Yuli Y. Kim

Cardiac Magnetic Resonance Parameters Predict Transplant-Free Survival in Fontan Patients

Background—Several clinical risk factors for death and heart transplantation have been identified in patients with Fontan circulation. It is unknown whether cardiac magnetic resonance (CMR) measurements of ventricular size and function are independently associated with these outcomes and further improve risk stratification. Methods and Results—Data on patients with Fontan circulation who had a CMR study from January 2002 to January 2011 were retrospectively reviewed. The end point was time to death or listing for heart transplantation after the CMR study. The median age of the 215 patients was 18.3 years (25th, 75th percentiles: 14, 26) with a median age at Fontan of 3.6 years (2.3, 7.1). During a median post-CMR follow-up period of 4.1 years (2.6, 6.2), 24 patients (11%) reached the end point: 20 deaths, 3 transplantations, and 1 transplantation listing. In a multivariable Cox regression model with clinical parameters only, protein-losing enteropathy was associated with transplantation-free survival. A multivariable model, including clinical and CMR parameters, showed that in addition to protein-losing enteropathy, ventricular indexed end-diastolic volume >125 mL/body surface area raised to the 1.3 power was associated with transplantation-free survival. A likelihood-ratio test comparing the 2 models showed that the addition of indexed end-diastolic volume resulted in a significantly improved end point prediction (P<0.001)—C-index increased from 0.63 to 0.79. Conclusions—CMR-derived ventricular indexed end-diastolic volume is an independent predictor of transplantation-free survival in patients late after the Fontan operation and adds incremental value over clinical symptoms alone for risk stratification.

Cardiac magnetic resonance parameters predict transplantation-free survival in patients with fontan circulation.

Background—Several clinical risk factors for death and heart transplantation have been identified in patients with Fontan circulation. It is unknown whether cardiac magnetic resonance (CMR) measurements of ventricular size and function are independently associated with these outcomes and further improve risk stratification. Methods and Results—Data on patients with Fontan circulation who had a CMR study from January 2002 to January 2011 were retrospectively reviewed. The end point was time to death or listing for heart transplantation after the CMR study. The median age of the 215 patients was 18.3 years (25th, 75th percentiles: 14, 26) with a median age at Fontan of 3.6 years (2.3, 7.1). During a median post-CMR follow-up period of 4.1 years (2.6, 6.2), 24 patients (11%) reached the end point: 20 deaths, 3 transplantations, and 1 transplantation listing. In a multivariable Cox regression model with clinical parameters only, protein-losing enteropathy was associated with transplantation-free survival. A multivariable model, including clinical and CMR parameters, showed that in addition to protein-losing enteropathy, ventricular indexed end-diastolic volume >125 mL/body surface area raised to the 1.3 power was associated with transplantation-free survival. A likelihood-ratio test comparing the 2 models showed that the addition of indexed end-diastolic volume resulted in a significantly improved end point prediction (P<0.001)—C-index increased from 0.63 to 0.79. Conclusions—CMR-derived ventricular indexed end-diastolic volume is an independent predictor of transplantation-free survival in patients late after the Fontan operation and adds incremental value over clinical symptoms alone for risk stratification.

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.

Resource Use Among Adult Congenital Heart Surgery Admissions in Pediatric Hospitals Risk Factors for High Resource Utilization and Association With Inpatient Death

Background—Pediatric hospitals frequently perform congenital heart surgery in adults with congenital heart disease. The impact of these admissions on pediatric hospital resources is unknown. Our goals were to examine resource use by adults undergoing congenital heart surgery in pediatric hospitals, explore the association between high resource use (HRU) and inpatient death, and identify HRU risk factors. Methods and Results—We obtained inpatient data from 42 pediatric hospitals from 2000 to 2008 and selected adult congenital heart (ACH) surgery admissions. We defined HRU admissions as those exceeding the 90th percentile for total hospital charges. We performed multivariable analyses using generalized estimating equations to identify risk factors for HRU. Of 97 563 congenital heart surgery admissions to pediatric hospitals, 3061 (3.1%) were adults, accounting for 2.2% of total hospital charges. The threshold for HRU was total hospital charges ≥

Risk Factors for Death After Adult Congenital Heart Surgery in Pediatric Hospitals

213 803. Although HRU admissions comprised 10% of admissions, they accounted for 34% of charges for all ACH surgery admissions. Mortality rate was 16% for HRU admissions and 0.7% for others (P<0.001). Multivariable analysis demonstrated higher case complexity: risk category 2 (adjusted odds ratio [AOR], 3.6; P=0.02), risk category 3 (AOR, 13.7; P<0.001), and risk category 4+ (AOR, 30.7; P<0.001) as compared with risk category 1; DiGeorge syndrome (AOR, 4.2; P=0.006); depression (AOR, 3.1; P<0.001); weekend admission (AOR, 2.6; P<0.001); and government insurance (AOR, 2.0; P<0.001) as risk factors for HRU. Conclusions—High resource use ACH surgery admissions are associated with significantly greater mortality rates. ACH admissions with greater surgical complexity, government insurance, DiGeorge syndrome, weekend admission, and depression were more likely to result in HRU.

