[Show abstract][Hide abstract] ABSTRACT: Aberrant cellular oxygen sensing (pseudo-hypoxia) is a leading theory for development of pheochromocytoma (PHEO) and paraganglioma (PGL).
To test the hypothesis that chronic hypoxia in patients with cyanotic congenital heart disease (CCHD, CHD) increases the risk for PHEO-PGL.
We investigated the association between CCHD and PHEO-PGL with 2 complementary studies: Study 1) An international consortium was established to identify patients with 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 non-cyanotic CHD and those without CHD using multivariable logistic regression adjusted for age, sex, and genetic PHEO-PGL syndromes.
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 20y (range 1-57y). Cases were young at diagnosis (median 31.5y, range 15-57) and 7/18 had multiple tumors (2 bilateral PHEO; 6 multi-focal or recurrent PGL) while 11 had single tumors (7 PHEO; 4 PGL). PGL were abdominal (13/17) or head/neck (4/17). Cases displayed a noradrenergic biochemical phenotype similar to reported hypoxia-related PHEO-PGL genetic syndromes, but without clinical signs of such syndromes. Study 2) Hospitalized CCHD patients had increased likelihood of PHEO-PGL (adjusted OR=6.0, 95%CI [2.6-13.7], p<0.0001) compared with those without CHD; patients with non-cyanotic CHD had no increased risk (OR=0.9, p=0.48).
There is a strong link between CCHD and PHEO-PGL. Whether these rare diseases co-associate due to hypoxic stress, common genetic or developmental factors, or some combination, requires further investigation.
The Journal of Clinical Endocrinology and Metabolism 01/2015; · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -Exercise oscillatory ventilation (EOV) refers to regular oscillations in minute ventilation (VE) during exercise. Its presence correlates with heart failure severity and worse prognosis in adults with acquired heart failure. We evaluated the prevalence and predictive value of EOV in patients with single ventricle Fontan physiology.
-We performed a cross-sectional analysis and prospective survival analysis of patients who had undergone a Fontan procedure and subsequent cardiopulmonary exercise test (CPET). Data were reviewed for baseline characteristics and incident mortality, heart transplant or non-elective cardiovascular hospitalization. EOV was defined as regular oscillations for >60% of exercise duration with amplitude>15% of average VE. Survival analysis was performed using Cox regression. Among 253 subjects, EOV was present in 37.5%. Patients with EOV were younger (18.8±9.0 vs. 21.7±10.1y, p=0.02). EOV was associated with higher NYHA functional class (p=0.02) and VE/VCO2 slope (36.8±6.9 vs. 33.7±5.7, p=0.0002), but not with peak VO2 (59.7±14.3 vs. 61.0±16.0% predicted, p=0.52) or non-invasive measures of cardiac function. The presence of EOV was associated with slightly lower mean cardiac index but other invasive hemodynamic variables were similar. Over a median follow-up of 5.5 years, 22 patients underwent transplant or died (n=19 primary deaths, 3 transplants with 2 subsequent deaths). EOV was associated with increased risk of death or transplant (hazard ratio=3.9, 95%CI 1.5-10.0, p=0.002) and also predicted the combined outcome of death, transplant or non-elective cardiovascular hospitalization after adjusting for NYHA functional class, peak VO2 and other covariates (multivariable hazard ratio=2.0, 95%CI 1.2-3.6, p=0.01).
-EOV is common in the Fontan population and strongly predicts lower transplant-free survival.
