[Show abstract][Hide abstract] ABSTRACT: Background-—Galectin-3 may play a role in cardiac and noncardiac fibrosis, and elevated circulating levels of this protein predict adverse outcomes in patients with heart failure who do not have congenital heart disease. We investigated galectin-3 in adults with single-ventricle Fontan circulation, patients who are prone to premature clinical deterioration in the context of extensive multiorgan fibrosis.
Methods and Results-—We measured plasma galectin-3 concentrations in 70 ambulatory adult Fontan patients and 21 age- and sex-matched control participants. Galectin-3 level was significantly higher in the Fontan group (11.85 ng/mL, interquartile range 9.9 to 15.0 ng/mL) versus the control group (9.4 ng/mL, interquartile range 8.2 to 10.8 ng/mL; P<0.001). Among Fontan patients, galectin-3 was positively correlated with age, uric acid, and high-sensitivity C-reactive protein and negatively correlated with estimated glomerular filtration rate. There was no significant relationship between galectin-3 and oxygen saturation, Fontan type, or ventricular morphology. Over a median follow-up of 461 days, 15 events occurred among the Fontan patients: 12 nonelective hospitalizations (with 2 subsequent deaths) and 3 deaths without prior hospitalization. Patients with elevated galectin-3 (n=19, defined as >2 SD above the control group mean value) had a higher risk of nonelective hospitalization or death (hazard ratio 6.0, 95% CI 2.1 to 16.8, P<0.001). This relationship persisted after individual adjustment for covariates including age, New York Heart
Association functional class, C-reactive protein, and estimated glomerular filtration rate and after multivariable adjustment for independently predictive covariates (hazard ratio 9.2, 95% CI 2.4 to 35.2, P=0.001).
Conclusions-—Galectin-3 concentrations are elevated among adults with a Fontan circulation, and elevated galectin-3 is associated with an increased risk of nonelective cardiovascular hospitalization or death. ( J Am Heart Assoc. 2016;5:e002706 doi: 10.1161/JAHA.115.002706)
Full-text · Article · Jan 2016 · Journal of the American Heart Association
[Show abstract][Hide abstract] ABSTRACT: Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk.
[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.
No preview · Article · Jan 2015 · The Journal of Clinical Endocrinology and Metabolism
[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.
Full-text · Article · Dec 2014 · Circulation Heart Failure
[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.
No preview · Article · Oct 2014 · The Canadian journal of cardiology
[Show abstract][Hide abstract] ABSTRACT: Background:
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.
The study included 288 consecutive patients ≥18 years of age who were evaluated between 1991 and 2010 after placement of a ≥18 mm conduit. Freedom from hemodynamic conduit dysfunction served as our primary outcome. Freedom from reintervention, overall mortality and heart transplantation were also evaluated.
Median age at conduit implant was 19 years and median follow-up duration was 13 years. Probabilities of survival without conduit dysfunction and reintervention at 5, 10 and 15 years were 87%, 63%, and 49%, and 95%, 81%, and 56%, respectively. Smaller conduit diameter (18-20mm) was associated with lower probability of survival without dysfunction in the entire study cohort, with prominent effects in patients in both the lowest and the highest age quartiles. Other parameters with similar associations were higher BMI, native anatomy of tetralogy of Fallot or truncus arteriosus, and active smoking.
Adult congenital heart disease patients with conduit diameter ≥18 mm had an approximately 50% chance of developing hemodynamic conduit dysfunction and undergoing conduit reintervention by 15 years of post-implant, and a 30% likelihood of undergoing conduit reoperation in the same time frame. The importance of these data is underscored by the increasing number of adults with congenital heart diseases seeking care and the recent advances in transcatheter valve replacement for dysfunctional conduits.
No preview · Article · Jun 2014 · International Journal of Cardiology
[Show abstract][Hide abstract] ABSTRACT: Objectives:
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.
A 34-question survey was developed to assess adult congenital heart disease clinicians' awareness, attitudes, and behavior relative to patient satisfaction and administered in-person or online to clinicians from the largely U.S.-based Adult Congenital Heart Association's database of adult congenital heart disease health care providers.
Overall, 267 questionnaires were filled out: 108 were collected in person (79% response rate) and 159 online (17.5% response rate). Responses were received from physicians (161); nurses (73); physician assistants (20); and others (13). Although 85% of clinicians believed it was important to inquire about patient satisfaction, only 28% reported routinely inquiring about this dimension of care. Only 34% claimed they had adequate training to cope with varying levels of patient satisfaction, 44% stated that their department utilized patient satisfaction surveys, and 37% received feedback from the hospital management in the preceding 12 months. In multivariate analyses, clinicians that received feedback from the hospital management and had adequate training were more likely to inquire about patient satisfaction.
Although patient satisfaction is perceived as an important dimension of quality care by adult congenital heart disease clinicians, most of them reported insufficient institutional support to achieve this. Our findings suggest that clinicians would benefit from health care organizations engaging them in the delivery of this dimension of health care quality.
No preview · Article · Jun 2014 · Congenital Heart Disease