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

Background—Despite the central role that pediatric hospitals play in the surgical treatment of congenital heart disease, little is known about outcomes of adult congenital cardiac surgical care in pediatric hospitals. Risk factors for inpatient death, including adult congenital heart (ACH) surgery volume, are poorly described. Methods and Results—We obtained inpatient data from 42 free-standing pediatric hospitals using the Pediatric Health Information System data base 2000 to 2008 and selected ACH surgery admissions (ages 18 to 49 years). We examined admission characteristics and hospital surgery volume. Of 97 563 total (pediatric and adult) congenital heart surgery admissions, 3061 (3.1%) were ACH surgery admissions. Median adult age was 22 years and 39% were between ages 25 to 49 years. Most frequent surgical procedures were pulmonary valve replacement, secundum atrial septal defect repair, and aortic valve replacement. Adult mortality rate was 2.2% at discharge. Multivariable analyses identified the following risk factors for death: age 25 to 34 years (adjusted odds ratio [AOR], 2.1; P=0.009), age 35 to 49 years (AOR, 3.2; P=0.001), male sex (AOR, 1.8; P=0.04), government-sponsored insurance (AOR, 1.8; P=0.03), and higher surgical risk categories 4+ (AOR, 21.5; P=0.001). After adjusting for case mix, pediatric hospitals with high ACH surgery volume had reduced odds for death (AOR, 0.4; P=0.003). There was no relationship between total congenital heart surgery volume and ACH inpatient mortality. Conclusions—Older adults, male sex, government-sponsored insurance, and greater surgical case complexity have the highest likelihood of in-hospital death when adult congenital surgery is performed in free-standing pediatric hospitals. After risk-adjustment, pediatric hospitals with high ACH surgery volume have the lowest inpatient mortality.

Successful cardiac transplantation outcomes in patients with adult congenital heart disease

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.

Approach to residual pulmonary valve dysfunction in adults with repaired tetralogy of Fallot

Objectives The purpose of our study is (1) to characterise patients with congenital heart disease undergoing heart transplantation by adult cardiac surgeons in a large academic medical centre and (2) to describe successful outcomes associated with our multidisciplinary approach to the evaluation and treatment of adults with congenital heart disease (ACHD) undergoing orthotopic heart transplantation (OHT). Background Heart failure is the leading cause of death in patients with ACHD leading to increasing referrals for OHT. Methods The Penn Congenital Transplant Database comprises a cohort of patients with ACHD who underwent OHT between March 2010 and April 2016. We performed a retrospective cohort study of the 20 consecutive patients. Original cardiac diagnoses include single ventricle palliated with Fontan (n=8), dextro-transposition of the great arteries after atrial switch (n=4), tetralogy of Fallot (n=4), pulmonary atresia (n=1), Ebstein anomaly (n=1), unrepaired ventricular septal defect (n=1) and Noonan syndrome with coarctation of the aorta (n=1). Results Eight patients required pretransplant inotropes and two required pretransplant mechanical support. Nine patients underwent heart–liver transplant and three underwent heart–lung transplant. Three patients required postoperative mechanical circulatory support. Patients were followed for an average of 38 months as of April 2016, with 100% survival at 30 days and 1 year and 94% overall survival (19/20 patients). Conclusions ACHD–OHT patients require highly specialised, complex and multidisciplinary healthcare. The success of our programme is attributed to using team-based, patient-centred care including our multidisciplinary staff and specialists across programmes and departments.

Single-center outcomes of combined heart and liver transplantation in the failing Fontan

Residual right ventricular outflow tract and pulmonary valve disease is common in adults with repaired tetralogy of Fallot. Chronic severe pulmonary regurgitation as a result of surgical repair can lead to myriad complications including right ventricular dysfunction, decreased exercise tolerance, right heart failure and symptomatic arrhythmias. The aim of restoring pulmonary valve integrity is to preserve right ventricular size and function with the intent of mitigating the development of symptoms and poor long-term outcomes. Right ventricular size thresholds by cardiac MRI have emerged beyond which reverse right ventricular remodelling after pulmonary valve replacement is less likely. Though pulmonary valve replacement has been shown to improve right ventricular dimensions and symptoms, no consistent improvement in right ventricular ejection fraction or objective measures of exercise capacity have been demonstrated. Furthermore, there are no long-term studies showing that normalisation of right ventricular size results in improved clinical outcomes. New transcatheter techniques of percutaneous pulmonary valve replacement have emerged with good short-term and mid-term outcomes, further adding to the complexity in determining ‘when’ and ‘how’ right ventricular outflow tract and pulmonary valve intervention should occur. With improved survival of these patients, the trend towards earlier pulmonary valve replacement at smaller right ventricular size and rapidly evolving transcatheter pulmonary valve techniques, the clinician must balance the goals of preserving right ventricular size and function in an attempt to prevent untoward outcomes with risks of multiple interventions in a patients lifetime.

Tetralogy of Fallot: General Principles of Management.

Long‐term outcomes of the Fontan operation include Fontan failure and liver disease. Combined heart‐liver transplantation (CHLT) is an option for select patients although limited data exist on this strategy. A retrospective review of Fontan patients 18 years or older referred for cardiac transplant evaluation between 2000 and 2013 at the Hospital of the University of Pennsylvania was performed. All patients were considered for potential CHLT. Clinical variables such as demographics, perioperative factors, and short‐term outcomes were reviewed. Of 17 referrals for cardiac transplantation, seven Fontan patients underwent CHLT. All patients who underwent CHLT had either advanced fibrosis or cirrhosis on liver biopsy. There were no perioperative deaths. The most common postoperative morbidity was acute kidney injury. Short‐term complications include one episode of acute liver rejection but no cardiac rejection greater than 1R. CHLT is an acceptable therapeutic option for patients with failing Fontan physiology who exhibit concomitant advanced liver fibrosis. However, optimal patient selection is currently undefined, and long‐term outcomes are not known.