[Show abstract][Hide abstract] ABSTRACT: Patients with early repair of an isolated atrial septal defect (ASD) are expected to have unremarkable right ventricular (RV) and pulmonary circulation physiology. Some studies, however, suggest persistent functional impairment. We aimed to examine the role of abnormal RV and pulmonary vascular response to exercise in patients who had undergone ASD closure. Using a previously published data set, we reviewed invasive exercise cardiopulmonary testing with right-sided hemodynamic data for 12 asymptomatic patients who had undergone ASD closure. The 5 (42%) patients with impaired maximal oxygen uptake ([Formula: see text]) were older and exhibited a lower peak cardiac index (5.6 ± 0.8 vs. 9.0 ± 1.2 L/min/m(2); P = .005) because of abnormal stroke volume augmentation (+3.2 ± 3.9 vs. +17.4 ± 10.2 mL/m(2); P = .02). While all resting hemodynamic variables were similar, patients with low [Formula: see text] tended to have abnormal total pulmonary vascular resistance change during exercise (+11% ± 41% vs. -28% ± 26%; P = .06) and had a steeper relation between mean pulmonary arterial pressure and cardiac index (5.8 ± 0.6 vs. 2.2 ± 0.1 L/min/m(2); P = .02). The increase in peak mean RV power during exercise was also significantly lower in the impaired-[Formula: see text] patients (4.7 ± 1.6 vs. 7.6 ± 2.1 J/s; P = .04). As described in the original study, despite normal resting hemodynamics, a subset of asymptomatic patients with repaired ASD had diminished exercise capacity. Our analysis allows us to conclude that this is due to a combination of abnormal pulmonary vascular response to exercise and impaired RV function.
[Show abstract][Hide abstract] ABSTRACT: Background
Patent foramen ovale (PFO) may be a risk factor for unexplained (“cryptogenic”) stroke or transient ischemic attack (TIA). We sought to determine the efficacy and safety of transcatheter PFO closure compared with antithrombotic therapy for secondary prevention of cerebrovascular events among patients with cryptogenic stroke.
We performed a systematic review and meta-analysis of Medline and Embase (inception – March 2013) for randomized clinical trials (RCTs) comparing transcatheter PFO closure to medical therapy in subjects with cryptogenic stroke. Data were independently extracted on trial conduct quality, baseline characteristics, efficacy, and safety events from published manuscripts and appendices. Risk ratios (RR) and 95% CIs for the composite of stroke or TIA, and adverse cardiovascular events including atrial fibrillation/flutter were constructed.
Three RCTs of 2,303 subjects with prior stroke, TIA, or systemic arterial embolism (mean age 45.7 years, 47.3% women, mean follow-up 2.6 years) were included. PFO closure did not significantly reduce the risk of recurrent stroke/TIA (3.7% vs. 5.2%; RR 0.73, 95% CI, 0.50-1.07; P=0.10); however, an increased risk of incident atrial fibrillation/flutter was detected (3.8% vs. 1.0%; RR 3.67, 95% CI, 1.95-6.89; P<0.0001). No significant heterogeneity was detected for any endpoint among subgroups of patients stratified by age, sex, index cardiovascular event, device type, inter-atrial shunt size, and presence of an atrial septal aneurysm (all P-interactions ≥0.09).
Meta-analysis of RCTs assessing transcatheter PFO closure for secondary prevention of cerebrovascular events in subjects with cryptogenic stroke does not demonstrate benefit compared with antithrombotic therapy, and suggests potential risks.
The Canadian journal of cardiology 10/2014; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Subpulmonary ventricular outflow conduits are utilized routinely to repair complex congenital cardiac abnormalities, but are limited by the inevitable degeneration and need for reintervention. Data on conduit durability and propensity to dysfunction in the adult population are limited.
International Journal of Cardiology 06/2014; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patient-centered care and patient satisfaction represent key dimensions of health care quality. This is relevant for the growing number of patients with life-long conditions. In the present study, our goal was to examine clinicians' attitudes and behavior with respect to patient satisfaction in adult congenital heart disease outpatient clinics.
