and bicuspid aortic valve (BAV), hypoplastic aortic arch (HAA), and coarctation of the aorta (CoA). LVOTO in these families shows a wide clinical spectrum with some family members having severe anomalies such as hypoplastic left heart, and others only minor anomalies such as mild aortic valve stenosis. This supports the suggestion that all anomalies of the LVOTO spectrum are developmentally related and can be caused by a single gene defect.     

Echocardiographic features of adult tetralogy of Fallot with natural palliative correction by patent ductus arteriosus

A thirty-year-old man with the diagnosis of the tetralogy of Fallot and patent ductus arteriosus was admitted to our hospital because of a syncope. He reported no previous symptoms. We diagnosed adult tetralogy of Fallot, which included all four characteristic anomalies: ventricular septal defect, overriding aorta, pulmonary artery stenosis, and right ventricular hypertrophy. The associated persistent ductus arteriosus and the presence of compensatory arteriovenous communications produced a continuous flow load on the left ventricle, which resulted in moderate left ventricular hypertrophy, but without symptoms of pulmonary congestion or cardiac decompensation. Anatomic diagnosis and hemodynamic assessment were established by transthoracic and transesophageal echocardiography, with incidental finding of a quadricuspid aortic valve. To the best of our knowledge, our case of the adult form of Fallot's tetralogy associated with both patent ductus arteriosus and quadricuspid aortic valve is the first one ever described. It is well known that patients with tetralogy of Fallot who do not undergo operation in childhood have short survival, which depends predominantly on the degree of pulmonary artery stenosis and early development of collateral circulation to the lungs. Long-term persistence of natural aortopulmonary anastomosis with systemic collateral circulation to the lungs and remodeling of the heart, with better hemodynamic balance as well as the presence of mild pulmonary artery stenosis probably enhanced the survival of our patient.     

Angled aorta ("sigmoid septum") as a cause of hypertrophic subaortic stenosis

Review of the hearts of seven patients in whom hypertrophic obstructive cardiomyopathy had been diagnosed by the usual clinical and morphologic criteria revealed diminished angles between the interventricular septa and ascending aortas in three cases. The angles in these three hearts were 90 to 110 degrees, as compared with a mean value of 145 degrees in the other four hearts with hypertrophic obstructive cardiomyopathy and 140 +/- 14 degrees in 55 control hearts. None of the patients with hypertrophic subaortic stenoses and angled aortic roots died of the heart disease, and none had either asymmetric ventricular hypertrophy or evidence of familial cardiomyopathy. It is proposed that in patients with angled aortic roots and left ventricular hypertrophy, subaortic obstruction may develop due to narrowing of the left ventricular outflow tract, resulting in clinical and morphologic findings of hypertrophic obstructive cardiomyopathy. In hearts with angled aortic roots the top of the ventricular septum is tipped toward the mitral valve, rather than tapered toward the aorta, as in normal hearts. This configuration narrows the outflow tract of the left ventricle and can result in systolic anterior motion of the mitral valve, the illusion of asymmetric septal hypertrophy when studied by M-mode echocardiography, a subaortic pressure gradient, and a subaortic endocardial plaque. This less serious form of hypertrophic subaortic stenosis should be distinguished from other forms of hypertrophic obstructive cardiomyopathy.     

