Anji T. Yetman

Long-term outcome in patients with Marfan syndrome: is aortic dissection the only cause of sudden death?

OBJECTIVES We sought to assess outcomes in a series of young patients with Marfan syndrome and to define the prevalence of ventricular arrhythmias in this patient population. BACKGROUND While sudden death is a well-recognized outcome in Marfan syndrome, ventricular arrhythmias are not well described. METHODS Patients were followed with echocardiography, electrocardiography, and ambulatory electrocardiography. The prevalence and associated factors for ventricular dysrhythmias were defined. RESULTS Seventy patients with Marfan syndrome diagnosed at birth to 52 years were followed for a period of up to 24 years. All patients had cardiovascular involvement and were started on medical therapy. No patient died from aortic dissection, while 4% died from arrhythmias. Ventricular arrhythmias were present in 21% and were associated with increased left ventricular size, mitral valve prolapse, and abnormalities of repolarization. CONCLUSIONS Cardiac complications are rare in young patients with Marfan syndrome receiving medical therapy and close clinical follow-up. Sudden death still occurs, and appears more common in patients with a dilated left ventricle. Left ventricular dilation may predispose to alterations of repolarization and fatal ventricular arrhythmias.

The dilated aorta in patients with congenital cardiac defects.

Many patients with congenital cardiac disease are at risk for progressive aortic dilation. The mechanisms underlying aortic dilation in this patient cohort are described, and the similarities to the pathophysiologic alterations seen in Marfan syndrome are highlighted. Indications for treatment are discussed.

Importance of the Clinical Recognition of Loeys-Dietz Syndrome in the Neonatal Period

We describe 5 patients who presented with musculoskeletal abnormalities in the neonatal period. All patients were initially suspected to have Larsen syndrome or Beals syndrome but were subsequently diagnosed with a TGFBR2 mutation diagnostic of Loeys-Dietz syndrome. Patients had progressive aortic enlargement, which necessitated surgical intervention for 3 patients and resulted in the death of 1 patient. Delay in diagnosis of Loeys-Dietz syndrome may be associated with adverse prognosis.

Left ventricular diastolic dysfunction in children and young adults with Marfan syndrome

Adults with Marfan syndrome (MFS) demonstrate abnormal aortic elastic properties manifest by decreased aortic distensibility and increased aortic stiffness. Left ventricular (LV) diastolic dysfunction has been reported in adults with MFS. The objective of this study was to assess the frequency of LV diastolic dysfunction in a group of children and young adults with MFS and to determine whether diastolic dysfunction is associated with hemodynamic alterations of the aorta. Review of echocardiographic findings in 40 patients with MFS was performed to assess LV size, systolic function, isovolumic relaxation time (IVRT), mitral inflow velocities, deceleration time (DT) of mitral E wave, and aortic root dimension. No patient had significant valvar disease or was on any cardiac medication at the time of study. A group of 40 age and sex-matched healthy subjects undergoing echocardiography served as controls. Significant differences in LV diastolic function were found between MFS patients and controls. MFS patients had prolonged DT and IVRT and decreased mitral E/A ratio, suggesting impaired LV relaxation. No relationship between aortic root dimension and diastolic performance was identified. Left ventricular diastolic dysfunction may be an early marker of myocardial involvement in young MFS patients occurring independently of aortic root dilatation.

Mitral valve replacement in children: predictors of long-term outcome

BACKGROUND Mitral valve replacement (MVR) in children has been associated with a high complication rate. We sought to assess predictors of outcomes in children undergoing MVR. METHODS A retrospective review of clinical, surgical, and echocardiographic records of patients undergoing MVR was performed. Between 1982 and 2000, 53 children underwent 76 MVR procedures at a median age of 5 years (range, 1 day to 18 years) and weight of 17 kg (range, 3 to 121 kg). Eighteen patients (34%) had more than one MVR. Previous cardiac surgery had been performed in 39 (74%), with 27 (51%) undergoing previous mitral repair. Patients were followed for 9.2 +/- 4.8 (range, 2 to 20) years. RESULTS There were 14 patient deaths, with 6 patients dying within 30 days, and five transplants (36%). Ten-year freedom from reoperation was 66%. Long-term survivors were older at initial repair (7.0 vs 2.5 years, p = 0.02), with a lower incidence of residual cardiac lesions (3% vs 37%, p < 0.001) and a lower incidence of surgical procedures at the time of MVR (31% vs 63%, p = 0.04). Survivors had better left ventricular function preoperatively (ejection fraction, 68% vs 54%; p = 0.001) and placement of a prosthetic valve within 1 z-score of the echocardiographically measured mitral valve annulus (p = 0.02). CONCLUSIONS Adverse outcome after MVR is common, particularly in the young child undergoing palliative surgery or requiring additional surgical procedures. Preoperative assessment of mitral valve size and ventricular function is essential for risk stratification of these patients.