[Show abstract][Hide abstract] ABSTRACT: Impaired exercise capacity is common after the Fontan procedure and is attributed to cardiovascular limits. The Fontan circulation, however, is also distinctively vulnerable to unfavorable lung mechanics. This study aimed to define the prevalence and physiologic relevance of pulmonary dysfunction in patients with Fontan physiology. We analyzed Pediatric Heart Network Fontan Cross-sectional Study data to assess the prevalence and pattern of abnormal spirometry in Fontan patients (6-18yo), and investigated the relationship between low forced vital capacity (FVC) and maximum exercise variables including peak VO2 (pVO2) among those who demonstrated adequate effort (n=260). Average age, at time of exercise testing and Fontan completion respectively, was 13.2±3.0y and 3.5±2.2y. Aerobic capacity was reduced, pVO2=67.3±15.6% predicted. FVC averaged 79.0±14.8%pred, with 45.8% having FVC<lower limit of normal. Only 7.7% demonstrated obstructive spirometry. Patients with low FVC had lower pVO2 (64.4±15.9 vs. 69.7±14.9%pred, p<0.01); low FVC independently predicted lower pVO2 after adjusting for relevant covariates. Among those with pVO2<80%pred (n=204/260), 22.5% demonstrated a pulmonary mechanical contribution to exercise limitation (breathing reserve<20%). Those with both low FVC and ventilatory inefficiency (VE/VCO2>40) had markedly reduced pVO2 (61.5±15.3% vs. 72.0±14.9%pred,p<0.01) and a higher prevalence of pulmonary mechanical limit compared with patients with normal FVC and efficient ventilation (36.1% vs. 4.8%). In conclusion, abnormal FVC is common in young patients following the Fontan procedure and is independently associated with reduced exercise capacity. A large subset has pathologically low breathing reserve, consistent with pulmonary mechanical contribution to exercise limitation.
AJP Heart and Circulatory Physiology 05/2014; · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For more than half a century growing numbers of practitioners and clinician-scientists have created systems for and practiced healthcare delivery within centers of expertise for young and older adults with congenital heart disease (ACHD). To date, this has been driven largely by energy, enthusiasm, and shared mission without supportive data demonstrating the benefit of such ACHD care programs in the lives of patients and families served by this developing field. Now, for the first time, Marelli and colleagues present in this issue of Circulation good evidence that there is a survival advantage to adult congenital heart patients being cared for by ACHD specialists(1). This confirms what those working in this field had long assumed and hoped, but to date could not substantiate.
[Show abstract][Hide abstract] ABSTRACT: In this perspective, the International Right Heart Foundation Working Group moves a step forward to develop a common language to describe the development and defects that exemplify the common syndrome of right heart failure. We first propose fundamental definitions of the distinctive components of the right heart circulation and provide consensus on a universal definition of right heart failure. These definitions will form the foundation for describing a uniform nomenclature for right heart circulatory failure with a view to foster collaborative research initiatives and conjoint education in an effort to provide insight into echanisms of disease unique to the right heart.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2014; 33(2):123–126. · 5.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transient elastography (TE) offers a noninvasive correlate with the degree of hepatic fibrosis. However, factors other than fibrosis affect liver stiffness. We sought to determine whether hepatic congestion related to hemodynamics in Fontan circulation influences liver stiffness measurement (LSM) assessed by TE.
We studied 45 subjects with Fontan circulation undergoing cardiac catheterization with or without simultaneous liver biopsy. Subjects underwent TE within 5 days before catheterization. Clinical history, hemodynamic and biopsy data, and hepatic biomarkers were collected. Five subjects who had previously undergone liver biopsy and TE were also included.
Median age was 13.1 years (range 2.4-57.8); median time since Fontan was 9.9 years (range 0.1-32.5). No subject had known hepatitis C. Mean LSM for the entire cohort was 21.4 ± 10.8 kPa. Univariate regression analysis using LSM as a continuous outcome variable shows significant correlations with age (R = 0.35, P = .01), time since Fontan (R = 0.41, P = .003), Fontan pressure (R = 0.31, P = .04), cardiac index (R = 0.33, P = .03), pulmonary vascular resistance (R = 0.34, P = .03), systemic arterial oxygen saturation (R = 0.31, P = .04), and platelet count (R = 0.29, P = .05). On multiple regression analysis, Fontan pressure (β = 0.901, P = .03) and cardiac index (β = 2.703, P = .02) were significant predictors of LSM with overall model R(2) = 0.206. Univariate analysis shows LSM to be associated with more severe centrilobular fibrosis (P = .05).
Higher LSM is associated with unfavorable Fontan hemodynamics and advanced centrilobular hepatic fibrosis. TE may be a useful tool for identifying Fontan patients who warrant invasive testing.