Jonathan Ginns

Pheochromocytoma and Paraganglioma in Cyanotic Congenital Heart Disease

CONTEXT Aberrant cellular oxygen sensing is a leading theory for development of pheochromocytoma (PHEO) and paraganglioma (PGL). OBJECTIVE The objective of the study was to test the hypothesis that chronic hypoxia in patients with cyanotic congenital heart disease (CCHD) increases the risk for PHEO-PGL. DESIGN/SETTING/PARTICIPANTS We investigated the association between CCHD and PHEO-PGL with two complementary studies: study 1) an international consortium was established to identify congenital heart disease (CHD) patients with a PHEO-PGL diagnosis confirmed by pathology or biochemistry and imaging; study 2) the 2000-2009 Nationwide Inpatient Survey, a nationally representative discharge database, was used to determine population-based cross-sectional PHEO-PGL frequency in hospitalized CCHD patients compared with noncyanotic CHD and those without CHD using multivariable logistic regression adjusted for age, sex, and genetic PHEO-PGL syndromes. RESULTS In study 1, we identified 20 PHEO-PGL cases, of which 18 had CCHD. Most presented with cardiovascular or psychiatric symptoms. Median cyanosis duration for the CCHD PHEO-PGL cases was 20 years (range 1-57 y). Cases were young at diagnosis (median 31.5 y, range 15-57 y) and 7 of 18 had multiple tumors (two bilateral PHEO; six multifocal or recurrent PGL), whereas 11 had single tumors (seven PHEO; four PGL). PGLs were abdominal (13 of 17) or head/neck (4 of 17). Cases displayed a noradrenergic biochemical phenotype similar to reported hypoxia-related PHEO-PGL genetic syndromes but without clinical signs of such syndromes. In study 2, hospitalized CCHD patients had an increased likelihood of PHEO-PGL (adjusted odds ratio 6.0, 95% confidence interval 2.6-13.7, P < .0001) compared with those without CHD; patients with noncyanotic CHD had no increased risk (odds ratio 0.9, P = .48). CONCLUSIONS There is a strong link between CCHD and PHEO-PGL. Whether these rare diseases coassociate due to hypoxic stress, common genetic or developmental factors, or some combination requires further investigation.

The value of dual-source 64-slice CT coronary angiography in the assessment of patients presenting to an acute chest pain service.

BACKGROUND The absence of radiological evidence of plaque on computed tomographic coronary angiography (CTCA) reliably excludes obstructive coronary artery disease. METHODS We studied patients who presented to our emergency department with chest pain and were admitted to our chest pain assessment service. If they were free of pain and without high-risk features of myocardial ischaemia including elevation of serum biomarkers they underwent CTCA and performed a standard treadmill exercise test. RESULTS Eighty-nine patients aged 56.3+/-8.6 years were admitted. Eleven of them had selective angiography; CTCA identified all who had obstructive disease. More than half of the 85 patients who had normal values of cardiac troponin and of the 75 with a negative exercise test had radiological evidence of disease. During follow-up for 355+/-72 days none died, suffered myocardial infarction or required coronary artery surgery: two with obstructive disease underwent percutaneous coronary intervention 1 and 7 days after the index study. CONCLUSIONS The CTCA findings were significantly correlated with those of selective angiography and with troponin status and increased the ascertainment of coronary artery disease in a cohort of patients at low risk for clinically significant ischaemic heart disease.

Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association

Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention.

Adult congenital heart disease and pregnancy

Adults with congenital heart disease now form the largest group of women with cardiac disease becoming pregnant in the developed world. This is both a mark of impressive steps forward in the management of congenital heart disease and also a challenge to the medical community to develop systems of care that will best serve these women and their babies. Each woman with congenital heart disease presents a unique pattern of challenges for the cardiologist, obstetrician, and anesthesiologist, and their care should be tailored to deal with their individual circumstances. As this population of patients continues to grow, we must continue to learn and improve our diagnostic tools and management strategies to refine their care. This review intends to focus on reviewing the outcomes in this set of patients and also an approach to the assessment and the management of these patients, primarily for an audience of obstetricians, pediatricians, and anesthesiologists.