Cardiovascular surgery in children with Marfan syndrome or Loeys-Dietz syndrome

OBJECTIVE This study was undertaken to assess the frequency and outcome of cardiovascular surgery in children with Marfan or Loeys-Dietz syndrome. METHODS A retrospective review from 2 regional Marfan subspecialty clinics was performed. Between 1997 and 2007, 204 children with Marfan syndrome and 17 children with Loeys-Dietz syndrome were followed serially. Of these patients, 35 were identified who had undergone cardiovascular surgery at 18 years of age or less. Demographic, echocardiographic, and surgical data were collected. RESULTS Surgery was performed at a median of 3 years (0-15 years) after diagnosis and a mean age of 11.5 +/- 6.2 years. Aortic root replacement was the initial surgery in 30 patients, and mitral valve surgery was the initial surgery in 8 patients, with 3 patients undergoing both. Aortic root replacement was performed using a composite root replacement in 9 patients and valve-sparing techniques in 21 patients (remodeling in 8 patients and reimplantation in 13 patients). Eight patients underwent reoperation at a mean of 4.7 +/- 3.0 years after aortic surgery: 3 for aortic insufficiency, 2 for dissection, 2 for valve thrombosis, and 1 for a distal aneurysm. Adverse outcomes included reoperation in 8 patients, aneurysm in 1 patient, and death due to dissection or stroke in 3 patients. Variables associated with an adverse outcome included preoperative aortic insufficiency, valve replacement, and absence of angiotensin-converting enzyme inhibitor therapy. CONCLUSION Patients with Marfan or Loeys-Dietz syndrome requiring surgery during childhood have a favorable long-term outcome. Those undergoing valve-sparing root replacement or mitral valve repair have a low risk for reoperation. Postoperative angiotensin-converting enzyme inhibitor therapy confers clinical benefit.

The extracardiac Fontan procedure without cardiopulmonary bypass: technique and intermediate-term results

BACKGROUND The extracardiac Fontan procedure (ECF) usually requires cardiopulmonary bypass (CPB). In this report, the results and techniques of this procedure without CPB at a single institution are presented. METHODS Between August 1992 and December 2001, ECF without CPB was achieved in 24 of 44 patients undergoing an ECF. Mean age at surgery was 5.9 +/- 2.9 years, and mean weight was 20.7 +/- 12.6 kg. Diagnoses were tricuspid atresia in 9 patients, single-ventricle with pulmonary outflow tract obstruction in 7, pulmonary atresia/intact septum in 5, and other complex single-ventricle physiology in 3. Initial palliation was by arterial to pulmonary artery shunt in 21 and pulmonary artery banding in 1. A bidirectional cavopulmonary connection was created in 23 patients. A temporary inferior vena caval-to-atrial shunt was used to complete the procedure without CPB. Median graft size was 16 mm (range 14 to 20 mm). RESULTS There was no early mortality, and 68% of patients were discharged without complications. Complications included persistent cyanosis in 4 patients, persistent pleural effusions in 2 (one chylous), and phrenic nerve injury in 1. Median postoperative hospital stay was 16 days (range 10 to 50) days. At a mean follow-up of 44 +/- 28 months, there was no conduit obstruction. One patient died 11 months postoperatively, and 1 patient received a heart transplant 26 months post-ECF. CONCLUSIONS At intermediate term follow-up, the ECF without CPB appears to be safe and technically reproducible in selected cases. Ongoing follow-up of these patients is necessary to document the theoretical advantages of avoiding CPB.

Management of pediatric hypertrophic cardiomyopathy.

Purpose of review As the underlying genetic basis of hypertrophic cardiomyopathy is being characterized, there has been increasing recognition of the wide spectrum and variable evolution of this disease within the pediatric age range. This review outlines recent evidence relevant to the diagnosis, management, and prognosis of hypertrophic cardiomyopathy specific to children and adolescents. Recent findings Studies of putative causal genes are leading to the discovery of factors affecting the variability of phenotypic expression and possible avenues for new therapies. Nonetheless, the use of genetic testing currently remains for research purposes only. Echocardiography is the primary means for evaluation, with an increasing focus on diastolic performance. Useful prognostic information can be obtained from the safe performance of cardiopulmonary stress testing. Sudden death can occur in children, although the risk factors are likely different than in adults. The role and mechanisms for possible ischemia remain controversial, and likely differ between individuals. Activity restrictions are recommended, with medical therapy reserved for those who are symptomatic. For those with important left ventricular outflow obstruction, surgical myectomy may be indicated, with little current role for alcohol septal ablation. Advances in implantable defibrillators now make this therapy feasible in younger children. Summary There are important differences from adults in the approach to the diagnosis and management of hypertrophic cardiomyopathy in children and adolescents. Care regarding prognostication and therapy must be taken given the potential life-long implications.

Distal Aortic and Peripheral Arterial Aneurysms in Patients With Marfan Syndrome

To the Editor: The mainstay of clinical surveillance for the unoperated patient with Marfan syndrome (MFS) is echocardiography. Because the aorta is not routinely imaged beyond its ascending component, the overall incidence of distal or peripheral arterial disease in MFS is unknown. We sought to

Cardiovascular Pharmacotherapy in Patients with Marfan Syndrome

The cardiovascular complications of Marfan syndrome (MFS) remain the primary source of morbidity and mortality in affected patients. Over the last decade, the underlying pathogenesis of these cardiovascular abnormalities has been the focus of much research. Such research has shed light on the potential role of several novel medical therapies and their ability to prevent cardiovascular disease progression. This paper summarizes the research underlying new medical therapies and provides a review of the scientific foundation underlying all current medical therapies used for prevention of cardiovascular disease in patients with MFS, including β-adrenoceptor antagonists, calcium channel antagonists, ACE inhibitors, and angiotensin receptor antagonists.