自体心包补片修补主动脉瓣环辅助主动脉瓣置换

背景：在主动脉置换过程中常遇到瓣环钙化、瓣周囊肿等特殊情况,这时一般应用特殊技术辅助主动脉瓣置换。 目的：观察自体心包补片修补主动脉瓣环辅助主动脉瓣置换治疗钙化性主动脉瓣狭窄并瓣环钙化的临床可行性。 方法：回顾性分析2009年1月至 2012年1月郑州大学第一附属医院42例钙化性主动脉瓣狭窄并瓣环钙化患者的临床资料,并通过统计学软件处理自体心包补片修补主动脉瓣环技术辅助主动脉瓣置换前后的主动脉瓣有效瓣口面积指数、最大跨瓣压差、血流峰值速度、左室射血分数等数据,分析自体心包补片修补主动脉瓣环技术辅助主动脉瓣置换的应用效果。 结果与结论：无置换中死亡病例,置换中主动脉阻断时间为52-88(63.0±18.1) min,体外循环时间为78-122(102.6±25.1) min,置换后1例患者出现急性肾功能衰竭,经床旁血透治疗后治愈。余患者无严重置换并发症。置换后住院天数为7-20(13.6±5.5) d。置换后多普勒超声心动图示：瓣膜功能良好,均未发现主动脉瓣周漏。置换后6个月的主动脉瓣有效瓣口面积指数、最大跨瓣压差、血流峰值速度、左室射血分数均有显著改善,与置换前比较差异均有显著性意义(P < 0.05)。证实对置换适应证合适的特殊换瓣患者,自体心包补片修补主动脉瓣环辅助主动脉瓣置换可取得满意的外科治疗效果,且操作安全简单,是一项可行的技术。     

个体化治疗预防小主动脉瓣环瓣膜置换后瓣膜与患者的不匹配

背景：小主动脉瓣环主动脉瓣置换是心外科手术的难点,治疗不当可能出现瓣膜与患者不匹配现象,使左室流出道狭窄、跨瓣压差增大,引起左室后负荷增加致心肌肥厚甚至充血性心力衰竭。 目的：总结预防小主动脉瓣环瓣膜置换后发生人工心脏瓣膜与患者不匹配的治疗策略。 方法：小主动脉瓣环均主动脉瓣置换患者85例。瓣口直径>17 mm,≤19 mm的患者,选19 mm SJM Regent 瓣;对瓣口直径≤17 mm的患者,用牛心包补片加宽瓣环,再选19 mm SJM Regent 瓣行瓣膜置换;对于瓣口直径>19 mm,≤21 mm,选21 mm Hancock II ultra生物瓣置换。治疗后应用超声心动图测量有效瓣口面积指数、左心室重量指数、室间隔厚度、左心室后壁厚度、跨瓣峰速、跨瓣压差和跨瓣平均压。出院后通过门诊对患者进行随访,定期复查超声心动图。 结果与结论：治疗后早期无死亡病例,均治愈出院。随访时间为6个月-3年。主要并发症为低心排综合征2例、二次开胸止血1例、呼吸机依赖2例。所以患者均未出现脑栓塞或脑出血等脑部并发症。无瓣膜功能失调或卡瓣。未发现牛心包补片撕裂、瘤样膨出、钙化、血栓形成、免疫反应和感染等情况。81例获随访,随访率为 95%(81/85)。NYHA心功能分级Ⅰ级65例,Ⅱ级16例。各不同瓣环直径患者治疗后跨主动脉瓣峰速和平均压差均明显降低,有效瓣口面积指数明显增加,左心室重量指数、室间隔厚度和左心室后壁厚度均明显降低,均未出现人工心脏瓣膜与患者不匹配。置换21 mm Hancock II ultra 生物瓣和21 mm SJM Regent 瓣组间的比较,前者获得了更好的跨瓣峰速和平均压差,以及更好的左心室重塑指标。19 mm Regent 瓣患者治疗后体质量和体表面积较治疗前明显增加。结果提示对于小主动脉瓣环的患者应采取个体化的治疗策略预防主动脉瓣置换后瓣膜与患者不匹配的发生。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

Left ventricular aneurysm, aortic valve disease and coronary narrowing in a patient with Hunter's syndrome.

Hunter's syndrome (mucopolysaccharidosis type 2, MPS 2) is an inherited disorder of glycosaminoglycan degradation commonly associated with cardiac disease. We present the case of a young man with unusual cardiac manifestations of this syndrome. When mixed aortic valve disease was noted in childhood, other classical features of the milder form of Hunter's syndrome were present. There was no symptomatic or echocardiographic cardiovascular deterioration until age 27 when the patient presented in severe biventricular failure. Investigations demonstrated cardiomegaly and a large apical left ventricular aneurysm. The patient died suddenly soon after this diagnosis. Post mortem examination demonstrated a hypertrophied left ventricle with a 6-cm apical aneurysm. Coronary arterial walls were diffusely thickened but with only mild lumenal stenosis. Mitral and aortic valve disease was also present. There is one previous report of ventricular aneurysm in Hunter's syndrome. Pathophysiological contributions to aneurysm formation may include abnormal coronary flow, the presence of aortic stenosis and abnormal myocardium. This patient's sudden deterioration after a long period of clinical stability reinforces the need for careful follow-up of patients with cardiac manifestations of Hunter's disease.     