Ventricular assist device for failing systemic ventricle in an adult with prior mustard procedure.

The Mustard procedure is a palliative surgical procedure used to repair complete transposition of the great arteries. Cardiac transplantation remains the only definitive therapy for patients who develop heart failure after a Mustard procedure. However, pulmonary hypertension represents a major hemodynamic contraindication. The use of a ventricular assist device as destination therapy has not yet been established after a Mustard procedure. Here, we present the case of a 41-year-old patient who presented with systemic right ventricular failure following Mustard procedure complicated by pulmonary hypertension. The patient received a HeartMate II (Thoratec, Pleasanton, CA) ventricular assist device as a bridge to decision.

Procedural Success and Adverse Events in Pulmonary Artery Stenting: Insights From the NCDR.

BACKGROUND Risk factors associated with outcomes for pulmonary artery (PA) stenting remain poorly defined. OBJECTIVES The goal of this study was to determine the effect of patient and procedural characteristics on rates of adverse events and procedural success. METHODS Registry data were collected, and 2 definitions of procedural success were pre-specified for patients with biventricular circulation: 1) 20% reduction in right ventricular pressure or 50% increase in PA diameter; and 2) 25% reduction in right ventricular pressure or 50% decrease in PA gradient or post-procedure ratio of in-stent minimum to pre-stent distal diameter >80%. A separate definition of procedural success based on normalization of PA diameter was pre-specified for patients with single ventricle palliation. RESULTS Between January 2011 and January 2014, a total of 1,183 PA stenting procedures were performed at 59 institutions across 1,001 admissions; 262 (22%) procedures were performed in patients with a single ventricle. The rate of procedural success was 76% for definition 1, 86% for definition 2, and 75% for single ventricle patients. In the multivariate analysis, ostial stenosis was significantly associated with procedural success for biventricular patients according to both definitions. The overall complication rate was 14%, with 9% of patients experiencing death or a major adverse event (MAE). According to multivariate analysis, weight <4 kg, having a single ventricle, and emergency status were significantly associated with death or MAEs. CONCLUSIONS In our analysis, success was >75% across all definitions, and adverse events were relatively common. Biventricular patients with an ostial stenosis had a higher probability of a successful outcome. Patients who had a single ventricle, weight <4 kg, or who underwent an emergency procedure had a higher risk of death or MAE. These findings may help inform patient selection for PA stenting.

Is systemic right ventricular function by cardiac MRI related to the degree of tricuspid regurgitation in congenitally corrected transposition of the great arteries

BACKGROUND AND METHODS Systemic right ventricular dysfunction and tricuspid regurgitation (TR) are frequently encountered in patients with congenitally corrected transposition of the great arteries (CCTGA). Studies using echocardiography have suggested a relationship between the degree of TR and systemic right ventricular dysfunction; however, assessment of systemic right ventricular function by echocardiography is limited. Cardiac MRI (CMR) is the gold standard for volumetric assessment of the systemic right ventricle. We performed a retrospective cohort study at our center evaluating all adult patients with CCTGA who underwent a CMR between 1/1999 and 1/2013 to determine the relationship between the degree of TR and systemic right ventricular function. RESULTS Of the 33 patients identified, 12 had ≤ mild TR (37%), 13 had moderate TR (40%), and 8 had severe TR (24%). Mean age at CMR was 38 years (23-64). Mean right ventricular ejection fraction (45% vs. 41% vs. 42%, p=0.68) and mean indexed right ventricular end diastolic volume (122 ml/m(2) vs. 136 ml/m(2) vs. 138 ml/m(2)p=0.36) were not significantly different for patients with ≤ mild TR, moderate TR or severe TR. The degree of TR was not associated with additional congenital lesions, prior procedures, presence of an intraventricular conduction delay, or decreased left ventricular function. CONCLUSION No association between the degree of TR and right ventricular volume or ejection fraction by CMR was identified. Failure to show worsening function or increased volume with greater degrees of TR suggests that the degree of regurgitation alone may not fully explain the heterogeneity in right ventricular size and function.