Computer modeling of the effects of aortic valve stenosis and arterial system afterload on left ventricular hypertrophy

The degree of left ventricular hypertrophy is generally thought to reflect the severity of aortic stenosis. However, the compounded influence of arterial system load is poorly understood. We developed a computer model to investigate the effects of aortic valve stenosis in combination with various systemic arterial parameters in the development of left ventricular hypertrophy. Data show that an increased peripheral resistance and/or aortic valve resistance, results in an increase in left ventricular wall thickness and mass, while peak systolic wall stress remains constant. Changing arterial compliance to above normal level would not induce significant changes in wall thickness, while reduction in arterial compliance below normal would cause an increase in ventricular wall thickness. When a double load is imposed on the left ventricle by way of a stenotic valve and an increased arterial afterload, a greater and an aggregated increase in wall thickness results, hastening the hypertrophic process.     

Aortico-left ventricular tunnel, an unusual congenital cardiac anomaly in adult: application of a new operative technique

Aortico-left ventricular tunnel is a rare congenital cardiac anomaly. A 45-year-old man was referred to our clinic with unstable angina pectoris. The patient had an aortico-left ventricular tunnel that had been operated on 15 years before and that now showed a recurrence. We performed a new surgical technique, including closure of orifices of the tunnel by resection of the aorta at the left coronary ostium, reconstruction of the aorta with patch plasty, and formation of a neo-left main branch by applying a saphenous magna vein patch at the noncoronary cusp. In this technique, the possibility of aortic regurgitation caused by stretching and distortion of the aortic ring and leaflets by primary suture closure of tunnel is eliminated. The postoperative 2-D colored Doppler echocardiography and cardiac MRI showed an excellent result of the procedure. Coronary flow could be restored, and thus anginal symptoms disappeared.     

Neonatal Williams syndrome presenting as an isolated supravalvular pulmonary stenosis

An infant with normal facies and none of the extracardiac anomalies usually associated with Williams syndrome presented at birth with an echocardiographic pattern of supravalvular pulmonary stenosis and displastic pulmonary valve. A clinical reappraisal was planned at 3 months of age, but the girl died suddenly at home at 2 months of age. At autopsy, both ventricles were hypertrophic, and the valves showed mild dysplasia. The walls of the great arteries were thick, with a "washed leather" consistency, but there was no gross evidence of discrete stenosis. The histologic mosaic appearance of the media of the great arteries, due to elastosis and extreme disarray of the elastic lamellae, prompted a postmortem diagnosis of supravalvar aortic stenosis and suggested a diagnosis of Williams syndrome, which was subsequently confirmed by fluorescence in situ hybridization. Pediatricians and pathologists should be alerted that Williams syndrome in the newborn may present as an isolated supravalvular pulmonary stenosis, whereas supravalvular aortic stenosis becomes clinically significant only a few months later.     

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。     

Inheritance analysis of congenital left ventricular outflow tract obstruction malformations: Segregation, multiplex relative risk, and heritability

The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71-0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1-6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects.     

Left ventricular muscle mass regression after aortic valve replacement

Implanting a valve that will reduce left ventricular mass is critical in aortic stenosis. Regression of left ventricular hypertrophy in 46 aortic valve replacement (AVR) patients receiving a St. Jude Medical (SJM) valve was assessed by serial electrocardiographic and echocardiographic studies during the preoperative, immediate, and late postoperative periods. The patients were divided into three groups according to valve size; 19 mm group (n=9), 21 mm group (n=20), and 23+mm group (n=17). There was no surgical mortality. The NYHA functional class improved from an average of 2.2+/-0.8 preoperatively to 1.3+/-0.5 post-operatively. Left ventricular muscle mass index (LVMI) regression failed to reach statistical significance in the 19 mm group, whereas in the other two groups a steady decrease in the LVMI occurred with follow up. ECG findings were less remarkable showing insignificant differences in voltage among the three groups (p=0.000). In conclusion, the current data suggest that the 19 mm SJM valve may not result in satisfactory left ventricular muscle mass regression despite adequate function, even in small patients. Therefore, additional procedures to accommodate a larger valve may be warranted in the aortic annulus smaller than 21 mm.     

A novel miniature ventricular assist device for hemodynamic support

The HemoDynamics Systems enabler is a new cardiac assist pump that can expel blood from the left ventricle and provide pulsatile flow in the aorta. We evaluated the efficacy of the 18 Fr enabler. The enabler was inserted from the left ventricular apex into the ascending aorta in eight sheep. Heart failure (mild, moderate, and severe) was induced by microsphere injection into the coronary arteries to reduce cardiac output by 10-30%, 31-50%, and more than 50% from baseline, respectively. The enabler was activated, and its flow was increased to approximately 2.0 L/min. Hemodynamic variables were recorded before and after activation. In moderate heart failure, cardiac output and mean aortic pressure increased from 2.3 +/- 0.6 L/min and 59 +/- 12 mm Hg before assist to 2.8 +/- 0.6 L/min and 70 +/- 8 mm Hg at 30 minutes after activation, respectively (p < 0.01). Left atrial pressure decreased from 17 +/- 3 to 13 +/- 4 mm Hg (p < 0.05). Similar findings were observed in mild and severe heart failure. Despite its small diameter, the enabler significantly improved the hemodynamics of failing hearts and may potentially serve as a means of peripheral left ventricular support. Further study is warranted.     

Pathology of the diffuse variant of supravalvar aortic stenosis.

Supravalvar aortic stenosis is a rare congenital heart anomaly, producing left ventricular outflow tract obstruction. Of the two anatomic variants that have been described, diffuse type is the rarest. We report five such cases in children between two months and nine years of age. None had features of Williams syndrome. The entire aorta was involved in three cases, with abdominal aortic coarctation in two cases. Stenosis was mainly due to involvement of the media, which showed smooth muscle hypertrophy, abnormal elastic fibers, and mild collagenization. Predominant intimal change was seen in one case. Pulmonary, coronary, arch, renal, and common iliac arteries were also involved.     

A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta

Aim: Myocardial remodelling during pressure overload might contribute to development of heart failure. Reverse remodelling normally occurs following aortic valve replacement for aortic stenosis; however, the details and regulatory mechanisms of reverse remodelling remain unknown. Thus, an experimental model of reverse remodelling would allow for studies of this process. Although models of aortic banding are widely used, only few reports of debanding models exist. The aim of this study was to establish a banding–debanding model in the mouse with repetitive careful haemodynamic evaluation by high‐resolution echocardiography. Methods: C57Bl/6 mice were subjected to ascending aortic banding and subsequent debanding. Cardiac geometry and function were evaluated by echocardiography, and left ventricular myocardium was analysed by histology and quantitative real‐time polymerase chain reaction. Results: The degree of aortic banding was controlled by non‐invasive estimation of the gradient, and we found a close correlation between left ventricular mass estimated by echocardiography and weight at the time of killing. Aortic banding led to left ventricular hypertrophy, fibrosis and expression of foetal genes, indicating myocardial remodelling. Echocardiography revealed concentric left ventricular remodelling and myocardial dysfunction. Following debanding, performed via a different incision, there was rapid regression of left ventricular weight and normalization of both cardiac geometry and function by 14 days. Conclusions: We have established a reproducible and carefully characterized mouse model of reverse remodelling by banding and debanding of the ascending aorta. Such a model might contribute to increased understanding of the reversibility of cardiac pathology, which in turn might give rise to new strategies in heart failure treatment.