The Tricuspid Valve in Adult Congenital Heart Disease

The tricuspid valve is frequently affected in adults with congenital heart disease but is also frequently overlooked. Disease of this valve can occur primarily or develop secondary to changes in the right ventricle caused by other disease states. The embryology and anatomy of the tricuspid valve are important to understanding pathogenesis of valve dysfunction in congenital heart disease. Clinical findings can be subtle. Multimodality imaging may be necessary to fully assess the cause and impact of tricuspid valve lesions. More research is needed in pathophysiology, imaging, and treatment in this area.

Postoperative tricuspid regurgitation after adult congenital heart surgery is associated with adverse clinical outcomes

OBJECTIVE Many patients with adult congenital heart disease will require cardiac surgery during their lifetime, and some will have concomitant tricuspid regurgitation. However, the optimal management of significant tricuspid regurgitation at the time of cardiac surgery remains unclear. We assessed the determinants of adverse outcomes in patients with adult congenital heart disease and moderate or greater tricuspid regurgitation undergoing cardiac surgery for non-tricuspid regurgitation-related indications. METHODS All adult patients with congenital heart disease and greater than moderate tricuspid regurgitation who underwent cardiac surgery for non-tricuspid regurgitation-related indications were included in a retrospective study at the Schneeweiss Adult Congenital Heart Center. Cohorts were defined by the type of tricuspid valve intervention at the time of surgery. The primary end point of interest was a composite of death, heart transplantation, and reoperation on the tricuspid valve. RESULTS A total of 107 patients met inclusion criteria, and 17 patients (17%) reached the primary end point. A total of 68 patients (64%) underwent tricuspid valve repair, 8 patients (7%) underwent tricuspid valve replacement, and 31 patients (29%) did not have a tricuspid valve intervention. By multivariate analysis, moderate or greater postoperative tricuspid regurgitation was associated with a hazard ratio of 6.12 (1.84-20.3) for the primary end point (P = .003). In addition, failure to perform a tricuspid valve intervention at the time of surgery was associated with an odds ratio of 4.17 (1.26-14.3) for moderate or greater postoperative tricuspid regurgitation (P = .02). CONCLUSIONS Moderate or greater postoperative tricuspid regurgitation was associated with an increased risk of death, transplant, or reoperation in adult patients with congenital heart disease undergoing cardiac surgery for non-tricuspid regurgitation-related indications. Concomitant tricuspid valve intervention at the time of cardiac surgery should be considered in patients with adult congenital heart disease with moderate or greater preoperative tricuspid regurgitation.

Familial ventricular aneurysms and septal defects map to chromosome 10p15

AIMS Although ventricular septal defects (VSD) are the most common congenital heart lesion, familial clustering has been described only in rare instances. The aim of this study was to identify genetic factors and chromosomal regions contributing to VSD. METHODS AND RESULTS A unique, large kindred segregating various forms of septal pathologies-including VSD, ventricular septal aneurysms, and atrial septal defects (ASD)-was ascertained and characterized clinically and genetically. Eighteen family members in three generations could be studied, out of whom 10 are affected (2 ASD, 3 septal aneurysm, 4 VSD, and 1 tetralogy of Fallot). Parametric multipoint LOD scores reach significance on chromosome 10p15.3-10p15.2 (max. 3.29). The LOD score support interval is in a gene-poor region where deletions have been reported to associate with septal defects, but that is distinct from the DiGeorge syndrome 2 region on 10p. Multiple linkage analysis scenarios suggest that tetralogy of Fallot is a phenocopy and genetically distinct from the autosomal dominant form of septal pathologies observed in this family. CONCLUSION This study maps a rare familial form of VSD/septal aneurysms to chromosome 10p15 and extends the spectrum of the genetic heterogeneity of septal pathologies. Fine mapping, haplotype construction, and resequencing will provide a unique opportunity to study the pathogenesis of septal defects and shed light on molecular mechanisms of septal development.